Patterns of Plasmodium vivax and Plasmodium falciparum malaria underscore importance of data collection from private health care facilities in India.

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Gupta, Sangeeta; Gunter, James T; Novak, Robert J; Regens, James L

2009-10-12

This study describes patterns of falciparum and vivax malaria in a private comprehensive-care, multi-specialty hospital in New Delhi from July 2006 to July 2008. Malarial morbidity by Plasmodium species (Plasmodium falciparum, Plasmodium vivax, or Plasmodium sp.) was confirmed using microscopy and antigen tests. The influence of seasonal factors and selected patient demographics on morbidity was evaluated. The proportions of malaria cases caused by P. falciparum at the private facility were compared to data from India's National Vector Borne Disease Control Programme (NVBDCP) during the same period for the Delhi region. In New Delhi, P. faciparum was the dominant cause of cases requiring treatment in the private hospital during the period examined. The national data reported a smaller proportion of malaria cases caused by P. falciparum in the national capital region than was observed in a private facility within the region. Plasmodium vivax also caused a large proportion of the cases presenting clinically at the private hospital during the summer and monsoon seasons. The proportion of P. falciparum malaria cases tends to be greatest during the post-monsoon season while the proportion of P. vivax malaria cases tends to be greatest in the monsoon season. Private hospital data demonstrate an under-reporting of malaria case incidences in the data from India's national surveillance programme during the same period for the national capital region.

Directly-observed therapy (DOT for the radical 14-day primaquine treatment of Plasmodium vivax malaria on the Thai-Myanmar border

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Thanyavanich Nipon

2010-11-01

Full Text Available Abstract Background Plasmodium vivax has a dormant hepatic stage, called the hypnozoite, which can cause relapse months after the initial attack. For 50 years, primaquine has been used as a hypnozoitocide to radically cure P. vivax infection, but major concerns remain regarding the side-effects of the drug and adherence to the 14-day regimen. This study examined the effectiveness of using the directly-observed therapy (DOT method for the radical treatment of P. vivax malaria infection, to prevent reappearance of the parasite within the 90-day follow-up period. Other potential risk factors for the reappearance of P. vivax were also explored. Methods A randomized trial was conducted from May 2007 to January 2009 in a low malaria transmission area along the Thai-Myanmar border. Patients aged ≥ 3 years diagnosed with P. vivax by microscopy, were recruited. All patients were treated with the national standard regimen of chloroquine for three days followed by primaquine for 14 days. Patients were randomized to receive DOT or self-administered therapy (SAT. All patients were followed for three months to check for any reappearance of P. vivax. Results Of the 216 patients enrolled, 109 were randomized to DOT and 107 to SAT. All patients recovered without serious adverse effects. The vivax reappearance rate was significantly lower in the DOT group than the SAT group (3.4/10,000 person-days vs. 13.5/10,000 person-days, p = 0.021. Factors related to the reappearance of vivax malaria included inadequate total primaquine dosage received (P. vivax-genotype infection, and presence of P. falciparum infection during the follow-up period. Conclusions Adherence to the 14-day primaquine regimen is important for the radical cure of P. vivax malaria infection. Implementation of DOT reduces the reappearance rate of the parasite, and may subsequently decrease P. vivax transmission in the area.

Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model.

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Leanne J Robinson

2015-10-01

Full Text Available The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P. vivax and P. ovale infection, illness, and transmission in Papua New Guinean children.From 17 August 2009 to 20 May 2010, 524 children aged 5-10 y from East Sepik Province in Papua New Guinea (PNG participated in a randomised double-blind placebo-controlled trial of blood- plus liver-stage drugs (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and primaquine [PQ], 20 d, 10 mg/kg total dose (261 children or blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20 d (263 children. Participants, study staff, and investigators were blinded to the treatment allocation. Twenty children were excluded during the treatment phase (PQ arm: 14, PL arm: 6, and 504 were followed actively for 9 mo. During the follow-up time, 18 children (PQ arm: 7, PL arm: 11 were lost to follow-up. Main primary and secondary outcome measures were time to first P. vivax infection (by qPCR, time to first clinical episode, force of infection, gametocyte positivity, and time to first P. ovale infection (by PCR. A basic stochastic transmission model was developed to estimate the potential effect of mass drug administration (MDA for the prevention of recurrent P. vivax infections. Targeting hypnozoites through PQ treatment reduced the risk of having at least one qPCR-detectable P. vivax or P. ovale infection during 8 mo of follow-up (P. vivax: PQ arm 0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p < 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13, 0.77], p = 0.011 and the risk of having at least one clinical P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002. PQ also reduced the molecular force of P. vivax blood-stage infection in the first 3 mo of follow-up (PQ arm 1.90/y

Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

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Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

1997-01-01

Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

Seasonal variations of vivax and falciparum malaria: an observation at a tertiary care hospital

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Jamil, S.; Khan, M.N.

2012-01-01

Background: Malaria is a major public health problem in the malaria endemic zones of the world. Various factors influence the prevalence of malaria. This study was conducted to determine the variation in frequency of Plasmodium vivax and Plasmodium falciparum malaria in different seasons of the year in Khyber Teaching Hospital, Peshawar. Methods: A total of 411 patients were included in the study. All these febrile patients were reported to have trophozoites of either Plasmodium vivax or Plasmodium falciparum malaria on Giemsa stained thick and thin smears. The frequency of vivax and falciparum malaria was worked out and statistically analysed for different season of the year. The study was carried out from 2nd Jan 2004 till 31st December 2008. Results: Out of total 411 diagnosed malaria cases, total 134 (32.60%) presented in the autumn season (vivax=33.58%, and falciparum=66.42%), 37 (9%) in winter season (vivax=32.4%, and falciparum=67.6%), 76 (18.49%) in spring season (vivax=93.4% and falciparum 6.6%) and 164 (39.90%) in summer season (vivax=89.6, and falciparum=10.4%). The malaria showed a highly significant pattern in different seasons of the year (p=0.00) in a way that Plasmodium falciparum malaria reached its highest frequency in autumn and winter seasons while Plasmodium vivax malaria reached its peak frequency in spring and summer seasons. Conclusion: There was highly significant seasonal variation of vivax and falciparum malaria. There is arrival of Plasmodium falciparum in autumn which peaks in winter followed by arrival of Plasmodium vivax in spring till the end of summer. (author)

Microsatellite DNA analysis revealed a drastic genetic change of Plasmodium vivax population in the Republic of Korea during 2002 and 2003.

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Moritoshi Iwagami

Full Text Available Vivax malaria was successfully eliminated in the Republic of Korea (South Korea in the late 1970s, but it was found to have re-emerged from 1993. In order to control malaria and evaluate the effectiveness of malaria controls, it is important to develop a spatiotemporal understanding of the genetic structure of the parasite population. Here, we estimated the population structure and temporal dynamics of the transmission of Plasmodium vivax in South Korea by analyzing microsatellite DNA markers of the parasite.We analyzed 14 microsatellite DNA loci of the P. vivax genome from 163 South Korean isolates collected from 1994 to 2008. Allelic data were used to analyze linkage disequilibrium (LD, genetic differentiation and population structure, in order to make a detailed estimate of temporal change in the parasite population. The LD analysis showed a gradual decrease in LD levels, while the levels of genetic differentiation between successive years and analysis of the population structure based on the Bayesian approach suggested that a drastic genetic change occurred in the South Korean population during 2002 and 2003.Although relapse and asymptomatic parasite carriage might influence the population structure to some extent, our results suggested the continual introduction of P. vivax into South Korea through other parasite population sources. One possible source, particularly during 2002 and 2003, is North Korea. Molecular epidemiology using microsatellite DNA of the P. vivax population is effective for assessing the population structure and temporal dynamics of parasite transmission; information that can assist in the elimination of vivax malaria in endemic areas.

Plasmodium vivax populations revisited: mitochondrial genomes of temperate strains in Asia suggest ancient population expansion

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Miao Miao

2012-02-01

Full Text Available Abstract Background Plasmodium vivax is the most widely distributed human malaria parasite outside of Africa, and its range extends well into the temperate zones. Previous studies provided evidence for vivax population differentiation, but temperate vivax parasites were not well represented in these analyses. Here we address this deficit by using complete mitochondrial (mt genome sequences to elucidate the broad genetic diversity and population structure of P. vivax from temperate regions in East and Southeast Asia. Results From the complete mtDNA sequences of 99 clinical samples collected in China, Myanmar and Korea, a total of 30 different haplotypes were identified from 26 polymorphic sites. Significant differentiation between different East and Southeast Asian parasite populations was observed except for the comparison between populations from Korea and southern China. Haplotype patterns and structure diversity analysis showed coexistence of two different groups in East Asia, which were genetically related to the Southeast Asian population and Myanmar population, respectively. The demographic history of P. vivax, examined using neutrality tests and mismatch distribution analyses, revealed population expansion events across the entire P. vivax range and the Myanmar population. Bayesian skyline analysis further supported the occurrence of ancient P. vivax population expansion. Conclusions This study provided further resolution of the population structure and evolution of P. vivax, especially in temperate/warm-temperate endemic areas of Asia. The results revealed divergence of the P. vivax populations in temperate regions of China and Korea from other populations. Multiple analyses confirmed ancient population expansion of this parasite. The extensive genetic diversity of the P. vivax populations is consistent with phenotypic plasticity of the parasites, which has implications for malaria control.

Monitoring of clinical efficacy and in vitro sensitivity of Plasmodium vivax to chloroquine in area along Thai Myanmar border during 2009-2010

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Rungsihirunrat Kanchana

2011-02-01

Full Text Available Abstract Background In Thailand, the proportion of Plasmodium vivax infection has become equal to Plasmodium falciparum. Reports of a trend of gradual decline of in vitro sensitivity of P. vivax to chloroquine in some areas of the country, together with accumulating evidences of chloroquine resistance P. vivax in other parts of the world, emphasize the need for closely and continuously monitoring clinical efficacy in conjunction with in vitro sensitivity of P. vivax isolates. Methods The study was conducted at Mae Tao clinic for migrant workers, Tak Province during March 2008 - August 2009. A total of 130 patients (17 Thais and 113 Burmeses; 64 males and 66 females with mono-infection of P. vivax malaria, aged between 15-60 years and weighing more than 40 kg, were included in the study. Patients received treatment with chloroquine (2,000 mg chloroquine phosphate over three days and the anti-relapse drug primaquine (15 mg for 14 days. In vitro sensitivity of P. vivax isolates was evaluated by schizont maturation inhibition assay. Results All patients showed satisfactory response to treatment. The cure rate was virtually 100% within the follow-up period of 42 days. Neither recurrence of P. vivax parasitaemia nor appearance of P. falciparum occurred during the investigation period. In vitro data showed a stable sensitivity of chloroquine in this area since 2006. Geometric mean and median (95% CI values of IC50 for chloroquine were 100.1 and 134.7 (1.1-264.9 nM, respectively. Conclusion In vivo results suggest that the standard regimen of chloroquine was still very effective for the treatment of blood infections with P. vivax in the Thai-Myanmar border area. In vitro sensitivity data however, raise the possibility of potential advent of resistance in the future. Regular monitoring of the chloroquine sensitivity of P. vivax is essential to facilitate the early recognition of treatment failures and to expedite the formulation of appropriate changes to

Chloroquine-Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial.

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Awab, Ghulam Rahim; Imwong, Mallika; Bancone, Germana; Jeeyapant, Atthanee; Day, Nicholas P J; White, Nicholas J; Woodrow, Charles J

2017-12-01

Afghanistan's national guidelines recommend primaquine (PQ) for radical treatment of Plasmodium vivax malaria, but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency. Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25 mg base/kg/day for 14 days) (CQ+PQ) in patients aged 6 months and older with microscopy confirmed P. vivax infection. In the CQ+PQ group, G6PD deficiency was excluded by fluorescent spot testing. The primary outcome was P. vivax recurrence assessed by survival analysis over one year follow-up. Of 593 patients enrolled, 570 attended at or after 14 days of follow-up. Plasmodium vivax recurrences occurred in 37 (13.1%) of 282 patients in the CQ+PQ arm versus 86 (29.9%) of 288 in the CQ arm (Cox proportional hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.25-0.54) (intention-to-treat analysis). Protection against recurrence was greater in the first 6 months of follow-up (HR 0.082; 95% CI 0.029-0.23) than later (HR 0.65, 95% CI 0.41-1.03). Five of seven patients requiring hospital admission were considered possible cases of PQ-related hemolysis, and PQ was stopped in a further six; however, in none of these cases did hemoglobin fall by ≥ 2 g/dL or to below 7 g/dL, and genotyping did not detect any cases of Mediterranean variant G6PD deficiency. PQ 0.25 mg/kg/day for 14 days prevents relapse of P. vivax in Afghanistan. Patient visits during the first week may improve adherence. Implementation will require deployment of point-of-care phenotypic tests for G6PD deficiency.

Plasmodium vivax Malaria in Cambodia

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Siv, Sovannaroth; Roca-Feltrer, Arantxa; Vinjamuri, Seshu Babu; Bouth, Denis Mey; Lek, Dysoley; Rashid, Mohammad Abdur; By, Ngau Peng; Popovici, Jean; Huy, Rekol; Menard, Didier

2016-01-01

The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed. PMID:27708187

Plasmodium vivax: is it changing course?

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Khan, M.B.; Qadir, A.; Shaheen, N.; Babar, N.F.

2013-01-01

Objective: To determine the haematological parameters in patients with Plasmodium vivax malaria. Study Design: Descriptive study. Place and Duration of Study: The study was carried out at the Department of Medicine and Department of Pathology, Military Hospital Rawalpindi, Pakistan from 1st June 2010 to 30th September 2010. Methodology: Two hundred and sixteen patients were with confirmed Plasmodium vivax (P.vivax) infection. Demographic and malariometric data of all patients suffering from P.vivax was collected on a patient data form. The diagnosis of P.vivax malaria was established by peripheral blood film (PBF) and Rapid diagnostic test (RDT). All haematological parameters e.g. white blood cells (WBCs), platelet count, bilirubin levels were noted. Results: The mean age was 25.10 +- 5.35 years. Out of 216 patients 183 patients (84.7%) were males and thirty three patients (15.3%) were females. Thrombocytopenia was found in 186 patients (86.1%). Leucopoenia was noted in 37 patients (17.1%). Anaemia was found in 17 patients (7.8%). Increased bilrubin levels were noted in 65 patients (30%). Increased alanine transaminase levels were present in 32 patients (14.8%). Nine patients had serum creatinine levels more than 1.2 mg/dl (4.1%). Conclusion: Plasmodium vivax malaria although considered benign has the potential to cause serious haematological derangements in affected individuals. (author)

Plasmodium vivax merozoite surface protein-3 alpha: a high-resolution marker for genetic diversity studies.

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Prajapati, Surendra Kumar; Joshi, Hema; Valecha, Neena

2010-06-01

Malaria, an ancient human infectious disease caused by five species of Plasmodium, among them Plasmodium vivax is the most widespread human malaria species and causes huge morbidity to its host. Identification of genetic marker to resolve higher genetic diversity for an ancient origin organism is a crucial task. We have analyzed genetic diversity of P. vivax field isolates using highly polymorphic antigen gene merozoite surface protein-3 alpha (msp-3 alpha) and assessed its suitability as high-resolution genetic marker for population genetic studies. 27 P. vivax field isolates collected during chloroquine therapeutic efficacy study at Chennai were analyzed for genetic diversity. PCR-RFLP was employed to assess the genetic variations using highly polymorphic antigen gene msp-3 alpha. We observed three distinct PCR alleles at msp-3 alpha, and among them allele A showed significantly high frequency (53%, chi2 = 8.22, p = 0.001). PCR-RFLP analysis revealed 14 and 17 distinct RFLP patterns for Hha1 and Alu1 enzymes respectively. Further, RFLP analysis revealed that allele A at msp-3 alpha is more diverse in the population compared with allele B and C. Combining Hha1 and Alu1 RFLP patterns revealed 21 distinct genotypes among 22 isolates reflects higher diversity resolution power of msp-3 alpha in the field isolates. P. vivax isolates from Chennai region revealed substantial amount of genetic diversity and comparison of allelic diversity with other antigen genes and microsatellites suggesting that msp-3 alpha could be a high-resolution marker for genetic diversity studies among P. vivax field isolates.

Plasmodium vivax hospitalizations in a monoendemic malaria region: severe vivax malaria?

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Quispe, Antonio M; Pozo, Edwar; Guerrero, Edith; Durand, Salomón; Baldeviano, G Christian; Edgel, Kimberly A; Graf, Paul C F; Lescano, Andres G

2014-07-01

Severe malaria caused by Plasmodium vivax is no longer considered rare. To describe its clinical features, we performed a retrospective case control study in the subregion of Luciano Castillo Colonna, Piura, Peru, an area with nearly exclusive vivax malaria transmission. Severe cases and the subset of critically ill cases were compared with a random set of uncomplicated malaria cases (1:4). Between 2008 and 2009, 6,502 malaria cases were reported, including 106 hospitalized cases, 81 of which fit the World Health Organization definition for severe malaria. Of these 81 individuals, 28 individuals were critically ill (0.4%, 95% confidence interval = 0.2-0.6%) with severe anemia (57%), shock (25%), lung injury (21%), acute renal failure (14%), or cerebral malaria (11%). Two potentially malaria-related deaths occurred. Compared with uncomplicated cases, individuals critically ill were older (38 versus 26 years old, P < 0.001), but similar in other regards. Severe vivax malaria monoinfection with critical illness is more common than previously thought. © The American Society of Tropical Medicine and Hygiene.

Plasmodium vivax malaria among pregnant women in Eastern Sudan

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Duria Abdulwhab Rayis

2016-06-01

Full Text Available Objective: To determine the epidemiology of malaria [especially Plasmodium vivax (P. vivax] among pregnant women in Eastern Sudan. Methods: A cross sectional study was conducted in the antenatal care of New Halfa hospital, Eastern Sudan to investigate the prevalence, manifestations and determinants of malaria (especially P. vivax among pregnant women. Results: Out of 2 378 pregnant women, there were 48 (2.0% and 36 (1.5% Plasmodium falciparum (P. falciparum and P. vivax infection, respectively. There was no significant difference in the age, parity, gestational age between women with malaria and healthy controls. The mean ± SD of the temperature was significantly higher in patients with P. vivax than in patient with P. falciparum malaria [(38.6 ± 0.7 °C vs. (38.1 ± 0.6 °C, P = 0.001]. Patients with P. vivax malaria had slightly (not reach statistical significance lower hemoglobin level compared with P. falciparum malaria and healthy controls. The geometric parasite count showed no significant difference between patients with P. vivax and P. falciparum malaria infections (12 189.9 vs. 9 755.1 trophozoite/µL, P = 0.356. Conclusions: P. vivax malaria is an existing health problem in Eastern Sudan. Further research is also needed.

Effect of training the communication skills with cognitive-behavioral model to drug dependent couples on communication patterns and recurrent relapse

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M. Rahbarian

2016-12-01

Full Text Available Background: One of the main challenges in methadone maintenance treatment is relapse and lack of sustainability on treatment. Therefore, considering the effective factors in this regard and reducing it through psychological interventions as an adjunct to medication is necessary. Objective: The current study aimed to determine the effectiveness of communication skill training based on cognitive-behavioral model on communication patterns and recurrent relapse in drug dependent couples. Methods: This study was a quasi-experimental intervention with pretest-posttest and control group in 2013 which carried on 40 couple referred to public addiction treatment center of Qazvin city. These people had troubled communication patterns and were selected using convenience sampling and were divided into two groups of intervention and control, randomly. Two groups were assessed by relapse prediction scale (RPS and structured clinical interview for DSM (SCID-I for men and communication pattern questionnaire (CPQ for couples in pre and post-test. Intervention group received 9 two hours sessions of communication skill training based on cognitive-behavioral model. Data were analyzed using Levin and Box tests and multivariate analysis of covariance (MANCOVA. Findings: The difference between the intervention and control groups in the constructive communication pattern with 51% (p<0/05, in mutual avoidance pattern with 61% (p<0/0001 and in the demand / withdraw pattern with 45% (p<0/05 was statistically significant. Also, the difference between the two groups in the rate of relapse with 64% (p<0/0001 was statistically significant. Conclusion: According to the findings it seems group training of communication skill based on cognitive-behavioral model can improve the communication patterns in drug-dependent couples, as well as prevents relapse in men.

The effect of zinc and vitamin C supplementation on hemoglobin and hematocrit levels and immune response in patients with Plasmodium vivax malaria.

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Zen Rahfiludin, M; Ginandjar, Praba

2013-09-01

Plasmodium vivax infection in humans can relapse and is associated with iron deficiency. The immune response plays an important role in preventing relapse. In this study we analyzed the effect of zinc and vitamin C supplementation on hemoglobin and hematocrit levels and immune response in patients with P. vivax malaria. We measured immune response by examining interferon gamma (IFN-gamma) and interleukin-10 (IL-10) levels. Subjects were divided into either treatment or control groups. The treatment group received daily zinc and vitamin C supplementation for 45 days. Compliance with supplement consumption was recorded weekly. After 45 days of supplementation, IFN-gamma and IL-1 levels were remeasured. All study subjects in both groups had normal hemoglobin and hematocrit levels. The hemoglobin levels increased only in the supplementation group (p=0.011), while hematocrit levels increased in both the supplementation (p=0.001) and control (p=0.023) groups. IFN-gamma decreased slightly in the supplementation group, but the change was not significant (p=0.688). IL-10 increased slightly in both the supplementation and the control groups, but the change were not significant (p=0.421 and p=0.556, respectively), suggesting the elevated hemoglobin and hematocrit levels were unrelated to immune response.

Is chloroquine still effective for the treatment of vivax malaria in children in northern punjab of pakistan?

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Subhani, F.A.; Shaheen, S.; Nawaz, M.A.

2013-01-01

Introduction: Every year more than one billion persons in the world suffer from malaria. It kills about 1-3 million people in the world per year. In Pakistan estimated burden of malaria is 1.6 million cases each year. As most of people belong to poor socioeconomic group, it is essential that cost effective remedial measures must be taken. Moreover judicious use of antimalarials is required to avoid development of resistance. Objective: To determine the frequency of types of malaria and frequency of cases responding to chloroquine as first line treatment in vivax malaria in children of Northern Punjab of Pakistan. Study Design: Descriptive study. Place and Duration of Study: From Jun 2011 to Sept 2012 at Combined Military Hospital Gujranwala in children reporting from surrounding areas both rural and urban with clinical suspicion of malaria. Materials and Methods: During the study period, 175 children were admitted with clinical suspicion of malaria. Out of which 102 were smear positive for malarial parasites, 13 cases were excluded from the study as they lost to follow up, leaving a total of 89 children in the study. Patients under study remained admitted till the fever settled and malarial parasites were negative on smear. Chloroquine was used as first line treatment in cases with vivax malaria. On discharge from hospital, parents of children were advised fortnightly follow up for 28 days. Results: Out of 89 children approx 54% were males and 46% were females. Mean age of participants was 5.91 years. The minimum age was 1 year and maximum 11 years (SD +- 3.09) out of the 89 cases, 84 (94.3%) had vivax malaria, 2 (2.24%) had falciparum malaria and 3 (3.37%) had mixed infection. Our study showed that 79 (94%) cases of vivax malaria fully responded to chloroquine, 5 (6%) cases treated with Chloroquine reported with relapse. Conclusion: Chloroquine is still the drug of choice in vivax malaria. (author)

Temporal changes in incidence and pattern of central nervous system relapses in children with acute lymphoblastic leukaemia treated on four consecutive Medical Research Council Trials, 1985–2001

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Krishnan, Shekhar; Wade, Rachel; Moorman, Anthony V; Mitchell, Chris; Kinsey, Sally E; Eden, TOB; Parker, Catriona; Vora, Ajay; Richards, Sue; Saha, Vaskar

2009-01-01

Despite the success of contemporary treatment protocols in childhood acute lymphoblastic leukaemia (ALL), relapse within the central nervous system (CNS) remains a challenge. To better understand this phenomenon, we have analysed the changes in incidence and pattern of CNS relapses in 5564 children enrolled on four successive MRC-ALL trials between 1985 and 2001. Changes in the incidence and pattern of CNS relapses were examined and the relationship with patient characteristics assessed. Factors affecting post-relapse outcome were determined. Overall, relapses declined by 49%. Decreases occurred primarily in non-CNS and combined relapses with a progressive shift towards later (≥30 months from diagnosis) relapses (p<0·0001). Although isolated CNS relapses declined, the proportional incidence and timing of relapse remained unchanged. Age and presenting white cell count were risk factors for CNS relapse. On multivariate analysis, the time to relapse and the trial period influenced post-relapse outcomes. Relapse trends differed within biological subtypes. In ETV6-RUNX1 ALL, relapse patterns mirrored overall trends while in High Hyperdiploidy ALL, these appear to have plateaued over the latter two trial periods. Intensive systemic and intrathecal chemotherapy have decreased the overall CNS relapse rates and changed the patterns of recurrence. The heterogeneity of therapeutic response in the biological subtypes suggests room for further optimisation using currently available chemotherapy. PMID:20016529

Seeing the signs: Using the course of residual depressive symptomatology to predict patterns of relapse and recurrence of major depressive disorder.

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Verhoeven, Floor E A; Wardenaar, Klaas J; Ruhé, Henricus G Eric; Conradi, Henk Jan; de Jonge, Peter

2018-02-01

Major depressive disorder (MDD) is characterized by high relapse/recurrence rates. Predicting individual patients' relapse/recurrence risk has proven hard, possibly due to course heterogeneity among patients. This study aimed to (1) identify homogeneous data-driven subgroups with different patterns of relapse/recurrence and (2) identify associated predictors. For a year, we collected weekly depressive symptom ratings in 213 primary care MDD patients. Latent class growth analyses (LCGA), based on symptom-severity during the 24 weeks after no longer fulfilling criteria for the initial major depressive episode (MDE), were used to identify groups with different patterns of relapse/recurrence. Associations of baseline predictors with these groups were investigated, as were the groups' associations with 3- and 11-year follow-up depression outcomes. LCGA showed that heterogeneity in relapse/recurrence after no longer fulfilling criteria for the initial MDE was best described by four classes: "quick symptom decline" (14.0%), "slow symptom decline" (23.3%), "steady residual symptoms" (38.7%), and "high residual symptoms" (24.1%). The latter two classes showed lower self-esteem at baseline, and more recurrences and higher severity at 3-year follow-up than the first two classes. Moreover, the high residual symptom class scored higher on neuroticism and lower on extraversion and self-esteem at baseline. Interestingly, the steady residual symptoms and high residual symptoms classes still showed higher severity of depressive symptoms after 11 years. Some measures were associated with specific patterns of relapse/recurrence. Moreover, the data-driven relapse/recurrence groups were predictive of long-term outcomes, suggesting that patterns of residual symptoms could be of prognostic value in clinical practice. © 2017 Wiley Periodicals, Inc.

Patterns and Timing of Initial Relapse in Patients Subsequently Undergoing Transplantation for Hodgkin's Lymphoma

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Dhakal, Sughosh; Biswas, Tithi; Liesveld, Jane L.; Friedberg, Jonathan W.; Phillips, Gordon L.; Constine, Louis S.

2009-01-01

Purpose: To evaluate the patterns and timing of initial recurrence in patients with Hodgkin's lymphoma (HL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplantation to enhance our understanding of the natural history of this disease and its modern treatment strategies and to direct approaches to disease surveillance. Methods and Materials: The records of 69 patients with HL who had undergone high-dose chemotherapy with autologous stem cell transplantation in our center between May 1992 and June 2006 were analyzed. The initial diagnosis had been made between April 1982 and January 2005 at a median patient age of 33 years (range, 19-65). The patients were segregated according to the initial stage (Stage I-II vs. III-IV). Results: Early-stage HL patients developed a relapse at a median of 2.1 years (range, 0.5-10.3), with 91% of relapses at the initial disease site, 71% of which (65% overall) were only in previously involved sites. Advanced-stage HL patients developed a relapse at a median of 1.5 years (range, 0.6-10.5), with 97% at the initial site, 71% of which (69% overall) were only in previously involved sites. Single-site relapses occurred in 47% of early- vs. 26% of advanced-stage patients, and extranodal relapses occurred in 12% of early- vs. 31% of advanced-stage patients. Conclusions: Almost all patients with HL who develop relapse and subsequently undergo high-dose chemotherapy with autologous stem cell transplantation initially developed recurrence in previously involved disease sites. Early-stage HL relapses often occurred in single sites, and advanced-stage disease relapses were more likely in multiple and extranodal sites. The interval to recurrence was brief, suggesting that the frequency of screening should be the greatest in the early post-therapy years.

Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia.

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Pablo S Fontoura

2016-12-01

Full Text Available Malaria burden in Brazil has reached its lowest levels in 35 years and Plasmodium vivax now accounts for 84% of cases countrywide. Targeting residual malaria transmission entrenched in the Amazon is the next major challenge for ongoing elimination efforts. Better strategies are urgently needed to address the vast reservoir of asymptomatic P. vivax carriers in this and other areas approaching malaria elimination.We evaluated a reactive case detection (RCD strategy tailored for P. vivax transmission in farming settlements in the Amazon Basin of Brazil. Over six months, 41 cases detected by passive surveillance triggered four rounds of RCD (0, 30, 60, and 180 days after index case enrollment, using microscopy- and quantitative real-time polymerase chain reaction (qPCR-based diagnosis, comprising subjects sharing the household (HH with the index case (n = 163, those living in the 5 nearest HHs within 3 km (n = 878, and individuals from 5 randomly chosen control HHs located > 5 km away from index cases (n = 841. Correlates of infection were identified with mixed-effects logistic regression models. Molecular genotyping was used to infer local parasite transmission networks.Subjects in index and neighbor HHs were significantly more likely to be parasitemic than control HH members, after adjusting for potential confounders, and together harbored > 90% of the P. vivax biomass in study subjects. Clustering patterns were temporally stable. Four rounds of microscopy-based RCD would identify only 49.5% of the infections diagnosed by qPCR, but 76.8% of the total parasite biomass circulating in the proximity of index HHs. However, control HHs accounted for 27.6% of qPCR-positive samples, 92.6% of them from asymptomatic carriers beyond the reach of RCD. Molecular genotyping revealed high P. vivax diversity, consistent with complex transmission networks and multiple sources of infection within clusters, potentially complicating malaria elimination efforts.

Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia

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Abdullah, Noor Rain; Barber, Bridget E.; William, Timothy; Norahmad, Nor Azrina; Satsu, Umi Rubiah; Muniandy, Prem Kumar; Ismail, Zakiah; Grigg, Matthew J.; Jelip, Jenarun; Piera, Kim; von Seidlein, Lorenz; Yeo, Tsin W.; Anstey, Nicholas M.; Price, Ric N.; Auburn, Sarah

2013-01-01

Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A S >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A S  = 0.07 [P = 0.0076] in KM, and I A S = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria

African origin of the malaria parasite Plasmodium vivax.

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Liu, Weimin; Li, Yingying; Shaw, Katharina S; Learn, Gerald H; Plenderleith, Lindsey J; Malenke, Jordan A; Sundararaman, Sesh A; Ramirez, Miguel A; Crystal, Patricia A; Smith, Andrew G; Bibollet-Ruche, Frederic; Ayouba, Ahidjo; Locatelli, Sabrina; Esteban, Amandine; Mouacha, Fatima; Guichet, Emilande; Butel, Christelle; Ahuka-Mundeke, Steve; Inogwabini, Bila-Isia; Ndjango, Jean-Bosco N; Speede, Sheri; Sanz, Crickette M; Morgan, David B; Gonder, Mary K; Kranzusch, Philip J; Walsh, Peter D; Georgiev, Alexander V; Muller, Martin N; Piel, Alex K; Stewart, Fiona A; Wilson, Michael L; Pusey, Anne E; Cui, Liwang; Wang, Zenglei; Färnert, Anna; Sutherland, Colin J; Nolder, Debbie; Hart, John A; Hart, Terese B; Bertolani, Paco; Gillis, Amethyst; LeBreton, Matthew; Tafon, Babila; Kiyang, John; Djoko, Cyrille F; Schneider, Bradley S; Wolfe, Nathan D; Mpoudi-Ngole, Eitel; Delaporte, Eric; Carter, Richard; Culleton, Richard L; Shaw, George M; Rayner, Julian C; Peeters, Martine; Hahn, Beatrice H; Sharp, Paul M

2014-01-01

Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.

African origin of the malaria parasite Plasmodium vivax

Science.gov (United States)

Liu, Weimin; Li, Yingying; Shaw, Katharina S.; Learn, Gerald H.; Plenderleith, Lindsey J.; Malenke, Jordan A.; Sundararaman, Sesh A.; Ramirez, Miguel A.; Crystal, Patricia A.; Smith, Andrew G.; Bibollet-Ruche, Frederic; Ayouba, Ahidjo; Locatelli, Sabrina; Esteban, Amandine; Mouacha, Fatima; Guichet, Emilande; Butel, Christelle; Ahuka-Mundeke, Steve; Inogwabini, Bila-Isia; Ndjango, Jean-Bosco N.; Speede, Sheri; Sanz, Crickette M.; Morgan, David B.; Gonder, Mary K.; Kranzusch, Philip J.; Walsh, Peter D.; Georgiev, Alexander V.; Muller, Martin N.; Piel, Alex K.; Stewart, Fiona A.; Wilson, Michael L.; Pusey, Anne E.; Cui, Liwang; Wang, Zenglei; Färnert, Anna; Sutherland, Colin J.; Nolder, Debbie; Hart, John A.; Hart, Terese B.; Bertolani, Paco; Gillis, Amethyst; LeBreton, Matthew; Tafon, Babila; Kiyang, John; Djoko, Cyrille F.; Schneider, Bradley S.; Wolfe, Nathan D.; Mpoudi-Ngole, Eitel; Delaporte, Eric; Carter, Richard; Culleton, Richard L.; Shaw, George M.; Rayner, Julian C.; Peeters, Martine; Hahn, Beatrice H.; Sharp, Paul M.

2014-01-01

Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa. PMID:24557500

Longitudinal and Cross-Sectional Genetic Diversity in the Korean Peninsula Based on the P vivax Merozoite Surface Protein Gene.

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Kim, Jung-Yeon; Suh, Eun-Jung; Yu, Hyo-Soon; Jung, Hyun-Sik; Park, In-Ho; Choi, Yien-Kyeoug; Choi, Kyoung-Mi; Cho, Shin-Hyeong; Lee, Won-Ja

2011-12-01

Vivax malaria has reemerged and become endemic in Korea. Our study aimed to analyze by both longitudinal and cross-sectional genetic diversity of this malaria based on the P vivax Merozoite Surface Protein (PvMSP) gene parasites recently found in the Korean peninsula. PvMSP-1 gene sequence analysis from P vivax isolates (n = 835) during the 1996-2010 period were longitudinally analyzed and the isolates from the Korean peninsula through South Korea, the demilitarized zone and North Korea collected in 2008-2010 were enrolled in an overall analysis of MSP-1 gene diversity. New recombinant subtypes and severe multiple-cloneinfection rates were observed in recent vivax parasites. Regional variation was also observed in the study sites. This study revealed the great complexity of genetic variation and rapid dissemination of genes in P vivax. It also showed interesting patterns of diversity depending, on the region in the Korean Peninsula. Understanding the parasiteninsula. Under genetic variation may help to analyze trends and assess the extent of endemic malaria in Korea.

Preclinical assessment of viral vectored and protein vaccines targeting the Duffy-binding protein region II of Plasmodium vivax

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Simone C de Cassan

2015-07-01

Full Text Available Malaria vaccine development has largely focused on Plasmodium falciparum; however a reawakening to the importance of P. vivax has spurred efforts to develop vaccines against this difficult to treat and at times severe form of relapsing malaria, which constitutes a significant proportion of human malaria cases worldwide. The almost complete dependence of P. vivax red blood cell invasion on the interaction of the P. vivax Duffy-binding protein region II (PvDBP_RII with the human Duffy antigen receptor for chemokines (DARC, makes this antigen an attractive vaccine candidate against blood-stage P. vivax. Here, we generated both preclinical and clinically-compatible adenoviral and poxviral vectored vaccine candidates expressing the Salvador I allele of PvDBP_RII – including human adenovirus serotype 5 (HAdV5, chimpanzee adenovirus serotype 63 (ChAd63 and modified vaccinia virus Ankara (MVA vectors. We report on the antibody and T cell immunogenicity of these vaccines in mice or rabbits, either used alone in a viral vectored prime-boost regime, or in ‘mixed-modality’ adenovirus prime – protein-in-adjuvant boost regimes (using a recombinant protein PvDBP_RII protein antigen formulated in Montanide®ISA720 or Abisco®100 adjuvants. Antibodies induced by these regimes were found to bind to native parasite antigen from P. vivax infected Thai patients and were capable of inhibiting the binding of PvDBP_RII to its receptor DARC using an in vitro binding inhibition assay. In recent years, recombinant ChAd63 and MVA vectors have been quickly translated into human clinical trials for numerous antigens from P. falciparum as well as a growing number of other pathogens. The vectors reported here are immunogenic in small animals, elicit antibodies against PvDBP_RII and have recently entered clinical trials which will provide the first assessment of the safety and immunogenicity of the PvDBP_RII antigen in humans.

Epidemiology of Plasmodium vivax Malaria in Peru.

Science.gov (United States)

Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E; Moreno, Marta; Lescano, Andres G; Sanchez, Juan F; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M

2016-12-28

Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine-primaquine for P. vivax Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. © The American Society of Tropical Medicine and Hygiene.

Epidemiology of Plasmodium vivax Malaria in Peru

Science.gov (United States)

Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E.; Moreno, Marta; Lescano, Andres G.; Sanchez, Juan F.; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.

2016-01-01

Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s–2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005–2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine–primaquine for P. vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. PMID:27799639

N-Terminal Plasmodium vivax Merozoite Surface Protein-1, a Potential Subunit for Malaria Vivax Vaccine

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Fernanda G. Versiani

2013-01-01

Full Text Available The human malaria is widely distributed in the Middle East, Asia, the western Pacific, and Central and South America. Plasmodium vivax started to have the attention of many researchers since it is causing diseases to millions of people and several reports of severe malaria cases have been noticed in the last few years. The lack of in vitro cultures for P. vivax represents a major delay in developing a functional malaria vaccine. One of the major candidates to antimalarial vaccine is the merozoite surface protein-1 (MSP1, which is expressed abundantly on the merozoite surface and capable of activating the host protective immunity. Studies have shown that MSP-1 possesses highly immunogenic fragments, capable of generating immune response and protection in natural infection in endemic regions. This paper shows humoral immune response to different proteins of PvMSP1 and the statement of N-terminal to be added to the list of potential candidates for malaria vivax vaccine.

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

International Nuclear Information System (INIS)

Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Eagan, Patricia; Gruber, Deborah; Gruber, Michael L.

2012-01-01

Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1–37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R 2 = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

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Narayana, Ashwatha, E-mail: ashwatha.narayana@nyumc.org [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Kunnakkat, Saroj D. [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Medabalmi, Praveen [Department of Biostatistics, New York University Langone Medical Center, New York, NY (United States); Golfinos, John; Parker, Erik [Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Knopp, Edmond [Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Zagzag, David [Department of Pathology, New York University Langone Medical Center, New York, NY (United States); Eagan, Patricia [Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Atlantic Health System, Overlook Hospital, Summit, NJ (United States); Gruber, Deborah [Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Gruber, Michael L. [Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Atlantic Health System, Overlook Hospital, Summit, NJ (United States)

2012-01-01

Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R{sup 2} = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

soma vivax in Tselemti woreda , Tigray, Ethiopia

African Journals Online (AJOL)

field. Material and Methods. Study Area. The study was carried out at Mekelle Regional Laboratory from November 2002 to April 2003. T. vivax isolate was collected from ... the order of 5-10 trypanosomes per high power microscope field (40X). ..... their studies of the infectivity for mice of Nigerian isolates of T. vivax, that.

Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations

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Aurelio Lopez

2015-01-01

Full Text Available We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients and more aggressive forms of disease (32 patients were the most common patterns of relapse. After second-line therapy, 75 (51.7% patients achieved at partial response and 16 (11% complete response (CR. Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037, in patients achieving CR (28.3 vs. 14.8 months; P=0.04, and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007.

Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations☆

Science.gov (United States)

Lopez, Aurelio; Mateos, Maria-Victoria; Oriol, Albert; Valero, Marta; Martínez, Joaquín; Lorenzo, Jose Ignacio; Perez, Montserrat; Martinez, Rafael; de Paz, Raquel; Granell, Miguel; De Arriba, Felipe; Blanchard, M. Jesús; Peñalver, Francisco Javier; Bello, Jose Luis; Martin, Maria Luisa; Bargay, Joan; Blade, Joan; Lahuerta, Juan Jose; San Miguel, Jesús F.; de la Rubia, Javier

2015-01-01

We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007). PMID:26500850

Frequency of thrombocytopenia in plasmodium vivax malaria

International Nuclear Information System (INIS)

Nadeem, A.; Malik, T.M.; Malik, H.S.

2014-01-01

Objective: To determine the frequency of thrombocytopenia in Plasmodium vivax (P.vivax) malaria cases at two hospitals. Study Design: Cross-sectional descriptive study. Place and Duration of Study: The study was conducted at the departments of Pathology, Combined Military Hospitals Malir and Sibi, Pakistan from Jul 2011 to Mar 2012. Patients and Methods: A total of 2709 samples were collected from febrile patients for detection of malaria parasite (944 from CMH Malir and 1765 from CMH Sibi). Cases having infection with P. falciparum alone or having mixed infection with P. Vivax and P. falciparum were excluded from the study. Both thick and thin film microscopy and immunochromatographic method (OptiMA L-IT) were used for detection of malarial parasite. Platelet counts were done using automated haematology analyser (Sysmex KX 21) with re-evaluation of low counts with manual methods. Results: Total of 170 patients were found positive for P. vivax malaria (44 from CMH Malir and 126 from CMH Sibi). Platelet counts ranged from 21 - 457 * 10/sub 9/ with a mean of 134 * 10/sub 9/. Ninety five (2.1%) from CMH Malir and 4.2% from CMH Sibi out of 170 patients had thrombocytopenia, and the difference in thrombocytopenia at the two hospitals was insignificant (0.017). Conclusion: Thrombocytopenia in patients with P. vivax infection is equally prevalent in the two hospitals, representing a widely different geographical area and should prompt a more thorough search for malaria parasite. (author)

Clinical and molecular surveillance of drug resistant vivax malaria in Myanmar (2009-2016).

Science.gov (United States)

Nyunt, Myat Htut; Han, Jin-Hee; Wang, Bo; Aye, Khin Myo; Aye, Kyin Hla; Lee, Seong-Kyun; Htut, Ye; Kyaw, Myat Phone; Han, Kay Thwe; Han, Eun-Taek

2017-03-16

One of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance. While epidemiology and surveillance of the drug resistance in falciparum malaria is being explored globally, there are few studies on drug resistance vivax malaria. To assess the spread of drug-resistant vivax malaria in Myanmar, a multisite, prospective, longitudinal study with retrospective analysis of previous therapeutic efficacy studies, was conducted. A total of 906 from nine study sites were included in retrospective analysis and 208 from three study sites in prospective study. Uncomplicated vivax mono-infected patients were recruited and monitored with longitudinal follow-up until day 28 after treatment with chloroquine. Amplification and sequence analysis of molecular markers, such as mutations in pvcrt-O, pvmdr1, pvdhps and pvdhfr, were done in day-0 samples in prospective study. Clinical failure cases were found only in Kawthaung, southern Myanmar and western Myanmar sites within 2009-2016. Chloroquine resistance markers, pvcrt-O 'AAG' insertion and pvmdr1 mutation (Y976F) showed higher mutant rate in southern and central Myanmar than western site: 66.7, 72.7 vs 48.3% and 26.7, 17.0 vs 1.7%, respectively. A similar pattern of significantly higher mutant rate of antifolate resistance markers, pvdhps (S382A, K512M, A553G) and pvdhfr (F57L/I, S58R, T61M, S117T/N) were noted. Although clinical failure rate was low, widespread distribution of chloroquine and antifolate resistance molecular makers alert to the emergence and spread of drug resistance vivax malaria in Myanmar. Proper strategy and action plan to eliminate and contain the resistant strain strengthened together with clinical and molecular surveillance on drug resistance vivax is recommended.

EVALUATION OF CIRCUMSPOROZOITE PROTEIN OF Plasmodium vivax TO ESTIMATE ITS PREVALENCE IN OIAPOQUE , AMAPÁ STATE, BRAZIL, BORDERING FRENCH GUIANA

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Margarete do Socorro Mendonça GOMES

Full Text Available SUMMARY Malaria is a major health problem for people who live on the border between Brazil and French Guiana. Here we discuss Plasmodium vivax distribution pattern in the town of Oiapoque, Amapá State using the circumsporozoite (CS gene as a marker. Ninety-one peripheral blood samples from P. vivax patients have been studied. Of these, 64 individuals were from the municipality of Oiapoque (Amapá State, Brazil and 27 patients from French Guiana (August to December 2011. DNA extraction was performed, and a fragment of the P. vivax CS gene was subsequently analyzed using PCR/RFLP. The VK210 genotype was the most common in both countries (48.36% in Brazil and 14.28% in French Guiana, followed by the P. vivax-like (1.10% in both Brazil and French Guiana and VK247 (1.10% only in Brazil in single infections. We were able to detect all three CS genotypes simultaneously in mixed infections. There were no statistically significant differences either regarding infection site or parasitaemia among individuals with different genotypes. These results suggest that the same genotypes circulating in French Guiana are found in the municipality of Oiapoque in Brazil. These findings suggest that there may be a dispersion of parasitic populations occurring between the two countries. Most likely, this distribution is associated with prolonged and/or more complex transmission patterns of these genotypes in Brazil, bordering French Guiana.

Plasmodium vivax cerebral malaria complicated with venous sinus thrombosis in Colombia

Institute of Scientific and Technical Information of China (English)

Miguel A Pinzn; Juan C Pineda; Fernando Rosso; Masaru Shinchi; Fabio Bonilla-Abada

2013-01-01

Complicated malaria is usually due to Plasmodium falciparum. Nevertheless, Plasmodium vivax is infrequently related with life-threatening complications. Few cases have been reported of severe Plasmodium vivax infection, and most of them from Southeast Asia and India. We report the first case of cerebral malaria due to Plasmodium vivax in Latin America, complicated with sagittal sinus thrombosis and confirmed by a molecular method.

Plasmodium vivax Biology: Insights Provided by Genomics, Transcriptomics and Proteomics

Science.gov (United States)

Bourgard, Catarina; Albrecht, Letusa; Kayano, Ana C. A. V.; Sunnerhagen, Per; Costa, Fabio T. M.

2018-01-01

During the last decade, the vast omics field has revolutionized biological research, especially the genomics, transcriptomics and proteomics branches, as technological tools become available to the field researcher and allow difficult question-driven studies to be addressed. Parasitology has greatly benefited from next generation sequencing (NGS) projects, which have resulted in a broadened comprehension of basic parasite molecular biology, ecology and epidemiology. Malariology is one example where application of this technology has greatly contributed to a better understanding of Plasmodium spp. biology and host-parasite interactions. Among the several parasite species that cause human malaria, the neglected Plasmodium vivax presents great research challenges, as in vitro culturing is not yet feasible and functional assays are heavily limited. Therefore, there are gaps in our P. vivax biology knowledge that affect decisions for control policies aiming to eradicate vivax malaria in the near future. In this review, we provide a snapshot of key discoveries already achieved in P. vivax sequencing projects, focusing on developments, hurdles, and limitations currently faced by the research community, as well as perspectives on future vivax malaria research. PMID:29473024

A proline racemase based PCR for identification of Trypanosoma vivax in cattle blood.

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Regassa Fikru

Full Text Available A study was conducted to develop a Trypanosoma vivax (T. vivax specific PCR based on the T. vivax proline racemase (TvPRAC gene. Forward and reverse primers were designed that bind at 764-783 bp and 983-1002 bp of the gene. To assess its specificity, TvPRAC PCR was conducted on DNA extracted from different haemotropic pathogens: T. vivax from Nigeria, Ethiopia and Venezuela, T. congolense Savannah type, T. brucei brucei, T. evansi, T. equiperdum, T. theileri, Theileria parva, Anaplasma marginale, Babesia bovis and Babesia bigemina and from bovine, goat, mouse, camel and human blood. The analytical sensitivity of the TvPRAC PCR was compared with that of the ITS-1 PCR and the 18S PCR-RFLP on a dilution series of T. vivax DNA in water. The diagnostic performance of the three PCRs was compared on 411 Ethiopian bovine blood specimens collected in a former study. TvPRAC PCR proved to be fully specific for T. vivax, irrespective of its geographical origin. Its analytical sensitivity was lower than that of ITS-1 PCR. On these bovine specimens, TvPRAC PCR detected 8.3% T. vivax infections while ITS-1 PCR and 18S PCR-RFLP detected respectively 22.6 and 6.1% T. vivax infections. The study demonstrates that a proline racemase based PCR could be used, preferably in combination with ITS-1 PCR, as a species-specific diagnostic test for T. vivax infections worldwide.

Parasitemia characteristics of Plasmodium vivax malaria patients in the Republic of Korea.

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Huh, Ae-Jung; Kwak, Yee Gyung; Kim, Eu Suk; Lee, Kkot Sil; Yeom, Joon-Sup; Cho, Yong-Kyun; Kim, Chang-Seok; Park, Jae-Won

2011-01-01

Parasitemia characteristics of Plasmodium vivax malaria in temperate regions may differ from those in tropical zones. However, most parasitological and clinical features of P. vivax malaria have been investigated in the latter. In this study, we investigated 383 malaria patients to clarify the parasitemia characteristics of a P. vivax strain in the Republic of Korea (ROK). The mean parasitemia (8,396/µL) was less than half of tropical P. vivax malaria, and multiple invasions of erythrocytes were not rare (53.5% of the patients, 2.4% of the total investigated RBCs), but less than the observations in tropical zones. The intervals between the first symptom onset and diagnosis were significantly longer in gametocyte (+) patients than in gametocyte (-) patients. Only half of the total patients had both genders of gametocytes (191 of 353), and the male gametocyte density (169/µL) was lower than that of P. vivax strains of a previous study. Multiple invasions of erythrocytes and gametocytemia were coincident factors of the degree of anemia in P. vivax malaria. The present findings demonstrate the P. vivax strain in ROK reveals relatively low parasitemia and low male to female gametocyte ratio. The low ratio may be related with low transmission efficacy.

Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

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Lima, Nathália F.; Batista, Camilla L.; Bastos, Melissa da Silva; Nicolete, Vanessa C.; Fontoura, Pablo S.; Gonçalves, Raquel M.; Viana, Susana Ariane S.; Menezes, Maria José; Scopel, Kézia Katiani G.; Cavasini, Carlos E.; Malafronte, Rosely dos Santos; da Silva-Nunes, Mônica; Vinetz, Joseph M.; Castro, Márcia C.; Ferreira, Marcelo U.

2014-01-01

Background New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Methods Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P

Sero-epidemiological evaluation of changes in Plasmodium falciparum and Plasmodium vivax transmission patterns over the rainy season in Cambodia

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Cook Jackie

2012-03-01

Full Text Available Abstract Background In Cambodia, malaria transmission is low and most cases occur in forested areas. Sero-epidemiological techniques can be used to identify both areas of ongoing transmission and high-risk groups to be targeted by control interventions. This study utilizes repeated cross-sectional data to assess the risk of being malaria sero-positive at two consecutive time points during the rainy season and investigates who is most likely to sero-convert over the transmission season. Methods In 2005, two cross-sectional surveys, one in the middle and the other at the end of the malaria transmission season, were carried out in two ecologically distinct regions in Cambodia. Parasitological and serological data were collected in four districts. Antibodies to Plasmodium falciparum Glutamate Rich Protein (GLURP and Plasmodium vivax Merozoite Surface Protein-119 (MSP-119 were detected using Enzyme Linked Immunosorbent Assay (ELISA. The force of infection was estimated using a simple catalytic model fitted using maximum likelihood methods. Risks for sero-converting during the rainy season were analysed using the Classification and Regression Tree (CART method. Results A total of 804 individuals participating in both surveys were analysed. The overall parasite prevalence was low (4.6% and 2.0% for P. falciparum and 7.9% and 6.0% for P. vivax in August and November respectively. P. falciparum force of infection was higher in the eastern region and increased between August and November, whilst P. vivax force of infection was higher in the western region and remained similar in both surveys. In the western region, malaria transmission changed very little across the season (for both species. CART analysis for P. falciparum in the east highlighted age, ethnicity, village of residence and forest work as important predictors for malaria exposure during the rainy season. Adults were more likely to increase their antibody responses to P. falciparum during the

Effect of training the communication skills with cognitive-behavioral model to drug dependent couples on communication patterns and recurrent relapse

OpenAIRE

M. Rahbarian; R. Hossein zadeh; P. Doosti

2016-01-01

Background: One of the main challenges in methadone maintenance treatment is relapse and lack of sustainability on treatment. Therefore, considering the effective factors in this regard and reducing it through psychological interventions as an adjunct to medication is necessary. Objective: The current study aimed to determine the effectiveness of communication skill training based on cognitive-behavioral model on communication patterns and recurrent relapse in drug dependent couples. Me...

In Vivo Susceptibility of Plasmodium Vivax to Chloroquine in Southeastern Iran

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S Dittrich

2012-06-01

Full Text Available Background: Plasmodium vivax is the predominant species causes of malaria with about 90% total annual reported malaria in Iran. This study conducted to determine the susceptibility of Plasmodium vivax isolates to chloroquine in Sistan and Balochistan Province, southeastern Iran.Methods: A total 270 subjects with symptomatic malaria and confirmed P. vivax infection completed the designed 28-day in vivo study. The thick and thin film blood smears were screened for malaria parasites by microscopy. The nested PCR was applied using the Plasmodium 18 subunit ribosomal ribonu­cleic (Ssr RNA genes for detecting mixed infections and diagnosis of parasites in the samples with low parasite on days 0, 5, 6, 7, and 28. Results: P. vivax was cleared in 15%, 50%, 95%, and 100% of patients on days 1, 2, 3, 4 respectively by microscopy assessment. Six patients were exhibited specific P. vivax band in nested PCR on day 5. No recurrence was observed on days 7, 14 and 28. Mean (±standard deviation parasite clearance time was 2.41 (±0.8 days. Conclusion: P. vivax is still susceptible to chloroquine in Southeatern Iran. This finding is compati­ble with results of neighboring countries Pakistan and Afghanistan.

Understanding the population genetics of Plasmodium vivax is essential for malaria control and elimination

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Arnott Alicia

2012-01-01

Full Text Available Abstract Traditionally, infection with Plasmodium vivax was thought to be benign and self-limiting, however, recent evidence has demonstrated that infection with P. vivax can also result in severe illness and death. Research into P. vivax has been relatively neglected and much remains unknown regarding the biology, pathogenesis and epidemiology of this parasite. One of the fundamental factors governing transmission and immunity is parasite diversity. An understanding of parasite population genetic structure is necessary to understand the epidemiology, diversity, distribution and dynamics of natural P. vivax populations. In addition, studying the population structure of genes under immune selection also enables investigation of the dynamic interplay between transmission and immunity, which is crucial for vaccine development. A lack of knowledge regarding the transmission and spread of P. vivax has been particularly highlighted in areas where malaria control and elimination programmes have made progress in reducing the burden of Plasmodium falciparum, yet P. vivax remains as a substantial obstacle. With malaria elimination back on the global agenda, mapping of global and local P. vivax population structure is essential prior to establishing goals for elimination and the roll-out of interventions. A detailed knowledge of the spatial distribution, transmission and clinical burden of P. vivax is required to act as a benchmark against which control targets can be set and measured. This paper presents an overview of what is known and what is yet to be fully understood regarding P. vivax population genetics, as well as the importance and application of P. vivax population genetics studies.

Plasmodium vivax: modern strategies to study a persistent parasite's life cycle.

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Galinski, Mary R; Meyer, Esmeralda V S; Barnwell, John W

2013-01-01

Plasmodium vivax has unique attributes to support its survival in varying ecologies and climates. These include hypnozoite forms in the liver, an invasion preference for reticulocytes, caveola-vesicle complex structures in the infected erythrocyte membrane and rapidly forming and circulating gametocytes. These characteristics make this species very different from P. falciparum. Plasmodium cynomolgi and other related simian species have identical biology and can serve as informative models of P. vivax infections. Plasmodium vivax and its model parasites can be grown in non-human primates (NHP), and in short-term ex vivo cultures. For P. vivax, in the absence of in vitro culture systems, these models remain highly relevant side by side with human clinical studies. While post-genomic technologies allow for greater exploration of P. vivax-infected blood samples from humans, these come with restrictions. Two advantages of NHP models are that infections can be experimentally tailored to address hypotheses, including genetic manipulation. Also, systems biology approaches can capitalise on computational biology combined with set experimental infection periods and protocols, which may include multiple sampling times, different types of samples, and the broad use of "omics" technologies. Opportunities for research on vivax malaria are increasing with the use of existing and new methodological strategies in combination with modern technologies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

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2012-01-01

Background Plasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed. Methods Fifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs. Results Thirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII. Conclusions PvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine. PMID:22380592

Cross-reactive anti-PfCLAG9 antibodies in the sera of asymptomatic parasite carriers of Plasmodium vivax

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Costa, Joana D'Arc Neves; Zanchi, Fernando Berton; Rodrigues, Francisco Lurdevanhe da Silva; Honda, Eduardo Rezende; Katsuragawa, Tony Hiroschi; Pereira, Dhélio Batista; Taborda, Roger Lafontaine Mesquita; Tada, Mauro Shugiro; Ferreira, Ricardo de Godoi Mattos; Pereira-da-Silva, Luiz Hildebrando

2013-01-01

The PfCLAG9 has been extensively studied because their immunogenicity. Thereby, the gene product is important for therapeutics interventions and a potential vaccine candidate. Antibodies against synthetic peptides corresponding to selected sequences of the Plasmodium falciparum antigen PfCLAG9 were found in sera of falciparum malaria patients from Rondônia, in the Brazilian Amazon. Much higher antibody titres were found in semi-immune and immune asymptomatic parasite carriers than in subjects suffering clinical infections, corroborating original findings in Papua Guinea. However, sera of Plasmodium vivax patients from the same Amazon area, in particular from asymptomatic vivax parasite carriers, reacted strongly with the same peptides. Bioinformatic analyses revealed regions of similarity between P. falciparum Pfclag9 and the P. vivax ortholog Pvclag7. Indirect fluorescent microscopy analysis showed that antibodies against PfCLAG9 peptides elicited in BALB/c mice react with human red blood cells (RBCs) infected with both P. falciparum and P. vivax parasites. The patterns of reactivity on the surface of the parasitised RBCs are very similar. The present observations support previous findings that PfCLAG9 may be a target of protective immune responses and raises the possibility that the cross reactive antibodies to PvCLAG7 in mixed infections play a role in regulate the fate of Plasmodium mixed infections. PMID:23440122

Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo.

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Adeshina I Adekunle

2015-03-01

Full Text Available The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine, or the blood and liver stages of infection (chloroquine + primaquine. In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90-96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG.

Genetic diversity of plasmodium vivax merozoite surface protein-3alpha (Pvmsp-3alpha) gene in Jhapa District of Nepal

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Adhikari, Madhav; Ranjitkar, Samir; Schousboe, Mette Leth

2012-01-01

In Nepal, Plasmodium vivax accounts for approximately 80-90% of the malaria cases, but limited studies have been conducted on the genetic diversity of this parasite population. This study was carried out to determine the genetic diversity of P. vivax population sampled from subjects living...... in an endemic area of Jhapa District by analyzing the polymorphic merozoite surface protein-3alpha (Pvmsp-3alpha) gene by using PCR-restriction fragment length polymorphism. Three distinct genotypes were obtained from 96 samples; type A: 40 (71%), type B: 7 (13%), and type C: 9 (16%) which could be categorized...... into 13 allelic patterns: A1-A9, B1, B2, C1 and C2. These results indicated a high genetic diversity within the studied P. vivax population. As the transmission rate of malaria is low in Nepal, the diversity is most likely due to migration of people between the malaria endemic regions, either within...

Placental histopathological changes associated with Plasmodium vivax infection during pregnancy.

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Rodrigo M Souza

Full Text Available Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41, P. vivax exposure (n = 59 or P. falciparum exposure (n = 19. We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045, placental barrier thickness (OR, 25.59, P = 0.021 and mononuclear cells (OR, 4.02, P = 0.046 were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A

Developing Plasmodium vivax Resources for Liver Stage Study in the Peruvian Amazon Region.

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Orjuela-Sanchez, Pamela; Villa, Zaira Hellen; Moreno, Marta; Tong-Rios, Carlos; Meister, Stephan; LaMonte, Gregory M; Campo, Brice; Vinetz, Joseph M; Winzeler, Elizabeth A

2018-04-13

To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region. Here, we report an in vitro culture system carried out on site in a malaria-endemic region for liver stage parasites of P. vivax sporozoites obtained from An. darlingi, the main malaria vector in the Americas. P. vivax sporozoites were obtained by dissection of salivary glands from infected An. darlingi mosquitoes and purified by Accudenz density gradient centrifugation. HC04 liver cells were exposed to P. vivax sporozoites and cultured up to 9 days. To overcome low P. vivax patient parasitemias, potentially lower mosquito vectorial capacity, and humid, nonsterile environmental conditions, a new antibiotic cocktail was included in tissue culture to prevent contamination. Culturing conditions supported exoerythrocytic (EEF) P. vivax liver stage growth up to 9 days and allowed for maturation into intrahepatocyte merosomes. Some of the identified small forms were resistant to atovaquone (1 μM) but sensitive to the phosphatidylinositol 4-kinase inhibitor, KDU691 (1 μM). This study reports a field-accessible EEF production process for drug discovery in a malaria-endemic site in which viable P. vivax sporozoites are used for drug studies using hepatocyte infection. Our data demonstrate that the development of meaningful, field-based resources for P. vivax liver stage drug screening and liver stage human malaria experimentation in the Amazon region is feasible.

Micro-epidemiology and spatial heterogeneity of P. vivax parasitaemia in riverine communities of the Peruvian Amazon: A multilevel analysis.

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Carrasco-Escobar, Gabriel; Gamboa, Dionicia; Castro, Marcia C; Bangdiwala, Shrikant I; Rodriguez, Hugo; Contreras-Mancilla, Juan; Alava, Freddy; Speybroeck, Niko; Lescano, Andres G; Vinetz, Joseph M; Rosas-Aguirre, Angel; Llanos-Cuentas, Alejandro

2017-08-14

Malaria has steadily increased in the Peruvian Amazon over the last five years. This study aimed to determine the parasite prevalence and micro-geographical heterogeneity of Plasmodium vivax parasitaemia in communities of the Peruvian Amazon. Four cross-sectional active case detection surveys were conducted between May and July 2015 in four riverine communities in Mazan district. Analysis of 2785 samples of 820 individuals nested within 154 households for Plasmodium parasitaemia was carried out using light microscopy and qPCR. The spatio-temporal distribution of Plasmodium parasitaemia, dominated by P. vivax, was shown to cluster at both household and community levels. Of enrolled individuals, 47% had at least one P. vivax parasitaemia and 10% P. falciparum, by qPCR, both of which were predominantly sub-microscopic and asymptomatic. Spatial analysis detected significant clustering in three communities. Our findings showed that communities at small-to-moderate spatial scales differed in P. vivax parasite prevalence, and multilevel Poisson regression models showed that such differences were influenced by factors such as age, education, and location of households within high-risk clusters, as well as factors linked to a local micro-geographic context, such as travel and occupation. Complex transmission patterns were found to be related to human mobility among communities in the same micro-basin.

Prevalence of Plasmodium vivax VK210 and VK247 subtype in Myanmar

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Kang Yoon-Joong

2010-07-01

Full Text Available Abstract Background Plasmodium vivax is divided into two subtypes, a dominant form, VK210 and a variant form, VK247. This division is dependent on the amino acid composition of the circumsporozoite (CS protein. In this study, the prevalence of the VK247 variant form of P. vivax was investigated in Myanmar. Methods The existence of malaria parasites in blood samples was determined by microscopic examination, polymerase chain reaction (PCR and DNA hybridization assays. To test for antibodies against P. vivax and Plasmodium falciparum in blood samples, an indirect immunofluorescence antibody test (IFAT was performed using asexual blood antigens. An enzyme-linked immunosorbent assay with synthetic VK210 and VK247 antigens was carried out to discriminate between the P. vivax subtypes. Results By thick smear examination, 73 (n = 100 patients were single infected with P. vivax, one with P. falciparum and 13 with both species. By thin smear, 53 patients were single infected with P. vivax, eight with only P. falciparum and 16 with both. Most of the collected blood samples were shown to be P. vivax positive (n = 95 by PCR. All cases that were positive for P. falciparum by PCR (n = 43 were also positive for P. vivax. However, 52 cases were single infected with P. vivax. IFAT showed antibody titres from 1:32 to 1:4,096. Additionally, using specific antibodies for VK210 and VK247, ELISA showed that 12 patients had antibodies for only the VK210 subtype, 4 patients had only VK247 subtype antibodies and 21 patients had antibodies for both subtypes. Using a DNA hybridization test, 47 patients were infected with the VK210 type, one patient was infected with VK247 and 23 patients were infected with both subtypes. Conclusions The proportion of the VK247 subtype in Myanmar was 43.1% (n = 25 among 58 positive cases by serodiagnosis and 25.6% (n = 24 among 94 positive cases by genetic diagnosis. In both diagnostic methods, the infection status of malaria patients is

The origins of African Plasmodium vivax; insights from mitochondrial genome sequencing.

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Richard Culleton

Full Text Available Plasmodium vivax, the second most prevalent of the human malaria parasites, is estimated to affect 75 million people annually. It is very rare, however, in west and central Africa, due to the high prevalence of the Duffy negative phenotype in the human population. Due to its rarity in Africa, previous studies on the phylogeny of world-wide P. vivax have suffered from insufficient samples of African parasites. Here we compare the mitochondrial sequence diversity of parasites from Africa with those from other areas of the world, in order to investigate the origin of present-day African P. vivax. Mitochondrial genome sequencing revealed relatively little polymorphism within the African population compared to parasites from the rest of the world. This, combined with sequence similarity with parasites from India, suggests that the present day African P. vivax population in humans may have been introduced relatively recently from the Indian subcontinent. Haplotype network analysis also raises the possibility that parasites currently found in Africa and South America may be the closest extant relatives of the ancestors of the current world population. Lines of evidence are adduced that this ancestral population may be from an ancient stock of P. vivax in Africa.

Insights into the Cytoadherence Phenomenon of Plasmodium vivax: The Putative Role of Phosphatidylserine

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Paulo Renato Totino

2017-09-01

Full Text Available Plasmodium vivax is the most geographically widespread and the dominant human malaria parasite in most countries outside of sub-Saharan Africa and, although it was classically recognized to cause benign infection, severe cases and deaths caused by P. vivax have remarkably been reported. In contrast to Plasmodium falciparum, which well-known ability to bind to endothelium and placental tissue and form rosettes is related to severity of the disease, it has been a dogma that P. vivax is unable to undergo cytoadherent phenomena. However, some studies have demonstrated that red blood cells (RBCs infected by P. vivax can cytoadhere to host cells, while the molecules participating in this host–parasite interaction are still a matter of speculation. In the present overview, we address the evidences currently supporting the adhesive profile of P. vivax and, additionally, discuss the putative role of phosphatidylserine—a cell membrane phospholipid with cytoadhesive properties that has been detected on the surface of Plasmodium-parasitized RBCs.

Kinetoplast adaptations in American strains from Trypanosoma vivax

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Greif, Gonzalo; Rodriguez, Matías; Reyna-Bello, Armando; Robello, Carlos; Alvarez-Valin, Fernando

2015-01-01

Highlights: • American T. vivax strains exhibit a drastic process of mitochondrial genome degradation. • T. vivax mitochondrial genes have among the fastest evolutionary rates in eukaryotes. • High rates of kDNA evolution are associated with relaxation of selective constrains. • Relaxed selective pressures are the result of mechanical transmission. • The evolutionary strategy of T. vivax differs from that of T. brucei-species complex. - Abstract: The mitochondrion role changes during the digenetic life cycle of African trypanosomes. Owing to the low abundance of glucose in the insect vector (tsetse flies) the parasites are dependent upon a fully functional mitochondrion, capable of performing oxidative phosphorylation. Nevertheless, inside the mammalian host (bloodstream forms), which is rich in nutrients, parasite proliferation relies on glycolysis, and the mitochondrion is partially redundant. In this work we perform a comparative study of the mitochondrial genome (kinetoplast) in different strains of Trypanosoma vivax. The comparison was conducted between a West African strain that goes through a complete life cycle and two American strains that are mechanically transmitted (by different vectors) and remain as bloodstream forms only. It was found that while the African strain has a complete and apparently fully functional kinetoplast, the American T. vivax strains have undergone a drastic process of mitochondrial genome degradation, in spite of the recent introduction of these parasites in America. Many of their genes exhibit different types of mutations that are disruptive of function such as major deletions, frameshift causing indels and missense mutations. Moreover, all but three genes (A6-ATPase, RPS12 and MURF2) are not edited in the American strains, whereas editing takes place normally in all (editable) genes from the African strain. Two of these genes, A6-ATPase and RPS12, are known to play an essential function during bloodstream stage

Kinetoplast adaptations in American strains from Trypanosoma vivax

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Greif, Gonzalo [Unidad de Biología Molecular, Institut Pasteur de Montevideo (Uruguay); Rodriguez, Matías [Sección Biomatemática, Facultad de Ciencias, Universidad de la Republica (Uruguay); Reyna-Bello, Armando [Departamento de Ciencias de la Vida, Carrera en Ingeniería en Biotecnología, Universidad de las Fuerzas Armadas (Ecuador); Centro de Estudios Biomédicos y Veterinarios, Universidad Nacional Experimental Simón Rodríguez-IDECYT, Caracas (Venezuela, Bolivarian Republic of); Robello, Carlos [Unidad de Biología Molecular, Institut Pasteur de Montevideo (Uruguay); Departamento de Bioquímica, Facultad de Medicina, Universidad de la República Uruguay (Uruguay); Alvarez-Valin, Fernando, E-mail: falvarez@fcien.edu.uy [Sección Biomatemática, Facultad de Ciencias, Universidad de la Republica (Uruguay)

2015-03-15

Highlights: • American T. vivax strains exhibit a drastic process of mitochondrial genome degradation. • T. vivax mitochondrial genes have among the fastest evolutionary rates in eukaryotes. • High rates of kDNA evolution are associated with relaxation of selective constrains. • Relaxed selective pressures are the result of mechanical transmission. • The evolutionary strategy of T. vivax differs from that of T. brucei-species complex. - Abstract: The mitochondrion role changes during the digenetic life cycle of African trypanosomes. Owing to the low abundance of glucose in the insect vector (tsetse flies) the parasites are dependent upon a fully functional mitochondrion, capable of performing oxidative phosphorylation. Nevertheless, inside the mammalian host (bloodstream forms), which is rich in nutrients, parasite proliferation relies on glycolysis, and the mitochondrion is partially redundant. In this work we perform a comparative study of the mitochondrial genome (kinetoplast) in different strains of Trypanosoma vivax. The comparison was conducted between a West African strain that goes through a complete life cycle and two American strains that are mechanically transmitted (by different vectors) and remain as bloodstream forms only. It was found that while the African strain has a complete and apparently fully functional kinetoplast, the American T. vivax strains have undergone a drastic process of mitochondrial genome degradation, in spite of the recent introduction of these parasites in America. Many of their genes exhibit different types of mutations that are disruptive of function such as major deletions, frameshift causing indels and missense mutations. Moreover, all but three genes (A6-ATPase, RPS12 and MURF2) are not edited in the American strains, whereas editing takes place normally in all (editable) genes from the African strain. Two of these genes, A6-ATPase and RPS12, are known to play an essential function during bloodstream stage

Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

International Nuclear Information System (INIS)

Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej; Rapalino, Otto; Caruso, Paul; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

2014-01-01

Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for

Genetic diversity of plasmodium vivax merozoite surface protein-3alpha (Pvmsp-3alpha) gene in Jhapa District of Nepal.

Science.gov (United States)

Adhikari, Madhav; Ranjitkar, Samir; Schousboe, Mette Leth; Alifrangis, Michael; Imwong, Mallika; Bhatta, Dwij Raj; Banjara, Megha Raj

2012-03-01

In Nepal, Plasmodium vivax accounts for approximately 80-90% of the malaria cases, but limited studies have been conducted on the genetic diversity of this parasite population. This study was carried out to determine the genetic diversity of P. vivax population sampled from subjects living in an endemic area of Jhapa District by analyzing the polymorphic merozoite surface protein-3alpha (Pvmsp-3alpha) gene by using PCR-restriction fragment length polymorphism. Three distinct genotypes were obtained from 96 samples; type A: 40 (71%), type B: 7 (13%), and type C: 9 (16%) which could be categorized into 13 allelic patterns: A1-A9, B1, B2, C1 and C2. These results indicated a high genetic diversity within the studied P. vivax population. As the transmission rate of malaria is low in Nepal, the diversity is most likely due to migration of people between the malaria endemic regions, either within the country or between Nepal and India. Similar prevalence of the three genotypes of Pvmsp-3alpha between the two countries likely supports the latter explanation.

Coinfection of Plasmodium vivax and Epstein-Barr virus: case report

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Fatih Akin

2013-02-01

Full Text Available Malaria is an acute and chronic illness characterized by paroxysms of fever, chills, sweats, fatigue, anemia, and splenomegaly. It is still an important health problem in malaria-endemic countries. Children living in malaria-endemic areas have elevated Epstein-Barr Virus (EBV loads in the circulation and acute malaria infection leads to increased levels of circulating EBV that are cleared after anti-malaria treatment. There are many reports about the association of Plasmodium falciparum (P. falciparum malaria and EBV infection. Here we report a case who had coinfection of Plasmodium vivax (P. vivax malaria and EBV infection. To the best of our knowledge this is the first case indicating the association of P. vivax malaria and EBV infection.

Development of a single nucleotide polymorphism barcode to genotype Plasmodium vivax infections.

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Mary Lynn Baniecki

2015-03-01

Full Text Available Plasmodium vivax, one of the five species of Plasmodium parasites that cause human malaria, is responsible for 25-40% of malaria cases worldwide. Malaria global elimination efforts will benefit from accurate and effective genotyping tools that will provide insight into the population genetics and diversity of this parasite. The recent sequencing of P. vivax isolates from South America, Africa, and Asia presents a new opportunity by uncovering thousands of novel single nucleotide polymorphisms (SNPs. Genotyping a selection of these SNPs provides a robust, low-cost method of identifying parasite infections through their unique genetic signature or barcode. Based on our experience in generating a SNP barcode for P. falciparum using High Resolution Melting (HRM, we have developed a similar tool for P. vivax. We selected globally polymorphic SNPs from available P. vivax genome sequence data that were located in putatively selectively neutral sites (i.e., intergenic, intronic, or 4-fold degenerate coding. From these candidate SNPs we defined a barcode consisting of 42 SNPs. We analyzed the performance of the 42-SNP barcode on 87 P. vivax clinical samples from parasite populations in South America (Brazil, French Guiana, Africa (Ethiopia and Asia (Sri Lanka. We found that the P. vivax barcode is robust, as it requires only a small quantity of DNA (limit of detection 0.3 ng/μl to yield reproducible genotype calls, and detects polymorphic genotypes with high sensitivity. The markers are informative across all clinical samples evaluated (average minor allele frequency > 0.1. Population genetic and statistical analyses show the barcode captures high degrees of population diversity and differentiates geographically distinct populations. Our 42-SNP barcode provides a robust, informative, and standardized genetic marker set that accurately identifies a genomic signature for P. vivax infections.

Development of a Single Nucleotide Polymorphism Barcode to Genotype Plasmodium vivax Infections

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Baniecki, Mary Lynn; Faust, Aubrey L.; Schaffner, Stephen F.; Park, Daniel J.; Galinsky, Kevin; Daniels, Rachel F.; Hamilton, Elizabeth; Ferreira, Marcelo U.; Karunaweera, Nadira D.; Serre, David; Zimmerman, Peter A.; Sá, Juliana M.; Wellems, Thomas E.; Musset, Lise; Legrand, Eric; Melnikov, Alexandre; Neafsey, Daniel E.; Volkman, Sarah K.; Wirth, Dyann F.; Sabeti, Pardis C.

2015-01-01

Plasmodium vivax, one of the five species of Plasmodium parasites that cause human malaria, is responsible for 25–40% of malaria cases worldwide. Malaria global elimination efforts will benefit from accurate and effective genotyping tools that will provide insight into the population genetics and diversity of this parasite. The recent sequencing of P. vivax isolates from South America, Africa, and Asia presents a new opportunity by uncovering thousands of novel single nucleotide polymorphisms (SNPs). Genotyping a selection of these SNPs provides a robust, low-cost method of identifying parasite infections through their unique genetic signature or barcode. Based on our experience in generating a SNP barcode for P. falciparum using High Resolution Melting (HRM), we have developed a similar tool for P. vivax. We selected globally polymorphic SNPs from available P. vivax genome sequence data that were located in putatively selectively neutral sites (i.e., intergenic, intronic, or 4-fold degenerate coding). From these candidate SNPs we defined a barcode consisting of 42 SNPs. We analyzed the performance of the 42-SNP barcode on 87 P. vivax clinical samples from parasite populations in South America (Brazil, French Guiana), Africa (Ethiopia) and Asia (Sri Lanka). We found that the P. vivax barcode is robust, as it requires only a small quantity of DNA (limit of detection 0.3 ng/μl) to yield reproducible genotype calls, and detects polymorphic genotypes with high sensitivity. The markers are informative across all clinical samples evaluated (average minor allele frequency > 0.1). Population genetic and statistical analyses show the barcode captures high degrees of population diversity and differentiates geographically distinct populations. Our 42-SNP barcode provides a robust, informative, and standardized genetic marker set that accurately identifies a genomic signature for P. vivax infections. PMID:25781890

Coma Associated with Microscopy-Diagnosed Plasmodium vivax: A Prospective Study in Papua, Indonesia

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Hardianto, Setiawan O.; Tjitra, Emiliana; Kenangalem, Enny; Sugiarto, Paulus; Price, Ric N.; Anstey, Nicholas M.

2011-01-01

Background Coma complicates Plasmodium falciparum infection but is uncommonly associated with P. vivax. Most series of vivax coma have been retrospective and have not utilized molecular methods to exclude mixed infections with P. falciparum. Methods We prospectively enrolled patients hospitalized in Timika, Indonesia, with a Glasgow Coma Score (GCS) ≤10 and P. vivax monoinfection on initial microscopy over a four year period. Hematological, biochemical, serological, radiological and cerebrospinal fluid (CSF) examinations were performed to identify other causes of coma. Repeat microscopy, antigen detection and polymerase chain reaction (PCR) were performed to exclude infections with other Plasmodium species. Results Of 24 patients fulfilling enrolment criteria, 5 had clear evidence for other non-malarial etiologies. PCR demonstrated 10 mixed infections and 3 P. falciparum monoinfections. 6 (25%) patients had vivax monoinfection and no apparent alternative cause, with a median GCS of 9 (range 8–10) and a median coma duration of 42 (range 36–48) hours. CSF leukocyte counts were coma was estimated at 1 in 29,486 clinical vivax infections with no deaths. In comparison, the risk of falciparum-associated coma was estimated at 1 in 1,276 clinical infections with an 18.5% mortality rate. Conclusions P. vivax-associated coma is rare, occurring 23 times less frequently than that seen with falciparum malaria, and is associated with a high proportion of non-malarial causes and mixed infections using PCR. The pathogenesis of coma associated with vivax malaria, particularly the role of comorbidities, is uncertain and requires further investigation. PMID:21666785

Nationwide genetic surveillance of Plasmodium vivax in Papua New Guinea reveals heterogeneous transmission dynamics and routes of migration amongst subdivided populations.

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Fola, Abebe A; Nate, Elma; Abby Harrison, G L; Barnadas, Céline; Hetzel, Manuel W; Iga, Jonah; Siba, Peter; Mueller, Ivo; Barry, Alyssa E

2018-03-01

The Asia Pacific Leaders in Malaria Alliance (APLMA) have committed to eliminate malaria from the region by 2030. Papua New Guinea (PNG) has the highest malaria burden in the Asia-Pacific region but with the intensification of control efforts since 2005, transmission has been dramatically reduced and Plasmodium vivax is now the dominant malaria infection in some parts of the country. To gain a better understanding of the transmission dynamics and migration patterns of P. vivax in PNG, here we investigate population structure in eight geographically and ecologically distinct regions of the country. A total of 219 P. vivax isolates (16-30 per population) were successfully haplotyped using 10 microsatellite markers. A wide range of genetic diversity (H e =0.37-0.87, R s =3.60-7.58) and significant multilocus linkage disequilibrium (LD) was observed in six of the eight populations (I A S =0.08-0.15 p-value<0.05) reflecting a spectrum of transmission intensities across the country. Genetic differentiation between regions was evident (Jost's D=0.07-0.72), with increasing divergence of populations with geographic distance. Overall, P. vivax isolates clustered into three major genetic populations subdividing the Mainland lowland and coastal regions, the Islands and the Highlands. P. vivax gene flow follows major human migration routes, and there was higher gene flow amongst Mainland parasite populations than among Island populations. The Central Province (samples collected in villages close to the capital city, Port Moresby), acts as a sink for imported infections from the three major endemic areas. These insights into P. vivax transmission dynamics and population networks will inform targeted strategies to contain malaria infections and to prevent the spread of drug resistance in PNG. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of Trypanosoma vivax in cattle in central Sudan

International Nuclear Information System (INIS)

Fadl, M.; Babiker, H.I.; Bakheit, M.A.; A Rahman, A.H.

2000-01-01

The study was conducted to validate an antibody-detection ELISA test (Ab-ELISA) using pre-coated ELISA plates with crude antigen preparation of Trypanosoma vivax and to study the prevalence of T. vivax infection in central Sudan. A total of 704 blood samples were collected from cattle in central Sudan, a known endemic area of T. vivax infection. Additionally, 74 blood samples were collected from northern Sudan (Atbra town), an area presumed to be T. vivax-free. Sera were collected during the period September 1998 to May 1999 during three different seasons (summer, autumn and winter). Under the existing laboratory conditions, the test showed a clear distinction between different controls, i.e. strong positive control (C++), weak positive control (C+), negative control (C-) and the conjugate control (Cc). A percent positivity of 25% was taken as a cut-off value to determine the positivity or negativity of the test. The acceptable optical density range of strong positive control (C++) was 0.65-1.22. Lower and upper percent positivity limits for different controls were also determined. The study showed that T. vivax is endemic in central Sudan with 1.4% prevalence based on parasitological examination and 29.26% on Ab-ELISA. The infection rate was significantly higher during the autumn and winter than in summer. Young cattle showed significantly lower infection rates than adults as indicated by both the parasitological and the Ab-ELISA test. In relation to husbandry practice, migratory cattle showed significantly higher rates of prevalence than resident cattle. There was no significant difference in average packed red cell volume (PCV) values between ELISA positive and ELISA negative animals. Calves of less than one year of age showed significantly lower PCV values when belonging to migratory herds than to resident herds. (author)

Population genetic structure and natural selection of apical membrane antigen-1 in Plasmodium vivax Korean isolates.

Science.gov (United States)

Kang, Jung-Mi; Lee, Jinyoung; Cho, Pyo-Yun; Moon, Sung-Ung; Ju, Hye-Lim; Ahn, Seong Kyu; Sohn, Woon-Mok; Lee, Hyeong-Woo; Kim, Tong-Soo; Na, Byoung-Kuk

2015-11-16

Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is a leading candidate antigen for blood stage malaria vaccine. However, antigenic variation is a major obstacle in the development of an effective vaccine based on this antigen. In this study, the genetic structure and the effect of natural selection of PvAMA-1 among Korean P. vivax isolates were analysed. Blood samples were collected from 66 Korean patients with vivax malaria. The entire PvAMA-1 gene was amplified by polymerase chain reaction and cloned into a TA cloning vector. The PvAMA-1 sequence of each isolate was sequenced and the polymorphic characteristics and effect of natural selection were analysed using the DNASTAR, MEGA4, and DnaSP programs. Thirty haplotypes of PvAMA-1, which were further classified into seven different clusters, were identified in the 66 Korean P. vivax isolates. Domain II was highly conserved among the sequences, but substantial nucleotide diversity was observed in domains I and III. The difference between the rates of non-synonymous and synonymous mutations suggested that the gene has evolved under natural selection. No strong evidence indicating balancing or positive selection on PvAMA-1 was identified. Recombination may also play a role in the resulting genetic diversity of PvAMA-1. This study is the first comprehensive analysis of nucleotide diversity across the entire PvAMA-1 gene using a single population sample from Korea. Korean PvAMA-1 had limited genetic diversity compared to PvAMA-1 in global isolates. The overall pattern of genetic polymorphism of Korean PvAMA-1 differed from other global isolates and novel amino acid changes were also identified in Korean PvAMA-1. Evidences for natural selection and recombination event were observed, which is likely to play an important role in generating genetic diversity across the PvAMA-1. These results provide useful information for the understanding the population structure of P. vivax circulating in Korea and have important

Rheopathologic Consequence of Plasmodium vivax Rosette Formation.

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Rou Zhang

2016-08-01

Full Text Available Malaria parasites dramatically alter the rheological properties of infected red blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance. This study highlights correlation between rosette formation and altered membrane deformability of P. vivax-infected erythrocytes, where the rosette-forming infected erythrocytes are significantly more rigid than their non-rosetting counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding force of 440pN resulting in stable rosette formation even under high physiological shear flow stress. Rosetting may contribute to the sequestration of PvIRBC schizonts in the host microvasculature or spleen.

Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

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Raquel M Gonçalves

Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

Design, construction and validation of a Plasmodium vivax microarray for the transcriptome profiling of clinical isolates

KAUST Repository

Boopathi, Pon Arunachalam

2016-10-09

High density oligonucleotide microarrays have been used on Plasmodium vivax field isolates to estimate whole genome expression. However, no microarray platform has been experimentally optimized for studying the transcriptome of field isolates. In the present study, we adopted both bioinformatics and experimental testing approaches to select best optimized probes suitable for detecting parasite transcripts from field samples and included them in designing a custom 15K P. vivax microarray. This microarray has long oligonucleotide probes (60 mer) that were in-situ synthesized onto glass slides using Agilent SurePrint technology and has been developed into an 8X15K format (8 identical arrays on a single slide). Probes in this array were experimentally validated and represents 4180 P. vivax genes in sense orientation, of which 1219 genes have also probes in antisense orientation. Validation of the 15K array by using field samples (n =14) has shown 99% of parasite transcript detection from any of the samples. Correlation analysis between duplicate probes (n = 85) present in the arrays showed perfect correlation (r(2) = 0.98) indicating the reproducibility. Multiple probes representing the same gene exhibited similar kind of expression pattern across the samples (positive correlation, r >= 0.6). Comparison of hybridization data with the previous studies and quantitative real-time PCR experiments were performed to highlight the microarray validation procedure. This array is unique in its design, and results indicate that the array is sensitive and reproducible. Hence, this microarray could be a valuable functional genomics tool to generate reliable expression data from P. vivax field isolates. (C) 2016 Published by Elsevier B.V.

Design, construction and validation of a Plasmodium vivax microarray for the transcriptome profiling of clinical isolates

KAUST Repository

Boopathi, Pon Arunachalam; Subudhi, Amit; Middha, Sheetal; Acharya, Jyoti; Mugasimangalam, Raja Chinnadurai; Kochar, Sanjay Kumar; Kochar, Dhanpat Kumar; Das, Ashis

2016-01-01

High density oligonucleotide microarrays have been used on Plasmodium vivax field isolates to estimate whole genome expression. However, no microarray platform has been experimentally optimized for studying the transcriptome of field isolates. In the present study, we adopted both bioinformatics and experimental testing approaches to select best optimized probes suitable for detecting parasite transcripts from field samples and included them in designing a custom 15K P. vivax microarray. This microarray has long oligonucleotide probes (60 mer) that were in-situ synthesized onto glass slides using Agilent SurePrint technology and has been developed into an 8X15K format (8 identical arrays on a single slide). Probes in this array were experimentally validated and represents 4180 P. vivax genes in sense orientation, of which 1219 genes have also probes in antisense orientation. Validation of the 15K array by using field samples (n =14) has shown 99% of parasite transcript detection from any of the samples. Correlation analysis between duplicate probes (n = 85) present in the arrays showed perfect correlation (r(2) = 0.98) indicating the reproducibility. Multiple probes representing the same gene exhibited similar kind of expression pattern across the samples (positive correlation, r >= 0.6). Comparison of hybridization data with the previous studies and quantitative real-time PCR experiments were performed to highlight the microarray validation procedure. This array is unique in its design, and results indicate that the array is sensitive and reproducible. Hence, this microarray could be a valuable functional genomics tool to generate reliable expression data from P. vivax field isolates. (C) 2016 Published by Elsevier B.V.

Differential perpetuation of malaria species among Amazonian Yanomami Amerindians.

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Laserson, K F; Wypij, D; Petralanda, I; Spielman, A; Maguire, J H

1999-05-01

To determine whether malaria perpetuates within isolated Amerindian villages in the Venezuelan Amazon, we surveyed malaria infection and disease among 1,311 Yanomami in three communities during a 16-month period. Plasmodium vivax was generally present in each of these small, isolated villages; asymptomatic infection was frequent, and clinical disease was most evident among children less than five years of age (odds ratio [OR] = 6.3, 95% confidence interval [CI] = 1.4-29.2) and among persons experiencing parasitemias > or = 1,000 parasites/mm3 of blood (OR = 45.0, 95% CI = 5.5-370.7). Plasmodium falciparum, in contrast, was less prevalent, except during an abrupt outbreak in which 72 infections resulted in symptoms in all age groups and at all levels of parasitemia, and occasionally were life-threatening. The observed endemic pattern of P. vivax infection may derive from the capacity of this pathogen to relapse, while the epidemic pattern of P. falciparum infection may reflect occasional introductions of strains carried by immigrants or residents of distant villages and the subsequent disappearance of this non-relapsing pathogen.

Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome.

Science.gov (United States)

Yoshihara, S; Ikegame, K; Kaida, K; Taniguchi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Soma, T; Ogawa, H

2012-05-01

Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

A comparative in silico linear B-cell epitope prediction and characterization for South American and African Trypanosoma vivax strains.

Science.gov (United States)

Guedes, Rafael Lucas Muniz; Rodrigues, Carla Monadeli Filgueira; Coatnoan, Nicolas; Cosson, Alain; Cadioli, Fabiano Antonio; Garcia, Herakles Antonio; Gerber, Alexandra Lehmkuhl; Machado, Rosangela Zacarias; Minoprio, Paola Marcella Camargo; Teixeira, Marta Maria Geraldes; de Vasconcelos, Ana Tereza Ribeiro

2018-02-27

Trypanosoma vivax is a parasite widespread across Africa and South America. Immunological methods using recombinant antigens have been developed aiming at specific and sensitive detection of infections caused by T. vivax. Here, we sequenced for the first time the transcriptome of a virulent T. vivax strain (Lins), isolated from an outbreak of severe disease in South America (Brazil) and performed a computational integrated analysis of genome, transcriptome and in silico predictions to identify and characterize putative linear B-cell epitopes from African and South American T. vivax. A total of 2278, 3936 and 4062 linear B-cell epitopes were respectively characterized for the transcriptomes of T. vivax LIEM-176 (Venezuela), T. vivax IL1392 (Nigeria) and T. vivax Lins (Brazil) and 4684 for the genome of T. vivax Y486 (Nigeria). The results presented are a valuable theoretical source that may pave the way for highly sensitive and specific diagnostic tools. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Variable number of tandem repeats of 9 Plasmodium vivax genes among Southeast Asian isolates.

Science.gov (United States)

Wang, Bo; Nyunt, Myat Htut; Yun, Seung-Gyu; Lu, Feng; Cheng, Yang; Han, Jin-Hee; Ha, Kwon-Soo; Park, Won Sun; Hong, Seok-Ho; Lim, Chae-Seung; Cao, Jun; Sattabongkot, Jetsumon; Kyaw, Myat Phone; Cui, Liwang; Han, Eun-Taek

2017-06-01

The variable number of tandem repeats (VNTRs) provides valuable information about both the functional and evolutionary aspects of genetic diversity. Comparative analysis of 3 Plasmodium falciparum genomes has shown that more than 9% of its open reading frames (ORFs) harbor VNTRs. Although microsatellites and VNTR genes of P. vivax were reported, the VNTR polymorphism of genes has not been examined widely. In this study, 230 P. vivax genes were analyzed for VNTRs by SERV, and 33 kinds of TR deletions or insertions from 29 P. vivax genes (12.6%) were found. Of these, 9 VNTR fragments from 8 P. vivax genes were used for PCR amplification and sequence analysis to examine the genetic diversity among 134 isolates from four Southeast Asian countries (China, Republic of Korea, Thailand, and Myanmar) with different malaria endemicity. We confirmed the existence of extensive polymorphism of VNTR fragments in field isolates. This detection provides several suitable markers for analysis of the molecular epidemiology of P. vivax field isolates. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

Science.gov (United States)

Tachibana, Shin-Ichiro; Sullivan, Steven A; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M Q; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W; Escalante, Ananias A; Carlton, Jane M; Tanabe, Kazuyuki

2012-09-01

P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

Insights into an Optimization of Plasmodium vivax Sal-1 In Vitro Culture: The Aotus Primate Model

Science.gov (United States)

Obaldía, Nicanor; Nuñez, Marlon; Dutary, Sahir; Lim, Caeul; Barnes, Samantha; Kocken, Clemens H. M.; Duraisingh, Manoj T.; Adams, John H.; Pasini, Erica M.

2016-01-01

Malaria is one of the most significant tropical diseases, and of the Plasmodium species that cause human malaria, P. vivax is the most geographically widespread. However, P. vivax remains a relatively neglected human parasite since research is typically limited to laboratories with direct access to parasite isolates from endemic field settings or from non-human primate models. This restricted research capacity is in large part due to the lack of a continuous P. vivax in vitro culture system, which has hampered the ability for experimental research needed to gain biological knowledge and develop new therapies. Consequently, efforts to establish a long-term P. vivax culture system are confounded by our poor knowledge of the preferred host cell and essential nutrients needed for in vitro propagation. Reliance on very heterogeneous P. vivax field isolates makes it difficult to benchmark parasite characteristics and further complicates development of a robust and reliable culture method. In an effort to eliminate parasite variability as a complication, we used a well-defined Aotus-adapted P. vivax Sal-1 strain to empirically evaluate different short-term in vitro culture conditions and compare them with previous reported attempts at P. vivax in vitro culture Most importantly, we suggest that reticulocyte enrichment methods affect invasion efficiency and we identify stabilized forms of nutrients that appear beneficial for parasite growth, indicating that P. vivax may be extremely sensitive to waste products. Leuko-depletion methods did not significantly affect parasite development. Formatting changes such as shaking and static cultures did not seem to have a major impact while; in contrast, the starting haematocrit affected both parasite invasion and growth. These results support the continued use of Aotus-adapted Sal-1 for development of P. vivax laboratory methods; however, further experiments are needed to optimize culture conditions to support long-term parasite

Acquired Antibody Responses against Plasmodium vivax Infection Vary with Host Genotype for Duffy Antigen Receptor for Chemokines (DARC)

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Maestre, Amanda; Muskus, Carlos; Duque, Victoria; Agudelo, Olga; Liu, Pu; Takagi, Akihide; Ntumngia, Francis B.; Adams, John H.; Sim, Kim Lee; Hoffman, Stephen L.; Corradin, Giampietro; Velez, Ivan D.; Wang, Ruobing

2010-01-01

Background Polymorphism of the Duffy Antigen Receptor for Chemokines (DARC) is associated with susceptibility to and the severity of Plasmodium vivax malaria in humans. P. vivax uses DARC to invade erythrocytes. Individuals lacking DARC are ‘resistant’ to P. vivax erythrocytic infection. However, susceptibility to P. vivax in DARC+ individuals is reported to vary between specific DARC genotypes. We hypothesized that the natural acquisition of antibodies to P. vivax blood stages may vary with the host genotype and the level of DARC expression. Furthermore, high parasitemia has been reported to effect the acquisition of immunity against pre-erythrocytic parasites. We investigated the correlation between host DARC genotypes and the frequency and magnitude of antibodies against P. vivax erythrocytic stage antigens. Methodology/Findings We assessed the frequencies and magnitudes of antibody responses against P. vivax and P. falciparum sporozoite and erythrocytic antigens in Colombian donors from malaria-endemic regions. The frequency and level of naturally-acquired antibodies against the P. vivax erythrocytic antigens merozoite surface protein 1 (PvMSP1) and Duffy binding protein (PvDBP) varied with the host DARC genotypes. Donors with one negative allele (FY*B/FY*Bnull and FY*A/FY*Bnull) were more likely to have anti-PvMSP1 and anti-PvDBP antibodies than those with two positive alleles (FY*B/FY*B and FY*A/FY*B). The lower IgG3 and IgG1 components of the total IgG response may account for the decreased responses to P. vivax erythrocytic antigens with FY*A/FY*B and FY*B/FY*B genotypes. No such association was detected with P. falciparum erythrocytic antigens, which does not use DARC for erythrocyte invasion. Conclusion/Significance Individuals with higher DARC expression, which is associated with higher susceptibility to P. vivax infection, exhibited low frequencies and magnitudes of P. vivax blood-stage specific antibody responses. This may indicate that one of the

Acquired antibody responses against Plasmodium vivax infection vary with host genotype for duffy antigen receptor for chemokines (DARC.

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Amanda Maestre

2010-07-01

Full Text Available Polymorphism of the Duffy Antigen Receptor for Chemokines (DARC is associated with susceptibility to and the severity of Plasmodium vivax malaria in humans. P. vivax uses DARC to invade erythrocytes. Individuals lacking DARC are 'resistant' to P. vivax erythrocytic infection. However, susceptibility to P. vivax in DARC+ individuals is reported to vary between specific DARC genotypes. We hypothesized that the natural acquisition of antibodies to P. vivax blood stages may vary with the host genotype and the level of DARC expression. Furthermore, high parasitemia has been reported to effect the acquisition of immunity against pre-erythrocytic parasites. We investigated the correlation between host DARC genotypes and the frequency and magnitude of antibodies against P. vivax erythrocytic stage antigens.We assessed the frequencies and magnitudes of antibody responses against P. vivax and P. falciparum sporozoite and erythrocytic antigens in Colombian donors from malaria-endemic regions. The frequency and level of naturally-acquired antibodies against the P. vivax erythrocytic antigens merozoite surface protein 1 (PvMSP1 and Duffy binding protein (PvDBP varied with the host DARC genotypes. Donors with one negative allele (FY*B/FY*Bnull and FY*A/FY*Bnull were more likely to have anti-PvMSP1 and anti-PvDBP antibodies than those with two positive alleles (FY*B/FY*B and FY*A/FY*B. The lower IgG3 and IgG1 components of the total IgG response may account for the decreased responses to P. vivax erythrocytic antigens with FY*A/FY*B and FY*B/FY*B genotypes. No such association was detected with P. falciparum erythrocytic antigens, which does not use DARC for erythrocyte invasion.Individuals with higher DARC expression, which is associated with higher susceptibility to P. vivax infection, exhibited low frequencies and magnitudes of P. vivax blood-stage specific antibody responses. This may indicate that one of the primary mechanisms by which P. vivax evades

Increased susceptibility of blood type O individuals to develop anemia in Plasmodium vivax infection.

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Resende, Sarah Stela; Milagres, Vanessa Gonçalves; Chaves, Daniel Gonçalves; Fontes, Cor Jesus Fernandes; Carvalho, Luzia Helena; Sousa, Tais Nobrega; Brito, Cristiana Ferreira Alves de

2017-06-01

Plasmodium vivax has been reported to cause severe malaria, and one of the main resulting complications is anemia. Considering that P. vivax infects only young erythrocytes, anemia has been associated with the destruction of infected and non-infected erythrocytes. However, few studies have focused on understanding the relationship between the pathogenesis of P. vivax malaria and human genetic polymorphisms. Although ABO groups seem to influence the outcome of Plasmodium falciparum malaria, the association between P. vivax and ABO blood groups has been minimally investigated. Thus, we investigate the correlation between ABO blood groups and anemia induced by P. vivax infection. Five single nucleotide polymorphisms at the ABO gene were genotyped by PCR-RFLP and Real-Time PCR in P. vivax-infected subjects. The ABO blood types were associated with the hematological data of the patients. Our main finding was that type O infected-individuals showed lower levels of hemoglobin and hematocrit compared to type A-infected individuals. The correlation between ABO blood groups and hemoglobin levels remained significant when a multiple linear regression was applied with the possible confounding effects of clinical-epidemiologic variables taken into account. The finding that type O individuals have a higher frequency of anemia is a first step to understand the mechanisms involved in malaria anemia, which could be associated to increased destruction of type O erythrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras.

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Lopez, Ana Cecilia; Ortiz, Andres; Coello, Jorge; Sosa-Ochoa, Wilfredo; Torres, Rosa E Mejia; Banegas, Engels I; Jovel, Irina; Fontecha, Gustavo A

2012-11-26

Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite's circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras. Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed. A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n = 77) for pvama-1; 23 (n = 84) for pvcsp; and 23 (n = 35) for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2) was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n = 30) block 2 (K1, MAD20, and RO33), and both allelic families described for the central domain of pfmsp-2 (n = 11) (3D7 and FC27) were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.

Mining geographic variations of Plasmodium vivax for active surveillance: a case study in China.

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Shi, Benyun; Tan, Qi; Zhou, Xiao-Nong; Liu, Jiming

2015-05-27

Geographic variations of an infectious disease characterize the spatial differentiation of disease incidences caused by various impact factors, such as environmental, demographic, and socioeconomic factors. Some factors may directly determine the force of infection of the disease (namely, explicit factors), while many other factors may indirectly affect the number of disease incidences via certain unmeasurable processes (namely, implicit factors). In this study, the impact of heterogeneous factors on geographic variations of Plasmodium vivax incidences is systematically investigate in Tengchong, Yunnan province, China. A space-time model that resembles a P. vivax transmission model and a hidden time-dependent process, is presented by taking into consideration both explicit and implicit factors. Specifically, the transmission model is built upon relevant demographic, environmental, and biophysical factors to describe the local infections of P. vivax. While the hidden time-dependent process is assessed by several socioeconomic factors to account for the imported cases of P. vivax. To quantitatively assess the impact of heterogeneous factors on geographic variations of P. vivax infections, a Markov chain Monte Carlo (MCMC) simulation method is developed to estimate the model parameters by fitting the space-time model to the reported spatial-temporal disease incidences. Since there is no ground-truth information available, the performance of the MCMC method is first evaluated against a synthetic dataset. The results show that the model parameters can be well estimated using the proposed MCMC method. Then, the proposed model is applied to investigate the geographic variations of P. vivax incidences among all 18 towns in Tengchong, Yunnan province, China. Based on the geographic variations, the 18 towns can be further classify into five groups with similar socioeconomic causality for P. vivax incidences. Although this study focuses mainly on the transmission of P. vivax

Lipid peroxidation and antioxidant enzymes activity in Plasmodium vivax malaria patients evolving with cholestatic jaundice

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2013-01-01

Background Plasmodium vivax infection has been considered a benign and self-limiting disease, however, recent studies highlight the association between vivax malaria and life-threatening manifestations. Increase in reactive oxygen species has already been described in vivax malaria, as a result of the increased metabolic rate triggered by the multiplying parasite, and large quantities of toxic redox-active byproducts generated. The present study aimed to study the oxidative stress responses in patients infected with P. vivax, who developed jaundice (hyperbilirubinaemia) in the course of the disease, a common clinical complication related to this species. Methods An evaluation of the lipid peroxidation and antioxidant enzymes profile was performed in 28 healthy individuals and compared with P. vivax infected patients with jaundice, i.e., bilirubin jaundice (34 patients), on day 1 (D1) and day 14 (D14) after anti-malarial therapy. Results Hyperbilirubinaemia was more frequent among women and patients experiencing their first malarial infection, and lower haemoglobin and higher lactate dehydrogenase levels were observed in this group. Malondialdehyde levels and activity of celuroplasmin and glutathione reductase were increased in the plasma from patients with P. vivax with jaundice compared to the control group on D1. However, the activity of thioredoxin reductase was decreased. The enzymes glutathione reductase, thioredoxin reductase, thiols and malondialdehyde also differed between jaundiced versus non-jaundiced patients. On D14 jaundice and parasitaemia had resolved and oxidative stress biomarkers were very similar to the control group. Conclusion Cholestatic hyperbilirubinaemia in vivax malaria cannot be totally disassociated from malaria-related haemolysis. However, significant increase of lipid peroxidation markers and changes in antioxidant enzymes in patients with P. vivax-related jaundice was observed. These results suggest oxidative processes contributing

Caveolins and flotillin-2 are present in the blood stages of Plasmodium vivax.

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Bracho, Carmen; Dunia, Irene; Romano, Mirtha; Raposo, Graça; De La Rosa, Mercedes; Benedetti, Ennio-Lucio; Pérez, Hilda A

2006-07-01

Blood stages of Plasmodium vivax induce the development of caveolae and caveola-vesicle complexes (CVC) in the membrane of their host erythrocyte. Caveolae are found in almost all types of cells and are involved in endogenous processes as calcium and cholesterol homeostasis, cell signalling, transporting, ligand internalization and transcytosis of serum components. Major structural components of caveolae are the proteins caveolins and flotillins. The functional role of caveolae in the P. vivax-infected erythrocyte is not properly understood. As these organelles have been shown to contain malaria antigens, it has been suggested that they are involved in the transport and release of specific parasite antigens from the infected erythrocyte and in the uptake of plasma proteins. Using specific antibodies to classical caveolae proteins and an immunolocalization approach, we found caveolin-2, caveolin-3, and flotillin-2 in the vesicle profiles and some CVC of P. vivax-infected erythrocytes. Caveolin-1-3 were not found in uninfected erythrocytes. This is the first report of identification and localization of caveolins in the CVC present in erythrocytes infected with P. vivax, thereby providing evidence of the role of this particular organelle in the protein-trafficking pathway that connect parasite-encoded proteins with the erythrocyte cytoplasm and the cell surface throughout the asexual blood cycle of vivax malaria parasite.

Unexpectedly long incubation period of Plasmodium vivax malaria, in the absence of chemoprophylaxis, in patients diagnosed outside the transmission area in Brazil

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da Silveira Bressan Clarisse

2011-05-01

Full Text Available Abstract Background In 2010, Brazil recorded 3343,599 cases of malaria, with 99.6% of them concentrated in the Amazon region. Plasmodium vivax accounts for 86% of the cases circulating in the country. The extra-Amazonian region, where transmission does not occur, recorded about 566 cases imported from the Amazonian area in Brazil and South America, from Central America, Asia and African countries. Prolonged incubation periods have been described for P. vivax malaria in temperate climates. The diversity in essential biological characteristics is traditionally considered as one possible explanation to the emergence of relapse in malaria and to the differences in the duration of the incubation period, which can also be explained by the use of chemoprophylaxis. Studying the reported cases of P. vivax malaria in Rio de Janeiro, where there is no vector transmission, has made it possible to evaluate the extension of the incubation period and to notice that it may be extended in some cases. Methods Descriptive study of every malaria patients who visited the clinic in the last five years. The mean, standard deviation, median, minimum and maximum of all incubation periods were analysed. Results From the total of 80 patients seen in the clinic during the study time, with confirmed diagnosis of malaria, 49 (63% were infected with P. vivax. Between those, seven had an estimated incubation period varying from three to 12 months and were returned travellers from Brazilian Amazonian states (6 and Indonesia (1. None of them had taken malarial chemoprophylaxis. Conclusions The authors emphasize that considering malaria as a possible cause of febrile syndrome should be a post-travel routine, independent of the time elapsed after exposure in the transmission area, even in the absence of malaria chemoprophylaxis. They speculate that, since there is no current and detailed information about the biological cycle of human malaria plasmodia's in Brazil, it is possible

Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.

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Jessica B Hostetler

2016-10-01

Full Text Available Plasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite's ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP in merozoites and the Duffy antigen receptor for chemokines (DARC on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P. vivax genomes contain two copies of the PvDBP gene. The frequency of this duplication is particularly high in Madagascar, where there is also evidence for P. vivax infection in DARC-negative individuals. The functional significance and global prevalence of this duplication, and whether there are other copy number variations at the PvDBP locus, is unknown.Using whole-genome sequencing and PCR to study the PvDBP locus in P. vivax clinical isolates, we found that PvDBP duplication is widespread in Cambodia. The boundaries of the Cambodian PvDBP duplication differ from those previously identified in Madagascar, meaning that current molecular assays were unable to detect it. The Cambodian PvDBP duplication did not associate with parasite density or DARC genotype, and ranged in prevalence from 20% to 38% over four annual transmission seasons in Cambodia. This duplication was also present in P. vivax isolates from Brazil and Ethiopia, but not India.PvDBP duplications are much more widespread and complex than previously thought, and at least two distinct duplications are circulating globally. The same duplication boundaries were identified in parasites from three continents, and were found at high prevalence in human populations where DARC-negativity is essentially absent. It is therefore unlikely that PvDBP duplication is associated with infection of DARC-negative individuals, but functional tests will be required to confirm this hypothesis.

The Robust and Modulated Biomarker Network Elicited by the Plasmodium vivax Infection Is Mainly Mediated by the IL-6/IL-10 Axis and Is Associated with the Parasite Load

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Allyson Guimarães da Costa

2014-01-01

Full Text Available Background. Recent studies have shown that the inflammatory process, including the biomarker production, and the intense activation of innate immune responses are greater in the malaria caused by Plasmodium vivax than other species. Here, we examined the levels of serum biomarkers and their interaction during acute malaria. Material and Methods. Blood samples were collected from P. vivax-infected patients at admission and from healthy donors. Levels of serum biomarkers were measured by Cytometric Bead Assay or ELISA. Results. P. vivax infection triggered the production of both inflammatory and regulatory biomarkers. Levels of IL-6, CXCL-8, IFN-γ, IL-5, and IL-10 were higher in P. vivax-infected patients than in healthy donors. On the other hand, malaria patients produced lower levels of TNF-α, IL-12p70, and IL-2 than healthy individuals. While the levels of IL-10 and IL-6 were found independent on the number of malaria episodes, higher levels of these cytokines were seen in patients with higher parasite load. Conclusion. A mixed pattern of proinflammatory and regulatory biomarkers is produced in P. vivax malaria. Analysis of biomarker network suggests that IL-10 and IL-6 are a robust axis in malaria patients and that this interaction seems to be associated with the parasite load.

Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

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Kalincik, Tomas

2015-01-01

Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. © 2015 S. Karger AG, Basel.

Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

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Ribeiro, Bruno de Paulo; Cassiano, Gustavo Capatti; de Souza, Rodrigo Medeiros; Cysne, Dalila Nunes; Grisotto, Marcos Augusto Grigolin; de Azevedo dos Santos, Ana Paula Silva; Marinho, Cláudio Romero Farias; Machado, Ricardo Luiz Dantas; Nascimento, Flávia Raquel Fernandes

2016-01-01

Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection. PMID:26943639

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

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Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

2017-12-01

To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

Genome-wide diversity and differentiation in New World populations of the human malaria parasite Plasmodium vivax.

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de Oliveira, Thais C; Rodrigues, Priscila T; Menezes, Maria José; Gonçalves-Lopes, Raquel M; Bastos, Melissa S; Lima, Nathália F; Barbosa, Susana; Gerber, Alexandra L; Loss de Morais, Guilherme; Berná, Luisa; Phelan, Jody; Robello, Carlos; de Vasconcelos, Ana Tereza R; Alves, João Marcelo P; Ferreira, Marcelo U

2017-07-01

The Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax. We used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences), Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19). We found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10-4 and 6.2 × 10-4) as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed) in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between parasite lineages from geographically diverse sites

Cluster of Imported Vivax Malaria in Travelers Returning From Peru.

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Weitzel, Thomas; Labarca, Jaime; Cortes, Claudia P; Rosas, Reinaldo; Balcells, M Elvira; Perret, Cecilia

2015-01-01

We report a cluster of imported vivax malaria in three of five Chilean travelers returning from Peru in March 2015. The cluster highlights the high risk of malaria in the Loreto region in northern Peru, which includes popular destinations for international nature and adventure tourism. According to local surveillance data, Plasmodium vivax is predominating, but Plasmodium falciparum is also present, and the incidence of both species has increased during recent years. Travelers visiting this region should be counseled about the prevention of malaria and the options for chemoprophylaxis. © 2015 International Society of Travel Medicine.

A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

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Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

2015-01-01

Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

Expression of Plasmodium vivax crt-o Is Related to Parasite Stage but Not Ex Vivo Chloroquine Susceptibility.

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Pava, Zuleima; Handayuni, Irene; Wirjanata, Grennady; To, Sheren; Trianty, Leily; Noviyanti, Rintis; Poespoprodjo, Jeanne Rini; Auburn, Sarah; Price, Ric N; Marfurt, Jutta

2016-01-01

Chloroquine (CQ)-resistant Plasmodium vivax is present in most countries where P. vivax infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivax crt-o (pvcrt-o) has been correlated with in vivo CQ resistance in an area with low-grade resistance. We assessed pvcrt-o expression in isolates from Papua (Indonesia), where P. vivax is highly CQ resistant. Ex vivo drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-o were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-o expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivax β-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivax aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5; P determinant of ex vivo drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivax drug resistance. Copyright © 2015 Pava et al.

Marker discovery in Trypanosoma vivax through GSS and comparative analysis. Preliminary data and perspectives

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Davila, A.M.R.; Guerreiro, L.T.A.; Souza, S.S.

2005-01-01

Trypanosoma vivax is a haemoparasite affecting the livestock industry in South America and Africa. Despite the high economic relevance of the disease caused by T. vivax, little work has been done on its molecular characterization, in contrast with human trypanosomes, such as T. brucei and T. cruzi. The present study reports the construction of a semi-normalized genomic library and the sequencing of 160 Genome Sequence Survey (GSS) ends of T. vivax. The analyses of this preliminary data show that this simple and rapid approach worked well to generate some potential new markers for this species. (author)

Fitness components and natural selection: why are there different patterns on the emergence of drug resistance in Plasmodium falciparum and Plasmodium vivax?

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Schneider Kristan A

2013-01-01

Full Text Available Abstract Background Considering the distinct biological characteristics of Plasmodium species is crucial for control and elimination efforts, in particular when facing the spread of drug resistance. Whereas the evolutionary fitness of all malarial species could be approximated by the probability of being taken by a mosquito and then infecting a new host, the actual steps in the malaria life cycle leading to a successful transmission event show differences among Plasmodium species. These “steps” are called fitness components. Differences in terms of fitness components may affect how selection imposed by interventions, e.g. drug treatments, differentially acts on each Plasmodium species. Thus, a successful malaria control or elimination programme should understand how differences in fitness components among different malaria species could affect adaptive evolution (e.g. the emergence of drug resistance. In this investigation, the interactions between some fitness components and natural selection are explored. Methods A population-genetic model is formulated that qualitatively explains how different fitness components (in particular gametocytogenesis and longevity of gametocytes affect selection acting on merozoites during the erythrocytic cycle. By comparing Plasmodium falciparum and Plasmodium vivax, the interplay of parasitaemia and gametocytaemia dynamics in determining fitness is modelled under circumstances that allow contrasting solely the differences between these two parasites in terms of their fitness components. Results By simulating fitness components, it is shown that selection acting on merozoites (e.g., on drug resistant mutations or malaria antigens is more efficient in P. falciparum than in P. vivax. These results could explain, at least in part, why resistance against drugs, such as chloroquine (CQ is highly prevalent in P. falciparum worldwide, while CQ is still a successful treatment for P. vivax despite its massive use

Naloxone injections into CA3 disrupt pattern completion associated with relapse from cocaine seeking

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Kirk, Ryan A.; Clark, Jascha K.; Moore, Angela; Keefe, Kristen

2016-01-01

The goal of the present research was to assess the degree to which a pattern completion process operates in cue-induced relapse to cocaine-seeking behavior. Using a novel cue-preference version of the place preference task, rats were administered cocaine or saline, which resulted in a preference for the cocaine-paired cues. After 21 days of abstinence and prior to the preference test, for one group, PBS or naloxone was injected into the CA3 subregion of the hippocampus and for a second group, saline or naloxone was injected systemically. The results indicated that infusions of naloxone into CA3 or systemic injections produced a marked disruption for one and two cues, but had minimal disruptive effect for three or four cues, suggesting that naloxone injections disrupt CA3 function and trigger a deficit in a pattern completion process. Thus, it appears that cue-based activation of the dorsal CA3 might be a critical trigger via a pattern completion process. Based on additional analyses it appears that there is a disruption primarily for object touches for one cue naloxone injections into the CA3 or systemic injections, but no effect on time (spatial context). PMID:26815290

A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children.

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Cristian Koepfli

Full Text Available When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax ((molFOB, i.e. the number of genetically distinct blood-stage infections over time, and compared it to previously reported values for P. falciparum.P. vivax (molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years.On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR = 1.99, 95% confidence interval (CI95 [1.80, 2.19], (molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001 compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02.P. vivax (molFOB is considerably higher than P. falciparum (molFOB (5.5 clones/child/year-at-risk. The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1

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Patarroyo Manuel E

2011-10-01

Full Text Available Abstract Background Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P. vivax rhoptry neck protein 1 (PvRON1 and examine its antigenicity in natural P. vivax infections. Methods The PvRON1 encoding gene, which is homologous to that encoding the P. falciparum apical sushi protein (ASP according to the plasmoDB database, was selected as our study target. The pvron1 gene transcription was evaluated by RT-PCR using RNA obtained from the P. vivax VCG-1 strain. Two peptides derived from the deduced P. vivax Sal-I PvRON1 sequence were synthesized and inoculated in rabbits for obtaining anti-PvRON1 antibodies which were used to confirm the protein expression in VCG-1 strain schizonts along with its association with detergent-resistant microdomains (DRMs by Western blot, and its localization by immunofluorescence assays. The antigenicity of the PvRON1 protein was assessed using human sera from individuals previously exposed to P. vivax malaria by ELISA. Results In the P. vivax VCG-1 strain, RON1 is a 764 amino acid-long protein. In silico analysis has revealed that PvRON1 shares essential characteristics with different antigens involved in invasion, such as the presence of a secretory signal, a GPI-anchor sequence and a putative sushi domain. The PvRON1 protein is expressed in parasite's schizont stage, localized in rhoptry necks and it is associated with DRMs. Recombinant protein recognition by human sera indicates that this antigen can trigger an immune response during a natural infection with P. vivax. Conclusions This study shows the identification and characterization of

High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

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Löscher Thomas

2006-07-01

Full Text Available Abstract Background In Ethiopia, malaria is caused by both Plasmodium falciparum and Plasmodium vivax. Drug resistance of P. falciparum to sulfadoxine-pyrimethamine (SP and chloroquine (CQ is frequent and intense in some areas. Methods In 100 patients with uncomplicated malaria from Dilla, southern Ethiopia, P. falciparum dhfr and dhps mutations as well as P. vivax dhfr polymorphisms associated with resistance to SP and P. falciparum pfcrt and pfmdr1 mutations conferring CQ resistance were assessed. Results P. falciparum and P. vivax were observed in 69% and 31% of the patients, respectively. Pfdhfr triple mutations and pfdhfr/pfdhps quintuple mutations occurred in 87% and 86% of P. falciparum isolates, respectively. Pfcrt T76 was seen in all and pfmdr1 Y86 in 81% of P. falciparum. The P. vivax dhfr core mutations N117 and R58 were present in 94% and 74%, respectively. Conclusion These data point to an extraordinarily high frequency of drug-resistance mutations in both P. falciparum and P. vivax in southern Ethiopia, and strongly support that both SP and CQ are inadequate drugs for this region.

Genetic diversity of Plasmodium Vivax revealed by the merozoite surface protein-1 icb5-6 fragment.

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Ruan, Wei; Zhang, Ling-Ling; Feng, Yan; Zhang, Xuan; Chen, Hua-Liang; Lu, Qiao-Yi; Yao, Li-Nong; Hu, Wei

2017-06-05

Plasmodium vivax remains a potential cause of morbidity and mortality for people living in its endemic areas. Understanding the genetic diversity of P. vivax from different regions is valuable for studying population dynamics and tracing the origins of parasites. The PvMSP-1 gene is highly polymorphic and has been used as a marker in many P. vivax population studies. The aim of this study was to investigate the genetic diversity of the PvMSP-1 gene icb5-6 fragment and to provide more genetic polymorphism data for further studies on P. vivax population structure and tracking of the origin of clinical cases. Nested PCR and sequencing of the PvMSP-1 icb5-6 marker were performed to obtain the nucleotide sequences of 95 P. vivax isolates collected from Zhejiang province, China. To investigate the genetic diversity of PvMSP-1, the 95 nucleotide sequences of the PvMSP-1 icb5-6 fragment were genotyped and analyzed using DnaSP v5, MEGA software. The 95 P. vivax isolates collected from Zhejiang province were either indigenous cases or imported cases from different regions around the world. A total of 95 sequences ranging from 390 to 460 bp were obtained. The 95 sequences were genotyped into four allele-types (Sal I, Belem, R-III and R-IV) and 17 unique haplotypes. R-III and Sal I were the predominant allele-types. The haplotype diversity (Hd) and nucleotide diversity (Pi) were estimated to be 0.729 and 0.062, indicating that the PvMSP-1 icb5-6 fragment had the highest level of polymorphism due to frequent recombination processes and single nucleotide polymorphism. The values of dN/dS and Tajima's D both suggested neutral selection for the PvMSP-1icb5-6 fragment. In addition, a rare recombinant style of R-IV type was identified. This study presented high genetic diversity in the PvMSP-1 marker among P. vivax strains from around the world. The genetic data is valuable for expanding the polymorphism information on P. vivax, which could be helpful for further study on

High incidence of Plasmodium vivax malaria in newly arrived Eritrean refugees in Sweden since May 2014.

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Sonden, K; Castro, E; Törnnberg, L; Stenstrom, C; Tegnell, A; Farnert, A

2014-09-04

Since May 2014, an increase in Plasmodium vivax malaria has been observed in Sweden. As of 31 August 2014, 105 malaria cases have been reported in newly arrived Eritrean refugees, 84 of them P. vivax. The patients were mainly young men and reported migration through Ethiopia and/or Sudan. Severe anaemia and long symptom duration reflect inadequate healthcare during migration. Countries currently hosting Eritrean refugees need to consider P. vivax malaria in this group of migrants.

Multiplicity and diversity of Plasmodium vivax infections in a highly endemic region in Papua New Guinea.

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Cristian Koepfli

2011-12-01

Full Text Available Plasmodium vivax is highly endemic in the lowlands of Papua New Guinea and accounts for a large proportion of the malaria cases in children less than 5 years of age. We collected 2117 blood samples at 2-monthly intervals from a cohort of 268 children aged 1 to 4.5 years and estimated the diversity and multiplicity of P. vivax infection. All P. vivax clones were genotyped using the merozoite surface protein 1 F3 fragment (msp1F3 and the microsatellite MS16 as molecular markers. High diversity was observed with msp1F3 (H(E = 88.1% and MS16 (H(E = 97.8%. Of the 1162 P. vivax positive samples, 74% harbored multi-clone infections with a mean multiplicity of 2.7 (IQR = 1-3. The multiplicity of P. vivax infection increased slightly with age (P = 0.02, with the strongest increase in very young children. Intensified efforts to control malaria can benefit from knowledge of the diversity and MOI both for assessing the endemic situation and monitoring the effects of interventions.

Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies

OpenAIRE

Payne, Ruth O.; Silk, Sarah E.; Elias, Sean C.; Milne, Kathryn H.; Rawlinson, Thomas A.; Llewellyn, David; Shakri, A. Rushdi; Jin, Jing; Labb?, Genevi?ve M.; Edwards, Nick J.; Poulton, Ian D.; Roberts, Rachel; Farid, Ryan; J?rgensen, Thomas; Alanine, Daniel G.W.

2017-01-01

BACKGROUND: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vac...

Severe malaria vivax with sepsis bacterial: a case report

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Tarigan, P.; Ginting, F.

2018-03-01

Malaria cases are often misdiagnosis by clinicians in tropical areas like Indonesia. Some cases show overlapping signs and symptoms of another infection that are common in the tropical areas such as typhoid, dengue, and leptospirosis. It can be misdiagnosed in practice and led to a wrong management that can end fatally. Severe malaria is usually caused by Plasmodium falciparum. P. vivax can also cause severe malaria but the cases reported are uncommon. Since infections with severe P. vivax that generally results in serious disease is quite uncommon in Indonesia, their identification and management are important. We report a case of severe malaria with sepsis, renal injury and hepatic impairment associated with malaria in a 70-year-old male. Clinical manifestations included anemia, sepsis, and elevated serum creatinine, urea, total bilirubin, and procalcitonin. The rapid diagnostic test for malaria and microscopic examination of blood smears were positive for P. vivax. The patient was treated as severe malaria with intravenous artesunate for six days, followed by oral treatment of primaquine for 14 days. Intravenous fluid therapy, antipyretic, anti-malaria and antibiotic treatment were administered. The patient was stable and then discharged from the hospital. The prognosis depends much on early diagnosis and appropriate supportive treatment.

Genome-wide diversity and differentiation in New World populations of the human malaria parasite Plasmodium vivax.

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Thais C de Oliveira

2017-07-01

Full Text Available The Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax.We used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences, Peru (PER, n = 23, Colombia (COL, n = 31, and Mexico (MEX, n = 19.We found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10-4 and 6.2 × 10-4 as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092. Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between parasite lineages from geographically

Genome-wide diversity and differentiation in New World populations of the human malaria parasite Plasmodium vivax

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de Oliveira, Thais C.; Rodrigues, Priscila T.; Menezes, Maria José; Gonçalves-Lopes, Raquel M.; Bastos, Melissa S.; Lima, Nathália F.; Barbosa, Susana; Gerber, Alexandra L.; Loss de Morais, Guilherme; Berná, Luisa; Phelan, Jody; Robello, Carlos; de Vasconcelos, Ana Tereza R.

2017-01-01

Background The Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax. Methods We used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences), Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19). Principal findings/Conclusions We found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10−4 and 6.2 × 10−4) as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed) in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between

Long-Term Outcomes and Patterns of Relapse of Early-Stage Extranodal Marginal Zone Lymphoma Treated With Radiation Therapy With Curative Intent

International Nuclear Information System (INIS)

Teckie, Sewit; Qi, Shunan; Lovie, Shona; Navarrett, Scott; Hsu, Meier; Noy, Ariela; Portlock, Carol; Yahalom, Joachim

2015-01-01

Purpose: To report the long-term outcome and patterns of relapse of a large cohort of marginal zone lymphoma (MZL) patients treated with curative-intent radiation therapy (RT) alone. Patients and Methods: We reviewed the charts of 490 consecutive patients with stage IE or IIE MZL referred between 1992 and 2012 to our institution. Of those, 244 patients (50%) were treated with RT alone. Pathology was confirmed by hematopathologists at our institution. Patient and disease factors were analyzed for association with relapse-free survival (RFS) and overall survival (OS). Results: Median age of the cohort was 59 years, and median follow-up was 5.2 years. Ann Arbor stage was IE in 92%. Most common disease sites were stomach (50%), orbit (18%), non-thyroid head-and-neck (8%), skin (8%), and breast (5%). Median RT dose was 30 Gy. Five-year OS and RFS were 92% and 74%, respectively. Cumulative incidence of disease-specific death was just 1.1% by 5 years. Sixty patients (24%) developed relapse of disease; 10 were in the RT field. Crude rate of transformation to pathologically confirmed large-cell lymphoma was 1.6%. On multivariable analysis, primary disease site (P=.007) was independently associated with RFS, along with age (P=.04), presence of B-symptoms (P=.02), and International Prognostic Index risk group (P=.03). All disease sites except for head-and-neck had worse RFS relative to stomach. Conclusion: Overall and cause-specific survival are high in early-stage extra-nodal MZL treated with curative RT alone. In this large cohort of 244 patients, most patients did not experience relapse of MZL after curative RT; when relapses did occur, the majority were in distant sites. Stomach cases were less likely to relapse than other anatomic sites. Transformation to large-cell lymphoma was rare

Plasmodium vivax Diversity and Population Structure across Four Continents.

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Koepfli, Cristian; Rodrigues, Priscila T; Antao, Tiago; Orjuela-Sánchez, Pamela; Van den Eede, Peter; Gamboa, Dionicia; van Hong, Nguyen; Bendezu, Jorge; Erhart, Annette; Barnadas, Céline; Ratsimbasoa, Arsène; Menard, Didier; Severini, Carlo; Menegon, Michela; Nour, Bakri Y M; Karunaweera, Nadira; Mueller, Ivo; Ferreira, Marcelo U; Felger, Ingrid

2015-01-01

Plasmodium vivax is the geographically most widespread human malaria parasite. To analyze patterns of microsatellite diversity and population structure across countries of different transmission intensity, genotyping data from 11 microsatellite markers was either generated or compiled from 841 isolates from four continents collected in 1999-2008. Diversity was highest in South-East Asia (mean allelic richness 10.0-12.8), intermediate in the South Pacific (8.1-9.9) Madagascar and Sudan (7.9-8.4), and lowest in South America and Central Asia (5.5-7.2). A reduced panel of only 3 markers was sufficient to identify approx. 90% of all haplotypes in South Pacific, African and SE-Asian populations, but only 60-80% in Latin American populations, suggesting that typing of 2-6 markers, depending on the level of endemicity, is sufficient for epidemiological studies. Clustering analysis showed distinct clusters in Peru and Brazil, but little sub-structuring was observed within Africa, SE-Asia or the South Pacific. Isolates from Uzbekistan were exceptional, as a near-clonal parasite population was observed that was clearly separated from all other populations (FST>0.2). Outside Central Asia FST values were highest (0.11-0.16) between South American and all other populations, and lowest (0.04-0.07) between populations from South-East Asia and the South Pacific. These comparisons between P. vivax populations from four continents indicated that not only transmission intensity, but also geographical isolation affect diversity and population structure. However, the high effective population size results in slow changes of these parameters. This persistency must be taken into account when assessing the impact of control programs on the genetic structure of parasite populations.

Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

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Pan, Hubert Y.; Morani, Ajaykumar; Wang, Wei-Lien; Hess, Kenneth R.; Paulino, Arnold C.; Ludwig, Joseph A.; Lin, Patrick P.; Daw, Najat C.; Mahajan, Anita

2015-01-01

Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant

Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

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Moon, James J; Suh, Heikyung; Polhemus, Mark E; Ockenhouse, Christian F; Yadava, Anjali; Irvine, Darrell J

2012-01-01

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

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James J Moon

Full Text Available The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide acid (PLGA "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA, was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs. Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

Oligohydramnios in a pregnant Pakistani woman with Plasmodium vivax malaria.

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Binello, Nicolò; Brunetti, Enrico; Cattaneo, Federico; Lissandrin, Raffaella; Malfitano, Antonello

2014-04-23

In the Western world, the diagnosis and management of Plasmodium vivax malaria in pregnant women can be challenging, and the pathogenesis of adverse outcomes for both the mother and the foetus is still poorly known. The authors describe the case of a 29-year-old Pakistani woman at the 29th week of her second pregnancy, who was admitted to the Hospital following the abrupt onset of fever. At the time of admission, she had been living in Italy without travelling to any malaria-endemic areas for eight months. She was diagnosed with vivax malaria after a thin blood smear revealed the presence of plasmodial trophozoites and gametocytes and treated accordingly. Due to the onset of oligohydramnios, she underwent caesarian section at the 31st week of pregnancy with no further complications. Histological examination of the placenta showed no evidence of plasmodial infection, but was inconclusive. It is unclear whether oligohydramnios is a complication of pregnancy-related Plasmodium vivax malaria. Given the long latency of hypnozoites, every febrile pregnant patient with a previous stay in an endemic area should be screened for malaria with a thick and a thin blood smear.

Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America

DEFF Research Database (Denmark)

Schousboe, Mette L; Ranjitkar, Samir; Rajakaruna, Rupika S

2014-01-01

diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations. METHODS: The genetic diversity of eight P. vivax populations (n = 543) was investigated by using two microsatellites (MS), m1501 and m......3502, chosen because of their seven and eight base-pair (bp) repeat lengths, respectively. These were compared with published data of the same loci from six other P. vivax populations. RESULTS: In total, 1,440 P. vivax samples from 14 countries on three continents were compared. There was highest...... heterozygosity within Asian populations, where expected heterozygosity (He) was 0.92-0.98, and alleles with a high repeat number were more common. Pairwise FST revealed significant differentiation between most P. vivax populations, with the highest divergence found between Asian and South American populations...

Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries

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Abba, Katharine; Kirkham, Amanda J; Olliaro, Piero L; Deeks, Jonathan J; Donegan, Sarah; Garner, Paul; Takwoingi, Yemisi

2014-01-01

Background In settings where both Plasmodium vivax and Plasmodium falciparum infection cause malaria, rapid diagnostic tests (RDTs) need to distinguish which species is causing the patients' symptoms, as different treatments are required. Older RDTs incorporated two test lines to distinguish malaria due to P. falciparum, from malaria due to any other Plasmodium species (non-falciparum). These RDTs can be classified according to which antibodies they use: Type 2 RDTs use HRP-2 (for P. falciparum) and aldolase (all species); Type 3 RDTs use HRP-2 (for P. falciparum) and pLDH (all species); Type 4 use pLDH (fromP. falciparum) and pLDH (all species). More recently, RDTs have been developed to distinguish P. vivax parasitaemia by utilizing a pLDH antibody specific to P. vivax. Objectives To assess the diagnostic accuracy of RDTs for detecting non-falciparum or P. vivax parasitaemia in people living in malaria-endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria, and to identify which types and brands of commercial test best detect non-falciparum and P. vivax malaria. Search methods We undertook a comprehensive search of the following databases up to 31 December 2013: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; and IndMED. Selection criteria Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in non-falciparum endemic areas. Data collection and analysis For each study, two review authors independently extracted a standard set of data using a tailored data extraction form. We grouped comparisons by type of RDT (defined by the combinations of antibodies used), and combined in meta-analysis where appropriate. Average sensitivities and

Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4.

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Byoung-Kuk Na

2010-10-01

Full Text Available Multiple cysteine proteases of malaria parasites are required for maintenance of parasite metabolic homeostasis and egress from the host erythrocyte. In Plasmodium falciparum these proteases appear to mediate the processing of hemoglobin and aspartic proteases (plasmepsins in the acidic food vacuole and the hydrolysis of erythrocyte structural proteins at neutral pH. Two cysteine proteases, vivapain (VX-2 and VX-3 have been characterized in P. vivax, but comprehensive studies of P. vivax cysteine proteases remain elusive.We characterized a novel cysteine protease of P. vivax, VX-4, of which orthologs appears to have evolved differentially in primate plasmodia with strong cladistic affinity toward those of rodent Plasmodium. Recombinant VX-4 demonstrated dual substrate specificity depending on the surrounding micro-environmental pH. Its hydrolyzing activity against benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA and Z-Phe-Arg-MCA was highest at acidic pH (5.5, whereas that against Z-Arg-Arg-MCA was maximal at neutral pH (6.5-7.5. VX-4 preferred positively charged amino acids and Gln at the P1 position, with less strict specificity at P3 and P4. P2 preferences depended on pH (Leu at pH 5.5 and Arg at pH 7.5. Three amino acids that delineate the S2 pocket were substituted in VX-4 compared to VX-2 and VX-3 (Ala90, Gly157 and Glu180. Replacement of Glu180 abolished activity against Z-Arg-Arg-MCA at neutral pH, indicating the importance of this amino acid in the pH-dependent substrate preference. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. VX-4 showed maximal activity against actin at neutral pH, and that against P. vivax plasmepsin 4 and hemoglobin was detected at neutral/acidic and acidic pH, respectively.VX-4 demonstrates pH-dependent substrate switching, which might offer an efficient mechanism for the specific cleavage of different substrates in different intracellular

Clinical and parasitological profiles of patients with non-complicated Plasmodium falciparum and Plasmodium vivax malaria in northwestern Colombia

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Knudson-Ospina, Angélica; Sánchez-Pedraza, Ricardo; Pérez-Mazorra, Manuel Alberto; Cortés-Cortés, Liliana Jazmín; Guerra-Vega, Ángela Patricia; Nicholls-Orejuela, Rubén Santiago

2015-01-01

Antecedentes. En Colombia existen pocos estudios que buscan encontrar diferencias clínicas y parasitológicas en la malaria causada por Plasmodium falciparum y Plasmodium vivax. Objetivo. Describir el perfil clínico y parasitológico de las malarias por Plasmodium falciparum y Plasmodium vivax no complicadas en Tierralta, Córdoba, Colombia. Materiales y métodos. Se evaluaron pacientes con paludismo no complicado por Plasmodium falciparum y Plasmodium vivax según los protocolos estandarizados po...

The susceptibility of Anopheles lesteri to infection with Korean strain of Plasmodium vivax

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Kim Tong-Soo

2009-03-01

Full Text Available Abstract Background Following its recent re-emergence, malaria has gained renewed attention as a serious infectious disease in Korea. Three species of the Hyrcanusgroup, Anopheles lesteri, Anopheles sinensis and Anopheles pullus, have long been suspected malaria vectors. However, opinions about their vector ability are controversial. The present study was designed with the aim of determining the susceptibility of these mosquitoes to a Korean isolate of Plasmodium vivax. Also, An. sinensis is primarily suspected to be vector of malaria in Korea, but in Thailand, the same species is described to have less medical importance. Therefore, comparative susceptibility of Thai and Korean strains of An. sinensis with Thai strain of P. vivax may be helpful to understand whether these geographically different strains exhibit differences in their susceptibility or not. Methods The comparative susceptibility of An. lesteri, An. sinensis and An. pullus was studied by feeding laboratory-reared mosquitoes on blood from patients carrying gametocytes from Korea and Thailand. Results In experimental feeding with Korean strain of P. vivax, oocysts developed in An. lesteri, An. sinensis and An. pullus. Salivary gland sporozoites were detected only in An. lesteri and An. sinensis but not in An. pullus. Large differences were found in the number of sporozoites in the salivary glands, with An. lesteri carrying much higher densities, up to 2,105 sporozoites in a single microscope field of 750 × 560 μM, whereas a maximum of 14 sporozoites were found in any individual salivary gland of An. sinensis. Similar results were obtained from a susceptibility test of two different strains of An. sinensis to Thai isolate of P. vivax, and differences in vector susceptibility according to geographical variation were not detected. Conclusion The high sporozoite rate and sporozoite loads of An. lesteri indicate that this species is highly susceptible to infection with P. vivax

Global host metabolic response to Plasmodium vivax infection: a 1H NMR based urinary metabonomic study

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Sengupta Arjun

2011-12-01

Full Text Available Abstract Background Plasmodium vivax is responsible for the majority of malarial infection in the Indian subcontinent. This species of the parasite is generally believed to cause a relatively benign form of the disease. However, recent reports from different parts of the world indicate that vivax malaria can also have severe manifestation. Host response to the parasite invasion is thought to be an important factor in determining the severity of manifestation. In this paper, attempt was made to determine the host metabolic response associated with P. vivax infection by means of NMR spectroscopy-based metabonomic techniques in an attempt to better understand the disease pathology. Methods NMR spectroscopy of urine samples from P. vivax-infected patients, healthy individuals and non-malarial fever patients were carried out followed by multivariate statistical analysis. Two data analysis techniques were employed, namely, Principal Component Analysis [PCA] and Orthogonal Projection to Latent Structure Discriminant Analysis [OPLS-DA]. Several NMR signals from the urinary metabolites were further selected for univariate comparison among the classes. Results The urine metabolic profiles of P. vivax-infected patients were distinct from those of healthy individuals as well as of non-malarial fever patients. A highly predictive model was constructed from urine profile of malarial and non-malarial fever patients. Several metabolites were found to be varying significantly across these cohorts. Urinary ornithine seems to have the potential to be used as biomarkers of vivax malaria. An increasing trend in pipecolic acid was also observed. The results suggest impairment in the functioning of liver as well as impairment in urea cycle. Conclusions The results open up a possibility of non-invasive analysis and diagnosis of P. vivax using urine metabolic profile. Distinct variations in certain metabolites were recorded, and amongst these, ornithine may have the

Plasmodium vivax dhfr and dhps mutations in isolates from Madagascar and therapeutic response to sulphadoxine-pyrimethamine

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Jahevitra Martial

2008-02-01

Full Text Available Abstract Background Four of five Plasmodium species infecting humans are present in Madagascar. Plasmodium vivax remains the second most prevalent species, but is understudied. No data is available on its susceptibility to sulphadoxine-pyrimethamine, the drug recommended for intermittent preventive treatment during pregnancy. In this study, the prevalence of P. vivax infection and the polymorphisms in the pvdhfr and pvdhps genes were investigated. The correlation between these polymorphisms and clinical and parasitological responses was also investigated in P. vivax-infected patients. Methods Plasmodium vivax clinical isolates were collected in eight sentinel sites from the four major epidemiological areas for malaria across Madagascar in 2006/2007. Pvdhfr and pvdhps genes were sequenced for polymorphism analysis. The therapeutic efficacy of SP in P. vivax infections was assessed in Tsiroanomandidy, in the foothill of the central highlands. An intention-to-treat analysis of treatment outcome was carried out. Results A total of 159 P. vivax samples were sequenced in the pvdhfr/pvdhps genes. Mutant-types in pvdhfr gene were found in 71% of samples, and in pvdhps gene in 16% of samples. Six non-synonymous mutations were identified in pvdhfr, including two novel mutations at codons 21 and 130. For pvdhps, beside the known mutation at codon 383, a new one was found at codon 422. For the two genes, different combinations were ranged from wild-type to quadruple mutant-type. Among the 16 patients enrolled in the sulphadoxine-pyrimethamine clinical trial (28 days of follow-up and after adjustment by genotyping, 3 (19%, 95% CI: 5%–43% of them were classified as treatment failure and were pvdhfr 58R/117N double mutant carriers with or without the pvdhps 383G mutation. Conclusion This study highlights (i that genotyping in the pvdhfr and pvdhps genes remains a useful tool to monitor the emergence and the spread of P. vivax sulphadoxine

A molecular survey of acute febrile illnesses reveals Plasmodium vivax infections in Kedougou, southeastern Senegal.

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Niang, Makhtar; Thiam, Laty Gaye; Sow, Abdourahmane; Loucoubar, Cheikh; Bob, Ndeye Sakha; Diop, Fode; Diouf, Babacar; Niass, Oumy; Mansourou, Annick; Varela, Marie Louise; Perraut, Ronald; Sall, Amadou A; Toure-Balde, Aissatou

2015-07-19

Control efforts towards malaria due to Plasmodium falciparum significantly decreased the incidence of the disease in many endemic countries including Senegal. Surprisingly, in Kedougou (southeastern Senegal) P. falciparum malaria remains highly prevalent and the relative contribution of other Plasmodium species to the global malaria burden is very poorly documented, partly due to the low sensitivity of routine diagnostic tools. Molecular methods offer better estimate of circulating Plasmodium species in a given area. A molecular survey was carried out to document circulating malaria parasites in Kedougou region. A total of 263 long-term stored sera obtained from patients presenting with acute febrile illness in Kedougou between July 2009 and July 2013 were used for malaria parasite determination. Sera were withdrawn from a collection established as part of a surveillance programme of arboviruses infections in the region. Plasmodium species were characterized by a nested PCR-based approach targeting the 18S small sub-unit ribosomal RNA genes of Plasmodium spp. Of the 263 sera screened in this study, Plasmodium genomic DNA was amplifiable by nested PCR from 62.35% (164/263) of samples. P. falciparum accounted for the majority of infections either as single in 85.97% (141/164) of Plasmodium-positive samples or mixed with Plasmodium ovale (11.58%, 19/164) or Plasmodium vivax (1.21%, 2/164). All 19 (11.58%) P. ovale-infected patients were mixed with P. falciparum, while no Plasmodium malariae was detected in this survey. Four patients (2.43%) were found to be infected by P. vivax, two of whom were mixed with P. falciparum. P. vivax infections originated from Bandafassi and Ninefesha villages and concerned patients aged 4, 9, 10, and 15 years old, respectively. DNA sequences alignment and phylogenetic analysis demonstrated that sequences from Kedougou corresponded to P. vivax, therefore confirming the presence of P. vivax infections in Senegal. The results confirm the

Distribution of Mutations Associated with Antifolate and Chloroquine Resistance among Imported Plasmodium vivax in the State of Qatar.

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Bansal, Devendra; Acharya, Anushree; Bharti, Praveen K; Abdelraheem, Mohamed H; Elmalik, Ashraf; Abosalah, Salem; Khan, Fahmi Y; ElKhalifa, Mohamed; Kaur, Hargobinder; Mohapatra, Pradyumna K; Sehgal, Rakesh; Idris, Mohammed A; Mahanta, Jagadish; Singh, Neeru; Babiker, Hamza A; Sultan, Ali A

2017-12-01

Plasmodium vivax is the most prevalent parasite worldwide, escalating by spread of drug resistance. Currently, in Qatar, chloroquine (CQ) plus primaquine are recommended for the treatment of P. vivax malaria. The present study examined the prevalence of mutations in dihydrofolate reductase ( dhfr ), dihydropteroate synthase ( dhps ) genes and CQ resistance transporter ( crt-o ) genes, associated with sulphadoxine-pyrimethamine (SP) and chloroquine resistance, among imported P. vivax cases in Qatar. Blood samples were collected from patients positive for P. vivax and seeking medical treatment at Hamad General Hospital, Doha, during 2013-2016. The Sanger sequencing method was performed to examine the single nucleotide polymorphisms in Pvdhfr , Pvdhps , and Pvcrt-o genes. Of 314 examined P. vivax isolates, 247 (78.7%), 294 (93.6%) and 261 (83.1%) were successfully amplified and sequenced for Pvdhfr , Pvdhps , and Pvcrt-o , respectively. Overall, 53.8% ( N = 133) carried mutant alleles (58R/117N) in Pvdhfr , whereas 77.2% ( N = 227) and 90% ( N = 235) isolates possessed wild type allele in Pvdhps and Pvcrt-o genes, respectively. In addition, a total of eleven distinct haplotypes were detected in Pvdhfr / Pvdhps genes. Interestingly, K10 insertion in the Pvcrt-o gene was observed only in patients originating from the Indian subcontinent. The results suggested that CQ remains an acceptable treatment regimen but further clinical data are required to assess the effectiveness of CQ and SP in Qatar to support the current national treatment guidelines. In addition, limited distribution of genetic polymorphisms associated with CQ and SP resistance observed in imported P. vivax infections, necessitates regular monitoring of drug resistant P. vivax malaria in Qatar.

Severity of thrombocytopenia in patients with plasmodium vivax malaria; a single center study

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Hafeez, M.; Lodhi, F.R.

2015-01-01

Thrombocytopenia has been frequently observed in plasmodium vivax malaria in different studies. Finding out the severity of thrombocytopenia is perhaps equally important, as it has practical as well as prognostic implications. The objective of the study was to assess the severity of thrombocytopenia in patients suffering from malaria caused by plasmodium vivax. Methods: This cross-sectional study was carried out at Combined Military Hospital (CMH) Malir, Karachi, which is a tertiary care Hospital for all military personnel and their families in the province of Sindh. All patients of smear positive Vivax malaria during the study period were included, and those having hrombocytopenia from any other reason were excluded. They were treated with anti-malarial drugs and their platelet counts were monitored till they normalized and discharged from the hospital. Thrombocytopenia was defined as platelets count of <150,000/cu mm. Results were analysed by SPSS 11. Results: Out of 150 cases, 133 (88%) had thrombocytopenia. Their ages ranged from 15 to 55; mean age was 35 with SD ± 20. Low platelet count observed was between 11000 and 146000/cu mm with SD ± 27404. Mean value was 79 832/cu mm. None of the patient had any bleeding episode requiring a blood transfusion. Conclusion: Plasmodium vivax associated thrombocytopenia has a benign outcome irrespective of severity of the platelet counts. (author)

[Therapeutic response of Plasmodium vivax to chloroquine in Bolivia].

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Añez, Arletta; Navarro-Costa, Dennis; Yucra, Omar; Garnica, Cecilia; Melgar, Viviana; Moscoso, Manuel; Arteaga, Ricardo; Nakao, Gladys

2012-01-01

Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.

Avaliação clínico-laboratorial de bovinos Nelore infectados experimentalmente com Trypanosoma vivax Clinical and laboratorial evaluation of Nellore cattle experimentally infected with Trypanosoma vivax

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Maria A. M. Schenk

2001-12-01

Full Text Available Avaliaram-se as alterações clínico-laboratoriais de seis bezerros Nelore, de ambos os sexos, inoculados experimentalmente com 10(7 organismos viáveis de Trypanosoma vivax, isolados de bovinos da região de Poconé, Estado de Mato Grosso. Os animais foram observados diariamente, durante 30 dias, quanto aos parâmetros de temperatura retal, volume globular (VG, parasitemia, produção de anticorpos, coloração de mucosas, comportamento e apetite. Determinaram-se os níveis séricos de aspartato aminotransferase (AST, fosfatase alcalina (FA, gama glutamiltransferase (GGT, creatina kinase (CK, colesterol, uréia, creatinina, cálcio, fósforo e o perfil eletroforético das proteínas séricas aos 4, 8, 12, 16, 23 e 30 dias pós-inoculação (DPI. Durante os 6 meses seguintes, os animais foram observados semanalmente, avaliando-se a temperatura retal, o VG e a parasitemia. T. vivax foi evidenciado a partir do terceiro e quarto DPI em todos os bezerros e persistiu até o 30° DPI em cinco dos seis animais em estudo. Ocorreu um decréscimo significativo (pIn order to evaluate the clinical-laboratorial alterations, six Nellore calves were inoculated with 10(7 Trypanosoma vivax isolated from Poconé region, Mato Grosso, Brazil. The animals were evaluated daily for rectal temperature, packed cell volume (PCV, parasitemia, antibody production, color of mucous membranes, behavior and appetite. Blood and serum samples for biochemical evaluation for aspartate aminotransferase (AST, alkaline phosphatase (AF, gamma glutamyltransferase (GGT, cholesterol, urea, creatinine, creatine kinase (CK, calcium, phosphorus and proteinogram were collected on days 4, 8, 12, 16, 23 and 30 post inoculation (DPI. During the following 6 months rectal temperature, PCV and parasitemia were evaluated weekly. T. vivax was evidenced from 1 DPI in all calves and persisted until day 30 in five of six animals. A remarkable decrease (p<0.05 of PCV mean value (25% was observed on 10

The evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (MSP-9), in Plasmodium vivax and closely related species.

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Chenet, Stella M; Pacheco, M Andreína; Bacon, David J; Collins, William E; Barnwell, John W; Escalante, Ananias A

2013-12-01

The merozoite surface protein-9 (MSP-9) has been considered a target for an anti-malarial vaccine since it is one of many proteins involved in the erythrocyte invasion, a critical step in the parasite life cycle. Orthologs encoding this antigen have been found in all known species of Plasmodium parasitic to primates. In order to characterize and investigate the extent and maintenance of MSP-9 genetic diversity, we analyzed DNA sequences of the following malaria parasite species: Plasmodium falciparum, Plasmodium reichenowi, Plasmodium chabaudi, Plasmodium yoelii, Plasmodium berghei, Plasmodium coatneyi, Plasmodium gonderi, Plasmodium knowlesi, Plasmodium inui, Plasmodium simiovale, Plasmodium fieldi, Plasmodium cynomolgi and Plasmodium vivax and evaluated the signature of natural selection in all MSP-9 orthologs. Our findings suggest that the gene encoding MSP-9 is under purifying selection in P. vivax and closely related species. We further explored how selection affected different regions of MSP-9 by comparing the polymorphisms in P. vivax and P. falciparum, and found contrasting patterns between these two species that suggest differences in functional constraints. This observation implies that the MSP-9 orthologs in human parasites may interact differently with the host immune response. Thus, studies carried out in one species cannot be directly translated into the other. Copyright © 2013 Elsevier B.V. All rights reserved.

First report of Trypanosoma vivax outbreak in dairy cattle in São Paulo state, Brazil Primeiro relato de surto por Trypanosoma vivax em vacas leiteiras no estado de São Paulo, Brasil

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Fabiano Antonio Cadioli

2012-06-01

Full Text Available This is the first description of a Trypanosoma vivax outbreak in the state of São Paulo (municipality of Lins. Fever, jaundice, decreased milk production, weight loss, profuse diarrhea, abortion, anemia, leukocytosis and hyperfibrinogenemia were observed in the affected animals. Thirty-one cows and calves died out of a total of 1080 in the herd. Three cows showed neurological symptoms like dysmetria, ataxia, muscle weakness, ptyalism, lymph node enlargement and submandibular edema. Flagellated hemoparasites were observed in blood smears. The species was diagnosed as T. vivax by means of PCR. This T.vivax strain showed resistance to diaminazene aceturate and the infection spread quickly at the herd. From the ELISA test, 599 serum samples (98.36% were positive for anti-T.vivax IgG antibodies. This outbreak occurred during a very dry period, which indicates that other factors were involved in the outbreak, such as absence of tabanids and large populations of Haematobia irritans and Stomoxys calcitrans. The increases in these populations may have been due to the use of biosolid waste from sugar and ethanol plants in the sugarcane plantations surrounding the dairy farm.Esta é a primeira descrição de um surto de Trypanosomavivax ocorrido no Estado de São Paulo, no município de Lins. Animais acometidos apresentaram febre, icterícia, diminuição da produção de leite, perda de peso, diarreia profusa, abortos, anemia, leucocitose e hiperfibrigenemia. Foram registrados 31 óbitos de vacas e bezerros em 1.080 bovinos no total. Três vacas apresentaram sintomatologia nervosa, como dismetria, ataxia e fraqueza muscular, além de ptialismo, aumento de linfonodos e edema submandibular. Hemoparasitas flagelados foram observados em esfregaços sanguíneos, e a espécie de tripanossomo foi diagnosticada como T.vivax por PCR. A cepa de T. vivax mostrou ser resistente ao tratamento com aceturato de diaminozeno e a infecção disseminou rapidamente no

Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma

International Nuclear Information System (INIS)

Mira, J.G.; Livingston, R.B.; Moore, T.N.

1982-01-01

The value of radiotherapy to the chest (RC) in disseminated small cell lung carcinoma (SCLC) has been questioned. Two protocols for disseminated SCLC from the Southwest Oncology Group (SWOG) have been compared. The first one included radiotherapy (RT), 3000 rad in two weeks, to the primary tumor, mediastinum and supraclavicular areas, while the second one deleted any RC. Multidrug chemotherapy (CT) and brain RT were used in both protocols. Nonresponders to CT were removed from the study. Our main findings are as follows: (1) Initial chest relapses (patients with no initial extrathoracic relapse) have increased from 24-55% when RC is not given (P = 0.0001). Overall chest relapse (adding those patients that relapsed simultaneously in the chest plus other sites) in the second protocol was 73%. (2) Amount of response to CT does not influence the chances for relapse. Even complete responders to CT have a high chance for chest relapse. (3) Sites of relapse without RC are mainly in the primary tumor, ipsilateral hilus and mediastinum. (4) With RC, relapses shift to the chest periphery, mostly to the lung outside the radiotherapy field and to the pleura. (5) The two very different CT regimens have produced similar percentages and duration of response. (6) CT schema with periodic reinductions prolongs duration of response and survival over schema with continuous maintenance. Hence, interruption of CT to allow RC does not seem to adversely influence CT efficacy

Sensitive Detection of Plasmodium vivax Using a High-Throughput, Colourimetric Loop Mediated Isothermal Amplification (HtLAMP Platform: A Potential Novel Tool for Malaria Elimination.

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Sumudu Britton

2016-02-01

Full Text Available Plasmodium vivax malaria has a wide geographic distribution and poses challenges to malaria elimination that are likely to be greater than those of P. falciparum. Diagnostic tools for P. vivax infection in non-reference laboratory settings are limited to microscopy and rapid diagnostic tests but these are unreliable at low parasitemia. The development and validation of a high-throughput and sensitive assay for P. vivax is a priority.A high-throughput LAMP assay targeting a P. vivax mitochondrial gene and deploying colorimetric detection in a 96-well plate format was developed and evaluated in the laboratory. Diagnostic accuracy was compared against microscopy, antigen detection tests and PCR and validated in samples from malaria patients and community controls in a district hospital setting in Sabah, Malaysia.The high throughput LAMP-P. vivax assay (HtLAMP-Pv performed with an estimated limit of detection of 1.4 parasites/ μL. Assay primers demonstrated cross-reactivity with P. knowlesi but not with other Plasmodium spp. Field testing of HtLAMP-Pv was conducted using 149 samples from symptomatic malaria patients (64 P. vivax, 17 P. falciparum, 56 P. knowlesi, 7 P. malariae, 1 mixed P. knowlesi/P. vivax, with 4 excluded. When compared against multiplex PCR, HtLAMP-Pv demonstrated a sensitivity for P. vivax of 95% (95% CI 87-99%; 61/64, and specificity of 100% (95% CI 86-100%; 25/25 when P. knowlesi samples were excluded. HtLAMP-Pv testing of 112 samples from asymptomatic community controls, 7 of which had submicroscopic P. vivax infections by PCR, showed a sensitivity of 71% (95% CI 29-96%; 5/7 and specificity of 93% (95% CI87-97%; 98/105.This novel HtLAMP-P. vivax assay has the potential to be a useful field applicable molecular diagnostic test for P. vivax infection in elimination settings.

Higher Complexity of Infection and Genetic Diversity of Plasmodium vivax Than Plasmodium falciparum across all Malaria Transmission Zones of Papua New Guinea

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Fola, Abebe A.; Harrison, G. L. Abby; Hazairin, Mita Hapsari; Barnadas, Céline; Hetzel, Manuel W.; Iga, Jonah; Siba, Peter M.; Mueller, Ivo; Barry, Alyssa E.

2017-01-01

Plasmodium falciparum and Plasmodium vivax have varying transmission dynamics that are informed by molecular epidemiology. This study aimed to determine the complexity of infection and genetic diversity of P. vivax and P. falciparum throughout Papua New Guinea (PNG) to evaluate transmission dynamics across the country. In 2008–2009, a nationwide malaria indicator survey collected 8,936 samples from all 16 endemic provinces of PNG. Of these, 892 positive P. vivax samples were genotyped at PvMS16 and PvmspF3, and 758 positive P. falciparum samples were genotyped at Pfmsp2. The data were analyzed for multiplicity of infection (MOI) and genetic diversity. Overall, P. vivax had higher polyclonality (71%) and mean MOI (2.32) than P. falciparum (20%, 1.39). These measures were significantly associated with prevalence for P. falciparum but not for P. vivax. The genetic diversity of P. vivax (PvMS16: expected heterozygosity = 0.95, 0.85–0.98; PvMsp1F3: 0.78, 0.66–0.89) was higher and less variable than that of P. falciparum (Pfmsp2: 0.89, 0.65–0.97). Significant associations of MOI with allelic richness (rho = 0.69, P = 0.009) and expected heterozygosity (rho = 0.87, P < 0.001) were observed for P. falciparum. Conversely, genetic diversity was not correlated with polyclonality nor mean MOI for P. vivax. The results demonstrate higher complexity of infection and genetic diversity of P. vivax across the country. Although P. falciparum shows a strong association of these parameters with prevalence, a lack of association was observed for P. vivax and is consistent with higher potential for outcrossing of this species. PMID:28070005

Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America.

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Jovel, Irina T; Mejía, Rosa E; Banegas, Engels; Piedade, Rita; Alger, Jackeline; Fontecha, Gustavo; Ferreira, Pedro E; Veiga, Maria I; Enamorado, Irma G; Bjorkman, Anders; Ursing, Johan

2011-12-19

In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P

Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka

DEFF Research Database (Denmark)

Schousboe, Mette L; Rajakaruna, Rupika S; Salanti, Ali

2007-01-01

into the level of drug pressure caused by SP use and presumably other antifolate drugs. In Sri Lanka, chloroquine (CQ) with primaquine (PQ) and SP with PQ is used as first and second line treatment, respectively, against uncomplicated Plasmodium falciparum and/or P. vivax infections. CQ/PQ is still efficacious...... against P. vivax infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to P. vivax SP resistance is low. However, this has not been assessed in Sri Lanka as in most other parts of Asia. This study describes the prevalence and distribution of SNPs related to P. vivax SP...... and 383, 553 and 585 of the Pvdhps gene by applying PCR followed by a hybridization step using sequence specific oligonucleotide probes (SSOPs) in an ELISA format. RESULTS: In the study period, the government of Sri Lanka recorded 2,149 P. vivax cases from the nine districts out of which, 454 (21...

Neutral polymorphisms in putative housekeeping genes and tandem repeats unravels the population genetics and evolutionary history of Plasmodium vivax in India.

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Surendra K Prajapati

Full Text Available The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75 from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the housekeeping genes were selectively neutral, confirming the suitability of housekeeping genes for inferring the evolutionary history of P. vivax. In addition, a genetic differentiation test using housekeeping gene polymorphism data showed a lack of geographical structuring between the five regions of India. The coalescence analysis of the time to the most recent common ancestor estimate yielded an ancient TMRCA (232,228 to 303,030 years and long-term population history (79,235 to 104,008 of extant P. vivax on the Indian subcontinent. Analysis of 18 tandem repeat loci polymorphisms showed substantial allelic diversity and heterozygosity per locus, and analysis of potential bottlenecks revealed the signature of a stable P. vivax population, further corroborating our ancient age estimates. For the first time we report a comparable evolutionary history of P. vivax inferred by nuclear genetic markers (putative housekeeping genes to that inferred from mitochondrial genome diversity.

Neutral polymorphisms in putative housekeeping genes and tandem repeats unravels the population genetics and evolutionary history of Plasmodium vivax in India.

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Prajapati, Surendra K; Joshi, Hema; Carlton, Jane M; Rizvi, M Alam

2013-01-01

The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75) from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the housekeeping genes were selectively neutral, confirming the suitability of housekeeping genes for inferring the evolutionary history of P. vivax. In addition, a genetic differentiation test using housekeeping gene polymorphism data showed a lack of geographical structuring between the five regions of India. The coalescence analysis of the time to the most recent common ancestor estimate yielded an ancient TMRCA (232,228 to 303,030 years) and long-term population history (79,235 to 104,008) of extant P. vivax on the Indian subcontinent. Analysis of 18 tandem repeat loci polymorphisms showed substantial allelic diversity and heterozygosity per locus, and analysis of potential bottlenecks revealed the signature of a stable P. vivax population, further corroborating our ancient age estimates. For the first time we report a comparable evolutionary history of P. vivax inferred by nuclear genetic markers (putative housekeeping genes) to that inferred from mitochondrial genome diversity.

Duffy Negative Antigen Is No Longer a Barrier to Plasmodium vivax – Molecular Evidences from the African West Coast (Angola and Equatorial Guinea)

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Mendes, Cristina; Dias, Fernanda; Figueiredo, Joana; Mora, Vicenta Gonzalez; Cano, Jorge; de Sousa, Bruno; do Rosário, Virgílio E.; Benito, Agustin; Berzosa, Pedro; Arez, Ana Paula

2011-01-01

Background Plasmodium vivax shows a small prevalence in West and Central Africa due to the high prevalence of Duffy negative people. However, Duffy negative individuals infected with P. vivax have been reported in areas of high prevalence of Duffy positive people who may serve as supply of P. vivax strains able to invade Duffy negative erythrocytes. We investigated the presence of P. vivax in two West African countries, using blood samples and mosquitoes collected during two on-going studies. Methodology/Findings Blood samples from a total of 995 individuals were collected in seven villages in Angola and Equatorial Guinea, and 820 Anopheles mosquitoes were collected in Equatorial Guinea. Identification of the Plasmodium species was achieved by nested PCR amplification of the small-subunit rRNA genes; P. vivax was further characterized by csp gene analysis. Positive P. vivax-human isolates were genotyped for the Duffy blood group through the analysis of the DARC gene. Fifteen Duffy-negative individuals, 8 from Equatorial Guinea (out of 97) and 7 from Angola (out of 898), were infected with two different strains of P. vivax (VK210 and VK247). Conclusions In this study we demonstrated that P. vivax infections were found both in humans and mosquitoes, which means that active transmission is occurring. Given the high prevalence of infection in mosquitoes, we may speculate that this hypnozoite-forming species at liver may not be detected by the peripheral blood samples analysis. Also, this is the first report of Duffy negative individuals infected with two different strains of P. vivax (VK247 and classic strains) in Angola and Equatorial Guinea. This finding reinforces the idea that this parasite is able to use receptors other than Duffy to invade erythrocytes, which may have an enormous impact in P. vivax current distribution. PMID:21713024

Partial Sequence Analysis of Merozoite Surface Proteine-3α Gene in Plasmodium vivax Isolates from Malarious Areas of Iran

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H Mirhendi

2008-12-01

Full Text Available Background: Approximately 85-90% of malaria infections in Iran are attributed to Plasmodium vivax, while little is known about the genetic of the parasite and its strain types in this region. This study was designed and performed for describing genetic characteristics of Plasmodium vivax population of Iran based on the merozoite surface protein-3α gene sequence. Methods: Through a descriptive study we analyzed partial P. vivax merozoite surface protein-3α gene sequences from 17 clinical P. vivax isolates collected from malarious areas of Iran. Genomic DNA was extracted by Q1Aamp® DNA blood mini kit, amplified through nested PCR for a partial nucleotide sequence of PvMSP-3 gene in P. vivax. PCR-amplified products were sequenced with an ABI Prism Perkin-Elmer 310 sequencer machine and the data were analyzed with clustal W software. Results: Analysis of PvMSP-3 gene sequences demonstrated extensive polymorphisms, but the sequence identity between isolates of same types was relatively high. We identified specific insertions and deletions for the types A, B and C variants of P. vivax in our isolates. In phylogenetic comparison of geographically separated isolates, there was not a significant geo­graphical branching of the parasite populations. Conclusion: The highly polymorphic nature of isolates suggests that more investigations of the PvMSP-3 gene are needed to explore its vaccine potential.

A clinical tool to predict Plasmodium vivax recurrence in Malaysia.

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Mat Ariffin, Norliza; Islahudin, Farida; Kumolosasi, Endang; Makmor-Bakry, Mohd

2017-12-08

Recurrence rates of Plasmodium vivax infections differ across various geographic regions. Interestingly, South-East Asia and the Asia-Pacific region are documented to exhibit the most frequent recurrence incidences. Identifying patients at a higher risk for recurrences gives valuable information in strengthening the efforts to control P. vivax infections. The aim of the study was to develop a tool to identify P. vivax- infected patients that are at a higher risk of recurrence in Malaysia. Patient data was obtained retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016. Patients with incomplete data were excluded. A total of 2044 clinical P. vivax malaria cases treated with primaquine were included. Data collected were patient, disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were used to develop a clinical risk score, while the remaining third (n = 682) was used for validation. Using multivariate analysis, age (p = 0.03), gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found to be predictors of recurrence after controlling for other confounding factors; these predictors were then used in developing the final model. The beta-coefficient values were used to develop a clinical scoring tool to predict possible recurrence. The total scores ranged between 0 and 8. A higher score indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence interval [CI]: 1.562-2.487; p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve of the developed (n = 1362) and validated model (n = 682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value useful tool in targeting patients at a higher risk for recurrence for closer monitoring during follow-up, after treatment with primaquine.

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

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White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

2016-09-22

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and

EXPERIMENTAL INFECTION BY Trypanosoma vivax IN GOATS INFECÇÃO EXPERIMENTAL EM CAPRINOS COM Trypanosoma vivax

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Francisco David Nascimento Sousa

2008-10-01

Full Text Available

Four goats were infected intravenously with 1.0 mL of cattle blood containing about 1.25 x 10⁵ Trypanosoma vivax derived from spontaneous outbreak in cattle at Catolé do Rocha city, Paraíba, Brazil. Other four goats were used as controls. Parasitemia and body temperature were determined daily for 40 days. Animals were weighted each 7 days, and blood samples for blood cells counts were collected each 5 days. It was obtained a sample of liquor from each animal before death; cerebrospinal fluid samples were submitted to biochemical and cytological evaluations, density determination and parasite detection. A positive correlation was found between body temperature and parasitemia in infected animals. These animals presented anemia, leukopenia, hypoglycemia, decreased serum levels of total proteins and cholesterol, and nervous symptoms. Examination of cerebrospinal fluid resulted in decrease of glucose levels and increase in lactate dehydrogenase, cell counts and presence of the parasite. At necropsy it was found pale carcass, generalized infartation of lymphonodes, pulmonary edema, and liquid accumulation of pericardium. Histological changes were characterized by interstitial pneumonia, miocarditis, cardiac fibrosis, meningitis, and encephalitis. All observed changes confirm patogenicity of T. vivax.

Modelling the incidence of Plasmodium vivax and Plasmodium falciparum malaria in Afghanistan 2006-2009.

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Alegana, Victor A; Wright, Jim A; Nahzat, Sami M; Butt, Waqar; Sediqi, Amad W; Habib, Naeem; Snow, Robert W; Atkinson, Peter M; Noor, Abdisalan M

2014-01-01

Identifying areas that support high malaria risks and where populations lack access to health care is central to reducing the burden in Afghanistan. This study investigated the incidence of Plasmodium vivax and Plasmodium falciparum using routine data to help focus malaria interventions. To estimate incidence, the study modelled utilisation of the public health sector using fever treatment data from the 2012 national Malaria Indicator Survey. A probabilistic measure of attendance was applied to population density metrics to define the proportion of the population within catchment of a public health facility. Malaria data were used in a Bayesian spatio-temporal conditional-autoregressive model with ecological or environmental covariates, to examine the spatial and temporal variation of incidence. From the analysis of healthcare utilisation, over 80% of the population was within 2 hours' travel of the nearest public health facility, while 64.4% were within 30 minutes' travel. The mean incidence of P. vivax in 2009 was 5.4 (95% Crl 3.2-9.2) cases per 1000 population compared to 1.2 (95% Crl 0.4-2.9) cases per 1000 population for P. falciparum. P. vivax peaked in August while P. falciparum peaked in November. 32% of the estimated 30.5 million people lived in regions where annual incidence was at least 1 case per 1,000 population of P. vivax; 23.7% of the population lived in areas where annual P. falciparum case incidence was at least 1 per 1000. This study showed how routine data can be combined with household survey data to model malaria incidence. The incidence of both P. vivax and P. falciparum in Afghanistan remain low but the co-distribution of both parasites and the lag in their peak season provides challenges to malaria control in Afghanistan. Future improved case definition to determine levels of imported risks may be useful for the elimination ambitions in Afghanistan.

Hemolytic uremic syndrome associated with Plasmodium vivax malaria successfully treated with plasma exchange

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V S Keskar

2014-01-01

Full Text Available We report a case of hemolytic uremic syndrome (HUS in an adult patient with Plasmodium vivax malaria. The patient presented with worsening anemia, persistent thrombocytopenia and acute kidney injury. HUS was diagnosed based on the high serum lactate dehydrogenase, elevated reticulocyte count and presence of schistocytes on peripheral blood smear. Kidney biopsy showed features of thrombotic microangiopathy. Complete hematological remission was achieved after five sessions of therapeutic plasma exchange. Renal function partially recovered and stabilized at discharge. Vivax malaria, generally considered benign, may be rarely associated with HUS.

Pattern of occult nodal relapse diagnosed with 18F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy

International Nuclear Information System (INIS)

Lépinoy, Alexis; Cochet, Alexandre; Cueff, Adèle; Cormier, Luc; Martin, Etienne; Maingon, Philippe; Bosset, Jean François; Brunotte, François; Créhange, Gilles

2014-01-01

Introduction: The purpose of this study was to describe the pattern of nodal relapse with 18 F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. Materials and methods: Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTV RTOG ). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. Results: Fourteen patients (45.2%) had a relapse outside the CTV RTOG . Of the 17 patients with a positive node inside the CTV RTOG , 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTV RTOG had ⩾2 positive nodes on FCH PET/CT (OR = 8.75, [95% CI: 1.38–54.80], p = 0.020). Relapses that occurred outside the CTV RTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2–L3. Conclusion: 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2–L3 safely to cover 95% of nodal stations at risk of an occult relapse

Frequent Spread of Plasmodium vivax Malaria Maintains High Genetic Diversity at the Myanmar-China Border, Without Distance and Landscape Barriers.

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Lo, Eugenia; Lam, Nancy; Hemming-Schroeder, Elizabeth; Nguyen, Jennifer; Zhou, Guofa; Lee, Ming-Chieh; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

2017-12-05

In Myanmar, civil unrest and the establishment of internally displaced person (IDP) settlements along the Myanmar-China border have impacted malaria transmission. Microsatellite markers were used to examine source-sink dynamics for Plasmodium vivax between IDP settlements and surrounding villages in the border region. Genotypic structure and diversity were compared across the 3 years following the establishment of IDP settlements, to infer demographic history. We investigated whether human migration and landscape heterogeneity contributed to P. vivax transmission. P. vivax from IDP settlements and local communities consistently exhibited high genetic diversity within populations but low polyclonality within individuals. No apparent genetic structure was observed among populations and years. P. vivax genotypes in China were similar to those in Myanmar, and parasite introduction was unidirectional. Landscape factors, including distance, elevation, and land cover, do not appear to impede parasite gene flow. The admixture of P. vivax genotypes suggested that parasite gene flow via human movement contributes to the spread of malaria both locally in Myanmar and across the international border. Our genetic findings highlight the presence of large P. vivax gene reservoirs that can sustain transmission. Thus, it is important to reinforce and improve existing control efforts along border areas. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Plasmodium vivax and Plasmodium falciparum infections in the Republic of Djibouti: evaluation of their prevalence and potential determinants.

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Khaireh, Bouh Abdi; Briolant, Sébastien; Pascual, Aurélie; Mokrane, Madjid; Machault, Vanessa; Travaillé, Christelle; Khaireh, Mohamed Abdi; Farah, Ismail Hassan; Ali, Habib Moussa; Abdi, Abdul-Ilah Ahmed; Ayeh, Souleiman Nour; Darar, Houssein Youssouf; Ollivier, Lénaïck; Waiss, Mohamed Killeh; Bogreau, Hervé; Rogier, Christophe; Pradines, Bruno

2012-11-28

Formerly known as a hypoendemic malaria country, the Republic of Djibouti declared the goal of pre-eliminating malaria in 2006. The aim of the present study was to evaluate the prevalence of Plasmodium falciparum, Plasmodium vivax and mixed infections in the Djiboutian population by using serological tools and to identify potential determinants of the disease and hotspots of malaria transmission within the country. The prevalence of P. falciparum and P. vivax within the districts of the capital city and the rest of the Republic of Djibouti were assessed using 13 and 2 serological markers, respectively. The relationship between the immune humeral response to P. falciparum and P. vivax and variables such as age, gender, wealth status, urbanism, educational level, distance to rivers/lakes, living area, having fever in the last month, and staying in a malaria-endemic country more than one year was estimated and analysed by questionnaires administered to 1910 Djiboutians. Multivariate ordinal logistic regression models of the immune humeral response were obtained for P. falciparum and P. vivax. The P. falciparum and P. vivax seroprevalence rates were 31.5%, CI95% [29.4-33.7] and 17.5%, CI95% [15.8-19.3], respectively. Protective effects against P. falciparum and P. vivax were female gender, educational level, and never having visited a malaria-endemic area for more than one year. For P. falciparum only, a protective effect was observed for not having a fever in the last month, living more than 1.5 km away from lakes and rivers, and younger ages. This is the first study that assessed the seroprevalence of P. vivax in the Republic of Djibouti. It is necessary to improve knowledge of this pathogen in order to create an effective elimination programme. As supported by recent observations on the subject, the Republic of Djibouti has probably demonstrated a real decrease in the transmission of P. falciparum in the past seven years, which should encourage authorities to

Plasmodium vivax and Plasmodium falciparum infections in the Republic of Djibouti: evaluation of their prevalence and potential determinants

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Khaireh Bouh Abdi

2012-11-01

Full Text Available Abstract Background Formerly known as a hypoendemic malaria country, the Republic of Djibouti declared the goal of pre-eliminating malaria in 2006. The aim of the present study was to evaluate the prevalence of Plasmodium falciparum, Plasmodium vivax and mixed infections in the Djiboutian population by using serological tools and to identify potential determinants of the disease and hotspots of malaria transmission within the country. Methods The prevalence of P. falciparum and P. vivax within the districts of the capital city and the rest of the Republic of Djibouti were assessed using 13 and 2 serological markers, respectively. The relationship between the immune humeral response to P. falciparum and P. vivax and variables such as age, gender, wealth status, urbanism, educational level, distance to rivers/lakes, living area, having fever in the last month, and staying in a malaria-endemic country more than one year was estimated and analysed by questionnaires administered to 1910 Djiboutians. Multivariate ordinal logistic regression models of the immune humeral response were obtained for P. falciparum and P. vivax. Results The P. falciparum and P. vivax seroprevalence rates were 31.5%, CI95% [29.4-33.7] and 17.5%, CI95% [15.8-19.3], respectively. Protective effects against P. falciparum and P. vivax were female gender, educational level, and never having visited a malaria-endemic area for more than one year. For P. falciparum only, a protective effect was observed for not having a fever in the last month, living more than 1.5 km away from lakes and rivers, and younger ages. Conclusions This is the first study that assessed the seroprevalence of P. vivax in the Republic of Djibouti. It is necessary to improve knowledge of this pathogen in order to create an effective elimination programme. As supported by recent observations on the subject, the Republic of Djibouti has probably demonstrated a real decrease in the transmission of P. falciparum

Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil.

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Costa, Allyson Guimarães; Ramasawmy, Rajendranath; Ibiapina, Hiochelson Najibe Santos; Sampaio, Vanderson Souza; Xábregas, Lilyane Amorim; Brasil, Larissa Wanderley; Tarragô, Andréa Monteiro; Almeida, Anne Cristine Gomes; Kuehn, Andrea; Vitor-Silva, Sheila; Melo, Gisely Cardoso; Siqueira, André Machado; Monteiro, Wuelton Marcelo; Lacerda, Marcus Vinicius Guimarães; Malheiro, Adriana

2017-01-01

Plasmodium vivax malaria (Pv-malaria) is still considered a neglected disease despite an alarming number of individuals being infected annually. Malaria pathogenesis occurs with the onset of the vector-parasite-host interaction through the binding of pathogen-associated molecular patterns (PAMPs) and receptors of innate immunity, such as toll-like receptors (TLRs). The triggering of the signaling cascade produces an elevated inflammatory response. Genetic polymorphisms in TLRs are involved in susceptibility or resistance to infection, and the identification of genes involved with Pv-malaria response is important to elucidate the pathogenesis of the disease and may contribute to the formulation of control and elimination tools. A retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the state of Amazonas, Brazil. Genetic polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 325 patients infected with P. vivax and 274 healthy individuals without malaria history in the prior 12 months from the same endemic area. Parasite load was determined by qPCR. Simple and multiple logistic/linear regressions were performed to investigate association between the polymorphisms and the occurrence of Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T (TLR9 -1486C/T) genotypes appear to be risk factors for infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI: 1.054-4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI: 1.159-3.177, p = 0.010]; respectively). Fever (COEF = 7599.46, 95% CI = 3063.80-12135.12, p = 0.001) and the C/C genotype of TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83-30540.44, p = 0.014) were independently associated with increased parasitemia in patients with Pv-malaria. Variants of TLRs may predispose individuals to infection by P. vivax. The TLR5 R392StopCodon and TLR9 -1486C/T variants

Association of TLR variants with susceptibility to Plasmodium vivax malaria and parasitemia in the Amazon region of Brazil.

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Allyson Guimarães Costa

Full Text Available Plasmodium vivax malaria (Pv-malaria is still considered a neglected disease despite an alarming number of individuals being infected annually. Malaria pathogenesis occurs with the onset of the vector-parasite-host interaction through the binding of pathogen-associated molecular patterns (PAMPs and receptors of innate immunity, such as toll-like receptors (TLRs. The triggering of the signaling cascade produces an elevated inflammatory response. Genetic polymorphisms in TLRs are involved in susceptibility or resistance to infection, and the identification of genes involved with Pv-malaria response is important to elucidate the pathogenesis of the disease and may contribute to the formulation of control and elimination tools.A retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the state of Amazonas, Brazil. Genetic polymorphisms (SNPs in different TLRs, TIRAP, and CD14 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis in 325 patients infected with P. vivax and 274 healthy individuals without malaria history in the prior 12 months from the same endemic area. Parasite load was determined by qPCR. Simple and multiple logistic/linear regressions were performed to investigate association between the polymorphisms and the occurrence of Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon and T/T (TLR9 -1486C/T genotypes appear to be risk factors for infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI: 1.054-4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI: 1.159-3.177, p = 0.010]; respectively. Fever (COEF = 7599.46, 95% CI = 3063.80-12135.12, p = 0.001 and the C/C genotype of TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83-30540.44, p = 0.014 were independently associated with increased parasitemia in patients with Pv-malaria.Variants of TLRs may predispose individuals to infection by P. vivax. The TLR5 R392StopCodon and TLR9 -1486C

Quantitative Determination of Plasmodium vivax Gametocytes by Real-Time Quantitative Nucleic Acid Sequence-Based Amplification in Clinical Samples

NARCIS (Netherlands)

Beurskens, Martijn; Mens, Pètra; Schallig, Henk; Syafruddin, Din; Asih, Puji Budi Setia; Hermsen, Rob; Sauerwein, Robert

2009-01-01

Microscopic detection of Plasmodium vivax gametocytes, the sexual life stage of this malaria parasite, is insensitive because P vivax parasitaemia is low. To detect and quantity gametocytes a more sensitive, quantitative realtime Pvs25-QT-NASBA based oil Pvs25 mRNA was developed and tested in two

Clinical Manifestations, Treatment, and Outcome of Hospitalized Patients with Plasmodium vivax Malaria in Two Indian States: A Retrospective Study

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Jagjit Singh

2013-01-01

Full Text Available This was a retrospective study done on 110 patients hospitalized with P. vivax malaria in three medical college hospitals, one in the union territory of Chandigarh and the other two in Gujarat, that is, Ahmedabad and Surat. The clinical presentation, treatment, and outcome were recorded. As per WHO criteria for severity, 19 of 110 patients had severe disease—six patients had clinical jaundice with hepatic dysfunction, three patients had severe anemia, three had spontaneous bleeding, two had acute respiratory distress syndrome, and one had cerebral malaria, hyperparasitemia, renal failure, circulatory collapse, and metabolic acidosis. All patients with severe P. vivax malaria survived, but one child with cerebral malaria had neurological sequelae. There was wide variation in the antimalarial treatment received at the three centres. Plasmodium vivax malaria can no longer be considered a benign condition. WHO guidelines for treatment of P. vivax malaria need to be reinforced.

Development of in-vitro radiometric assay for the rapid assessment of chloroquine resistant plasmodium vivax

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Myint Oo; Myo Khin; Nwe Nwe Oo

1997-01-01

Previously, resistance of malaria parasite to chloroquine has been restricted only to Plasmodium falciparum. Recently, there have been many reports of chloroquine-resistant Plasmodium vivax. One of the mechanisms of chloroquine resistance is the decreased uptake of chloroquine or rapid efflux of the drug from the food vacuole of the parasite. In this study, we have measured the rapid efflux of IH-chloroquine in fifty blood samples from patients with P Vivax infection. All 50 patients were hospitalised for 28 days for the standard treatment with chloroquine. It was found that seven patients who did not respond to the standard regimen of chloroquine have parasites with rapid effluxes of IH-chloroquine. Since rapid effluxes of IH-chloroquine in the resistant parasites showed strong correlation with in vivo 28 days clinical trial, this assay could be used as rapid assessment of chloroquine resistance in patients with P vivax infection

Development of in-vitro radiometric assay for the rapid assessment of chloroquine resistant plasmodium vivax

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Oo, Myint; Khin, Myo; Oo, Nwe Nwe [Department of Medical Research, Yangon (Myanmar)

1997-12-01

Previously, resistance of malaria parasite to chloroquine has been restricted only to Plasmodium falciparum. Recently, there have been many reports of chloroquine-resistant Plasmodium vivax. One of the mechanisms of chloroquine resistance is the decreased uptake of chloroquine or rapid efflux of the drug from the food vacuole of the parasite. In this study, we have measured the rapid efflux of IH-chloroquine in fifty blood samples from patients with P Vivax infection. All 50 patients were hospitalised for 28 days for the standard treatment with chloroquine. It was found that seven patients who did not respond to the standard regimen of chloroquine have parasites with rapid effluxes of IH-chloroquine. Since rapid effluxes of IH-chloroquine in the resistant parasites showed strong correlation with in vivo 28 days clinical trial, this assay could be used as rapid assessment of chloroquine resistance in patients with P vivax infection.

Evaluation of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation.

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Lee, Nam-Ki; Kim, Young-Kyun; Yun, Pil-Young; Kim, Jong-Wan

2013-01-01

The aim of this study was to evaluate of the patterns of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation (MS-MO). The subjects consisted of 15 patients with minimal pre-surgical orthodontic preparation (1.37 ± 1.69 months). Lateral cephalograms were taken in pre-surgical (T0), post-surgical 1 month (T1) and immediately after debonding (T2) stages. To evaluate the surgical changes (T1-T0) and the relapse (T2-T1), the linear and angular measurements were analyzed using paired t-test. Pearson's correlation coefficients of the horizontal and vertical relapses of Pog and Me to other measurements were calculated. Pog or Me in T1 were displaced rotationally on Ar-Pog or Ar-Me lines in T2 to evaluate the remaining surgical relapse except the rotational relapse from total relapse. The mandible relapsed anteriorly 3.53 mm (Pog) and 4.00 mm (Me) and superiorly 2.72 mm (Pog) and 2.44 mm (Me). FH to Ar-Pog and FH to Ar-Me decreased by about 2°. Pure surgical relapses at Pog and Me, except rotational relapses, were about 0.5 mm anteriorly and inferiorly 0.8 mm. The vertical relapse might induce mandibular rotation with the horizontal relapse. For an accurate prediction after MS-MO, the rotational relapse might be considered. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

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Kawai Satoru

2010-02-01

Full Text Available Abstract Background The 200 kDa merozoite surface protein 1 (MSP-1 of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. Plasmodium vivax, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to P. vivax-related malaria parasites greatly differ among host species (albeit other factors. It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity. Results We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (msp1 from P. vivax and nine P. vivax-related simian malaria parasites. The inferred phylogenetic tree of msp1 significantly differed from that of the mitochondrial genome, with a striking displacement of P. vivax from a position close to P. cynomolgi in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to P. inui and P. hylobati and the other leading to P. vivax, P. fieldi and P. cynomolgi. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of msp1 polymorphisms between P. vivax, P. inui and P. cynomolgi revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species

Recurrencias de malaria por Plasmodium vivax según el uso de primaquina: análisis de estudios descriptivos longitudinales Plasmodium vivax malaria recurrence according to the use of primaquine: analysis of longitudinal descriptive studies

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Jaime Carmona-Fonseca

2012-09-01

Full Text Available ANTECEDENTES: la primaquina (PQ es el único medicamento disponible en el mercado para prevenir recurrencias del paludismo por Plasmodium vivax pero varios aspectos suyos se desconocen. OBJETIVO: comparar regímenes de PQ para prevenir recurrencias de malaria vivax. METODOLOGÍA: revisión sistemática de datos. RESULTADOS: 1. ¿Según los estudios descriptivos, la PQ es eficaz para prevenir las recurrencias del paludismo vivax? Sí. La comparación de estudios que no usaron PQ con otros que sí la aplicaron, en cualquier esquema, mostró que si no se usa PQ la recurrencia es altamente probable. 2. ¿Tienen la misma eficacia dosis diarias (mg/kg iguales pero dosis totales diferentes? La dosis total de 75 mg es tanto o más eficaz que la de 210 mg. 3. ¿La eficacia anti-recurrencias depende del lugar donde sucede la infección? Si. Hay variación según país y región. 4. ¿La frecuencia de recurrencias depende del tiempo de seguimiento post tratamiento? La respuesta no es uniforme para todos los lugares. CONCLUSIONES: la PQ resultó eficaz para prevenir las recurrencias, pero no fue 100%. Las dosis totales de 210 y de 75 mg tuvieron igual eficacia, pero 75 mg sólo han sido evaluados en India, donde P. vivax parece ser más sensible a la PQ que en otros lugares. Parece indudable la influencia del lugar en la proporción de recurrencias, incluso con una misma dosis total. El papel del tiempo de seguimiento no resultó claro. Deben evaluarse esquemas alternativos al estándar, que tiene eficacia promedio de 90% o más.BACKGROUND: primaquine (PQ is the only drug available in the market to prevent Plasmodium vivax malaria recurrence, but several aspects are still unknown. OBJECTIVE: To compare PQ regimens to prevent recurrence of vivax malaria. METHODS: systematic review and meta-analysis of data. RESULTS: 1. According to descriptive studies, is PQ effective in preventing recurrence of vivax malaria? Yes. The comparison of studies that did not use

Malaria rapid diagnostic tests: Plasmodium falciparum infections with high parasite densities may generate false positive Plasmodium vivax pLDH lines

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van Esbroeck Marjan

2010-07-01

Full Text Available Abstract Background Most malaria rapid diagnostic tests (RDTs detect Plasmodium falciparum and an antigen common to the four species. Plasmodium vivax-specific RDTs target P. vivax-specific parasite lactate dehydrogenase (Pv-pLDH. Previous observations of false positive Pv-pLDH test lines in P. falciparum samples incited to the present study, which assessed P. vivax-specific RDTs for the occurrence of false positive Pv-pLDH lines in P. falciparum samples. Methods Nine P. vivax-specific RDTs were tested with 85 P. falciparum samples of high (≥2% parasite density. Mixed P. falciparum/P. vivax infections were ruled out by real-time PCR. The RDTs included two-band (detecting Pv-pLDH, three-band (detecting P. falciparum-antigen and Pv-pLDH and four-band RDTs (detecting P. falciparum, Pv-pLDH and pan-pLDH. Results False positive Pv-pLDH lines were observed in 6/9 RDTs (including two- three- and four-band RDTs. They occurred in the individual RDT brands at frequencies ranging from 8.2% to 29.1%. For 19/85 samples, at least two RDT brands generated a false positive Pv-pLDH line. Sixteen of 85 (18.8% false positive lines were of medium or strong line intensity. There was no significant relation between false positive results and parasite density or geographic origin of the samples. Conclusion False positive Pv-pLDH lines in P. falciparum samples with high parasite density occurred in 6/9 P. vivax-specific RDTs. This is of concern as P. falciparum and P. vivax are co-circulating in many regions. The diagnosis of life-threatening P. falciparum malaria may be missed (two-band Pv-pLDH RDT, or the patient may be treated incorrectly with primaquine (three- or four-band RDTs.

Population Density, Climate Variables and Poverty Synergistically Structure Spatial Risk in Urban Malaria in India.

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Mauricio Santos-Vega

2016-12-01

Full Text Available The world is rapidly becoming urban with the global population living in cities projected to double by 2050. This increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. In particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. Interestingly India, as opposed to Africa, harbors a mosquito vector, Anopheles stephensi, which thrives in the man-made environments of cities and acts as the vector for both Plasmodium vivax and Plasmodium falciparum, making the malaria problem a truly urban phenomenon. Here we address the role and determinants of within-city spatial heterogeneity in the incidence patterns of vivax malaria, and then draw comparisons with results for falciparum malaria.Statistical analyses and a phenomenological transmission model are applied to an extensive spatio-temporal dataset on cases of Plasmodium vivax in the city of Ahmedabad (Gujarat, India that spans 12 years monthly at the level of wards. A spatial pattern in malaria incidence is described that is largely stationary in time for this parasite. Malaria risk is then shown to be associated with socioeconomic indicators and environmental parameters, temperature and humidity. In a more dynamical perspective, an Inhomogeneous Markov Chain Model is used to predict vivax malaria risk. Models that account for climate factors, socioeconomic level and population size show the highest predictive skill. A comparison to the transmission dynamics of falciparum malaria reinforces the conclusion that the spatio-temporal patterns of risk are strongly driven by extrinsic factors.Climate forcing and socio-economic heterogeneity act synergistically at local scales on the population dynamics of urban malaria in this city. The stationarity of malaria risk patterns provides a

Population Density, Climate Variables and Poverty Synergistically Structure Spatial Risk in Urban Malaria in India.

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Santos-Vega, Mauricio; Bouma, Menno J; Kohli, Vijay; Pascual, Mercedes

2016-12-01

The world is rapidly becoming urban with the global population living in cities projected to double by 2050. This increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. In particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. Interestingly India, as opposed to Africa, harbors a mosquito vector, Anopheles stephensi, which thrives in the man-made environments of cities and acts as the vector for both Plasmodium vivax and Plasmodium falciparum, making the malaria problem a truly urban phenomenon. Here we address the role and determinants of within-city spatial heterogeneity in the incidence patterns of vivax malaria, and then draw comparisons with results for falciparum malaria. Statistical analyses and a phenomenological transmission model are applied to an extensive spatio-temporal dataset on cases of Plasmodium vivax in the city of Ahmedabad (Gujarat, India) that spans 12 years monthly at the level of wards. A spatial pattern in malaria incidence is described that is largely stationary in time for this parasite. Malaria risk is then shown to be associated with socioeconomic indicators and environmental parameters, temperature and humidity. In a more dynamical perspective, an Inhomogeneous Markov Chain Model is used to predict vivax malaria risk. Models that account for climate factors, socioeconomic level and population size show the highest predictive skill. A comparison to the transmission dynamics of falciparum malaria reinforces the conclusion that the spatio-temporal patterns of risk are strongly driven by extrinsic factors. Climate forcing and socio-economic heterogeneity act synergistically at local scales on the population dynamics of urban malaria in this city. The stationarity of malaria risk patterns provides a basis for more

Development of a chimeric Plasmodium berghei strain expressing the repeat region of the P. vivax circumsporozoite protein for in vivo evaluation of vaccine efficacy.

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Espinosa, Diego A; Yadava, Anjali; Angov, Evelina; Maurizio, Paul L; Ockenhouse, Christian F; Zavala, Fidel

2013-08-01

The development of vaccine candidates against Plasmodium vivax-the most geographically widespread human malaria species-is challenged by technical difficulties, such as the lack of in vitro culture systems and availability of animal models. Chimeric rodent Plasmodium parasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. We report the successful development and characterization of chimeric Plasmodium berghei parasites bearing the type I repeat region of P. vivax circumsporozoite protein (CSP). The P. berghei-P. vivax chimeric strain develops normally in mosquitoes and produces highly infectious sporozoites that produce patent infection in mice that are exposed to the bites of as few as 3 P. berghei-P. vivax-infected mosquitoes. Using this transgenic parasite, we demonstrate that monoclonal and polyclonal antibodies against P. vivax CSP strongly inhibit parasite infection and thus support the notion that these antibodies play an important role in protective immunity. The chimeric parasites we developed represent a robust model for evaluating protective immune responses against P. vivax vaccines based on CSP.

A Large Plasmodium vivax Reservoir and Little Population Structure in the South Pacific.

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Cristian Koepfli

Full Text Available The importance of Plasmodium vivax in malaria elimination is increasingly being recognized, yet little is known about its population size and population genetic structure in the South Pacific, an area that is the focus of intensified malaria control.We have genotyped 13 microsatellite markers in 295 P. vivax isolates from four geographically distinct sites in Papua New Guinea (PNG and one site from Solomon Islands, representing different transmission intensities.Diversity was very high with expected heterozygosity values ranging from 0.62 to 0.98 for the different markers. Effective population size was high (12'872 to 19'533 per site. In PNG population structuring was limited with moderate levels of genetic differentiation. F ST values (adjusted for high diversity of markers were 0.14-0.15. Slightly higher levels were observed between PNG populations and Solomon Islands (F ST = 0.16.Low levels of population structure despite geographical barriers to transmission are in sharp contrast to results from regions of low P. vivax endemicity. Prior to intensification of malaria control programs in the study area, parasite diversity and effective population size remained high.

Plasmodium vivax thrombospondin related adhesion protein: immunogenicity and protective efficacy in rodents and Aotus monkeys

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Angélica Castellanos

2007-06-01

Full Text Available The thrombospondin related adhesion protein (TRAP is a malaria pre-erythrocytic antigen currently pursued as malaria vaccine candidate to Plasmodium falciparum. In this study, a long synthetic peptide (LSP representing a P. vivax TRAP fragment involved in hepatocyte invasion was formulated in both Freund and Montanide ISA 720 adjutants and administered by IM and subcutaneous routes to BALB/c mice and Aotus monkeys. We measured specific humoral immune responses in both animal species and performed a sporozoite challenge in Aotus monkeys to assess the protective efficacy of the vaccine. After immunization both mice and Aotus seroconverted as shown by ELISA, and the specific anti-peptide antibodies cross reacted with the parasite in IFAT assays. Only two out of six immunized animals became infected after P. vivax sporozoite challenge as compared with four out of six animals from the control group. These results suggest that this TRAP fragment has protective potential against P. vivax malaria and deserves further studies as vaccine candidate.

Simultaneous detection of Plasmodium vivax and Plasmodium falciparum gametocytes in clinical isolates by multiplex-nested RT-PCR.

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Kuamsab, Napaporn; Putaporntip, Chaturong; Pattanawong, Urassaya; Jongwutiwes, Somchai

2012-06-10

Gametocyte carriage is essential for malaria transmission and endemicity of disease; thereby it is a target for malaria control strategies. Malaria-infected individuals may harbour gametocytes below the microscopic detection threshold that can be detected by reverse transcription polymerase chain reaction (RT-PCR) targeting gametocyte-specific mRNA. To date, RT-PCR has mainly been applied to the diagnosis of Plasmodium falciparum gametocytes but very limited for that of Plasmodium vivax. A multiplex-nested RT-PCR targeting Pfs25 and Pvs25 mRNA specific to mature gametocytes of P. falciparum and P. vivax, respectively, was developed. The assay was evaluated using blood samples collected in rainy and dry seasons from febrile patients,in a malaria-endemic area in Thailand. Malaria diagnosis was performed by Giemsa-stained blood smears and 18S rRNA PCR. The multiplex-nested RT-PCR detected Pfs25 mRNA in 75 of 86 (87.2%) P. falciparum-infected individuals and Pvs25 mRNA in 82 of 90 (91.1%) P. vivax malaria patients diagnosed by 18S rRNA PCR. Gametocytes were detected in 38 (eight P. falciparum and 30 P. vivax) of 157 microscopy positive samples, implying that a large number of patients harbour sub-microscopic gametocytaemia. No seasonal differences in gametocyte carriage were observed for both malaria species diagnosed by multiplex-nested RT-PCR. With single-nested RT-PCR targeting Pfs25 or Pvs25 mRNA as standard, the multiplex-nested RT-PCR offered sensitivities of 97.4% and 98.9% and specificities of 100% and 98.8% for diagnosing mature gametocytes of P. falciparum and P. vivax, respectively. The minimum detection limit of the multiplex-nested PCR was 10 copies of templates. The multiplex-nested RT-PCR developed herein is useful for simultaneous assessment of both P. falciparum and P. vivax gametocyte carriage that is prevalent and generally sympatric in several malaria-endemic areas outside Africa.

Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume

International Nuclear Information System (INIS)

Piroth, Marc D.; Galldiks, Norbert; Pinkawa, Michael; Holy, Richard; Stoffels, Gabriele; Ermert, Johannes; Mottaghy, Felix M.; Shah, N. Jon; Langen, Karl-Josef; Eble, Michael J.

2016-01-01

O-(2-18 F-fluoroethyl)-L-tyrosine-(FET)-PET may be helpful to improve the definition of radiation target volumes in glioblastomas compared with MRI. We analyzed the relapse patterns in FET-PET after a FET- and MRI-based integrated-boost intensity-modulated radiotherapy (IMRT) of glioblastomas to perform an optimized target volume definition. A relapse pattern analysis was performed in 13 glioblastoma patients treated with radiochemotherapy within a prospective phase-II-study between 2008 and 2009. Radiotherapy was performed as an integrated-boost intensity-modulated radiotherapy (IB-IMRT). The prescribed dose was 72 Gy for the boost target volume, based on baseline FET-PET (FET-1) and 60 Gy for the MRI-based (MRI-1) standard target volume. The single doses were 2.4 and 2.0 Gy, respectively. Location and volume of recurrent tumors in FET-2 and MRI-2 were analyzed related to initial tumor, detected in baseline FET-1. Variable target volumes were created theoretically based on FET-1 to optimally cover recurrent tumor. The tumor volume overlap in FET and MRI was poor both at baseline (median 12 %; range 0–32) and at time of recurrence (13 %; 0–100). Recurrent tumor volume in FET-2 was localized to 39 % (12–91) in the initial tumor volume (FET-1). Over the time a shrinking (mean 12 (5–26) ml) and shifting (mean 6 (1–10 mm) of the resection cavity was seen. A simulated target volume based on active tumor in FET-1 with an additional safety margin of 7 mm around the FET-1 volume covered recurrent FET tumor volume (FET-2) significantly better than a corresponding target volume based on contrast enhancement in MRI-1 with a same safety margin of 7 mm (100 % (54–100) versus 85 % (0–100); p < 0.01). A simulated planning target volume (PTV), based on FET-1 and additional 7 mm margin plus 5 mm margin for setup-uncertainties was significantly smaller than the conventional, MR-based PTV applied in this study (median 160 (112–297) ml versus 231 (117–386) ml, p < 0

Assessment of an automated capillary system for Plasmodium vivax microsatellite genotyping.

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Manrique, Paulo; Hoshi, Mari; Fasabi, Manuel; Nolasco, Oscar; Yori, Pablo; Calderón, Martiza; Gilman, Robert H; Kosek, Margaret N; Vinetz, Joseph M; Gamboa, Dionicia

2015-08-21

Several platforms have been used to generate the primary data for microsatellite analysis of malaria parasite genotypes. Each has relative advantages but share a limitation of being time- and cost-intensive. A commercially available automated capillary gel cartridge system was assessed in the microsatellite analysis of Plasmodium vivax diversity in the Peruvian Amazon. The reproducibility and accuracy of a commercially-available automated capillary system, QIAxcel, was assessed using a sequenced PCR product of 227 base pairs. This product was measured 42 times, then 27 P. vivax samples from Peruvian Amazon subjects were analyzed with this instrument using five informative microsatellites. Results from the QIAxcel system were compared with a Sanger-type sequencing machine, the ABI PRISM(®) 3100 Genetic Analyzer. Significant differences were seen between the sequenced amplicons and the results from the QIAxcel instrument. Different runs, plates and cartridges yielded significantly different results. Additionally, allele size decreased with each run by 0.045, or 1 bp, every three plates. QIAxcel and ABI PRISM systems differed in giving different values than those obtained by ABI PRISM, and too many (i.e. inaccurate) alleles per locus were also seen with the automated instrument. While P. vivax diversity could generally be estimated using an automated capillary gel cartridge system, the data demonstrate that this system is not sufficiently precise for reliably identifying parasite strains via microsatellite analysis. This conclusion reached after systematic analysis was due both to inadequate precision and poor reproducibility in measuring PCR product size.

Infection of Laboratory-Colonized Anopheles darlingi Mosquitoes by Plasmodium vivax

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Moreno, Marta; Tong, Carlos; Guzmán, Mitchel; Chuquiyauri, Raul; Llanos-Cuentas, Alejandro; Rodriguez, Hugo; Gamboa, Dionicia; Meister, Stephan; Winzeler, Elizabeth A.; Maguina, Paula; Conn, Jan E.; Vinetz, Joseph M.

2014-01-01

Anopheles darlingi Root is the most important malaria vector in the Amazonia region of South America. However, continuous propagation of An. darlingi in the laboratory has been elusive, limiting entomological, genetic/genomic, and vector–pathogen interaction studies of this mosquito species. Here, we report the establishment of an An. darlingi colony derived from wild-caught mosquitoes obtained in the northeastern Peruvian Amazon region of Iquitos in the Loreto Department. We show that the numbers of eggs, larvae, pupae, and adults continue to rise at least to the F6 generation. Comparison of feeding Plasmodium vivax ex vivo of F4 and F5 to F1 generation mosquitoes showed the comparable presence of oocysts and sporozoites, with numbers that corresponded to blood-stage asexual parasitemia and gametocytemia, confirming P. vivax vectorial capacity in the colonized mosquitoes. These results provide new avenues for research on An. darlingi biology and study of An. darlingi–Plasmodium interactions. PMID:24534811

Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest

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Daniela Camargos Costa

2014-08-01

Full Text Available Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4% and in wild Alouatta clamitans monkeys (n = 20, 35% from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

Analysis of von Willebrand factor A domain-related protein (WARP polymorphism in temperate and tropical Plasmodium vivax field isolates

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Zakeri Sedigheh

2009-06-01

Full Text Available Abstract Background The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs, among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP, is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. Methods Clinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991 which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp. Results Amplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT to A (GCT and R (AGA to S (AGT] in comparison with the Sal-I sequence. Conclusion This study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

Imported Asymptomatic Bancroftian Filariasis Discovered from a Plasmodium vivax Infected Patient: A Case Report from Singapore

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Jean-Marc Chavatte

2017-01-01

Full Text Available Human lymphatic filariasis is a vector-borne disease mainly caused by the parasitic nematode Wuchereria bancrofti and transmitted worldwide within the tropical and subtropical regions. Singapore was once endemic for bancroftian filariasis but recent reports are scarce and the disease is nearly forgotten. The case report presented here reports the incidental hospital laboratory finding of an asymptomatic microfilaremia in a relapsing Plasmodium vivax imported case during a malaria treatment follow-up appointment. The parasite was identified by microscopy as W. bancrofti and retrospective investigation of the sample collected during malaria onset was found to be also positive. Additional confirmation was obtained by DNA amplification, sequencing, and phylogenetic analysis of the mitochondrial cox1 gene that further related the parasite to W. bancrofti strains from the Indian region. Considering the large proportion of asymptomatic filariasis with microfilaremia, the high number of migrants and travellers arriving from the surrounding endemic countries, and the common presence of local competent mosquito vectors, Singapore remains vulnerable to the introduction, reemergence, and the spread of lymphatic filariasis. This report brings out from the shadow the potential risk of lymphatic filariasis in Singapore and could help to maintain awareness about this parasitic disease and its public health importance.

Relapsing-Remitting MS (RRMS)

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Full Text Available ... MS Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting ... Here Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ... Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the Society ...

Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

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Dhakal, Sughosh; Bates, James E. [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Casulo, Carla; Friedberg, Jonathan W.; Becker, Michael W.; Liesveld, Jane L. [Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Constine, Louis S., E-mail: louis_constine@urmc.rochester.edu [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States)

2016-10-01

Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from further analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.

Resistance of infection by Plasmodium vivax to chloroquine in Bolivia.

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Añez, Arletta; Moscoso, Manuel; Laguna, Ángel; Garnica, Cecilia; Melgar, Viviana; Cuba, Mauren; Gutierrez, Sonia; Ascaso, Carlos

2015-07-01

Chloroquine (CQ) over three days plus primaquine (PQ) for seven days is the treatment of choice of infections by Plasmodium vivax in Bolivia, where 95% of the cases of malaria are attributed to this species. The aim of this study was to evaluate the therapeutic efficacy of CQ in this setting. Patients in the Amazon region of northern Bolivia, were included in the study from May to November 2011 and the therapeutic efficacy of CQ was evaluated over a 28-day follow-up period. Patients with P. vivax mono-infection received 25 mg/Kg body weight of CQ over three days. The concentrations of CQ + desethylchloroquine (DCQ) in blood were determined at days 7 and 28 of follow up; at follow-up and on the day of treatment failure was administered PQ. One hundred patients fulfilled the inclusion criteria, two were lost to follow up and another two were later excluded for protocol violation. Of the 96 patients who completed the follow up 10 showed TF; one presented continued parasitaemia until day 7 of follow up, three on day 21 and six on day 28 of follow up. The geometric mean of CQ + DCQ on day 7 was 321.7 ng/ml (range 197-535 ng/ml). In six patients with TF the CQ + DCQ concentrations in blood on the day of TF were >100 ng/ml. The rate of resistance was 6.5%. The present study demonstrates the presence of resistance to CQ in the treatment of malaria by P. vivax in the Amazon region of Bolivia. New clinical trials are needed to establish alternative treatments against these parasites in this region of South America.

Could Plasmodium vivax malaria trigger malnutrition? Revisiting the Bradford Hill criteria to assess a causal relationship between two neglected problems

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Wuelton Marcelo Monteiro

2016-06-01

Full Text Available Abstract: The benign characteristics formerly attributed to Plasmodium vivax infections have recently changed owing to the increasing number of reports of severe vivax malaria resulting in a broad spectrum of clinical complications, probably including undernutrition. Causal inference is a complex process, and arriving at a tentative inference of the causal or non-causal nature of an association is a subjective process limited by the existing evidence. Applying classical epidemiology principles, such as the Bradford Hill criteria, may help foster an understanding of causality and lead to appropriate interventions being proposed that may improve quality of life and decrease morbidity in neglected populations. Here, we examined these criteria in the context of the available data suggesting that vivax malaria may substantially contribute to childhood malnutrition. We found the data supported a role for P. vivax in the etiology of undernutrition in endemic areas. Thus, the application of modern causal inference tools, in future studies, may be useful in determining causation.

Modelling the Incidence of Plasmodium vivax and Plasmodium falciparum Malaria in Afghanistan 2006–2009

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Alegana, Victor A.; Wright, Jim A.; Nahzat, Sami M.; Butt, Waqar; Sediqi, Amad W.; Habib, Naeem; Snow, Robert W.; Atkinson, Peter M.; Noor, Abdisalan M.

2014-01-01

Background Identifying areas that support high malaria risks and where populations lack access to health care is central to reducing the burden in Afghanistan. This study investigated the incidence of Plasmodium vivax and Plasmodium falciparum using routine data to help focus malaria interventions. Methods To estimate incidence, the study modelled utilisation of the public health sector using fever treatment data from the 2012 national Malaria Indicator Survey. A probabilistic measure of attendance was applied to population density metrics to define the proportion of the population within catchment of a public health facility. Malaria data were used in a Bayesian spatio-temporal conditional-autoregressive model with ecological or environmental covariates, to examine the spatial and temporal variation of incidence. Findings From the analysis of healthcare utilisation, over 80% of the population was within 2 hours’ travel of the nearest public health facility, while 64.4% were within 30 minutes’ travel. The mean incidence of P. vivax in 2009 was 5.4 (95% Crl 3.2–9.2) cases per 1000 population compared to 1.2 (95% Crl 0.4–2.9) cases per 1000 population for P. falciparum. P. vivax peaked in August while P. falciparum peaked in November. 32% of the estimated 30.5 million people lived in regions where annual incidence was at least 1 case per 1,000 population of P. vivax; 23.7% of the population lived in areas where annual P. falciparum case incidence was at least 1 per 1000. Conclusion This study showed how routine data can be combined with household survey data to model malaria incidence. The incidence of both P. vivax and P. falciparum in Afghanistan remain low but the co-distribution of both parasites and the lag in their peak season provides challenges to malaria control in Afghanistan. Future improved case definition to determine levels of imported risks may be useful for the elimination ambitions in Afghanistan. PMID:25033452

Plasmodium vivax associated severe malaria complications among children in some malaria endemic areas of Ethiopia.

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Ketema, Tsige; Bacha, Ketema

2013-07-08

Although, Plasmodium vivax is a rare parasite in most parts of Africa, it has significant public health importance in Ethiopia. In some parts of the country, it is responsible for majority of malaria associated morbidity. Recently severe life threatening malaria syndromes, frequently associated to P. falciparum, has been reported from P. vivax mono-infections. This prompted designing of the current study to assess prevalence of severe malaria complications related to P. vivax malaria in Ethiopia. The study was conducted in two study sites, namely Kersa and Halaba Kulito districts, located in southwest and southern parts of Ethiopia, respectively. Children, aged ≤ 10 years, who visited the two health centers during the study period, were recruited to the study. Clinical and demographic characteristics such as age, sex, temperature, diarrhea, persistent vomiting, confusion, respiratory distress, hepatomegaly, splenomegaly, hemoglobinuria, and epitaxis were assessed for a total of 139 children diagnosed to have P. vivax mono-infection. Parasitological data were collected following standard procedures. Hemoglobin and glucose level were measured using portable hemocue instrument. Median age of children was 4.25 ± 2.95 years. Geometric mean parasite count and mean hemoglobin level were 4254.89 parasite/μl and 11.55 g/dl, respectively. Higher prevalence rate of malaria and severe malaria complications were observed among children enrolled in Halaba district (P infection (OR = 1.9, 95% CI, 1.08 to 3.34), while female had higher risk to anemia (OR = 1.91, 95% CI, 1.08 - 3.34). The observed number of anemic children was 43%, of which most of them were found in age range from 0-3 years. Furthermore, P. vivax malaria was a risk factor for incidence of anemia (P lower than those reported from other countries. However, incidence of severe malaria complications in one of the sites, Halaba district, where there is highest treatment failure to first line drug, could have

Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms.

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Rossarin Suwanarusk

2007-10-01

Full Text Available Treatment failure of chloroquine for P. vivax infections has reached high levels in the eastern provinces of Indonesia, however, in vitro characterization of chloroquine resistance and its associated molecular profile have yet to be determined.Using a modified schizont maturation assay we investigated the in vitro chloroquine susceptibility profile and molecular polymorphisms of P. vivax isolates collected from Papua, Indonesia, where high levels of clinical chloroquine treatment failure have been reported, and from Thailand, where chloroquine treatment is generally effective.The geometric mean chloroquine IC(50 for P. vivax isolates from Papua (n = 145 was 312 nM [95%CI: 237-411 nM] compared to 46.8 nM [95%CI: 34.7-63.1 nM] from Thailand (n = 81; p<0.001. Correlating with the known clinical efficacy of the area, a cut off for chloroquine resistance was defined as 220 nM, a level exceeded in 13.6% (11/81 of Thai isolates and 65% (94/145 of Papuan isolates; p<0.001. Several sequence polymorphisms in pvcrt-o and pvmdr1, and difference in pvmdr1 copy number were identified. A Y976F mutation in pvmdr1 was present in 96% (123/128 of Papuan isolates and 25% (17/69 of Thai isolates; p<0.001. Overall, the geometric mean chloroquine IC(50 in isolates with the Y976F mutation was 283 nM [95%CI: 211-379], compared to 44.5 nM [95%CI: 31.3-63.4] in isolates with the wild type; p< 0.001. Pvmdr1 amplification occurred in 23% (15/66 of Thai isolates compared to none (0/104 of Indonesian isolates (p<0.001, but was not associated with increased chloroquine resistance after controlling for geographical location.In vitro susceptibility testing of P. vivax discriminates between populations with differing levels of clinical efficacy of chloroquine. The pvmdr1 polymorphism at Y976F may provide a useful tool to highlight areas of emerging chloroquine resistance, although further studies defining its clinical correlates are needed.

Correlation Between Haematological Parameters, Kidney Function Tests and Liver Function Tests in Plasmodium Falciparum and Vivax Malaria

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Mitul Chhatriwala

2017-12-01

Full Text Available Abstract: Malaria remains a major cause of morbidity and mortality in India. Plasmodium falciparum remains the main culprit although cases with vivax malaria are on the rise. Severe malaria as defined by the WHO criteria has high rate of complications and mortality. In our study we recruited microscopy positive falciparum and vivax malaria patients. Haematological and biochemical laboratory investigations were carried out in recruited patients. Both parameters were found to be significantly derailed in falciparum cases as compared to vivax. A direct correlation has been observed between kidney function tests (serum creatinine,serum urea and direct bilirubin levels across all cases of malaria. Hence these parameters can be used to identify and monitor the progress of cases of severe malaria as significant proportion of patients fulfilled the criteria of severe malaria in the cohort.

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase

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O'Neil Michael T

2008-04-01

Full Text Available Abstract Background In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. Methods The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Results Synonymous and non-synonymous single nucleotide polymorphisms (SNPs within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel. SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. Conclusion It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts

First outbreak and subsequent cases of Trypanosoma vivax in the state of Goiás, Brazil

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Thiago Souza Azeredo Bastos

Full Text Available Abstract Trypanosomiasis caused by Trypanosoma vivax has increased the reports in Brazil in the last decade. An outbreak is herein first reported in the state of Goiás, from May 2016 to January 2017. The outbreak start occurred in the city of Ipameri (Goiás after the introduction of 18 auctioned cows from the state of Minas Gerais. Direct parasitological test (blood smears and polymerase chain reactions targeting the catL genes diagnosed T. vivax infection. Fifty six cows from a herd of 161 were infected; 12 died during the outbreak and 44 animals persistently positive (by blood smears even after chemical treatment were discarded. After this first case, five other cases were detected in state of Goiás. The spread of this disease can be linked to the commercialization of animals carrying T. vivax, allied to the iatrogenic transmission practice, using a single needle and syringe for all cows, during oxytocin administration before each milking.

Perfil clínico y parasitológico de la malaria por Plasmodium falciparum y Plasmodium vivax no complicada en Córdoba, Colombia.

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Angélica Knudson Ospina; Ricardo Sánchez Pedraza; Manuel Alberto Pérez Mazorra; Liliana Jazmín Cortés Cortés; Ángela Patricia Guerra Vega; Rubén Santiago Nicholls Orejuela

2015-01-01

Antecedentes. En Colombia existen pocos estudios que buscan encontrar diferencias clínicas y parasitológicas en la malaria causada por Plasmodium falciparum y Plasmodium vivax.  Objetivo. Describir el perfil clínico y parasitológico de las malarias por Plasmodium falciparum y Plasmodium vivax no complicadas en Tierralta, Córdoba, Colombia. Materiales y métodos. Se evaluaron pacientes con paludismo no complicado por Plasmodium falciparum y Plasmodium vivax según los protocolos estandariz...

The periodicity of Plasmodium vivax and Plasmodium falciparum in Venezuela.

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Grillet, María-Eugenia; El Souki, Mayida; Laguna, Francisco; León, José Rafael

2014-01-01

We investigated the periodicity of Plasmodium vivax and P. falciparum incidence in time-series of malaria data (1990-2010) from three endemic regions in Venezuela. In particular, we determined whether disease epidemics were related to local climate variability and regional climate anomalies such as the El Niño Southern Oscillation (ENSO). Malaria periodicity was found to exhibit unique features in each studied region. Significant multi-annual cycles of 2- to about 6-year periods were identified. The inter-annual variability of malaria cases was coherent with that of SSTs (ENSO), mainly at temporal scales within the 3-6 year periods. Additionally, malaria cases were intensified approximately 1 year after an El Niño event, a pattern that highlights the role of climate inter-annual variability in the epidemic patterns. Rainfall mediated the effect of ENSO on malaria locally. Particularly, rains from the last phase of the season had a critical role in the temporal dynamics of Plasmodium. The malaria-climate relationship was complex and transient, varying in strength with the region and species. By identifying temporal cycles of malaria we have made a first step in predicting high-risk years in Venezuela. Our findings emphasize the importance of analyzing high-resolution spatial-temporal data to better understand malaria transmission dynamics. Copyright © 2013 Elsevier B.V. All rights reserved.

[Relapse: causes and consequences].

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Thomas, P

2013-09-01

Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

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Lis R V Antonelli

2014-09-01

Full Text Available Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+CD16- (classical, CD14(+CD16(+ (inflammatory, and CD14loCD16(+ (patrolling cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+ cells, in particular the CD14(+CD16(+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+CD16(+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+CD16(+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.

Búsqueda e identificación de nuevos candidatos a vacuna contra la malaria producida por Plasmodium vivax

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Andrés Mauricio Pinzón Velasco

2004-07-01

bioinformáticas, estableciendo diversos patrones de alineamiento, así como niveles de similitud no menores al 40%. A pesar de un riguroso enmascaramiento tanto de las secuencias protéicas de P. falciparum, como del genoma de P. vivax, en este último fue evidente una alta presencia de regiones repetitivas que no fueron enmascaradas por ninguna de las fuentes de ADN repetitivo presente en la base de datos de REPBASE, lo cual lleva a pensar que dichas regiones pueden ser específicas de este tipo de organismos. Finalmente se encontraron coincidencias entre 76 secuencias proteicas con actividad antigénica de P. falciparum y el genoma hasta ahora secuenciado de P. vivax, que cumplían con los requisitos mínimos para establecer los niveles de coincidencia, entre las cuales se determinó que cuatro constituyen importantes candidatos a una vacuna contra la malaria producida por P. vivax.

The structure of Plasmodium vivax phosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix

International Nuclear Information System (INIS)

Arakaki, Tracy; Neely, Helen; Boni, Erica; Mueller, Natasha; Buckner, Frederick S.; Van Voorhis, Wesley C.; Lauricella, Angela; DeTitta, George; Luft, Joseph; Hol, Wim G. J.; Merritt, Ethan A.

2007-01-01

The crystal structure of a phosphatidylethanolamine-binding protein from P. vivax, a homolog of Raf-kinase inhibitor protein (RKIP), has been solved to a resolution of 1.3 Å. The inferred interaction surface near the anion-binding site is found to include a distinctive left-handed α-helix. The structure of a putative Raf kinase inhibitor protein (RKIP) homolog from the eukaryotic parasite Plasmodium vivax has been studied to a resolution of 1.3 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protozoan protein is topologically similar to previously studied members of the phosphatidylethanolamine-binding protein (PEBP) sequence family, but exhibits a distinctive left-handed α-helical region at one side of the canonical phospholipid-binding site. Re-examination of previously determined PEBP structures suggests that the P. vivax protein and yeast carboxypeptidase Y inhibitor may represent a structurally distinct subfamily of the diverse PEBP-sequence family

High rates of relapse in adolescents crack users after inpatient clinic discharge

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Rosemeri Siqueira Pedroso

Full Text Available ABSTRACT Objective The objective of the present study was to evaluate 88 adolescent crack users referred to hospitalization and to follow them up after discharge to investigate relapse and factors associated with treatment. Methods Cohort (30 and 90 days after discharge from a psychiatric hospital and a rehab clinic for treatment for chemical dependency in Porto Alegre between 2011 and 2012. Instruments: Semi-structured interview, conducted to evaluate the sociodemographic profile of the sample and describe the pattern of psychoactive substance use; Crack Use Relapse Scale/CURS; Questionnaire Tracking Users to Crack/QTUC; K-SADS-PL. Results In the first follow-up period (30 days after discharge, 65.9% of participants had relapsed. In the second follow-up period (90 days after discharge, 86.4% of participants had relapsed. Conclusion This is one of the first studies that show the extremely high prevalence of early relapse in adolescent crack users after discharge, questioning the cost/benefit of inpatient treatment for this population. Moreover, these results corroborate studies which suggested, young psychostimulants users might need tailored intensive outpatient treatment with contingency management and other behavioral strategies, in order to increase compliance and reduce drug or crime relapse, but this specific therapeutic modality is still scarce and must be developed in Brazil.

Estimated effect of climatic variables on the transmission of Plasmodium vivax malaria in the Republic of Korea.

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Kim, Young-Min; Park, Jae-Won; Cheong, Hae-Kwan

2012-09-01

Climate change may affect Plasmodium vivax malaria transmission in a wide region including both subtropical and temperate areas. We aimed to estimate the effects of climatic variables on the transmission of P. vivax in temperate regions. We estimated the effects of climatic factors on P. vivax malaria transmission using data on weekly numbers of malaria cases for the years 2001-2009 in the Republic of Korea. Generalized linear Poisson models and distributed lag nonlinear models (DLNM) were adopted to estimate the effects of temperature, relative humidity, temperature fluctuation, duration of sunshine, and rainfall on malaria transmission while adjusting for seasonal variation, between-year variation, and other climatic factors. A 1°C increase in temperature was associated with a 17.7% [95% confidence interval (CI): 16.9, 18.6%] increase in malaria incidence after a 3-week lag, a 10% rise in relative humidity was associated with 40.7% (95% CI: -44.3, -36.9%) decrease in malaria after a 7-week lag, a 1°C increase in the diurnal temperature range was associated with a 24.1% (95% CI: -26.7, -21.4%) decrease in malaria after a 7-week lag, and a 10-hr increase in sunshine per week was associated with a 5.1% (95% CI: -8.4, -1.7%) decrease in malaria after a 2-week lag. The cumulative relative risk for a 10-mm increase in rainfall (≤ 350 mm) on P. vivax malaria was 3.61 (95% CI: 1.69, 7.72) based on a DLNM with a 10-week maximum lag. Our findings suggest that malaria transmission in temperate areas is highly dependent on climate factors. In addition, lagged estimates of the effect of rainfall on malaria are consistent with the time necessary for mosquito development and P. vivax incubation.

Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatment

DEFF Research Database (Denmark)

Hajek, Peter; Tønnesen, Philip; Arteaga, Carmen

2009-01-01

AIM: While older behavioural and pharmacological approaches to preventing relapse to smoking show little efficacy, a recent randomized trial of an extended course of varenicline reported positive results. In this secondary analysis, trial data were examined to see whether smokers who manage......, 44% of the 12-week abstainers were abstinent from the target quit date (TQD), while the rest stopped smoking later. We examined the relationship between quit pattern and the varenicline versus placebo difference in continuous abstinence rates at week 52 and contributions of baseline patient...... characteristics. RESULTS: With increasing delay in initial quitting, 12-month success rates declined. Participants who had their last cigarette at week 11 of open-label treatment had quit rates at 52 weeks of 5.7% compared with 54.9% in those who last smoked in week 1 [odds ratio (OR) 20.3 (6.3, 65.9); P

Predicting Relapse among Young Adults: Psychometric Validation of the Advanced Warning of Relapse (AWARE) Scale

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Kelly, John F.; Hoeppner, Bettina B.; Urbanoski, Karen A.; Slaymaker, Valerie

2011-01-01

Objective Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure - the Advance WArning of RElapse scale (AWARE) scale (Miller and Harris, 2000) in an understudied but clinically important sample of young adults. Method Inpatient youth (N=303; Age 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Results Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. Conclusions The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. PMID:21700396

Predicting relapse among young adults: psychometric validation of the Advanced WArning of RElapse (AWARE) scale.

Science.gov (United States)

Kelly, John F; Hoeppner, Bettina B; Urbanoski, Karen A; Slaymaker, Valerie

2011-10-01

Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure-the Advance WArning of RElapse (AWARE) scale (Miller & Harris, 2000) in an understudied but clinically important sample of young adults. Inpatient youth (N=303; Ages 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized, non-inferiority, trial

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Woodrow Charles J

2010-04-01

Full Text Available Abstract Background Afghanistan's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection, the parasite responsible for the majority of its malaria burden. Chloroquine resistance in P. vivax is emerging in Asia. Therapeutic responses across Afghanistan have not been evaluated in detail. Methods Between July 2007 and February 2009, an open-label, randomized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted. Consistent with current national guidelines, primaquine was not administered. Subjects were followed up daily during the acute phase of illness (days 0-3 and weekly until day 56. The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment, with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine (Δ = 5% difference in proportion of failures. Results Of 2,182 individuals with positive blood films for P. vivax, 536 were enrolled in the trial. The day 28 cure rate was 100% in both treatment groups. Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine. At day 56, there were more recurrent infections in the chloroquine arm (8.9%, 95% CI 6.0-13.1% than the dihydroartemisinin-piperaquine arm (2.8%, 95% CI 1.4-5.8%, a difference in cumulative recurrence rate of 6.1% (2-sided 90%CI +2.6 to +9.7%. The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine (p = 0.003. Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence. Both regimens were well tolerated and no serious adverse events were reported. Conclusions Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan. In a setting where radical

Point-of-care G6PD diagnostics for Plasmodium vivax malaria is a clinical and public health urgency

OpenAIRE

Baird, J. Kevin

2015-01-01

Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Recent clinical evidence discredits the long-held notion of this infection as intrinsically benign revealing an often threatening course associated with mortality. Most acute attacks by this species derive from latent forms in the human liver called hypnozoites. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against fu...

Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

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Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

2011-01-01

Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

Costs Associated with Malaria in Pregnancy in the Brazilian Amazon, a Low Endemic Area Where Plasmodium vivax Predominates

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Bôtto-Menezes, Camila; Bardají, Azucena; dos Santos Campos, Giselane; Fernandes, Silke; Hanson, Kara; Martínez-Espinosa, Flor Ernestina; Menéndez, Clara; Sicuri, Elisa

2016-01-01

Background Information on costs associated with malaria in pregnancy (MiP) in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon. Methods/Principal Findings Between January 2011 and March 2012 patient costs for the treatment of MiP were collected through an exit survey at a tertiary referral hospital and at a primary health care centre in the Manaus metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with malaria were interviewed after an outpatient consultation or at discharge after admission. Seventy-three interviews were included in the analysis. Ninety-six percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In 2010, the total median costs from the patient perspective were estimated at US $45.91 and US $216.29 for an outpatient consultation and an admission, respectively. When multiple P. vivax infections during the same pregnancy were considered, patient costs increased up to US $335.85, representing the costs of an admission plus an outpatient consultation. Provider direct and overhead cost data were obtained from several sources. The provider cost associated with an outpatient case, which includes several consultations at the tertiary hospital was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum malaria episode. The cost of an inpatient day and average admission of 3 days was US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis and treatment of all malaria cases reported in pregnant women in Manaus in 2010 (N = 364) were US $17,038.50, of which 92.4% (US$ 15,741.14) due to P. vivax infection. Conclusion Despite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P

Costs Associated with Malaria in Pregnancy in the Brazilian Amazon, a Low Endemic Area Where Plasmodium vivax Predominates.

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Camila Bôtto-Menezes

2016-03-01

Full Text Available Information on costs associated with malaria in pregnancy (MiP in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon.Between January 2011 and March 2012 patient costs for the treatment of MiP were collected through an exit survey at a tertiary referral hospital and at a primary health care centre in the Manaus metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with malaria were interviewed after an outpatient consultation or at discharge after admission. Seventy-three interviews were included in the analysis. Ninety-six percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In 2010, the total median costs from the patient perspective were estimated at US $45.91 and US $216.29 for an outpatient consultation and an admission, respectively. When multiple P. vivax infections during the same pregnancy were considered, patient costs increased up to US $335.85, representing the costs of an admission plus an outpatient consultation. Provider direct and overhead cost data were obtained from several sources. The provider cost associated with an outpatient case, which includes several consultations at the tertiary hospital was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum malaria episode. The cost of an inpatient day and average admission of 3 days was US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis and treatment of all malaria cases reported in pregnant women in Manaus in 2010 (N = 364 were US $17,038.50, of which 92.4% (US$ 15,741.14 due to P. vivax infection.Despite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P. falciparum. The information generated may

Social settings and addiction relapse.

Science.gov (United States)

Walton, M A; Reischl, T M; Ramanthan, C S

1995-01-01

Despite addiction theorists' acknowledgment of the impact of environmental factors on relapse, researchers have not adequately investigated these influences. Ninety-six substance users provided data regarding their perceived risk for relapse, exposure to substances, and involvement in reinforcing activities. These three setting attributes were assessed in their home, work, and community settings. Reuse was assessed 3 months later. When controlling for confounding variables, aspects of the home settings significantly distinguished abstainers from reusers; perceived risk for relapse was the strongest predictor of reuse. Exposure to substances and involvement in reinforcing activities were not robust reuse indicators. The work and community settings were not significant determinants of reuse. These findings offer some initial support for the utility of examining social settings to better understand addiction relapse and recovery. Identification of setting-based relapse determinants provides concrete targets for relapse prevention interventions.

Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse.

Science.gov (United States)

Ogden, Angela; Rida, Padmashree C G; Knudsen, Beatrice S; Kucuk, Omer; Aneja, Ritu

2015-10-28

Although docetaxel significantly improves survival in a variety of malignancies, its clinical utility is severely restricted by acquired chemoresistance and disease relapse. To uncover the mechanisms underlying these all too common occurrences, an abundance of research has focused on mutations and gene expression patterns; however, these findings are yet to translate into improved outcomes for patients being administered this drug. These analyses have overlooked a promising lead in the quest to discern key mediators of resistance and relapse following docetaxel therapy: polyploidization. This process is manifested following docetaxel-mediated mitotic arrest by the appearance of giant, multinucleated cells, which slipped from mitosis without undergoing cytokinesis. Polyploid cells generally possess supernumerary centrosomes, are chromosomally instable, and resist chemotherapy. We thus suspect that chemoresistance and relapse following treatment with docetaxel might be combatted by co-administration of centrosome declustering drugs, which could selectively destroy polyploid cells given that normal cells do not possess amplified centrosomes, an intriguing paradigm that warrants further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif.

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Nora Céspedes

Full Text Available Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.

Relapsing-Remitting MS (RRMS)

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Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite

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Alba Marina Gimenez

2017-10-01

Full Text Available Plasmodium vivax is the most common species that cause malaria outside of the African continent. The development of an efficacious vaccine would contribute greatly to control malaria. Recently, using bacterial and adenoviral recombinant proteins based on the P. vivax circumsporozoite protein (CSP, we demonstrated the possibility of eliciting strong antibody-mediated immune responses to each of the three allelic forms of P. vivax CSP (PvCSP. In the present study, recombinant proteins representing the PvCSP alleles (VK210, VK247, and P. vivax-like, as well as a hybrid polypeptide, named PvCSP-All epitopes, were generated. This hybrid containing the conserved C-terminal of the PvCSP and the three variant repeat domains in tandem were successfully produced in the yeast Pichia pastoris. After purification and biochemical characterization, they were used for the experimental immunization of C57BL/6 mice in a vaccine formulation containing the adjuvant Poly(I:C. Immunization with a recombinant protein expressing all three different allelic forms in fusion elicited high IgG antibody titers reacting with all three different allelic variants of PvCSP. The antibodies targeted both the C-terminal and repeat domains of PvCSP and recognized the native protein on the surface of P. vivax sporozoites. More importantly, mice that received the vaccine formulation were protected after challenge with chimeric Plasmodium berghei sporozoites expressing CSP repeats of P. vivax sporozoites (Pb/PvVK210. Our results suggest that it is possible to elicit protective immunity against one of the most common PvCSP alleles using soluble recombinant proteins expressed by P. pastoris. These recombinant proteins are promising candidates for clinical trials aiming to develop a multiallele vaccine against P. vivax malaria.

Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivax and Plasmodium falciparum in two districts of Nepal

DEFF Research Database (Denmark)

Ranjitkar, Samir; Schousboe, Mette L; Thomsen, Thomas

2011-01-01

ABSTRACT: BACKGROUND: Sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) against Plasmodium falciparum in highly...... endemic areas. However, SP is still used against P. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of P. falciparum and Plasmodium vivax CQ and SP resistance to determine...... and P. vivax for CQ (Pfcrt, Pfmdr1, Pvmdr1) and SP (Pfdhfr, Pfdhps, Pvdhfr), using various PCR-based methods. RESULTS AND DISCUSSION: Positive P. vivax and P. falciparum infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based...

The Cost of Relapse in Schizophrenia.

Science.gov (United States)

Pennington, Mark; McCrone, Paul

2017-09-01

Schizophrenia is a chronic and debilitating mental illness characterised by periods of relapse that require resource intensive management. Quantifying the cost of relapse is central to the evaluation of the cost effectiveness of treating schizophrenia. We aimed to undertake a comprehensive search of the available literature on the cost of relapse. We performed a search on multiple databases (MEDLINE, Embase, PsycINFO and Health Management Information Consortium) for any study reporting a cost of relapse or data from which such a cost could be calculated. Costs are reported in 2015 international dollars. We found 16 studies reporting costs associated with relapse over a defined period of time and identified a cost associated with hospitalisation for relapse in 43 studies. Eight clinical decision analyses also provided cost estimates. Studies from the US report excess costs of relapse of $6033-$32,753 (2015 Purchasing Power Parity dollars [PPP$]) over periods of 12-15 months. European studies report excess costs of $8665-$18,676 (2015 PPP$) over periods of 6-12 months. Estimates of the cost of hospitalisation for relapse are more diverse, and associated with marked differences in typical length of stay across jurisdictions. Wide ranges in the estimated cost of relapse may reflect differences in sample section and relapse definition as well as practice styles and differences in resource costs. Selection of the most appropriate cost estimate should be guided by the definition of relapse and the analysis setting.

Traffic pathways of Plasmodium vivax antigens during intraerythrocytic parasite development.

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Bracho, Carmen; Dunia, Irene; De, La Rosa Mercedes; Benedetti, Ennio-Lucio; Perez, Hilda A

2002-03-01

We investigated the secretory traffic of a Plasmodium vivax antigen (Pv-148) synthesised by the parasite during the blood cycle, exported into the host cell cytosol and then transported to the surface membrane of the infected erythrocyte. Studies of the ultrastructure of erythrocytes infected with P. vivax showed that intracellular schizogony is accompanied by the generation of parasite-induced membrane profiles in the erythrocyte cytoplasm. These structures are detectable soon after the parasite invades the erythrocyte and develop an elaborate organisation, leading to a tubovesicular membrane (TVM) network, in erythrocytes infected with mature trophozoites. Interestingly, the clefts formed stacked, flattened cisternae resembling a classical Golgi apparatus. The TVM network stained with the fluorescent Golgi marker Bodipy-ceramide. Specific immunolabelling showed that Pv-148 was transferred from the parasite to the erythrocyte surface membrane via the clefts and the TVM network. These findings suggest that the TVM network is part of the secretory pathways involved in parasite protein transport across the Plasmodium-infected erythrocyte and that Pv- 148 may represent a marker that links the parasite with the host cell cytoplasm and, in turn, with the extracellular milieu.

Alcohol consumption and symptoms as predictors for relapse of DSM-5 alcohol use disorder.

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Tuithof, Marlous; ten Have, Margreet; van den Brink, Wim; Vollebergh, Wilma; de Graaf, Ron

2014-07-01

Alcohol consumption levels and alcohol use disorder (AUD) symptoms may serve as easily quantifiable markers for AUD relapse after remission and might help prevention workers identify at-risk individuals. We investigated the predictive value of alcohol consumption and AUD symptoms on relapse. Data are from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). We selected 506 people in ≥12-month DSM-5 AUD remission at baseline and assessed their status at 3-year follow-up. AUD symptoms and drinking patterns were assessed using the Composite International Diagnostic Interview 3.0. Time since remission was assessed retrospectively at baseline and ranged from 1 to 48 years. Predictors for relapse were examined using Cox regression analysis. Cumulative AUD relapse rate was 5.6% at 5 years, 9.1% at 10 years and 12.0% at 20 years. Relapse was predicted by both medium (15-28/22-42 drinks weekly for women/men) and high (≥29/43) past alcohol intake, 6+ lifetime AUD symptoms, 'impaired control over use', and at-risk (≥8/15) current intake. The risk of relapse was especially high when medium or high past intake or 6+ lifetime symptoms coincided with current at-risk drinking. Only a minority of people in DSM-5 AUD remission relapsed, but the risk of relapse increased substantially with the presence of at least one of the risk factors. Moreover, at-risk current drinking coupled with other risk factors substantially increased the likelihood of relapse. Therefore, current drinking may provide an adequate reference point for relapse prevention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Performance of an immunochromatography test for vivax malaria in the Amazon region, Brazil

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Alberto Ferreira Figueiredo Filho

2003-06-01

Full Text Available The study was carried out to evaluate the diagnostic performance of the ICT malaria Pf/PvTM test for vivax malaria diagnosis in Belém, Amazon region, Brazil. The results of blood malaria parasites examination using an immunochromatography test were compared with thick blood film (TBF examination. It was also evaluated the performance of this test storaged at three different temperatures (25°C, 30°C, and 37°C for 24 hours before use. Overall sensitivity of ICT Pf/PvTM was 61.8% with a specificity of 100%, positive and negative predictive value of 100% and 71.8%, respectively and accuracy of 80.6%. The test sensitivity was independent of the parasite density. This test needs to be further reviewed in order to have better performance for P. vivax malaria diagnosis.

Relapsing-Remitting MS (RRMS)

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Analysis of Polymorphisms in the Merozoite Surface Protein-3a Gene and Two Microsatellite Loci in Sri Lankan Plasmodium vivax: Evidence of Population Substructure in Sri Lanka

DEFF Research Database (Denmark)

Schousboe, Mette L; Rajakaruna, Rupika S; Amerasinghe, Priyanie H

2011-01-01

Abstract. The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3a (Pvmsp-3a) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3a, 11 alleles....... The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka....

Genotyping Plasmodium vivax isolates from the 2011 outbreak in Greece

DEFF Research Database (Denmark)

Spanakos, Gregory; Alifrangis, Michael; Schousboe, Mette L

2013-01-01

Plasmodium vivax malaria was common in Greece until the 1950s with epidemics involving thousands of cases every year. Greece was declared free of malaria by the World Health Organization in 1974. From 1974 to 2010, an average of 39 cases per year were reported, which were mainly imported. However...... during 2011 is described, to elucidate the possible origin and spread of the disease....

Substantial population structure of Plasmodium vivax in Thailand facilitates identification of the sources of residual transmission.

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Veerayuth Kittichai

2017-10-01

Full Text Available Plasmodium vivax transmission in Thailand has been substantially reduced over the past 10 years, yet it remains highly endemic along international borders. Understanding the genetic relationship of residual parasite populations can help track the origins of the parasites that are reintroduced into malaria-free regions within the country.A total of 127 P. vivax isolates were genotyped from two western provinces (Tak and Kanchanaburi and one eastern province (Ubon Ratchathani of Thailand using 10 microsatellite markers. Genetic diversity was high, but recent clonal expansion was detected in all three provinces. Substantial population structure and genetic differentiation of parasites among provinces suggest limited gene flow among these sites. There was no haplotype sharing among the three sites, and a reduced panel of four microsatellite markers was sufficient to assign the parasites to their provincial origins.Significant parasite genetic differentiation between provinces shows successful interruption of parasite spread within Thailand, but high diversity along international borders implies a substantial parasite population size in these regions. The provincial origin of P. vivax cases can be reliably determined by genotyping four microsatellite markers, which should be useful for monitoring parasite reintroduction after malaria elimination.

Substantial population structure of Plasmodium vivax in Thailand facilitates identification of the sources of residual transmission.

Science.gov (United States)

Kittichai, Veerayuth; Koepfli, Cristian; Nguitragool, Wang; Sattabongkot, Jetsumon; Cui, Liwang

2017-10-01

Plasmodium vivax transmission in Thailand has been substantially reduced over the past 10 years, yet it remains highly endemic along international borders. Understanding the genetic relationship of residual parasite populations can help track the origins of the parasites that are reintroduced into malaria-free regions within the country. A total of 127 P. vivax isolates were genotyped from two western provinces (Tak and Kanchanaburi) and one eastern province (Ubon Ratchathani) of Thailand using 10 microsatellite markers. Genetic diversity was high, but recent clonal expansion was detected in all three provinces. Substantial population structure and genetic differentiation of parasites among provinces suggest limited gene flow among these sites. There was no haplotype sharing among the three sites, and a reduced panel of four microsatellite markers was sufficient to assign the parasites to their provincial origins. Significant parasite genetic differentiation between provinces shows successful interruption of parasite spread within Thailand, but high diversity along international borders implies a substantial parasite population size in these regions. The provincial origin of P. vivax cases can be reliably determined by genotyping four microsatellite markers, which should be useful for monitoring parasite reintroduction after malaria elimination.

Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct

DEFF Research Database (Denmark)

Céspedes, Nora; Jiménez, Eliécer; Lopez-Perez, Mary

2014-01-01

BACKGROUND: The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in pa...

Singapore's Anopheles sinensis Form A is susceptible to Plasmodium vivax isolates from the western Thailand-Myanmar border.

Science.gov (United States)

Pang, Sook-Cheng; Andolina, Chiara; Malleret, Benoit; Christensen, Peter R; Lam-Phua, Sai-Gek; Razak, Muhammad Aliff Bin Abdul; Chong, Chee-Seng; Li, Daiqin; Chu, Cindy S; Russell, Bruce; Rénia, Laurent; Ng, Lee-Ching; Nosten, Francois

2017-11-16

Singapore has been certified malaria-free by the World Health Organization since November 1982. However, sporadic autochthonous malaria outbreaks do occur. In one of the most recent outbreaks of vivax malaria, an entomological investigation identified Anopheles sinensis as the most probable vector. As metaphase karyotype studies divided An. sinensis into two forms, A and B, with different vector competence: the investigation of vector competence of An. sinensis found in Singapore was thus pursued using Plasmodium vivax field isolates from the Thailand-Myanmar border. Adults and larvae An. sinensis were collected from Singapore from 14 different locations, using various trapping and collection methods between September 2013 and January 2016. Molecular identification of An. sinensis species were conducted by amplifying the ITS2 and CO1 region using PCR. Experimental infections of An. sinensis using blood from seven patients infected with P. vivax from the Thailand-Myanmar border were conducted with Anopheles cracens (An. dirus B) as control. Phylogenetic analysis showed that An. sinensis (F 22 , F 2 and collected from outbreak areas) found in Singapore was entirely Form A, and closely related to An. sinensis Form A from Thailand. Artificial infection of these Singapore strain An. sinensis Form A resulted in the development of oocysts in four experiments, with the number of sporozoites produced by one An. sinensis ranging from 4301 to 14,538. Infection experiments showed that An. sinensis Form A from Singapore was susceptible to Thai-Myanmar P. vivax strain, suggesting a potential role as a malaria vector in Singapore.

Enteroparasite and vivax malaria co-infection on the Brazil-French Guiana border: Epidemiological, haematological and immunological aspects.

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Rubens Alex de Oliveira Menezes

Full Text Available Malaria-enteroparasitic co-infections are known for their endemicity. Although they are prevalent, little is known about their epidemiology and effect on the immune response. This study evaluated the effect of enteroparasite co-infections with malaria caused by Plasmodium vivax in a border area between Brazil and French Guiana. The cross sectional study took place in Oiapoque, a municipality of Amapá, on the Amazon border. Malaria was diagnosed using thick blood smears, haemoglobin dosage by an automated method and coproparasitology by the Hoffman and Faust methods. The anti-PvMSP-119 IgG antibodies in the plasma were evaluated using ELISA and Th1 (IFN-γ, TNF-α and IL-2, and Th2 (IL-4, IL-5 and IL-10 cytokine counts were performed by flow cytometry. The participants were grouped into those that were monoinfected with vivax malaria (M, vivax malaria-enteroparasite co-infected (CI, monoinfected with enteroparasite (E and endemic controls (EC, who were negative for both diseases. 441 individuals were included and grouped according to their infection status: [M 6.9% (30/441], [Cl 26.5% (117/441], [E 32.4% (143/441] and [EC 34.2% (151/441]. Males prevailed among the (M 77% (23/30 and (CI 60% (70/117 groups. There was a difference in haemoglobin levels among the different groups under study for [EC-E], [EC-Cl], [E-M] and [Cl-M], with (p < 0.01. Anaemia was expressed as a percentage between individuals [CI-EC (p < 0.05]. In terms of parasitaemia, there were differences for the groups [CI-M (p < 0.05]. Anti-PvMSP-119 antibodies were detected in 51.2% (226/441 of the population. The level of cytokines evaluation revealed a large variation in TNF-α and IL-10 concentrations in the co-infected group. In this study we did not observe any influence of coinfection on the acquisition of IgG antibodies against PvMSP119, as well as on the profile of the cytokines that characterize the Th1 and Th2 patterns. However, co-infection increased TNF-α and IL-10

Field and experimental symptomless infections support wandering donkeys as healthy carriers of Trypanosoma vivax in the Brazilian Semiarid, a region of outbreaks of high mortality in cattle and sheep.

Science.gov (United States)

Rodrigues, Carla M F; Batista, Jael S; Lima, Joseney M; Freitas, Francisco J C; Barros, Isabella O; Garcia, Herakles A; Rodrigues, Adriana C; Camargo, Erney P; Teixeira, Marta M G

2015-10-28

The Brazilian Semiarid is the home of the largest herd of donkeys in South America and of outbreaks of Trypanosoma vivax infection of high mortality in dairy cattle and sheep. For a comprehensive understanding of the underlying mechanisms of these outbreaks and epidemiological role of donkeys, we surveyed for T. vivax in wandering donkeys and follow the experimental infection of donkeys and sheep with a highly virulent isolate from the Semiarid. Blood samples from 180 randomly selected wandering donkeys from the Brazilian Semiarid region were employed for PCV and parasitemia assessments and tested using the T. vivax-specific TviCATL-PCR assay. PCR-amplifed Cathepsin L (CATL) sequences were employed for genotyping and phylogenetic analysis. Four wandering donkeys were experimentally infected with a T. vivax isolate obtained during an outbreak of high mortality in the Semiarid; the control group consisted of two non-inoculated donkeys. We detected T. vivax in 30 of 180 wandering donkeys (16.6 %) using TviCATL-PCR. The prevalence was higher during the dry (15.5 %) than the wet season (1.1 %) and more females (23.1 %) than males (8.9 %) were infected. All the PCR-positive donkeys lacked patent parasitemia and showed normal values of body condition score (BCS) and packed cell volume (PCV). To evaluate the probable tolerance of donkeys to T. vivax, we inoculated five donkeys with a highly virulent isolate (TviBrRp) from the Semiarid. All inoculated donkeys became PCR-positive, but their parasitemia was always subpatent. A control goat inoculated with TviBrRp showed increasing parasitemia concurrently with fever, declining PCV, tachycardia, mucous membrane pallor, enlarged lymph nodes and anorexia. None of these signs were observed in donkeys. However, T. vivax from wandering donkeys shared identical or highly similar genotypes (identified by Cathepsin L sequences) with isolates from cattle and sheep outbreaks of acute disease in the Semiarid. This is the first

Gender differences in alcohol and substance use relapse.

Science.gov (United States)

Walitzer, Kimberly S; Dearing, Ronda L

2006-03-01

This review explores gender differences in relapse and characteristics of relapse events in alcohol and substance use. For alcohol, relapse rates were similar across gender. Although negative mood, childhood sexual abuse, alcohol-related self-efficacy, and poorer coping strategies predicted alcohol relapse, gender did not moderate these effects. Gender did moderate the association between marriage and alcohol relapse. For women, marriage and marital stress were risk factors for alcohol relapse; among men, marriage lowered relapse risk. This gender difference in the role of marriage in relapse may be a result of partner differences in problem drinking. Alcoholic women are more likely to be married to heavy drinking partners than are alcoholic men; thus, alcoholic women may be put at risk of relapse by marriage and alcoholic men may be protected by marriage. There are fewer studies documenting gender differences in substance abuse relapse so conclusions are limited and tentative. In contrast to the lack of gender differences in alcohol relapse rates, women appear less likely to experience relapse to substance use, relative to men. Women relapsing to substance use appear to be more sensitive to negative affect and interpersonal problems. Men, in contrast, may be more likely to have positive experiences prior to relapse.

Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women.

Science.gov (United States)

Requena, Pilar; Rui, Edmilson; Padilla, Norma; Martínez-Espinosa, Flor E; Castellanos, Maria Eugenia; Bôtto-Menezes, Camila; Malheiro, Adriana; Arévalo-Herrera, Myriam; Kochar, Swati; Kochar, Sanjay K; Kochar, Dhanpat K; Umbers, Alexandra J; Ome-Kaius, Maria; Wangnapi, Regina; Hans, Dhiraj; Menegon, Michela; Mateo, Francesca; Sanz, Sergi; Desai, Meghna; Mayor, Alfredo; Chitnis, Chetan C; Bardají, Azucena; Mueller, Ivo; Rogerson, Stephen; Severini, Carlo; Fernández-Becerra, Carmen; Menéndez, Clara; Del Portillo, Hernando; Dobaño, Carlota

2016-10-01

P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy. Antibody responses against all antigens were detected in all populations, with PNG women presenting the highest levels overall. P. vivax infection at sample collection time was positively associated with antibody levels against PvLP1 (fold-increase: 1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at delivery), and P. falciparum co-infection was found to increase those responses (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR proteins at delivery were associated with higher birth weight (27 g increase per duplicating antibody levels, ppregnant women had significantly higher antigen-specific IFN-γ TH1 responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6 after PvLP2 stimulation than P. vivax-infected women (p<0.05). These data demonstrate that VIR antigens induce the natural acquisition of antibody and T cell memory responses that might be important in immunity to P. vivax during pregnancy in very diverse geographical settings.

Genetic Diversity and Natural Selection in 42 kDa Region of Plasmodium vivax Merozoite Surface Protein-1 from China-Myanmar Endemic Border.

Science.gov (United States)

Zhou, Xia; Tambo, Ernest; Su, Jing; Fang, Qiang; Ruan, Wei; Chen, Jun-Hu; Yin, Ming-Bo; Zhou, Xiao-Nong

2017-10-01

Plasmodium vivax merozoite surface protein-1 (PvMSP1) gene codes for a major malaria vaccine candidate antigen. However, its polymorphic nature represents an obstacle to the design of a protective vaccine. In this study, we analyzed the genetic polymorphism and natural selection of the C-terminal 42 kDa fragment within PvMSP1 gene (Pv MSP142) from 77 P. vivax isolates, collected from imported cases of China-Myanmar border (CMB) areas in Yunnan province and the inland cases from Anhui, Yunnan, and Zhejiang province in China during 2009-2012. Totally, 41 haplotypes were identified and 30 of them were new haplotypes. The differences between the rates of non-synonymous and synonymous mutations suggest that PvMSP142 has evolved under natural selection, and a high selective pressure preferentially acted on regions identified of PvMSP133. Our results also demonstrated that PvMSP142 of P. vivax isolates collected on China-Myanmar border areas display higher genetic polymorphisms than those collected from inland of China. Such results have significant implications for understanding the dynamic of the P. vivax population and may be useful information towards China malaria elimination campaign strategies.

Molecular Epidemiology of Epidemic Severe Malaria Caused by Plasmodium vivax in the State of Amazonas, Brazil

National Research Council Canada - National Science Library

Santos-Ciminera, Patricia D

2005-01-01

.... In Manaus, the capital of Amazonas, atypical cases of Plasmodium vivax infections, including patients presenting with severe thrombocytopenia and bleeding, led to the hypothesis that severe disease...

MRI patterns in recurrence of primary CNS lymphoma in immunocompetent patients

International Nuclear Information System (INIS)

Schulte-Altedorneburg, Gernot; Heuser, Lothar; Pels, Hendrik

2012-01-01

Highlights: ► PCNSL are rare but highly malignant brain tumors. ► PCNSL recur in different anatomic sites compared with initial presentation. ► Non-parenchymal contrast enhancement is a frequent finding at initialdiagnosis and at relapse. -- Abstract: Purpose: Primary CNS lymphomas (PCNSL) are highly malignant non-Hodgkin's B-cell lymphoma restricted to the CNS. While MRI features of PCNSL at initial presentation have been comprehensively described, literature on MRI-characteristics at relapse is sparse. The purpose of this study was to investigate anatomic location and contrast enhancement patterns at PCNSL recurrence by cranial MRI. Methods: Sixteen immunocompetent patients (9 men, 7 women, median age 65 years) with histologically proven PCNSL and initial response to a standardized polychemotherapy, but suffering from a relapse were consecutively recorded. Native and contrast-enhanced MRI examinations carried out at initial presentation and at time of relapse were compared. Anatomical site of parenchymal enhancement, frequency and presence of non-parenchymal contrast enhancement (i.e. ventricular, superficial, subependymal) patterns at initial presentation and at relapse were recorded and compared. Results: Local recurrence was found at the site of the initial tumor presentation in four of the 16 cases. Six of 11 patients presenting a unilateral PCNSL at initial presentation had a bilateral involvement at relapse. In two cases, recurrence appeared solely on the contralateral side without involvement of the hemisphere initially affected. At both dates, subependymal enhancement was the most often found non-parenchymal pattern (six at initial presentation, and five at relapse). The number of patients with a ventricular contrast enhancement increased from one at initial presentation to four at relapse. Conclusions: PCNSL tend to recur in different parenchymal anatomic sites as compared with the site of the initial tumor presentation. Contrast-enhancing non

Clinical factors related to schizophrenia relapse.

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Porcelli, Stefano; Bianchini, Oriana; De Girolamo, Giovanni; Aguglia, Eugenio; Crea, Luciana; Serretti, Alessandro

2016-01-01

Relapses represent one of the main problems of schizophrenia management. This article reviews the clinical factors associated with schizophrenia relapse. A research of the last 22 years of literature data was performed. Two-hundred nineteen studies have been included. Three main groups of factors are related to relapse: factors associated with pharmacological treatment, add-on psychotherapeutic treatments and general risk factors. Overall, the absence of a maintenance therapy and treatment with first generation antipsychotics has been associated with higher risk of relapse. Further, psychotherapy add-on, particularly with cognitive behaviour therapy and psycho-education for both patients and relatives, has shown a good efficacy for reducing the relapse rate. Among general risk factors, some could be modified, such as the duration of untreated psychosis or the substance misuse, while others could not be modified as male gender or low pre-morbid level of functioning. Several classes of risk factors have been proved to be relevant in the risk of relapse. Thus, a careful assessment of the risk factors here identified should be performed in daily clinical practice in order to individualise the relapse risk for each patient and to provide a targeted treatment in high-risk subjects.

Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study.

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Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

2016-08-18

Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Forty MMT patients were included and received a 12-month follow-up. All patients were given baseline resting-state fMRI scans by using a 3.0 T GE Signa Excite HD whole-body MRI system. Monthly self-report and urine test were used to assess heroin relapse or non-relapse. Subjective craving was measured with visual analog scale. The correlation between ReHo and the degree of heroin relapse was analyzed. Compared with the non-relapsers, ReHo values were increased in the bilateral medial orbitofrontal cortex, right caudate, and right cerebellum of the heroin relapsers while those in the left parahippocampal gyrus, left middle temporal gyrus, right lingual gyrus, and precuneus were decreased in heroin relapsers. Importantly, altered ReHo in the right caudate were positively correlated with heroin relapse rates or subjective craving response. Using the resting-state fMRI technique by analysis of ReHo, we provided the first resting-state fMRI evidence that right caudate may serve as a potential biomarker for heroin relapse prediction and also as a promising target for reducing relapse risk.

Design of Plasmodium vivax Hypoxanthine-Guanine Phosphoribosyltransferase Inhibitors as Potential Antimalarial Therapeutics

Czech Academy of Sciences Publication Activity Database

Keough, D. T.; Rejman, Dominik; Pohl, Radek; Zborníková, Eva; Hocková, Dana; Croll, T.; Edstein, M. D.; Birrell, G. W.; Chavchich, M.; Naesens, L. M. J.; Pierens, G. K.; Brereton, I. M.; Guddat, L. W.

2018-01-01

Roč. 13, č. 1 (2018), s. 82-90 ISSN 1554-8929 R&D Projects: GA ČR(CZ) GA16-06049S; GA ČR GA15-11711S Institutional support: RVO:61388963 Keywords : plasmodium vivax * inhibitor * pyrrolidine nucleotide bisphosphonate * HXGPRT Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 4.995, year: 2016

Monitoring of Plasmodium vivax and Plasmodium falciparum response to chloroquine in Bandar-Abbas district, Hormozgan province, Iran

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Nateghpour M M

2009-06-01

Full Text Available "n Normal 0 false false false EN-GB X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Malaria is an important parasitic vector-borne disease with considerable infectivity and world-wide distribution. Since prevalence of chloroquine resistance in Plasmodium falciparum at the malarious areas such as Iran and reliable reports from many countries indicating emergence of chloroquine- resistant strains of P.vivax, this study was conducted to monitor the current response of vivax and falciparum plasmodia to chloroquine in Bandar-Abbas district, a malarious area in Iran."n"nMethods: The study was conducted at the Bandar-Abbas district in Hormozgan province, Iran. 123 patients were enrolled and considered. The patients were treated with a standard 3-day regimen of chloroquine and were followed-up clinically and parasitologically. The results were interpreted as mean parasite clearance time (MPCT in P. vivax and early treatment failure (ETF, late treatment failure (LTF and adequate clinical and parasitological response (ACPR in P. falciparum."n"nResults: The patients with vivax malaria were responded to the regimen of chloroquine within 24-216 hours. Most cases of the parasite clearance time occurred at 48 hours (50.40%, and less of them at 120, 168, 192 and 216 hours

Detection of relapse in early stage Hodgkin's disease: role of routine follow up studies

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Torrey, Margaret J; Poen, Joseph C; Hoppe, Richard T

1995-07-01

Purpose: To examine the costs and benefits of an established practice of routine follow-up in a cohort of patients treated with radiation therapy for early stage Hodgkin's disease. Materials and Methods: We retrospectively examined patterns of follow-up and methods of relapse detection among 709 patients with Ann Arbor Stage I-II Hodgkin's disease treated with sub-total lymphoid irradiation (STLI) or total lymphoid irradiation (TLI) between 1969-1994. We determined the probability of relapse detection for each of 7 routine follow up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of overall survival following salvage therapy. Results: Relapse has occurred in 157 patients (22%) at a median 1.9 years (range 0-13 years) following treatment. 133 relapses (85%) occurred during the first 5 years of follow. Detailed information concerning the method of relapse detection was available on 107 patients. These 107 patients form the basis of this analysis. Relapse was identified by history (Hx) alone in 55% of patients, physical exam (PE) in 14%, chest x-ray (CXR) in 23% and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study - erythrocyte sedimentation rate (ESR). The rate of relapse detection was highest for a combination of history and physical exam (78/10,000 exams) followed by CXR (26/10,000 exams), KUB (10/10,000 exams) and ESR (1/10,000 tests). Complete blood count (CBC) and serum chemistries were never the primary factor in detecting HD relapse. Radiographs accounted for greater than 60% of charges while laboratory studies and physician charges accounted for approximately 20% each. The projected charges (1994 dollars) of relapse detection by routine follow up Hx and PE was [dollar]10,600 compared with [dollar]68,200 for CXR, [dollar]141,800 for KUB and [dollar]156,400 for ESR. 10 year actuarial survival following salvage therapy was 65% overall, 65% for patients in whom

Detection of relapse in early stage Hodgkin's disease: role of routine follow up studies

International Nuclear Information System (INIS)

Torrey, Margaret J.; Poen, Joseph C.; Hoppe, Richard T.

1995-01-01

Purpose: To examine the costs and benefits of an established practice of routine follow-up in a cohort of patients treated with radiation therapy for early stage Hodgkin's disease. Materials and Methods: We retrospectively examined patterns of follow-up and methods of relapse detection among 709 patients with Ann Arbor Stage I-II Hodgkin's disease treated with sub-total lymphoid irradiation (STLI) or total lymphoid irradiation (TLI) between 1969-1994. We determined the probability of relapse detection for each of 7 routine follow up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of overall survival following salvage therapy. Results: Relapse has occurred in 157 patients (22%) at a median 1.9 years (range 0-13 years) following treatment. 133 relapses (85%) occurred during the first 5 years of follow. Detailed information concerning the method of relapse detection was available on 107 patients. These 107 patients form the basis of this analysis. Relapse was identified by history (Hx) alone in 55% of patients, physical exam (PE) in 14%, chest x-ray (CXR) in 23% and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study - erythrocyte sedimentation rate (ESR). The rate of relapse detection was highest for a combination of history and physical exam (78/10,000 exams) followed by CXR (26/10,000 exams), KUB (10/10,000 exams) and ESR (1/10,000 tests). Complete blood count (CBC) and serum chemistries were never the primary factor in detecting HD relapse. Radiographs accounted for greater than 60% of charges while laboratory studies and physician charges accounted for approximately 20% each. The projected charges (1994 dollars) of relapse detection by routine follow up Hx and PE was [dollar]10,600 compared with [dollar]68,200 for CXR, [dollar]141,800 for KUB and [dollar]156,400 for ESR. 10 year actuarial survival following salvage therapy was 65% overall, 65% for patients in whom

[Research and control of relapse tuberculosis cases].

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Yamagishi, Fumio; Toyota, Makoto

2009-12-01

With this symposium, we focused on the relapse of tuberculosis in Japan. Out of 19,893 tuberculosis patients registered in 2007 in Japan, 7.48% were classified as relapse cases. Relapse cases have the risk of acquired drug resistance. But we have few analyses of the proportion of relapse tuberculosis cases with standard short course regimens for six months, factors contributing to tuberculosis relapse and the proportion of drug resistance among relapse TB cases in Japan. Therefore we analyzed the relapse tuberculosis cases in two rural areas and three urban areas. We also analyzed the proportion of drug resistance among relapse cases with the data of drug susceptibility survey of Ryoken. 1. Research of relapse tuberculosis cases: Makoto TOYOTA (Kochi City Public Health Center). To clarify the relapse rate and factors contributing to tuberculosis relapse, we investigated the relapse tuberculosis cases in the municipality where the proportion of elderly tuberculosis patients was high. Out of 902 tuberculosis patients registered in Kochi City Public Health Center during 10 years, 20 pulmonary tuberculosis patients were confirmed relapse cases with initial registered records. Pretreatment cavitations, sputum culture positivity at 2 months, medical miss-management (e.g. number of doses, duration of therapy) and poor adherence were considered to be factors contributing to tuberculosis relapse. Out of 20 relapse cases, 12 cases were detected with symptoms, while only 3 cases were detected by examination in law. 2. A clinical study on relapse cases of pulmonary tuberculosis: Shuichi TAKIKAWA (National Hospital Organization Nishibeppu National Hospital). The relapse of pulmonary tuberculosis was investigated. In the cases with a treatment history before short course chemotherapy, drug resistance rate was high, and thus it needs to be cautious of drug resistance at the time of the retreatment. In the cases with a treatment history of short course chemotherapy, relapse cases

Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

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Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

2015-01-01

Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

Relapse prevention and smoking cessation.

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Davis, J R; Glaros, A G

1986-01-01

A multicomponent smoking relapse prevention treatment based on Marlatt and Gordon's (1980) model of the relapse process was developed and evaluated. Behavior-analytic methods were used to develop assessment instruments, training situations, and coping responses. The prevention components were presented in the context of a basic broad-spectrum stop-smoking program, and were compared with the basic program plus discussion control, and the basic program alone. Smoking-related dependent variables generally did not differ between groups at any time from pre-treatment to 12 month follow-up. Only the subjects in the relapse prevention condition improved problem-solving and social skills needed to cope with high-risk situations. These subjects also tended to take longer to relapse and smoke fewer cigarettes at the time of relapse. Subjects above the median level of competence on measures of social skill at post-treatment remained abstinent significantly longer. Maintenance of non-smoking was found to be related to the degree of competence with which individuals deal with high-risk situations. Results are discussed in relation to models of compliance with therapeutic regimens.

Correction to: Polymorphisms in chloroquine resistance-associated genes in Plasmodium vivax in Ethiopia.

Science.gov (United States)

Golassa, Lemu; Erko, Berhanu; Baliraine, Frederick N; Aseffa, Abraham; Swedberg, Göte

2018-05-02

After publication of the original article [1], it came to the authors' attention that the primers mentioned in Table 1 for the amplification of the pvcrt-o gene of Plasmodium vivax are not the ones actually used for the experiments. The correct primers and PCR product size are as below.

Point-of-care G6PD diagnostics for Plasmodium vivax malaria is a clinical and public health urgency.

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Baird, J Kevin

2015-12-14

Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Recent clinical evidence discredits the long-held notion of this infection as intrinsically benign revealing an often threatening course associated with mortality. Most acute attacks by this species derive from latent forms in the human liver called hypnozoites. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against future attacks (hypnozoitocidal). The only hypnozoitocide available is primaquine, a drug causing life-threatening acute hemolytic anemia in patients with the inherited blood disorder glucose-6-phosphate dehydrogenase (G6PD) deficiency. This disorder affects 400 million people worldwide, at an average prevalence of 8 % in malaria-endemic nations. In the absence of certain knowledge regarding the G6PD status of patients infected by P. vivax, providers must choose between the risk of harm caused by primaquine and that caused by the parasite by withholding therapy. Resolving this dilemma requires the availability of point-of-care G6PD diagnostics practical for use in the impoverished rural tropics where the vast majority of malaria patients seek care.

Relapsing polychondritis: commentary

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R.D. Altman

2011-09-01

Full Text Available Relapsing Polychondritis (RP is a multisystem disease of unknown etiology characterized by episodic inflammation of cartilage and potentially progressive degeneration of cartilaginous tissue, such as auricular, nasal and laryngotracheobronchial cartilage. However, many other proteoglycan- rich structures may be involved, such as inner ear, eyes, blood vessels, heart and kidneys (1- 4. RP was first described by Jacksh-Wartenhorst in 1923, who named it “polychondropathia” (5. Pearson et al. (6 introduced the term “relapsing polychondritis” in 1960...

Site of relapse after chemotherapy alone for stage I and II Hodgkin's disease

International Nuclear Information System (INIS)

Shahidi, Mehdi; Kamangari, Nahid; Ashley, Sue; Cunningham, David; Horwich, Alan

2006-01-01

Background: Short course chemotherapy followed by radiotherapy is a standard treatment for early Hodgkin's disease. There is yet no consensus regarding the appropriate radiotherapy portal following chemotherapy. A good guide to the adjuvant radiotherapy field is the site of relapse in patients treated with chemotherapy alone. Patients and methods: From 1980 to 1996, 61 patients with stage I and II supradiaphragmatic Hodgkin's disease were treated with chemotherapy alone at the Royal Marsden Hospital. We undertook a retrospective review and failure analysis to define the pattern of recurrence. Results: After a median follow-up of 6.5 years, 24 patients had relapsed giving a 5-year relapse rate of 40%. The 5 and 10-year actuarial survival rates were 94 and 89%, respectively with cause-sepecific survival being 94% at 5 and 10 years. Two-thirds of the relapses were nodal and supradiaphragmatic. Twenty patients (83%) relapsed in the initially involved sites of disease and this was the sole site of recurrence in 11 (45%) of patients. In retrospect, it appeared that at least 12 recurrences could have been prevented by involved field radiotherapy. Review of detailed imaging data (available in 9 out of 11 patients with recurrences in initial sites of disease) showed that the relapses were always in the initially involved nodes. Conclusion: After chemotherapy alone in early stage HD most initial recurrences are nodal. Loco-regional recurrences are in the originally involved nodes. Based on limited data it appears that involved nodal RT is equivalent to involved field radiotherapy and may halve the risk of recurrence

Trypanosomosis due to Trypanosoma vivax in ruminants in Latin America: A review

International Nuclear Information System (INIS)

Dwinger, R.H.; Hall, M.J.R.

2000-01-01

The history and the present situation of T. vivax infections in Latin America are reviewed. Clinical signs, diagnostic aspects, therapy and control of the disease are briefly discussed. In view of the recent emergence of bovine trypanosomosis in areas where it previously never existed, it is advisable to invest in improving the diagnosis and control of the disease in Latin America. (author)

Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

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Kriz, Jan; Reinartz, Gabriele [Department of Radiation Oncology, University of Münster, Münster (Germany); Dietlein, Markus; Kobe, Carsten; Kuhnert, Georg [Department of Nuclear Medicine, University of Cologne, Cologne (Germany); Haverkamp, Heinz [First Department of Internal Medicine, University of Cologne, Cologne (Germany); Haverkamp, Uwe [Department of Radiation Oncology, University of Münster, Münster (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University of Marburg, Marburg (Germany); Herfarth, Klaus [Department of Radiation Oncology, University Heidelberg, Heidelberg (Germany); Lukas, Peter [Department of Radiation Oncology, University of Innsbruck, Innsbruck (Austria); Schmidberger, Heinz [Department of Radiation Oncology, University of Mainz, Mainz (Germany); Staar, Susanne [Department of Radiation Oncology, Klinikum Bremen-Mitte, Bremen (Germany); Hegerfeld, Kira [Department of Radiation Oncology, University of Münster, Münster (Germany); Baues, Christian [Department of Radiation Oncology, University of Cologne, Cologne (Germany); Engert, Andreas [First Department of Internal Medicine, University of Cologne, Cologne (Germany); Eich, Hans Theodor, E-mail: hans.eich@ukmuenster.de [Department of Radiation Oncology, University of Münster, Münster (Germany)

2015-05-01

Purpose: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. Methods and Materials: All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluated all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. Results: A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. Conclusions: The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses.

Socio-economic correlates of relapsed patients admitted in a Nigerian mental health institution.

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Gbiri, Caleb A; Badru, Fatai A; Ladapo, Harry T O; Gbiri, Adefolakemi A

2011-03-01

Relapse in psychiatric disorders is highly distressing, costly and engenders burn-out syndrome among mental-health workers. To study the socio-economic factors associated with relapse in individual admitted with psychiatric disorders and the pattern of socio-economic impact of relapse in those groups. A cross-sectional survey of all relapsed patients without cognitive deficit admitted into the federal Neuro-Psychiatric Hospital, Lagos, Nigeria between June and October 2007 was conducted using a self-validated Structured Interview Schedule (Relapse Socio-economic Impact Interview Schedule) and Key Informant Interview Guide. Secondary data were elicited from the patient folders, case notes, ward admission registers and nominal rolls. Data were summarised using mean, standard deviation, frequency and percentiles. Pearson's moment correlation coefficient was used to test the association among variables. The Mann-Whitney U-test was used to compare the pre-morbid and the post-morbid states. This study involved 102 respondents. Their mean age was 36.5 ± 9.8 years, mainly of male gender (72.5%) suffering from schizophrenic disorder (37.8%). Relapse and re-admission ranged between 2 and 12. Unemployment rate, marital separation and divorce increased more than 5-fold from pre-morbid to morbid states. Few (4.9%) could still settle their hospital/drug bills on their own, while most (95.1%) depended on family, philanthropist and government/waivers to pay for their bills. Their social relationships were negatively influenced with most of them expressing social isolation and low quality of life. There were significant relationships (Peconomic status, employment status and marital status of the respondents between the pre-morbid and post-morbid periods. The illness significantly affected the emotional status of the participants. Relapse and readmission in psychiatric patients have a negative impact on socio-economic well-being of patients, family and the society. Efforts should

Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera.

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Cabrera-Mora, Monica; Fonseca, Jairo Andres; Singh, Balwan; Oliveira-Ferreira, Joseli; Lima-Junior, Josué da Costa; Calvo-Calle, J Mauricio; Moreno, Alberto

2015-09-01

Plasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside sub-Saharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimeric Plasmodium yoelii proteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimeric protein based on the P. vivax CSP (PvCSP). In this engineered protein, regions of the PvCSP predicted to contain human T cell epitopes were genetically fused to an immunodominant B cell epitope derived from the N-terminal region I and to repeat sequences representing the two types of PvCSP repeats. The chimeric protein was expressed in soluble form with high yield. As the immune response to PvCSP has been reported to be genetically restricted in the murine model, we tested the immunogenicity of PvRMC-CSP in groups of six inbred strains of mice. PvRMC-CSP was able to induce robust antibody responses in all the mouse strains tested. Synthetic peptides representing the allelic forms of the P. vivax CSP were also recognized to a similar extent regardless of the mouse strain. Furthermore, the immunization regimen induced high frequencies of multifunctional CD4(+) and CD8(+) PvRMC-CSP-specific T cells. The depth and breadth of the immune responses elicited suggest that immunization with PvRMC-CSP can circumvent the genetic restriction of the immune response to P. vivax CSP. Interestingly, PvRMC-CSP was also recognized by naturally acquired antibodies from individuals living in areas where malaria is endemic. These features make PvRMC-CSP a promising vaccine candidate for further development. Copyright © 2015, American Society for Microbiology. All

Naturally Acquired Antibodies to Plasmodium vivax Duffy Binding Protein (DBP) in Rural Brazilian Amazon

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Souza-Silva, Flávia A.; da Silva-Nunes, Mônica; Sanchez, Bruno A. M.; Ceravolo, Isabela P.; Malafronte, Rosely S.; Brito, Cristiana F. A.; Ferreira, Marcelo U.; Carvalho, Luzia H.

2010-01-01

Duffy binding protein (DBP), a leading malaria vaccine candidate, plays a critical role in Plasmodium vivax erythrocyte invasion. Sixty-eight of 366 (18.6%) subjects had IgG anti-DBP antibodies by enzyme-linked immunosorbent assay (ELISA) in a community-based cross-sectional survey in the Brazilian Amazon Basin. Despite continuous exposure to low-level malaria transmission, the overall seroprevalence decreased to 9.0% when the population was reexamined 12 months later. Antibodies from 16 of 50 (36.0%) subjects who were ELISA-positive at the baseline were able to inhibit erythrocyte binding to at least one of two DBP variants tested. Most (13 of 16) of these subjects still had inhibitory antibodies when reevaluated 12 months later. Cumulative exposure to malaria was the strongest predictor of DBP seropositivity identified by multiple logistic regression models in this population. The poor antibody recognition of DBP elicited by natural exposure to P. vivax in Amazonian populations represents a challenge to be addressed by vaccine development strategies. PMID:20133990

Dynamics of intraocular IFN-γ, IL-17 and IL-10-producing cell populations during relapsing and monophasic rat experimental autoimmune uveitis.

Directory of Open Access Journals (Sweden)

Ulrike Kaufmann

Full Text Available A major limitation of most animal models of autoimmune diseases is that they do not reproduce the chronic or relapsing-remitting pattern characteristic of many human autoimmune diseases. This problem has been overcome in our rat models of experimentally induced monophasic or relapsing-remitting autoimmune uveitis (EAU, which depend on the inducing antigen peptides from retinal S-Antigen (monophasic EAU or interphotoreceptor retinoid-binding protein (relapsing EAU. These models enable us to compare autoreactive and regulatory T cell populations. Intraocular, but not peripheral T cells differ in their cytokine profiles (IFN-γ, IL-17 and IL-10 at distinct time points during monophasic or relapsing EAU. Only intraocular T cells concomitantly produced IFN-γ, IL-17 and/or IL-10. Monophasic EAU presented rising numbers of cells expressing IFN-γ and IL-17 (Th1/Th17 and cells expressing IL-10 or Foxp3. During relapsing uveitis an increase of intraocular IFN-γ+ cells and a concomitant decrease of IL-17+ cells was detected, while IL-10+ populations remained stable. Foxp3+ cells and cells expressing IL-10, even in combination with IFN-γ or IL-17, increased during the resolution of monophasic EAU, suggesting a regulatory role for these T cells. In general, cells producing multiple cytokines increased in monophasic and decreased in relapsing EAU. The distinct appearance of certain intraocular populations with characteristics of regulatory cells points to a differential influence of the ocular environment on T cells that induce acute and monophasic or relapsing disease. Here we provide evidence that different autoantigens can elicit distinct and differently regulated immune responses. IFN-γ, but not IL-17 seems to be the key player in relapsing-remitting uveitis, as shown by increased, synchronized relapses after intraocular application of IFN-γ. We demonstrated dynamic changes of the cytokine pattern during monophasic and relapsing-remitting disease

Plasma metabolomics reveals membrane lipids, aspartate/asparagine and nucleotide metabolism pathway differences associated with chloroquine resistance in Plasmodium vivax malaria

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Salinas, Jorge L.; Monteiro, Wuelton M.; Val, Fernando; Cordy, Regina J.; Liu, Ken; Melo, Gisely C.; Siqueira, Andre M.; Magalhaes, Belisa; Galinski, Mary R.; Lacerda, Marcus V. G.; Jones, Dean P.

2017-01-01

Background Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance. Methods An untargeted high-resolution metabolomics analysis was performed on plasma samples collected in a malaria clinic in Manaus, Brazil. Male and female patients with Plasmodium vivax were included (n = 46); samples were collected before CQ treatment and followed for 28 days to determine PvCR, defined as the recurrence of parasitemia with detectable plasma concentrations of CQ ≥100 ng/dL. Differentially expressed metabolic features between CQ-Resistant (CQ-R) and CQ-Sensitive (CQ-S) patients were identified using partial least squares discriminant analysis and linear regression after adjusting for covariates and multiple testing correction. Pathway enrichment analysis was performed using Mummichog. Results Linear regression and PLS-DA methods yielded 69 discriminatory features between CQ-R and CQ-S groups, with 10-fold cross-validation classification accuracy of 89.6% using a SVM classifier. Pathway enrichment analysis showed significant enrichment (p<0.05) of glycerophospholipid metabolism, glycosphingolipid metabolism, aspartate and asparagine metabolism, purine and pyrimidine metabolism, and xenobiotics metabolism. Glycerophosphocholines levels were significantly lower in the CQ-R group as compared to CQ-S patients and also to independent control samples. Conclusions The results show differences in lipid, amino acids, and nucleotide metabolism pathways in the plasma of CQ-R versus

Pathogenesis of reproductive failure induced by Trypanosoma vivax in experimentally infected pregnant ewes

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2013-01-01

The present study was aimed at investigating the effect of experimental infection by Trypanosoma vivax in different stages of pregnancy, determining the pathogenesis of reproductive failure, and confirming transplacental transmission. We used 12 pregnant ewes distributed into four experimental groups: G1, was formed by three ewes infected with T. vivax in the first third of pregnancy (30 days); G2 comprised three infected ewes in the final third of pregnancy (100 days); G3 and G4 were composed of three non-infected ewes with the same gestational period, respectively. Each ewe of G1 and G2 was inoculated with 1.25 × 105 tripomastigotes. Clinical examination, determination of parasitemia, serum biochemistry (albumin, total protein, glucose, cholesterol, and urea), packed cell volume (PCV), serum progesterone, and pathological examination were performed. Placenta, amniotic fluid, blood and tissues from the fetuses and stillbirths were submitted to PCR. Two ewes of G1 (Ewe 1 and 3) presented severe infection and died in the 34th and 35th days post-infection (dpi), respectively; but both fetuses were recovered during necropsy. In G2, Ewe 5 aborted two fetuses on the 130th day (30 dpi) of pregnancy; and Ewe 6 aborted one fetus in the 140th day (40 dpi) of gestation. Ewes 2 and 4 delivered two weak lambs that died five days after birth. Factors possibly involved with the reproductive failure included high parasitemia, fever, low PCV, body score, serum glucose, total protein, cholesterol, and progesterone. Hepatitis, pericarditis, and encephalitis were observed in the aborted fetuses. The presence of T. vivax DNA in the placenta, amniotic fluid, blood, and tissues from the fetuses confirms the transplacental transmission of the parasite. Histological lesion in the fetuses and placenta also suggest the involvement of the parasite in the etiopathogenesis of reproductive failure in ewes. PMID:23289625

The Relative Contribution of Symptomatic and Asymptomatic Plasmodium vivax and Plasmodium falciparum Infections to the Infectious Reservoir in a Low-Endemic Setting in Ethiopia.

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Tadesse, Fitsum G; Slater, Hannah C; Chali, Wakweya; Teelen, Karina; Lanke, Kjerstin; Belachew, Mulualem; Menberu, Temesgen; Shumie, Girma; Shitaye, Getasew; Okell, Lucy C; Graumans, Wouter; van Gemert, Geert-Jan; Kedir, Soriya; Tesfaye, Addisu; Belachew, Feleke; Abebe, Wake; Mamo, Hassen; Sauerwein, Robert; Balcha, Taye; Aseffa, Abraham; Yewhalaw, Delenasaw; Gadisa, Endalamaw; Drakeley, Chris; Bousema, Teun

2018-06-01

The majority of Plasmodium vivax and Plasmodium falciparum infections in low-endemic settings are asymptomatic. The relative contribution to the infectious reservoir of these infections compared to clinical malaria cases is currently unknown. We assessed infectivity of passively recruited symptomatic malaria patients (n = 41) and community-recruited asymptomatic individuals with microscopy-detected (n = 41) and polymerase chain reaction (PCR)-detected infections (n = 82) using membrane feeding assays with Anopheles arabiensis mosquitoes in Adama, Ethiopia. Malaria incidence and prevalence data were used to estimate the contributions of these populations to the infectious reservoir. Overall, 34.9% (29/83) of P. vivax- and 15.1% (8/53) P. falciparum-infected individuals infected ≥1 mosquitoes. Mosquito infection rates were strongly correlated with asexual parasite density for P. vivax (ρ = 0.63; P < .001) but not for P. falciparum (ρ = 0.06; P = .770). Plasmodium vivax symptomatic infections were more infectious to mosquitoes (infecting 46.5% of mosquitoes, 307/660) compared to asymptomatic microscopy-detected (infecting 12.0% of mosquitoes, 80/667; P = .005) and PCR-detected infections (infecting 0.8% of mosquitoes, 6/744; P < .001). Adjusting for population prevalence, symptomatic, asymptomatic microscopy-detected, and PCR-detected infections were responsible for 8.0%, 76.2%, and 15.8% of the infectious reservoir for P. vivax, respectively. For P. falciparum, mosquito infections were sparser and also predominantly from asymptomatic infections. In this low-endemic setting aiming for malaria elimination, asymptomatic infections were highly prevalent and responsible for the majority of onward mosquito infections. The early identification and treatment of asymptomatic infections might accelerate elimination efforts.

Plasmodium vivax sporozoite challenge in malaria-naïve and semi-immune Colombian volunteers

DEFF Research Database (Denmark)

Arévalo-Herrera, Myriam; Forero-Peña, David A.; Rubiano, Kelly

2014-01-01

induced in naïve and semi-immune volunteers by infected mosquito bites was compared. Methods: Seven malaria-naïve and nine semi-immune Colombian adults (n = 16) were subjected to the bites of 2-4 P. vivax sporozoite-infected Anopheles mosquitoes. Parasitemia levels, malaria clinical manifestations...

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

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Jason W Bennett

2016-02-01

Full Text Available A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001, a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP and a truncated repeat region that contains repeat sequences from both the VK210 (type 1 and the VK247 (type 2 parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

Reporte de cinco casos de malaria neonatal grave por Plasmodium vivax en Urabá, Colombia

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Juan Gabriel Piñeros

2008-12-01

Conclusión. Se trata de un reporte de cinco casos de malaria neonatal grave por P. vivax, especie que habitualmente no se relaciona con complicaciones, sin que existiera en ningún caso la sospecha clínica y con tratamiento inadecuado.

Oligohydramnios in a pregnant Pakistani woman with Plasmodium vivax malaria

OpenAIRE

Binello, Nicolò; Brunetti, Enrico; Cattaneo, Federico; Lissandrin, Raffaella; Malfitano, Antonello

2014-01-01

In the Western world, the diagnosis and management of Plasmodium vivax malaria in pregnant women can be challenging, and the pathogenesis of adverse outcomes for both the mother and the foetus is still poorly known. The authors describe the case of a 29-year-old Pakistani woman at the 29th week of her second pregnancy, who was admitted to the Hospital following the abrupt onset of fever. At the time of admission, she had been living in Italy without travelling to any malaria-endemic areas for...

Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review.

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Rustad, James K; Stern, Theodore A; Prabhakar, Maithri; Musselman, Dominique

2015-01-01

Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have

Salivary Glands Proteins Expression of Anopheles dirus A Fed on Plasmodium vivax- and Plasmodium falciparum-Infected Human Blood

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Saowanee Cotama

2013-01-01

Full Text Available Mosquitoes are able to adapt to feed on blood by the salivary glands which created a protein that works against the haemostasis process. This study aims to investigate the salivary glands proteins expression of 50 adult female An. dirus A mosquitoes, a main vector of malaria in Thailand, each group with an age of 5 days which were artificial membrane fed on sugar, normal blood, blood infected with P. vivax, and blood infected with P. falciparum. Then mosquito salivary gland proteins were analyzed by SDS-PAGE on days 0, 1, 2, 3, and 4 after feeding. The findings revealed that the major salivary glands proteins had molecular weights of 62, 58, 43, 36, 33, 30, and 18 kDa. One protein band of approximately 13 kDa was found in normal blood and blood infected with P. vivax fed on day 0. A stronger protein band, 65 kDa, was expressed from the salivary glands of mosquitoes fed with P. vivax- or P. falciparum-infected blood on only day 0, but none on days 1 to 4. The study shows that salivary glands proteins expression of An. dirus may affect the malaria parasite life cycle and the ability of mosquitoes to transmit malaria parasites in post-24-hour disappearance observation.

Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia.

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Ling, Judith; Baird, J Kevin; Fryauff, David J; Sismadi, Priyanto; Bangs, Michael J; Lacy, Mark; Barcus, Mazie J; Gramzinski, Robert; Maguire, Jason D; Kumusumangsih, Marti; Miller, Gerri B; Jones, Trevor R; Chulay, Jeffrey D; Hoffman, Stephen L

2002-10-01

The increasing prevalence of resistance to antimalarial drugs reduces options for malaria prophylaxis. Atovaquone/proguanil (Malarone; GlaxoSmithKline) has been >95% effective in preventing Plasmodium falciparum malaria in lifelong residents of areas of holoendemicity, but data from persons without clinical immunity or who are at risk for Plasmodium vivax malaria have not been described. We conducted a randomized, double-blinded study involving 297 people from areas of nonendemicity in Indonesia who migrated to Papua (where malaria is endemic) proguanil hydrochloride; n=148) or placebo (n=149) per day for 20 weeks. Hematologic and clinical chemistry values did not change significantly. The protective efficacy of atovaquone/proguanil was 84% (95% confidence interval [CI], 44%-95%) for P. vivax malaria, 96% (95% CI, 72%-99%) for P. falciparum malaria, and 93% (95% CI, 77%-98%) overall. Atovaquone/proguanil was well tolerated, safe, and effective for the prevention of drug-resistant P. vivax and P. falciparum malaria in individuals without prior malaria exposure who migrated to Papua, Indonesia.

The shape of the iceberg: quantification of submicroscopic Plasmodium falciparum and Plasmodium vivax parasitaemia and gametocytaemia in five low endemic settings in Ethiopia.

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Tadesse, Fitsum G; van den Hoogen, Lotus; Lanke, Kjerstin; Schildkraut, Jodie; Tetteh, Kevin; Aseffa, Abraham; Mamo, Hassen; Sauerwein, Robert; Felger, Ingrid; Drakeley, Chris; Gadissa, Endalamaw; Bousema, Teun

2017-03-03

The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia. Two cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively. Finger prick whole blood and plasma samples were collected. The prevalence and density of P. falciparum and P. vivax parasitaemia and gametocytaemia were determined by 18S rRNA quantitative PCR (qPCR) and pfs25 and pvs25 reverse transcriptase qPCR. Antibodies against blood stage antigens apical membrane antigen-1 (AMA-1) and merozoite surface protein-1 (MSP-1 19 ) were measured for both species. Whilst only 6 infections were detected by microscopy in 881 slides (0.7%), 107 of 845 blood samples (12.7%) were parasite positive by (DNA-based) qPCR. qPCR parasite prevalence between sites and surveys ranged from 3.8 to 19.0% for P. falciparum and 0.0 to 9.0% for P. vivax. The median density of P. falciparum infections (n = 85) was 24.4 parasites/µL (IQR 18.0-34.0) and the median density of P. vivax infections (n = 28) was 16.4 parasites/µL (IQR 8.8-55.1). Gametocyte densities by (mRNA-based) qRT-PCR were strongly associated with total parasite densities for both P. falciparum (correlation coefficient = 0.83, p = 0.010) and P. vivax (correlation coefficient = 0.58, p = 0.010). Antibody titers against P. falciparum AMA-1 and MSP-1 19 were higher in individuals who were P. falciparum parasite positive in both surveys (p < 0.001 for both comparisons). This study adds to the available evidence on the wide-scale presence of submicroscopic parasitaemia by quantifying submicroscopic parasite densities and concurrent gametocyte densities. There was considerable heterogeneity in the occurrence of P

Trypanosoma vivax infection dynamics in a cattle herd maintained in a transition area between Pantanal lowlands and highlands of Mato Grosso do Sul, Brazil Dinâmica de infecção de Trypanosoma vivax em rebanho bovino mantido numa área de transição entre o Pantanal e o planalto de Mato Grosso do Sul

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Charles F. Martins

2008-01-01

Full Text Available Trypanosoma vivax outbreaks in beef cattle in the Pantanal region of Mato Grosso do Sul state, Brazil, causes relevant economical impact due to weight loss, abortion and mortality. Cattle moved from the Pantanal to adjacent areas of this ecosystem for breeding and fattening is a common feature. Therefore an epidemiological study on breeding cows in the transition area between Pantanal lowland and adjacent highlands of Mato Grosso do Sul was performed to determine the T. vivax infection dynamics and outbreak risk. Three experimental groups were formed: Group 1 consisted of cows parasitologically negative by the Woo test and in the enzyme-linked immunosorbent assay for T. vivax antibody detection (Tv-ELISA-Ab; Group 2 parasitologically negative and positive in the Tv-ELISA-Ab; and in Group 3 cows were parasitologically positive and with positive reactions in the Tv-ELISA-Ab. During 24 months, the cows' dislodgment between the above established groups was monitored by Woo test and Tv-ELISA-Ab exams. The tabanid population was also monitored and the highest number occurred during the rainy season. Although parasitemias were detected only in the first four samplings of the experimental period, the cows could be considered as trypanotolerant, because no clinical signs were observed. Despite the higher T. vivax incidence during the dry season, no disease symptoms were seen. Even though T. vivax epidemiological situation in the herd was characterized as endemic with seasonal variation, the probability of outbreaks was null within the conditions of the study.Surtos de Trypanosoma vivax em bovinos de corte do Pantanal foram responsáveis por relevante impacto econômico, devido a perda de peso, abortos e mortalidade. Um manejo comum é o deslocamento de bovinos do Pantanal baixo para áreas adjacentes desse ecosistema para reprodução e engorda. Por essa razão, foi efetuado um estudo epidemiológico em rebanho de vacas movidas para uma área de transi

Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon.

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Pratt-Riccio, Lilian R; Chehuan, Yonne F; Siqueira, Maria José; das Graças Alecrim, Maria; Bianco-Junior, Cesare; Druilhe, Pierre; Brasseur, Philippe; de Fátima Ferreira-da-Cruz, Maria; Carvalho, Leonardo J M; Daniel-Ribeiro, Cláudio T

2013-08-12

The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon. The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test. As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials. The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10-20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health policies.

A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax.

Science.gov (United States)

March, Sandra; Ng, Shengyong; Velmurugan, Soundarapandian; Galstian, Ani; Shan, Jing; Logan, David J; Carpenter, Anne E; Thomas, David; Sim, B Kim Lee; Mota, Maria M; Hoffman, Stephen L; Bhatia, Sangeeta N

2013-07-17

The Plasmodium liver stage is an attractive target for the development of antimalarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable, and reproducible in vitro liver-stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum, including the release of infected merozoites and infection of overlaid erythrocytes, as well as the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput antimalarial drug screening and vaccine development. Copyright © 2013 Elsevier Inc. All rights reserved.

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

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Serhan Sevim

2016-09-01

Full Text Available Relapse in multiple sclerosis (MS is defined as a neurologic deficit associated with an acute inflammatory demyelinating event that lasts at least 24 hours in the absence of fever and infection. Myelinoclasis and axonal transection occur in relapses. Diagnosis, prognosis, treatment, and many other features of the disease are directly related to the relapses. MS starts as the relapsing-remitting (RRMS form in 85% of patients. A large number of relapses in the first years, polysymptomatic relapses, and pyramidal system, brain stem, and spinal cord involvement are signs of a poor outcome. The average frequency of relapses is approximately one per year during the first years of RRMS. The frequency of relapses increases during systemic infections, psychological stress, and in the postpartum first 3 months. Seventy-five percent of relapses are monosymptomatic. Pseudo-relapses and paroxysmal symptoms are distinguished from relapses by their sudden onset, sudden termination, and shorter duration. Contrast enhancement is valuable in imaging, but undetectable in most relapses. The regression in the first few weeks of relapses is explained by reduction of the edema, and by remyelination in the following months. Relapses and their features are also among the main determinants of treatment. High-dose methylprednisolone and early treatment with adrenocorticotropic hormone reduce post-relapse disability and shorten the duration of relapses. Plasmapheresis is a good option for patients who do not respond to steroid treatment. Identification of relapses by patients and physicians, distinguishing them from imitators, proper evaluation, treatment when necessary, and monitoring the results are of great importance for patients with MS. The educational levels of patients and physicians regarding these parameters should be increased. Well-designed studies that evaluate the long-term effect of relapse treatment on disability are needed.

Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification

OpenAIRE

Jovanović Tatjana; Lazarević Dušan; Nikolić Gordana

2012-01-01

Background/Aim. Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioi...

Acute phase proteins: a potential approach for diagnosing chronic infection by Trypanosoma vivax Proteínas de fase aguda: uma possível abordagem para diagnóstico de infecção crônica por Trypanosoma vivax

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Katyane de Sousa Almeida

2012-06-01

Full Text Available The present study aimed to assess potential changes in acute phase proteins in sheep experimentally infected with Trypanosoma vivax. There were studied eight male sheep, four used as controls and four infected with 10(5 T. vivax trypomastigotes. Blood samples were collected at two points times before infection and then at 5,7, 9, 11, 13, 15, 20, 30, 45, 60, 75, 90, 105 and 120 days post-infection (dpi. Blood samples were centrifuged and allotted, and acute phase proteins were then separated by electrophoresis on acrylamide gel containing sodium dodecyl sulfate. Protein concentrations were determined by computer-assisted densitometry. Total protein was determined by colorimetric biuret method. Trypanosomes were counted daily using a 5 mL aliquot of blood smear on a glass slide under a 22 × 22 mm coverslip. Parasites were counted in 100 microscopic fields (40× magnification, and then multiplied by a correction factor. The results were expressed as parasites per mL of blood. For statistical analyses, we used the Wilcoxon test at 5% significance level. There was found a reduction in several acute phase proteins and increase in antitrypsin and transferrin. This finding can be used for the diagnosis of T. vivax infection, especially in chronic infection.O objetivo do presente estudo foi verificar possíveis alterações nas proteínas de fase aguda em ovinos infectados experimentalmente com Trypanosoma vivax. Para tanto, foram utilizados oito ovinos machos, sendo quatro usados como controle e quatro infectados com 10(5 tripomastigotas de T. vivax. Colheram-se amostras de sangue em dois tempos antes da infecção e, posteriormente, aos 5, 7, 9, 11, 13, 15, 20, 30, 45, 60, 75, 90, 105 e 120 dias após a infecção (dpi; após centrifugação e aliquotização das amostras. As proteínas de fase aguda foram separadas por eletroforese em gel de acrilamida, contendo dodecil sulfato de sódio, e suas concentrações foram determinadas através de

Post-relapse survival in patients with Ewing sarcoma.

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Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

2015-06-01

Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

Population pharmacokinetics of a three-day chloroquine treatment in patients with Plasmodium vivax infection on the Thai-Myanmar border.

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Höglund, Richard; Moussavi, Younis; Ruengweerayut, Ronnatrai; Cheomung, Anurak; Äbelö, Angela; Na-Bangchang, Kesara

2016-02-29

A three-day course of chloroquine remains a standard treatment of Plasmodium vivax infection in Thailand with satisfactory clinical efficacy and tolerability although a continuous decline in in vitro parasite sensitivity has been reported. Information on the pharmacokinetics of chloroquine and its active metabolite desethylchloroquine are required for optimization of treatment to attain therapeutic exposure and thus prevent drug resistance development. The study was conducted at Mae Tao Clinic for migrant worker, Tak province, Thailand. Blood samples were collected from a total of 75 (8 Thais and 67 Burmeses; 36 males and 39 females; aged 17-52 years) patients with mono-infection with P. vivax malaria [median (95 % CI) admission parasitaemia 4898 (1206-29,480)/µL] following treatment with a three-day course of chloroquine (25 mg/kg body weight chloroquine phosphate over 3 days). Whole blood concentrations of chloroquine and desethylchloroquine were measured using high performance liquid chromatography with UV detection. Concentration-time profiles of both compounds were analysed using a population-based pharmacokinetic approach. All patients showed satisfactory response to standard treatment with a three-day course of chloroquine with 100 % cure rate within the follow-up period of 42 days. Neither recurrence of P. vivax parasitaemia nor appearance of P. falciparum occurred. A total of 1045 observations from 75 participants were included in the pharmacokinetic analysis. Chloroquine disposition was most adequately described by the two-compartment model with one transit compartment absorption model into the central compartment and a first-order transformation of chloroquine into desethylchloroquine with an additional peripheral compartment added to desethylchloroquine. First-order elimination from the central compartment of chloroquine and desethylchloroquine was assumed. The model exhibited a strong predictive ability and the pharmacokinetic parameters were

Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study

OpenAIRE

Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

2016-01-01

Background Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Met...

The neuropharmacology of relapse to food seeking: methodology, main findings, and comparison with relapse to drug seeking.

Science.gov (United States)

Nair, Sunila G; Adams-Deutsch, Tristan; Epstein, David H; Shaham, Yavin

2009-09-01

Relapse to old, unhealthy eating habits is a major problem in human dietary treatments. The mechanisms underlying this relapse are unknown. Surprisingly, until recently this clinical problem has not been systematically studied in animal models. Here, we review results from recent studies in which a reinstatement model (commonly used to study relapse to abused drugs) was employed to characterize the effect of pharmacological agents on relapse to food seeking induced by either food priming (non-contingent exposure to small amounts of food), cues previously associated with food, or injections of the pharmacological stressor yohimbine. We also address methodological issues related to the use of the reinstatement model to study relapse to food seeking, similarities and differences in mechanisms underlying reinstatement of food seeking versus drug seeking, and the degree to which the reinstatement procedure provides a suitable model for studying relapse in humans. We conclude by discussing implications for medication development and future research. We offer three tentative conclusions: (1)The neuronal mechanisms of food-priming- and cue-induced reinstatement are likely different from those of reinstatement induced by the pharmacological stressor yohimbine. (2)The neuronal mechanisms of reinstatement of food seeking are possibly different from those of ongoing food-reinforced operant responding. (3)The neuronal mechanisms underlying reinstatement of food seeking overlap to some degree with those of reinstatement of drug seeking.

Mounting resistance of uropathogens to antimicrobial agents: A retrospective study in patients with chronic bacterial prostatitis relapse.

Science.gov (United States)

Stamatiou, Konstantinos; Pierris, Nikolaos

2017-07-01

Despite recent progress in the management of chronic bacterial prostatitis (CBP), many cases relapse. Increased drug resistance patterns of responsible bacteria have been proposed as the most probable causative factor. Driven by the limited number of previous studies addressing this topic, we aimed to study whether antibiotic resistance increases in patients with CBP when relapse occurs. A secondary aim of this study was to determine the resistance patterns of responsible bacteria from patients with CBP. The study material consisted of bacterial isolates from urine and/or prostatic secretions obtained from patients with CBP. Bacterial identification was performed by using the Vitek 2 Compact system and susceptibility testing was performed by disc diffusion and/or the Vitek 2 system. Interpretation of susceptibility results was based on Clinical and Laboratory Standards Institute guidelines. A total of 253 samples from patients diagnosed with CBP for the first time (group A) and 137 samples from relapsing patients with a history of CBP and previous antibiotic treatment (group B) were analyzed. A significant reduction in bacterial resistance to the less used antibiotics (TMP-SMX, tetracyclines, aminoglycosides, penicillins, and macrolides) was noted. An increase in resistance to quinolones of many bacteria that cause CBP was also noted with the increase in resistance of enterococcus strains being alarming. Comparison of the resistance profile of CBP-responsible bacteria between samples from first-time-diagnosed patients and samples from relapsing patients revealed notable differences that could be attributed to previous antibiotic treatment.

Relapsing Polychondritis Following Alopecia Areata

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John C. Starr

2010-01-01

Full Text Available A case of alopecia areata followed by relapsing polychondritis is presented. Similar cases from the literature are reviewed and speculation about the relationship of these diseases is offered. Although the occurrence of these diseases together could be coincidental, an association seems immunologically plausible. Thus, relapsing polychondritis might be an unusual systemic manifestation of alopecia areata.

Multiple-clone infections of Plasmodium vivax: definition of a panel of markers for molecular epidemiology.

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de Souza, Aracele M; de Araújo, Flávia C F; Fontes, Cor J F; Carvalho, Luzia H; de Brito, Cristiana F A; de Sousa, Taís N

2015-08-25

Plasmodium vivax infections commonly contain multiple genetically distinct parasite clones. The detection of multiple-clone infections depends on several factors, such as the accuracy of the genotyping method, and the type and number of the molecular markers analysed. Characterizing the multiplicity of infection has broad implications that range from population genetic studies of the parasite to malaria treatment and control. This study compared and evaluated the efficiency of neutral and non-neutral markers that are widely used in studies of molecular epidemiology to detect the multiplicity of P. vivax infection. The performance of six markers was evaluated using 11 mixtures of DNA with well-defined proportions of two different parasite genotypes for each marker. These mixtures were generated by mixing cloned PCR products or patient-derived genomic DNA. In addition, 51 samples of natural infections from the Brazil were genotyped for all markers. The PCR-capillary electrophoresis-based method was used to permit direct comparisons among the markers. The criteria for differentiating minor peaks from artifacts were also evaluated. The analysis of DNA mixtures showed that the tandem repeat MN21 and the polymorphic blocks 2 (msp1B2) and 10 (msp1B10) of merozoite surface protein-1 allowed for the estimation of the expected ratio of both alleles in the majority of preparations. Nevertheless, msp1B2 was not able to detect the majority of multiple-clone infections in field samples; it identified only 6 % of these infections. The merozoite surface protein-3 alpha and microsatellites (PvMS6 and PvMS7) did not accurately estimate the relative clonal proportions in artificial mixtures, but the microsatellites performed well in detecting natural multiple-clone infections. Notably, the use of a less stringent criterion to score rare alleles significantly increased the sensitivity of the detection of multi-clonal infections. Depending on the type of marker used, a considerable

The development of an enzyme-linked immunosorbent assay for Trypanosoma vivax antibodies and its use in epidemiological surveys

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Claudio R Madruga

2006-11-01

Full Text Available There are data indicating that the distribution of Trypanosoma vivax in the Brazilian territory is expanding with potential to reach other areas, where the vectors are present. The detection of anti-trypanosomal antibodies in serum provides important information of the trypanosomal status in cattle herds. For this reason, an enzyme-linked immunosorbent assay (Tv-ELISA-Ab with crude antigen from one Brazilian isolate of T. vivax was developed and evaluated. The sensitivity and specificity were respectively 97.6 and 96.9%. In the evaluation of cross-reactions, three calves inoculated with T. evansi trypimastigotes blood forms showed optical densities (OD under the cut-off during the whole experimental period, except one at 45 days post-inoculation. With relation to Babesia bovis, B. bigemina, and Anaplasma marginale, which are endemic hemoparasites in the studied area, the cross-reactions were shown to be 5.7, 5.3, and 1.1%, respectively. The first serological survey of Pantanal and state of Pará showed that T. vivax is widespread, although regions within both areas had significantly different prevalences. Therefore, this Tv-ELISA-Ab may be a more appropriate test for epidemiological studies in developing countries because the diagnostic laboratories in most countries may be able to perform an ELISA, which is not true for polymerase chain reaction.

Second allogeneic hematopoietic SCT for relapsed ALL in children.

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Kato, M; Horikoshi, Y; Okamoto, Y; Takahashi, Y; Hasegawa, D; Koh, K; Takita, J; Inoue, M; Kigasawa, H; Ogawa, A; Sasahara, Y; Kawa, K; Yabe, H; Sakamaki, H; Suzuki, R; Kato, K

2012-10-01

A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4 ± 3.7%, the cumulative incidence of relapse was 44.1 ± 4.0% and non-relapse mortality was 18.8 ± 3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT.

Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery

NARCIS (Netherlands)

Dembele, L.; Gego, A.; Zeeman, A.M.; Franetich, J.F.; Silvie, O.; Rametti, A.; Grand, R. Le; Dereuddre-Bosquet, N.; Sauerwein, R.W.; Gemert, G.J. van; Vaillant, J.C.; Thomas, A.W.; Snounou, G.; Kocken, C.H.; Mazier, D.

2011-01-01

BACKGROUND: Amongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single

Evaluation of an antibody-detection ELISA using pre-coated plates in the diagnosis of Trypanosoma congolense and T. vivax infections in cattle in Mali

International Nuclear Information System (INIS)

Diall, O.; Bocoum, Z.; Sanogo, Y.

2000-01-01

Under the Coordinated Research Programme ''Use of immunoassay for improved diagnosis of trypanosomosis and monitoring trypanosomosis control programmes'', a new ELISA test has been validated. The test was designed for trypanosome specific antibody detection. The purpose of the work was to study the main parameters of the test (sensitivity and specificity) using reference sera provided by IAEA and field sera collected in Mali. The field sera were collected in different ecological zones and included sera from trypanosomosis endemic areas as well as sera from tsetse free areas. The test was performed according to the protocol proposed by IAEA. The results have shown a poor stability of the reference sera for both T. congolense and T. vivax. By using de-ionized water, we got better OD's for T. vivax C++ reference serum, while the T. congolense C++ had to be replaced by a locally produced reference serum. Under the above conditions, the T. congolense system gave quite encouraging results (sensitivity: 100%; specificity: 87.5-95%). This system was able to differentiate quite well animals from tsetse infected areas from those originating from tsetse free areas and could therefore be used in epidemiological surveys. The T. vivax system showed a good sensitivity (100%), but a poor specificity (37.5-57.5%). The T. vivax system could be improved by establishing a cut-off point based on local negative populations. (author)

Lapse and relapse following inpatient treatment of opiate dependence.

LENUS (Irish Health Repository)

Smyth, B P

2010-06-01

We conducted a prospective follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification. We measured the rate of relapse following discharge, and sought to identify factors that were associated with early relapse (i.e., a return to daily opiate use). Follow-up interviews were conducted with 109 patients, of whom, 99 (91%) reported a relapse. The initial relapse occurred within one week in 64 (59%) cases. Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age, greater heroin use prior to treatment, history of injecting, and a failure to enter aftercare. Unexpectedly, those who were in a relationship with an opiate user had significantly delayed relapse. Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse. In order to reduce relapse and the associated increased risk of fatal overdose, services providing residential opiate detoxification should prepare people for admission, strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome.

A classification framework for drug relapse prediction | Salleh ...

African Journals Online (AJOL)

mining algorithms, Artificial Intelligence Neural Network (ANN) is one of the best algorithms to predict relapse among drug addicts. This may help the rehabilitation center to predict relapse individually and the prediction result is hoped to prevent drug addicts from relapse. Keywords: classification; artificial neural network; ...

Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

DEFF Research Database (Denmark)

Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

2016-01-01

Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

Entomologic and molecular investigation into Plasmodium vivax transmission in Singapore, 2009.

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Ng, Lee-Ching; Lee, Kim-Sung; Tan, Cheong-Huat; Ooi, Peng-Lim; Lam-Phua, Sai-Gek; Lin, Raymond; Pang, Sook-Cheng; Lai, Yee-Ling; Solhan, Suhana; Chan, Pei-Pei; Wong, Kit-Yin; Ho, Swee-Tuan; Vythilingam, Indra

2010-10-29

Singapore has been certified malaria free since November 1982 by the World Health Organization and despite occasional local transmission, the country has maintained the standing. In 2009, three clusters of malaria cases were reported in Singapore. Epidemiological, entomological and molecular studies were carried out to investigate the three clusters, namely Mandai-Sungei Kadut, Jurong Island and Sembawang. A total of 29 malaria patients, with no recent travel history, were reported in the three clusters. Molecular analysis based on the msp3α and msp1 genes showed two independent local transmissions: one in Mandai-Sungei Kadut and another in Sembawang. Almost all cases within each cluster were epidemiologically linked. In Jurong Island cluster, epidemiological link remains uncertain, as almost all cases had a unique genetic profile. Only two cases shared a common profile and were found to be linked to the Mandai-Sungei Kadut cluster. Entomological investigation found Anopheles sinensis to be the predominant Anopheline in the two areas where local transmission of P. vivax was confirmed. Anopheles sinensis was found to be attracted to human bait and bites as early as 19:45 hrs. However, all Anopheles mosquitoes caught were negative for sporozoites and oocysts by dissection. Investigation of P. vivax cases from the three cluster areas confirmed the occurrence of local transmission in two areas. Although An. sinensis was the predominant Anopheline found in areas with confirmed transmission, the vector/s responsible for the outbreaks still remains cryptic.

Immunogenicity of Recombinant Proteins Consisting of Plasmodium vivax Circumsporozoite Protein Allelic Variant-Derived Epitopes Fused with Salmonella enterica Serovar Typhimurium Flagellin

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Leal, Monica Teixeira Andrade; Camacho, Ariane Guglielmi Ariza; Teixeira, Laís Helena; Bargieri, Daniel Youssef; Soares, Irene Silva; Tararam, Cibele Aparecida

2013-01-01

A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion vaccine is the first malaria vaccine to reach phase III clinical trials. Resistance to infection correlated with the production of antibodies to the immunodominant central repeat region of the CSP. In contrast to P. falciparum, vaccine development against the CSP of Plasmodium vivax malaria is far behind. Based on this gap in our knowledge, we generated a recombinant chimeric protein containing the immunodominant central repeat regions of the P. vivax CSP fused to Salmonella enterica serovar Typhimurium-derived flagellin (FliC) to activate the innate immune system. The recombinant proteins that were generated contained repeat regions derived from each of the 3 different allelic variants of the P. vivax CSP or a fusion of regions derived from each of the 3 allelic forms. Mice were subcutaneously immunized with the fusion proteins alone or in combination with the Toll-like receptor 3 (TLR-3) agonist poly(I·C), and the anti-CSP serum IgG response was measured. Immunization with a mixture of the 3 recombinant proteins, each containing immunodominant epitopes derived from a single allelic variant, rather than a single recombinant protein carrying a fusion of regions derived from each of 3 allelic forms elicited a stronger immune response. This response was independent of TLR-4 but required TLR-5/MyD88 activation. Antibody titers significantly increased when poly(I·C) was used as an adjuvant with a mixture of the 3 recombinant proteins. These recombinant fusion proteins are novel candidates for the development of an effective malaria vaccine against P. vivax. PMID:23863502

Observation d'une flambée de trypanosomose équine due à Trypanosoma vivax en zone urbaine au Sénégal

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Dehoux, JP.

1996-01-01

Full Text Available Observation of an Outbreak of Equine Trypanosomiasis due to Trypanosoma vivax in Urban Environment in Senegal. An outbreak of trypanosomiasis in imported and local horses and ponies occurred in September 1994 in a private horseriding farm near Dakar. Trypanosoma vivax was isolated. 5 mortalities (which a local pony were registered on 20 ill animals. The clinical signs were fever, depression, emaciation, anemia ad oedema. Curative treatment with intramuscular diminazene (3.5 mg/kg and prophylactic intravenous isometamidium (0.5 mg/kg were injected in October 1994 and July 1995. Glossina palpalis gambiensis was isolated near the farm.

Biological, immunological and functional properties of two novel multi-variant chimeric recombinant proteins of CSP antigens for vaccine development against Plasmodium vivax infection.

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Shabani, Samaneh H; Zakeri, Sedigheh; Salmanian, Ali H; Amani, Jafar; Mehrizi, Akram A; Snounou, Georges; Nosten, François; Andolina, Chiara; Mourtazavi, Yousef; Djadid, Navid D

2017-10-01

The circumsporozoite protein (CSP) of the malaria parasite Plasmodium vivax is a major pre-erythrocyte vaccine candidate. The protein has a central repeat region that belongs to one of repeat families (VK210, VK247, and the P. vivax-like). In the present study, computer modelling was employed to select chimeric proteins, comprising the conserved regions and different arrangements of the repeat elements (VK210 and VK247), whose structure is similar to that of the native counterparts. DNA encoding the selected chimeras (named CS127 and CS712) were synthetically constructed based on E. coli codons, then cloned and expressed. Mouse monoclonal antibodies (mAbs; anti-Pv-210-CDC and -Pv-247-CDC), recognized the chimeric antigens in ELISA, indicating correct conformation and accessibility of the B-cell epitopes. ELISA using IgG from plasma samples collected from 221 Iranian patients with acute P. vivax showed that only 49.32% of the samples reacted to both CS127 and CS712 proteins. The dominant subclass for the two chimeras was IgG1 (48% of the positive responders, OD 492 =0.777±0.420 for CS127; 48.41% of the positive responders, OD 492 =0.862±0.423 for CS712, with no statistically significant difference P>0.05; Wilcoxon signed ranks test). Binding assays showed that both chimeric proteins bound to immobilized heparan sulphate and HepG2 hepatocyte cells in a concentration-dependent manner, saturable at 80μg/mL. Additionally, anti-CS127 and -CS712 antibodies raised in mice recognized the native protein on the surface of P. vivax sporozoite with high intensity, confirming the presence of common epitopes between the recombinant forms and the native proteins. In summary, despite structural differences at the molecular level, the expression levels of both chimeras were satisfactory, and their conformational structure retained biological function, thus supporting their potential for use in the development of vivax-based vaccine. Copyright © 2017 Elsevier Ltd. All rights

Efficacy and safety of dihydroartemisinin-piperaquine in Indonesian children infected with uncomplicated Plasmodium falciparum and Plasmodium vivax

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Emiliana Tjitra

2011-12-01

Full Text Available Background Dihydroartemisinin-piperaquine (DPQ has been used since 2006 in Papua, Indonesia and is planned as an alternative artemisinin-based combination therapy for wider use in Indonesia. Confirmation of the drug’s efficacy and safety in children outside Papua is needed. Objective To measure the day-42 clinical and parasitological efficacy of DPQ in children with uncomplicated falciparum and vivax malaria. Methods This cross-sectional and observational study was held in Kalimantan and Sulawesi in 2010. Seventy and sixty children under 15 years of age with uncomplicated falciparum and vivax malaria were selected according to the 2003 WHO protocol for monitoring therapeutic efficacy of antimalarial treatments and was confirmed by microscopy and PCR. All subjects were treated with DPQ based on a dosage regimen of dihydroartemisinin 2-4 mg/kg BW/dose and piperaquine 16-32 mg/kg BW/dose, in single daily doses for 3 days and closely observed for 42 days. Data was analyzed using intention-to-treat (ITT and per protocol (PP populations. Results The mean fever and asexual parasite clearance times were 1.0 day and 1.6 days, respectively, in children with uncomplicated falciparum malaria, and 1.1 days and 1.2 days, respectively, in children with uncomplicatedvivax malaria. Clinical symptoms reduced over 50% by day 7. Hemoglobin recoveries showed improvement on days 14, 28 and 42, at 70.6%, 83.8%and 89.1%, respectively, in the falciparum malaria group, and 60.3%, 65,5% and 83.6%, respectively, in thevivax malaria group. Adequate clinical and parasitological response to DPQ on day 42 in the ITT and PP populations were reported as 98.6% (95% CI 92.3 to 99.7% and 100% (95% CI 94.7 to 100%, respectively, in the falciparum group, and 91.7% (95% CI 81.9 to 96.4% and 96.5% (95% CI 88.1 to 99.0%, respectively, the vivax group. Mild adverse events commonly noted were cough, abdominal pain, diarrhea, anorexia, and vomiting. Conclusion DPQ was effective against

Recovery from an acute relapse is associated with changes in motor resting-state connectivity in multiple sclerosis

DEFF Research Database (Denmark)

Dogonowski, Anne-Marie; Blinkenberg, Morten; Paulson, Olaf B.

2016-01-01

Resting-state functional MRI (rs-fMRI) of the brain has been successfully used to identify altered functional connectivity in the motor network in multiple sclerosis (MS).1 In clinically stable patients with MS, we recently demonstrated increased coupling between the basal ganglia and the motor...... network.1 Accordingly, rs-fMRI in MS is particularly suited to investigate functional reorganisation of the motor network in the remission phase after a relapse because the resting-state connectivity pattern is not influenced by interindividual differences in motor ability and task performance....... In this prospective rs-fMRI study, we mapped acute changes in resting-state motor connectivity in 12 patients with relapsing forms of MS presenting with an acute relapse involving an upper limb paresis. Previous functional MRI (fMRI) studies have shown that the activation of sensorimotor areas was stronger and more...

Mounting resistance of uropathogens to antimicrobial agents: A retrospective study in patients with chronic bacterial prostatitis relapse

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Konstantinos Stamatiou

2017-07-01

Full Text Available Purpose: Despite recent progress in the management of chronic bacterial prostatitis (CBP, many cases relapse. Increased drug resistance patterns of responsible bacteria have been proposed as the most probable causative factor. Driven by the limited number of previous studies addressing this topic, we aimed to study whether antibiotic resistance increases in patients with CBP when relapse occurs. A secondary aim of this study was to determine the resistance patterns of responsible bacteria from patients with CBP. Materials and Methods: The study material consisted of bacterial isolates from urine and/or prostatic secretions obtained from patients with CBP. Bacterial identification was performed by using the Vitek 2 Compact system and susceptibility testing was performed by disc diffusion and/or the Vitek 2 system. Interpretation of susceptibility results was based on Clinical and Laboratory Standards Institute guidelines. Results: A total of 253 samples from patients diagnosed with CBP for the first time (group A and 137 samples from relapsing patients with a history of CBP and previous antibiotic treatment (group B were analyzed. A significant reduction in bacterial resistance to the less used antibiotics (TMP-SMX, tetracyclines, aminoglycosides, penicillins, and macrolides was noted. An increase in resistance to quinolones of many bacteria that cause CBP was also noted with the increase in resistance of enterococcus strains being alarming. Conclusions: Comparison of the resistance profile of CBP-responsible bacteria between samples from first-time-diagnosed patients and samples from relapsing patients revealed notable differences that could be attributed to previous antibiotic treatment.

The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study.

Science.gov (United States)

Nguyen, Thuy-Nhien; von Seidlein, Lorenz; Nguyen, Tuong-Vy; Truong, Phuc-Nhi; Hung, Son Do; Pham, Huong-Thu; Nguyen, Tam-Uyen; Le, Thanh Dong; Dao, Van Hue; Mukaka, Mavuto; Day, Nicholas Pj; White, Nicholas J; Dondorp, Arjen M; Thwaites, Guy E; Hien, Tran Tinh

2018-05-01

A substantial proportion of Plasmodium species infections are asymptomatic with densities too low to be detectable with standard diagnostic techniques. The importance of such asymptomatic plasmodium infections in malaria transmission is probably related to their duration and density. To explore the duration of asymptomatic plasmodium infections and changes in parasite densities over time, a cohort of participants who were infected with Plasmodium parasites was observed over a 2-year follow-up period. In this open cohort study, inhabitants of four villages in Vietnam were invited to participate in baseline and subsequent 3-monthly surveys up to 24 months, which included the collection of venous blood samples. Samples were batch-screened using ultra-sensitive (u)PCR (lower limit of detection of 22 parasites per mL). Participants found to be infected by uPCR during any of these surveys were invited to join a prospective cohort and provide monthly blood samples. We estimated the persistence of Plasmodium falciparum and Plasmodium vivax infections and changes in parasite densities over a study period of 24 months. Between Dec 1, 2013, and Jan 8, 2016, 356 villagers participated in between one and 22 surveys. These study participants underwent 4248 uPCR evaluations (11·9 tests per participant). 1874 (32%) of 4248 uPCR tests indicated a plasmodium infection; 679 (36%) of 1874 tests were P falciparum monoinfections, 507 (27%) were P vivax monoinfections, 463 (25%) were co-infections with P falciparum and P vivax, and 225 (12%) were indeterminate species of Plasmodium. The median duration of P falciparum infection was 2 months (IQR 1-3); after accounting for censoring, participants had a 20% chance of having parasitaemia for 4 months or longer. The median duration of P vivax infection was 6 months (3-9), and participants had a 59% chance of having parasitaemia for 4 months or longer. The parasite densities of persistent infections oscillated; following ultralow

The Duffy binding protein as a key target for a Plasmodium vivax vaccine: lessons from the Brazilian Amazon

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Taís Nóbrega de Sousa

2014-08-01

Full Text Available Plasmodium vivax infects human erythrocytes through a major pathway that requires interaction between an apical parasite protein, the Duffy binding protein (PvDBP and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC. The importance of the interaction between PvDBP (region II, DBPII and DARC to P. vivax infection has motivated our malaria research group at Oswaldo Cruz Foundation (state of Minas Gerais, Brazil to conduct a number of immunoepidemiological studies to characterise the naturally acquired immunity to PvDBP in populations living in the Amazon rainforest. In this review, we provide an update on the immunology and molecular epidemiology of PvDBP in the Brazilian Amazon - an area of markedly unstable malaria transmission - and compare it with data from other parts of Latin America, as well as Asia and Oceania.

Causal Attributions about Disease-Onset and Relapse in Patients with Systemic Vasculitis

Science.gov (United States)

Grayson, Peter C.; Amudala, Naomi A.; McAlear, Carol A.; Leduc, Renée L.; Shereff, Denise; Richesson, Rachel; Fraenkel, Liana; Merkel, Peter A.

2014-01-01

Objectives Patients vary in their beliefs related to the cause of serious illness. The impact of these beliefs among patients with systemic vasculitis is not known. This study aimed to describe causal attributions about disease-onset and relapse in systemic vasculitis and to examine whether causal beliefs a) differ by type of vasculitis; and b) are associated with negative health outcomes. Methods Patients with vasculitis were recruited to complete an online questionnaire. Categories of causal beliefs were assessed with the Revised Illness Perception Questionnaire (IPQ-R). Differences in beliefs about disease-onset versus relapse were compared across different forms of vasculitis. Causal beliefs were assessed in association with several health outcomes including fatigue, functional impairments, and personal understanding of the condition. Results 692 patients representing 9 forms of vasculitis completed the questionnaire. The majority (90%) of patients had beliefs about the cause of their illness. Causal attributions were highly variable, but altered immunity and stress were the most commonly agreed upon causal beliefs. Frequencies of causal beliefs were strikingly similar across different forms of vasculitis, with few notable exceptions primarily in Behçet’s disease. Beliefs differed about causes of disease-onset versus relapse. Specific beliefs about disease-onset and relapse were weakly associated with fatigue, functional impairments, and understanding of the condition. Conclusion Patient beliefs related to the cause of systemic vasculitis are highly variable. Patterns of causal beliefs are associated with important negative health outcomes. Clinicians who care for patients with vasculitis should be mindful of these associations and consider asking about patients’ causal beliefs. PMID:24634202

Multiple Origins of Mutations in the mdr1 Gene—A Putative Marker of Chloroquine Resistance in P. vivax

DEFF Research Database (Denmark)

Schousboe, Mette L; Ranjitkar, Samir; Rajakaruna, Rupika S

2015-01-01

BACKGROUND: Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug...

Absence of Plasmodium inui and Plasmodium cynomolgi, but detection of Plasmodium knowlesi and Plasmodium vivax infections in asymptomatic humans in the Betong division of Sarawak, Malaysian Borneo.

Science.gov (United States)

Siner, Angela; Liew, Sze-Tze; Kadir, Khamisah Abdul; Mohamad, Dayang Shuaisah Awang; Thomas, Felicia Kavita; Zulkarnaen, Mohammad; Singh, Balbir

2017-10-17

Plasmodium knowlesi, a simian malaria parasite, has become the main cause of malaria in Sarawak, Malaysian Borneo. Epidemiological data on malaria for Sarawak has been derived solely from hospitalized patients, and more accurate epidemiological data on malaria is necessary. Therefore, a longitudinal study of communities affected by knowlesi malaria was undertaken. A total of 3002 blood samples on filter paper were collected from 555 inhabitants of 8 longhouses with recently reported knowlesi malaria cases in the Betong Division of Sarawak, Malaysian Borneo. Each longhouse was visited bimonthly for a total of 10 times during a 21-month study period (Jan 2014-Oct 2015). DNA extracted from blood spots were examined by a nested PCR assay for Plasmodium and positive samples were then examined by nested PCR assays for Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium cynomolgi and Plasmodium inui. Blood films of samples positive by PCR were also examined by microscopy. Genus-specific PCR assay detected Plasmodium DNA in 9 out of 3002 samples. Species-specific PCR identified 7 P. knowlesi and one P. vivax. Malaria parasites were observed in 5 thick blood films of the PCR positive samples. No parasites were observed in blood films from one knowlesi-, one vivax- and the genus-positive samples. Only one of 7 P. knowlesi-infected individual was febrile and had sought medical treatment at Betong Hospital the day after sampling. The 6 knowlesi-, one vivax- and one Plasmodium-infected individuals were afebrile and did not seek any medical treatment. Asymptomatic human P. knowlesi and P. vivax malaria infections, but not P. cynomolgi and P. inui infections, are occurring within communities affected with malaria.

Relapse patterns in WHO 2/3 nasopharyngeal cancer: Is there a difference between ethnic Asian vs. non-Asian patients?

International Nuclear Information System (INIS)

Corry, June; Fisher, Richard; Rischin, Danny; Peters, Lester J.

2006-01-01

Purpose: The purpose of this study was to assess whether ethnicity is an independent prognostic factor in patients with World Health Organization (WHO) type 2 or 3 nasopharyngeal carcinoma (NPC). Specifically, we examined the patterns of relapse observed in patients classified as 'Asian' (born in southern China or southeast Asia) or 'non-Asian' (born in Australia, Europe, the Middle East, or the Pacific Islands). Methods and Materials: All patients planned for radical treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. Pathology was reviewed to confirm WHO type 2 or 3 NPC. Patients were staged using the 1997 International Union Against Cancer (UICC) criteria. Mean potential follow-up time was 9.6 years (range, 1.0-18.5 years) Results: There were 158 patients: 86 Asian and 72 non-Asian. Stage groupings were: I-12 patients; II-32 patients; III-59 patients; and IV-55 patients. A staging computerized tomography was performed in 121 patients, and 53 (34%) also had a staging magnetic resonance imaging (MRI). The Asian patients had significantly more women, more patients aged <45, and more with performance status 0 than the non-Asians. Other putative prognostic factors were not significantly different between the groups. The 5-year rates for freedom from local recurrence (FLR), failure-free survival (FFS), and overall survival (OS) for Asian and non-Asian patients were 74% vs. 82%, 61% vs. 55%, and 75% vs. 63%, respectively. Corresponding 10-year figures were: 62% vs. 82%, 43% vs. 48%, and 58% vs. 49%, respectively. Multifactor analysis showed stage and the use of MRI for staging to be significant prognostic factors for all three endpoints. Age was also significant for FFS and OS. There were no significant differences in FFS or OS between Asian and non-Asian patients. However, the FLR interval was significantly worse in the Asian group (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.11-5.06), whereas

Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu

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Rogers William O

2010-04-01

Full Text Available Abstract Background Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. Methods In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. Results The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. Conclusion Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study

Preventing Relapse to Cigarette Smoking by Behavioral Skill Training.

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Hall, Sharon M.; And Others

1984-01-01

Crossed two relapse prevention conditions (skills training-vs-discussion control) with two levels of aversive smoking in volunteer subjects (N=123). Results indicated that relapse-prevention skill training did prevent relapse among cigarette smokers. Lighter smokers were more favorably influenced. (LLL)

Metaplastic carcinoma. Breast. Relapse. Chemotherapy and Radiotherapy

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Marquez, A.; Terrasa, J.; Garcia, J.M.; Rifa, J.

1996-01-01

Metaplastic carcinoma of the breast is a rare tumor. The appearance of unexpected mesenchymal elements within the epithelial tumors is the squamous metaplasia. These tumors have a different clinical behaviour that classical breast carcinoma. We present a case of metaplastic mammary carcinoma with multiple relapses treated with a combination of chemotherapy and radiotherapy. The use of chemotherapy after local treatment has enhanced the relapse-free survival. The combined treatment modality seems to produce some benefit in the management of the local relapses of this neoplasms

A focus of hyperendemic Plasmodium malariae-P. vivax with no P. falciparum in a primitive population in the Peruvian Amazon jungle.

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Sulzer, A J; Cantella, R; Colichon, A; Gleason, N N; Walls, K W

1975-01-01

Findings in a sample population in southeastern Peru with a very high rate of malaria infection, due to Plasmodium malariae and P. vivax with apparently no P. falciparum, are described. The proportion of persons with P. malariae in this sample population, as determined by slide examination, appears to be the greatest ever reported for any area before the introduction of control measures. Although very few P. vivax were found on stained slides, results of the indirect immunofluorescence test indicated that this species was probably as prevalent as P. malariae; the absence of P. falciparum was supported by results of serologic tests. Possible reasons for this focus of malaria with no P. falciparum are discussed.

Entomologic and molecular investigation into Plasmodium vivax transmission in Singapore, 2009

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Solhan Suhana

2010-10-01

Full Text Available Abstract Background Singapore has been certified malaria free since November 1982 by the World Health Organization and despite occasional local transmission, the country has maintained the standing. In 2009, three clusters of malaria cases were reported in Singapore. Methods Epidemiological, entomological and molecular studies were carried out to investigate the three clusters, namely Mandai-Sungei Kadut, Jurong Island and Sembawang. Results A total of 29 malaria patients, with no recent travel history, were reported in the three clusters. Molecular analysis based on the msp3α and msp1 genes showed two independent local transmissions: one in Mandai-Sungei Kadut and another in Sembawang. Almost all cases within each cluster were epidemiologically linked. In Jurong Island cluster, epidemiological link remains uncertain, as almost all cases had a unique genetic profile. Only two cases shared a common profile and were found to be linked to the Mandai-Sungei Kadut cluster. Entomological investigation found Anopheles sinensis to be the predominant Anopheline in the two areas where local transmission of P. vivax was confirmed. Anopheles sinensis was found to be attracted to human bait and bites as early as 19:45 hrs. However, all Anopheles mosquitoes caught were negative for sporozoites and oocysts by dissection. Conclusion Investigation of P. vivax cases from the three cluster areas confirmed the occurrence of local transmission in two areas. Although An. sinensis was the predominant Anopheline found in areas with confirmed transmission, the vector/s responsible for the outbreaks still remains cryptic.

Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group.

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Itonaga, H; Sawayama, Y; Taguchi, J; Honda, S; Taniguchi, H; Makiyama, J; Matsuo, E; Sato, S; Ando, K; Imanishi, D; Imaizumi, Y; Yoshida, S; Hata, T; Moriuchi, Y; Fukushima, T; Miyazaki, Y

2015-04-01

Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (PSCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

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Lao, Louis [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Hope, Andrew J. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Maganti, Manjula [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Cho, B. C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

2014-09-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

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Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

2014-01-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT

Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

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Foote, Matthew; Harvey, Jennifer; Porceddu, Sandro

2010-01-01

Purpose: To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). Patients and Methods: This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. Results: Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%) were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving ≥50Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). Conclusion: This study indicates a dose-response for subclinical and gross MCC. Doses of ≥50Gy for subclinical disease and ≥55Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.

Variation in Complexity of Infection and Transmission Stability between Neighbouring Populations of Plasmodium vivax in Southern Ethiopia.

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Sisay Getachew

Full Text Available P. vivax is an important public health burden in Ethiopia, accounting for almost half of all malaria cases. Owing to heterogeneous transmission across the country, a stronger evidence base on local transmission dynamics is needed to optimise allocation of resources and improve malaria interventions.In a pilot evaluation of local level P. vivax molecular surveillance in southern Ethiopia, the diversity and population structure of isolates collected between May and November 2013 were investigated. Blood samples were collected from microscopy positive P. vivax patients recruited to clinical and cross-sectional surveys from four sites: Arbaminch, Halaba, Badawacho and Hawassa. Parasite genotyping was undertaken at nine tandem repeat markers. Eight loci were successfully genotyped in 197 samples (between 36 and 59 per site. Heterogeneity was observed in parasite diversity and structure amongst the sites. Badawacho displayed evidence of unstable transmission, with clusters of identical clonal infections. Linkage disequilibrium in Badawacho was higher (IAS = 0.32, P = 0.010 than in the other populations (IAS range = 0.01-0.02 and declined markedly after adjusting for identical infections (IAS = 0.06, P = 0.010. Other than Badawacho (HE = 0.70, population diversity was equivalently high across the sites (HE = 0.83. Polyclonal infections were more frequent in Hawassa (67% than the other populations (range: 8-44%. Despite the variable diversity, differentiation between the sites was low (FST range: 5 x 10-3-0.03.Marked variation in parasite population structure likely reflects differing local transmission dynamics. Parasite genotyping in these heterogeneous settings has potential to provide important complementary information with which to optimise malaria control interventions.

Burden of a multiple sclerosis relapse: the patient's perspective.

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Oleen-Burkey, Merrikay; Castelli-Haley, Jane; Lage, Maureen J; Johnson, Kenneth P

2012-01-01

Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the

Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

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Peled, Jonathan U; Devlin, Sean M; Staffas, Anna; Lumish, Melissa; Khanin, Raya; Littmann, Eric R; Ling, Lilan; Kosuri, Satyajit; Maloy, Molly; Slingerland, John B; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Shono, Yusuke; Slingerland, Ann E; Docampo, Melissa D; Sung, Anthony D; Weber, Daniela; Alousi, Amin M; Gyurkocza, Boglarka; Ponce, Doris M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Taur, Ying; Pamer, Eric G; Jenq, Robert R; van den Brink, Marcel R M

2017-05-20

Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

Spatial variation in genetic diversity and natural selection on the thrombospondin-related adhesive protein locus of Plasmodium vivax (PvTRAP.

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Rattiporn Kosuwin

Full Text Available Thrombospondin-related adhesive protein (TRAP of malaria parasites is essential for sporozoite motility and invasions into mosquito's salivary gland and vertebrate's hepatocyte; thereby, it is a promising target for pre-erythrocytic vaccine. TRAP of Plasmodium vivax (PvTRAP exhibits sequence heterogeneity among isolates, an issue relevant to vaccine development. To gain insights into variation in the complete PvTRAP sequences of parasites in Thailand, 114 vivax malaria patients were recruited in 2006-2007 from 4 major endemic provinces bordering Myanmar (Tak in the northwest, n = 30 and Prachuap Khirikhan in the southwest, n = 25, Cambodia (Chanthaburi in the east, n = 29 and Malaysia (Yala and Narathiwat in the south, n = 30. In total, 26 amino acid substitutions were detected and 9 of which were novel, resulting in 44 distinct haplotypes. Haplotype and nucleotide diversities were lowest in southern P. vivax population while higher levels of diversities were observed in other populations. Evidences of positive selection on PvTRAP were demonstrated in domains II and IV and purifying selection in domains I, II and VI. Genetic differentiation was significant between each population except that between populations bordering Myanmar where transmigration was common. Regression analysis of pairwise linearized Fst and geographic distance suggests that P. vivax populations in Thailand have been isolated by distance. Sequence diversity of PvTRAP seems to be temporally stable over one decade in Tak province based on comparison of isolates collected in 1996 (n = 36 and 2006-2007. Besides natural selection, evidences of intragenic recombination have been supported in this study that could maintain and further generate diversity in this locus. It remains to be investigated whether amino acid substitutions in PvTRAP could influence host immune responses although several predicted variant T cell epitopes drastically altered the epitope

Validation of pre-coated ELISA tests to detect antibodies against T. congolense and T. vivax

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Shumba, W.

2000-01-01

The anti-trypanosomal antibody detecting enzyme linked immunosorbent assay (ELISA) was first described in 1977 and was further developed for use in large scale surveys in Zimbabwe. More recently, the IAEA initiated a programme to improve the robustness and standardisation of the assay. The IAEA supplied plates pre-coated with either a crude T. congolense or T. vivax antigen and the reagents necessary for analysing samples. Parasitologically positive and negative sera were used to validate and determine the cut-off values of the two tests. The samples were tested and results analysed using a variety of cut-off values. The tests provided similar information although the T. congolense pre-coated plates gave significantly higher optical density values than the plates coated with T. vivax. Sensitivity and specificity values were calculated using the different cut-off points. Results indicate that the test using T. congolense antigen had the highest specificity and sensitivity for a given cut-off value. Although the test could distinguish positive from negative sera, it was quite difficult to provide a suitable cut-off value, but the value should be dictated by the use of the test. (author)

Plasmodium vivax congenital malaria in an area of very low endemicity in Guatemala: implications for clinical and epidemiological surveillance in a malaria elimination context

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Castellanos María Eugenia

2012-12-01

Full Text Available Abstract This is a report of the first Plasmodium vivax congenital malaria case in Guatemala and the first case in Latin America with genotypical, histological and clinical characterization. The findings show that maternal P. vivax infection still occurs in areas that are in the pathway towards malaria elimination, and can be associated with detrimental health effects for the neonate. It also highlights the need in very low transmission areas of not only maintaining, but increasing awareness of the problem and developing surveillance strategies, based on population risk, to detect the infection especially in this vulnerable group of the population.

Relapse and craving in alcohol-dependent individuals

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van de Mheen, H,; Snelleman, M.; Schoenmakers, T.M.

2018-01-01

Background: Negative affective states and alcohol-related stimuli increase risk of relapse in alcohol dependence. In research and in clinical practice, craving is often used as another important indicator of relapse, but this lacks a firm empirical foundation. Objectives: The goal of the present

Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

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Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

2018-02-01

Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of relapse to any alcohol use after liver transplant.

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Rodrigue, James R; Hanto, Douglas W; Curry, Michael P

2013-12-01

Alcohol relapse after liver transplant heightens concern about recurrent disease, nonadherence to the immunosuppression regimen, and death. To develop a scoring system to stratify risk of alcohol relapse after liver transplant. Retrospective medical record review. All adult liver transplants performed from May 2002 to February 2011 at a single center in the United States. The incidence of return to any alcohol consumption after liver transplant. Thirty-four percent (40/118) of patients with a history of alcohol abuse/dependency relapsed to use of any alcohol after liver transplant. Nine of 25 hypothesized risk factors were predictive of alcohol relapse after liver transplant: absence of hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver disease diagnosis, low motivation for alcohol treatment, poor stress management skills, no rehabilitation relationship, limited social support, lack of nonmedical behavioral consequences, and continued engagement in social activities with alcohol present. Each independent predictor was assigned an Alcohol Relapse Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1 of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly higher rates of alcohol relapse and were more likely to return to pretransplant levels of drinking. Alcohol relapse rates are moderately high after liver transplant. The ARRA is a valid and practical tool for identifying pretransplant patients with alcohol abuse or dependency at elevated risk of any alcohol use after liver transplant.

Smoking relapse situations among a community-recruited sample of Spanish daily smokers.

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Piñeiro, Bárbara; López-Durán, Ana; Martínez-Vispo, Carmela; Fernández Del Río, Elena; Martínez, Úrsula; Rodríguez-Cano, Rubén; Míguez, M Carmen; Becoña, Elisardo

2017-12-01

Relapse is a common factor within the behavior change process. However, there is scarce and limited knowledge of smoking relapse situations in population-based samples. The aim of this study was to identify smoking relapse situations among a sample of Spanish relapsers from the general population. A sample of 775 relapsers was recruited among the general population using a snowball method. Participants completed a survey including sociodemographic, smoking-related and psychopathology variables. Smoking relapse situations were identified through specific questions assessing different aspects related to the last relapse episode. The majority of smoking relapse situations were attributed to positive affect (36.6%) and negative affect (34.3%), followed by lack of control (10.1%), smoking habit (6.7%), craving or nicotine withdrawal (6.3%), and social pressure (5.9%). Being unemployed and having a mental disorder in the past increased the likelihood of relapse in situations of negative affect. Being single and having quit smoking to save money were associated with an increased likelihood of relapse in situations of positive affect. Affect plays a significant role in smoking relapse among a community sample of unassisted Spanish smokers. Relapse may be much more of an affective and situational process than a habit, physiological or social pressure. Findings from this study may help develop tailored community smoking relapse prevention strategies or programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Extinction of relapsed fear does not require the basolateral amygdala.

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Lingawi, Nura W; Westbrook, R Frederick; Laurent, Vincent

2017-03-01

It is well established that extinguished fears are restored with the passage of time or a change in physical context. These fear restoration phenomena are believed to mimic the conditions under which relapse occurs in patients that have been treated for anxiety disorders by means of cue-exposure therapy. Here, we used a rodent model to extinguish relapsed fear and assess whether this new extinction prevents further relapse. We found that activity in the basolateral amygdala (BLA) is required to initially extinguish conditioned fear, but this activity was not necessary to subsequently extinguish relapsed fear. That is, extinction of spontaneously recovered or renewed fear was spared by BLA inactivation. Yet, this BLA-independent learning of extinction did not protect against further relapse: extinction of relapsed fear conducted without BLA activity was still likely to return after the passage of time or a shift in physical context. These findings have important clinical implications. They indicate that pharmacological agents with anxiolytic properties may disrupt initial cue-exposure therapy but may be useful when therapy is again needed due to relapse. However, they also suggest that these agents will not protect against further relapse, implying the need for developing drugs that target other brain regions involved in fear inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

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Chessells, J.; Leiper, A.; Rogers, D.

1984-01-01

Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients

Preventing relapse after incentivized choice treatment: A laboratory model.

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Bouton, Mark E; Thrailkill, Eric A; Bergeria, Cecilia L; Davis, Danielle R

2017-08-01

Two experiments with rats examined relapse of an operant behavior that occurred after the behavior was suppressed by reinforcing (incentivizing) an alternative behavior. In the first phase, a target response (R1) was reinforced. In a treatment phase, R1 was still reinforced, but a new response (R2) was introduced and associated with a larger reinforcer. As in human contingency management treatments, incentivizing R2 this way was effective at suppressing R1. However, when R2's reinforcement was discontinued, there was a robust and immediate relapse to R1. Experiment 1 found that the strength of R1 during relapse testing was not different from that seen in a no treatment control. Experiment 2 found that relapse could nevertheless be reduced by presenting reinforcers not contingent on responding during the test. Either the reinforcer for R1 or the reinforcer for R2 (which were qualitatively different types of food pellets) were effective. The experiments introduce a laboratory method for studying relapse and how to prevent it after contingency management treatments, and suggest at least one treatment that discourages relapse. The incentivized choice paradigm differs from other models of relapse of operant behavior (e.g., resurgence, renewal, reinstatement) in that it does not focus on the return of behaviors that are inhibited by extinction. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence and clinical manifestations of malaria in Aligarh, India.

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Asma, Umm-e; Taufiq, Farha; Khan, Wajihullah

2014-12-01

Malaria is one of the most widespread infectious diseases of tropical countries with an estimated 207 million cases globally. In India, there are endemic pockets of this disease, including Aligarh. Hundreds of Plasmodium falciparum and P. vivax cases with severe pathological conditions are recorded every year in this district. The aim of this study is to find out changes in liver enzymes and kidney markers. Specific diagnosis for P. falciparum and P. vivax was made by microscopic examination of Giemsa stained slides. Clinical symptoms were observed in both of these infections. Liver enzymes, such as AST, ALT, and ALP, and kidney function markers, such as creatinine and urea, were estimated by standard biochemical techniques. In Aligarh district, P. vivax, P. falciparum, and mixed infections were 64%, 34%, and 2%, respectively. In case of P. falciparum infection, the incidences of anemia, splenomegaly, renal failure, jaundice, and neurological sequelae were higher compared to those in P. vivax infection. Recrudescence and relapse rates were 18% and 20% in P. falciparum and P. vivax infections, respectively. Liver dysfunctions and renal failures were more common in P. falciparum patients, particularly in elderly patients. Artesunate derivatives must, therefore, be introduced for the treatment of P. falciparum as they resist to chloroquine as well as sulfadoxine-pyrimethamine combinations.

Efficacy of chloroquine for the treatment of Plasmodium vivax in the Saharan zone in Mauritania

OpenAIRE

Ould Ahmedou Salem, Mohamed Salem; Mohamed Lemine, Yeslim Ould; Deida, Jemila Mint; Lemrabott, Mohamed Aly Ould; Ouldabdallahi, Mohamed; Ba, Mamadou dit Dialaw; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Abdel Aziz, Mohamed Boubacar; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sidi Mohamed

2015-01-01

Background: In 2006, the Mauritanian Ministry of Health adopted a new therapeutic strategy based on the systematic use of artemisinin-based combination therapy (ACT), artesunate-amodiaquine and artemether-lumefantrine, for the first-and second-line treatment of uncomplicated malaria, respectively, regardless of Plasmodium spp. In the Saharan zone of the country, recent studies have shown that Plasmodium vivax largely predominates over Plasmodium falciparum. Anti-malarial drug response of P. v...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation Complementary & Alternative Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care ...

[Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

Science.gov (United States)

Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

2016-09-02

Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Postpartum smoking relapse--a thematic synthesis of qualitative studies.

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Notley, Caitlin; Blyth, Annie; Craig, Jean; Edwards, Alice; Holland, Richard

2015-11-01

Many women quit smoking during pregnancy, but relapse after the baby is born. To understand why and identify ways of preventing this, this study reviewed the qualitative literature on women's experience of postpartum smoking relapse. A systematic review of qualitative studies and process evaluations of trials. We undertook a thematic synthesis of published qualitative data. We screened 1336 papers. Twenty-two papers reporting on 16 studies were included, reporting on the views of 1031 postpartum women. Factors affecting relapse and barriers and facilitators to relapse prevention were identified around the key themes of beliefs, social influences, motivation, physiological factors and identity. Women's beliefs about smoking as a means of coping with stress and the need for social support, especially from a partner, emerged as important. Extrinsic motivation to quit during the pregnancy (for the health of the fetus) appeared to be a factor in prompting relapse after the baby was born. During the immediate postpartum period women believed that physiological changes influence cigarette cravings. The stress of caring for a newborn, sleeplessness and adjusting to a new mothering identity were also reported to be important. Among women who quit smoking during pregnancy, those who relapse postpartum talk commonly about no longer needing to protect the baby and the effects of stress. Partner support and a sense of changed identity are cited as factors preventing relapse. © 2015 Society for the Study of Addiction.

A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1†

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Nogueira, Paulo Afonso; Piovesan Alves, Fabiana; Fernandez-Becerra, Carmen; Pein, Oliver; Rodrigues Santos, Neida; Pereira da Silva, Luiz Hildebrando; Plessman Camargo, Erney; del Portillo, Hernando A.

2006-01-01

Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite. PMID:16622209

Identification of Protein Markers in Patients Infected with Plasmodium knowlesi, Plasmodium falciparum and Plasmodium vivax

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Alan Kang-Wai Mu

2014-11-01

Full Text Available Malaria is caused by parasitic protozoans of the genus Plasmodium and is one of the most prevalent infectious diseases in tropical and subtropical regions. For this reason, effective and practical diagnostic methods are urgently needed to control the spread of malaria. The aim of the current study was to identify a panel of new malarial markers, which could be used to diagnose patients infected with various Plasmodium species, including P. knowlesi, P. vivax and P. falciparum. Sera from malaria-infected patients were pooled and compared to control sera obtained from healthy individuals using the isobaric tags for relative and absolute quantitation (iTRAQ technique. Mass spectrometry was used to identify serum proteins and quantify their relative abundance. We found that the levels of several proteins were increased in pooled serum from infected patients, including cell adhesion molecule-4 and C-reactive protein. In contrast, the serum concentration of haptoglobin was reduced in malaria-infected individuals, which we verified by western blot assay. Therefore, these proteins might represent infectious markers of malaria, which could be used to develop novel diagnostic tools for detecting P. knowlesi, P. vivax and P. falciparum. However, these potential malarial markers will need to be validated in a larger population of infected individuals.

Relapse Prevention: An Overview of Marlatts Cognitive- Behavioral Model

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2008-11-01

Full Text Available Relapse prevention(RPis an important component of alcoholism treatment. The RP model proposed by Marlatt and Gordon suggests that both immediate determinants (e.g.,high- risk situations, coping skills, outcome expectancies, and the abstinence violation effect and covert antecedents (e.g., lifestyle factor and urges and cravings can contribute to relapse.The RP model also incorporates numerous specific and global intervention strategies that allow therapist and client to address each step of the relapse process. Specific interventions include identifying specific high-risk situations for each client and enhancing the client's skills for coping with those situations, increasing the client's self- efficacy, eliminating myths regarding alcohol's effects, managing lapses, and restructuring the client's perceptions of the relapse process. Global strategies comprise balancing the client's lifestyle and helping him or her develop positive addictions, employing stimulus control techniques and urgemanagement techniques, and developing relapse road maps. Several studies have provided theoretical and practical support for the RP model.

Predictive factors for relapse in patients on buprenorphine maintenance.

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Ferri, Michael; Finlayson, Alistair J Reid; Wang, Li; Martin, Peter R

2014-01-01

Despite the dramatic increase in the use of buprenorphine for the treatment of opioid dependence, clinical outcomes of this treatment approach continue to need evaluation. This study examines factors associated with relapse and retention during buprenorphine treatment in a sample of opioid dependent outpatients. In a retrospective chart review of 62 patients with opioid dependence, relapse was determined by self-report, urine toxicology screens, and by checking the state controlled substance monitoring database. Data was analyzed using two-way tests of association and logistic regression. Patients with comorbid anxiety disorders, active benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were significantly more likely to relapse. Patients who relapsed were also more likely to be on a higher buprenorphine maintenance dose. This study identifies relapse risk factors during buprenorphine treatment for opioid dependence. Future research is needed to determine whether modifying these factors may lead to improved treatment outcomes. © American Academy of Addiction Psychiatry.

Patterns of failure following high-dose chemotherapy and stem cell rescue for relapsed/refractory non-Hodgkin's lymphoma: implications for the use of adjuvant involved field radiotherapy

International Nuclear Information System (INIS)

Mundt, Arno J.; Williams, Stephanie F.; Hallahan, Dennis; Weichselbaum, Ralph R.

1996-01-01

Purpose: Recent data have suggested a benefit to involved-field radiotherapy (IFRT) in conjunction with high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) in patients with metastatic breast cancer, advanced neuroblastoma and relapsed/refractory Hodgkin's disease. The purpose of this study is to determine whether a similar role exists for IFRT in patients with relapsed/refractory Non-Hodgkin's Lymphoma (NHL) undergoing HDCT. Methods/Materials: Forty-nine adult patients with refractory (17) or relapsed (32) NHL underwent HDCT with SCR between 9/90 and 9/95. The most common histology was diffuse large cell (42.8%). Initial stages were I (3), II (23), III (5) and IV (18). All patients had a history of conventional chemotherapy (median regimens 2, range 1-3), 17 (34.7%) had previous RT. Treatment consisted of conventional dose induction chemotherapy followed by high-dose intensification with cytoxan, busulfan and either ara-C or VP-16. Seven patients (14.3%) received IFRT (median dose 34.5 Gy, range 20-45 Gy) to eleven sites of persistent disease following HDCT (HDCT+IFRT). Patients treated with RT to sites of progressive disease following HDCT (salvage RT) were not included in the HDCT+IFRT group. No patient received total body irradiation (TBI). One hundred sixty four sites were identified. Sites were designated as amenable or not to IFRT and divided into those achieving a complete response to induction (IndCR) and those which did not (non-IndCR). An amenable site is defined as disease localized to either an organ or nodal chain and encompassable within a standard RT portal. Relapse sites were designated as in previous (involved) sites (present prior to HDCT) or in new (uninvolved) sites. Median followup was 19.7 months (range, 1-57.3 months). Results: The 4-year actuarial progression-free (PFS), cause-specific (CSS) and overall (OS) survivals of the entire group were 36.4%, 45.9% and 34.9%, respectively. Excluding toxic deaths, 20 (47.6%) patients

Elimination of malaria due to Plasmodium vivax in central part of the People’s Republic of China: analysis and prediction based on modelling

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Zhao Chen

2014-11-01

Full Text Available Five provinces in central People’s Republic of China (P.R. China have successfully reduced the burden of malaria due to Plasmodium vivax in the last 7 years. The results of the Action Plan of China Malaria Elimination (APCME that com- menced in 2010 are analysed against the background of the progress reached by the national malaria control programme (NMEP that was launched in 2006. We examined the epidemiological changes in the number of autochthonous cases over time and discuss the feasibility of achieving the goal of malaria elimination by 2020. There was a total decline of 34,320 malaria cases between 2006 and 2012 arriving at an average annual incidence of 0.04 per 10,000 people by 2012. At the same time, the number of counties reporting autochthonous cases declined from 290 to 19. Spatial autocorrelation and Bayesian modelling were used to evaluate the datasets and predict the spatio-temporal pattern in the near future. The former approach showed that spatial clusters of P. vivax malaria existed in the study region during the study period, while the risk prediction map generated by the Bayesian model indicates that only sporadic malaria cases will appear during in the future. The results suggest that the initial NMEP approach and the follow-up APCME strategy have played a key role in reducing the threat of malaria in central P.R. China. However, to achieve the goal of malaria elimination by the end of the current decade, interven- tion plans must be adjusted with attention paid to those endemic counties still at risk according to the prediction map.

The epidemiology of Plasmodium vivax and Plasmodium falciparum malaria in China, 2004-2012: from intensified control to elimination.

Science.gov (United States)

Zhang, Qian; Lai, Shengjie; Zheng, Canjun; Zhang, Honglong; Zhou, Sheng; Hu, Wenbiao; Clements, Archie C A; Zhou, Xiao-Nong; Yang, Weizhong; Hay, Simon I; Yu, Hongjie; Li, Zhongjie

2014-11-03

In China, the national malaria elimination programme has been operating since 2010. This study aimed to explore the epidemiological changes in patterns of malaria in China from intensified control to elimination stages. Data on nationwide malaria cases from 2004 to 2012 were extracted from the Chinese national malaria surveillance system. The secular trend, gender and age features, seasonality, and spatial distribution by Plasmodium species were analysed. In total, 238,443 malaria cases were reported, and the proportion of Plasmodium falciparum increased drastically from population. The areas affected by Plasmodium vivax malaria shrunk, while areas affected by P. falciparum malaria expanded from 294 counties in 2004 to 600 counties in 2012. This study demonstrated that malaria has decreased dramatically in the last five years, especially since the Chinese government launched a malaria elimination programme in 2010, and areas with reported falciparum malaria cases have expanded over recent years. These findings suggest that elimination efforts should be improved to meet these changes, so as to achieve the nationwide malaria elimination goal in China in 2020.

Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments.

Science.gov (United States)

Martin, Alissa; Morgan, Elaine; Hijiya, Nobuko

2012-12-01

Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity and mortality in pediatrics. With contemporary chemotherapy, >85% of patients with newly diagnosed ALL survive. Unfortunately, 20% of these patients will relapse and for these children, outcomes remain poor despite our best known chemotherapy protocols. Most of these children will achieve a second complete remission, but maintaining this remission remains difficult. Because relapsed ALL is such a significant cause of morbidity and mortality, it is the focus of much research interest. Efforts have been made and continue to focus on understanding the underlying biology that drives relapse. The role of hematopoietic stem cell transplantation in relapsed ALL remains unclear, but many clinicians still favor this for high-risk patients given the poor prognosis with current chemotherapy alone. It is important to use new drugs with little cross-resistance in the treatment of relapsed ALL. New classes of agents are currently being studied. We also discuss prognostic factors and the biology of relapsed ALL.

Molecular Epidemiology of P. vivax in Iran: High Diversity and Complex Sub-Structure Using Neutral Markers, but No Evidence of Y976F Mutation at pvmdr1.

Science.gov (United States)

Hamedi, Yaghoob; Sharifi-Sarasiabi, Khojasteh; Dehghan, Farzaneh; Safari, Reza; To, Sheren; Handayuni, Irene; Trimarsanto, Hidayat; Price, Ric N; Auburn, Sarah

2016-01-01

Malaria remains endemic at low levels in the south-eastern provinces of Iran bordering Afghanistan and Pakistan, with the majority of cases attributable to P. vivax. The national guidelines recommend chloroquine (CQ) as blood-stage treatment for uncomplicated P. vivax, but the large influx of imported cases enhances the risk of introducing CQ resistance (CQR). The genetic diversity at pvmdr1, a putative modulator of CQR, and across nine putatively neutral short tandem repeat (STR) markers were assessed in P. vivax clinical isolates collected between April 2007 and January 2013 in Hormozgan Province, south-eastern Iran. One hundred blood samples were collected from patients with microscopy-confirmed P. vivax enrolled at one of five district clinics. In total 73 (73%) were autochthonous cases, 23 (23%) imported cases from Afghanistan or Pakistan, and 4 (4%) with unknown origin. 97% (97/100) isolates carried the F1076L mutation, but none carried the Y976F mutation. STR genotyping was successful in 71 (71%) isolates, including 57(57%) autochthonous and 11 (11%) imported cases. Analysis of population structure revealed 2 major sub-populations, K1 and K2, with further sub-structure within K2. The K1 sub-population had markedly lower diversity than K2 (HE = 0.06 vs HE = 0.82) suggesting that the sub-populations were sustained by distinct reservoirs with differing transmission dynamics, possibly reflecting local versus imported/introduced populations. No notable separation was observed between the local and imported cases although the sample size was limited. The contrasting low versus high diversity in the two sub-populations (K1 and K2) infers that a combination of local transmission and cross-border malaria from higher transmission regions shape the genetic make-up of the P. vivax population in south-eastern Iran. There was no molecular evidence of CQR amongst the local or imported cases, but ongoing clinical surveillance is warranted.

Molecular Epidemiology of P. vivax in Iran: High Diversity and Complex Sub-Structure Using Neutral Markers, but No Evidence of Y976F Mutation at pvmdr1.

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Yaghoob Hamedi

Full Text Available Malaria remains endemic at low levels in the south-eastern provinces of Iran bordering Afghanistan and Pakistan, with the majority of cases attributable to P. vivax. The national guidelines recommend chloroquine (CQ as blood-stage treatment for uncomplicated P. vivax, but the large influx of imported cases enhances the risk of introducing CQ resistance (CQR.The genetic diversity at pvmdr1, a putative modulator of CQR, and across nine putatively neutral short tandem repeat (STR markers were assessed in P. vivax clinical isolates collected between April 2007 and January 2013 in Hormozgan Province, south-eastern Iran. One hundred blood samples were collected from patients with microscopy-confirmed P. vivax enrolled at one of five district clinics. In total 73 (73% were autochthonous cases, 23 (23% imported cases from Afghanistan or Pakistan, and 4 (4% with unknown origin. 97% (97/100 isolates carried the F1076L mutation, but none carried the Y976F mutation. STR genotyping was successful in 71 (71% isolates, including 57(57% autochthonous and 11 (11% imported cases. Analysis of population structure revealed 2 major sub-populations, K1 and K2, with further sub-structure within K2. The K1 sub-population had markedly lower diversity than K2 (HE = 0.06 vs HE = 0.82 suggesting that the sub-populations were sustained by distinct reservoirs with differing transmission dynamics, possibly reflecting local versus imported/introduced populations. No notable separation was observed between the local and imported cases although the sample size was limited.The contrasting low versus high diversity in the two sub-populations (K1 and K2 infers that a combination of local transmission and cross-border malaria from higher transmission regions shape the genetic make-up of the P. vivax population in south-eastern Iran. There was no molecular evidence of CQR amongst the local or imported cases, but ongoing clinical surveillance is warranted.

Plasmodium vivax Tryptophan Rich Antigen PvTRAg36.6 Interacts with PvETRAMP and PvTRAg56.6 Interacts with PvMSP7 during Erythrocytic Stages of the Parasite.

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Kriti Tyagi

Full Text Available Plasmodium vivax is most wide spread and a neglected malaria parasite. There is a lack of information on parasite biology of this species. Genome of this parasite encodes for the largest number of tryptophan-rich proteins belonging to 'Pv-fam-a' family and some of them are potential drug/vaccine targets but their functional role(s largely remains unexplored. Using bacterial and yeast two hybrid systems, we have identified the interacting partners for two of the P. vivax tryptophan-rich antigens called PvTRAg36.6 and PvTRAg56.2. The PvTRAg36.6 interacts with early transcribed membrane protein (ETRAMP of P.vivax. It is apically localized in merozoites but in early stages it is seen in parasite periphery suggesting its likely involvement in parasitophorous vacuole membrane (PVM development or maintenance. On the other hand, PvTRAg56.2 interacts with P.vivax merozoite surface protein7 (PvMSP7 and is localized on merozoite surface. Co-localization of PvTRAg56.2 with PvMSP1 and its molecular interaction with PvMSP7 probably suggest that, PvTRAg56.2 is part of MSP-complex, and might assist or stabilize the protein complex at the merozoite surface. In conclusion, the PvTRAg proteins have different sub cellular localizations and specific associated functions during intra-erythrocytic developmental cycle.

Plasmodium vivax Tryptophan Rich Antigen PvTRAg36.6 Interacts with PvETRAMP and PvTRAg56.6 Interacts with PvMSP7 during Erythrocytic Stages of the Parasite

Science.gov (United States)

Tyagi, Kriti; Hossain, Mohammad Enayet; Thakur, Vandana; Aggarwal, Praveen; Malhotra, Pawan; Mohmmed, Asif; Sharma, Yagya Dutta

2016-01-01

Plasmodium vivax is most wide spread and a neglected malaria parasite. There is a lack of information on parasite biology of this species. Genome of this parasite encodes for the largest number of tryptophan-rich proteins belonging to ‘Pv-fam-a’ family and some of them are potential drug/vaccine targets but their functional role(s) largely remains unexplored. Using bacterial and yeast two hybrid systems, we have identified the interacting partners for two of the P. vivax tryptophan-rich antigens called PvTRAg36.6 and PvTRAg56.2. The PvTRAg36.6 interacts with early transcribed membrane protein (ETRAMP) of P.vivax. It is apically localized in merozoites but in early stages it is seen in parasite periphery suggesting its likely involvement in parasitophorous vacuole membrane (PVM) development or maintenance. On the other hand, PvTRAg56.2 interacts with P.vivax merozoite surface protein7 (PvMSP7) and is localized on merozoite surface. Co-localization of PvTRAg56.2 with PvMSP1 and its molecular interaction with PvMSP7 probably suggest that, PvTRAg56.2 is part of MSP-complex, and might assist or stabilize the protein complex at the merozoite surface. In conclusion, the PvTRAg proteins have different sub cellular localizations and specific associated functions during intra-erythrocytic developmental cycle. PMID:26954579

Characterization of Plasmodium vivax transmission-blocking activity in low to moderate malaria transmission settings of the Colombian Pacific coast.

Science.gov (United States)

Arévalo-Herrera, Myriam; Solarte, Yezid; Rocha, Leonardo; Alvarez, Diego; Beier, John C; Herrera, Sócrates

2011-02-01

Malaria infection induces antibodies capable of suppressing the infectivity of gametocytes and gametes, however, little is known about the duration of the antibody response, the parasite specificity, and the role of complement. We report the analyses of the transmission-blocking (TB) activity of sera collected from 105 Plasmodium vivax-infected and 44 non-infected individuals from a malaria endemic region of Colombia, using a membrane feeding assay in Anopheles albimanus mosquitoes. In infected donors we found that TB activity was antibody dose dependent (35%), lasted for 2-4 months after infection, and in 70% of the cases different P. vivax wild isolates displayed differential susceptibility to blocking antibodies. Additionally, in a number of assays TB was complement-dependent. Twenty-seven percent of non-infected individuals presented TB activity that correlated with antibody titers. Studies here provide preliminary data on factors of great importance for further work on the development of TB vaccines.

Spiritual Well-Being and Associated Factors with Relapse in Opioid Addicts.

Science.gov (United States)

Noormohammadi, Mohammad-Reza; Nikfarjam, Masoud; Deris, Fatemeh; Parvin, Neda

2017-03-01

Opioid dependence relapse is a complex and multidimensional problem, and lack of spiritual well-being is a major concern in opioid addicts. This study was conducted to determine spiritual well-being and factors associated with relapse among opioid addicts. This cross-sectional study was conducted from April 2015 to September 2015. According to purposive sampling, 312 eligible addicted patients were enrolled in the study. The patients had at least an attempt of detoxification in the past six months and referred to an outpatient detoxification clinic in Shahrekord (Southwest, Iran). They completed Paloutzian and Ellison's Spiritual Well-being Scale. A researcher-developed questionnaire consisting of demographic characteristics and 20 questions about associated factors with relapse was administered. Data were analysed by version 16.0 (SPSS Inc.,Chicago, IL) using one-way ANOVA, Pearson's correlation test, chi-square, Friedman test, and student's t-test. The most important factors associated with opioid dependence relapse consist of relation with an addict friend, unemployment, living expenses, family conflicts, and somatic pain. In the present study, 157 patients had never experienced relapse while the mean of relapse in the rest participants was (3.25±1.53) times. Furthermore, the addicted patients with relapse had significantly lower scores of spiritual well-being and its subscales compared with non-relapse patients (pspiritual well-being, family and economical, personal, and occupational factors as crucial factors in opiate addiction relapse.

Predictors of Exercise Relapse in a College Population.

Science.gov (United States)

Sullum, Julie; Clark, Matthew M.; King, Teresa K.

2000-01-01

Investigated factors that predicted exercise relapse among college students. Physically active undergraduates completed questionnaires measuring Prochaska's 10 processes for change of exercise, self-efficacy, and decisional balance. Exercise levels were assessed at baseline and 8 weeks later. At baseline, relapsers had significantly lower…

Tumor relapse present in oncologic nasal repair

International Nuclear Information System (INIS)

Galvez Chavez, Julio Cesar; Sanchez Wals, Lenia; Monzon Fernandez, Abel Nicolas; Morales Tirado, Roxana

2009-01-01

Tumor relapse is one of the more fearsome complications of the oncologic course and also to obscure the life prognosis, causing the loss of many reconstructions and of exhausting the repairing surgical possibilities. The aim of this study was to determine the relapse frequency, the repercussion on the repair and the subsequent medical course of patients operated on malign nasal tumors

Effectiveness of Mindfulness-Based Relapse Prevention in opioid Dependence Treatment &Mental Health

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2008-11-01

Findings: therapy compliance, retention in treatment, decrease in somatic symptoms, anxiety, social dysfunction and increase in health was significantly in both combination of psychological intervention method than the Naltroxan group. Mindfulness-based on relapse prevention was more effective than CBT relapse prevention in decreasing of, social dysfunction, relapse prevention, increase of therapy compliance, and health. Results: Mindfulness based relapse prevention was superior to CBT and Naltroxan and considerably increased effectiveness of opioid relapse prevention therapy.

Improved outcome after relapse in children with acute myeloid leukaemia

DEFF Research Database (Denmark)

Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran

2007-01-01

investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122......In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...... patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival...

Patterns of relapse following surgery and postoperative intensity modulated radiotherapy for oral and oropharyngeal cancer

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Collan, Juhani; Vaalavirta, Leila; Kajanti, Mikael; Tenhunen, Mikko; Saarilahti, Kauko (Dept. of Oncology, Helsinki Univ. Central Hospital, and Univ. of Helsinki, Helsinki (Finland)), E-mail: kauko.saarilahti@hus.fi; Lundberg, Marie; Baeck, Leif; Maekitie, Antti (Dept. of Otorhinolaryngology - Head and Neck Surgery, Helsinki Univ. Central Hospital, and Univ. of Helsinki, Helsinki (Finland))

2011-10-15

Background. To investigate the patterns of relapse following intensity modulated radiotherapy (IMRT) given after radical surgery for oral and oropharyngeal squamous cell cancer. Patients and methods. One hundred and two patients with oral or oropharyngeal cancer were treated with radical surgery followed by IMRT up to a mean total dose of 60 Gy between years 2001 and 2007. Thirty-nine of the patients (%) also received concomitant weekly cisplatin. Forty of the patients had oral and 62 had oropharyngeal cancer. Data on the tumour, patient and treatment factors were collected. Following therapy the patients were followed by clinical examination, endoscopy and MRI/CT at 2- to 3-months interval up to 2 years and thereafter at 6-month intervals. Results. The mean follow-up time of the patients was 55 months (range, 26-106 months). The rate for local tumour control for the whole cohort was 92.2%: 87.5% for oral cancer patients and 96.7% for oropharyngeal cancer patients. The 5-year disease specific survival was 90.2% and 5-year overall survival 84.3%. During the follow-up eight locoregional recurrences were observed, three at the primary tumour site and one at regional nodal site and four at both sites. The mean time to primary tumour recurrence was seven months (range, 2-10 months) and to nodal recurrence seven months (range, 2-12 months). Distant metastasis occurred in six (6%) patients. The factors associated with poor prognosis were the primary tumour size and tumour site with oral cancers having worse outcome. The treatment was well tolerated with no unexpected toxicities. The most frequent late toxicity was dysphagia necessitating permanent PEG in five patients. This was correlated with the advanced primary tumour size and resulting in wide tumour excision and reconstruction. Conclusions. Surgery combined with postoperative radiotherapy given as IMRT results in low level of tumour recurrence

Patterns of relapse following surgery and postoperative intensity modulated radiotherapy for oral and oropharyngeal cancer

International Nuclear Information System (INIS)

Collan, Juhani; Vaalavirta, Leila; Kajanti, Mikael; Tenhunen, Mikko; Saarilahti, Kauko; Lundberg, Marie; Baeck, Leif; Maekitie, Antti

2011-01-01

Background. To investigate the patterns of relapse following intensity modulated radiotherapy (IMRT) given after radical surgery for oral and oropharyngeal squamous cell cancer. Patients and methods. One hundred and two patients with oral or oropharyngeal cancer were treated with radical surgery followed by IMRT up to a mean total dose of 60 Gy between years 2001 and 2007. Thirty-nine of the patients (%) also received concomitant weekly cisplatin. Forty of the patients had oral and 62 had oropharyngeal cancer. Data on the tumour, patient and treatment factors were collected. Following therapy the patients were followed by clinical examination, endoscopy and MRI/CT at 2- to 3-months interval up to 2 years and thereafter at 6-month intervals. Results. The mean follow-up time of the patients was 55 months (range, 26-106 months). The rate for local tumour control for the whole cohort was 92.2%: 87.5% for oral cancer patients and 96.7% for oropharyngeal cancer patients. The 5-year disease specific survival was 90.2% and 5-year overall survival 84.3%. During the follow-up eight locoregional recurrences were observed, three at the primary tumour site and one at regional nodal site and four at both sites. The mean time to primary tumour recurrence was seven months (range, 2-10 months) and to nodal recurrence seven months (range, 2-12 months). Distant metastasis occurred in six (6%) patients. The factors associated with poor prognosis were the primary tumour size and tumour site with oral cancers having worse outcome. The treatment was well tolerated with no unexpected toxicities. The most frequent late toxicity was dysphagia necessitating permanent PEG in five patients. This was correlated with the advanced primary tumour size and resulting in wide tumour excision and reconstruction. Conclusions. Surgery combined with postoperative radiotherapy given as IMRT results in low level of tumour recurrence

Power2: Relapse Management with Adolescents Who Stutter.

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Blood, Gordon W.

1995-01-01

This article describes a cognitive-behavioral treatment package for relapse management in adolescents who stutter. The package includes game-based training techniques in problem solving, communication skills, and assertiveness; coping responses for stuttering episodes; and realistic expectations for fluency and relapse. Follow-up results with…

Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow.

Science.gov (United States)

Htun, Myo Win; Mon, Nan Cho Nwe; Aye, Khin Myo; Hlaing, Chan Myae; Kyaw, Myat Phone; Handayuni, Irene; Trimarsanto, Hidayat; Bustos, Dorina; Ringwald, Pascal; Price, Ric N; Auburn, Sarah; Thriemer, Kamala

2017-07-10

Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts. Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012. A total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0% (95% CI 71.6-97.9) in Myawaddy and 98.3% (95% CI 88.7-99.8) in Kawthoung. By day 2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and 2.5% (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855-0.876), with low inter-population differentiation (F ST 0.016-0.026, P Myanmar, particularly given the potential connectivity between parasite population at different sites.

Relapsing-Remitting MS (RRMS)

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Full Text Available ... without symptoms of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined ... a different mechanism of action in order to control the disease activity more effectively and help prevent ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ... and worsening, you and your MS care provider will likely want to consider a more aggressive treatment ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Rule Out For Clinicians Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation ... Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care Needs Resources for Specific Populations ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... the periods of remission. At different points in time, RRMS can be further characterized as either active ( ... increase in disability over a specified period of time following a relapse) or not worsening . An increase ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... attacks of inflammation (relapses) in the CNS, progressive forms of MS involve much less of this type ... and memory or information processing). People with progressive forms of MS are more likely to experience gradually ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Team Make the Most of Your Doctor Visits Advance Medical Directives d Find an MS Care Provider ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... as shown by the arrows, often occur as part of a relapse. However, new MRI lesions indicating ... course of your disease at different points in time helps you and your MS care provider discuss ...

Symptomatic relapse of HIV-associated cryptococcal meningitis in ...

African Journals Online (AJOL)

Objectives. Cryptococcal meningitis is the most common cause of adult meningitis in southern Africa. Much of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We studied the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal ...

Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

Science.gov (United States)

Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

2018-04-27

Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

Novel therapeutic options for relapsed hairy cell leukemia.

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Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

2015-01-01

The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

MRI diagnosis of bone marrow relapse in children with ALL

International Nuclear Information System (INIS)

Kan, J.H.; Hernanz-Schulman, Marta; Frangoul, Haydar A.; Connolly, Susan A.

2008-01-01

Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

MRI diagnosis of bone marrow relapse in children with ALL

Energy Technology Data Exchange (ETDEWEB)

Kan, J.H.; Hernanz-Schulman, Marta [Vanderbilt University, Department of Radiology and Radiological Sciences, Vanderbilt Children' s Hospital, Nashville, TN (United States); Frangoul, Haydar A. [Vanderbilt University, Department of Pediatric Hematology-Oncology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Connolly, Susan A. [Harvard Medical School, Department of Radiology, Boston Children' s Hospital, Boston, MA (United States)

2008-01-15

Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

Factors associated with relapse in schizophrenia | Kazadi | South ...

African Journals Online (AJOL)

Aim. Early identification and prevention of relapse in patients with schizophrenia has significant therapeutic and socioeconomic implications. The aim of this study was to determine the factors, if any, that may be associated with relapse in a group of patients in Johannesburg. Method. Patients were recruited from mental ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called ... either active (with relapses and/or evidence of new MRI activity) or not active , as well as ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations – are followed ... as well as the nerve fibers themselves. During these inflammatory attacks, activated immune cells cause small, localized ...

Prevalence of mutation and phenotypic expression associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum and Plasmodium vivax.

Science.gov (United States)

Zakai, Haytham A; Khan, Wajihullah; Asma, Umme

2013-09-01

Therapeutic efficacy of sulfadoxine-pyrimethamine (SP), which is commonly used to treat falciparum malaria, was assessed in isolates of Plasmodium falciparum (Welch, 1897) and Plasmodium vivax (Grassi et Feletti, 1890) ofAligarh, Uttar Pradesh, North India and Taif, Saudi Arabia during 2011-2012. Both the species showed mutations in dihydrofolate reductase (DHFR) enzyme as they have common biochemical drug targets. Mutation rate for pfdhfr was higher compared to pvdhfr because the drug was mainly given to treat falciparum malaria. Since both the species coexist, P. vivax was also exposed to SP due to faulty species diagnosis or medication without specific diagnosis. Low level of mutations against SP in P. falciparum of Saudi isolates indicates that the SP combination is still effective for the treatment of falciparum malaria. Since SP is used as first-line of treatment because of high level of resistance against chloroquine (CQ), it may result in spread of higher level of mutations resulting in drug resistance and treatment failure in near future. Therefore, to avoid further higher mutations in the parasite, use of better treatment regimens such as artesunate combination therapy must be introduced against SP combination.

Comparing Effectiveness of Mindfulness-Based Relapse Prevention with Treatment as Usual on Impulsivity and Relapse for Methadone-Treated Patients: A Randomized Clinical Trial.

Science.gov (United States)

Yaghubi, Mehdi; Zargar, Fatemeh; Akbari, Hossein

2017-07-01

Impulsivity is one of the causes of relapse that can affect treatment outcomes. Studies have shown that addiction treatments can reduce impulsivity in drug-dependent individuals. Studies also have suggested that mindfulness is associated with impulsivity. However, no study has investigated the effectiveness of the mindfulness-based intervention on impulsivity in opioid-dependent individuals. This study aimed to compare the effectiveness of mindfulness-based relapse prevention (MBRP) with treatment as usual (TAU) in terms of impulsivity and relapse for methadone-treated patients. The present randomized controlled clinical trial was performed in Kashan, Iran, in 2015. The study population was opioid-dependent patients referred to Maintenance Treatment Centers. Seventy patients were selected by random sampling and were assigned in two groups (MBRP and TAU) randomly. The participants of two groups filled out Barratt impulsivity scale (BIS-11) as a pre-test and 8 weeks later as post-test and 2 months later as a follow-up. Both groups received methadone-therapy. The MBRP group received 8 sessions of group therapy, while the control group did not receive any group psychotherapy session. Finally, data from 60 patients were analyzed statistically. The MBRP group had decreased impulsivity significantly (P relapse frequency (P relapse probability. These findings suggest that MBRP is useful for opioid-dependent individuals with high-level impulsivity, and relapse prevention.

Orexin Receptor Targets for Anti-Relapse Medication Development in Drug Addiction

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Ronald E. See

2011-06-01

Full Text Available Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches.

Relapse prevention in anorexia nervosa: Experiences of patients and parents.

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Berends, Tamara; van de Lagemaat, Marleen; van Meijel, Berno; Coenen, Jasmijn; Hoek, Hans W; van Elburg, Annemarie A

2018-03-24

One of the main aims of treatment after successful recovery from anorexia nervosa (AN) is to prevent a relapse. The Guideline Relapse Prevention (GRP) Anorexia Nervosa offers a structured approach to relapse prevention. This study explores how patients and their parents experience working with the guideline. It also describes the factors that support or hinder successful application of the guideline. A descriptive qualitative research design was chosen involving in-depth interviews with seventeen patients with anorexia nervosa and six sets of parents. Patients and family members were generally satisfied with the support provided by the GRP. It contributed significantly to a better understanding of the personal process of relapse. Patients and families valued being able to keep in touch with their professional during the aftercare programme. The GRP supports the patient's use of self-management strategies for relapse prevention. © 2018 Australian College of Mental Health Nurses Inc.

External-beam boost prior to total-body irradiation in relapsed NHL transplant patients

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Monson, Jedidiah M; Neuberg, Donna; Freedman, Arnold S; Tarbell, Nancy J; Nadler, Lee M; Mauch, Peter

1995-07-01

PURPOSE: To determine the impact of an external beam boost (EBB) on the outcome, relapse pattern and normal tissue toxicities of patients undergoing total-body irradiation (TBI) prior to bone marrow transplantation (BMT) for relapsed NHL. MATERIALS AND METHODS: Between 1982 and 1994, 299 patients at our institution underwent BMT for relapsed NHL. Patients underwent induction chemotherapy (CT) followed by conditioning with cyclophosphamide and 12 Gy TBI delivered in 6 fractions over 3 days. A total of 77 patients had persistent gross disease, defined as 2 cm or greater, after induction CT and received an EBB prior to BMT (EBB cohort). The median EBB dose was 28.8 Gy (range, 5-63), the median field size was 13 cm{sup 2} (range, 5-29.4) and the median time from EBB to BMT was 3 weeks (range, 1-20). A total of 222 patients were free of measurable disease or had disease measuring <2cm after CT and did not receive EBB (no-EBB cohort). To assess normal tissue toxicity, patients' simulation films and/or treatment records were reviewed for all 77 patients treated with local EBB and estimates were made of the percentage lung, heart and kidney in the radiation field. RESULTS: A total of 79 of 222 patients (36%) in the no-EBB cohort have relapsed; 33 of 77 patients (43%) in the EBB cohort have relapsed (p=0.28, by Fisher exact test). Median time to relapse after BMT was 54 months for the no-EBB cohort and 38 months for the EBB cohort (p=0.26, by log-rank test). The 3-year actuarial freedom from relapse (deaths in remission censored) was 59% for the no-EBB cohort (90% CI: 52-66%) and 51% for the EBB cohort (90% CI: 40-62%). Data on site of relapse was available for 101 of the 112 relapses (75 no-EBB, 26 EBB). For the no-EBB cohort 33 of 75 relapses (44%) were in sites of prior nodal disease only. For the EBB cohort, 12 of 26 relapses (46%) were in sites of prior nodal disease only, of these, only 6 (23%) were within the EBB treatment field. A total of 26 patients had thoracic

Molecular diagnosis of cattle trypanosomes in Venezuela: evidences of Trypanosoma evansi and Trypanosoma vivax infections.

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Ramírez-Iglesias, J R; Eleizalde, M C; Reyna-Bello, A; Mendoza, M

2017-06-01

In South America Trypanosoma evansi has been determined by molecular methods in cattle from Bolivia, Brazil, Colombia and Peru, reason for which the presence of this parasite is not excluded in Venezuelan livestock. Therefore, the aim of this study was to perform parasitological and molecular diagnosis of cattle trypanosomosis in small livestock units from two regions in this country. The parasitological diagnosis was carried out by MHCT and the molecular by PCR using genus-specific ITS1 primers that differentiate T. vivax and T. evansi infections. 47 cattle were evaluated in the "Laguneta de la Montaña" sector, Miranda State, where 3 animals were diagnosed as positive (6.4 %) by MHCT and 14 (30 %) by PCR as Trypanosoma spp., out of which 9 animals resulted positive for T. vivax , 3 for T. evansi and 2 with double infections. Whilst in the "San Casimiro" sector, State of Aragua, out of the 38 cattle evaluated 7 animals were diagnosed as positive (18.4 %) by MHCT and 19 (50 %) by PCR, determining only the presence of T. evansi in this locality. The molecular diagnosis by PCR using ITS1 primers allowed T. evansi detection in cattle field populations, which suggests the possible role of these animals as reservoirs in the epidemiology of the disease caused by T. evansi in Venezuela.

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Treating MS d Comprehensive Care Developing a Healthcare Team Make the Most of Your Doctor Visits Advance Medical Directives d Find an MS Care Provider Partners in MS Care d Managing Relapses Plasmapheresis d Rehabilitation Functional Electrical Stimulation (FES) ...

Understanding the impact of relapses in the overall course of MS; refinement of the 2 stage natural history model.

Science.gov (United States)

Scott, Thomas F

2017-04-15

Recent studies suggest a need for refinement of the traditional two phase model of relapse onset multiple sclerosis (RMS) to include dynamically changing subgroups within the broad category of secondary progressive MS (SPMS). These studies challenge the traditional notion that relapses play a minor role in comparison to a secondary progressive (perhaps degenerative) process. Patients fulfilling the broad definition for SPMS may take several courses, including variable rates and patterns of overall worsening. New paradigms or models for mapping the trajectory of disability in RMS and SPMS (clinical phenotyping), including periods of remission, may impact our understanding of the underlying pathology, and will be important in assessing treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

Science.gov (United States)

Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

2010-01-01

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

Intra and interpersonal determinants for relapse in drug addicts

Directory of Open Access Journals (Sweden)

Aline Cristina Zerwes Ferreira

2016-03-01

Full Text Available A descriptive qualitative research conducted with 20 drug addicts during treatment at a Center of Psychosocial Attention for Alcohol and other Drugs, aimed to identify intra and interpersonal determinants of relapse perceived by the drug addict. The data were collected through semi-structured interviews, submitted to Content Analysis, and organized into categories following predictive determinants for relapse. The relapse occurred by intrapersonal determinants, as self-efficacy expressed by self-confidence in interrupting the drug consumption; the result expectation by anticipation of pleasurable drug effects; the motivation by the absence of volition to interrupt the consumption; coping with the difficulty to confront daily problems; negative and positive emotional states; and craving. Interpersonal determinants expressed by social support were related to the influence of thirds. The identification of these determinants during treatment to favor relapse prevention and effective rehabilitation.

Host-parasite interaction: selective Pv-fam-a family proteins of Plasmodium vivax bind to a restricted number of human erythrocyte receptors.

Science.gov (United States)

Zeeshan, Mohammad; Tyagi, Rupesh Kumar; Tyagi, Kriti; Alam, Mohd Shoeb; Sharma, Yagya Dutta

2015-04-01

Plasmodium vivax synthesizes the largest number of 36 tryptophan-rich proteins belonging to the Pv-fam-a family. These parasite proteins need to be characterized for their biological function because tryptophan-rich proteins from other Plasmodium species have been proposed as vaccine candidates. Recombinant P. vivax tryptophan-rich antigens (PvTRAgs) were used to determine their erythrocyte-binding activity by a cell-based enzyme-linked immunosorbent assay, flow cytometry, and a rosetting assay. Only 4 (PvTRAg26.3, PvTRAg34, PvTRAg36, and PvTRAg36.6) of 21 PvTRAgs bind to host erythrocytes. The cross-competition data indicated that PvTRAg36 and PvTRAg34 share their erythrocyte receptors with previously described proteins PvTRAg38 and PvTRAg33.5, respectively. On the other hand, PvTRAg26.3 and PvTRAg36.6 cross-compete with each other and not with any other PvTRAg, indicating that these 2 proteins bind to the same but yet another set of erythrocyte receptor(s). Together, 10 of 36 PvTRAgs possess erythrocyte-binding activity in which each protein recognizes >1 erythrocyte receptor. Further, each erythrocyte receptor is shared by >1 PvTRAg. This redundancy may be useful for the parasite to invade red blood cells and cause disease pathogenesis, and it can be exploited to develop therapeutics against P. vivax malaria. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Increased multiple sclerosis relapses related to lower prevalence of pain

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José Vinícius Martins da Silva

2015-07-01

Full Text Available Objective The study aims to investigate the presence of pain amongst multiple sclerosis (MS patients. Method One hundred MS patients responded to questionnaires evaluating neuropathic and nociceptive pain, depression and anxiety. Statistical analysis was performed using the Mann–Whitney U, Chi-Square and two-tailed Fisher’s exact tests and multivariate logistic regression. Results Women had a statistically higher prevalence of pain (p = 0.037, and chances of having pain after the age of 50 reduced. Women with pain had a statistically significant lower number of relapses (p = 0.003, restricting analysis to those patients with more than one relapse. After the second relapse, each relapse reduced the chance of having pain by 46%. Presence of pain was independent of Expanded Disability Status Scale (EDSS anxiety, and depression. Conclusion Our findings suggest a strong inverse association between relapses and pain indicating a possible protective role of focal inflammation in the control of pain.

Muerte materna por malaria grave por Plasmodium vivax

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Nancy Arróspide

Full Text Available Se presenta el caso de una mujer de 19 años con 29 semanas de gestación, procedente de Llumpe (Ancash con antecedentes de viajes a las localidades de Chanchamayo (Junín y Rinconada (Ancash. Ingresó al Hospital de Chacas (Ancash por presentar mal estado general, deshidratación, dificultad respiratoria, ictericia, sensación de alza térmica y dolor abdominal, tuvo reporte de: hemoparásitos 60% en frotis sanguíneo. Fue transferida al Hospital Ramos Guardia (Huaraz donde presentó mayor dificultad respiratoria, coluria, hematuria, disminución del débito urinario y reporte de Plasmodium (+, luego fue transferida al Hospital Cayetano Heredia (Lima donde ingresó a la Unidad de Cuidados Intensivos (UCI, con evolución a falla multiorgánica, óbito fetal y muerte materna. Se confirmó infección por Plasmodium vivax. Destacamos la importancia de mejorar nuestras capacidades de diagnóstico y manejo para brindar un tratamiento adecuado y oportuno.

Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

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Garry Robert F

2011-01-01

Full Text Available Abstract Background The surface glycoprotein (SU, gp120 of the human immunodeficiency virus (HIV must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP to bind the Duffy Antigen Receptor for Chemokines (DARC and invade reticulocytes. Results Variable loop 3 (V3 of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins. Conclusion A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.

Strengths of families to limit relapse in mentally ill family members ...

African Journals Online (AJOL)

Background: Relapse prevention in mental health care is important. Utilising the strengths of families can be a valuable approach in relapse prevention. Studies on family strengths have been conducted but little has been done on the strengths of family members to help limit relapse in mental health care users. The purpose ...

DAÑO VELLOSO HIPOXICO EXTENSO EN VELLOSIDAD PLACENTARIA INFECTADA POR PLASMODIUM VIVAX.

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Olivar C. Castejon

2011-01-01

Full Text Available Objetivo: El propósito de este estudio de caso fue el determinar el daño velloso hipóxico extenso en una población de vellosidades obtenida de una placenta infectada por Plasmodium vivax y tratada con cloroquina cuantificando el daño en relación a otra población normal no infectada. Métodos: Un protocolo de observación se aplicó a la placenta infectada conteniendo las variables que definen el daño como la presencia de nódulos sincitiales, hipovascularidad vellosa y vellosidades fibróticas o avasculares cuyos porcentajes en la placenta estudio y control fueron medidos estadísticamente para estimar las diferencias significativas. Diez láminas teñidas con hematoxilina y eosina por cada placenta fueron empleadas determinándose el porcentaje de cada variable en 100 vellosidades en ambas placentas. Resultados: La placenta con P.vivax presentó entre un 29 y 58 % de nódulos sincitiales mientras que el control 3 y 24%. La fibrosis estromal entre 12 y 49%;la control entre 1 y 7%. La hipovascularidad entre 49 y 84%; la control entre 7 y 18%. Trombosis intervellosa, oclusión de la luz de vasos troncales,infartos y corangiosis se observaron en la infectada y no en el control. Conclusiones: Estos resultados sugieren un daño velloso hipóxico extenso en las vellosidades infectadas mientras que las del control permanecen normóxicas. Dicho daño pudiera impedir el suministro de gases y nutrientes que estimularía a nivel fetal la restricción del crecimiento intrauterino con la subsiguiente pérdida de peso fetal.

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

NARCIS (Netherlands)

P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

2005-01-01

textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

Alkaline phosphatase expression during relapse after orthodontic tooth movement

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Pinandi Sri Pudyani

2014-03-01

Full Text Available Background: The increasing of osteoblast activities during bone formation will be accompanied with the increasing expression of alkaline phosphatase enzyme (ALP. ALP can be obtained from clear fluid excreted by gingival crevicular fluid (GCF. Bone turnover, especially bone formation process, can be monitored through the expression of ALP secreted by GCF during orthodontic treatment. Thus, retention period is an important period that can be monitored through the level of bone metabolism around teeth. Purpose: This research were aimed to determine the relation of distance change caused by tooth relapse and ALP activities in gingival crevicular fluid after orthodontic; and to determine ALP as a potential biomarker of bone formation during retention period. Methods: Lower incisors of 25 guinea pigs were moved 3 mm to the distally by using open coil spring. Those relapse distance were measured and the gingival crevicular fluid was taken by using paper points to evaluate ALP levels on days 0, 3, 7, 14 and 21 respectivelly by using a spectrophotometer (405 nm. t-test and ANOVA test were conducted to determine the difference of ALP activities among the time intervals. The correlation regression analysis was conducted to determine the relation of distance change caused by the relapse tooth movement and ALP activities. Results: The greatest relapse movement was occurred on day 3 after open coil spring was removed. There was significant difference of the average of distance decrease among groups A1-A5 (p<0.05. It was also known that ALP level was increased on day 3, but there was no significant difference of the average level of ALP among groups A1-A5 (p>0.05. Finally, based on the results of correlation analysis between the ALP level decreasing and the relapse distance on both right and left of mesial and distal sides, it is known that there was no relation between those two variables (p>0.05. Conclusion: It can be concluded that relapse after orthodontic

Cladribine tablets for relapsing-remitting multiple sclerosis

DEFF Research Database (Denmark)

Rammohan, Kottil; Giovannoni, Gavin; Comi, Giancarlo

2012-01-01

BACKGROUND: In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses...... of CLARITY study data were conducted to determine the efficacy of cladribine tablets across patient subgroups stratified by baseline characteristics. METHODS: Relapse rates over the 96-week CLARITY study were analyzed in cohorts stratified by demographics; disease duration; treatment history and disease...... activity at baseline. RESULTS: In the intent-to-treat population (n=437, 433 and 456 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively), treatment with cladribine tablets 3.5 and 5.25mg/kg led to consistent improvements in ARR versus placebo in patients stratified by gender; age (≤40...

Relapse Prevention: An Introduction to Marlatt’s Cognitive – Behavior Model

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Farshad Nemati

2002-10-01

Full Text Available High rate of relapse after apparently successful treatment is a common problem facing with most approaches to treatment of drug dependency. This has led to the development of a variety of strategies for relapse prevention. Among these, Marlatt’s cognitive – behavioural model has received a good deal of attention. It is based on two major axes: Identification of warning sings and development of necessary skills for coping with risk situations. In fact, client’s perception relating to their abilities to cope with high - risk situations can lead to lapse. Relapes is a function of client’s reaction to this initial lapes.Since formal training for addiction counsellors typically includes instruction on Marlatt’s relapes taxonomy and intervention strategies have been designed based on his classification systems of high – risk stimuli, it is nececsary for addiction counsellors to become familiar with this system. This paper presents an overview of Marlatts taxonomy of high – risk situations for relapse and his approach to relapse prevention. Special attention is given to definition of relapse, stages of relaps and relapse prevention strategies.

Relapse and Craving in Alcohol-Dependent Individuals: A Comparison of Self-Reported Determinants.

Science.gov (United States)

Snelleman, Michelle; Schoenmakers, Tim M; van de Mheen, Dike

2018-06-07

Negative affective states and alcohol-related stimuli increase risk of relapse in alcohol dependence. In research and in clinical practice, craving is often used as another important indicator of relapse, but this lacks a firm empirical foundation. The goal of the present study is to explore and compare determinants for relapse and craving, using Marlatt's (1996) taxonomy of high risk situations as a template. We conducted semi-structured interviews with 20 alcohol-dependent patients about their most recent relapse and craving episodes. Interview transcripts were carefully reviewed for their thematic content, and codes capturing the thematic content were formulated. In total, we formulated 42 relapse-related codes and 33 craving-related codes. Descriptions of craving episodes revealed that these episodes vary in frequency and intensity. The presence of alcohol-related stimuli (n = 11) and experiencing a negative emotional state (n = 11) were often occurring determinants of craving episodes. Both negative emotional states (n = 17) and testing personal control (n = 11) were viewed as important determinants of relapses. Craving was seldom mentioned as a determinant for relapse. Additionally, participants reported multiple determinants preceding a relapse, whereas craving episodes were preceded by only one determinant. Patient reports do not support the claim that craving by itself is an important proximal determinant for relapse. In addition, multiple determinants were present before a relapse. Therefore, future research should focus on a complexity of different determinants.

Genetic diversity and natural selection of Plasmodium vivax multi-drug resistant gene (pvmdr1) in Mesoamerica.

Science.gov (United States)

González-Cerón, Lilia; Montoya, Alberto; Corzo-Gómez, Josselin C; Cerritos, Rene; Santillán, Frida; Sandoval, Marco A

2017-07-01

The Plasmodium vivax multidrug resistant 1 gene (pvmdr1) codes for a transmembrane protein of the parasite's digestive vacuole. It is likely that the pvmdr1 gene mutations occur at different sites by convergent evolution. In here, the genetic variation of pvmdr1 at three sites of the Mesoamerican region was studied. Since 1950s, malarious patients of those areas have been treated only with chloroquine and primaquine. Blood samples from patients infected with P. vivax were obtained in southern Mexico (SMX), in the Northwest (NIC-NW) and in the northeast (NIC-NE) of Nicaragua. Genomic DNA was obtained and fragments of pvmdr1 were amplified and sequenced. The nucleotide and amino acid changes as well as the haplotype frequency in pvmdr1 were determined per strain and per geographic site. The sequences of pvmdr1 obtained from the studied regions were compared with homologous sequences from the GenBank database to explore the P. vivax genetic structure. In 141 parasites, eight nucleotide changes (two changes were synonymous and other six were nonsynonymous) were detected in 1536 bp. The PvMDR1 amino acid changes Y976F, F1076FL were predominant in endemic parasites from NIC-NE and outbreak parasites in NIC-NW but absent in SMX. Thirteen haplotypes were resolved, and found to be closely related, but their frequency at each geographic site was different (P = 0.0001). The pvmdr1 codons 925-1083 gene fragment showed higher genetic and haplotype diversity in parasites from NIC-NE than the other areas outside Latin America. The haplotype networks suggested local diversification of pvmdr1 and no significant departure from neutrality. The F ST values were low to moderate regionally, but high between NIC-NE or NIC-NW and other regions inside and outside Latin America. The pvmdr1 gene might have diversified recently at regional level. In the absence of significant natural, genetic drift might have caused differential pvmdr1 haplotype frequencies at different geographic sites

Perfil clínico y parasitológico de la malaria por Plasmodium falciparum y Plasmodium vivax no complicada en Córdoba, Colombia.

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Angélica Knudson Ospina

2015-10-01

Conclusión. Se identificaron algunas diferencias clínicas entre los enfermos con Plasmodium vivax y los enfermos con Plasmodium falciparum, y las variables estudiadas se agruparon en cuatro perfiles que permiten una variedad de interpretaciones.

Frequency of relapse among Nigerian children with steroid‑sensitive ...

African Journals Online (AJOL)

Background: The clinical course of steroid‑sensitive nephrotic syndrome (SSNS) among Nigerian children has rarely been reported; this makes prognostication difficult. Objectives: The objective was to determine the frequency of relapses including frequent relapses (FR) and steroid‑dependence (SD) in a cohort of Nigerian ...

Prefrontal cortex plasticity mechanisms in drug seeking and relapse

NARCIS (Netherlands)

van den Oever, M.C.; Spijker, S.; Smit, A.B.; de Vries, T.J.

2010-01-01

Development of pharmacotherapy to reduce relapse rates is one of the biggest challenges in drug addiction research. The enduring nature of relapse suggests that it is maintained by long-lasting molecular and cellular adaptations in the neuronal circuitry that mediates learning and processing of

Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of relapse after transplantation.

Science.gov (United States)

Gress, Ronald E; Miller, Jeffrey S; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Landau, Dan A; Wu, Catherine J

2013-11-01

In the National Cancer Institute's Second Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Biology of Relapse discussed recent advances in understanding some of the host-, disease-, and transplantation-related contributions to relapse, emphasizing concepts with potential therapeutic implications. Relapse after hematopoietic stem cell transplantation (HSCT) represents tumor escape, from the cytotoxic effects of the conditioning regimen and from immunologic control mediated by reconstituted lymphocyte populations. Factors influencing the biology of the therapeutic graft-versus-malignancy (GVM) effect-and relapse-include conditioning regimen effects on lymphocyte populations and homeostasis, immunologic niches, and the tumor microenvironment; reconstitution of lymphocyte populations and establishment of functional immune competence; and genetic heterogeneity within the malignancy defining potential for clonal escape. Recent developments in T cell and natural killer cell homeostasis and reconstitution are reviewed, with implications for prevention and treatment of relapse, as is the application of modern genome sequencing to defining the biologic basis of GVM, clonal escape, and relapse after HSCT. Published by Elsevier Inc.

Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

Science.gov (United States)

Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

2017-01-01

We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by

PARATHYROID CANCER OCCURRING IN RELAPSING SECONDARY HYPERPARATHYROIDISM

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I. V. Kotova

2016-01-01

Full Text Available We present a clinical case of parathyroid cancer in a patient with relapsing secondary hyperparathyroidism at 4 years after subtotal parathyroidectomy. Its unique character is related to the combination of relapsing secondary hyperparathyroidism, parathyromatosis, ectopic of an adenomatous hyperplastic parathyroid gland into the thyroid gland, and parathyroid cancer. Several most complicated aspects of parathyroid surgery are disclosed, such as the choice of strategy for surgical intervention in secondary hyperparathyroidism, complexity of morphological and cytological diagnostics of this disorder.

Generation and analysis of the immunogenicity of recombinant proteins based on different forms of the circumsporozoite antigen of Plasmodium vivax for the development of a universal vaccine against malaria.

OpenAIRE

Lais Helena Teixeira

2014-01-01

O P. vivax é a segunda espécie mais prevalente causadora de malária no mundo. Medidas de controle ineficientes exigem o desenvolvimento de novas estratégias de prevenção, como vacinas, novas drogas e novos inseticidas. O objetivo geral do trabalho foi gerar uma formulação vacinal universal com proteínas e adenovírus recombinantes capazes de induzir anticorpos contra as diferentes formas alélicas da proteína circumsporozoíta (CSP) do P. vivax. As proteínas foram produzidas em E. coli e purific...

Functional symptoms in clinically definite MS--pseudo-relapse syndrome.

LENUS (Irish Health Repository)

Merwick, A

2012-02-03

Although the diagnostic criteria for multiple sclerosis (MS) have become more formalized and sensitive in the era of magnetic resonance imaging (MRI) scanning, the assessment of individual relapses may not always be straightforward or easily linked to a particular lesion seen on imaging. In addition, acute episodes often have to be assessed outside of normal working hours or when the individual patients usual medical team is not available. Often the emergency department physicians have little formal neurological training and are under time pressure to get patients through the system as quickly as possible. It is therefore possible to mislabel functional symptoms as being true relapses. To illustrate scenarios of possible pseudo-relapse, three clinical vignettes are described. Misclassification of functional symptoms as relapse carries a number of inherent risks. Functional symptoms can be multifactorial and may cause a burden of disease. A multidisciplinary approach may be useful in minimizing unnecessary harm and identify if there is more than meets the eye to an episode of clinical deterioration.

"I Was a Full Time Proper Smoker": A Qualitative Exploration of Smoking in the Home after Childbirth among Women Who Relapse Postpartum.

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Sophie Orton

Full Text Available Many women stop smoking during pregnancy but relapse shortly afterwards, potentially putting their infants at risk of secondhand smoke (SHS exposure. Women who were able to stop during pregnancy may be a motivated group, receptive to making behaviour changes postpartum to protect their infant from SHS exposure. Understanding more about their experiences of relapse, and if this influences home smoking behaviours and children's exposure to SHS in the home may help to inform intervention development to prevent infant SHS exposure.Guided by interpretative phenomenological methodology we conducted and analysed nine semi-structured interviews with women who quit smoking during pregnancy, but relapsed ≤3 months postpartum.Central to mothers' accounts of their smoking behaviours during pregnancy and postpartum was their desire to be a 'responsible mother'. Mothers described using strategies to protect their infant from SHS exposure, and held strong negative attitudes towards other smoking parents. After relapsing, mothers appeared to reposition themselves as 'social' or 'occasional' smokers rather than 'regular' smokers.Findings suggest that interventions to prevent/reduce infants' home SHS exposure should build on mothers' intentions to be responsible parents. As mothers who relapse principally view themselves as 'social' or 'occasional' smokers, interventions that are highlighted as relevant for women with these types of smoking patterns may be more likely to be responded to, and, ultimately, be effective.

"I Was a Full Time Proper Smoker": A Qualitative Exploration of Smoking in the Home after Childbirth among Women Who Relapse Postpartum.

Science.gov (United States)

Orton, Sophie; Coleman, Tim; Lewis, Sarah; Cooper, Sue; Jones, Laura L

2016-01-01

Many women stop smoking during pregnancy but relapse shortly afterwards, potentially putting their infants at risk of secondhand smoke (SHS) exposure. Women who were able to stop during pregnancy may be a motivated group, receptive to making behaviour changes postpartum to protect their infant from SHS exposure. Understanding more about their experiences of relapse, and if this influences home smoking behaviours and children's exposure to SHS in the home may help to inform intervention development to prevent infant SHS exposure. Guided by interpretative phenomenological methodology we conducted and analysed nine semi-structured interviews with women who quit smoking during pregnancy, but relapsed ≤3 months postpartum. Central to mothers' accounts of their smoking behaviours during pregnancy and postpartum was their desire to be a 'responsible mother'. Mothers described using strategies to protect their infant from SHS exposure, and held strong negative attitudes towards other smoking parents. After relapsing, mothers appeared to reposition themselves as 'social' or 'occasional' smokers rather than 'regular' smokers. Findings suggest that interventions to prevent/reduce infants' home SHS exposure should build on mothers' intentions to be responsible parents. As mothers who relapse principally view themselves as 'social' or 'occasional' smokers, interventions that are highlighted as relevant for women with these types of smoking patterns may be more likely to be responded to, and, ultimately, be effective.

TBI parameters and relapse of acute leukemia

International Nuclear Information System (INIS)

Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

1994-01-01

The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

The shape of the iceberg: quantification of submicroscopic Plasmodium falciparum and Plasmodium vivax parasitaemia and gametocytaemia in five low endemic settings in Ethiopia

NARCIS (Netherlands)

Tadesse, F.G.; Hoogen, L. van den; Lanke, K.H.; Schildkraut, J.; Tetteh, K.; Aseffa, A.; Mamo, H.; Sauerwein, R.; Felger, I.; Drakeley, C.; Gadissa, E.; Bousema, T.

2017-01-01

BACKGROUND: The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in

Elevated Serum IL-17 Expression at Cessation Associated with Graves’ Disease Relapse

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Jianhui Li

2018-01-01

Full Text Available Background. Antithyroid drug (ATD treatment occupies the cornerstone therapeutic modality of Graves’ disease (GD with a high relapse rate after discontinuation. This study aimed to assess potential risk factors for GD relapse especially serum interleukin-17 (IL-17 expression. Methods. Consecutive newly diagnosed GD patients who were scheduled to undergo ATD therapy from May 2011 to May 2014 were prospectively enrolled. Risk factors for GD relapse were analyzed by univariate and multivariate Cox proportional hazard analyses. The association between serum IL-17 expression at cessation and GD relapse was analyzed with relapse-free survival (RFS by the Kaplan–Meier survival analysis and log-rank test. Results. Of the 117 patients, 72 (61.5% maintained a remission for 12 months after ATD withdrawal and 45 (38.5% demonstrated GD relapse. The final multivariate Cox analysis indicated elevated IL-17 expression at cessation to be an independent risk factor for GD relapse within 12 months after ATD withdrawal (HR: 3.04, 95% CI: 1.14–7.67, p=0.021. Patients with higher expressions of IL-17 (≥median value at cessation demonstrated a significantly higher RFS than those with lower levels by the Kaplan–Meier analysis and log-rank test (p=0.028. Conclusions. This present study indicated elevated serum IL-17 expression at cessation to be a predictor for GD relapse within 12 months.

Respuesta terapéutica de Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia

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Arletta Añez

2012-12-01

Full Text Available Introducción. La determinación de la eficacia de la cloroquina contra Plasmodium vivax permite mejorar la capacidad de vigilancia de la resistencia a los antipalúdicos. Objetivo. Evaluar la eficacia terapéutica de la cloroquina como tratamiento de malaria no complicada por P. vivax en Riberalta, Guayaramerín y Yacuiba, Bolivia. Materiales y métodos. Se llevó a cabo un estudio de la eficacia in vivo en pacientes mayores de cinco años; se suministró cloroquina (25 mg/kg en tres días y se hizo seguimiento por 28 días, midiendo los niveles de cloroquina en sangre y desetilcloroquina, el día dos y el día de registro de reaparición de parasitemia. Para la evaluación de la incidencia acumulada de falla del tratamiento, se usó el análisis de supervivencia de Kaplan-Meier. Resultados. Se estudiaron 223 pacientes (Riberalta, 84; Guayaramerín, 80; Yacuiba, 59. Las mediasde densidad parasitaria (formas asexuadas del día 0 en Riberalta fueron de 6.147, en Guayaramerín, 4.251, y en Yacuiba, 5.214 parásitos/μl de sangre. En el mismo orden, los promedios de concentraciones sanguíneas de cloroquina-desetilcloroquina del día 2 fueron de 783, 817 y 815 ng/ml. Mientras en Yacuiba no se presentaron fracasos terapéuticos, en Riberalta ocurrieron con frecuencia de 6,2 % y en Guayaramerín de 10 %. Los valores de cloroquina y desetilcloroquina en sangre de pacientes con fracaso terapéutico fueron menores de 70 ng/ml en el día de reaparición de parasitemia. Conclusión. No se evidenció resistencia de P. vivax a la cloroquina en las tres regiones de evaluación en Bolivia. Se requieren mayores estudios de la concentración de la cloroquina en sangre. doi: http://dx.doi.org/10.7705/biomedica.v32i4.750

P. vivax malaria and dengue fever co-infection: a cross-sectional study in the Brazilian Amazon.

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Belisa M L Magalhães

2014-10-01

Full Text Available Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity.A cross-sectional study was conducted (2009 to 2011 in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1% presented P. vivax malaria mono-infection, 584 (37% dengue fever mono-infection, and 44 (2.8% were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected, deep bleeding (vs. P. vivax mono-infected, hepatomegaly, and jaundice (vs. dengue mono-infected.In endemic areas for dengue and malaria, jaundice (in dengue patients and spontaneous bleeding (in malaria patients should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group.

Impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients.

Science.gov (United States)

Wojnar, Marcin; Ilgen, Mark A; Jakubczyk, Andrzej; Wnorowska, Anna; Klimkiewicz, Anna; Brower, Kirk J

2008-10-01

The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined. A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months. Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, d.f.=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95% CI=1.13-6.95, p=0.026) and time to relapse (OR=2.10, 95% CI=1.18-3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity. This study is the first to document the relationship between pre-treatment impulsive suicide attempts and higher likelihood of post-treatment relapse in alcohol-dependent patents. Clinicians should routinely conduct an assessment for previous suicide attempts in patients with alcohol use disorders, and when impulsive suicidality is reported, they should recognize the increased risk for relapse and formulate their patients' treatment plans accordingly with the goals of reducing both alcoholic relapse and suicide rates.

CA-125 AUC as a predictor for epithelial ovarian cancer relapse.

Science.gov (United States)

Mano, António; Falcão, Amílcar; Godinho, Isabel; Santos, Jorge; Leitão, Fátima; de Oliveira, Carlos; Caramona, Margarida

2008-01-01

The aim of the present work was to evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse. Data from a hundred and eleven patients were submitted to two different approaches based on CA-125 AUC increase values to predict patient relapse. In Criterion A total CA-125 AUC normalized in time value (AUC(i)) was compared with the immediately previous one (AUC(i-1)) using the formulae AUC(i) > or = F * AUC(i-1) (several F values were tested) to find the appropriate close related increment associated to patient relapse. In Criterion B total CA-125 AUC normalised in time was calculated and several cut-off values were correlated with patient relapse prediction capacity. In Criterion A the best accuracy was achieved with a factor (F) of 1.25 (increment of 25% from the previous status), while in Criterion B the best accuracies were achieved with cut-offs of 25, 50, 75 and 100 IU/mL. The mean lead time to relapse achieved with Criterion A was 181 days, while with Criterion B they were, respectively, 131, 111, 63 and 11 days. Based on our results we believe that conjugation and sequential application of both criteria in patient relapse detection should be highly advisable. CA-125 AUC rapid burst in asymptomatic patients should be firstly evaluated using Criterion A with a high accuracy (0.85) and with a substantial mean lead time to relapse (181 days). If a negative answer was obtained then Criterion B should performed to confirm the absence of relapse.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria: implications for ex vivo drug susceptibility testing.

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Douglas H Kerlin

Full Text Available The emergence of highly chloroquine (CQ resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT, originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC(50 values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC(50 for CQ. Our findings indicate that EC(50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

Outcome After First Relapse in Children With Acute Lymphoblastic Leukemia : A Report Based on the Dutch Childhood Oncology Group (DCOG) Relapse ALL 98 Protocol

NARCIS (Netherlands)

van den Berg, H.; de Groot-Kruseman, H. A.; Damen-Korbijn, C. M.; de Bont, E. S. J. M.; Schouten-van Meeteren, A. Y. N.; Hoogerbrugge, P. M.

Background. We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late

Outcome after first relapse in children with acute lymphoblastic leukemia: a report based on the Dutch Childhood Oncology Group (DCOG) relapse all 98 protocol

NARCIS (Netherlands)

Berg, H. van den; Groot-Kruseman, H.A. de; Damen-Korbijn, C.M.; Bont, E.S. de; Schouten-van Meeteren, A.Y.; Hoogerbrugge, P.M.

2011-01-01

BACKGROUND: We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late

Outcome After First Relapse in Children With Acute Lymphoblastic Leukemia: A Report Based on the Dutch Childhood Oncology Group (DCOG) Relapse ALL 98 Protocol

NARCIS (Netherlands)

van den Berg, H.; de Groot-Kruseman, H. A.; Damen-Korbijn, C. M.; de Bont, E. S. J. M.; Schouten-van Meeteren, A. Y. N.; Hoogerbrugge, P. M.

2011-01-01

Background. We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late

Preventing postpartum smoking relapse: an opportunity for neonatal nurses.

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Forest, Sharron

2009-08-01

Smoking during pregnancy and exposure to environmental tobacco smoke have harmful and sometimes devastating effects on the health of the newborn. Although interventions for smoking cessation during pregnancy demonstrate effectiveness for increasing smoking abstinence, the majority of women relapse in the postpartum period. However, modifying contributing factors for relapse may improve the success of sustained abstinence. Many parents are eager to quit smoking and willing to participate in smoking cessation interventions. Through a population-based approach to healthcare, neonatal nurses are in an ideal position to prevent relapse and to promote smoking abstinence; they can coordinate and lead efforts for establishing smoking cessation strategies that integrate obstetric, newborn, and pediatric services.

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

Science.gov (United States)

Dayton, Vanessa J; McKenna, Robert W; Yohe, Sophia L; Dolan, Michelle M; Courville, Elizabeth; Alvarez, Harold; Linden, Michael A

2017-01-01

Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial.

Science.gov (United States)

Phyo, Aung Pyae; Jittamala, Podjanee; Nosten, François H; Pukrittayakamee, Sasithon; Imwong, Mallika; White, Nicholas J; Duparc, Stephan; Macintyre, Fiona; Baker, Mark; Möhrle, Jörg J

2016-01-01

Artefenomel (OZ439) is a novel synthetic trioxolane with improved pharmacokinetic properties compared with other antimalarial drugs with the artemisinin pharmacophore. Artefenomel has been generally well tolerated in volunteers at doses up to 1600 mg and is being developed as a partner drug in an antimalarial combination treatment. We investigated the efficacy, tolerability, and pharmacokinetics of artefenomel at different doses in patients with Plasmodium falciparum or Plasmodium vivax malaria. This phase 2a exploratory, open-label trial was done at the Hospital for Tropical Diseases, Bangkok, and the Shoklo Malaria Research Unit in Thailand. Adult patients with acute, uncomplicated P falciparum or P vivax malaria received artefenomel in a single oral dose (200 mg, 400 mg, 800 mg, or 1200 mg). The first cohort received 800 mg. Testing of a new dose of artefenomel in a patient cohort was decided on after safety and efficacy assessment of the preceding cohort. The primary endpoint was the natural log parasite reduction per 24 h. Definitive oral treatment was given at 36 h. This trial is registered with ClinicalTrials.gov, number NCT01213966. Between Oct 24, 2010, and May 25, 2012, 82 patients were enrolled (20 in each of the 200 mg, 400 mg, and 800 mg cohorts, and 21 in the 1200 mg cohort). One patient withdrew consent (before the administration of artefenomel) but there were no further dropouts. The parasite reduction rates per 24 h ranged from 0·90 to 1·88 for P falciparum, and 2·09 to 2·53 for P vivax. All doses were equally effective in both P falciparum and P vivax malaria, with median parasite clearance half-lives of 4·1 h (range 1·3-6·7) to 5·6 h (2·0-8·5) for P falciparum and 2·3 h (1·2-3·9) to 3·2 h (0·9-15·0) for P vivax. Maximum plasma concentrations, dose-proportional to 800 mg, occurred at 4 h (median). The estimated elimination half-life was 46-62 h. No serious drug-related adverse effects were reported; other adverse effects were

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Become an MS Activist Take Action Current Advocacy Issues Advocacy Results Advocacy News d Raise Awareness d ... MS are more likely to experience gradually worsening problems with walking and mobility, along with whatever other symptoms they may have. Diagnosing relapsing-remitting MS (RRMS) Learn More Learn More ... Room MS Prevalence ...

Recurrence and Relapse in Bipolar Mood Disorder

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S Gh Mousavi

2004-06-01

Full Text Available Background: Despite the effectiveness of pharmacotherapy in acute phase of bipolar mood disorder, patients often experience relapses or recurrent episodes. Hospitalization of patients need a great deal of financial and humanistic resources which can be saved through understanding more about the rate of relapse and factors affecting this rate. Methods: In a descriptive analytical study, 380 patients with bipolar disorder who were hospitalized in psychiatric emergency ward of Noor hospital, Isfahan, Iran, were followed. Each patient was considered for; the frequency of relapse and recurrence, kind of pharmachotherapy, presence of psychotherapeutic treatments, frequency of visits by psychiatrist and the rank of present episode. Results: The overall prevalence of recurrence was 42.2%. Recurrence was lower in patients using lithium carbonate or sodium valproate or combined therapy (about 40%, compared to those using carbamazepine (80%. Recurrence was higher in patients treated with only pharmacotherapy (44.5% compared to those treated with both pharmacotherapy and psychotherapy (22.2%. Patients who were visited monthy by psychiatrist had lower rate of recurrence compared to those who had irregular visits. Conclusion: The higher rate of recurrence observed in carbamazepine therapy may be due to its adverse reactions and consequently poor compliance to this drug. Lower rates of recurrence with psychotherapy and regular visits may be related to the preventive effects of these procedures and especially to the effective management of stress. Keywords: Bipolar Mood Disorder, Recurrence, Relapse.

Relapse to cocaine seeking in an invertebrate.

Science.gov (United States)

Amaning-Kwarteng, Akua O; Asif-Malik, Aman; Pei, Yue; Canales, Juan J

2017-06-01

Addiction is characterised by cycles of compulsive drug taking, periods of abstinence and episodes of relapse. The extinction/reinstatement paradigm has been extensively used in rodents to model human relapse and explore underlying mechanisms and therapeutics. However, relapse to drug seeking behaviour has not been previously demonstrated in invertebrates. Here, we used a cocaine conditioned place preference (CPP) paradigm in the flatworm, planarian, followed by extinction and reinstatement of drug seeking. Once baseline preference was established for one of two distinctly textured environments (i.e. compartments with a coarse or smooth surface), planarian received pairings of cocaine (5μM) in the non-preferred, and vehicle in the most preferred, environment, and were tested for conditioning thereafter. Cocaine produced robust CPP, measured as a significant increase in the time spent in the cocaine-paired compartment. Subsequently, planarian underwent extinction training, reverting back to their original preference within three sessions. Brief exposure to cocaine (5μM) or methamphetamine (5μM) reinstated cocaine-seeking behaviour. By contrast, the high affinity dopamine transporter inhibitor, (N-(n-butyl)-3α-[bis (4-fluorophenyl) methoxy]-tropane) (JHW007), which in rodents exhibits a neurochemical and behavioural profile distinct from cocaine, was ineffective. The present findings demonstrate for the first time reinstatement of extinguished cocaine seeking in an invertebrate model and suggest that the long-term adaptations underlying drug conditioning and relapse are highly conserved through evolution. Copyright © 2017 Elsevier Inc. All rights reserved.

A simple risk scoring system for prediction of relapse after inpatient alcohol treatment.

Science.gov (United States)

Pedersen, Mads Uffe; Hesse, Morten

2009-01-01

Predicting relapse after alcoholism treatment can be useful in targeting patients for aftercare services. However, a valid and practical instrument for predicting relapse risk does not exist. Based on a prospective study of alcoholism treatment, we developed the Risk of Alcoholic Relapse Scale (RARS) using items taken from the Addiction Severity Index and some basic demographic information. The RARS was cross-validated using two non-overlapping samples, and tested for its ability to predict relapse across different models of treatment. The RARS predicted relapse to drinking within 6 months after alcoholism treatment in both the original and the validation sample, and in a second validation sample it predicted admission to new treatment 3 years after treatment. The RARS can identify patients at high risk of relapse who need extra aftercare and support after treatment.

Laboratory diagnosis of tick-borne African relapsing fevers: latest developments

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Aurélien eFotso Fotso

2015-11-01

Full Text Available In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases responsible for mild to deadly spirochetemia. Cultured B. crocidurae, B. duttonii and B. hispanica circulate alongside at least six species which have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualised using dark-field microscopy, the organisms can also be detected using Wright-Giemsa or acridine orange stains.. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: Multispacer Sequence Typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorised pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against Borrelia crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper

The effectiveness of mindfulness-based relapse prevention on the prevention of relapse, craving and self-control in opiate-dependent individuals

OpenAIRE

alireza maredpour; Mahmmod Najafy; Farangiss amiri

2015-01-01

Abstract Objective: the aim of this study is to investigate the effectiveness of mindfulness-based relapse prevention on the prevention of relapse, craving and self-control in opiate-dependent individuals in Yasuj. Methodology: This quasi-experimental study applied pretest - posttest and a control group. The sample included 30 male patients with drug addiction in Yasuj who were chosen from addiction clinics based on criterion sampling. To collect the required data the short form of Self-Co...

Joint hyperlaxity prevents relapses in clubfeet treated by Ponseti method-preliminary results.

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Cosma, Dan Ionuţ; Corbu, Andrei; Nistor, Dan Viorel; Todor, Adrian; Valeanu, Madalina; Morcuende, Jose; Man, Sorin

2018-05-07

The aim of the study was to evaluate the role of joint hyperlaxity (by Beighton score) as a protective factor for clubfoot relapse. Patients with idiopathic clubfoot treated with the Ponseti method between January 2004 and December 2012, without other congenital foot deformity, and not previously treated by open surgery were included in either the Relapse group (n = 23) if it was a clubfoot relapse or the Control group (n = 19) if no relapse was noted. Joint laxity was evaluated using the Beighton score at the latest follow-up against the Normal group (n = 22, children matched by sex and age without clubfoot deformity). We found a significantly higher joint laxity in the Control group (4.58, 95% confidence interval [CI]: 2.1-7.06) as compared to the Relapse (3.17, 95% CI: 1.53-4.81, p = 0.032) and Normal (3.14, 95% CI: 1.78-4.5, p = 0.03) groups. The univariate logistic regression showed a 5.28-times increase in the risk of relapse for a Beighton score lower than 4/9 points (odds ratio = 5.28; 95% CI = 1.29-21.5; p = 0.018). Joint hyperlaxity could be a protective factor for clubfoot relapse.

An intervention study to prevent relapse in patients with schizophrenia

NARCIS (Netherlands)

van Meijel, B.; Kruitwagen, C.; van der Gaag, M.; Kahn, R.S.; Grypdonck, M.H.E.

2006-01-01

Purpose: To determine whether the use of relapse prevention plans (RPPs) in nursing practice is an effective intervention in reducing relapse rates among patients with schizophrenia. Design and Methods: Experimental design. Patients with schizophrenia (or a related psychotic disorder) and nurses

Impact of the Distance of Maxillary Advancement on Horizontal Relapse After Orthognathic Surgery.

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Fahradyan, Artur; Wolfswinkel, Erik M; Clarke, Noreen; Park, Stephen; Tsuha, Michaela; Urata, Mark M; Hammoudeh, Jeffrey A; Yamashita, Dennis-Duke R

2018-04-01

The maxillary horizontal relapse following Le Fort I advancement has been estimated to be 10% to 50%. This retrospective review examines the direct association between the amounts of maxillary advancement and relapse. We hypothesize that the greater the advancement, the greater the relapse amount. Patients with class III skeletal malocclusion underwent maxillary advancement with either a Le Fort I or a Le Fort I with simultaneous mandibular setback (bimaxillary surgery) from 2008 to 2015. Patients were assessed for a history of cleft lip or cleft palate. Patients with known syndromes were excluded. Cephalometric analysis was performed to compare surgical and postsurgical changes. Of 136 patients, 47.1% were males and 61.8% had a history of cleft. The mean surgery age was 18.9 (13.8-23) years and 53.7% underwent a bimaxillary procedure. A representative subgroup of 35 patients had preoperative, immediate postoperative, and an average of 1-year postoperative lateral cephalograms taken. The mean maxillary advancement was 6.3 mm and the horizontal relapse was 1.8 mm, indicating a 28.6% relapse. A history of cleft and amount of maxillary advancement were directly correlated, whereas bone grafting of the maxillary osteotomy sites was inversely correlated with the amount of relapse ( P < .05). Our data suggest positive correlation between amount of maxillary advancement and horizontal relapse as well as a positive correlation between history of cleft and horizontal relapse. Bone grafting of the maxillary osteotomy sites has a protective effect on the relapse.

Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis.

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Kalinina Ayuso, Viera; van de Winkel, Evelyne Leonce; Rothova, Aniki; de Boer, Joke Helena

2011-02-01

To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a

[Application of Competing Risks Model in Predicting Smoking Relapse Following Ischemic Stroke].

Science.gov (United States)

Hou, Li-Sha; Li, Ji-Jie; Du, Xu-Dong; Yan, Pei-Jing; Zhu, Cai-Rong

2017-07-01

To determine factors associated with smoking relapse in men who survived from their first stroke. Data were collected through face to face interviews with stroke patients in the hospital, and then repeated every three months via telephone over the period from 2010 to 2014. Kaplan-Meier method and competing risk model were adopted to estimate and predict smoking relapse rates. The Kaplan-Meier method estimated a higher relapse rate than the competing risk model. The four-year relapse rate was 43.1% after adjustment of competing risk. Exposure to environmental tobacco smoking outside of home and workplace (such as bars and restaurants) ( P =0.01), single ( P <0.01), and prior history of smoking at least 20 cigarettes per day ( P =0.02) were significant predictors of smoking relapse. When competing risks exist, competing risks model should be used in data analyses. Smoking interventions should give priorities to those without a spouse and those with a heavy smoking history. Smoking ban in public settings can reduce smoking relapse in stroke patients.

Depression relapse and ethological measures

NARCIS (Netherlands)

Hale, WWH; Jansen, JHC; Bouhuys, AL; vandenHoofdakker, RH

1997-01-01

Within the framework of interactional theories on depression, the question is raised whether depression relapse can be predicted by observable behavior of remitted patients and their interviewer during an interaction (i.e. discharge interview). Thirty-four patients were interviewed at hospital

Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

Science.gov (United States)

Ray, Sandipan; Renu, Durairaj; Srivastava, Rajneesh; Gollapalli, Kishore; Taur, Santosh; Jhaveri, Tulip; Dhali, Snigdha; Chennareddy, Srinivasarao; Potla, Ankit; Dikshit, Jyoti Bajpai; Srikanth, Rapole; Gogtay, Nithya; Thatte, Urmila; Patankar, Swati; Srivastava, Sanjeeva

2012-01-01

This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates

TOLLIP gene variant is associated with Plasmodium vivax malaria in the Brazilian Amazon.

Science.gov (United States)

Brasil, Larissa W; Barbosa, Laila R A; de Araujo, Felipe J; da Costa, Allyson G; da Silva, Luan D O; Pinheiro, Suzana K; de Almeida, Anne C G; Kuhn, Andrea; Vitor-Silva, Sheila; de Melo, Gisely C; Monteiro, Wuelton M; de Lacerda, Marcus V G; Ramasawmy, Rajendranath

2017-03-13

Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon. This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp ® DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP. Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r 2  = 0.037; D' = 0.27). These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.

Proteomic investigation of falciparum and vivax malaria for identification of surrogate protein markers.

Directory of Open Access Journals (Sweden)

Sandipan Ray

Full Text Available This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM (n = 20, vivax malaria (VM (n = 17 and healthy controls (HC (n = 20 were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC. Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05 serum proteins were identified in FM and VM respectively, and almost half (46.2% of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates

Eficacia de una prueba rápida para el diagnóstico de Plasmodium vivax en pacientes sintomáticos de Chiapas, México Eficacia de una prueba rápida para el diagnóstico de Plasmodium vivax en pacientes sintomáticos de Chiapas, México

Directory of Open Access Journals (Sweden)

Lilia González-Cerón

2005-07-01

Full Text Available OBJETIVO: Evaluar en condiciones de laboratorio la sensibilidad y especificidad de una prueba rápida de diagnóstico (OptiMAL, basada en tiras inmunorreactivas para detectar Plasmodium vivax en pacientes febriles del sur de Chiapas, México. MATERIAL Y MÉTODOS: Entre diciembre de 2000 a abril de 2002 se investigó la presencia de parásitos en muestras sanguíneas de 893 pacientes por examen microscópico de gotas gruesas teñidas con Giemsa (prueba de referencia. Otra gota de sangre de la misma punción fue empleada en las tiras inmunorreactivas para investigar la presencia de pLDH del parásito. Los resultados discordantes se resolvieron por PCR del gen de la subunidad ribosomal 18S del parásito para descartar infección. RESULTADOS: OptiMAL mostró una sensibilidad de 93.3% y especificidad de 99.5%, con valores predictivo positivo y negativo de 96.5 y 98.9%, respectivamente. La intensidad de las reacciones en las tiras OptiMAL correlacionaron con la densidad parasitaria (r=0.601, p=0.0001. CONCLUSIONES: La prueba rápida presentó sensibilidad y especificidad aceptables para detectar P. vivax en condiciones de laboratorio y podría ser útil para el diagnóstico de paludismo en operaciones de campo en México.OBJECTIVE: To evaluate, under laboratory conditions, the sensitivity and specificity of a rapid diagnostic test (OptiMAL, based on immunoreactive strips, to detect Plasmodium vivax infection in febrile patients in Southern Chiapas, Mexico. MATERIAL AND METHODS: The presence of parasites in blood samples of 893 patients was investigated by Giemsa-stained thick blood smear microscopic examination (gold standard. A blood drop from the same sample was smeared on immunoreactive strips to investigate the presence of the parasite pLDH. Discordant results were resolved by PCR amplification of the parasite's 18S SSU rRNA, to discard infection. RESULTS: OptiMAL had an overall sensitivity of 93.3% and its specificity was 99.5%. Its positive and

Breaking the rhythm of depression : Cognitive Behavior Therapy and relapse prevention for depression

NARCIS (Netherlands)

Bockting, Claudi L.H.

2010-01-01

A crucial part of the treatment of depression is the prevention of relapse and recurrence. Psychological interventions, especially cognitive behavior therapy (CBT) are helpful in preventing relapse and recurrence in depression. The effectivity of four types of relapse prevention cognitive behavior

Anca associated vasculitis : occurrence, prediction, prevention, and outcome of relapses

NARCIS (Netherlands)

Boomsma, Maarten Michiel

2001-01-01

During follow-up, relapses of disease activity occur in the majority of patients with ANCA associated vasculitis. The general objective brought together in this thesis was to further elucidate the characteristics and consequences of these relapses. Investigated items are the occurrence, the

Are there clinically useful predictors and early warning signs for pending relapse?

Science.gov (United States)

Gaebel, Wolfgang; Riesbeck, Mathias

2014-02-01

Despite the availability of effective long-term treatment strategies in schizophrenia, relapse is still common. Relapse prevention is one of the major treatment objectives, because relapse represents burden and costs for patients, their environment, and society and seems to increase illness progression at the biological level. Valid predictors for relapse are urgently needed to enable more individualized recommendations and treatment decisions to be made. Mainly recent evidence regarding predictors and early warning signs of relapse in schizophrenia was reviewed. In addition, data from the first-episode (long-term) study (FES; Gaebel et al., 2007, 2011) performed within the German Research Network on Schizophrenia were analyzed. On the basis of FES data, premorbid adjustment, residual symptoms and some side effects are significant predictors. Although a broad spectrum of potential parameters has been investigated in several other studies, only a few and rather general valid predictors were identified consistently. Data of the FES also indicated that predictive power could be enhanced by considering interacting conjunctions, as suggested by the Vulnerability-Stress-Coping model. Prospective studies, however, are rare. In addition, prodromal symptoms as course-related characteristics likewise investigated in the FES add substantially to early recognition of relapse and may serve as early warning signs, but prognosis nevertheless remains a challenge. Comprehensive and well-designed studies are needed to identify and confirm valid predictors for relapse in schizophrenia. In this respect, broadly accepted and specifically defined criteria for relapse would greatly facilitate comparison of results across studies. © 2013 Elsevier B.V. All rights reserved.

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

Science.gov (United States)

Nayan, Madhur; Jewett, Michael A S; Hosni, Ali; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Hansen, Aaron R; Chung, Peter; Warde, Padraig; Sweet, Joan; O'Malley, Martin; Atenafu, Eshetu G; Hamilton, Robert J

2017-01-01

Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. To determine cRR in CSI testicular cancer. We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Preventing Postpartum Smoking Relapse: A Randomized Clinical Trial.

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Levine, Michele D; Cheng, Yu; Marcus, Marsha D; Kalarchian, Melissa A; Emery, Rebecca L

2016-04-01

Most women who quit smoking during pregnancy will relapse postpartum. Previous efforts to prevent postpartum relapse have been unsuccessful at increasing rates of sustained abstinence. To evaluate the relative efficacy of 2 different approaches to prevent postpartum smoking relapse. Pregnant women who recently had quit smoking were recruited before the end of pregnancy. Intervention sessions were conducted through a combination of telephone calls and in-person visits beginning at delivery and continuing through 24 weeks postpartum. Participants completed assessments at the prenatal baseline and at 12, 24, and 52 weeks postpartum. Participants were recruited between March 2008 and December 2012. The dates of the analysis were April 2014 to February 2015. Women received postpartum-adapted, behavioral smoking relapse prevention intervention and were randomly assigned to an enhanced cognitive behavioral intervention that included additional specialized strategies and content focused on women's postpartum concerns about mood, stress, and weight (Strategies to Avoid Returning to Smoking [STARTS]) or a supportive, time and attention-controlled comparison (SUPPORT). Intervention began before delivery and continued through 24 weeks postpartum. The primary outcome was biochemically confirmed sustained tobacco abstinence at 52 weeks postpartum. Secondary outcomes were self-reported mood, levels of perceived stress, and degree of concern about smoking-related weight gain. The study cohort comprised 300 participants (150 randomly assigned to each group). Their mean (SD) age was 24.99 (5.65) years. Overall, 38.0% (114 of 300), 33.7% (101 of 300), and 24.0% (72 of 300) of the sample maintained abstinence at 12, 24, and 52 weeks' postpartum, respectively. There were no differences between the intervention groups in abstinence or time to relapse. Self-reported depressive symptoms and perceived stress significantly improved over time, and improvements were similar for both

Malaria diagnosis by PCR revealed differential distribution of mono and mixed species infections by Plasmodium falciparum and P. vivax in India.

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Siwal, Nisha; Singh, Upasana Shyamsunder; Dash, Manoswini; Kar, Sonalika; Rani, Swati; Rawal, Charu; Singh, Rajkumar; Anvikar, Anupkumar R; Pande, Veena; Das, Aparup

2018-01-01

Malaria is a vector-borne infectious disease, caused by five different species of the genus Plasmodium, and is endemic to many tropical and sub-tropical countries of the globe. At present, malaria diagnosis at the primary health care level in India is conducted by either microscopy or rapid diagnostic test (RDT). In recent years, molecular diagnosis (by PCR assay), has emerged as the most sensitive method for malaria diagnosis. India is highly endemic to malaria and shoulders the burden of two major malaria parasites, Plasmodium falciparum and P. vivax. Previous studies using PCR diagnostic assay had unraveled several interesting facts on distribution of malaria parasites in India. However, these studies had several limitations from small sample size to limited geographical areas of sampling. In order to mitigate these limitations, we have collected finger-prick blood samples from 2,333 malaria symptomatic individuals in nine states from 11 geographic locations, covering almost the entire malaria endemic regions of India and performed all the three diagnostic tests (microscopy, RDT and PCR assay) and also have conducted comparative assessment on the performance of the three diagnostic tests. Since PCR assay turned out to be highly sensitive (827 malaria positive cases) among the three types of tests, we have utilized data from PCR diagnostic assay for analyses and inferences. The results indicate varied distributional prevalence of P. vivax and P. falciparum according to locations in India, and also the mixed species infection due to these two species. The proportion of P. falciparum to P. vivax was found to be 49:51, and percentage of mixed species infections due to these two parasites was found to be 13% of total infections. Considering India is set for malaria elimination by 2030, the present malaria epidemiological information is of high importance.

Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification

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Jovanović Tatjana

2012-01-01

Full Text Available Background/Aim. Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioids in the two groups of opiate addicts treated by two different therapeutic modalities. Methods. The results of the two groups of opiate addicts were compared: the patients on substitution methadone treatment (M and the patients treated with opiate blocker naltrexone (B. In all the patients, clinical and instrumental evaluations confirmed depressive syndrome. Opioid relapses were diagnosed by the panel test for rapid detection of metabolites of opiates in urine. Then they were brought in connection with scores of depression and addiction variables. The Hamilton Depression Scale (HAMD and Zunge Depression Scale were the applied instruments for measuring the level of depression. All the subjects completed a questionnaire Pompidou (short version. Psychological measurements were carried out during a 6-month follow-up on three occasions. The presence of opiate metabolites in urine was controlled every two weeks. Results. Both groups of patients (M and B had high scores on HAMD during the study. The group on methadone had a strong depression in all three measurements. There was a drop in the level of depression in both experimental groups over time, which was accompanied by a decrease in the incidence of recurrence. In both tested groups the frequency of relapses was positively correlated with earlier addiction variables - intravenous application of opioids, the experience of overdose, the absence of immunization against hepatitis C and hepatitis C virus carriers

[Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification].

Science.gov (United States)

Jovanović, Tatjana; Lazarević, Dusan; Nikolić, Gordana

2012-04-01

Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioids in the two groups of opiate addicts treated by two different therapeutic modalities. The results of the two groups of opiate addicts were compared: the patients on substitution methadone treatment (M) and the patients treated with opiate blocker naltrexone (B). In all the patients, clinical and instrumental evaluations confirmed depressive syndrome. Opioid relapses were diagnosed by the panel test for rapid detection of metabolites of opiates in urine. Then they were brought in connection with scores of depression and addiction variables. The Hamilton Depression Scale (HAMD) and Zunge Depression Scale were the applied instruments for measuring the level of depression. All the subjects completed a questionnaire Pompidou (short version). Psychological measurements were carried out during a 6-month follow-up on three occasions. The presence of opiate metabolites in urine was controlled every two weeks. Both groups of patients (M and B) had high scores on HAMD during the study. The group on methadone had a strong depression in all three measurements. There was a drop in the level of depression in both experimental groups over time, which was accompanied by a decrease in the incidence of recurrence. In both tested groups the frequency of relapses was positively correlated with earlier addiction variables - intravenous application of opioids, the experience of overdose, the absence of immunization against hepatitis C and hepatitis C virus carriers. The opioid relapse behavior is associated with a

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

NARCIS (Netherlands)

Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

2006-01-01

BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

Relapse risk assessment of transplantation for patients with chronic myeloid leukaemia

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

Objective To analyse the risk factors of relapse before bone marrow transplantation (BMT) and to present the prognostic information as good as possible.Methods A total of 3142 patients, who underwent the allogeneic blood or bone marrow tran splantation between 1989 and 1997 and were documented in the European Group for Blood and Marrow transplantation (EBMT), were included. Six possible risk factors including type of donor, stage of disease, age, gender, donor@#-recipient sex co mbination and the waiting time from diagnosis to transplation of relapse were co nsidered. The time to relapse was analysed by Kaplan-Meier curves and Coxregre ssion with stratification on prognostic factors that did not satisfy the Proport ional Hazard Assumption.Results An amount of 447 patients relapsed out of all 3142 patients. The relapse rate was 14.2%. Type of donor and stage of disease showed a clear prognostic effect, but failed the proportional hazard assumption. Therefore, the data were stratified on the combination of type of donor and stage of disease. Within these strata a n additional significant effect of age could be observed. Relative risk of age ≥40 vs age <40 was 1.32 (95% confidence interval 1.09-1.59). The prognostic model is summarized graphically.Conclusions The combination of type of donor, stage of disease and age of recipient at transplantation are important prognostic factors for relapse after BMT.

P. vivax Malaria and Dengue Fever Co-infection: A Cross-Sectional Study in the Brazilian Amazon

Science.gov (United States)

Magalhães, Belisa M. L.; Siqueira, André M.; Alexandre, Márcia A. A.; Souza, Marcela S.; Gimaque, João B.; Bastos, Michele S.; Figueiredo, Regina M. P.; Melo, Gisely C.; Lacerda, Marcus V. G.; Mourão, Maria P. G.

2014-01-01

Background Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity. Methodology/Principal Findings A cross-sectional study was conducted (2009 to 2011) in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1%) presented P. vivax malaria mono-infection, 584 (37%) dengue fever mono-infection, and 44 (2.8%) were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected), deep bleeding (vs. P. vivax mono-infected), hepatomegaly, and jaundice (vs. dengue mono-infected). Conclusions/Significance In endemic areas for dengue and malaria, jaundice (in dengue patients) and spontaneous bleeding (in malaria patients) should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group. PMID:25340346

Relapse prevention in patients with schizophrenia : A nursing intervention study

NARCIS (Netherlands)

Meijel, Berno van

2003-01-01

This thesis describes a study into the development and testing of a nursing intervention with a view to preventing psychotic relapses in patients suffering from schizophrenia or a related disorder. The purpose of the intervention is to recognise the early signs of an oncoming psychotic relapse. If

Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals

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Yasmin Zakiniaeiz

2017-01-01

Full Text Available Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC, mid (MCC and posterior cingulate cortex (PCC, voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome. Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.

Relapsing/remitting type 1 diabetes

NARCIS (Netherlands)

van Megen, Kayleigh M.; Spindler, Matthew P.; Keij, Fleur M.; Bosch, Ineke; Sprangers, Fleur; van Royen-Kerkhof, Annet; Nikolic, Tatjana; Roep, Bart O.

2017-01-01

Aims/hypothesis: Type 1 diabetes is believed to be an autoimmune disease associated with irreversible loss of insulin secretory function that follows a chronic progressive course. However, it has been speculated that relapsing/remitting disease progression may occur in type 1 diabetes. Methods: We

Changes in circulating peptide YY and ghrelin are associated with early smoking relapse.

Science.gov (United States)

Lemieux, Andrine M; al'Absi, Mustafa

2018-01-01

Ghrelin and peptide YY (PYY) during ad libitum smoking have been associated with decreased reported craving (ghrelin) and increased positive affect (PYY), and higher baseline ghrelin levels predicted subsequent increased risk of smoking relapse. The current study assessed PYY and ghrelin during ad libitum smoking and again after the initial 48h of a smoking cessation attempt. The data compared smokers who abstained for 28days (n=37), smokers who relapsed (n=54), and nonsmokers (n=37). Plasma samples and subjective measures assessing craving and mood were collected at the beginning of each session. Results showed that relapsers experienced greater levels of distress (ps <0.01). While nonsmokers and abstainers showed no change in ghrelin across the initial 48h, relapsers declined (p <0.01). With PYY, relapsers increased (p <0.05) across the early abstinent phase. PYY and ghrelin may be useful predictors of relapse, specifically in reference to early withdrawal. Copyright © 2017. Published by Elsevier B.V.

Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

Science.gov (United States)

Laubach, J; Garderet, L; Mahindra, A; Gahrton, G; Caers, J; Sezer, O; Voorhees, P; Leleu, X; Johnsen, H E; Streetly, M; Jurczyszyn, A; Ludwig, H; Mellqvist, U-H; Chng, W-J; Pilarski, L; Einsele, H; Hou, J; Turesson, I; Zamagni, E; Chim, C S; Mazumder, A; Westin, J; Lu, J; Reiman, T; Kristinsson, S; Joshua, D; Roussel, M; O'Gorman, P; Terpos, E; McCarthy, P; Dimopoulos, M; Moreau, P; Orlowski, R Z; Miguel, J S; Anderson, K C; Palumbo, A; Kumar, S; Rajkumar, V; Durie, B; Richardson, P G

2016-05-01

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

The Value of Fecal Markers in Predicting Relapse in Inflammatory Bowel Diseases

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Bianca J. Galgut

2018-01-01

Full Text Available The inflammatory bowel diseases (IBDs are lifelong chronic illnesses that place an immense burden on patients. The primary aim of therapy is to reduce disease burden and prevent relapse. However, the occurrence of relapses is often unpredictable. Current disease monitoring is primarily by way of clinical indices, with relapses often only recognized once the inflammatory episode is established with subsequent symptoms and gut damage. The window between initial upregulation of the inflammatory response and the recognition of symptoms may provide an opportunity to prevent the relapse and associated morbidity. This review will describe the existing literature surrounding predictive indicators of relapse of IBD with a specific focus on fecal biomarkers. Fecal biomarkers offer promise as a convenient, non-invasive, low cost option for disease monitoring that is predictive of subsequent relapse. To exploit the potential of fecal biomarkers in this role, further research is now required. This research needs to assess multiple fecal markers in context with demographics, disease phenotype, genetics, and intestinal microbiome composition, to build disease behavior models that can provide the clinician with sufficient confidence to intervene and change the long-term disease course.

Resposta imune-humoral e proteinogramas séricos de bovinos naturalmente infectados pelo Trypanosoma vivax

OpenAIRE

Sampaio, Paulo Henrique [UNESP

2013-01-01

Em bovinos o protozoário Trypanosoma vivax causa enfermidade que pode levar à redução dos índices produtivos ou a morte do animal. O diagnóstico deste protozoário pode ser realizado por testes parasitológicos, sorológicos e moleculares. Entretanto estes testes não são capazes de fornecer prognóstico, indicar a fase da infecção e a responsividade ao tratamento instituído. Por outro lado, o proteinograma sérico pode fornecer tais informações. O objetivo do estudo foi determinar o perfil eletrof...

Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted individuals

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Meredith J Mchugh

2014-02-01

Full Text Available Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting state functional connectivity (rsFC in neural circuits arising from the amygdala; a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state fMRI connectivity (6 min was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry separate seeds were derived for the left and right basolateral (BLA and corticomedial (CMA amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive Compulsive Cocaine Use scale, Temperament and Character Inventory and the NEO-PI-R. Relapse within the first 30 days post-treatment (n = 24 was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21. Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.

Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

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Kim, Ji Hyun [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Tsai, Nicole [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Liu, An [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen J. [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

2014-05-01

Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

International Nuclear Information System (INIS)

Kim, Ji Hyun; Stein, Anthony; Tsai, Nicole; Schultheiss, Timothy E.; Palmer, Joycelynne; Liu, An; Rosenthal, Joseph; Forman, Stephen J.; Wong, Jeffrey Y.C.

2014-01-01

Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk

Primaquine double dose for 7 days is inferior to single-dose treatment for 14 days in preventing Plasmodium vivax recurrent episodes in Suriname

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Mac Donald-Ottevanger MS

2017-12-01

Full Text Available M Sigrid Mac Donald-Ottevanger,1 Malti R Adhin,2 Jeetendra Kumar Jitan,3 Gustavo Bretas,4 Stephen GS Vreden1 1Foundation for Scientific Research Suriname (SWOS, 2Department of Biochemistry, Anton de Kom University of Suriname, 3Department of Public Health, Ministry of Health, Paramaribo, Suriname; 4Independent consultant, Rio de Janeiro, Brazil Background: Recurrent episodes of Plasmodium vivax are caused by dormant liver stages of the parasite, which are not eradicated by choloroquine. Therefore, effective treatment also includes the use of primaquine (PQ. However, this secondary preventive therapy is often not effective, mostly due to poor adherence to the relatively long treatment course, justifying a comparative study of the efficacy of different durations of PQ treatment. Materials and methods: We included patients presenting with an acute and documented P. vivax infection from January 2006 to February 2008. All patients received chloroquine 25 mg/kg over a 3-day period. Subsequently, patients in group 7D received PQ 30 mg/day for 7 days, and patients in group 14D received standard PQ 15 mg/day for 14 days. All doses were given under supervision and patients were followed up for at least 6 months. The Kaplan–Meier method was used to estimate cumulative probability of recurrence up to 12 months after treatment initiation stratified by treatment group. Cox regression was used to assess possible determinants for recurrent parasitemia. Results: Forty-seven of the 79 included patients (59.5% were allocated to group 7D and 32 patients (40.5% were allocated to group 14D. Recurrent parasitemia was detected in 31.9% of the cases in group 7D compared to 12.5% of the cases in group 14D (hazard ratio [HR] =3.36, 95% CI 1.11–10.16. Cumulative probability for recurrent parasitemia at 3, 6, and 12 months was 0.201 (95% CI 0.106–0.362, 0.312 (95% CI 0.190–0.485, and 0.424 (95% CI 0.274– 0.615 for group 7D and 0.100 (95% CI 0.033–0.279, 0

Factors Associated with Relapse among Heroin Addicts: Evidence from a Two-Year Community-Based Follow-Up Study in China

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Chao Rong

2016-01-01

Full Text Available Background: Many countries including China are facing a serious opiate dependence problem. Anti-drug work effectiveness was affected by the high relapse rate all over the world. This study aims to analyze the factors influencing heroin addict relapse, and to provide evidence for generating relapse prevention strategies. Methods: A community-based follow-up study was conducted in China between October 2010 and September 2012. A total of 554 heroin addicts in accordance with the inclusion criteria from 81 streets in 12 districts of Shanghai, China were divided into 4 groups: group 1—daily dosage taken orally of 60 mL of methadone or under combined with psychological counseling and social supports (n = 130; group 2—daily dosage taken orally of over 60 mL of methadone combined with psychological counseling and social supports (n = 50; group 3—JTT (Jitai tablets combined with psychological counseling and social supports (n = 206; group 4—JTT combined with social supports (n = 168. Results: Log-rank test results showed that the cumulative relapse rate differences among four groups during the two-year follow-up period were not statistically significant (χ2 = 5.889, p = 0.117. Multivariate Cox regression analysis results showed that only three independent variables were still statistically significant, including compliance with participation in psychological counseling (OR = 3.563, p = 0.000, the years of drug use (OR = 1.078, p = 0.001and intervention model. Conclusions: Using the detoxification medications combined with appropriate psychological counseling and social support measures will help improve the effectiveness of relapse prevention, which is a kind of alternative community detoxification pattern. Appropriate and standard psychological counseling is very important for anti-drug treatment. The longer the drug addiction lasts, the longer the anti-drug treatment takes.

An Integrative Ambient Agent Model for Unipolar Depression Relapse Prevention

NARCIS (Netherlands)

Aziz, A.A.; Klein, M.C.A.; Treur, J.

2010-01-01

One of the challenges for persons with a history of unipolar depression is to stay healthy throughout their lifetime. In principle, having more severe prior onset cases escalates the risk to fall into a relapse. In this article, first a domain model of the process of depression, recovery and relapse

Factors associated with relapse in schizophrenia

African Journals Online (AJOL)

increases the economic burden on health care systems because of its associated morbidity .... Depression in schizophrenia has been associated with higher rates of relapse ... The researchers approached the psychiatric nursing staff of mental.

Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

Science.gov (United States)

Wang, Pei-Wen; Chen, I-Ya; Juo, Suh-Hang Hank; Hsi, Edward; Liu, Rue-Tsuan; Hsieh, Ching-Jung

2013-01-01

Background For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. Methods To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. Results Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). Conclusion Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse. PMID:24783027

“I Was a Full Time Proper Smoker”: A Qualitative Exploration of Smoking in the Home after Childbirth among Women Who Relapse Postpartum

Science.gov (United States)

Coleman, Tim; Lewis, Sarah; Cooper, Sue

2016-01-01

Background Many women stop smoking during pregnancy but relapse shortly afterwards, potentially putting their infants at risk of secondhand smoke (SHS) exposure. Women who were able to stop during pregnancy may be a motivated group, receptive to making behaviour changes postpartum to protect their infant from SHS exposure. Understanding more about their experiences of relapse, and if this influences home smoking behaviours and children’s exposure to SHS in the home may help to inform intervention development to prevent infant SHS exposure. Methods Guided by interpretative phenomenological methodology we conducted and analysed nine semi-structured interviews with women who quit smoking during pregnancy, but relapsed ≤3 months postpartum. Findings Central to mothers’ accounts of their smoking behaviours during pregnancy and postpartum was their desire to be a ‘responsible mother’. Mothers described using strategies to protect their infant from SHS exposure, and held strong negative attitudes towards other smoking parents. After relapsing, mothers appeared to reposition themselves as ‘social’ or ‘occasional’ smokers rather than ‘regular’ smokers. Conclusions Findings suggest that interventions to prevent/reduce infants' home SHS exposure should build on mothers' intentions to be responsible parents. As mothers who relapse principally view themselves as ‘social’ or ‘occasional’ smokers, interventions that are highlighted as relevant for women with these types of smoking patterns may be more likely to be responded to, and, ultimately, be effective. PMID:27308829

Patterns of care in the management of seminoma stage I

DEFF Research Database (Denmark)

Vossen, Carla Y; Horwich, Alan; Daugaard, Gedske

2012-01-01

Study Type - Therapy (practise pattern survey). Level of Evidence 3b. What's known on the subject? and What does the study add? The uncertainties about differences in relapse and rates of other late events such as second malignancy and cardiovascular events for the three post-orchidectomy strateg......Study Type - Therapy (practise pattern survey). Level of Evidence 3b. What's known on the subject? and What does the study add? The uncertainties about differences in relapse and rates of other late events such as second malignancy and cardiovascular events for the three post......-orchidectomy strategies in seminoma stage I patients has led to debates about whether the three strategies are equally effective and safe. The differences in interpretation of the data as well as the debates are likely to result in differences in treatment after orchidectomy in seminoma stage I patient management...

Predictors of marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status.

Science.gov (United States)

Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D; Glass, Andrew; Vosburg, Suzanne K; Comer, Sandra D; Foltin, Richard W

2013-02-01

Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. Study 1: data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal, and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers (n = 51; 10 ± 5 marijuana cigarettes/day) were enrolled. Study 2: to isolate the effects of cigarette smoking, marijuana intoxication, withdrawal, and relapse were assessed in daily marijuana and cigarette smokers (n = 15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU), and after at least 5 days without cigarettes (Quit). Study 1: 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (odds ratio: 19, p marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes (p 87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse, and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

Science.gov (United States)

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

A simple technique for correction of relapsed overjet.

Science.gov (United States)

Kakkirala, Neelima; Saxena, Ruchi

2014-01-01

Class III malocclusions are usually growth related discrepancies, which often become more severe when growth is completed Orthognathic surgery can be a part of the treatment plan, although a good number of cases can be treated non-surgically by camouflage treatment. The purpose of this report is to review the relapse tendency in patients treated non-surgically. A simple technique is described to combat one such post-treatment relapse condition in an adult patient who had undergone orthodontic treatment by extraction of a single lower incisor.

Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

OpenAIRE

Bolton, Michael J; Garry, Robert F

2011-01-01

Abstract Background The surface glycoprotein (SU, gp120) of the human immunodeficiency virus (HIV) must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP) to bind the Duffy Antigen Receptor for Chemokines (DARC) and invade reticulocytes. Results Variable loop 3 (V3) of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, ...