de Palacios Patricia
Full Text Available Abstract Background The six-dose regimen of artemether-lumefantrine (AL is now considered the gold standard for the treatment of uncomplicated Plasmodium falciparum malaria. There are few reports evaluating co-artemether in very young Nigerian infants and children. Results of the evaluation of the six-dose regimen in very young infants and children in Nigeria are presented in this report. Methods As part of a larger African study, this open label, non-comparative trial, assessed the efficacy and safety of six-dose regimen of AL tablets in 103 Nigerian infants and children weighing between five and 25 kg suffering from acute uncomplicated malaria. Treatment was administered under supervision over three days with children as in-patients. 12-lead ECG tracings were taken pre-treatment and at day 3. Results Ninety-three infants and children completed the study as stipulated by the protocol. Mean fever and parasite clearance times for the intent to treat population (ITT were 24.9 h ± (1.28 and 26 h ± (4.14 and the corresponding figures for the per-protocol population (PP were 19.24 h ± 13.9 and 25.62 h ± 11.25 respectively. Day 14 cure rates for the ITT and PP were 95.1% and 100% respectively while day 28 cure rates were 91.3% and 95.7% respectively. The overall PCR corrected day 28 cure rate was 95.1% for the ITT. The six-dose regimen of AL was well tolerated with no drug-related serious adverse events. Although six patients recorded a QTc prolongation of > 60 ms on D3 over D0 recording, no patient recorded a QTc interval > 500 ms. Conclusion The six-dose regimen of AL tablets is safe and effective for the treatment of acute uncomplicated malaria in Nigerian infants and children weighing between five and 25 kg. Trial registration NCT00709969
Chimma, Pattamawan; Roussilhon, Christian; Sratongno, Panudda; Ruangveerayuth, Ronnatrai; Pattanapanyasat, Kovit; Pérignon, Jean-Louis; Roberts, David J.; Druilhe, Pierre
Monocyte (MO) subpopulations display distinct phenotypes and functions which can drastically change during inflammatory states. We hypothesized that discrete MO subpopulations are induced during malaria infection and associated with anti-parasitic activity. We characterized the phenotype of blood MO from healthy malaria-exposed individuals and that of patients with acute uncomplicated malaria by flow cytometry. In addition, MO defense function was evaluated by an in vitro antibody dependent cellular inhibition (ADCI) assay. At the time of admission, the percentages and absolute numbers of CD16+ MO, and CCR2+CX3CR1+ MO, were high in a majority of patients. Remarkably, expression of CCR2 and CX3CR1 on the CD14high (hi) MO subset defined two subgroups of patients that also differed significantly in their functional ability to limit the parasite growth, through the ADCI mechanism. In the group of patients with the highest percentages and absolute numbers of CD14hiCCR2+CX3CR1+ MO and the highest mean levels of ADCI activity, blood parasitemias were lower (0.14±0.34%) than in the second group (1.30±3.34%; p = 0.0053). Data showed that, during a malaria attack, some patients' MO can exert a strong ADCI activity. These results bring new insight into the complex relationships between the phenotype and the functional activity of blood MO from patients and healthy malaria-exposed individuals and suggest discrete MO subpopulations are induced during malaria infection and are associated with anti-parasitic activity. PMID:19851453
Full Text Available Acute appendicitis is one of the most common abdominal emergencies requiring surgery. It still represents, however, a challenging diagnosis. In order to facilitate this process, several scoring systems were developed, namely, the Alvarado score, acute inflammatory response and Raja Isteri Pengiran Anak Saleha Appendicitis scores, which are the most used in clinical practice. This clinical condition encompasses a wide spectrum of clinical presentations, from the uncomplicated form to the one with diffuse peritonitis. Treatment of uncomplicated acute appendicitis remains a matter of discussion. Although appendectomy has been regarded as the gold-standard, conservative management with antibiotics is gaining more and more acceptance. The approach to appendectomy constitutes another controversial issue, namely, its performance through an open or a laparoscopic approach, which seems to be establishing itself, in some centers, as the standard of care. With this paper, we intend to give some insight on the aforementioned topics, through a review of the available literature on uncomplicated appendicitis.
Gbotosho, Grace O; Happi, Christian T; Folarin, Onikepe; Keyamo, Ochuko; Sowunmi, Akintunde; Oduola, Ayoade M J
The diagnosis of malaria in biological fluids other than blood using non-invasive, rapid diagnostic techniques provides a valuable approach in case management and epidemiological studies of malaria. Rapid detection of Plasmodium falciparum lactate dehydrogenase (pLDH) in saliva samples from 130 of 144 children with microscopically confirmed P. falciparum infection was evaluated using Optimal-IT dipsticks. Genotyping of parasites was also performed in saliva and blood samples from a cohort of patients by polymerase chain reaction (PCR). The sensitivity of the dipstick in whole-blood, whole-saliva, or supernatant of spun saliva samples was 97.2%, 77.9%, and 48.4%, respectively. The sensitivity of the dipstick in whole-saliva samples was significantly higher than in supernatant of spun saliva samples (P saliva samples, respectively. This finding shows rapid detection of pLDH in patient saliva.
Taylor-Robinson, David; Jones, Katharine; Garner, Paul; Sinclair, David
Uncomplicated malaria is where the person has symptomatic infection with malaria parasites, but no signs of vital organ disturbance. Uncomplicated malaria can progress to severe malaria, become chronic, or resolve, depending on host immunity and prompt access to appropriate treatment.Severe malaria is more likely to develop in people with no prior immunity, and accounts for over one million deaths worldwide each year.The choice between treatment regimens depends partly on backg...
BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine...... lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas......-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies...
Sowunmi, Akintunde; Gbotosho, Grace O; Happi, Christian T; Okuboyejo, Titilope M; Sijuade, Abayomi O; Michael, Obaro S; Adewoye, Elsie O; Folarin, Onikepe
The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.
Carrara, Verena I; Phyo, Aung P; Nwee, Paw; Soe, Ma; Htoo, Hsar; Arunkamomkiri, Jaruwan; Singhasivanon, Pratap; Nosten, François
Background The use of artemisinin derivatives has increased exponentially with the deployment of artemisinin combination therapy (ACT) in all malarious areas. They are highly effective and are considered safe, but in animal studies artemisinin derivatives produce neurotoxicity targeting mainly the auditory and vestibular pathways. The debate remains as to whether artemisinin derivatives induce similar toxicity in humans. Methods This prospective study assessed the effects on auditory function of a standard 3-day oral dose of artesunate (4 mg/kg/day) combined with mefloquine (25 mg/kg) in patients with acute uncomplicated falciparum malaria treated at the Shoklo Malaria Research Unit, on the Thai-Burmese border. A complete auditory evaluation with tympanometry, audiometry and auditory brainstem responses (ABR) was performed before the first dose and seven days after initiation of the antimalarial treatment. Results Complete auditory tests at day 0 (D0) and day 7 (D7) were obtained for 93 patients. Hearing loss (threshold > 25 dB) on admission was common (57%) and associated with age only. No patient had a threshold change exceeding 10 dB between D0 and D7 at any tested frequency. No patient showed a shift in Wave III peak latency of more than 0.30 msec between baseline and D7. Conclusion Neither audiometric or the ABR tests showed clinical evidence of auditory toxicity seven days after receiving oral artesunate and mefloquine. PMID:18986553
BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentr......BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine......-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies...... lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas...
Ünlü, Çagdas; Gunadi, Patrick M; Gerhards, Michael F; Boermeester, Marja A; Vrouenraets, Bart C
Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment of acute uncomplicated diverticulitis is feasible and safe, and which patients could benefit from outpatient care. A retrospective cohort study was carried out in two teaching hospitals using hospital registry codes for diverticulitis. All patients diagnosed with acute uncomplicated diverticulitis between January 2004 and January 2012, confirmed by imaging or colonoscopy, were included. Exclusion criteria were patients with recurrent diverticulitis, complicated diverticulitis (Hinchey stages 2, 3, and 4), and right-sided diverticulitis. Inpatient care was compared with outpatient care. Primary outcome was admission for outpatient care and the complication rate in both groups. Multivariate analysis was carried out to identify potential factors for inpatient care. Of 627 patients with diverticulitis, a total of 312 consecutive patients were identified with primary uncomplicated diverticulitis of the sigmoid colon; 194 patients had been treated as inpatients and 118 patients primarily as outpatients. In this last group, 91.5% had been treated successfully without diverticulitis-related complications or the need for hospital admission during a mean follow-up period of 48 months. Despite inherent patient selection in a retrospective cohort, ambulatory treatment of patients presenting with uncomplicated acute diverticulitis seems feasible and safe. In mildly ill and younger patients, hospital admission can be avoided.
Colborn, James M; Ylöstalo, Joni H; Koita, Ousmane A; Cissé, Ousmane H; Krogstad, Donald J
To examine human gene expression during uncomplicated P. falciparum malaria, we obtained three samples (acute illness, treatment, and recovery) from 10 subjects and utilized each subject's recovery sample as their baseline. At the time of acute illness (day 1), subjects had upregulation of innate immune response, cytokine, and inflammation-related genes (IL-1β, IL-6, TNF, and IFN-γ), which was more frequent with parasitemias >100,000 per μL and body temperatures ≥ 39°C. Apoptosis-related genes (Fas, BAX, and TP53) were upregulated acutely and for several days thereafter (days 1-3). In contrast, the expression of immune-modulatory (transcription factor 7, HLV-DOA, and CD6) and apoptosis inhibitory (c-myc, caspase 8, and Fas Ligand G) genes was downregulated initially and returned to normal with clinical recovery (days 7-10). These results indicate that the innate immune response, cytokine, and apoptosis pathways are upregulated acutely in uncomplicated malaria with concomitant downregulation of immune-modulatory and apoptosis inhibitory genes.
Juan Pablo Martínez
Full Text Available Introduction: Acute appendicitis is one of the main indications to abdominal surgery. When the appendicitis is not complicated, is possible to do an outpatient surgery. Objective: To describe postsurgical evolution of the patients who present uncomplicated acute appendicitis. Methods: A prospective study was carried out about the evolution of 100 patients with outpatient surgery for appendectomy by uncomplicated acute appendicitis. The study was performed in the Hospital Susana Lopez de Valencia (HSLV of Popayán, Colombia. A telephone survey was conducted during the 24 hours after surgery, to determinate potential complications like pain, nausea, vomiting and oral intolerance. Clinical histories were reviewed to determinate in case the patient has re-entered because of a possible post operative complication during 30 next days after surgical intervention. Histopathological findings were also reported. Results: During postsurgical follow up, 58% of the patients did not present any kind of pain, 95% tolerated oral route, 97% did not have vomiting and 90% did not have nausea. 3% re-entered because of type 1 infection around the surgical area, 4% because of pain. We found a histopathological concordance with the acute appendicitis diagnostic in 94% of the cases. All patients reported to be satisfied with the given attention in the postsurgery. Conclusions: Patients undergo appendectomy by uncomplicated acute appendicitis treated outpatient, has an appropriate tolerance to oral route and pain control.
Full Text Available Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in North Ethiopia. Methods. This prospective study was undertaken during August–November 2009 on 71 malaria patients that fulfilled the inclusion criteria set by the WHO. Patients were followed up for 28 days. Thick and thin blood films were prepared by Giemsa stain for microscopy to determine parasite density. A standard six-dose regimen of artemether-lumefantrine was administered over three days and was followed up with clinical and parasitological evaluations over 28 days. Results. The cure rate (ACPR was found to be high (97.2% in this study. The parasite and fever clearance time was also rapid. Artemether-lumefantrine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the study area showed 97.2% cure rate and only 2.8% failure rate. Conclusion. The result showed that the drug could continue as first line for the treatment of uncomplicated Plasmodium falciparum malaria in the study area. The efficacy of artemether-lumefantrine needs to be carefully monitored periodically in sentinel sites representing different areas of the country.
Isba, Rachel; Zani, Babalwa; Gathu, Michael; Sinclair, David
Background The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed as a one-day treatment. Although shorter treatment courses may improve adherence, the WHO recommends at least three days of the short-acting artemisinin component to eliminate 90% P. falciparum parasites in the bloodstream, before leaving the longer-acting partner drug to clear the remaining parasites. Objectives To evaluate the efficacy and safety of the artemisinin-naphthoquine combination for treating adults and children with uncomplicated P. falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; and LILACS up to January 2015. We also searched the metaRegister of Controlled Trials (mRCT) using 'malaria' and 'arte* OR dihydroarte*' as search terms. Selection criteria Randomized controlled trials comparing artemisinin-naphthoquine combinations with established WHO-recommended ACTs for the treatment of adults and children with uncomplicated malaria due to P. falciparum. Data collection and analysis Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. Main results Four trials, enrolling 740 adults and children, met the inclusion criteria. Artemisinin-naphthoquine was administered as a single dose (two
Kloprogge, Frank; Jullien, Vincent; Piola, Patrice; Dhorda, Mehul; Muwanga, Sulaiman; Nosten, François; Day, Nicholas P J; White, Nicholas J; Guerin, Philippe J; Tarning, Joel
Oral quinine is used for the treatment of uncomplicated malaria during pregnancy, but few pharmacokinetic data are available for this population. Previous studies have reported a substantial effect of malaria on the pharmacokinetics of quinine resulting from increased α-1-acid glycoprotein levels and decreased cytochrome P450 3A4 activity. The aim of this study was to investigate the pharmacokinetic properties of oral quinine in pregnant women with uncomplicated malaria in Uganda using a population approach. Data from 22 women in the second and third trimesters of pregnancy with uncomplicated Plasmodium falciparum malaria were analysed. Patients received quinine sulphate (10 mg of salt/kg) three times daily (0, 8 and 16 h) for 7 days. Plasma samples were collected daily and at frequent intervals after the first and last doses. A population pharmacokinetic model for quinine was developed accounting for different disposition, absorption, error and covariate models. Parasitaemia, as a time-varying covariate affecting relative bioavailability, and body temperature on admission as a covariate on elimination clearance, explained the higher exposure to quinine during acute malaria compared with the convalescent phase. Neither the estimated gestational age nor the trimester influenced the pharmacokinetic properties of quinine significantly. A population model was developed that adequately characterized quinine pharmacokinetics in pregnant Ugandan women with acute malaria. Quinine exposure was lower than previously reported in patients who were not pregnant. The measurement of free quinine concentration will be necessary to determine the therapeutic relevance of these observations. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Zani, Babalwa; Gathu, Michael; Donegan, Sarah; Olliaro, Piero L; Sinclair, David
Background The World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs. Objectives To evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013. Selection criteria Randomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria. Data collection and analysis Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy’ and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. Main results We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women. DHA-P versus artemether-lumefantrine In Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower
Full Text Available Abstract Background Artesunate (AS plus amodiaquine (AQ is one artemisinin-based combination (ACT recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested. Methods A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design and safety of fixed (F dose AS (25 mg/AQ (67.5 mg to loose (L AS (50 mg + AQ (153 mg in 750, P. falciparum-infected children from Burkina Faso aged 6 months to 5 years. Dosing was by age. Primary efficacy endpoint was Day (D 28, PCR-corrected, parasitological cure rate. Recipients of rescue treatment were counted as failures and new infections as cured. Documented, common toxicity criteria (CTC graded adverse events (AEs defined safety. Results Recruited and evaluable children numbered 750 (375/arm and 682 (90.9%, respectively. There were 8 (AS/AQ and 6 (AS+AQ early treatment failures and one D7 failure (AS+AQ. Sixteen (AS/AQ and 12 (AS+AQ patients had recurrent parasitaemia (PCR new infections 10 and 6, respectively. Fourteen patients per arm required rescue treatment for vomiting/spitting out study drugs. Efficacy rates were 92.1% in both arms: AS/AQ = 315/342 (95% CI: 88.7–94.7 vs. AS+AQ = 313/340 (95% CI: 88.6–94.7. Non-inferiority was demonstrated at two-sided α = 0.05: Δ (AS+AQ – AS/AQ = 0.0% (95% CI: -4.1% to 4.0%. D28, Kaplan Meier PCR-corrected cure rates (all randomized children were similar: 93.7% (AS/AQ vs. 93.2% (AS+AQ Δ = -0.5 (95% CI -4.2 to 3.0%. By D2, both arms had rapid parasite (F & L, 97.8% aparasitaemic and fever (97.2% [F], 96.0% [L] afebrile clearances. Both treatments were well tolerated. Drug-induced vomiting numbered 8/375 (2.1% and 6/375 (1.6% in the fixed and loose arms, respectively (p = 0.59. One patient developed asymptomatic, CTC grade 4 hepatitis (AST 1052, ALT 936. Technical difficulties precluded the assessment and risk of neutropaenia for all patients. Conclusion
Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria: a phase III, multicentric, open-label study.
Valecha, Neena; Savargaonkar, Deepali; Srivastava, Bina; Rao, B H Krishnamoorthy; Tripathi, Santanu K; Gogtay, Nithya; Kochar, Sanjay Kumar; Kumar, Nalli Babu Vijaya; Rajadhyaksha, Girish Chandra; Lakhani, Jitendra D; Solanki, Bhagirath B; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Anvikar, Anupkumar R
Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100% (140/140) in the FDC of arterolane maleate and PQP group, and 99.3% (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9% (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95% CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4% in the FDC of arterolane maleate and PQP group and 85.4% in the chloroquine group. Most of
King, Welfur C; Shuaib, Waqas; Vijayasarathi, Arvind; Fajardo, Carlos G; Cabrera, Waldo E; Costa, Juan L
Despite evidence demonstrating equivalent accuracy of sonography and computed tomography (CT) in the workup of mild/uncomplicated acute diverticulitis, CT is overwhelmingly performed as the initial diagnostic test, particularly in the acute setting. Our study evaluated potential radiation and turnaround time savings associated with performing sonography instead of CT as the initial diagnostic examination in the workup of suspected uncomplicated acute diverticulitis. We retrospectively reviewed medical records from January 2010 to December 2012 for patients presenting with clinical symptoms of acute diverticulitis. Patients were categorized as a whole and subgrouped by age (>40 and 40 years and 121 diverticulitis. © 2015 by the American Institute of Ultrasound in Medicine.
Hien, Tran Tinh; White, Nicholas J; Thuy-Nhien, Nguyen Thanh; Hoa, Nhu Thi; Thuan, Phung Duc; Tarning, Joel; Nosten, François; Magnusson, Baldur; Jain, Jay Prakash; Hamed, Kamal
The MIC of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle. To ensure the cure of malaria, the MIC must be exceeded until all parasites have been eliminated. The development of highly sensitive and accurate PCR quantitation of low-density malaria parasitemia enables the prospective pharmacokinetic-pharmacodynamic (PK-PD) characterization of antimalarial drug effects and now allows identification of the in vivo MIC. An adaptive design and a PK-PD modeling approach were used to determine prospectively the MIC of the new antimalarial cipargamin (KAE609) in adults with uncomplicated Plasmodium falciparum malaria in an open-label, dose-ranging phase 2a study. Vietnamese adults with acute P. falciparum malaria were allocated sequentially to treatment with a single 30-mg (n = 6), 20-mg (n = 5), 10-mg (n = 7), or 15-mg (n = 7) dose of cipargamin. Artemisinin-based combination therapy was given after parasite densities had fallen and then risen as cipargamin levels declined below the MIC but before a return of signs or symptoms. The rates of parasite clearance were dose dependent, with near saturation of the effect being seen at an adult dose of 30 mg. The developed PK-PD model accurately predicted the therapeutic responses in 23/25 patients. The predicted median in vivo MIC was 0.126 ng/ml (range, 0.038 to 0.803 ng/ml). Pharmacometric characterization of the relationship between antimalarial drug concentrations and parasite clearance rates following graded subtherapeutic antimalarial drug dosing is safe and provides a rational framework for dose finding in antimalarial drug development. (This study has been registered at ClinicalTrials.gov under identifier NCT01836458.). Copyright © 2017 Hien et al.
Hviid, L; Kurtzhals, J A; Goka, B Q
Frequencies and absolute numbers of peripheral T-cell subsets were monitored closely following acute Plasmodium falciparum malaria in 22 Ghanaian children from an area of hyperendemicity for seasonal malaria transmission. The children presented with cerebral or uncomplicated malaria (CM or UM......, respectively) or with severe malarial anemia. For all patients the frequencies and absolute numbers of peripheral T cells were lower than normal during the acute stage of disease. This lowering was most pronounced in the CM group and least pronounced in the UM group. Of particular interest, the CM patients...
Jackson, J D; Hammond, T
Acute uncomplicated diverticulitis is traditionally managed by inpatient admission for bowel rest, intravenous fluids and intravenous antibiotics. In recent years, an increasing number of publications have sought to determine whether care might instead be conducted in the community, with earlier enteral feeding and oral antibiotics. This systematic review evaluates the safety and efficacy of such an ambulatory approach. Medline, Embase and Cochrane Library databases were searched. All peer-reviewed studies that investigated the role of ambulatory treatment protocols for acute uncomplicated diverticulitis, either directly or indirectly, were eligible for inclusion. Nine studies were identified as being suitable for inclusion, including one randomised controlled trial, seven prospective cohort studies and one retrospective cohort study. All, except one, employed imaging as part of their diagnostic criteria. There was inconsistency between studies with regards to whether patients with significant co-morbidities were eligible for ambulatory care and whether bowel rest therapy was employed. Neither of these variables influenced outcome. Across all studies, 403 out of a total of 415 (97 %) participants were successfully treated for an episode of acute uncomplicated diverticulitis using an outpatient-type approach. Cost savings ranged from 35.0 to 83.0 %. Current evidence suggests that a more progressive, ambulatory-based approach to the majority of cases of acute uncomplicated diverticulitis is justified. Based on this evidence, the authors present a possible outpatient-based treatment algorithm. An appropriately powered randomised controlled trial is now required to determine its safety and efficacy compared to traditional inpatient management.
Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.
Toure, Offianan Andre; Rulisa, Stephen; Anvikar, Anupkumar R; Rao, Ballamudi S; Mishra, Pitabas; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Valecha, Neena
The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and
Full Text Available Acute hemorrhagic leukoencephalitis (AHLE, Hurst′s disease is a rare hyperacute variant of acute disseminated encephalomyelitis (ADEM characterized by severe, rapidly progressive clinical illness and hemorrhagic necrosis of white matter. Like ADEM, it is often preceded by viral illness or vaccination. Plasmodium vivax infection is usually uncomplicated and non-fatal with only a handful of reports of central nervous system complications. In this article, we report a previously unknown association between AHLE and P. vivax infection.
Ünlü, Çagdas; Gunadi, Patrick M.; Gerhards, Michael F.; Boermeester, Marja A.; Vrouenraets, Bart C.
Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment
Abdallah Tajeldin M
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the treatment of choice for uncomplicated Plasmodium falciparum malaria in most areas of the world, where malaria is endemic, including Sudan. However, few published data are available on the use of ACT for treatment of P. vivax malaria. Methods This study was conducted at a health centre in Kassala, eastern Sudan, from October to December 2011. Patients with uncomplicated P. vivax malaria received artemether-lumefantrine (AL tablets (containing 20mg artemether and 120 mg lumefantrine and were monitored for 28 days. Results Out of the 43 cases enrolled in this study, 38 completed the 28-day follow-up. Their mean age was 25.1 years (SD: 1.5. On day 3 following AL treatment, all of the patients were afebrile and aparasitaemic. By day 28, all 38 patients exhibited adequate clinical and parasitological responses to AL treatment. The cure rate was 100% and 88.4% for the per protocol analysis andfor the intention to treat analysis, respectively. Mild adverse effects (nausea, vomiting, abdominal pain, dizziness and/or rash that resolved spontaneously were observed in four (10.5% of the patients. Conclusion AL combination therapy was fully effective for treatment of P. vivax malaria in the study in eastern Sudan. Trial registration Trial. Gov: NCT01625871
Full Text Available Abstract Background Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria was assessed in Chumkiri, Kampot Province, Cambodia. Methods One hundred fifty-one subjects with uncomplicated falciparum malaria received directly observed therapy with 12 mg/kg artesunate (over three days and 25 mg/kg mefloquine, up to a maximum dose of 600 mg artesunate/1,000 mg mefloquine. One hundred nine subjects with uncomplicated vivax malaria received a total of 25 mg/kg chloroquine, up to a maximum dose of 1,500 mg, over three days. Subjects were followed for 42 days or until recurrent parasitaemia was observed. For P. falciparum infected subjects, PCR genotyping of msp1, msp2, and glurp was used to distinguish treatment failures from new infections. Treatment failure rates at days 28 and 42 were analyzed using both per protocol and Kaplan-Meier survival analysis. Real Time PCR was used to measure the copy number of the pfmdr1 gene and standard 48-hour isotopic hypoxanthine incorporation assays were used to measure IC50 for anti-malarial drugs. Results Among P. falciparum infected subjects, 47.0% were still parasitemic on day 2 and 11.3% on day 3. The PCR corrected treatment failure rates determined by survival analysis at 28 and 42 days were 13.1% and 18.8%, respectively. Treatment failure was associated with increased pfmdr1 copy number, higher initial parasitaemia, higher mefloquine IC50, and longer time to parasite clearance. One P. falciparum isolate, from a treatment failure, had markedly elevated IC50 for both mefloquine (130 nM and artesunate (6.7 nM. Among P. vivax infected subjects, 42.1% suffered recurrent P. vivax parasitaemia. None acquired new P. falciparum infection. Conclusion The results suggest that artesunate-mefloquine combination therapy is beginning to fail in southern
Rogers, William O; Sem, Rithy; Tero, Thong; Chim, Pheaktra; Lim, Pharath; Muth, Sinuon; Socheat, Duong; Ariey, Frédéric; Wongsrichanalai, Chansuda
Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria was assessed in Chumkiri, Kampot Province, Cambodia. One hundred fifty-one subjects with uncomplicated falciparum malaria received directly observed therapy with 12 mg/kg artesunate (over three days) and 25 mg/kg mefloquine, up to a maximum dose of 600 mg artesunate/1,000 mg mefloquine. One hundred nine subjects with uncomplicated vivax malaria received a total of 25 mg/kg chloroquine, up to a maximum dose of 1,500 mg, over three days. Subjects were followed for 42 days or until recurrent parasitaemia was observed. For P. falciparum infected subjects, PCR genotyping of msp1, msp2, and glurp was used to distinguish treatment failures from new infections. Treatment failure rates at days 28 and 42 were analyzed using both per protocol and Kaplan-Meier survival analysis. Real Time PCR was used to measure the copy number of the pfmdr1 gene and standard 48-hour isotopic hypoxanthine incorporation assays were used to measure IC50 for anti-malarial drugs. Among P. falciparum infected subjects, 47.0% were still parasitemic on day 2 and 11.3% on day 3. The PCR corrected treatment failure rates determined by survival analysis at 28 and 42 days were 13.1% and 18.8%, respectively. Treatment failure was associated with increased pfmdr1 copy number, higher initial parasitaemia, higher mefloquine IC50, and longer time to parasite clearance. One P. falciparum isolate, from a treatment failure, had markedly elevated IC50 for both mefloquine (130 nM) and artesunate (6.7 nM). Among P. vivax infected subjects, 42.1% suffered recurrent P. vivax parasitaemia. None acquired new P. falciparum infection. The results suggest that artesunate-mefloquine combination therapy is beginning to fail in southern Cambodia and that resistance is not confined to the provinces at
Full Text Available Stephan Ehrhardt, Christian G MeyerBernhard Nocht Institute for Tropical Medicine, Tropical Medicine Section, Hamburg, GermanyAbstract: The World Health Organization strongly recommends artemisinin-based combination therapy (ACT regimens for the treatment of uncomplicated Plasmodium falciparum malaria cases in endemic areas. Among the combinations of compounds that are available at present, excellent results have been obtained for the artemisinin derivative artemether, in a combination galenic preparation with lumefantrine (artemether–lumefantrine, AL. Here, the pharmacological properties and the therapeutic options of both substances are briefly reviewed and a cursory overview is given on recent trials that have compared the therapeutic effects of AL in the standard 6-dose regimen with other antimalarials and combinations. In order to ensure the most achievable and reliable adherence and compliance of children in the treatment of malaria, a dispersible formulation of AL is now attainable. Recent reports on the emergence of resistance to ACT regimens in Asia, however, are alarming.Keywords: artemether, lumefantrine, malaria, Plasmodium falciparum, dispersible formulation, treatment, therapy
Isanaka, Sheila; Langendorf, Céline; Berthé, Fatou; Gnegne, Smaila; Li, Nan; Ousmane, Nassirou; Harouna, Souley; Hassane, Hamidine; Schaefer, Myrto; Adehossi, Eric; Grais, Rebecca F
High-quality evidence supporting a community-based treatment protocol for children with severe acute malnutrition, including routine antibiotic use at admission to a nutritional treatment program, remains limited. In view of the costs and consequences of emerging resistance associated with routine antibiotic use, more evidence is required to support this practice. In a double-blind, placebo-controlled trial in Niger, we randomly assigned children who were 6 to 59 months of age and had uncomplicated severe acute malnutrition to receive amoxicillin or placebo for 7 days. The primary outcome was nutritional recovery at or before week 8. A total of 2412 children underwent randomization, and 2399 children were included in the analysis. Nutritional recovery occurred in 65.9% of children in the amoxicillin group (790 of 1199) and in 62.7% of children in the placebo group (752 of 1200). There was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs. placebo, 1.05; 95% confidence interval [CI], 0.99 to 1.12; P=0.10). In secondary analyses, amoxicillin decreased the risk of transfer to inpatient care by 14% (26.4% in the amoxicillin group vs. 30.7% in the placebo group; risk ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02). We found no benefit of routine antibiotic use with respect to nutritional recovery from uncomplicated severe acute malnutrition in Niger. In regions with adequate infrastructure for surveillance and management of complications, health care facilities could consider eliminating the routine use of antibiotics in protocols for the treatment of uncomplicated severe acute malnutrition. (Funded by Médecins sans Frontières Operational Center Paris; ClinicalTrials.gov number, NCT01613547.).
Huang, Chenxi; Alamili, Mahdi; Rosenberg, Jacob; Gögenur, Ismail
The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. Twelve patients with uncomplicated acute diverticulitis completed this observational study, which composed of 3 sessions of continuous HRV recording from 9 PM to 8 AM during ongoing diverticulitis and at complete remission (baseline). The blood samples were collected at each study session measuring C-reactive protein (CRP) and leukocytes. This study showed that the trajectories of the HRV indices were decreased both in time and frequency domains during acute diverticulitis compared to baseline. In particular, the indices reflecting the balance of sympathetic and parasympathetic activities were affected: standard deviation of normal-to-normal beats (P = .003), low-frequency power (P diverticulitis suggesting inflammatory involvement in the observed HRV alterations. We found substantial HRV depression in relation to acute uncomplicated diverticulitis, and this was associated with the elevated CRP levels. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Nilima A Kshirsagar,1 Nithya J Gogtay,1 Diego Moran,2 Gregory Utz,3 Ashok Sethia,4 Shirsendu Sarkar,5 Pol Vandenbroucke6 1Seth G S Medical College and KEM Hospital, Mumbai, India; 2Hospital San Andrés de Tumaco, Narino, Colombia; 3US Naval Medical Research Unit 6, Lima, Peru; 4Gita Bhawan Hospital and Research Centre, Indore, 5Pfizer, Mumbai, India; 6Pfizer, New York, NY, USA Background: To explore the use of azithromycin–chloroquine (AZCQ for the treatment of malaria, we conducted double-blind, randomized, non-inferiority studies in India, Colombia, and Suriname comparing the combination of azithromycin 1 g and chloroquine (CQ 600 mg base once daily (QD for 3 days versus atovaquone–proguanil (AP or chloroquine plus sulfadoxine–pyrimethamine (SPCQ in adults with acute uncomplicated Plasmodium falciparum malaria.Methods: Patients were hospitalized until three documented negative blood smears and followed through Day 42. The primary end point was parasitologic cure at Day 28.Results: In India, parasite clearance rates were 84% and 94% for AZCQ and SPCQ, respectively (95% confidence interval [CI] for the difference: –22.6, 0.8. In Colombia and Suriname, parasite clearance rates were 57% and 99% for AZCQ and AP, respectively (95% CI: –52, –32. A subsequent open-label, non-comparative third study using a 2 g dose of azithromycin and 600 mg of CQ in India and Colombia resulted in an overall efficacy rate of 97%.Conclusion: In India, Colombia, and Suriname, 1 g azithromycin with CQ QD for 3 days was inferior to established comparator agents. An improved response rate was observed when the dose of azithromycin was increased to 2 g. Keywords: acute, uncomplicated malaria, antimalarial, azithromycin, chloroquine, malaria, parasitologic cure rate, plasmodium
Lorente, Leyre; Cots, Francesc; Alonso, Sandra; Pascual, Marta; Salvans, Silvia; Courtier, Ricard; Gil, M José; Grande, Luis; Pera, Miguel
Outpatient treatment of uncomplicated acute diverticulitis is safe and effective. The aim of this study was to determine the impact of outpatient treatment on the reduction of healthcare costs. A retrospective cohort study comparing 2 groups was performed. In the outpatient treatment group, patients diagnosed with uncomplicated acute diverticulitis were treated with oral antibiotics at home. In the hospital treatment group, patients met the criteria for outpatient treatment but were admitted to hospital and received intravenous antibiotic therapy. Cost estimates have been made using the hospital cost accounting system based on total costs, the sum of all variable costs (direct costs) plus overhead expenses divided by activity (indirect costs). A total of 136 patients were included, 90 in the outpatient treatment group and 46 in the hospital group. There were no differences in the characteristics of the patients in both groups. There were also no differences in the treatment failure rate in both groups (5.5% vs. 4.3%; P=.7). The total cost per episode was significantly lower in the outpatient treatment group (882 ± 462 vs. 2.376 ± 830 euros; P=.0001). Outpatient treatment of acute diverticulitis is not only safe and effective but also reduces healthcare costs by more than 60%. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.
Huang, Chenxi; Alamili, Mahdi; Rosenberg, Jacob
BACKGROUND: The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. METHODS: Twelve patients with uncomplicated acute diverticulitis completed this observational study......, which composed of 3 sessions of continuous HRV recording from 9 PM to 8 AM during ongoing diverticulitis and at complete remission (baseline). The blood samples were collected at each study session measuring C-reactive protein (CRP) and leukocytes. RESULTS: This study showed that the trajectories...... of the HRV indices were decreased both in time and frequency domains during acute diverticulitis compared to baseline. In particular, the indices reflecting the balance of sympathetic and parasympathetic activities were affected: standard deviation of normal-to-normal beats (P = .003), low-frequency power (P...
Full Text Available Stephen GS Vreden,1 Rakesh D Bansie,2 Jeetendra K Jitan,3 Malti R Adhin4 1Foundation for Scientific Research Suriname (SWOS, 2Department of Internal Medicine, Academic Hospital Paramaribo, 3Department of Public Health, Ministry of Health, 4Department of Biochemistry, Anton de Kom University of Suriname, Paramaribo, Suriname Background: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life. Methods: The study was conducted in Paramaribo, the capital of Suriname, from July 2013 until July 2014. Patients with uncomplicated Plasmodium falciparum infection were included and received artesunate mono-therapy for three days. Day 3 parasitaemia, treatment outcome after 28 days and parasite half-life were determined. The latter was assessed with the parasite clearance estimator from the WorldWide Antimalarial Resistance Network (WWARN. Results: Thirty-nine patients were included from July 2013 until July 2014. The day 3 parasitemia was 10%. Eight patients (20.5% could be followed up until day 28 and showed adequate clinical and parasitological response. Parasite half-life could only be determined from ten data series (25.7%. The median parasite half-life was 5.16 hours, and seven of these data series had a half-life ≥5 hours, still comprising 17.9% of the total data series. Conclusion: The low follow-up rate and the limited analyzable data series preclude clear conclusions about the efficacy of artesunate monotherapy in Suriname and the parasite half
Full Text Available Abstract Background Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. Methods Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA were also performed to enable a comparison with literature values and different modeling strategies. Results The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug
Full Text Available Abstract Background Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS effects of both drug components and there are no detailed reports in very young children. Methods Children, aged between three months and five years, with acute uncomplicated Plasmodium falciparum malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28. Results From December 1994 to July 1997, 91 children with uncomplicated P. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033. Conclusion In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of
Lyke, Kirsten E; Burges, Robin B; Cissoko, Yacouba; Sangare, Lansana; Kone, Abdoulaye; Dao, Modibo; Diarra, Issa; Fernandez-Vina, Marcelo A; Plowe, Christopher V; Doumbo, Ogobara K; Sztein, Marcelo B
...) peripheral blood mononuclear cells collected from 774 Malian children, aged 3 months to 14 years, with severe Plasmodium falciparum malaria matched to uncomplicated malaria or healthy controls...
Full Text Available Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4(+ FOXP3(+ CD127(-/low; Tregs we compared cellular responses between Gambian children (n = 124 with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later. Thus, while Tregs may not regulate acute malarial inflammation, they may limit memory responses to levels that subsequently facilitate parasite clearance without causing immunopathology. Importantly, we identified a population of FOXP3(-, CD45RO(+ CD4(+ T cells which coproduce IL-10 and IFN-gamma. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulators of acute malarial inflammation.
Zamora, Felipe; Ramírez, Oscar; Vergara, Juana; Arévalo-Herrera, Myriam; Herrera, Sócrates
Prevalence of malaria-related anemia in disease-endemic regions of the American continents has been poorly studied. We describe the relationships between hemoglobin level and race, Plasmodium species, and days of illness in 150 Colombian patients with uncomplicated malaria diagnosed by thick blood smear. Hemoglobin was measured at admission and a standardized questionnaire was used to determine days of illness and other variables. Associations between hemoglobin and the variables were estimated and adjusted according to the other covariates using regression analysis. Plasmodium falciparum and P. vivax were found in similar proportions and mild anemia was present in 50% of the patients. Volunteers were classified as Afro-Colombians (61%) and non-Afro-Colombians (39%). An inverse relationship between hemoglobin and days of illness was identified, and a statistical interaction was found between race and P. falciparum infection in determining the hemoglobin concentration. These observations could guide the design of research to better understand malarial anemia.
Rodrigo Nunes Rodrigues-da-Silva
Full Text Available Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.
Eko, Frederick N; Ryb, Gabriel E; Drager, Leslie; Goldwater, Eva; Wu, Jacqueline J; Counihan, Timothy C
Early surgery for appendicitis is thought to avoid complications associated with appendiceal rupture. This study was to evaluate the effect of timing of surgery on complications, length of stay (LOS) and cost in patients undergoing appendectomy. Retrospective review of 396 patients with appendectomies from January 1, 2005 to December 31, 2007 was performed. Demographic data, time of presentation, physical findings, diagnostic data, operating room times, LOS, cost and complications were collected. Patients were divided into 4 groups based on time from presentation to appendectomy. Pathology confirmed appendicitis in 354 (89%) patients. Most patients (90%) had surgery within 18 h of presentation. Timing of surgery did not affect the incidence of purulent peritonitis (P = 0.883), abscess (P = 0.841) or perforation (P = 0.464). LOS was significantly shorter for patients with emergency department registration to operating room times less than 18 h (P < 0.0001). Costs were significantly higher for patients with times to operating room greater than 18 h (P < 0.001). Timing of surgery did not affect the incidence of complications or perforated appendicitis. However, delay in surgical consultation and surgery are associated with increased LOS and increased hospital costs. The optimal timing of appendectomy for uncomplicated acute appendicitis appears to be within 18 h of emergency department presentation.
Mwaiswelo, Richard; Ngasala, Billy; Gil, J Pedro; Malmberg, Maja; Jovel, Irina; Xu, Weiping; Premji, Zul; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas
We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. Patients with acute uncomplicated P. falciparum malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007-2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012-2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2-100), 122/127 (96.1%) (95% CI, 92.6-99.5), and 206/207 (99.5%) (95% CI, 98.6-100) in 2007-2008, 2012-2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ2trend test = 0.06, P = 0.90). Pretreatment P. falciparum multidrug-resistant gene 1 (Pfmdr1) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (P cure rate remained high after 8 years of its wide-scale use in Bagamoyo district for the treatment of uncomplicated P. falciparum malaria despite an increase in prevalence of pretreatment Pfmdr1 N86 and Pfcrt K76 between 2006 and 2014.
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the in vivo efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam®, Mephaquin®, and Mefloquina-AC® Farma given in combination with artesunate. Methods Thirty-nine non-pregnant adults with P. falciparum mono-infection were randomly assigned to receive artesunate in combination with either (1 Lariam, (2 Mephaquin, or (3 Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours, 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol. Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data. Results By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14–15 days and time to maximum plasma concentration of 45–52 hours. The maximal concentration (Cmax and interquartile range was 2,820 ng
Kloprogge, Frank; Jullien, Vincent; Piola, Patrice; Dhorda, Mehul; Muwanga, Sulaiman; Nosten, François; Day, Nicholas P. J.; White, Nicholas J; Philippe J Guerin; Tarning, Joel
Objectives Oral quinine is used for the treatment of uncomplicated malaria during pregnancy, but few pharmacokinetic data are available for this population. Previous studies have reported a substantial effect of malaria on the pharmacokinetics of quinine resulting from increased α-1-acid glycoprotein levels and decreased cytochrome P450 3A4 activity. The aim of this study was to investigate the pharmacokinetic properties of oral quinine in pregnant women with uncomplicated malaria in Uganda u...
Grigoryan, Larissa; Zoorob, Roger; Shah, Jesal; Wang, Haijun; Arya, Monisha; Trautner, Barbara W
Reducing inappropriate antibiotic prescribing is currently a global health priority. Current guidelines recommend against antibiotic treatment for acute uncomplicated bronchitis. We studied antibiotic prescribing patterns for uncomplicated acute bronchitis and identified predictors of inappropriate antibiotic prescribing. We used the Epic Clarity database (electronic medical record system) to identify all adult patients with acute bronchitis in family medicine clinics from 2011 to 2016. We excluded factors that could justify antibiotic use, such as suspected pneumonia, COPD or immunocompromising conditions. Of the 3616 visits for uncomplicated acute bronchitis, 2244 (62.1%) resulted in antibiotic treatment. The rates of antibiotic prescribing were similar across the years, p value for trend = 0.07. Antibiotics were most frequently prescribed in the age group of 18-39 years (66.9%), followed by the age group of 65 years and above (59.0%), and the age group of 40-64 years (58.7%), p value acute bronchitis, particularly in younger adults.
A. D. Kaprin
Full Text Available Abstract:Acute pyelonephritis is one of the common diseases both in outpatient and in the hospital practice. The leading causative agent of this disease is E. coli. Obstructive uropathy, foreign body, vesicoureteral reflux, sexual activity, use of local contraceptives contribute to the upward development of urinary infection. The goals of antimicrobial therapy for acute uncomplicated pyelonephritis are: relief of symptoms, restoration of social activity, prevention of complications and relapse prevention. The choice of an antimicrobial agent in most cases is carried out empirically based on the data on the dominant pathogens and their regional resistance. In acute uncomplicated pyelonephritis duration of antimicrobial therapy should be 7–14 days. The drugs of choice for treatment of acute uncomplicated pyelonephritis non-severe in adults are ciprofloxacin and levofloxacin, ceftibuten and cefixime. Patients with acute uncomplicated pyelonephritis severe emergency hospitalization is shown in urological outpatient and parenteral antimicrobial therapy (carbapenems or protected aminopenicillins combined with or without amikacin with subsequent conversion to oral drugs and infusion therapy.
Ridgway, P F
Despite the high prevalence of hospitalization for left iliac fossa tenderness, there is a striking lack of randomized data available to guide therapy. The authors hypothesize that an oral antibiotic and fluids are not inferior to intravenous (IV) antibiotics and \\'bowel rest\\' in clinically diagnosed acute uncomplicated diverticulitis.
Elhassan, I M; Hviid, L; Satti, G
To explain the observation that acute Plasmodium falciparum malaria is associated with a transient inability of peripheral blood cells to respond to antigenic stimulation in vitro, we have postulated the disease-induced reallocation of peripheral lymphocytes, possibly by adhesion to inflamed...... with the control donors. In addition, we found a disease-induced depletion of T cells with high expression of the LFA-1 antigen, particularly in the CD4+ subset. The results obtained provide further support for the hypothesis of T cell reallocation to inflamed endothelium in acute P. falciparum malaria....
Teklemariam, Michael; Assefa, Ashenafi; Kassa, Moges; Mohammed, Hussien; Mamo, Hassen
Malaria, particularly due to Plasmodium falciparum, remains a major public health threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line antimalarial drug against uncomplicated P. falciparum malaria in the country since 2004. Regular monitoring of antimalarial drugs is recommended by the World Health Organization (WHO) to help early detection of drug resistant strains of the parasite and contain their rapid spread. The objective of this study was to assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia. The study site was Setit Humera, northwest Ethiopia. Single-arm prospective study of a 28-day follow-up was conducted from October 2014 to January 2015 according to the revised WHO 2009 drug efficacy study protocol. Study end-points were classified into primary end-point and secondary end-point. While the primary end-point was the day-28 adequate clinical and parasitological response the secondary end-points were clinical and parasitological evaluations (parasite, fever and gametocyte clearance rate, incidence of drug adverse events) and the relative increment in hemoglobin (Hb) level from baseline to day (D) 14 and D28. A total of 92 patients were enrolled and 79 had completed the 28-day follow-up period. The overall cure rate was 98.8% with 95% confidence interval of 0.915-0.998 without polymerase chain reaction correction. The parasite clearance rate was high with fast resolution of clinical symptoms; 100% of the study participants cleared parasitaemia and fever on D3. Gametocyte carriage was reduced from 7% on D0 to 1% on D3 and complete clearance was achieved on D14. Mean Hb concentration significantly increased on D28 compared to that on D14. There was no serious adverse event. AL was efficacious and safe in a high-transmission setting for treatment of uncomplicated falciparum malaria.
Full Text Available Abstract Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO recommends artemisinin-based combination therapy (ACT to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the
Brochmann, N D; Schultz, J K; Jakobsen, G S; Øresland, T
This study aimed to evaluate the implementation of nonantibiotic management of acute uncomplicated diverticulitis at a large university hospital in Norway with regard to management failure, disease recurrence and complications. On 1 January 2013 we implemented a new policy for the management of acute uncomplicated diverticulitis without antibiotics. Antibiotic treatment was only provided in the case of defined criteria. All patients admitted from 1 January 2013 to 30 June 2014 with a CT-verified, left-sided, acute uncomplicated diverticulitis were included in the study and evaluated retrospectively, with 12 months' follow-up. Of 244 admissions with acute uncomplicated diverticulitis, 177 (73%) were managed without antibiotics. Among these there were seven (4%) management failures, including five patients in whom a deteriorating clinical picture prompted antibiotic treatment and two readmissions within 1 month due to persisting symptoms. The only complication in this group was one fistula (diverticulitis requiring hospital care and two (1%) underwent elective surgery within the first year. Twenty (8%) patients met predefined exemption criteria and received antibiotics from admission, six (30%) of whom developed complications. The recurrence rate in this group was 10% and none had surgery performed. The 47 (20%) policy violators treated with antibiotics from admission had no complications. Their recurrence rate was 11% and one (2%) patient underwent elective surgery. This study confirms that nonantibiotic management of acute uncomplicated diverticulitis is safe and feasible. Most complications occurred in a small group of high-risk patients treated with antibiotics. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.
Full Text Available Festus I Aghedo,1 Resqua A Shehu,2 Rabiu A Umar,2 Mohammed N Jiya,3 Osaro Erhabor4 1Department of Haematology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria; 2Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria; 3Department of Paediatrics, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria; 4Department of Haematology, Faculty of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria Objective: To assess antioxidant vitamin levels among preschool children with plasmodium malarial infection. Methods: We assessed antioxidant vitamin levels by using a standard procedure in 130 malaria-parasitized preschool children. Packed cell volume and parasite density were also evaluated. Forty healthy age- and gender-matched nonparasitized children were included as controls. Results: Plasmodium falciparum was the causative species in all subjects. The mean malaria parasitemia was 4529.45 ± 1237.5/µL. The mean antioxidant concentrations for vitamins A, C, and E among plasmodium-parasitized subjects were 33.15 ± 1.79 µg/dL, 0.51 ± 0.02 mg/dL, and 0.61 ± 0.02 mg/dL, respectively. The mean concentrations of vitamins A, C, and E among the non-malaria-parasitized controls were 69.72 ± 1.71 µg/dL, 1.25 ± 0.04 mg/dL, and 1.31 ± 0.04 mg/dL respectively. We observed that the mean antioxidant concentrations of vitamins A, C, and E were significantly lower among plasmodium-parasitized subjects compared with non-parasitized controls (P = 0.01. Malaria parasitemia correlated negatively with antioxidant concentrations and packed cell volume (r = -0.736 and -0.723, P = 0.001. We observed that the higher the level of parasitemia, the lower the antioxidant concentration. Conclusion: Our study has shown that the antioxidant levels in plasmodium-parasitized children in the North-West of Nigeria are low and that the more severe the malarial infection, the lower the antioxidant level and the
A. D. Kaprin; A. A. Kostin; S. V. Popov
Abstract:Acute pyelonephritis is one of the common diseases both in outpatient and in the hospital practice. The leading causative agent of this disease is E. coli. Obstructive uropathy, foreign body, vesicoureteral reflux, sexual activity, use of local contraceptives contribute to the upward development of urinary infection. The goals of antimicrobial therapy for acute uncomplicated pyelonephritis are: relief of symptoms, restoration of social activity, prevention of complications and relaps...
de Oliveira, Alexandre Macedo; Chavez, Jorge; de Leon, Gabriel Ponce; Durand, Salomon; Arrospide, Nancy; Roberts, Jacquelin; Cabezas, Cesar; Marquiño, Wilmer
We evaluated the efficacy and effectiveness of mefloquine (MQ) plus artesunate (AS) to treat patients with uncomplicated malaria in the Peruvian Amazon Basin in April 2005–March 2006. Patients ≥ 1 year of age with fever (axillary temperature ≥ 37.5°C) or history of fever and Plasmodium falciparum monoinfection were included. Patients received antimalarial treatment with MQ (12.5 mg/kg/day for two days) and AS (4.0 mg/kg/day for three days) either by directly observed therapy or without directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed on the basis of clinical and parasitologic outcomes. Ninety-six patients were enrolled in each study group; nine patients were lost to follow-up. All patients, except for one in the observed group, demonstrated adequate clinical and parasitologic response; none had detectable parasitemia on day 3. The efficacy of MQ + AS efficacy was 98.9% (95% confidence interval = 94.1–100.0%) and the effectiveness was 100.0% (95% confidence interval = 95.9–100.0%). Our study shows that MQ + AS is highly efficacious in the Peruvian Amazon. PMID:21896825
Okech, Bernard A.; Existe, Alexandre; Romain, Jean R.; Memnon, Gladys; Victor, Yves Saint; de Rochars, Madsen Beau; Fukuda, Mark
Chloroquine (CQ) has been used for malaria treatment in Haiti for several decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a 42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was seasonal, with peak observations between October and January; 88% (107 of 121) of patients consented to participate. Sixty patients successfully completed the 42-day follow-up, whereas 47 patients withdrew consent or were lost to follow-up. The mean parasite density declined rapidly within the first few days after treatment. Seven patients did not clear their malaria infections and were clinically asymptomatic; therefore, they were considered late parasitological failures. About 90% (95% confidence interval = 84.20–97.90) of patients had no detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for recrudescence, reinfection, and CQ serum levels was not done in the seven patients, and therefore, their CQ resistance status is unresolved. CQ resistance surveillance by patient follow-up, in vitro drug sensitivity studies, and molecular markers is urgently needed in Haiti. PMID:25601993
Abba, Katharine; Kirkham, Amanda J; Olliaro, Piero L; Deeks, Jonathan J; Donegan, Sarah; Garner, Paul; Takwoingi, Yemisi
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
Chuang, Shu-Hung; Chen, Pai-Hsi; Chang, Chih-Ming; Lin, Chih-Sheng
To compare the clinical outcome of single-incision laparoscopic cholecystectomy (SILC) and three-incision laparoscopic cholecystectomy (3ILC) for acute cholecystitis. From July 2009 to September 2012, 136 patients underwent SILC or 3ILC for acute cholecystitis at a tertiary referral hospital. One experienced surgeon performed every procedure using 5 or 10 mm 30-degree laparoscopes, straight instruments, and conventional ports. Five patients with perforated gallbladder and diffuse peritonitis and 23 patients with mild acute cholecystitis were excluded. The remaining 108 patients were divided into complicated and uncomplicated groups according to pathologic findings. Patient demography, clinical data, operative results and complications were recorded and analyzed. Fifty patients with gangrenous cholecystitis, gallbladder empyema, or hydrops were classified as the complicated group, and 58 patients with acute cholecystitis were classified as the uncomplicated group. Twenty-three (46.0%) of the patients in the complicated group (n = 50) and 39 (67.2%) of the patients in the uncomplicated group (n = 58) underwent SILC; all others underwent 3ILC. The postoperative length of hospital stay (PLOS) was significantly shorter in the SILC subgroups than the 3ILC subgroups (3.5 ± 1.1 d vs 4.6 ± 1.3 d, P acute cholecystitis. The main benefit is a faster recovery than that achieved with 3ILC.
Full Text Available To date no comparative trials have been done, to our knowledge, of fixed-dose artemisinin combination therapies (ACTs for the treatment of Plasmodium falciparum malaria in pregnancy. Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world. The objective of this study was to compare the efficacy, tolerability, and safety of artemether-lumefantrine, the most widely used fixed ACT, with 7 d artesunate monotherapy in the second and third trimesters of pregnancy.An open-label randomised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d (AL or artesunate monotherapy 7 d (AS7 was conducted in Karen women in the border area of northwestern Thailand who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy. The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery, as estimated by Kaplan-Meier survival analysis. Infants were assessed at birth and followed until 1 y of life. Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy. Both regimens were very well tolerated. The cure rates (95% confidence interval for the intention to treat (ITT population were: AS7 89.2% (82.3%-96.1% and AL 82.0% (74.8%-89.3%, p = 0.054 (ITT; and AS7 89.7% (82.6%-96.8% and AL 81.2% (73.6%-88.8%, p = 0.031 (per-protocol population. One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up. Birth outcomes and infant (up to age 1 y outcomes did not differ significantly between the two groups. The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL.The current standard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with
Hoglund Richard M
Full Text Available Abstract Background Pregnancy is associated with an increased risk of developing a malaria infection and a higher risk of developing severe malaria. The pharmacokinetic properties of many anti-malarials are also altered during pregnancy, often resulting in a decreased drug exposure. Piperaquine is a promising anti-malarial partner drug used in a fixed-dose combination with dihydroartemisinin. The aim of this study was to investigate the population pharmacokinetics of piperaquine in pregnant and non-pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria. Method Symptomatic patients received a standard dose regimen of the fixed dose oral piperaquine-dihydroartemisinin combination treatment. Densely sampled plasma aliquots were collected and analysed using a previously described LC-MS/MS method. Data from 12 pregnant and 12 non-pregnant women were analysed using nonlinear mixed-effects modelling. A Monte Carlo Mapped Power (MCMP analysis was conducted based on a previously published study to evaluate the power of detecting covariates in this relatively small study. Results A three-compartment disposition model with a transit-absorption model described the observed data well. Body weight was added as an allometric function on all clearance and volume parameters. A statistically significant decrease in estimated terminal piperaquine half-life in pregnant compared with non-pregnant women was found, but there were no differences in post-hoc estimates of total piperaquine exposure. The MCMP analysis indicated a minimum of 13 pregnant and 13 non-pregnant women were required to identify pregnancy as a covariate on relevant pharmacokinetic parameters (80% power and p=0.05. Pregnancy was, therefore, evaluated as a categorical and continuous covariate (i.e. estimate gestational age in a full covariate approach. Using this approach pregnancy was not associated with any major change in piperaquine elimination clearance. However, a trend of
Teja-Isavadharm, Paktiya; Siriyanonda, Duangsuda; Rasameesoraj, Maneerat; Limsalakpeth, Amporn; Chanarat, Nitima; Komcharoen, Natthasorn; Weina, Peter J; Saunders, David L; Gettayacamin, Montip; Scott Miller, R
The US Army designed artelinate/lysine salt (AL) to overcome the instability of sodium artesunate in aqueous solution (AS). To select the most efficacious artemisinin treatment, direct comparison was performed in an uncomplicated non-human primate malaria model. Splenectomized rhesus monkeys were inoculated with Plasmodium coatneyi and on day six, single equimolar loading dose of IV AL (11.8 mg kg(-1)) or IV AS (8 mg kg(-1)) were administered followed by 1/2 the first dose once daily for 2 more days. Blood smear were performed twice daily and the number of parasites were counted microscopically. Blood samples were obtained after the first dose within 6 h for pharmacokinetic (PK) and ex vivo pharmacodynamic evaluation by simultaneously measuring plasma drug concentration and anti-malarial activity against Plasmodium falciparum in vitro. The anti-P. coatneyi in vivo activity of both compounds were comparable, but the ex vivo anti-P. falciparum potency of the IV AS regimen as administered was sevenfold higher than that of IV AL. Comparing in vivo pharmacodynamics of AL and AS, daily assessed parasite counts showed comparable 99 % parasite clearance times (PC99: 2.03, 1.84 day), parasite clearance rates (5.34, 4.13 per min) and clearance half-life (PCt1/2: 7.79, 10.1 h). This study showed strong and significant inverse correlation between PCt1/2 and t1/2 of AS + DHA, and AUC0-∞ of DHA, and correlated with Vz of AS (r(2) > 0.7, p ≤ 0.002). Lastly, following IV AL, there was a modest inverse correlation between PCt1/2 and Cmax (r(2) 0.6, p ≤ 0.04). Although all tested monkeys recrudesced subsequently, two died following AL regimen before parasite clearance. While the aetiology of those deaths could not be definitively determined, pathologic evidence favoured a sepsis-like syndrome and suggested that severe malaria was more likely than drug toxicity. The model demonstrated that both AS and DHA contributed to the anti-malarial activity of IV AS, while
Full Text Available The article is dedicated to the problem of acute rhinosinusitis in children. It contains data from our own research upon hypertonic solution efficacy and suitability in complex therapy of rhinosinusitis. It was shown that inclusion of hypertonic solution of sea water spray into treatment scheme of acute rhinosinusitis allows to reach amelioration of nasal functions and patient’s well being in short term, reduces total duration of the disease, thus decresing the risk of complications development. Key words: rhinosinusitis, treatment, childhood, hypertonic solution, sea water. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 124–129.
Klein Klouwenberg, Peter; Sasi, Philip; Bashraheil, Mahfudh; Awuondo, Ken; Bonten, Marc; Berkley, James; Marsh, Kevin; Borrmann, Steffen
In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV) infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists. We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period. Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1) infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50) infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively), largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation. The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.
Etherington, J. M.
Alcohol-related problems are common among patients in emergency departments. Primary care physicians must recognize and treat a variety of alcohol-related and alcohol-induced problems: alcohol withdrawal, alcohol-related seizures, delirium tremens, malnutrition, concomitant illness, poisoning, trauma, and lack of social support. This paper focuses an recognizing and managing acute alcohol withdrawal.
Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Li, Yuan; Zhou, Zongguang
Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a
Purkait, Radheshyam; Mukherji, Aritra; Sinhamahapatra, Tapankumar; Bhadra, Ramchandra
Acute Disseminated Encephalomyelitis (ADEM) is a multifocal, monophasic, acute demyelinating disease of the brain and spinal cord, which is commonly preceded by viral infections and occasionally bacterial infections or immunizations. Its occurrence following malarial infection, especially Plasmodium vivax Malaria is very uncommon. We report an 11-year girl who presented with clinical features of encephalopathy and generalized convulsions, 10 days following complete recovery from the Plasmodium vivax Malaria. Diagnosis of ADEM as a complication of Plasmodium vivax Malaria was made based on acute onset of neurological events, characteristic findings on Magnetic Resonance Imaging (MRI) of brain and prompt response to corticosteroid therapy. Follow-up MRI, 6 months after discharge, showed complete resolution of change found on the initial MRI. To the best of our knowledge, only two such cases have been reported in the English literature till date.
Delgado Vicente, Miriam; Lecaroz Agara, Mª Concepción; Barrios Andrés, José Luis; Canut Blasco, Andrés
To assess process-of-care indicators and outcomes in acute pyelonephritis (APN) in a general hospital emergency department, and compare them between uncomplicaed and complicated APN. Retrospective study of consecutive patients discharged with a diagnosis of APN. We studied health processof- care indicators (percentage admitted, avoidable hospitalization, appropriate initial antibiotic therapy, urine and blood cultures) and outcomes (hospital length of stay [LOS], discharge from the emergency department, revisits, mortality, yields of microbiological tests ordered). A total of 529 cases (59% of them complicated) were included. Patients with uncomplicated APN were significantly younger on average (mean, 39 years) than patients with complicated APN (56 years). Escherichia coli was the most common pathogen identified, although the percentage of E coli infection was lower in patients with complicated APN (78%) than in patients with uncomplicated APN (95%). The rates of admission and orders for urine and blood cultures were significantly higher and hospital LOS was longer in the group with complicated APN. Moreover, these patients had even longer stays if the initial antibiotic therapy was inappropriate. Significantly more patients with uncomplicated APN were discharged from the emergency department. Sixty-one percent of patients with uncomplicated APN were admitted; 9% of these cases were considered avoidable hospitalizations. Complicated APN is diagnosed more often in older patients, and E coli infection causes a smaller proportion of these cases. Hospital LOS is longer in complicated APN and more urine and blood cultures are ordered. Patients with uncomplicated APN are more often discharged from the emergency department, although the number of avoidable hospitalizations seems high based on the rate found in this study.
Taylor Walter RJ
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is being widely promoted as a strategy to counteract the increase in Plasmodium falciparum antimalarial drug resistance. Methods A randomized, double-blind, placebo-controlled, clinical trial of the efficacy, effect on gametocytes and safety of the addition of artesunate/placebo (4 mg/kg/day × 3 d to amodiaquine (10 mg/kg/day × 3 d was conducted in Choco department, a low intensity transmission area in northwest Colombia. Results From 2,137 screened subjects, 85 entered the study: 43 in the amodiaquine plus placebo and 42 in the amodiaquine plus artesunate groups. Potentially eligible cases failed to qualify mostly because they were not available for follow-up visits (73%. Based on a per protocol analysis, the therapeutic response to both treatments was high: amodiaquine/placebo 35/36, 97.2% (95% CI 85.5–99.9, and amodiaquine/artesunate 32/32, 100% (89.1–100 after PCR genotyping. The Kaplan-Meier survival estimates based on all eligible patients enrolled (amodiaquine/placebo: n = 42; amodiaquine/artesunate: n = 41 were similar in the two study groups (P = 0.3. The addition of artesunate significantly decreased gametocyte carriage on Day 4 (OR = 0.1 95% CI 0.02–0.6, Day 7 (OR = 0.2 95%CI 0.04–0.9, Day 14 (OR = 0.09 95% CI 0–0.8, and Day 21 (OR95%CI 0–0.9. Most subjects in both groups (81% in amodiaquine/placebo and 75.6% in amodiaquine/artesunate reported at least one drug related adverse event. Symptoms were generally mild and self-limiting and there was no serious adverse event. Two patients on amodiaquine/artesunate voluntarily withdrew from study because they could not tolerate the medication. Conclusion Both drug regimens were effective in this area of Colombia. The addition of artesunate reduced gametocyte carriage and did not adversely affect tolerability. In this set of patients, the rate of adverse events was higher than in other studies. Patients' follow-up is
Osorio, Lyda; Gonzalez, Iveth; Olliaro, Piero; Taylor, Walter R J
Artemisinin-based combination therapy (ACT) is being widely promoted as a strategy to counteract the increase in Plasmodium falciparum antimalarial drug resistance. A randomized, double-blind, placebo-controlled, clinical trial of the efficacy, effect on gametocytes and safety of the addition of artesunate/placebo (4 mg/kg/day x 3 d) to amodiaquine (10 mg/kg/day x 3 d) was conducted in Choco department, a low intensity transmission area in northwest Colombia. From 2,137 screened subjects, 85 entered the study: 43 in the amodiaquine plus placebo and 42 in the amodiaquine plus artesunate groups. Potentially eligible cases failed to qualify mostly because they were not available for follow-up visits (73%). Based on a per protocol analysis, the therapeutic response to both treatments was high: amodiaquine/placebo 35/36, 97.2% (95% CI 85.5-99.9), and amodiaquine/artesunate 32/32, 100% (89.1-100) after PCR genotyping. The Kaplan-Meier survival estimates based on all eligible patients enrolled (amodiaquine/placebo: n = 42; amodiaquine/artesunate: n = 41) were similar in the two study groups (P = 0.3). The addition of artesunate significantly decreased gametocyte carriage on Day 4 (OR = 0.1 95% CI 0.02-0.6), Day 7 (OR = 0.2 95%CI 0.04-0.9), Day 14 (OR = 0.09 95% CI 0-0.8), and Day 21 (OR95%CI 0-0.9). Most subjects in both groups (81% in amodiaquine/placebo and 75.6% in amodiaquine/artesunate) reported at least one drug related adverse event. Symptoms were generally mild and self-limiting and there was no serious adverse event. Two patients on amodiaquine/artesunate voluntarily withdrew from study because they could not tolerate the medication. Both drug regimens were effective in this area of Colombia. The addition of artesunate reduced gametocyte carriage and did not adversely affect tolerability. In this set of patients, the rate of adverse events was higher than in other studies. Patients' follow-up is problematic in areas with dispersed population and affects the
Boermeester, Marja A; Humes, David J; Velmahos, George C; Søreide, Kjetil
Acute colonic diverticulitis is a common clinical condition. Severity of the disease is based on clinical, laboratory, and radiological investigations and dictates the need for medical or surgical intervention. Recent clinical trials have improved the understanding of the natural history of the disease resulting in new approaches to and better evidence for the management of acute diverticulitis. We searched the Cochrane Library (years 2004-2015), MEDLINE (years 2004-2015), and EMBASE (years 2004-2015) databases. We used the search terms "diverticulitis, colonic" or "acute diverticulitis" or "divertic*" in combination with the terms "management," "antibiotics," "non-operative," or "surgery." Registers for clinical trials (such as the WHO registry and the https://clinicaltrials.gov/ ) were searched for ongoing, recruiting, or closed trials not yet published. Antibiotic treatment can be avoided in simple, non-complicated diverticulitis and outpatient management is safe. The management of complicated disease, ranging from a localized abscess to perforation with diffuse peritonitis, has changed towards either percutaneous or minimally invasive approaches in selected cases. The role of laparoscopic lavage without resection in perforated non-fecal diverticulitis is still debated; however, recent evidence from two randomised controlled trials has found a higher re-intervention in this group of patients. A shift in management has occurred towards conservative management in acute uncomplicated disease. Those with uncomplicated acute diverticulitis may be treated without antibiotics. For complicated diverticulitis with purulent peritonitis, the use of peritoneal lavage appears to be non-superior to resection.
Leang, Rithea; Canavati, Sara E; Khim, Nimol; Vestergaard, Lasse S; Borghini Fuhrer, Isabelle; Kim, Saorin; Denis, Mey Bouth; Heng, Pisal; Tol, Bunkea; Huy, Rekol; Duparc, Stephan; Dondorp, Arjen M; Menard, Didier; Ringwald, Pascal
Pyronaridine-artesunate efficacy for the treatment of uncomplicated Plasmodium falciparum malaria was assessed in an area of artemisinin resistance in western Cambodia. This nonrandomized, single-arm, observational study was conducted between 2014 and 2015. Eligible patients were adults or children with microscopically confirmed P. falciparum infection and fever. Patients received pyronaridine-artesunate once daily for 3 days, dosed according to body weight. The primary outcome was an adequate clinical and parasitological response (ACPR) on day 42, estimated by using Kaplan-Meier analysis, PCR adjusted to exclude reinfection. One hundred twenty-three patients were enrolled. Day 42 PCR-crude ACPRs were 87.2% (95% confidence interval [CI], 79.7 to 92.6%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 82.1% (95% CI, 68.4 to 90.2%) for Pailin. Day 42 PCR-adjusted ACPRs were 87.9% (95% CI, 80.6 to 93.2%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 84.0% (95% CI, 70.6 to 91.7%) for Pailin (P = 0.353 by a log rank test). Day 28 PCR-crude and -adjusted ACPRs were 93.2% (95% CI, 82.9 to 97.4%) and 88.1% (95% CI, 75.3 to 94.5%) for Pursat and Pailin, respectively. A significantly lower proportion of patients achieved day 3 parasite clearance in Pailin (56.4% [95% CI, 43.9 to 69.6%]) than in Pursat (86.7% [95% CI, 76.8 to 93.8%]; P = 0.0019). Fever clearance was also extended at Pailin versus Pursat (P life (90%) for first-line treatment of P. falciparum malaria in western Cambodia despite high efficacy elsewhere in Asia and Africa. (This study has been registered at ClinicalTrials.gov under registration number NCT02389439.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Daniels, L.; Unlu, C.; Korte, N. de; Dieren, S. van; Stockmann, H.B.; Vrouenraets, B.C.; Consten, E.C.; Hoeven, J.A. van der; Eijsbouts, Q.A.; Faneyte, I.F.; Bemelman, W.A.; Dijkgraaf, M.G.; Boermeester, M.A.; Reuver, P.R.; et al.,
BACKGROUND: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis. METHODS: Patients with
Full Text Available Abstract Background Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum. Objective The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia. Methods Between 2005 and 2006, 304 children (6-59 months old with uncomplicated P. falciparum were enrolled, randomized to AL (101 or DHA/PQP (203 and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Recurrent infections were genotyped to distinguish between recrudescence and new infection. Results No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p Conclusion DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia. Trial Registration ISRCTN16263443, at http://www.controlled-trials.com/isrctn
Daniel G Wootton
Full Text Available The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS for the treatment of uncomplicated falciparum malaria.Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years and 107 children (median age 38 months with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP population using mean time to reduce baseline parasitemia by 90% (PC90. A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT population.In the Day 3 PP population for the adult group (N = 85, mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5], 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2] and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2] groups. For children in the Day 3 PP population (N = 92, mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0], though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0] and 12.8 h (-7.4 h [95%CI -12.9, -1.8], respectively. An analysis of mean time
Wootton, Daniel G.; Opara, Hyginus; Biagini, Giancarlo A.; Kanjala, Maxwell K.; Duparc, Stephan; Kirby, Paula L.; Woessner, Mary; Neate, Colin; Nyirenda, Maggie; Blencowe, Hannah; Dube-Mbeye, Queen; Kanyok, Thomas; Ward, Stephen; Molyneux, Malcolm; Dunyo, Sam; Winstanley, Peter A.
The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil−dapsone (CPG−DDS) for the treatment of uncomplicated falciparum malaria. Methods Open-label clinical trial comparing CPG−DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years) and 107 children (median age 38 months) with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG–DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0−3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP) population using mean time to reduce baseline parasitemia by 90% (PC90). A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT) population. Results In the Day 3 PP population for the adult group (N = 85), mean time to PC90 was 19.1 h in the CPG−DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference −6.6 h [95%CI −11.8, −1.5]), 2 mg/kg (10.7 h; −8.4 h [95%CI −13.6, −3.2]) and 4 mg/kg (10.3 h; −8.7 h [95%CI −14.1, −3.2]) groups. For children in the Day 3 PP population (N = 92), mean time to PC90 was 21.1 h in the CPG−DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; −3.3 h [95%CI −8.6, 2.0]), though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG−DDS; 14.4 h (treatment difference −6.4 h [95%CI −11.7, −1.0]) and 12.8 h (−7
Piccoli, Giorgina B; Consiglio, V; Colla, L; Mesiano, P; Magnano, A; Burdese, M; Marcuccio, C; Mezza, E; Veglio, V; Piccoli, G
The definition of acute pyelonephritis is controversial. There are two contrasting approaches: (1) acute pyelonephritis is a severe infectious disease involving the kidney parenchyma, and specific imaging techniques are required for diagnosis; (2) acute pyelonephritis is a urinary tract infection, and diagnosis and therapy follow simplified clinical and laboratory pathways. In this study, recent randomized controlled trials (RCTs) were systematically reviewed and the diagnostic and therapeutic approaches to acute 'uncomplicated' pyelonephritis were analysed. Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR) and Chinal were searched employing Mesh, Emtree and free terms on 'pyelonephritis'. Limits included human, period (1995-2004), and trials-reviews (where available). In total, 904 references and 175 full-text were retrieved; 29 were pertinent RCTs. Seven RCTs were added from reference lists (indexed on urinary tract infections). Imaging examinations were performed in 11 of 14 studies on children (diagnostic requisite in two) and in two studies on adults; scarring was not analysed in adults. Clinical definitions varied widely (fever >37.8 to >39 degrees C, culture titres 10(4) >10(5)). Studies on adults were limited to short-term end-points (microbiological sterilization, clinical improvement). Duration of therapy was 4-20 days. The trend was towards shorter periods of therapy, mainly on an outpatient basis; intravenous therapy, if performed, was usually limited to the first 1-3 days. For acute uncomplicated pyelonephritis, the tendency is towards 2 weeks of mainly oral antibiotic therapy. However, the recent literature on adults does not discriminate among different upper urinary tract infections nor does it provide data on renal scarring. While cost constraints point towards short-term therapies, further studies are needed to assess the prevalence and long-term effect of kidney scars.
Kotwani, Anita; Holloway, Kathleen
To obtain information on prescribing rates and choice of antibiotics for acute, uncomplicated respiratory tract infections (RTIs) in the community. Antibiotic use in acute, uncomplicated RTIs consisting of common cold/sore throat/cough for not more than five days was surveyed in the community (December 2007-November 2008) using patient exit interviews at public and private facilities from four localities in New Delhi. Data were collected from 10 public sector facilities and 20 private clinics over one year. The percentage of acute, uncomplicated RTIs patients receiving antibiotics in general and using the Anatomical Therapeutic Chemical classification and the Defined Daily Dose (ATS/DDD) were analysed. At public and private facilities, 45% (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed at least one antibiotic, respectively. The main antibiotic class calculated as percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI patients at private clinics was cephalosporins, J01DA (39%), followed by fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA (15%). Newer members from each class were prescribed; older antibiotics such as co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the main class of antibiotic prescribed was penicillins (31%), followed by macrolides (25%), fluoroquinolones (20%) and cephalosporins (10%). Study clearly shows overuse and inappropriate choice of antibiotics for the treatment of acute, uncomplicated RTIs which are mainly due to virus and do not require antibiotic treatment. Results of the study warrant interventional strategies to promote rational use of antibiotics to decrease the overgrowing threat of antibiotic resistance. © 2014 John Wiley & Sons Ltd.
Peter Klein Klouwenberg
Full Text Available BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists. MATERIALS AND METHODS: We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period. DISCUSSION: Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1 infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50 infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively, largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation. CONCLUSION: The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.
Bharti, Praveen K; Shukla, Man M; Ringwald, Pascal; Krishna, Sri; Singh, Pushpendra P; Yadav, Ajay; Mishra, Sweta; Gahlot, Usha; Malaiya, Jai P; Kumar, Amit; Prasad, Shambhu; Baghel, Pradeep; Singh, Mohan; Vadadi, Jaiprakash; Singh, Mrigendra P; Bustos, Maria Dorina G; Ortega, Leonard I; Christophel, Eva-Maria; Kashyotia, Sher S; Sonal, Gagan S; Singh, Neeru
Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required. This was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450-680. A total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24-48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24-72 h). Additionally, no adverse event was
Full Text Available Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR of IMCI-pneumonia classified patients, and multiple quantitative (qPCR investigations of nasopharyngeal (NPH (all patients and rectal (GE swabs (diarrhoea patients. For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98% and 153/164 (93% of patients and 158/166 (95% and 144/165 (87% of controls, respectively. Overall, 57% (387/677 had IMCI-pneumonia, but only 12% (42/342 had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%, influenza A/B (22.3%, rhinovirus (10.5% and group-A streptococci (6.4%, CXR-confirmed pneumonia (6.2%, Shigella (4.3% were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83 without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74% patients, but only 152 (22% had an infection retrospectively considered to require
Hviid, L; Theander, T G; Abu-Zeid, Y A
convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due......Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...
Hviid, L; Theander, T G; Abu-Zeid, Y A
Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...... convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due...
Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial.
Mwaiswelo, Richard; Ngasala, Billy; Jovel, Irina; Aydin-Schmidt, Berit; Gosling, Roland; Premji, Zul; Mmbando, Bruno; Björkman, Anders; Mårtensson, Andreas
The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission settings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged ≥1 year, with the exception of pregnant and lactating women, were enrolled and treated with AL plus a single PQ dose (0.25 mg/kg) or AL alone under supervision. PQ was administered together with the first AL dose. Clinical and laboratory assessments were performed at 0, 8, 24, 36, 48, 60, and 72 h and on days 7, 14, 21, and 28. The primary end-point was a polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) on day 28. Secondary outcomes included: fever and asexual parasitaemia clearance, proportion of patients with PCR-determined parasitaemia on day 3, and proportion of patients with Pfmdr1 N86Y and Pfcrt K76T on days 0, 3 and day of recurrent infection. Overall 220 patients were enrolled, 110 were allocated AL + PQ and AL, respectively. Parasite clearance by microscopy was fast, but PCR detectable parasitaemia on day 3 was 31/109 (28.4 %) and 29/108 (26.9 %) in patients treated with AL + PQ and AL, respectively (p = 0.79). Day 28 PCR-adjusted ACPR and re-infection rate was 105/105 (100 %) and 101/102 (99 %) (p = 0.31), and 5/107 (4.7 %) and 5/8 (4.8 %) (p = 0.95), in AL + PQ and AL arm, respectively. There was neither any statistically significant difference in the proportion of Pfmdr1 N86Y or Pfcrt K76T
Nespoli, Luca; Lo Bianco, Giulia; Uggeri, Fabio; Romano, Fabrizio; Nespoli, Angelo; Bernasconi, Davide Paolo; Gianotti, Luca
To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P diverticulitis.
Osman Maha E
Full Text Available Abstract Background Artemisinin-based combination therapy is increasingly being adopted as first-line antimalarial therapy. The choice of appropriate therapy depends on efficacy, cost, side effects, and simplicity of administration. Methods the efficacy of fixed co-formulated (f artesunate-sulfamethoxypyrazine-pyrimethamine (AS+SMP f administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. Results seventy-three patients (39 and 34 in the fixed and the loose regimen of AS+SMP respectively completed the 28-days of follow-up. On day 3; all patients in both groups were a parasitaemic but one patient in the fixed group of AS+SMP f was still febrile. Polymerase chain reaction genotyping adjusted cure rates on day 28 were 92.3% and 97.1% (P > 0.05 for the fixed and loose combination of AS+SMP respectively. Three (4.1% patients (one in the fixed and two patients in the loose group of AS+SMP in the study suffered drug-related adverse effects. Gametocytaemia was not detected during follow-up in any of the patients. Conclusion both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice.
Full Text Available Feven Wudneh,1,2 Ashenafi Assefa,3 Desalegn Nega,3 Hussien Mohammed,3 Hiwot Solomon,4 Tadesse Kebede,2 Adugna Woyessa,3 Yibeltal Assefa,3 Amha Kebede,3 Moges Kassa3 1Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, 2Biomedical Department, College of Health Sciences and Medicine, Dilla University, Dilla, 3Malaria and Other Parasitological and Entomological Research Team, Bacterial, Parasitic and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, 4Malaria Research Team, Disease Prevention and Control Directorate, Federal Ministry of Health, Addis Ababa, Ethiopia Purpose: Following the increased Plasmodium falciparum resistance to chloroquine and sulfadoxine/pyrimethamine, Ethiopia adopted artemether/lumefantrine (AL as the first-line treatment for uncomplicated P. falciparum in 2004. According to the recommendation of the World Health Organization, this study was carried out for regular monitoring of the efficacy of AL in treating the uncomplicated P. falciparum malaria in Metema district, Gondar Zone, Northwest Ethiopia.Patients and methods: This is a one-arm prospective 28-day in vivo therapeutic efficacy study among the uncomplicated P. falciparum malaria patients aged 6 months and older. The study was conducted from October 2014 to January 2015, based on the revised World Health Organization protocol of 2009 for surveillance of antimalarial drug therapeutic efficacy study. Standard six-dose regimen of AL was given twice daily for 3 days, and then the treatment outcomes were assessed on days 0, 1, 2, 3, 7, 14, 21, 28, and any other unscheduled day for emergency cases.Results: There were 91 study subjects enrolled in this study, of whom 80 study subjects completed the full follow-up schedules and showed adequate clinical and parasitological responses on day 28, with no major adverse event. Per protocol analysis, the unadjusted
Unlü, Cağdaş; de Korte, Niels; Daniels, Lidewine; Consten, Esther C. J.; Cuesta, Miguel A.; Gerhards, Michael F.; van Geloven, Anna A. W.; van der Zaag, Edwin S.; van der Hoeven, Joost A. B.; Klicks, Rutger; Cense, Huib A.; Roumen, Rudi M. H.; Eijsbouts, Quirijn A. J.; Lange, Johan F.; Fockens, Paul; de Borgie, Corianne A. J. M.; Bemelman, Wilem A.; Reitsma, Johannes B.; Stockmann, Hein B. A. C.; Vrouenraets, Bart C.; Boermeester, Marja A.
Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in
C.̧. Ünlü; N. de Korte (Niels); L. Daniels (Lidewine); E.C. Consten (Esther); M.A. Cuesta (Miguel); M.F. Gerhards (Michael); A.A. van Geloven (Anna); E.S. van der Zaag (Edwin); J.A.B. van der Hoeven (Joost); R. Klicks (Rutger); H.A. Cense (Huib); R.M. Roumen (Rudi); Q.A. Eijsbouts (Quirijn); J.F. Lange (Johan); P. Fockens (Paul); C.A. de Borgie (Corianne); W.A. Bemelman (Willem); J.B. Reitsma (Johannes); H.B.A.C. Stockmann; B.C. Vrouenraets (Bart); M.A. Boermeester (Marja)
textabstractBackground. Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are
Full Text Available Pancytopeni,a as an initial manifestation of acute plasmodium vivax malaria is extremely rare and mainly reported with plasmodium falciparum. We report a 37- year old Nepali patient who recently came to Saudi Arabia and presented with a three-week history of intermittent fever, chills and rigor. She was found to have spleenomegaly, pancytopenia, hyperferrtinemia, and hypofibronogenemia with positive peripheral blood smear for plasmodium vivax. The patient had a full recovery from pancytopenia with oral chloroquine.
Huston, Jared M; Kao, Lillian S; Chang, Phillip K; Sanders, James M; Buckman, Sara; Adams, Charles A; Cocanour, Christine S; Parli, Sarah E; Grabowski, Julia; Diaz, Jose; Tessier, Jeffrey M; Duane, Therese M
Acute appendicitis is the most common abdominal surgical emergency in the United States, with a lifetime risk of 7%-8%. The treatment paradigm for complicated appendicitis has evolved over the past decade, and many cases now are managed by broad-spectrum antibiotics. We determined the role of non-operative and operative management in adult patients with uncomplicated appendicitis. Several meta-analyses have attempted to clarify the debate. Arguably the most influential is the Appendicitis Acuta (APPAC) Trial. According to the non-inferiority analysis and a pre-specified non-inferiority margin of -24%, the APPAC did not demonstrate non-inferiority of antibiotics vs. appendectomy. Significantly, however, the operations were nearly always open, whereas the majority of appendectomies in the United States are done laparoscopically; and laparoscopic and open appendectomies are not equivalent operations. Treatment with antibiotics is efficacious more than 70% of the time. However, a switch to an antimicrobial-only approach may result in a greater probability of antimicrobial-associated collateral damage, both to the host patient and to antibiotic susceptibility patterns. A surgery-only approach would result in a reduction in antibiotic exposure, a consideration in these days of focus on antimicrobial stewardship. Future studies should focus on isolating the characteristics of appendicitis most susceptible to antibiotics, using laparoscopic operations as controls and identifying long-term side effects such as antibiotic resistance or Clostridium difficile colitis.
Matsiegui, Pierre-Blaise; Missinou, Michel A; Issifou, Saadou; Necek, Magdalena; Mavoungou, Elie
We assessed the ability of ibuprofen to modulate tumor necrosis factor alpha (TNF-alpha), soluble tumor necrosis factor receptor type I (sTNFR-I), and soluble tumor necrosis factor receptor type II (sTNFR-II) responses during the treatment of fever in uncomplicated Plasmodium falciparum malaria, in a placebo-controlled, randomized, double-blind study of 50 pediatric patients in Lambaréné, Gabon. Treatment of the malaria involved the patients receiving intravenous quinine (12 mg/kg of quinine dihydrochloride every 12 h for 72 h) followed by a single dose of oral sulfadoxine/pyrimethamine (25 mg and 1.25 mg/kg). Fever was treated by mechanical treatment plus either ibuprofen (7 mg/kg every 8 h) or placebo during the hospitalization period. We determined serum concentrations of TNF-alpha, sTNFR-I, and sTNFR-II in peripheral blood throughout the treatment period in the two groups: ibuprofen and placebo groups. TNF-alpha levels were found to be positively correlated with body temperature. In contrast, TNF receptors levels did not differ between the two groups and the antipyretic effect of ibuprofen was not correlated with specific changes in sTNFR-I and sTNFR-II production. Our data suggest that TNF-alpha is involved in malarial fever, but soluble TNF receptors play no major role in fever modulation.
Dorkenoo Monique A
Full Text Available Abstract Background Malaria remains a major public health problem in Togo. The national malaria control programme in Togo changed the anti-malarial treatment policy from monotherapy to artemisinin combination therapy in 2004. This study reports the results of therapeutic efficacy studies conducted on artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Togo, between 2005 and 2009. Methods Children between 6 and 59 months of age, who were symptomatically infected with P. falciparum, were treated with either artemether-lumefantrine or artesunate-amodiaquine. The primary end-point was the 28-day cure rate, PCR-corrected for reinfection and recrudescence. Studies were conducted according to the standardized WHO protocol for the assessment of the efficacy of anti-malarial treatment. Differences between categorical data were compared using the chi-square test or the Fisher’s exact test where cell counts were ≤ 5. Differences in continuous data were compared using a t-test. Results A total of 16 studies were conducted in five sentinel sites, with 459, 505 and 332 children included in 2005, 2007 and 2009, respectively. The PCR-corrected 28-day cure rates using the per-protocol analysis were between 96%-100% for artemether-lumefantrine and 94%-100% for artesunate-amodiaquine. Conclusions Both formulations of artemisinin-based combination therapy were effective over time and no severe adverse events related to the treatment were reported during the studies.
Serge Brice Assi
Full Text Available The objective of this study was to monitor the effectiveness of artesunate-amodiaquine fixed-dose combination tablets (ASAQ Winthrop® in the treatment of uncomplicated Plasmodium falciparum malaria in Côte d’Ivoire. Two enrolment periods (November 2009 to May 2010 and March to October 2013 were compared using an identical design. Subjects with proven monospecific P. falciparum infection according to the WHO diagnostic criteria were eligible. 290 patients during each period received a dose of ASAQ Winthrop tablets appropriate for their age. The primary outcome measure was PCR-corrected adequate clinical and parasitological response at Day 28 in the per protocol population (255 in Period 1 and 240 in Period 2. This was achieved by 95.7% of patients during Period 1 and 96.3% during Period 2. Over 95% of patients were afebrile at Day 3 and complete parasite clearance was achieved at Day 3 in >99% of patients. Nineteen adverse events in nineteen patients were considered as possibly related to treatment, principally vomiting, abnormal liver function tests, and pruritus. There was no evidence for loss of effectiveness over the three-year period in spite of strong drug pressure. This trial was registered in the US Clinical Trials Registry (clinical.trials.gov under the identifier number NCT01023399.
Lau, Yee-Ling; Lee, Wenn-Chyau; Tan, Lian-Huat; Kamarulzaman, Adeeba; Syed Omar, Sharifah Faridah; Fong, Mun-Yik; Cheong, Fei-Wen; Mahmud, Rohela
Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient's condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission.
Gray, Alyson M; Arguin, Paul M; Hamed, Kamal
Data from clinical studies show that artemether-lumefantrine (AL) is effective and well tolerated in adults and children with uncomplicated Plasmodium falciparum malaria. However, data on effectiveness and safety of AL in patients in non-endemic settings are limited. A 5-year surveillance plan included all AL-treated adult and paediatric patients with confirmed or suspected P. falciparum malaria in the USA, as reported to the National Malaria Surveillance System at the Centers for Disease Control and Prevention. Descriptive analyses included demographics, baseline characteristics, clinical effectiveness, and safety. From May 2010 to April 2015, demographics and baseline characteristics were collected for 203 patients and safety data for 108 patients. Treatment effectiveness data at day 7 were collected for 117 patients and at day 28 for 98 patients. The majority of patients were male (58.6 %), Black (62.6 %), non-Hispanic (92.6 %), and likely malaria non-immune (80.8 %). The median age was 32 (range 1-88) years and the median body mass index was 25.5 (range 13.8-42.4) kg/m(2). All patients with effectiveness data had confirmed (n = 116) or suspected (n = 1) malaria. The overall cure rate for patients treated with AL was 91.5 % (95 % CI 84.8-95.8 %) at day 7 and 96.9 % (95 % CI 91.3-99.4 %) at day 28. Adverse events were reported in four (3.7 %) patients, and there were no new or unexpected safety signals. AL was effective and well tolerated in the treatment of likely non-immune patients with P. falciparum malaria.
High Rate of Treatment Failures in Nonimmune Travelers Treated With Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria in Sweden: Retrospective Comparative Analysis of Effectiveness and Case Series.
Sondén, Klara; Wyss, Katja; Jovel, Irina; Vieira da Silva, Antero; Pohanka, Anton; Asghar, Muhammad; Homann, Manijeh Vafa; Gustafsson, Lars L; Hellgren, Urban; Färnert, Anna
Artemisinin-based combination therapy (ACT) is the first-line treatment of Plasmodium falciparum malaria. Since the introduction of artemether-lumefantrine (AL) for treatment of uncomplicated malaria in Sweden, treatment failures have been reported in adults. A retrospective comparative analysis of treatment regimen for P. falciparum malaria in adults in Stockholm during 2000-2015 was performed to evaluate the effectiveness of AL. Parasite genotyping and drug concentrations were investigated in the AL treatment failures. Among the total 397 P. falciparum episodes, 310 were treated with oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were administered initial intravenous therapy (38 artesunate and 49 quinine) followed by oral treatments. Five late treatment failures were detected after AL and one slow response to AP. The effectiveness of AL alone was 94.7% (95% confidence interval [CI], 88.1%-98.3%), compared with 99.5% for other oral regimens (P = .003). All AL failures occurred in European men and the effectiveness in this group was only 73.7% (95% CI, 48.8%-90.0%). Genotyping confirmed recrudescence of the initial parasite populations and drug resistance markers revealed no clinically significant resistance patterns. Lumefantrine concentrations suggested subtherapeutic concentrations in at least 2 cases. Our findings indicate a high rate of symptomatic late treatment failures after 6-dose AL regime in nonimmune adults, especially in men. Our report warrants the need to establish optimal dosing of AL in adults and to alert clinicians about the importance of informing patients regarding the risk of parasites reappearing weeks after AL treatment. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
Sippola, S; Grönroos, J; Tuominen, R; Paajanen, H; Rautio, T; Nordström, P; Aarnio, M; Rantanen, T; Hurme, S; Salminen, P
An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P appendicitis incurred lower costs than those who had surgery. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.
Hachimi, M A; Hatim, E A; Moudden, M K; Elkartouti, A; Errami, M; Louzi, L; Hanafi, S M; Mahmoudi, A
Severe malaria causes nearly one million deaths annually in endemic areas and is a public health priority worldwide. Severity associated with the occurrence of acute respiratory distress syndrome (ARDS) is a well-known complication of infection with Plasmodium falciparum and can reach 25% of infected adults. However, ARDS is less often described with other Plasmodium species. We report the case of a young Moroccan soldier who died in an array of ARDS related to malaria of Plasmodium ovale 7 months after his return from an endemic country. Copyright © 2013. Published by Elsevier Masson SAS.
Huang, Chenxi; Alamili, Mahdi; Nielsen, Claus Henrik
responses are believed to cause postoperative sleep disturbances, as inflammatory responses can alter sleep architecture through cytokine-brain interactions. Our aim was to investigate alteration of sleep architecture during acute infection and its relationships to inflammation and clinical symptoms....... Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during...... was reduced 4% and 7% the first (p = 0.006) and second (p = 0.014) nights of diverticulitis, compared to baseline, respectively. The rapid eye movement sleep was reduced 33% the first night (p = 0.016), compared to baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement sleep, rapid...
A randomized, open-label, comparative efficacy trial of artemether-lumefantrine suspension versus artemether-lumefantrine tablets for treatment of uncomplicated Plasmodium falciparum malaria in children in western Kenya
Akhwale Willis S
Full Text Available Abstract Background Artemether/lumefantrine (AL has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region. Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria. However, oral paediatric formulations are urgently needed, as the tablets are difficult to administer to young children, who cannot swallow whole tablets or tolerate the bitter taste of the crushed tablets. Methods A randomized, controlled, open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6–59 months, treated over three days with either six-dose of artemether/lumefantrine tablets (Coartem® or three-dose of artemether/lumefantrine suspension (Co-artesiane® for uncomplicated falciparum malaria in western Kenya. The children were followed-up with clinical, parasitological and haematological evaluations over 28 days. Results Ninety three percent (124/133 and 90% (121/134 children in the AL tablets and AL suspension arms respectively completed followed up. A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0% at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40. Both drugs effectively cleared gametocytes and were well tolerated, with no difference in the overall incidence of adverse events. Conclusion The once daily three-dose of artemether-lumefantrine suspension (Co-artesiane® was not superior to six-dose artemether-lumefantrine tablets (Coartem® for the treatment of uncomplicated malaria in children below five years of age in western Kenya. Trial registration ClinicalTrials.gov NCT00529867
Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments.
Sowunmi, Akintunde; Akano, Kazeem; Ntadom, Godwin; Ayede, Adejumoke I; Ibironke, Folasade O; Aderoyeje, Temitope; Adewoye, Elsie O; Fatunmbi, Bayo; Oguche, Stephen; Okafor, Henrietta U; Watila, Ismaila; Meremikwu, Martin; Agomo, Philip; Ogala, William; Agomo, Chimere; Folarin, Onikepe A; Gbotosho, Grace O; Happi, Christian T
Artemisinin-based combination treatments (ACTs) are the first-line treatments of uncomplicated Plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children. Therapeutic efficacy of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine was evaluated in 437 anaemic and 909 non-anaemic malarious children following treatment during a seven-year period (2008-2014). Patterns of temporal changes in haematocrit were classified based on haematocrit values Fall in haematocrit/1 000 asexual parasites cleared from peripheral blood was significantly greater at lower compared to higher parasitaemias (P line treatments. These ACTs may also conserve haematocrit at high parasitaemias and in anaemic children. Pan African Clinical Trial Registry PACTR201508001188143 , 3 July 2015; PACTR201510001189370 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015.
Full Text Available The Republic of the Congo adopted artemisinin-based combination therapies (ACTs in 2006: artesunate-amodiaquine and artemether-lumefantrine as the first-line and second-line drugs, respectively. The baseline efficacy of artemether-lumefantrine was evaluated between March and July 2006 in Brazzaville, the capital city of Congo. Seventy-seven children aged between 6 months and 10 years were enrolled in a nonrandomized study. The children were treated under supervision with 6 doses of artemether-lumefantrine and followed up for 28 days in accordance with the 2003 World Health Organization guideline. Pretreatment (i.e., day 0 and recrudescent Plasmodium falciparum isolates between day 14 and day 28 were compared by the polymerase chain reaction to distinguish between true recrudescence and reinfection. The overall cure rate on day 28 was 96.9% after PCR correction. Reported adverse effects included pruritus and dizziness. Artemether-lumefantrine was highly efficacious in Brazzaville.
Full Text Available Abstract Background Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. Methods A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d and mefloquine (125 mg/d. Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. Results From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. Conclusion African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed.
A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos
Mayxay, Mayfong; Keomany, Sommay; Khanthavong, Maniphone; Souvannasing, Phoutthalavanh; Stepniewska, Kasia; Khomthilath, Tiengthong; Keola, Siamphay; Pongvongsa, Tiengkham; Phompida, Samlane; Ubben, David; Valecha, Neena; White, Nicholas J.; Newton, Paul N.
We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study. PMID:21118925
Taylor, C B; Bandura, A; Ewart, C K; Miller, N H; DeBusk, R F
The effects of wives' involvement in their husbands' performance of treadmill exercise testing 3 weeks after clinically uncomplicated acute myocardial infarction was compared in 10 wives who did not observe the test, 10 who observed the test, and 10 who observed and participated in the test themselves. In a counseling session after the treadmill test, couples were fully informed about the patient's capacity to perform various physical activities. Wives' final ratings of confidence (perceived efficacy) in their husbands' physical and cardiac capability were significantly (p less than 0.05) higher in those who also performed the test than in the other 2 groups. Only wives who walked on the treadmill increased their ratings of their husbands' physical and cardiac efficacy to a level equivalent to those of their husbands. Spouses' and patients' perceptions of patients' cardiac capability after treadmill testing and counseling at 3 weeks were significantly correlated with peak treadmill heart rate and workload at 11 and 26 weeks. Efficacy ratings at 3 weeks were slightly better than peak 3-week treadmill heart rate and workload as predictors of treadmill performance at 11 and 26 weeks. Participation in treadmill testing early after acute myocardial infarction is an effective means for reassuring spouses about the capacity of their partners to resume their customary physical activities with safety.
Full Text Available Introduction. Sleep disturbances are commonly found in patients in the postoperative period. Sleep disturbances may give rise to several complications including cardiopulmonary instability, transient cognitive dysfunction and prolonged convalescence. Many factors including host inflammatory responses are believed to cause postoperative sleep disturbances, as inflammatory responses can alter sleep architecture through cytokine-brain interactions. Our aim was to investigate alteration of sleep architecture during acute infection and its relationships to inflammation and clinical symptoms.Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during which study endpoints were measured by polysomnography recordings, self-reported discomfort scores and blood samples of cytokines. One month later, the patients, who now were in complete remission, were readmitted and the endpoints were re-measured (the baseline values.Results. Total sleep time was reduced 4% and 7% the first (p = 0.006 and second (p = 0.014 nights of diverticulitis, compared to baseline, respectively. The rapid eye movement sleep was reduced 33% the first night (p = 0.016, compared to baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement sleep, rapid eye movement sleep and fatigue.Conclusion. Total sleep time and rapid eye movement sleep were reduced during nights with active diverticulitis and correlated with markers of inflammation.
Wu, Cheng-Hsien; Chen, Chien-Cheng; Wang, Chao-Jan; Wong, Yon-Cheong; Wang, Li-Jen; Huang, Chen-Chih; Lo, Wan-Chak; Chen, Huan-Wu
In acute cholecystitis, the presence of gangrene is associated with higher morbidity and mortality and necessitates open surgical intervention rather than laparoscopic cholecystectomy. As Murphy's sign may be absent, gangrene may not be detected ultrasonographically. This retrospective study evaluated indications of acute gangrenous cholecystitis on computed tomography (CT) in 25 patients, who were proven as having acute cholecysitis surgically and pathologically within 3 days of pre-operative CT. The CT images were reviewed by two board-certified radiologists blind to the initial CT report. Acute gangrenous cholecystitis was significantly correlated with the CT signs of perfusion defect (PD) of the gallbladder wall (P = 0.02), pericholecystic stranding (PS) (P = 0.028), and no-gallstone condition (No-ST) (P = 0.026). The presence of PD was associated with acute gangrenous cholecystitis with a relatively high accuracy (80%), a sensitivity of 70.6%, a specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 61.5%. The combination CT signs of PD or No-ST improved the accuracy for acute gangrenous cholecystitis to 92%, with a sensitivity, specificity, PPV, and NPV of 88.2%, 100%, 100%, and 80%, respectively. Other CT signs were highly specific for acute gangrenous cholecystitis but of low sensitivity, including mucosal hemorrhage, mucosal sloughing, wall irregularity, pericholecystic abscess, gas formation, and portal venous thrombosis. CT was found to accurately diagnose acute cholecystitis, with the presence of PD, PS, or No-ST significantly correlated with that of gangrenous change. Thus, CT is useful in the preoperative detection of acute gangrenous cholecystitis.
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
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
Boermeester, Marja A.; Humes, David J.; Velmahos, George C.; Søreide, Kjetil
Acute colonic diverticulitis is a common clinical condition. Severity of the disease is based on clinical, laboratory, and radiological investigations and dictates the need for medical or surgical intervention. Recent clinical trials have improved the understanding of the natural history of the
de Mey, Christian; Peil, Hubertus; Kölsch, Stephan; Bubeck, Jürgen; Vix, Jean-Michel
Sore throat is the hallmark of acute pharyngitis. Although usually caused by viral infections, it is frequently treated with antibiotics. Such inappropriate use of antibiotics might best be challenged by offering efficacious and safe symptomatic pain relief instead. However, there is need for robust evidence to support such alternatives. Presently, the evidence from randomised, placebo-controlled, double-blind clinical trials (RCT) with the local anaesthetic ambroxol (CAS 23828-92-4) in the treatment of sore throat is being reviewed. This relates to five RCT in 1,772 patients; 1,713 were evaluable with regard to efficacy. Treatment with ambroxol lozenges was statistically significantly superior to placebo in reducing sore throat pain intensity with a high level of consistency of the estimated effect across the different studies. The effect had an early onset and lasted up to at least 3 h after a single first lozenge. The pain relief was associated with a statistically superior regression of pharyngeal redness and inflammation; with ambroxol, the overall efficacy was more frequently rated as at least "good". Treatment with the ambroxol lozenges was well tolerated. There was heterogeneity in reporting adverse events: in one later study with less severe baseline pain intensity there was more frequent reporting of hypoaesthesia of the oral cavity and tongue as an untoward phenomenon. In patients with more severe baseline pain this reflection of the medication's pharmacological action was only rarely reported as untoward. It is concluded that lozenges containing 20 mg ambroxol are a safe and efficacious treatment for acute uncomplicated sore throat of recent onset in adult patients.
de Mey, C; Koelsch, S; Richter, E; Pohlmann, T; Sousa, R
A pooled analysis is presented of 7 placebo-controlled RCT that investigated lozenges containing ambroxol for pain relief in acute sore throat.2 242 patients were treated with different ambroxol doses or control treatments, 2 183 were evaluable for efficacy. The present analysis is focused on the recommended dose of 20 mg (AXL20): 856 patients were treated with AXL20, 847 with matched placebo lozenges (PL).The average reduction in pain intensity over the first 3 h after the first AXL20 ranged from 38% to 52% of the maximum achievable effect (MAE). The overall treatment difference between AXL20 and PL was 11% (95% CI: 8-13%) of the MAE (post-hoc meta-analysis). The corresponding NNT was 6.0 (CI: 4.7-8.4) for an average pain reduction from baseline of 33% of the MAE over the first 3 h.71.9, 79.0, and 85.3% of the AXL20-patients scored the efficacy as "very good or good" at the end of the 1(st), 2(nd) and 3(rd) day, respectively, vs. 57.5, 64.4, and 70.4% of the PL-patients resulting in odds ratios of 1.9 (CI: 1.5-2.3) for the 1(st), 2.1 (CI: 1.7-2.6) for the 2(nd) and 2.43 (CI: 1.8-3.3) for the 3(rd) day.At the end of treatment 'no redness' or 'slightly red' was scored on pharyngeal inspection in 84.4% and 77.3% of AXL20- and PL-patients (OR: 1.6, CI: 1.3-1.9).AXL20-treatment was well tolerated and is safe and efficacious for acute uncomplicated sore throat of recent onset in adolescent and adult patients. © Georg Thieme Verlag KG Stuttgart · New York.
Varadhan, Krishna K; Neal, Keith R
Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis. PMID:22491789
Tzamalis, Argyrios; Chalvatzis, Nikolaos; Anastasopoulos, Eleftherios; Tzetzi, Despina; Dimitrakos, Stavros
We report a rare case of acute postoperative Staphylococcus schleiferi endophthalmitis following an uneventful cataract extraction. An 83-year-old woman underwent uneventful phacoemulsification without receiving the usual intracameral cefuroxime solution due to cephalosporin intolerance. Two days postoperatively, she presented with acute ocular pain and blurred vision in the operated eye. Ophthalmic examination revealed signs of acute keratitis and endophthalmitis. Corneal scrapes and vitreous taps were sent for cultivation and analysis. The patient received intravitreal antibiotics at the same time. Cultivation grew S schleiferi, a pathogen commonly found in dogs. Following microbiological report, the patient received a repeated intravitreal injection of 1 mg/0.1 mL vancomycin combined with fortified topical vancomycin drops. One week later, the inflammation subsided completely while the corneal ulcer healed and visual acuity improved dramatically. Further examination revealed the existence of the same pathogen in a specimen obtained from the dog owned by the patient's family. This description of S schleiferi endophthalmitis highlights the need to provide alternative intracameral antibiotic solution in the operating room and avoid direct contact with dogs during the first postoperative period after intraocular surgery.
de Korte, N.; Unlü, C.; Boermeester, M. A.; Cuesta, M. A.; Vrouenreats, B. C.; Stockmann, H. B. A. C.
The value of antibiotics in the treatment of acute uncomplicated left-sided diverticulitis is not well established. The aim of this review was to assess whether or not antibiotics contribute to the (uneventful) recovery from acute uncomplicated left-sided diverticulitis, and which types of
Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial
Full Text Available Abstract Background In 2005, the Democratic Republic of Congo (DRC adopted artesunate and amodiaquine (ASAQ as first-line anti-malarial treatment. In order to compare the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine (AL, a randomized, non-inferiority open-label trial was conducted in Katanga. Methods Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolled and randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed. Results Between April 2008 and March 2009, 301 children were included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131 in the ASAQ group and 15.2% (19/125 in the AL group. After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8 in the ASAQ group and 99.1% (95%CI, 94.9-99.9 in the AL group (difference −0.7%, one sided 95% CI −3.1. Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated. Conclusion Both ASAQ and AL are highly effective and currently adequate as the first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country, such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces. Trial registration The protocol was registered with the clinicaltrials.gov, open clinical trial registry under the identifier number NCT01567423.
de Mey, C; Patel, J; Lakha, D R; Richter, E; Koelsch, S
Compare the efficacy and tolerability of oral spray formulations delivering 2.5, 5, and 10 mg ambroxol (AXS) per application (4 actuations/application) in relieving acute sore throat vs. spraying a matched placebo solution. Multi-centre, placebo-controlled, randomised, double-blind trial with up to 6 daily applications of the assigned medication for up to 3 days. 511 outpatients with acute sore throat were enrolled, 494 were treated. Up to 6 spray applications per day as needed for up to 3 days. All treatments led to a reduction in pain intensity (PI); the mean cumulative PI-reductions over the first 2 h after the 1(st) dose (SPIDnorm(0-2)) were 24.7, 26.6, 26.0, and 32.2% (SEM: 0.023) of the predose PI for treatment with placebo, and the 2.5, 5, and 10 mg AXS, respectively. These mean reductions were 2 (CI: -3.6; 7.5), 1.3 (CI: -4.3; 6.8), and 7.5 (CI: 2.0;13.1) percent points larger than for placebo. The 2.5 and 5 mg AXS were not distinguishable from placebo, but the 10 mg AXS was evidently superior. The numbers needed to treat (NNT) when comparing 10 mg AXS with placebo, were 9.5 and 8.8 for an average pain relief of 33 and 50% of the maximum achievable effect over the first 2 h. 10 mg AXS showed a statistically significantly superior pain reduction relative to the placebo spray. Treatment with 10 mg AXS reaches an extent of pain relief that can be accepted to be clinically meaningful and was well tolerated. © Georg Thieme Verlag KG Stuttgart · New York.
Grelpois, Gérard; Sabbagh, Charles; Cosse, Cyril; Robert, Brice; Chapuis-Roux, Emilie; Ntouba, Alexandre; Lion, Thierry; Regimbeau, Jean-Marc
Day case surgery (DCS) for uncomplicated acute appendicitis (NCAA) is evaluated. The objective of this prospective, single-center, descriptive, nonrandomized, intention-to-treat cohort study was to assess the feasibility of DCS for NCAA with a critical analysis of the reasons for exclusion and treatment failures and a focus on patients discharged to home and admitted for DCS on the following day. From April 2013 to December 2015, NCAA patients meeting the inclusion criteria were included in the study. The primary end point was the success rate for DCS (length of stay less than 12 hours) in the intention-to-treat population (all NCAA) and in the per-protocol population (no pre- or perioperative exclusion criteria). The secondary end points were morbidity, DCS quality criteria, predictive factors for successful DCS, patient satisfaction, quality of life, and reasons for pre- or perioperative exclusion. A subgroup of patients discharged to home the day before operation was also analyzed. A total of 240 patients were included. The success rate of DCS was 31.5% in the intention-to-treat population and 91.5% in the per-protocol population. The rates of unplanned consultations, hospitalization, and reoperation were 13%, 4%, and 1%, respectively. An analysis of the reasons for DCS exclusion showed that 73% could have been modified. For the 68 patients discharged to home on the day before operation, the DCS success rate was 91%. Day case surgery is feasible in NCAA. A critical analysis of the reasons for exclusion from DCS showed that it should be possible to dramatically increase the eligible population. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Smith, Michael J
In 2001, the American Academy of Pediatrics published clinical practice guidelines for the management of acute bacterial sinusitis (ABS) in children. The technical report accompanying those guidelines included 21 studies that assessed the diagnosis and management of ABS in children. This update to that report incorporates studies of pediatric ABS that have been performed since 2001. Overall, 17 randomized controlled trials of the treatment of sinusitis in children were identified and analyzed. Four randomized, double-blind, placebo-controlled trials of antimicrobial therapy have been published. The results of these studies varied, likely due to differences in inclusion and exclusion criteria. Because of this heterogeneity, formal meta-analyses were not performed. However, qualitative analysis of these studies suggests that children with greater severity of illness at presentation are more likely to benefit from antimicrobial therapy. An additional 5 trials compared different antimicrobial therapies but did not include placebo groups. Six trials assessed a variety of ancillary treatments for ABS in children,and 3 focused on subacute sinusitis. Although the number of pediatric trials has increased since 2001, there are still limited data to guide the diagnosis and management of ABS in children. Diagnostic and treatment guidelines focusing on severity of illness at the time of presentation have the potential to identify those children most likely to benefit from antimicrobial therapy and at the same time minimize unnecessary use of antibiotics
Wie, Seong-Heon; Kim, Hyung Wook; Chang, U-Im
The objectives of this study were to evaluate the clinical effectiveness of gentamicin as an initial empirical antimicrobial agent and to determine the effects of gentamicin resistance on clinical outcomes in women with uncomplicated acute pyelonephritis (APN). We analyzed data of 2,033 women with a diagnosis of APN admitted to Catholic University St. Vincent's Hospital. Of those, we enrolled 274 cases of community-acquired uncomplicated APN due to Escherichia coli who received gentamicin as initial antibiotics. Of these 274 patients, 47 patients had gentamicin-resistant (GM-R) E. coli APN, and 227 patients had gentamicin-susceptible (GM-S) E. coli APN. The early clinical response rates were 55.3% (26/47) versus 81.5% (185/227) at 72 hours; 61.7% (29/47) versus 96.9% (220/227) at 96 hours in the GM-R and GM-S groups, which was significantly higher in the GM-S group (pResistance of E. coli to gentamicin, bacteremia, and C-reactive protein level showed independent effects on early clinical failure. Aminoglycoside such as gentamicin can be an alternative antibiotic option for initial empirical therapy of community-acquired uncomplicated APN as the fluoroquinolone-sparing or broad-spectrum cephalosporin-sparing agents in an era of increasing antimicrobial resistance, especially in areas where medical resources are limited or antibiotic resistance rate of the uropathogens is high.
Tang, Yan; Joyner, Chester J; Cabrera-Mora, Monica; Saney, Celia L; Lapp, Stacey A; Nural, Mustafa V; Pakala, Suman B; DeBarry, Jeremy D; Soderberg, Stephanie; Kissinger, Jessica C; Lamb, Tracey J; Galinski, Mary R; Styczynski, Mark P
Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax malaria) that may affect erythropoiesis. An appropriate erythropoietic response did not occur to compensate for anaemia during acute cynomolgi malaria despite an increase in erythropoietin levels. During this period, there were significant perturbations in the bone marrow transcriptome. In contrast, relapses did not induce anaemia and minimal changes in the bone marrow transcriptome were detected. The differentially expressed genes during acute infection were primarily related to ongoing inflammatory responses with significant contributions from Type I and Type II Interferon transcriptional signatures. These were associated with increased frequency of intermediate and non-classical monocytes. Recruitment and/or expansion of these populations was correlated with a decrease in the erythroid progenitor population during acute infection, suggesting that monocyte-associated inflammation may have contributed to anaemia. The decrease in erythroid progenitors was associated with downregulation of genes regulated by GATA1 and GATA2, two master regulators of erythropoiesis, providing a potential molecular basis for these findings. These data suggest the possibility that malarial anaemia may be driven by monocyte-associated disruption of GATA1/GATA2 function in erythroid progenitors resulting in insufficient erythropoiesis during acute infection.
Mohamed, Abdelrahim O; Abdel Hamid, Muzamil M; Mohamed, Omer S; Elkando, Nuha S; Suliman, Abdelmaroof; Adam, Mariam A; Elnour, Fahad Awad Ali; Malik, Elfatih M
Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable. The objective of this study was to evaluate the therapeutic efficacies of dihydroartemisinin/piperaquine (DHA-PPQ) and AS/SP in an area of unstable transmission in Blue Nile State, Sudan in 2015-16. A total of 148 patients with uncomplicated malaria were recruited in the study from November 2015 to end of January 2016. Seventy-five patients received DHA-PPQ while 73 received AS/SP. Patients were monitored for clinical and parasitological outcomes following the standard WHO protocol for a period of 42 days for DHA-PPQ and 28 days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance from day 7 onwards. Fifty-five patients completed the DHA-PPQ arm protocol with success cure rate of 98.2% (95% CI 90.3-100%) and one late clinical failure 1.8% (95% CI 0.0-9.7%). The AS/SP showed adequate clinical and parasitological response (ACPR) of 83.6% (95% CI 71.9-91.8%), early treatment failure was 1.6% (95% CI 0.0-8.8%) and late parasitological failure (LPF) was 14.8% (95% CI 7-26.2%). The respective PCR uncorrected LPF was 20%. DHA-PPQ is an efficacious ACT and candidate for replacement of first-line treatment in Sudan while AS/SP showed high treatment failure rate and must be replaced.
Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial
Full Text Available Abstract Background The use of artemisinin-based combination therapy (ACT is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ and artemether-lumefantrine (AL - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR after polymerase chain reaction (PCR correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182 and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182, PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03. No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during
The efficacy and tolerability of artemisinin-piperaquine (Artequick®) versus artesunate-amodiaquine (Coarsucam™) for the treatment of uncomplicated Plasmodium falciparum malaria in south-central Vietnam.
Thanh, Nguyen Xuan; Trung, Trieu Nguyen; Phong, Nguyen Chinh; Quang, Huynh Hong; Dai, Bui; Shanks, G Dennis; Chavchich, Marina; Edstein, Michael D
In Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine is currently used for first-line treatment of uncomplicated Plasmodium falciparum malaria. However, limited efficacy and tolerability data are available on alternative forms of ACT in Vietnam in case there is a reduction in the susceptibility of dihydroartemisinin-piperaquine. A study was conducted to compare the efficacy and tolerability of two fixed-dose formulations of ACT, artemisinin-piperaquine (Artequick®, ARPQ) and artesunate-amodiaquine (Coarsucam™, ASAQ) for the treatment of P. falciparum malaria in south-central Vietnam. A randomized, open-label trial was conducted comparing the efficacy of a two-day regimen of ARPQ (~2.8 mg/kg artemisinin plus ~17.1 mg/kg of piperaquine per day) and a three-day regimen of ASAQ (~4.7 mg/kg of artesunate plus ~12.6 mg/kg of amodiaquine per day) for the treatment of children and adults with uncomplicated falciparum malaria. Primary efficacy endpoint was day 42, PCR-corrected, parasitological cure rate. Secondary endpoints were parasite and fever clearance times and tolerability. Of 128 patients enrolled, 63 were administered ARPQ and 65 ASAQ. Of the patients who completed the 42 days follow-up period or had a recurrence of malaria, 55 were on ARPQ (30 children, 25 adults) and 59 were on ASAQ (31 children, 28 adults). Recrudescent parasitaemia was PCR-confirmed for one patient in each treatment group, with cure rates at day 42 of 98% (95% CI: 88-100) for both forms of ACT. The median parasite clearance time was significantly slower in the ARPQ group compared with the ASAQ group (48 h vs. 36 h, Pmalaria. Although the two-day course of ARPQ was equally as effective as the three-day course of ASAQ, parasite and fever clearance times were shorter with ASAQ. Further studies are warranted in different regions of Vietnam to determine the nationwide efficacy of ASAQ. Australian New Zealand Clinical Trials Registry Number, ACTRN
Kurtzhals, J A; Reimert, C M; Tette, E
of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness...... than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear...... to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria....
van de Laar Floris A
Full Text Available Abstract Background Acute urinary tract infections (UTI are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (102 or 103 or 105 CFU/ml. We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making. Methods Searches were performed through PubMed (1966 to April 2010, EMBASE (1973 to April 2010, Cochrane library (1973 to April 2010, Google scholar and reference checking. Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 102 CFU/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model. Results Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 102 CFU/ml; 55.4% at ≥ 103 CFU/ml and 44.8% at ≥ 102 CFU/ml ≥ 105 CFU/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 102 CFU/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41, frequency (+LR 1.10 95% CI 1.04-1.16, hematuria (+LR 1.72 95%CI 1.30-2.27, nocturia (+LR 1.30 95% CI 1.08-1.56 and urgency (+LR 1.22 95% CI 1.11-1.34 all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83 decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of UTI to
Giesen, Leonie GM
Abstract Background Acute urinary tract infections (UTI) are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (102 or 103 or 105 CFU\\/ml). We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making. Methods Searches were performed through PubMed (1966 to April 2010), EMBASE (1973 to April 2010), Cochrane library (1973 to April 2010), Google scholar and reference checking. Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 102 CFU\\/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model. Results Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 102 CFU\\/ml; 55.4% at ≥ 103 CFU\\/ml and 44.8% at ≥ 102 CFU\\/ml ≥ 105 CFU\\/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 102 CFU\\/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41), frequency (+LR 1.10 95% CI 1.04-1.16), hematuria (+LR 1.72 95%CI 1.30-2.27), nocturia (+LR 1.30 95% CI 1.08-1.56) and urgency (+LR 1.22 95% CI 1.11-1.34) all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83) decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of
Full Text Available Abstract Background Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days. II A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time
Adjei, George O; Goka, Bamenla Q; Kitcher, Emmanuel
evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels......Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs) with hearing...... is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n = 37), artemether-lumefantrine (n = 35), or amodiaquine (n = 8) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared...
Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A
Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P Mandala et al.
Objectives. To assess therapeutic efficacy of sulfadoxineyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa. Se'tting. Tonga district with a population of 116 418 and subject to seasonal malaria, with an average annual incidence ; 3 200 ...
George O. Adjei
Full Text Available Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n=37, artemether-lumefantrine (n=35, or amodiaquine (n=8 in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children (n=57 from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls (P<0.001. The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs.
Hussein, Z; Eaves, J; Hutchinson, D B; Canfield, C J
The population pharmacokinetics of atovaquone were examined in 458 black, Oriental, and Malay patients with acute Plasmodium falciparum malaria receiving atovaquone alone or concomitantly with other drugs. Oral clearance (CL/F) showed a 0.674 power relationship with weight and is similar in Oriental and Malay subjects but 58.5% lower in black subjects. On the basis of mean body weight, the population estimate of CL/F is 3.28, 8.49, and 9.13 L/hr in black, Oriental, and Malay subjects, respectively. The relationship between apparent volume of distribution (V area/F) and weight was linear and similar in all three races at 7.98 L/kg. The population estimate of V area/F is 345, 383, and 428 L in black, Oriental, and Malay subjects, respectively. The bioavailability of the high and low doses of atovaquone was similar. Neither CL/F nor V area/F were significantly affected by age, gender, and the coadministration with chloroguanide (proguanil), pyrimethamine, and tetracycline. Half-life (t1/2) showed a 0.326 power relationship with weight; thus, the population estimate of t1/2 in black, Oriental, and Malay subjects is 72.9, 31.3, and 32.5 hours, respectively. The final magnitudes of interpatient variability in CL/F and V area/F were 68% and 49%, respectively.
Full Text Available Human herpes viruses (HHVs are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8. We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0 and 14 days later (after treatment, or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.
Artemisinin-Based Combination Therapy Versus Quinine or Other Combinations for Treatment of Uncomplicated Plasmodium falciparum Malaria in the Second and Third Trimester of Pregnancy: A Systematic Review and Meta-Analysis
Burger, Renée J.; van Eijk, Anna M.; Bussink, Milena; Hill, Jenny; ter Kuile, Feiko O.
The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria in the second and third trimesters of pregnancy. We conducted a meta-analysis to compare efficacy, safety and tolerability of ACTs versus quinine and other
Shabanzadeh, Daniel M; Wille-Jørgensen, Peer
Diverticulitis is an inflammatory complication to the very common condition diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics with reference to the microbiology, extrapolation from trials on complicated intra-abdominal infections and clinical experience....
Knudson, Angélica; Nicholls, Rubén Santiago; Guerra, Angela Patricia; Sánchez, Ricardo
Few studies describe the clinical presentations of uncomplicated Plasmodium falciparum malaria in the province of Córdoba in an endemic area of northwestern Colombia. Profiles of patients with uncomplicated Plasmodium falciparum malaria were described from two twons of Córdoba, Tierrata and Puerto Libertador, based on clinical, epidemiological and laboratory variables. Patients were examined according to standard WHO/PAHO protocols for assessment of antimalarial drug efficacy. Clinical data and parasitological information was collected as well. A multiple correspondence multivariate analysis was used to compare the profiles of 127 patients with uncomplicated Plasmodium falciparum malaria. Of the 127 patients,105 completed the 14-day follow-up and 7 had adequate clinical response. Between 80% and 98% of patients exhibited at least one of the most frequent symptoms of uncomplicated malaria, and 80.3% had asthenia as the most frequent symptom. The multivariate analysis grouped the variables into five distinguishable clusters of clinical profiles. These groups showed similarities with the classical clinical descriptions of uncomplicated malaria encountered in the literature. The low frequency of patients with adequate clinical response hampered the association analysis. In Córdoba, therapeutic failure to chloroquine treatment is high in treating uncomplicated Plasmodium falciparum malaria. Multivariate analysis summarized variables related to epidemiological and clinical aspects and permitted a more objective approach to the interpretation of the findings.
Pre-discharge stress echocardiography and exercise ECG for risk stratification after uncomplicated acute myocardial infarction: results of the COSTAMI-II (cost of strategies after myocardial infarction) trial
Desideri, A; Fioretti, P M; Cortigiani, L; Trocino, G; Astarita, C; Gregori, D; Bax, J; Velasco, J; Celegon, L; Bigi, R; Pirelli, S; Picano, E
Objective: To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction. Design: 262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3–5) pharmacological stress echocardiography (n = 132) or conventional pre-discharge (day 7–9) maximum symptom limited exercise ECG (n = 130). Results: No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant). Conclusion: Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise. PMID:15657220
Kurtzhals, J A; Rodrigues, O; Addae, M
To study the importance of bone marrow inhibition in the pathogenesis of malarial anaemia, haematological and parasitological parameters were followed in patients with acute malaria. Three patient categories were studied, severe malarial anaemia (SA), cerebral malaria (CM) and uncomplicated malaria...... clearance RDW increased dramatically, reaching the highest levels 1-2 weeks later. Although severe anaemia was corrected by blood transfusion during the first 3 d of treatment, the peak RDW correlated significantly with the initial EPO levels. This suggests that Plasmodium falciparum infection causes...
Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial
Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia
an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria. METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days...... to children aged 6 months-15 years with uncomplicated P. falciparum mono-infection. Intake was observed and AL was given with milk. Children were seen on days 0, 1, 2 and 3 and then weekly days 7-42. Recurring P. falciparum were classified as recrudescence or new infections by genotyping. Between November...
Ndounga, Mathieu; Pembe Issamou Mayengue; Casimiro, Prisca Nadine; Koukouikila-Koussounda, Félix; Bitemo, Michel; Diassivy Matondo, Brunelle; Ndounga Diakou, Lee Aymar; Basco, Leonardo K; Ntoumi, Francine
The Republic of Congo adopted a new anti-malarial treatment policy in 2006, with artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as the first- and second-line anti-malarial drugs, respectively. Only three clinical studies had been conducted before the policy change. A randomized study on these two artemisinin-based combinations was conducted, and the effect that sickle cell trait may have on treatment outcomes was evaluated in children under 10 years old followed during 12 months in Brazzaville in 2010-2011. A cohort of 330 children under 10 years of age living in a suburban area in the south of Brazzaville were passively followed for registration of malaria episodes. Uncomplicated Plasmodium falciparum episodes were randomly treated with co-formulated ASAQ (Coarsucam(®)) or AL (Coartem(®)). Patients were followed according to the 2009 World Health Organization protocol for the evaluation of anti-malarial drug efficacy. Plasmodium falciparum recrudescent isolates were compared to pre-treatment isolates by polymerase chain reaction (PCR) to distinguish between re-infection and recrudescence. PCR-uncorrected and PCR-corrected responses to treatment were determined using per protocol analysis. Haemoglobin type (AA, AS, SS) was determined by PCR. Of 282 clinical malaria episodes registered during 1-year follow-up period, 262 children with uncomplicated malaria were treated with ASAQ (129 patients) or AL (133 patients). The PCR-corrected efficacy, expressed as the percentage of adequate clinical and parasitological response, was 97.0 % for ASAQ and 96.4 % for AL. Among ASAQ-treated patients, 112 (86.8 %) carried AA genotype and 17 (13.2 %) were AS carriers. The PCR-corrected efficacy was 96.4 % for AA-carriers and 100 % for AS-carriers treated with ASAQ [relative risk (RR) = 0.96; 95 % confidence interval, 0.93-1.00, p = 0.5]. Among 133 AL-treated children, 109 (82 %) carried AA, and 24 (18 %) AS genotypes. The PCR-corrected efficacy was 96.7 % among AA
Antibiotics-first strategy for uncomplicated acute appendicitis in adults is associated with increased rates of peritonitis at surgery. A systematic review with meta-analysis of randomized controlled trials comparing appendectomy and non-operative management with antibiotics.
Podda, Mauro; Cillara, Nicola; Di Saverio, Salomone; Lai, Antonio; Feroci, Francesco; Luridiana, Gianluigi; Agresta, Ferdinando; Vettoretto, Nereo
Acute appendicitis is the most common surgical diagnosis in young patients, with lifetime prevalence of about 7%. Debate remains on whether uncomplicated AA should be operated or not. Aim of this meta-analysis of randomized controlled trials was to assess current evidence on antibiotic treatment for uncomplicated AA compared to standard surgical treatment. Systematic literature search was performed using PubMed, EMBASE, Medline, Google Scholar and Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing antibiotic therapy (AT) and surgical therapy-appendectomy (ST) for uncomplicated AA. Trials were reviewed for primary outcome measures: treatment efficacy based on 1 year follow-up, recurrence at 1 year follow-up, complicated appendicitis with peritonitis identified at the time of surgical operation and post-intervention complications. Secondary outcomes were length of hospital stay and period of sick leave. Five RCTs comparing AT and ST qualified for inclusion in meta-analysis, with 1.351 patients included: 632 in AT group and 719 in ST group. Higher rate of treatment efficacy based on 1 year follow-up was found in ST group (98.3% vs 75.9%, P appendicitis with peritonitis identified at time of surgical operation was higher in AT group (19.9% vs 8.5%, P = 0.02). No statistically significant differences were found when comparing AT and ST groups for the outcomes of overall post-intervention complications (4.3% vs 10.9%, P = 0.32), post-intervention complications based on the number of patients who underwent appendectomy (15.8% vs 10.9%, P = 0.35), length of hospital stay (3.24 ± 0.40 vs 2.88 ± 0.39, P = 0.13) and period of sick leave (8.91 ± 1.28 vs 10.27 ± 0.24, P = 0.06). With significantly higher efficacy and low complication rates, appendectomy remains the most effective treatment for patients with uncomplicated AA. The subgroups of patients with uncomplicated AA where antibiotics can be more
Full Text Available Two years after the introduction of free Artesunate-Amodiaquine (ASAQ and Artemether-Lumefantrine (AL for the treatment of uncomplicated malaria in public health facilities in Côte d’Ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. It was a multicentre open randomised clinical trial of 3-day ASAQ treatment against AL for the treatment of 2 parallel groups of patients aged 2 years and above. The endpoints were (1 Adequate Clinical and Parasitological Response (ACPR at day 28 and (2 the clinical and biological tolerability. Of the 300 patients who were enrolled 289, with 143 (49.5% and 146 (50.5% in the ASAQ and AL groups, respectively, correctly followed the WHO 2003 protocol we used. The PCR-corrected ACPR was 99.3% for each group. More than 94% of patients no longer showed signs of fever, 48 hours after treatment. Approximately 78% of the people in the ASAQ group had a parasite clearance time of 48 hours or less compared to 81% in the AL group (p=0.496. Both drugs were found to be well tolerated by the patients. This study demonstrates the effectiveness and tolerability of ASAQ and AL supporting their continuous use for the treatment of uncomplicated P. falciparum malaria infection in Côte d’Ivoire.
Tangpukdee, Noppadon; Krudsood, Srivicha; Thanachartwet, Vipa; Duangdee, Chatnapa; Paksala, Siriphan; Chonsawat, Putza; Srivilairit, Siripan; Looareesuwan, Sornchai; Wilairatana, Polrat
In acute uncomplicated falciparum malaria, there is a continuum from mild to severe malaria. However, no mathematical system is available to predict uncomplicated falciparum malaria patients turning to severe malaria. This study aimed to devise a simple and reliable model of Malaria Severity Prognostic Score (MSPS). The study was performed in adult patients with acute uncomplicated falciparum malaria admitted to the Bangkok Hospital for Tropical Diseases between 2000 and 2005. Total 38 initia...
Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence
Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick; Kaur, Harparkash; Duparc, Stephan; Ishengoma, Deus S.; Magnussen, Pascal; Alifrangis, Michael; Sutherland, Colin J.
Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite susceptibility to ACT
Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi
In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi
In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. PMID:26755155
Efficacy of amodiaquine, sulphadoxine-pyrimethamine and their combination for the treatment of uncomplicated Plasmodium falciparum malaria in children in Cameroon at the time of policy change to artemisinin-based combination therapy
Full Text Available Abstract Background The efficacy of amodiaquine (AQ, sulphadoxine-pyrimethamine (SP and the combination of SP+AQ in the treatment of Cameroonian children with clinical malaria was investigated. The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time. Methods Seven hundred and sixty children aged 6-59 months with uncomplicated falciparum malaria were studied in three ecologically different regions of Cameroon - Mutengene (littoral equatorial forest, Yaoundé (forest-savannah mosaic and Garoua (guinea-savannah. Study children were randomized to receive either AQ, SP or the combination AQ+SP. Clinical outcome was classified according to WHO criteria, as either early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF or adequate clinical and parasitological response (ACPR. The occurrence of mutations in pfcrt, pfmdr1, dhfr and dhps genes was studied by either RFLP or dot blot techniques and the prevalence of these mutations related to parasitological and therapeutic failures. Results After correction for the occurrence of re-infection by PCR, ACPRs on day 28 for AQ, SP and AQ+SP were 71.2%, 70.1% and 80.9%, in Garoua, 79.2%, 62.5%, and 81.9% in Mutengene, and 80.3%, 67.5% and 76.2% in Yaoundé respectively. High levels of Pfcrt 76T (87.11% and Pfmdr1 86Y mutations (73.83% were associated with quinoline resistance in the south compared to the north, 31.67% (76T and 22.08% (86Y. There was a significant variation (p dhps gene was extremely rare (0.3% and occurred only in Mutengene while the pfmdr1 1034K and 1040D mutations were not detected in any of the three sites. Conclusion In this study the prevalence of molecular markers for quinoline and anti-folate resistances showed high levels and differed between the south and north of Cameroon. AQ, SP and AQ+SP treatments were well tolerated but with low levels of efficacy that
T-Regulatory Cells and Inflammatory and Inhibitory Cytokines in Malawian Children Residing in an Area of High and an Area of Low Malaria Transmission During Acute Uncomplicated Malaria and in Convalescence.
Nyirenda, Tonney S; Molyneux, Malcolm E; Kenefeck, Rupert; Walker, Lucy S K; MacLennan, Calman A; Heyderman, Robert S; Mandala, Wilson L
Malaria still infects many Malawian children, and it is a cause of death in some of them. Regulatory T cells (Tregs) help in negating immune-related pathology, it but can also favor multiplication of malaria parasites. The question remains whether children recovering from uncomplicated malaria (UCM) have higher Tregs and interleukin (IL)-10 levels in convalescence. We recruited children between the ages of 6 and 60 months presenting with acute UCM in Blantyre (low transmission area) and Chikwawa (high transmission area). We observed the children after 1 month and 3 months and analyzed their blood samples for parasitemia, lymphocyte subsets, and levels of the cytokines interferon (IFN)-γ, IL-10, and transforming growth factor (TGF)-β. Blood samples from age-matched controls were also analyzed for the same parameters. Compared with controls, acute UCM was associated with mild lymphopenia, splenomegaly, and high levels of IFN-γ, tumor necrosis factor-α, and IL-10, which normalized in convalescence. In Chikwawa, Treg counts were significantly (P < .0001) higher in convalescence compared with acute disease, whereas in Blantyre, these were as low as in healthy controls both during acute disease and in convalescence. Blantyre had a higher percentage of parasiteamic children (15% versus 12%) in convalescence compared with Chikwawa, but none of these developed symptomatic malaria during the study duration. Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa. The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance. We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.
Kavishe, Reginald A; Paulo, Petro; Kaaya, Robert D
) is the recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania. METHODS: A total of 687 Plasmodium...
Sánchez-Velázquez, Patricia; Grande, Luis; Pera, Miguel
Acute diverticulitis occurs in up to 25% of patients with diverticulosis. The majority of cases are mild or uncomplicated and it has become a frequent reason for consultation in the emergency department. On the basis of the National Inpatient Sample database from the USA, 86% of patients admitted with diverticulitis were treated with medical therapy. However, several recent studies have shown that outpatient treatment with antibiotics is safe and effective. The aim of this systematic review is to update the evidence published in the outpatient treatment of uncomplicated acute diverticulitis. We performed a systematic review according to the PRISMA guidelines and searched in MEDLINE and Cochrane databases all English-language articles on the management of acute diverticulitis using the following search terms: 'diverticulitis', 'outpatient', and 'uncomplicated'. Data were extracted independently by two investigators. A total of 11 articles for full review were yielded: one randomized controlled trial, eight prospective cohort studies, and two retrospective cohort studies. Treatment successful rate on an outpatient basis, which means that no further complications were reported, ranged from 91.5 to 100%. Fewer than 8% of patients were readmitted in the hospital. Intolerance to oral intake and lack of family or social support are common exclusion criteria used for this approach, whereas severe comorbidities are not definitive exclusion criteria in all the studies. Ambulatory treatment of uncomplicated acute diverticulitis is safe, effective, and economically efficient when applying an appropriate selection in most reviewed studies.
Relationship between plasma and red blood cell concentrations of quinine in Brazilian children with uncomplicated Plasmodium falciparummalaria on oral therapy Relação entre as concentrações plasmáticas e eritrocitárias de quinina em crianças com malária por Plasmodium falciparum não complicada em terapia via oral
José L.F. Vieira
Full Text Available We determined the relationship between plasma and red blood cell concentrations of quinine in children with uncomplicated falciparum malaria from an endemic area of Amazonian region. Quinine was determined by high performance liquid chromatography with ultraviolet detection. In the steady state the ratio between plasma and red blood cell quinine concentration was 1.89 ± 1.25 ranging from 1.05 to 2.34. This result demonstrated that quinine do not concentrate in red blood cell of Brazilian children and characterize the absence of interracial difference in this relationship.Neste estudo foi determinada a relação entre as concentrações plasmáticas e eritrocitárias de quinina em crianças com malária falciparum não complicada, oriundas de área endêmica da Região Amazônica. A quinina foi detrminada por cromatografia líquida de alta eficiência. No estado de equilíbrio, a relação foi 1,89 ± 1,25 variando de 1,05 a 2,34. Estes resultados demonstraram que a quinina não se concentra nos eritrócitos das crianças e caracterizaram a ausência de diferença racial nesta relação.
Hommel, Benjamin; Galloula, Alexandre; Simon, Anne; Buffet, Pierre
International audience; BACKGROUND: Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. METHODS: A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoi...
Objectives. To assess the therapeutic efficacy of sulfadoxinepyrimethamine (SP) after 5 years of use as first-line treatment of uncomplicated Plasmodium falciparum malaria, and thus guide the selection of artemisinin-based combination therapy in Mpumalanga, South Africa. Design. An open-label, in vivo therapeutic ...
Adjei, George O; Goka, Bamenla Q; Enweronu-Laryea, Christabel C
BACKGROUND: Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria....../57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group...
Population Pharmacokinetic Analysis of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Healthy Subjects, Subjects with Various Degrees of Renal Function, and Patients with Complicated Urinary Tract Infection or Acute Uncomplicated Pyelonephritis.
Kawaguchi, Nao; Katsube, Takayuki; Echols, Roger; Wajima, Toshihiro
Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to perform a population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with various degrees of renal function, and patients with complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram-negative pathogens and to calculate the fraction of the time during the dosing interval where the free drug concentration in plasma exceeds the MIC ( fT MIC ). Population PK models were developed with three renal function markers, body surface area-adjusted estimated glomerular filtration rate (eGFR), absolute eGFR, and creatinine clearance, on the basis of 2,571 plasma concentrations from 91 subjects without infection and 238 patients with infection. The population PK models with each renal function marker adequately described the plasma cefiderocol concentrations. Clear relationships of total clearance (CL) to all renal function markers were observed. Body weight and disease status (with or without infection) were also significant covariates. The CL in patients with infection was 26% higher than that in subjects without infection. The fT MIC values were more than 75% in all patients (and were 100% in most patients), suggesting that a sufficient exposure to cefiderocol was provided by the tested dose regimens (2 g every 8 h as the standard dose regimen) for the treatment of cUTI or AUP caused by Gram-negative pathogens. Copyright © 2018 Kawaguchi et al.
Bassat, Quique; González, Raquel; Machevo, Sónia; Nahum, Alain; Lyimo, John; Maiga, Hamma; Mårtensson, Andreas; Bashraheil, Mahfudh; Ouma, Peter; Ubben, David; Walter, Verena; Nwaiwu, Obiyo; Kipkeu, Chemtai; Lefèvre, Gilbert; Ogutu, Bernhards; Menéndez, Clara
Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population. Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated P. falciparum malaria in infants and children in Africa were analysed according to body weight group. The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.
Full Text Available Abstract Background The epidemiology of malaria in the Senegal River Gorgol valley, southern Mauritania, requires particular attention in the face of ongoing and predicted environmental and climate changes. While “malaria cases” are reported in health facilities throughout the year, past and current climatic and ecological conditions do not favour transmission in the dry season (lack of rainfall and very high temperatures. Moreover, entomological investigations in neighbouring regions point to an absence of malaria transmission in mosquito vectors in the dry season. Because the clinical signs of malaria are non-specific and overlap with those of other diseases (e.g. acute respiratory infections and diarrhoea, new research is needed to better understand malaria transmission patterns in this region to improve adaptive, preventive and curative measures. Methods We conducted a multipurpose cross-sectional survey in the city of Kaédi in April 2011 (dry season, assessing three major disease patterns, including malaria. Plasmodium spp. parasite rates were tested among children aged 6–59 months who were recruited from a random selection of households using a rapid diagnostic test and microscopic examination of Giemsa-stained thick and thin blood films. Acute respiratory infection and diarrhoea were the two other diseases investigated, administering a parental questionnaire to determine the reported prevalence among participating children. Findings No Plasmodium infection was found in any of the 371 surveyed preschool-aged children using two different diagnostic methods. Acute respiratory infections and diarrhoea were reported in 43.4% and 35.0% of the participants, respectively. About two thirds of the children with acute respiratory infections and diarrhoea required medical follow-up by a health worker. Conclusions Malaria was absent in the present dry season survey in the capital of the Gorgol valley of Mauritania, while acute respiratory
Stapleton, Ann E
Acute uncomplicated urinary tract infection (UTI) is a common clinical problem, accounting for millions of outpatient visits in the USA annually. Although routinely obtaining urine cultures in UTI is not recommended, there are circumstances in which obtaining a pre-therapy culture may be warranted or chosen by clinicians, such as when indicated by the need for careful antimicrobial stewardship. This review focuses on understanding reasons for obtaining a pre-therapy culture, methods of collection, and appropriately interpreting urine culture data.
Enevold, Anders; Lusingu, John P; Mmbando, Bruno
the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha(+)-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area......The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect...
Quaye, I K; Ekuban, F A; Goka, B Q
The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe malarial anaemia, or uncomplicated malaria and 42 age-matched h......The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe malarial anaemia, or uncomplicated malaria and 42 age...
O'Kane, Dermot B; Dave, Sameer K; Gore, Neel; Patel, Farhaan; Hoffmann, Tammy C; Trill, Jeanne L; Del Mar, Chris B
Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women, characterised by dysuria and urinary frequency. Urinary alkalisers are widely used in some countries for the symptomatic treatment of uncomplicated UTI, and they are recommended in some national formularies. However, there is a lack of empirical evidence to support their use for UTI and some healthcare guidelines advise against their use. We aimed to look at the benefits and harms of the use of urinary alkalisers for the treatment of uncomplicated UTIs in adult women. We searched the Cochrane Kidney and Transplant Specialised Register to 19 January 2016 through contact with the Trials Search Co-ordinator using search terms relevant to this review. All randomised controlled trials (RCTs) and quasi-RCTs on the use of (any) urinary alkalisers (either exclusively or non-exclusively) for the symptomatic treatment of uncomplicated UTI amongst women aged 16 and over, were included. Studies were eligible if they included patients whose diagnosis of UTI was decided by symptoms alone, or positive urine dipstick test or urine culture; and patients with recurrent UTI, provided patients had no symptoms of UTI in the two weeks prior to the onset of symptoms that lead them to seek medical advice. Studies were ineligible if they studied patients with complicated UTIs; immune-compromising conditions; acute pyelonephritis; or chronic conditions such as interstitial cystitis. Three authors independently assessed and screened papers, and this was repeated by two separate authors (independently). An additional investigator acted as arbitrator, where necessary. There were no papers which fulfilled the inclusion criteria for this review, and therefore no data extraction was performed. Our search identified 172 potential studies for inclusion. However, following assessment none fulfilled the inclusion criteria for this review. Until relevant evidence is generated from randomised trials, the safety
in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug. TRIAL REGISTRATION: Clinicaltrials.gov NCT00440999.
Mockenhaupt, F.P.; Ehrhardt, S.; Dzisi, S.Y.; Bousema, T.; Wassilew, N.; Schreiber, J.; Anemana, S.D.; Cramer, J.P.; Otchwemah, R.N.; Sauerwein, R.W.; Eggelte, T.A.; Bienzle, U.
The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) alone, SP plus amodiaquine (AQ), and SP plus artesunate (AS) was assessed in a randomized, placebo-controlled, and double-blind trial among 438 children with uncomplicated Plasmodium falciparum malaria in northern Ghana. Clinical and
Perch, M; Kofoed, Pe; Fischer, Torge
Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are significantly elevated and of prognostic value in patients suffering from serious infectious diseases such as HIV and tuberculosis. Our objective was to investigate suPAR levels during symptomatic malaria infection and 7...... days after treatment. Children younger than 6 years who presented with fever or other symptoms compatible with malaria were enrolled. Blood films and samples were collected on day 0 and day 7. Twenty-five children were allocated to each of three groups according to the amount of Plasmodium falciparum...... detected in their initial blood film. Children in group 1 had parasite densities in excess of 20 parasites per 200 leucocytes. The median plasma suPAR level was 6.49 ng/mL (interquartile range [IQR]: 4.90-7.61) and correlated to parasitemia (Spearman 0.43, P
Full Text Available Abstract Background Severe and cerebral malaria are associated with endothelial activation. Angiopoietin-1 (ANG-1 and angiopoietin-2 (ANG-2 are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of whole blood angiopoietin (ANG levels as biomarkers of disease severity in Plasmodium falciparum malaria. Methods The utility of whole blood ANG levels was examined in Thai patients to distinguish cerebral (CM; n = 87 and severe (non-cerebral malaria (SM; n = 36 from uncomplicated malaria (UM; n = 70. Comparative statistics are reported using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared test, as appropriate. Multivariate binary logistic regression was used to examine differences in whole blood protein levels between groups (UM, SM, CM, adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver operating characteristic curve analysis was used to assess the diagnostic accuracy of the ANGs in their ability to distinguish between UM, SM and CM. Cumulative organ injury scores were obtained for patients with severe disease based on the presence of acute renal failure, jaundice, severe anaemia, circulatory collapse or coma. Results ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM there were significant decreases in ANG-1 (p Conclusions These results suggest that whole blood ANG-1/2 levels are promising clinically informative biomarkers of disease severity in malarial syndromes.
Mohapatra, Sarita; Samantaray, Jyotish C; Arulselvi, Subramaniyan; Ghosh, Arnab
Disseminated intravascular coagulation (DIC) due to Plasmodium vivax is scarcely reported in comparison to Plasmodium falciparum. In complicated malaria, thrombocytopaenia and haemostatic alterations lead to increased activation of coagulation cascade and fibrinolytic system. Thromboelastography (TEG) is a haemostasis system which measures the viscoelastic strength of blood clot in the coagulation pathway. It detects the initial derangement in clotting cascade involving in platelet interaction and fibrinolysis. Hence, it can document the early changes in coagulation in vitro, and thereby guide the management. The current study was aimed at detection of DIC in patients with P. vivax malaria based on TEG. Ethylene diamine tetraacetic acid (EDTA) blood samples from acute febrile patients were tested by microscopy and immunochromatographic test for malaria. A total of 31 confirmed cases of vivax malaria were enrolled for this study. All the samples were tested by thromboelastography and conventional tests parameters for detection of any coagulation derangement. Of 31, 17 (55%) were classified as complicated and 14/31 (45%) were uncomplicated. Among 23 cases with thrombocytopaenia, non-overt (early stage) DIC was detected in 18 cases by TEG and 17 cases by the conventional methods. It seems that the burden of DIC in vivax malaria is much higher than the world literature reported. TEG can be utilized as an important tool for early detection of DIC and guiding the management in malaria patients.
A total of 56 pre-menopausal women with uncomplicated UTIs caused by fluoroquinolone-resistant strains were included. Urine cultures were carried ... Chinese herbal therapy may be an acceptable alternative for the treatment of uncomplicated UTIs caused by fluoroquinolone-resistant uropathogens. Key words: Chinese ...
Lis R V Antonelli
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.
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
Hviid, L; Theander, T G; Elhassan, I M
). In the present study we show that clinical episodes of P. falciparum malaria produced an increase in plasma levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1). The increase was transient and subsided slowly (sICAM-1) or rapidly (sELAM-1) following drug cure. The increases in plasma sICAM-1 and sELAM-1 were......Acute P. falciparum malaria is associated with a loss of antigen-responsiveness of peripheral T cells, depletion of T cells characterized by high surface expression of the adhesion molecule LFA-1, and increased plasma levels of the T-cell activation marker soluble IL-2 receptor (sIL-2R......-1. Taken together, these observations suggest that acute P. falciparum malaria is characterized by a state of endothelial inflammation associated with the adherence of activated T cells....
Full Text Available The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15 or 1,500 mg chloroquine (base over a 3 day period (n=14 (phase 1. The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9 or atovaquone/proguanil as before (n=5 (phase 2. In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] versus 8% [1/13], P<0.0001. In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]. There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.
Enevold, Anders; Lusingu, John P; Mmbando, Bruno; Alifrangis, Michael; Lemnge, Martha M; Bygbjerg, Ib C; Theander, Thor G; Vestergaard, Lasse S
The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha(+)-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area of intense malaria transmission where 202 individuals 0-19 years of age were monitored clinically for a period of 6 months. RBC polymorphisms were assessed with molecular methods, and plasma antibodies to P. falciparum variant surface antigens (anti-VSA IgG) and glutamate-rich protein (anti-GLURP IgG) were measured with flow cytometry and ELISA assays, respectively. Regression analyses showed that alpha(+)-thalassemia was associated with a reduced risk of uncomplicated malaria episodes and that this advantageous effect seemed to be more predominant in children older than 5 years of age, but was independent of levels of antibodies to VSA and GLURP.
Full Text Available Abstract Background Because of the emergence of chloroquine resistance in Mali, artemether-lumefantrine (AL or artesunate-amodiaquine (AS+AQ are recommended as first-line therapy for uncomplicated malaria, but have not been available in Mali until recently because of high costs. Methods From July 2005 to January 2006, a randomized open-label trial of three oral antimalarial combinations, namely AS+AQ, artesunate plus sulphadoxine-pyrimethamine (AS+SP, and amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP, was conducted in Faladje, Mali. Parasite genotyping by polymerase chain reaction (PCR was used to distinguish new from recrudescent Plasmodium falciparum infections. Results 397 children 6 to 59 months of age with uncomplicated Plasmodium falciparum malaria were enrolled, and followed for 28 days to assess treatment efficacy. Baseline characteristics were similar in all three treatment groups. The uncorrected rates of adequate clinical and parasitologic response (ACPR were 55.7%, 90.8%, and 97.7% in AS+AQ, AS+SP, and AQ+SP respectively (p Conclusion The combination of AQ+SP provides a potentially low cost alternative for treatment of uncomplicated P. falciparum infection in Mali and appears to have the added value of longer protective effect against new infection.
Herricks, Thurston; Seydel, Karl B.; Molyneux, Malcolm; Taylor, Terrie; Rathod, Pradipsinh K.
Splenic filtration of Plasmodium falciparum infected red blood cells has been hypothesized to influence malaria pathogenesis. We have developed a minimum cylindrical diameter (MCD) filtration model which estimates physical splenic filtration during malaria infection. The key parameter in the model is the minimum cylindrical diameter (MCD), the smallest tube or cylinder that a red blood cell (RBC) can traverse without lysing. The MCD is defined by a relationship between the RBC surface area and volume. In the MCD filtration model, the MCD filtration function represents the probability of a cell becoming physically removed from circulation. This modeling approach was implemented at a field site in Blantyre, Malawi. We analyzed peripheral blood samples from 120 study participants in 4 clinically defined groups (30 subjects each): cerebral malaria, uncomplicated malaria, aparasitemic coma, and healthy controls. We found statistically significant differences in the surface area and volumes of uninfected RBCs when healthy controls were compared to malaria patients. The estimated filtration rates generated by the MCD model corresponded to previous observations in ex vivo spleen experiments and models of red blood cell loss during acute malaria anemia. There were no differences in the estimated splenic filtration rates between cerebral malaria and uncomplicated malaria patients. The MCD filtration model estimates that at time of admission, 1 ring-stage infected RBC is physically filtered by the spleen for each parasite that remains in peripheral circulation. This field study is the first to use microfluidic devices to identify rheological diversity in RBC populations associated with malaria infection and illness in well characterized groups of children living in a malaria endemic area. PMID:22892025
Dekker, E.; Romijn, J. A.; Ekberg, K.; Wahren, J.; van Thien, H.; Ackermans, M. T.; Thuy, L. T.; Chandramouli, V.; Kager, P. A.; Landau, B. R.; Sauerwein, H. P.
Although glucose production is increased in severe malaria, the influence of uncomplicated malaria on glucose production is unknown. Therefore, we measured in eight adult Vietnamese patients with uncomplicated falciparum malaria and eight healthy Vietnamese controls glucose production (by infusion
Nosseir, Sandy B; Lind, Lawrence R; Winkler, Harvey A
Recurrent urinary tract infections most often present with symptoms of irritative voiding. In most cases, they are caused by reinfection with a previously isolated organism. Patients with one or more symptoms of uncomplicated recurrent urinary tract infection should undergo thorough examination and screening for underlying comorbidities that increase susceptibility. When frequent reinfections, empiric treatment relapse, persistent infections, or risk factors for complicated infections are encountered, patients may benefit from urodynamics, cystoscopy, renal ultrasound, intravenous urogram, or voiding cystourethrogram to evaluate for anatomic, functional, or metabolic abnormalities affecting the urinary tract (e.g., stones, stricture, obstruction, vesicoureteral reflux, lesions, detrusor underactivity). These patients may benefit from culture-guided empiric treatment and further evaluation by urology, nephrology, or infectious disease specialists. In patients with a history of uncomplicated urinary tract infections, empiric treatment guided by local antimicrobial resistance may efficiently treat a suspected recurrence. After successful treatment of the acute infection, postcoital prophylaxis, continuous prophylaxis, or self-start empiric treatment may be selected based on frequency of recurrent infections, temporal relation to intercourse, and patient characteristics. Ancillary measures such as probiotics, cranberry products, or local estrogen replacement may also be considered. This article will review the current definition, epidemiology, pathogenesis, diagnosis, work-up, treatment, treatment side effects, and prevention of recurrent urinary tract infections in women. A suggested algorithm for evaluation and treatment based on current literature is provided.
Dambe, Rosalia; Sande, John; Ali, Doreen; Chilima, Ben; Dodoli, Wilfred; Michelo, Charles; Malenga, Grace; Phiri, Kamija S
The resistance of malaria parasites to sulphadoxine-pyrimethamine (SP) in 2007 led to the Malawi Ministry of Health changing to artemether-lumefantrine (AL) as first-line for uncomplicated malaria treatment. This study determined the efficacy and safety of AL for the treatment of uncomplicated Plasmodium falciparum malaria among six to 59 months old Malawian children. This was a prospective study of children six to 59 months old treated with AL after presenting with uncomplicated malaria in the six health facilities in Malawi. The children were followed up on days 1, 2, 3, 7, 14, 21 and 28 days post-treatment and assessed for clinical and parasitological responses. The Kaplan Meier survival estimate was used to measure the efficacy of AL by calculating the cumulative risk of failure at day 28. A total of 322 children were recruited into the study across the six sites. The overall intention-to-treat (ITT) polymerase chain reaction (PCR)-corrected cure rate was 93.4%. Per protocol overall PCR-corrected cure rates for the study sites were; Karonga 98.0%, Kawale 97.4%, Machinga 90.2%, Mangochi 95.4% and Rumphi 91.3%. Nkhotakota study site had the lowest cure rate of 78.0%. There is evidence of good efficacy of AL in Malawi notwithstanding geographical contrasts and this supports the continued use of AL as the first-line treatment for uncomplicated malaria. However there may be need to further investigate the comparatively low efficacy rate found in Nkhotakota district in order to identify possible determinants of treatment failure.
Ashley, Elizabeth A; Dhorda, Mehul; Fairhurst, Rick M; Amaratunga, Chanaki; Lim, Parath; Suon, Seila; Sreng, Sokunthea; Anderson, Jennifer M; Mao, Sivanna; Sam, Baramey; Sopha, Chantha; Chuor, Char Meng; Nguon, Chea; Sovannaroth, Siv; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chotivanich, Kesinee; Chutasmit, Kitipumi; Suchatsoonthorn, Chaiyaporn; Runcharoen, Ratchadaporn; Hien, Tran Tinh; Thuy-Nhien, Nguyen Thanh; Thanh, Ngo Viet; Phu, Nguyen Hoan; Htut, Ye; Han, Kay-Thwe; Aye, Kyin Hla; Mokuolu, Olugbenga A; Olaosebikan, Rasaq R; Folaranmi, Olaleke O; Mayxay, Mayfong; Khanthavong, Maniphone; Hongvanthong, Bouasy; Newton, Paul N; Onyamboko, Marie A; Fanello, Caterina I; Tshefu, Antoinette K; Mishra, Neelima; Valecha, Neena; Phyo, Aung Pyae; Nosten, Francois; Yi, Poravuth; Tripura, Rupam; Borrmann, Steffen; Bashraheil, Mahfudh; Peshu, Judy; Faiz, M Abul; Ghose, Aniruddha; Hossain, M Amir; Samad, Rasheda; Rahman, M Ridwanur; Hasan, M Mahtabuddin; Islam, Akhterul; Miotto, Olivo; Amato, Roberto; MacInnis, Bronwyn; Stalker, Jim; Kwiatkowski, Dominic P; Bozdech, Zbynek; Jeeyapant, Atthanee; Cheah, Phaik Yeong; Sakulthaew, Tharisara; Chalk, Jeremy; Intharabut, Benjamas; Silamut, Kamolrat; Lee, Sue J; Vihokhern, Benchawan; Kunasol, Chanon; Imwong, Mallika; Tarning, Joel; Taylor, Walter J; Yeung, Shunmay; Woodrow, Charles J; Flegg, Jennifer A; Das, Debashish; Smith, Jeffery; Venkatesan, Meera; Plowe, Christopher V; Stepniewska, Kasia; Guerin, Philippe J; Dondorp, Arjen M; Day, Nicholas P; White, Nicholas J
Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; Clinical
Duffy, Michael F; Noviyanti, Rintis; Tsuboi, Takafumi
BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements...... of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range...... of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria. METHODS: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from...
Medical Prescription Pitfalls of Uncomplicated Urinary Tract Infections in Government Healthcare Facilities in Zambia. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information about how ...
Objectives: The aim of this evaluation was to identify pitfalls in medical prescriptions of uncomplicated urinary tract infections in government healthcare facilities in Zambia. Design: This was a cross sectional and government healthcare facilities were conveniently sampled. Main outcome measures: Rate of compliance to ...
Full Text Available B cells and antibodies are essential for the protective immune response against a blood-stage Plasmodium infection. Although extensive research has focused on memory as well as plasma B-cell responses during infection, little is known about how malaria affects B-cell development and splenic maturation into marginal zone B (MZB and follicular B (FoB cells. In this study, we show that acute Plasmodium chabaudi AS infection in C57Bl/6 mice causes severe disruption of B lymphopoiesis in the bone marrow, affecting in particular pro-, pre-, and immature B cells as well as the expression of the bone marrow B-cell retention chemokine CXCL12. In addition, elevated apoptosis of transitional T2 and marginal zone (MZ B cells was observed during and subsequent to the control of the first wave of parasitemia. In contrast, Folllicular (Fo B cells levels were retained in the spleen throughout the infection, suggesting that these are essential for parasite clearance and proper infection control.
Bachur, Richard G; Lipsett, Susan C; Monuteaux, Michael C
Nonoperative management (NOM) of uncomplicated pediatric appendicitis has promise but remains poorly studied. NOM may lead to an increase in resource utilization. Our objective was to investigate the trends in NOM for uncomplicated appendicitis and study the relevant clinical outcomes including subsequent appendectomy, complications, and resource utilization. Retrospective analysis of administrative data from 45 US pediatric hospitals. Patients appendicitis between 2010 and 2016 were studied. NOM was defined by an ED visit for uncomplicated appendicitis treated with antibiotics and the absence of appendectomy at the index encounter. The main outcomes included trends in NOM among children with uncomplicated appendicitis and frequency of subsequent diagnostic imaging, ED visits, hospitalizations, and appendectomy during 12-month follow-up. 99 001 children with appendicitis were identified, with a median age of 10.9 years. Sixty-six percent were diagnosed with nonperforated appendicitis, of which 4190 (6%) were managed nonoperatively. An increasing number of nonoperative cases were observed over 6 years (absolute difference, +20.4%). During the 12-month follow-up period, NOM patients were more likely to have the following: advanced imaging (+8.9% [95% confidence interval (CI) 7.6% to 10.3%]), ED visits (+11.2% [95% CI 9.3% to 13.2%]), and hospitalizations (+43.7% [95% CI 41.7% to 45.8%]). Among patients managed nonoperatively, 46% had a subsequent appendectomy. A significant increase in NOM of nonperforated appendicitis was observed over 6 years. Patients with NOM had more subsequent ED visits and hospitalizations compared with those managed operatively at the index visit. A substantial proportion of patients initially managed nonoperatively eventually had an appendectomy. Copyright © 2017 by the American Academy of Pediatrics.
Full Text Available Augmentin (Amoxycillin 3 . gm combined with 250 mg clavulanic acid and ampicillin 3.5 gin and I gm probenecid orally were evaluated in 50 patients for treatment of uncomplicated gonorrhoea. Success rates of 80% and 100% were obtained with augmentin and ampicillin with probenecid respectively in non-PPNG strains. None of 4 PPNG strains responded to ampicillin-probnecid. Augmentin in single oral dose cannot be recommended for the treatment of non-PPNG strains in India.
Scheelings, T F; McLaren, P J; Tatarczuch, L; Slocombe, R F
A wild-caught, adult female Leadbeater's possum (Gymnobelideus leadbeateri) died while in captivity after suffering from chronic ill-thrift that progressed to acute respiratory distress. On histopathological examination of tissues, the cause of death was determined to be severe acute pneumonia with pulmonary oedema associated with an intracellular protozoan parasite present within erythrocytes. Transmission electron microscopy was performed on lung tissues and organisms consistent for Plasmodium sp. were identified within numerous erythrocytes. Molecular characterisation of the parasite from DNA extracted from tissue blocks of fixed lung determined the organism to belong to the genus Plasmodium (100% similarity to Plasmodium species when a BLAST analysis was performed); however, speciation of the organism was not possible. This is the first report of Plasmodium sp. infection and subsequent disease in a native Australian mammal. The lifecycle of this parasite remains unknown. It is also unknown what effects haemoparasitism may have on the population dynamics of this endangered possum species. © 2016 Australian Veterinary Association.
Population A comprised of 164 children (75 acute uncomplicated malaria (UM), 48 cerebral malaria (CM) and 41 severe malarial anaemia (SMA), while Population B comprised of 225 children (115 UM, 55 CM, 55 SMA). Results showed a high level of genetic diversity and multiplicity of P.falciparum infections in the two ...
Hommel, Benjamin; Galloula, Alexandre; Simon, Anne; Buffet, Pierre
Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoites and schizonts, thick and thin smears also showed Howell-Jolly bodies, pointing to functional hyposplenism. This was later confirmed by the presence of a calcified spleen in the context of S/β + sickle-cell syndrome in a patient previously unaware of this condition. Malaria may reveal hyposplenism. Although Howell-Jolly bodies are morphologically similar to nuclei of young Plasmodium trophozoite, distinction on smears is based on the absence of cytoplasm and irregular size of Howell-Jolly bodies. In the patient reported here, hyposplenism was revealed by the occurrence of P. malariae infection relatively late in life. Timely diagnosis of hyposplenism resulted in the implementation of appropriate measures to prevent overwhelming infection with capsulated bacteria. This observation highlights the importance of diagnosing hyposplenism in patients with malaria despite the morphological similarities between ring nuclei and Howell-Jolly bodies on thick smears.
Ursing, Johan; Kofoed, Poul-Erik; Rodrigues, Amabelia
In 2008, Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria. Previously, 3 times the standard dose of chloroquine, that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter (pfcrt) 76T allele...
Full Text Available Chloroquine (CQ resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1% of the patients were cured and 44 (37.9% failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP and 20 received chlorpheniramine + chloroquine (CH+CQ combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05. There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92% while those of CH+CQ was 85%. There was a significant difference in parasite clearance time (p = 0.01 between the two groups. The 38% treatment failure for CQ reported in this study is higher than the 10% recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.
Selemani, Majige; Masanja, Irene M; Kajungu, Dan; Amuri, Mbaraka; Njozi, Mustafa; Khatib, Rashid A; Abdulla, Salim; de Savigny, Don
Improving malaria case management is partially dependent on health worker compliance with clinical guidelines. This study assessed health worker factors associated with correct anti-malarial prescribing practices at two sites in rural Tanzania. Repeated cross-sectional health facility surveys were conducted during high and low malaria transmission seasons in 2010 and collected information on patient consultations and health worker characteristics. Using logistic regression, the study assessed health worker factors associated with correct prescription for uncomplicated malaria defined as prescription of artemisinin-based combination therapy (ACT) for patients with fever and Plasmodium falciparum asexual infection based on blood slide or malaria rapid diagnostic test (RDT) according to national treatment guidelines. The analysis included 685 patients with uncomplicated malaria who were seen in a health facility with ACT in stock, and 71 health workers practicing in 30 health facilities. Overall, 58% of malaria patients were correctly treated with ACT. Health workers with three or more years' work experience were significantly more likely than others to prescribe correctly (adjusted odds ratio (aOR) 2.9; 95% confidence interval (CI) 1.2-7.1; p = 0.019). Clinical officers (aOR 2.2; 95% CI 1.1-4.5; p = 0.037), and nurse aide or lower cadre (aOR 3.1; 95% CI 1.3-7.1; p = 0.009) were more likely to correctly prescribe ACT than medical officers. Training on ACT use, supervision visits, and availability of job aids were not significantly associated with correct prescription. Years of working experience and health worker cadre were associated with correct ACT prescription for uncomplicated malaria. Targeted interventions to improve health worker performance are needed to improve overall malaria case management.
Stam, M A W; Draaisma, W A; van de Wall, B J M; Bolkenstein, H E; Consten, E C J; Broeders, I A M J
The optimal diet for uncomplicated diverticulitis is unclear. Guidelines refrain from recommendation due to lack of objective information. The aim of the study was to determine whether an unrestricted diet during a first acute episode of uncomplicated diverticulitis is safe. A prospective cohort study was performed of patients diagnosed with diverticulitis for the first time between 2012 and 2014. Requirements for inclusion were radiologically proven modified Hinchey Ia/b diverticulitis, American Society of Anesthesiologists class I-III and the ability to tolerate an unrestricted diet. Exclusion criteria were the use of antibiotics and suspicion of inflammatory bowel disease or malignancy. All included patients were advised to take an unrestricted diet. The primary outcome parameter was morbidity. Secondary outcome measures were the development of recurrence and ongoing symptoms. There were 86 patients including 37 (43.0%) men. All patients were confirmed to have taken an unrestricted diet. There were nine adverse events in seven patients. These consisted of readmission for pain (five), recurrent diverticulitis (one) and surgery (three) for ongoing symptoms (two) and Hinchey Stage III (one). Seventeen (19.8%) patients experienced continuing symptoms 6 months after the initial episode and 4 (4.7%) experienced recurrent diverticulitis. The incidence of complications among patients taking an unrestricted diet during an initial acute uncomplicated episode of diverticulitis was in line with that reported in the literature. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.
S L Wadhwa
Full Text Available Gonorrhoea constitutes nine per cent of the sexually transmitted diseases seen at the department of Dermatology and Venereology, Nair Hospital, Bombay. Fifty cases of uncomplicated males were treated with doxycycline 200mgs iv on the first day and 100 mgs, iv for 2 more - a total of 400 mgs doxycycline. Smears for gonococci and blood V D R L were treatment. The cases were reviewed every week for a period 3 weeks. Three cases showed a positive serology and 44 cases responded well to therapy giving a success rate of 88%. Side effects were minimal.
Full Text Available The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed to look for early signs of systemic complications. In fact, severe malaria is a life threatening but treatable disease. The protean and nonspecific clinical findings occurring in malaria (fever, malaise, headache, myalgias, jaundice and sometimes gastrointestinal symptoms of nausea, vomiting and diarrhoea may lead physicians who see malaria infrequently to a wrong diagnosis, such as influenza (particularly during the seasonal epidemic flu, dengue, gastroenteritis, typhoid fever, viral hepatitis, encephalitis. Physicians should be aware that malaria is not a clinical diagnosis but must be diagnosed, or excluded, by performing microscopic examination of blood films. Prompt diagnosis and appropriate treatment are then crucial to prevent morbidity and fatal outcomes. Although Plasmodium falciparum malaria is the major cause of severe malaria and death, increasing evidence has recently emerged that Plasmodium vivax and Plasmodium knowlesi can also be severe and even fatal.
Full Text Available Background . Urinary tract infections (UTIs represent 10-20% of all community-acquired infections. Escherichia coli remains the most commonly isolated microorganism. Because of the dominance of these bacteria, routine laboratory tests are not recommended in making the first UTI diagnosis. However, careful monitoring of all etiological agents of ncomplicated UTIs should be an important strategy for empirical therapy. Objectives . A determination of the incidence of UTI bacterial etiological agents in outpatients. Material and methods. The results of urine cultures were analyzed. The samples were obtained in the period from 01.2011 to 03.2013 from outpatients of all age groups. Results . The rods of Escherichia coli were the most frequently identified microorganisms responsible for uncomplicated UTIs. They were isolated from 52% of infected patients. Every fourth case of UTI indicated the participation of Enterococcus spp. And Streptococcus agalactiae . The next 21% of infections were caused by Gram-negative bacteria other than E. coli . The role of coagulase-negative staphylococci was insignificant and equaled less than 2%. Conclusions . Despite the dominant role of E. coli in urinary tract infections, there has been a decrease in the frequency of its isolation. However, the natural resistance of Enterococcus spp. to antibiotics increases the number of urinary tract infections caused by these bacteria. Streptococcus agalactiae is a UTI cause with similar frequency in women of reproductive age and postmenopausal women. Monitoring of the incidence of uncomplicated infections facilitates empirical treatment and prevents UTI recurrence.
Etoka-Beka, Mandingha Kosso; Ntoumi, Francine; Kombo, Michael; Deibert, Julia; Poulain, Pierre; Vouvoungui, Christevy; Kobawila, Simon Charles; Koukouikila-Koussounda, Felix
To investigate the proportion of malaria infection in febrile children consulting a paediatric hospital in Brazzaville, to determine the prevalence of submicroscopic malaria infection, to characterise Plasmodium falciparum infection and compare the prevalence of uncomplicated P. falciparum malaria according to haemoglobin profiles. Blood samples were collected from children aged malaria and 21% with submicroscopic infection. The mean parasite density in children with uncomplicated malaria was 42 824 parasites/μl of blood. The multiplicity of infection (MOI) was 1.59 in children with uncomplicated malaria and 1.69 in children with submicroscopic infection. The mean haemoglobin level was 10.1 ± 1.7 for children with uncomplicated malaria and 12.0 ± 8.6 for children with submicroscopic infection. About 13% of the children harboured the sickle cell trait (HbAS); the rest had normal haemoglobin (HbAA). No difference in prevalence of uncomplicated malaria and submicroscopic infection, parasite density, haemoglobin level, MOI and P. falciparum genetic diversity was observed according to haemoglobin type. The low prevalence of uncomplicated malaria in febrile Congolese children indicates the necessity to investigate carefully other causes of fever. © 2016 John Wiley & Sons Ltd.
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.
India being a tropical country, parasitic infections especially with Plasmodium species are very common in this region. The present case report is that of Plasmodium vivax, Plasmodium falciparum and dengue co‑infection in a 6 months pregnant lady who was timely diagnosed and appropriately treated followed by a ...
Añez, Arletta; Navarro-Costa, Dennis; Yucra, Omar; Garnica, Cecilia; Melgar, Viviana; Moscoso, Manuel; Arteaga, Ricardo; Nakao, Gladys
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.
Full Text Available Problem: We are not aware of studies in Colombia on levels of specific IgE in children without malaria and only one is available in children with uncomplicated malaria. Objective: To measure anti-Plasmodium IgE in children with or without malaria according to sex, nutritional status, and the presence of intestinal helminthes, and the relations with hematologic variables. Methodology: anti-Plasmodium IgE was measured in 335 children without malaria and in 125 with uncomplicated malaria (P. vivax: 116; P. falciparum: 9. Measurement was done with the ELISA technique, with a crude antigen extract of P. falciparum FCB-2 strain. We used Sigma`s conjugated anti-anti-IgE A3525. IgE was measured and expressed as optical density (absorbance. Results: Anti-Plasmodium IgE in children without malaria was 0.808 ± 0.508 (cutoff point used to define high level: 0.584 and 1.968 ± 1.237 in children with malaria (p = 0.000000. Anti-Plasmodium IgE levels showed no significant difference according to plasmodial species but there was significant difference by sex and nutritional status. In children without malaria, the level of anti-Plasmodium IgE was higher in those with the presence of roundworm, whipworm and hookworm, but the difference was significant only for roundworms. The level of anti-Plasmodium IgE showed significant positive linear correlation with the number of eggs of Ascaris and whipworm per gram of stool. Conclusions: In Urabá, children with or without malaria have elevated levels of anti-Plasmodium IgE, that are higher in women and in those affected by malaria.
Molecular surveillance of Plasmodium falciparum drug resistance markers reveals partial recovery of chloroquine susceptibility but sustained sulfadoxine-pyrimethamine resistance at two sites of different malaria transmission intensities in Rwanda
Kateera, Fredrick; Nsobya, Sam L.; Tukwasibwe, Steven; Hakizimana, Emmanuel; Mutesa, Leon; Mens, Petra F.; Grobusch, Martin P.; van Vugt, Michèle; Kumar, Nirbhay
Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda replaced CQ with amodiaquine (AQ)+sulfadoxine-pyrimethamine (SP) in 2001, and subsequently with artemether-lumefantrine (AL) in 2006, as first-line treatments for uncomplicated malaria. Following years
Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in the em>P. falciparum dihydropteroate synthase gene
Alifrangis, Michael; Lusingu, John P; Mmbando, Bruno
In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two vill...
Full Text Available Acute renal failure disseminated intravascular coagulation,acute respiratory distress syndrome (ARDS, hypoglycemia,coma or epileptic seizures are manifestationsof severe Plasmodium (P. falciparum malaria. P. vivaxmalaria is rarely associated with severe complications.We report a case of 30-year-old male refugee comingfrom Pakistan, has been found in hospital garden as unconscious.After therapy of pneumonia requiring intensivecare unit and intensive supportive care, the patient leftinvasive mechanical ventilation (IMV. Because of continuedfever and chills attacks focused on malaria diagnosis,Plasmodium vivax malaria detected on thick peripheralblood smear. After intensive supportive care and specificanti-plasmodial therapy, the patient recovered and wasdischarged from hospital. The use of IMV vivax-malariarelated ARDS was associated with a good outcome. JClin Exp Invest 2013; 4 (2: 226-228Key words: ARDS, Plasmodium vivax, pneumonia, respiratoryfailure
Abdulla, Salim; Achan, Jane; Adam, Ishag
Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are importa...
Hviid, L; Theander, T G; Abdulhadi, N H
Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area...... of Sudan were analyzed for expression of cell surface antigens associated with T lymphocyte adhesion, activation and maturation. The results were compared to results from T cells obtained from the same donors either before the attack, or during convalescence. Most donors showed a remarkable loss of T cells...... peripheral CD3+ T lymphocytes expressed LFA-1, which had a clearly bimodal distribution on these cells. The T cell subpopulation having high LFA-1 expression (LFA-1++) was composed of both memory and unprimed T cells, according to their expression of CD45RA and CD45R0. Analysis of expression of membrane...
Conclusion: This study demonstrated no increase in surgical complications after LA in patients with complicated acute appendicitis when compared with those who had uncomplicated disease. Therefore, LA may be considered the first-choice treatment option for both uncomplicated and complicated acute appendicitis.
Adukpo, Selorme; Gyan, Ben A; Ofori, Michael F; Dodoo, Daniel; Velavan, Thirumalaisamy P; Meyer, Christian G
Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells 1 (TREM-1) enhances inflammatory responses by increasing secretion of IL-8 and other Th1 cytokines. In contrast, TREM-like transcript 1 (TREML-1) promotes anti-inflammatory responses by binding to TREM-1 ligands and competing with TREM-1, thus antagonizing TREM-1 activation to reduce inflammation. Endothelial protein C receptor (EPCR) also mediates anti-inflammatory responses by activating endothelial protein C (PC). Upon microbial stimulation, soluble forms of TREM-1 (sTREM-1) and soluble EPCR (sEPCR) are released. Their plasma levels reflect the degree of inflammation and the severity of infection. In a cross-sectional study comparing patients with severe with uncomplicated malaria, sTREM-1, soluble TREML-1 (sTREML-1) and sEPCR plasma levels as well as plasma levels of sEPCR derived from convalescent patients were quantified. Samples were collected on admittance of paediatric patients infected with Plasmodium falciparum to hospitals in Accra, Ghana. Distinct genetic regions of the genes encoding TREM-1, EPCR, interleukin (IL)-8 and IL-18 encompassing known genetic polymorphisms that influence plasma levels underwent DNA sequencing. Higher sTREM-1 levels were observed among children suffering from severe malaria compared to those with uncomplicated malaria (P = 0.049). Low TREM-1 to TREML-1 ratios were associated with uncomplicated malaria (P = 0.033). The TREM1 rs2234237T variant causing the amino acid exchange Thr25Ser, which has been associated with higher TREM-1 plasma levels, was significantly more frequent among patients with severe malaria than in those with uncomplicated malaria (P = 0.036). Low levels of sEPCR were observed in severe and uncomplicated malaria, while variant genotypes of IL8, IL18 and EPCR did not show any association. Higher plasma levels of sTREM-1 alone or relative to s
Nov 19, 2007 ... structure. Key words: Protein model, AMA-1, apical membrane antigen-1, Plasmodium cynomolgi. ... sional (3D) structure of a protein are of great assistance ... parent/template. The model was generated using SWISS-MODEL v 3.7. an automated protein modeling server available at www.expasy.org.
Therapeutic efficacy of sulfadoxine-pyrimethamine for. Plasmodium falciparum malaria. A study 5 years after implementation of combination therapy in Mpumalanga,. South Africa. Aaron Mabuza, John Govere, Kobus .... Parasitological success was defined as conversion from a positive smear at recruitment to a negative ...
Balasubramanian, Ishwarya; Fleming, Christina; Mohan, Helen M; Schmidt, Karl; Haglind, Eva; Winter, Des C
Management of diverticular disease has undergone a paradigm shift, with movement towards a less invasive management strategy. In keeping with this, outpatient management of uncomplicated diverticulitis (UD) has been advocated in several studies, but concerns still remain regarding the safety of this practice. To assess outcomes of out-patient management of acute UD. A comprehensive search for published studies using the search terms 'uncomplicated diverticulitis', 'mild diverticulitis' and 'out-patient' was performed. The primary outcomes were failure of medical treatment. Secondary outcomes were recurrence rate at follow up and medical cost savings. The search yielded 192 publications. Of these, 10 studies met the inclusion criteria including 1 randomized controlled trial, 6 clinical controlled trials and 3 case series. There was no difference in failure rates of medical treatment (6.5 vs. 4.6%, p = 0.32) or in recurrence rates (13.0 vs. 12.1%, p = 0.81) between those receiving ambulatory care and in-patient care for UD. Ambulatory treatment is associated with an estimated daily cost savings of between 600 and 1,900 euros per patient treated. Meta-analysis of data was not possible due to heterogeneity in study designs and inclusion criteria. Ambulatory management of acute UD is reasonable in selected patients. © 2016 S. Karger AG, Basel.
Full Text Available Abstract Artemisinin-based combination therapies (ACTs are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance.
Full Text Available Abstract Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713
Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G
Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5 degrees C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. The fever clearance time using a fever threshold of 37.5 degrees C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8 degrees C or 38.0 degrees C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. The trial registration number is: NCT00167713.
Happi, C T; Gbotosho, G O; Folarin, O A; Akinboye, D O; Yusuf, B O; Ebong, O O; Sowunmi, A; Kyle, D E; Milhous, W; Wirth, D F; Oduola, A M J
Mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes have been used as means to predict treatment failure to sulfadoxine-pyrimethamine (SP) and for monitoring/surveillance of resistance to the drug in many areas where malaria is endemic. However, patients responses to treatment are significantly dependent on factors like host immunity profile of treated patients. In order to investigate the relationship between molecular markers of SP resistance, host immunity and clinical outcome, the association between pre-treatment dhfr and dhps genotypes, age and treatment outcomes was evaluated in 109 children treated with SP for acute uncomplicated malaria in Ibadan, Nigeria. Seventy-three percent of the children were cured with the drug, while 27% failed treatment after 28 days of follow-up. All children infected with parasites harboring less than two dhfr/dhps mutations were cured with SP. The dhfr triple (Asn-108/Ile-51/Arg-59) mutants or the dhps double mutants (Gly-437/Glu-540) were independently associated with SP treatment failure in children aged less than 5 years, but not in older children. The dhfr and dhps quintuple mutant (dhfr triple mutant+dhps double mutant) was the genotype most strongly associated with SP treatment failure (OR=24.72, 95%CI=8.24-74.15) in both younger and older children.
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
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
Mônica da Silva-Nunes
Full Text Available We analyzed prospectively 326 laboratory-confirmed, uncomplicated malarial infections (46.3% due to Plasmodium vivax, 35.3% due to P. falciparum, and 18.4% mixed-species infections diagnosed in 162 rural Amazonians aged 5-73 years. Thirteen symptoms (fever, chills, sweating, headache, myalgia, arthralgia, abdominal pain, nausea, vomiting, dizziness, cough, dyspnea, and diarrhea were scored using a structured questionnaire. Headache (59.8%, fever (57.1%, and myalgia (48.4% were the most frequent symptoms. Ninety-six (29.4% episodes, all of them diagnosed during cross-sectional surveys of the whole study population (96.9% by molecular technique only, were asymptomatic. Of 93 symptom-less infections left untreated, only 10 became symptomatic over the next two months following diagnosis. Fever was perceived as " intense " in 52.6% of 230 symptomatic malaria episodes, with no fever reported in 19.1% episodes although other symptoms were present. We found significant differences in the prevalence and perceived intensity of fever and other clinical symptoms in relation to parasite load at the time of diagnosis and patient's age, cumulative exposure to malaria, recent malaria morbidity, and species of malaria parasite. These factors are all likely to affect the effectiveness of malaria control strategies based on active or passive detection of febrile subjects in semi-immune populations.
MCKENZIE, F. ELLIS; JEFFERY, GEOFFREY M.; COLLINS, WILLIAM E.
We analyzed records of malariotherapy patients sequentially or simultaneously inoculated with Plasmodium falciparum and Plasmodium malariae. Gametocyte production was enhanced in P. falciparum by prior or concurrent P. malariae infection but diminished or unaffected in P. malariae by P. falciparum. Conversely, asexual-form production was diminished in P. malariae but unaffected in P. falciparum. PMID:12452496
MONGELA, STELA; Enweji, Nizar; MNONG’ONE, NAIZIHIJWA; Minde, Mercy; Kamugisha, Erasmus; Swedberg, Göte
The high prevalence of sickle cell disease (SCD) and trait in Sub-Saharan Africa coincides with thedistribution of Plasmodium falciparum malaria. Due to prolonged heavy use of chloroquine (CQ) as anantimalarial, drug resistance has developed. Many countries including Tanzania abandoned the use of CQfor uncomplicated malaria, except its use as prophylaxis in patients with sickle cell disease. This studyinvestigated the prevalence of malaria in SCD patients and mutations associated with CQ resi...
Sodowski, Krzysztof; Cnota, Wojciech; Czuba, Bartosz; Borowski, Dariusz; Wielgos, Miroslaw; Kaminski, Pawel; Jaczyńska, Renata; Włoch, Agata; Kuka, Dorota; Zwirska-Korczala, Krystyna; Szaflik, Krzysztof
The ductus venosus is the very important part of fetal venous circulation. It plays a central role in return of venous blood from the placenta. This unique shunt carries well-oxygenated blood from the umbilical vein through the inferior atrial inlet on its way across the foramen ovale. Using Doppler ultrasound, it is possible to assess the blood flow in fetal vessels including ductus venosus. It is observed, in animal and human studies, that the typical waveform for blood flow in ductus venosus in early pregnancy can be different depending on numerous conditions e.g. fetal karyotype. This study is performed to assess the physiologic parameters of blood flow in ductus venosus in uncomplicated early pregnancy. 404 women were examined between 11+0 and 13+6 weeks (+ days) of gestation by ultrasound. Fetal crown-rump length (CRL) was measured to assess the gestational age. The assessment of risk of fetal abnormalities was based on nuchal translucency (NT) measurement. The ductus venosus blood flow with color and spectral Doppler was obtained in all patients. The following features were assessed: pulsatility index (PI), and direction of flow (positive/negative) during atrial contraction (wave A). All cases were followed up to 22 weeks of gestation when the control scan was performed. 30 cases were excluded from the uncomplicated group due to: high risk of fetal abnormalities, fetal loss, confirmed fetal abnormalities and utero-placental pathology. 374 women were considered as uncomplicated pregnancy. In both uncomplicated and complicated groups the mean values for pulsatility index (PI) were established. The mean PI value in uncomplicated pregnancies was: 0.91 (SD +/- 0.32). No significant differences between groups were noticed. In 370 cases of uncomplicated pregnancy the A wave direction was positive but in 1.1% of cases the reverse flow in atrial contraction was observed.
Karunaweera, Nadira D; Wijesekera, Subadra K; Wanasekera, Deepani; Mendis, Kamini N; Carter, Richard
The paroxysms of Plasmodium vivax malaria are antiparasite responses that, although distressing to the human host, almost never impart serious acute pathology. Using plasma and blood cells from P. vivax patients, the cellular and noncellular mediators of these events have been studied ex vivo. The host response during a P. vivax paroxysm was found to involve T cells, monocytes and neutrophils, and the activity, among others, of the pyrogenic cytokines tumor necrosis factor alpha and interleukin 2 in addition to granulocyte macrophage-colony stimulating factor. However, interferon gamma activity, associated with serious acute pathogenesis in other studies on malaria, was absent. Induction of the cytokines active during a P. vivax paroxysm depends upon the presence of parasite products, which are released into the plasma before the paroxysm. Chemical identification of these natural parasite products will be important for our understanding of pathogenesis and protection in malaria.
Full Text Available To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever.A randomized, open-label, active control trial with two parallel arms.Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal.Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria.Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days.The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse.Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval fever clearance times were 92 hours (84-114 hours for gatifloxacin recipients and 138 hours (105-164 hours for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p<0.0001. 19 out of 70 (27% patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1% in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p<0.001. Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death numbered 29. They were determined to be (95% confidence interval 37.6 % (27.14%-50.2% in the cefixime group and 3.5% (2.2%-11.5% in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p<0.0001. There was one death in the cefixime group.Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime.Current Controlled Trials ISRCTN75784880.
Background: Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria. Methods: We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes. Findings: We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor. Conclusion: IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection. 2014 Huang et al.
Kim, Jae-Gyum; Choi, Jeong-Yoon; Kim, Sung Un; Jung, Jin-Man; Kwon, Do-Young; Park, Moon Ho; Oh, Kyungmi
Headache may be a warning sign of subsequent stroke in patients with vertebral artery dissection (VAD). Even though the headache characteristics of VAD have been described predominantly in patients with extracranial VAD and neurological complications, headache semiology is not well known in patients with uncomplicated intracranial vertebral artery dissection (ICVAD). In the present study, we attempt to identify the headache semiology that characterizes ICVAD and validate the revised version of the International Classification of Headache Disorders (ICHD-3 beta) criteria for headache attributed to intracranial artery dissection. Six patients with neurologically uncomplicated ICVAD presented at a participating medical center, and eight similar patients were reviewed in the literature. Combining these data, we analyzed headache characteristics of patients with uncomplicated ICVAD according to their pain onset and duration, nature, intensity, location, aggravating and relieving factors, associated symptoms, response to medication, and prognosis. Headache in uncomplicated ICVAD usually has an acute mode of onset (11/14) and persistent (10/14) temporal feature. Pain that has a throbbing quality (nine of 14) and severe intensity (13/14) on the ipsilesional (10/14) and occipitonuchal area (12/14) is a headache prototype in ICVAD. Additionally, headache was intensified by head flexion and rotation (three of six), and relieved by head extension and supine positioning (five of six). Headache of all patients in the present study fulfilled the ICHD-3 beta criteria. Headache semiology of uncomplicated ICVAD is mostly homogenous in the present study. These characteristics may be helpful in the diagnosis of uncomplicated ICVAD. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Hines, Michelle C; Al-Salamah, Tareq; Heil, Emily L; Mallemat, Haney; Witting, Michael D; Johnson, Jennifer K; Winters, Michael E; Hayes, Bryan D
Urine cultures are not always performed for female Emergency Department (ED) patients with uncomplicated urinary tract infection (UTI). Accordingly, hospital, and even ED-specific, antibiograms might be skewed toward elderly patients with many comorbidities and relatively high rates of antimicrobial resistance, and thus do not accurately reflect otherwise healthy women. Our ED antibiogram indicates Escherichia coli resistance rates for ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX) of 42%, 26%, and 33%, respectively. This study aims to compare resistance rates of urinary E. coli from otherwise healthy women with uncomplicated UTI and pyelonephritis in the ED to rates in our ED antibiogram. Females > 18 years old with acute onset of urinary frequency, urgency, or dysuria with pyuria identified on urinalysis (white blood cell count > 10/high-power field) were prospectively enrolled in the ED of an urban, academic medical center. Exclusion criteria indicating a complicated UTI were consistent with Infectious Diseases Society of America guidelines. Susceptibility patterns of E. coli to ciprofloxacin, levofloxacin, and TMP-SMX in the study group were compared to our ED antibiogram. Forty-five patients grew E. coli. Pyelonephritis was suspected in nine (20%) subjects. Compared with the ED antibiogram, significantly lower rates of resistance to ciprofloxacin (2% vs. 42%, p < 0.001), levofloxacin (2% vs. 26%, p < 0.001), and TMP-SMX (16% vs. 33%, p = 0.016) were observed. Six patients grew non-E. coli uropathogens. All were susceptible to both levofloxacin and TMP-SMX. ED antibiograms may overestimate resistance rates for uropathogens causing uncomplicated UTIs. In cases where nitrofurantoin cannot be used, fluoroquinolones and possibly TMP-SMX may remain viable options for treatment of uncomplicated UTI and pyelonephritis in women. Copyright © 2015 Elsevier Inc. All rights reserved.
Hogan, John; Sehgal, Rishabh; Murphy, Dermot; O'Leary, Peter; Coffey, J Calvin
The usefulness of inflammatory indices in assessment of the severity of acute diverticulitis remains unestablished. The aim of this study was to determine whether inflammatory indices and hematological ratios could be utilised to differentiate between uncomplicated and complicated diverticulitis. Hematological and inflammatory indices were recorded for each admission with CT confirmed acute diverticulitis (101 complicated, 127 uncomplicated). Cases were divided into training (n = 57) and test sets (n = 171). A classification and regression tree (CART) analysis was employed in the training set to identify optimal inflammatory marker cut-off points associated with complicated diverticulitis. Samples (test set) were then categorized as (A) greater than and (B) less than CART identified cut-off points. The predictive properties of inflammatory marker cut-off points in distinguishing severity of diverticulitis were assessed using a univariate logistic regression analysis, summary receiver operating characteristic curves and confusion matrix generation. C-reactive protein >109 mg/ml (OR 3.07, 95% CI 1.43-6.61, p = 0.004, area under the curve; AUC = 0.64) and white cell lymphocyte ratio (WLR) >17.72 (OR 4.23, 95% CI 1.95-9.17, p 21 × 109/l (p = 0.02, AUC = 0.60) and lymphocyte count >0.55 × 109/l (p = 0.009, AUC = 0.60) were less accurate. Widely used inflammatory indices are useful in the depiction of complicated diverticulitis. The indices cut-off points highlighted in this study should be considered at the time of diagnosis in combination with radiological features of complicated diverticulitis. © 2016 S. Karger AG, Basel.
First page Back Continue Last page Overview Graphics. Parasites Cryptosporidium parvum, Leishmania, Plasmodium falciparum (malaria), Schistosoma. Cancer-associated antigens Carcinoembryonic antigen (CEA), melanoma-associated antigen, the MHC molecule HLA-B7.
Buchs, Nicolas C; Mortensen, Neil J; Ris, Frederic; Morel, Philippe; Gervaz, Pascal
While diverticular disease is extremely common, the natural history (NH) of its most frequent presentation (i.e., sigmoid diverticulitis) is poorly investigated. Relevant information is mostly restricted to population-based or retrospective studies. This comprehensive review aimed to evaluate the NH of simple sigmoid diverticulitis. While there is a clear lack of uniformity in terminology, which results in difficulties interpreting and comparing findings between studies, this review demonstrates the benign nature of simple sigmoid diverticulitis. The overall recurrence rate is relatively low, ranging from 13% to 47%, depending on the definition used by the authors. Among different risk factors for recurrence, patients with C-reactive protein > 240 mg/L are three times more likely to recur. Other risk factors include: Young age, a history of several episodes of acute diverticulitis, medical vs surgical management, male patients, radiological signs of complicated first episode, higher comorbidity index, family history of diverticulitis, and length of involved colon > 5 cm. The risk of developing a complicated second episode (and its corollary to require an emergency operation) is less than 2%-5%. In fact, the old rationale for elective surgery as a preventive treatment, based mainly on concerns that recurrence would result in a progressively increased risk of sepsis or the need for a colostomy, is not upheld by the current evidence. PMID:26649154
A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks\\' gestation from July 1999 to July 2007 were included. Pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks\\' gestation and 1 in 37 after 34 weeks\\' gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks\\' gestation, suggesting that a policy of elective preterm delivery warrants evaluation.
O' Connell, AnnaMarie [Children' s University Hospital, Radiology Department, Dublin 1 (Ireland); Donoghue, Veronica B. [Children' s University Hospital, Radiology Department, Dublin 1 (Ireland); National Maternity Hospital, Radiology Department, Dublin (Ireland)
Classic metaphyseal lesion (CML) is the term given to a fracture that most often occurs in the posteromedial aspect of the distal femur, proximal tibia, distal tibia, and proximal humerus in infants; this finding is strongly associated with non-accidental injury. To demonstrate that the CML may occur following simple lower segment caesarean section (LSCS). A review of 22 years of an obstetric practice that delivers 8,500 babies per year. We identified three neonates born by elective LSCS, each with distal femoral metaphyseal fractures on postpartum radiographs. All caesarean sections were elective and uncomplicated. External cephalic version was not employed preoperatively. Postpartum radiographs demonstrated a fracture of the distal femoral metaphysis in each neonate, typical of a CML. We propose that a CML can occur in the setting of a simple, elective and uncomplicated LSCS where no external cephalic version is employed. (orig.)
Djimde Abdoulaye A.
Full Text Available Artemisinin-based combination therapies decrease Plasmodium gametocyte carriage. However, the role of artesunate in monotherapy in vivo, the mechanisms involved, and the utility of gametocyte carriage as a potential tool for the surveillance of antimalarial resistance are poorly understood. In 2010–2011, we conducted an open-label, prospective efficacy study of artesunate as monotherapy in children 1–10 years of age with uncomplicated falciparum malaria in Bougoula-Hameau, Mali. Standard oral doses of artesunate were administered for 7 days and patients were followed up for 28 days. The data were compared to a similar study conducted in 2002–2004. Of 100 children enrolled in the 2010–2011 study, 92 were analyzed and compared to 217 children enrolled in the 2002–2004 study. The proportion of gametocyte carriers was unchanged at the end of treatment (23% at baseline vs. 24% on day 7, p = 1.0 and did not significantly decline until day 21 of follow-up (23% vs. 6%, p = 0.003. The mean gametocyte density at inclusion remained unchanged at the end of treatment (12 gametocytes/μL vs. 16 gametocytes/μL, p = 0.6. Overall, 46% of the 71 initial non-carriers had gametocytes detected by day 7. Similar results were found in the 2002–2004 study. In both studies, although gametocyte carriage significantly decreased by the end of the 28-day follow-up, artesunate did not clear mature gametocytes during treatment and did not prevent the appearance of new stage V gametocytes as assessed by light microscopy. Baseline gametocyte carriage was significantly higher 6 years after the deployment of artemisinin-based combination therapies in this setting.
Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.
Joo, Jeong Il; Park, Hyoung-Chul; Kim, Min Jeong; Lee, Bong Hwa
The aim of the present study is to determine the feasibility and safety of antibiotics for uncomplicated simple appendicitis in pregnancy. We conducted a 6-year prospective observational study on 20 pregnant women in whom uncomplicated simple appendicitis (appendiceal diameter ≤11 mm and with no signs of appendicoliths, perforation, or abscess) was radiologically verified and managed with a 4-day course of antibiotics. Treatment failure rate, defined as the need for an appendectomy during hospitalization and recurrence in the follow-up period (median 25 months), and maternal or fetal complications during the pregnancy were evaluated. Mean age of patients was 33.4 years, and gestational age was 17.8 weeks. Three patients failed to respond to antibiotic therapy during hospitalization and underwent subsequent appendectomy (2 suppurative and 1 perforated appendicitis). There was 1 wound infection postoperatively. During follow-up, 2 patients during their ongoing pregnancy experienced recurrence at 3 and 6 months post-treatment, and a new course of antibiotics was determined. Patients also experienced recurrence at 8 and 10 months post-treatment and underwent appendectomy. Treatment failure occurred in 5 patients (25%) with no fetal complications during the pregnancy. Antibiotic therapy for uncomplicated appendicitis in pregnancy may be a feasible treatment option without severe maternal and fetal complications. Copyright © 2017 Elsevier Inc. All rights reserved.
Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Gilchrist, James J; Graham, Stephen M; Pensulo, Paul; Mwimaniwa, Grace; Banda, Meraby; Taylor, Terrie E; Molyneux, Elizabeth E; Drayson, Mark T; Ward, Steven A; Molyneux, Malcolm E; MacLennan, Calman A
Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69(+) NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4(+) lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria. Copyright © 2016 Mandala et al.
Sahin, Erdem; Madendag, Yusuf; Tayyar, Ahter Tanay; Sahin, Mefkure Eraslan; Col Madendag, Ilknur; Acmaz, Gokhan; Unsal, Deniz; Senol, Vesile
The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios. A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34 + 0-36 + 6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1-8 cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups. Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery borderline AFI group (p = .040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p = .014). Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL, a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required. Methods One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers msp-1 and msp-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in pfmdr1 was also carried out in the samples obtained from patients before and after the treatment. Results The PCR corrected cure rates were high at both the sites viz. 100% (n = 53 in Assam and 98.6% (n = 71 in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91 and 184 (91.3%, n = 91 of pfmdr1 gene. Conclusion AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria
Price, R.; Nosten, F.; Simpson, J. A.; Luxemburger, C.; Phaipun, L.; ter Kuile, F.; van Vugt, M.; Chongsuphajaisiddhi, T.; White, N. J.
The factors affecting the development of patent Plasmodium falciparum gametocytemia were assessed in 5,682 patients entered prospectively into a series of antimalarial drug trials conducted in an area of low and seasonal transmission on the western border of Thailand. Of the 4,565 patients with
Full Text Available Background The current first line drugs for treating uncomplicated malaria are artemisinin (ART combination therapies. However, Plasmodium falciparum parasites resistant to ART and partner drugs are spreading, which threatens malaria control efforts. Rodent malaria species are useful models for understanding antimalarial resistance, in particular genetic variants responsible for cross resistance to different compounds. Methods The Plasmodium berghei RC strain (PbRC is described as resistant to different antimalarials, including chloroquine (CQ and ART. In an attempt to identify the genetic basis for the antimalarial resistance trait in PbRC, its genome was sequenced and compared with five other previously sequenced P. berghei strains. Results We found that PbRC is eight-fold less sensitive to the ART derivative artesunate than the reference strain PbANKA. The genome of PbRC is markedly different from other strains, and 6,974 single nucleotide variants private to PbRC were identified. Among these PbRC private variants, non-synonymous changes were identified in genes known to modulate antimalarial sensitivity in rodent malaria species, including notably the ubiquitin carboxyl-terminal hydrolase 1 gene. However, no variants were found in some genes with strong evidence of association with ART resistance in P. falciparum such as K13 propeller protein. Discussion The variants identified in PbRC provide insight into P. berghei genome diversity and genetic factors that could modulate CQ and ART resistance in Plasmodium spp.
Yayan, Josef; Rasche, Kurt
Malaria is an acute, life-threatening infectious disease that spreads in tropical and subtropical regions. Malaria is mainly brought over to Germany by travelers, so the disease can be overlooked due to its nonspecific symptoms and a lack of experience of attending physicians. The aim of this study was to analyze, retrospectively, epidemiological and clinical data from patients examined for malaria. Patient data were collected from hospital charts at the Department of Internal Medicine, Saarland University Medical Center, Germany, for the period of 2004-2012. The data of patients with and without malaria were compared in terms of their epidemiological, demographic, clinical, and medical treatment aspects. We identified found 15 patients with malaria (28.3 %, mean age 42.3 ± 16.5 years, three females [20 %]; 95 % confidence interval of 0.2-0.4) out of the 53 patients examined. Mainly locals brought malaria over to Homburg, Germany (p = 0.009). Malaria tropica was the most common species (p < 0.0001). One patient (6.7 %) with malaria, who had recently traveled, had a mixed infection of Plasmodium falciparum and Plasmodium malariae (p = 0.670). Malaria is characterized by thrombocytopenia (p = 0.047) and elevated C-reactive protein (p = 0.019) in serum, and fever is the leading symptom (p = 0.031). In most cases, malaria was brought from Ghana (33.3 %). Further, patients had contracted malaria despite malaria prophylaxis (33.3 %, p = 0.670). In conclusion, malaria test should be used in patients with fever after a journey from Africa. Malaria caused by Plasmodium falciparum is the most common species of brought over malaria. Mixed-species Plasmodium falciparum and Plasmodium malariae are uncommon in travelers with malaria.
Full Text Available Symptomatic uncomplicated diverticular disease (SUDD is a syndrome characterized by recurrent abdominal symptoms in patients with colonic diverticula. There is some evidence that a high-fiber diet or supplemental fibers may reduce symptoms in SUDD patients and a high-fiber diet is commonly suggested for these patients. This systematic review aims to update the evidence on the efficacy of fiber treatment in SUDD, in terms of a reduction in symptoms and the prevention of acute diverticulitis. According to PRISMA, we identified studies on SUDD patients treated with fibers (PubMed and Scopus. The quality of these studies was evaluated by the Jadad scale. The main outcome measures were a reduction of abdominal symptoms and the prevention of acute diverticulitis. Nineteen studies were included, nine with dietary fiber and 10 with supplemental fiber, with a high heterogeneity concerning the quantity and quality of fibers employed. Single studies suggest that fibers, both dietary and supplemental, could be beneficial in SUDD, even if the quality is very low, with just one study yielding an optimal score. The presence of substantial methodological limitations, the heterogeneity of the therapeutic regimens employed, and the lack of ad hoc designed studies, did not permit a summary of the outcome measure. Thus, the benefit of dietary or supplemental fiber in SUDD patients still needs to be established.
Le Thi, Diem Thuy; Le, Ngoc Hung; Nguyen, Canh Hung; Phan Thi, Danh; Na-Bangchang, Kesara
The pharmacokinetics of dihydroartemisinin (DHA) in a 5-day oral monotherapy regimen was investigated in ten adult Vietnamese patients with uncomplicated falciparum malaria. The patients were treated with a total dose of 900 mg DHA divided as single daily doses of 300, 300, 100, 100, and 100 mg from day 0 through day 4. There were no differences in the concentrations of DHA within the first two days of treatment. The pharmacokinetics of DHA in the acute phase, however, was significantly different from that in the convalescent phase of malaria. Reduced half-life (T(1/2z)) and lower area under concentration curve (AUC(infinity)) values were observed on the final day of treatment in comparison to those obtained on the first day. These decreases in T(1/2z) and AUC(infinity) were observed in concordance with increased drug clearance (CL/F). Furthermore, the time required to reach maximum plasma DHA concentration (T(max)) on day 4 was shorter than that on day 0. Together, these findings suggest that the change in pharmacokinetics of DHA is related to the physiological change in malaria patients between the acute and convalescent phases of the disease.
Kofoed, Poul-Erik; Ursing, Johan; Poulsen, Anja
The aim of the present study was to compare different doses of chloroquine (CQ) and amodiaquine (AQ) for the treatment of falciparum malaria in children. Children with Plasmodium falciparum monoinfection were allocated by block randomisation to treatment with CQ 50/kg mg or 25 mg/kg or AQ 15 mg...... for the treatment groups CQ 50/kg mg or 25 mg/kg and AQ 15 mg/kg or 30 mg/kg were 90%, 76%, 92% and 94%, respectively; the PCR-adjusted ACPR rates on Day 28 were 92%, 80%, 94% and 94%, respectively. No differences in adverse effects were observed. AQ has a high cure rate given as 30 mg/kg and 15 mg/kg, although...... it is not superior to treatment with CQ 50 mg/kg. However, 25 mg/kg of CQ is less efficient. As an interim option, Guinea-Bissau could change the recommended first-line treatment of uncomplicated malaria to CQ 50 mg/kg, reserving AQ as a partner drug for a future combination therapy....
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plasmodium species antigen detection assays. 866... Plasmodium species antigen detection assays. (a) Identification. A Plasmodium species antigen detection assay... malaria caused by the four malaria species capable of infecting humans: Plasmodium falciparum, Plasmodium...
Barnwell John W
Full Text Available Abstract More attention is being focused on malaria today than any time since the world's last efforts to achieve eradication over 40 years ago. The global community is now discussing strategies aimed at dramatically reducing malarial disease burden and the eventual eradication of all types of malaria, everywhere. As a consequence, Plasmodium vivax, which has long been neglected and mistakenly considered inconsequential, is now entering into the strategic debates taking place on malaria epidemiology and control, drug resistance, pathogenesis and vaccines. Thus, contrary to the past, the malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year. This review brings these issues to light and provides an overview of P. vivax vaccine development, then and now. Progress had been slow, given inherent research challenges and minimal support in the past, but prospects are looking better for making headway in the next few years. P. vivax, known to invade the youngest red blood cells, the reticulocytes, presents a strong challenge towards developing a reliable long-term culture system to facilitate needed research. The P. vivax genome was published recently, and vivax researchers now need to coordinate efforts to discover new vaccine candidates, establish new vaccine approaches, capitalize on non-human primate models for testing, and investigate the unique biological features of P. vivax, including the elusive P. vivax hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas of research will be essential to eradicate malaria. And to this end, the education and training of future generations of dedicated "malariologists" to advance our knowledge, understanding and the development of new interventions against each of the malaria species infecting humans also will be essential.
Moore, Brioni R; Davis, Wendy A; Clarke, Philip M; Robinson, Leanne J; Laman, Moses; Davis, Timothy M E
A recent randomized trial showed that artemisinin-naphthoquine (AN) was non-inferior to artemether-lumefantrine (AL) for falciparum malaria and superior for vivax malaria in young Papua New Guinean children. The aim of this study was to compare the cost-effectiveness of these two regimens. An incremental cost-effectiveness analysis was performed using data from 231 children with Plasmodium falciparum and/or Plasmodium vivax infections in an open-label, randomized, parallel-group trial. Recruited children were randomized 1:1 to receive once daily AN for 3 days with water or twice daily AL for 3 days given with fat. World Health Organisation (WHO) definitions were used to determine clinical/parasitological outcomes. The cost of transport between the home and clinic, plus direct health-care costs, served as a basis for determining each regimen's incremental cost per incremental treatment success relative to AL by Day 42 and its cost per life year saved. In the usual care setting, AN was more effective for the treatment of uncomplicated malaria in children aged 0.5-5.9 years. AL and AN were equally efficacious for the treatment of falciparum malaria, however AN had increased anti-malarial treatment costs per patient of $10.46, compared with AL. AN was the most effective regimen for treatment of vivax malaria, but had increased treatment costs of $14.83 per treatment success compared with AL. Whilst AN has superior overall efficacy for the treatment of uncomplicated malaria in PNG children, AL was the less costly regimen. An indicative extrapolation estimated the cost per life year saved by using AN instead of AL to treat uncomplicated malaria to be $12,165 for girls and $12,469 for boys (discounted), which means AN may not be cost-effective and affordable for PNG at current cost. However, AN may become acceptable should it become WHO prequalified and/or should donated/subsidized drug supply become available.
Ramasamy, R; Ramasamy, M; Yasawardena, S
There is considerable interest in using merozoite proteins in a vaccine against falciparum malaria. Observations that antibodies to merozoite surface proteins block invasion are a basis for optimism. This article draws attention to important and varied aspects of how antibodies to Plasmodium
Ma'ayeh, Marwan; McClennen, Evan; Chamchad, Dmitri; Geary, Michael; Brest, Norman; Gerson, Andrew
The umbilical coiling index (UCI) is a measure of the number of coils in the umbilical cord in relation to its length. Hypercoiled cords with a UCI of >0.3 coils/cm have been associated with adverse fetal and neonatal outcomes. The primary aim is to determine the accuracy of UCI measured on second trimester ultrasound in predicting UCI at birth. The secondary outcome is to investigate the association between hypercoiling of the umbilical cord on prenatal ultrasound and adverse maternal, fetal and neonatal outcomes. This was a prospective cohort study of uncomplicated singleton pregnancies. Seventy two patients were included in the study. UCI was measured in the second trimester ultrasound, and compared to UCI measured postnatally. Outcomes of patients with hypercoiled cords on ultrasound were compared to outcomes of patients with normocoiled cords. Our results failed to show a strong correlation between the UCI determined with ultrasound, and the UCI determined with examination of the umbilical cord after delivery. We also did not demonstrate that measurement of the UCI on second trimester ultrasound is able to predict adverse maternal, fetal or neonatal outcomes. This study suggests that measurement of the umbilical coiling index should not be part of routine second trimester sonography in patients with uncomplicated singleton pregnancies, with no other medical or surgical comorbidities.
Querques, Lea; Querques, Giuseppe; Cascavilla, Maria Lucia; Triolo, Giacinto; Lattanzio, Rosangela; Introini, Ugo; Bandello, Francesco
We report on a 36-year-old man who developed photic maculopathy in the left eye shortly after uncomplicated cataract surgery. The visual acuity (VA) of the left eye was 6/39 and spectral domain optical coherence tomography (SD-OCT), performed one week after surgery, revealed a hyporeflective space in the outer retina (a 'partial-thickness hole') at the fovea. Microperimetry showed a relative central scotoma and multifocal electroretinogram (ERG) showed reduced responses within the central 10°. Two months later, VA in the felt eye improved to 6/6 and SD-OCT showed an almost complete resolution of the 'partial-thickness hole'. Microperimetry showed the resolution of the relative scotoma at the fovea and multifocal ERG showed improved responses within the central 10°. SD-OCT, microperimetry and multifocal ERG are useful tools in the diagnosis and follow-up of photic maculopathy after uncomplicated cataract surgery. Its natural history may be characterised by resolution of both morphological and functional changes shortly after surgery. © 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.
Hughes, G Chad; Andersen, Nicholas D; McCann, Richard L
Acute type B aortic dissection (identified within 2 weeks of symptom onset), as described using the Stanford classification, involves the aorta distal to the left subclavian artery and accounts for 25%-40% of all aortic dissections. The traditional treatment paradigm of medical management for uncomplicated acute type B dissection and open surgical intervention for early or late complications of type B dissection is currently undergoing a period of evolution as a result of the influence of minimally invasive thoracic endovascular aortic repair options. Thoracic endovascular repair has replaced open surgical repair as the preferred treatment for complicated acute type B dissection, and may also prove beneficial for prophylactic repair of uncomplicated acute type B dissection for high-risk patients. This review discusses the management of acute type B aortic dissection and long-term treatment considerations. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Full Text Available Measurement of malaria burden is fraught with complexity, due to the natural history of the disease, delays in seeking treatment or failure of case management. Attempts to establish an appropriate case definition for a malaria episode has often resulted in ambiguities and challenges because of poor information about treatment seeking, patterns of infection, recurrence of fever and asymptomatic infection. While the primary reason for treating malaria is to reduce disease burden, the effects of treatment are generally ignored in estimates of the burden of malaria morbidity, which are usually presented in terms of numbers of clinical cases or episodes, with the main data sources being reports from health facilities and parasite prevalence surveys. The use of burden estimates that do not consider effects of treatment, leads to under-estimation of the impact of improvements in case management. Official estimates of burden very likely massively underestimate the impact of the roll-out of ACT as first-line therapy across Africa. This paper proposes a novel approach for estimating burden of disease based on the point prevalence of malaria attributable disease, or equivalently, the days with malaria fever in unit time. The technique makes use of data available from standard community surveys, analyses of fever patterns in malaria therapy patients, and data on recall bias. Application of this approach to data from Zambia for 2009-2010 gave an estimate of 2.6 (95% credible interval: 1.5-3.7 malaria attributable fever days per child-year. The estimates of recall bias, and of the numbers of days with illness contributing to single illness recalls, could be applied more generally. To obtain valid estimates of the overall malaria burden using these methods, there remains a need for surveys to include the whole range of ages of hosts in the population and for data on seasonality patterns in confirmed case series.
Full Text Available Abstract Background Presented here are the results of a comparative trial on the efficacy of three artemisinin-based combinations conducted from May to October 2004, in Pool Province, Republic of Congo. Methods The main outcome was the proportion of cases of true treatment success at day 28. Recrudescences were distinguished from re-infections by PCR analysis. A total of 298 children of 6–59 months were randomized to receive either artesunate + SP (AS+SP, artesunate + amodiaquine (AS+AQ or artemether + lumefantrine (AL, of which 15 (5% were lost to follow-up. Results After 28 days, there were 21/85 (25% recurrent parasitaemias in the AS+SP group, 31/97 (32% in the AS+AQ group and 13/100 (13% in the AL group. The 28-day PCR-corrected cure rate was 90.1% [95% CI 80.7–95.9] for AS+SP, 98.5% [95% CI 92.0–100] for AS+AQ and 100% [95.8–100] for AL, thereby revealing a weaker response to AS+SP than to AL (p = 0.003 and to AS+AQ (p = 0.06. A potential bias was the fact that children treated with AL were slightly older and in better clinical condition, but logistic regression did not identify these as relevant factors. There was no significant difference between groups in fever and parasite clearance time, improvement of anaemia and gametocyte carriage at day 28. No serious adverse events were reported. Conclusion Considering the higher efficacy of AL as compared to AS+SP and the relatively high proportion of cases with re-infections in the AS+AQ group, we conclude that AL is clinically more effective than AS+SP and AS+AQ in this area of the Republic of Congo. Implementation of the recently chosen new national first-line AS+AQ should be monitored closely.
Kant, GD; Dullaart, RPF; Smit, AJ
Uncomplicated Type I (insulin-dependent) diabetes mellitus is characterized by generalized vasodilatation. Its possible correlates, increased microvascular permeability and endothelial dysfunction, have been associated with long-term complications. The objective was to study the effects of acute
Full Text Available Abstract Background In Tanzania, drug-resistant malaria parasites are an increasing public health concern. Because of widespread chloroquine (CQ resistance Tanzania changed its first line treatment recommendations for uncomplicated malaria from CQ to sulfadoxine-pyrimethamine (SP in 2001. Loss of SP sensitivity is progressing rapidly. SP resistance is associated with mutations in the dihydrofolate reductase (pfdhfr and dihydropteroate synthase (pfdhps genes. Methods In samples from 86 patients with uncomplicated Plasmodium falciparum malaria from Mbeya and Matema, Mbeya region, south-western Tanzania, the occurrence of mutations was investigated in the pfcrt and pfmdr1 genes which are associated with CQ resistance and in pfdhfr and pfdhps, conferring SP resistance, as well in cytb which is linked to resistance to atovaquone. Results Pfcrt T76 occurs in 50% and pfmdr1 Y86 in 51.7%. Pfdhfr triple mutations coexisting with pfdhps double mutations were detected in 64.3% of the P. falciparum isolates. This quintuple mutation is seen as a possible predictive molecular marker for SP treatment failure. Mutations of the cytb gene were not detected. Conclusion These findings of a high prevalence of mutations conferring SP resistance correspond to data of in vivo SP efficacy studies in other regions of Tanzania and underline the recommendation of changing first-line treatment to artemisinin-based combination therapy.
Full Text Available We examined the prevalence of specific perinatal complications of monochorionic-diamniotic twin pregnancies in cases without any abnormal findings until the second trimester of pregnancy. This was a retrospective cohort study performed at a tertiary perinatal center in Tokyo, Japan. There were 88 cases of uncomplicated monochorionic-diamniotic twin pregnancies at 28 weeks of gestation. In five of them (5.7%, there were serious complications associated with placental circulatory imbalance between the twins during the third trimester of pregnancy. Two cases were complicated by twin–twin transfusion syndrome, two cases were complicated by twin anemia–polycythemia sequence, and one case was complicated by acute twin–twin transfusion syndrome. In the five cases, no abnormal ultrasonographic findings or symptoms were recognized one or two weeks prior to the diagnosis. Fifty-eight cases (65.9% were delivered at term uneventfully. Serious complications due to placental circulatory imbalance between twins occurred in about 6% of cases during the third trimester of pregnancy.
Hryniewiecki, Tomasz; Sitkiewicz, Dariusz; Rawczyńska-Englert, Irena
Infective endocarditis especially where blood culture is negative frequently causes problems in diagnosis despite of many nonspecific inflammation parameters. Procalcitonin (PCT) concentration is a new marker of severe bacterial and fungal infection. The aim of this study was to evaluate the usefulness of PCT concentration assessment in the diagnosis of uncomplicated infective endocarditis of bacterial etiology. The study group consisted of 30 patients with ongoing infective endocarditis in the course of acquired valvular heart disease. The diagnosis of bacterial endocarditis was established according to the Duke criteria on the basis of: clinical examination, laboratory investigations (inflammatory parameters, transthoracic and transesophageal echocardiography) and positive blood cultures. Patients with sepsis, concomitant infections and in an early postoperative period were excluded. Two control groups consisted of: 10 patients without endocarditis and other infections and another 10 patients without endocarditis and with an urinary tract infection. Serum procalcitonin concentrations were measured by an immunoluminometric assay (LUMItest PCT set). Mean serum PCT concentrations in patients with endocarditis (0.12 +/- 0.13, range 0-0.4 ng/ml) were significantly higher than in control group without infection (0.03 +/- 0.05, range 0-0.1 ng/ml) and higher than in control group with an urinary tract infection (0.02 +/- 0.04, range 0-0.1 ng/ml). However in 12 patients (of 30) were below sensitivity of the method and in the rest were within normal range (< 0.5 ng/ml). Serum PCT concentration assessment seems to have no value in the diagnosis of uncomplicated infective endocarditis.
Schaeffer, Jacob S; Shakhnovich, Irina; Sieck, Kyle N; Kallies, Kara J; Davis, Clark A; Cogbill, Thomas H
Health-care costs and risks of radiation and intravenous contrast exposure challenge computed tomography angiography (CTA) as the standard surveillance method after endovascular abdominal aortic aneurysm repair (EVAR). We reviewed our experience using Duplex ultrasound scan (DUS) as an initial and subsequent surveillance technique after uncomplicated EVAR. The medical records of patients who underwent EVAR from 2004 to 2014 with at least 1 postoperative imaging study were retrospectively reviewed. Duplex ultrasound scan was the primary modality, with CTA reserved for patients with suspicious findings. Mean follow-up was 3.2 years for 266 patients. Fifty-seven endoleaks (7 type I, 50 type II) were detected in 51 patients (19%). Nineteen (33%) endoleaks were identified and monitored by DUS alone. Nine (16%) endoleaks were identified on CTA without prior DUS. Twenty-two (39%) endoleaks were identified on DUS and confirmed by CTA; 6 of these patients had a secondary intervention. When compared to subsequent CTA, there were 7 discordant results: 4 false-negative and 3 false-positive endoleaks on DUS. Two of these patients with discordant results required intervention. Follow-up CTA was not obtained for the other 2 patients due to severe comorbidities including renal disease. One of these patients eventually developed abdominal aortic aneurysm rupture and death. Among 88 patients with both DUS and CTA, positive predictive value and negative predictive value for DUS were 0.88 and 0.94, respectively. Sac size on DUS compared to CTA resulted in an interclass correlation coefficient of r = .84. In our experience, DUS was safe and effective for initial and follow-up surveillance after uncomplicated EVAR.
Fasubaa, O B; Ogunniyi, S O; Dare, F O; Isawumi, A I; Ezechi, O C; Orji, E O
Caesarean section among the Yoruba of western Nigerian is surrounded by a lot of fears, miseries, aversion, guilt and misconceptions for reasons varying from the desire by women to have a natural vaginal birth, fear of surgery, morbidity and deaths from the operation and prolonged hospital stay. To examine issues of reduced hospital stay following Caesarean section with a view of making the operation more acceptable and proffering solution to some of the problems faced by women when Caesarean section is indicated. A prospective case control study. Wesley Guild Hospital, Ilesha, Nigeria from 1st July, 1997 to 30th June, 1998. One hundred consecutive patients who had uncomplicated Caesarean section, randomised into two groups of short (three days) and prolonged (seven to eight days) hospital stay respectively. Observations of patients in both groups were made by an independent observer on day seven post-operation and the main outcomes measured included: wound infection rates, ability to maintain erect posture, mood changes, neonatal sepsis rate, immunisation rate of the neonates and average hospital bills. The findings revealed that wound infection rates of six per cent and ten per cent among the short and prolonged hospitalised patients respectively are not significantly different. Patients with short stay have better erect posture, lower incidence of depressive mood, lower neonatal sepsis rate, lower hospital bill and are more satisfied with early home discharge. Embracing the concept of early home discharge after Caesarean section in uncomplicated cases may remove some of the psychological upsets and economical impediments associated with the operation and make the operation more acceptable.
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
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
Oduro, A R; Anyorigiya, T; Anto, F; Amenga-Etego, L; Ansah, N A; Atobrah, P; Ansah, P; Koram, K; Hodgson, A
Although the use of artesunate-amodiaquine treatment is growing in Africa, data on its effectiveness are limited. In only the second published comparison of supervised and unsupervised treatments with this combination, Ghanaian children with uncomplicated malaria have recently been investigated in an open-label, randomized, comparative study. Children aged 6-120 months attending the Navrongo War Memorial hospital between November 2005 and December 2006 were enrolled if they had uncomplicated Plasmodium falciparum malaria and at least one of their parents/guardians gave their informed consent. Overall, 638 patients were screened, 357 were found to have P. falciparum infection, and 308 of these satisfied the other selection criteria and were enrolled. The subjects were divided randomly into two treatment arms. All the children were scheduled to receive 10 mg amodiaquine/kg and 4 mg artesunate/kg daily for 3 days but only 154 (the 'supervised') were given all their treatments in hospital, with each dose directly observed. Although the other 154 children (the 'unsupervised') were given their first dose in hospital, under supervision, they were then sent home with the tablets they required to complete treatment. Study participation lasted for 28 days, with follow-up on days 3, 7, 14, 21 and 28. During follow-up, axillary temperatures, any emergent signs and symptoms, and concomitant drug consumption were recorded and haemoglobin concentrations and malarial parasitaemias and gametocytaemias were measured. All but seven of the 308 subjects completed the study. At enrolment the subjects had a mean age of 45.0 months, a mean weight of 14.8 kg, a mean axillary temperature of 37.9 degrees C and a geometric mean parasitaemia of 11,367 asexual stages/microl. About 55% of the children investigated were girls. There were no significant baseline difference between the two treatment arms. Although there was also no difference in the clearance of fever and parasitaemia between the
Montagna, Georgina N; Matuschewski, Kai; Buscaglia, Carlos A
Plasmodium, the causative agent of malaria, employs its own actin/myosin-based motor for forward locomotion, penetration of molecular and cellular barriers, and invasion of target cells. The sporozoite is unique amongst the extracellular Plasmodium developmental forms in that it has to cross considerable distances and different tissues inside the mosquito and vertebrate hosts to ultimately reach a parenchymal liver cell, the proper target cell where to transform and replicate. Throughout this dangerous journey, the parasite alternates between being passively transported by the body fluids and using its own active cellular motility to seamlessly glide through extracellular matrix and cell barriers. But irrespective of the chosen path, the sporozoite is compelled to keep on moving at a fairly fast pace to escape destruction by host defense mechanisms. Here, we highlight and discuss recent findings collected in Plasmodium sporozoites and related parasites that shed new light on the biological significance of apicomplexan motility and on the structure and regulation of the underlying motor machinery.
López-Martínez, Briceida; Calderón-Jaimes, Ernesto; Olivar-López, Víctor; Parra-Ortega, Israel; Alcázar-López, Virginia; Castellanos-Cruz, María Del Carmen; de la Garza-López, Alicia
Urinary tract infection in children is well recognized as a cause of acute morbidity and chronic medical conditions. As a result, appropriate use of antimicrobial agents, however, increases antibiotic resistance and complicates its treatment due to increased patient morbidity, costs, rates of hospitalization, and use of broader-spectrum antibiotics. The goal of this study was to determine antibiotic susceptibility to commonly used agents for urinary tract infection against recent urinary isolates. A total of 457 consecutive children attending the emergency room at the Hospital Infantil de México Federico Gómez with symptoms of uncomplicated lower urinary tract infection were eligible for inclusion. Patients who had had symptoms for≥7 days and those who had had previous episodes of urinary tract infection, received antibiotics or other complicated factors were excluded. Midstream and catheter urine specimens were collected. All isolates were identified and the in vitro activities of antimicrobials were determined. The most frequently isolated urinary pathogens were as follows: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). The resistance to trimetoprim/sulfametoxazol (%) was 73.7, 62.2, 100, 52, and 50, respectively, for E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis and Enterobacter spp., 92.5 for Enterococcus faecalis (E. faecalis) and 49.9 for Enterococcus faecium (E. faecium). Ampicillin was 86.3, 45, 100, 47.9, and 66.6% for the same strains, ciprofloxacin 33.8, 9, 18.8, 0, 0%, nitrofurantoin 4.4, 13, 97.7, 70, 0%; to E. faecalis 0% and 16.7% to E. faecium. Frequently prescribed empirical agents for uncomplicated urinary tract infection demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates. Copyright © 2014 Hospital
Full Text Available The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2 plus single dose primaquine (0.75mg/kg on day2 for P. falciparum infections, or with chloroquine (days 0-2 plus 14 days primaquine (3.5mg/kg total over 14 days for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374.Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections. Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3 hours for P. falciparum, 20.0 (IQR: 9.5-22.7 hours for P. vivax and 16.6 (IQR: 10.0-46.0 hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174 had severe G6PD deficiency (<10% activity, five participants (5/174 had mild G6PD deficiency (10-60% activity. The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0% and -7.4% (95%CI: -4.5 to -10.4% respectively.The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather
Fabiana Maria de Souza Leoratti
Full Text Available The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria.Blood samples were collected from P. vivax-infected patients at admission (day 0 and 30-45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2 were also evaluated in neutrophils from malaria patients.Both monocytes and neutrophils from P. vivax-infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8.Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria.
Full Text Available Background & aim: Jaundice is one of the most significant problems to consider in the neonatal period. The aim of this study was to determine the impact of oral zinc sulfate on uncomplicated neonatal jaundice using comparison of effect of just phototherapy with the effect of combination of phototherapy and oral zinc sulfate. Methods: The present double blind randomized clinical trial was carried out on 78 normal term neonates with the age of 2-7 days who were admitted for uncomplicated jaundice in neonatal ward of Imam Sajjad Hospital of Yasuj University of Medical Sciences. These infants were divided to experimental group (40 cases and control group (38 cases using block random allocation. In the control group, phototherapy was done alone and experimental group received elemental zinc orally as 10 mg daily for 5 days in combination with phototherapy. The total bilirubin serum levels were measured at the beginning of the study , 6 hours, 12 hours, and 24 hours after the beginning of the study, discharge, and one week after discharge. The collected data were analyzed by the Chi Square test, independent t-test, and analysis of variance with repeated measurement. Results: There were no significant statistical difference between the experimental group and control group in sex, age, birth weight, hemoglobin, reticulocyte percentage, G6PD deficiency, and of serum total bilirubin level at the beginning of study(p>0.05. Analysis of variance with repeated measurement showed that there were no significant statistical difference between the total bilirubin serum level at 6 hours, 12 hours, 24 hours after beginning of the study, discharge, and one week after discharge (p>0.05. Also, the mean of hospitalization duration was not significantly different between the two groups (p>0.05. Conclusion: Although oral zinc salts inhibit the enterohepatic circulation of bilirubin, however probably not effective in the treatment of neonatal physiologic
Adjei, George O; Goka, Bamenla Q; Binka, Fred
Artemether-lumefantrine (AL; Coartem, Riamet) is the first fixed-dose artemisinin combination therapy (ACT) regimen to be manufactured under Good Manufacturing Practice conditions, and is the most widely adopted ACT regimen used in malaria control programs. AL is approved for the treatment...... of uncomplicated malaria in adults, children and infants, and as treatment of uncomplicated malaria in nonimmune travelers returning from malarious areas. AL is efficacious for treating uncomplicated malaria in children and the frequency of associated adverse events is not higher than other available ACT regimens....... In this review, available evidence on efficacy and safety of AL in the treatment of uncomplicated malaria, with emphasis on children where appropriate, and focusing on characteristics that are potentially important for malaria control policy decisions, are presented and discussed....
Yeka, Adoke; Lameyre, Valerie; Afizi, Kibuuka; Fredrick, Mudangha; Lukwago, Robinson; Kamya, Moses R; Talisuna, Ambrose O
The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT), artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26). For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5%) was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]). PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18), ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed) was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in malaria. Current Controlled Trials NCT00699920.
Maiga, Hamma; Djimde, Abdoulaye A; Beavogui, Abdoul H; Toure, Ousmane; Tekete, Mamadou; Sangare, Cheick Papa O; Dara, Antoine; Traore, Zoumana I; Traore, Oumar B; Dama, Souleymane; N'Dong, Christelle; Niangaly, Hamidou; Diallo, Nouhoum; Dembele, Demba; Sagara, Issaka; Doumbo, Ogobara K
Plasmodium falciparum resistance to artemisinin has been reported in South-East Asia. Long half-life drugs are increasingly being used for malaria prevention. The potential spread of parasite resistance to these regimens is real and makes regular efficacy surveillance a priority. From August to December 2004 and July to December 2005, a randomized open label trial of sulphadoxine-pyrimethamine (SP) + artesunate (AS) versus SP + amodiaquine (AQ), and SP alone, was conducted in two villages of Mali. PCR was used to distinguish new infections from recrudescent P. falciparum infections. Patients were followed for 28 days to assess treatment efficacy. Overall 912 children aged between six to 59 months, with uncomplicated P. falciparum malaria were recruited. Baseline characteristics were similar in the three treatment arms. Crude ACPRs were 94.9%; 98.6% and 93.5% for SP + AS; SP + AQ and SP alone arms respectively (SP + AS versus SP + AQ, p = 0.01; SP + AS versus SP, p = 0.5; SP + AQ versus SP, p = 0.001). After PCR adjustment, cACPRs were 99%; 100% and 97.2% for SP + AS; SP + AQ and SP alone arms, respectively (SP + AS versus SP + AQ, p = 0.25; SP + AS versus SP, p = 0.12; SP + AQ versus SP, p = 0.007). Sulphadoxine-pyrimethamine + amodiaquine therapy was as efficacious as sulphadoxine-pyrimethamine + artesunate, but more efficacious than sulphadoxine-pyrimethamine alone in the treatment of uncomplicated P. falciparum malaria in Mali.
Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini
The most significant and efficient measures against Plasmodium knowlesi outbreaks are efficient anti malaria drug, biological control in form of predatory mosquitoes and culling control strategies. In this paper optimal control theory is applied to a system of ordinary differential equation. It describes the disease transmission and Pontryagin's Maximum Principle is applied for analysis of the control. To this end, three control strategies representing biological control, culling and treatment were incorporated into the disease transmission model. The simulation results show that the implementation of the combination strategy during the epidemic is the most cost-effective strategy for disease transmission.
Grillet, María-Eugenia; El Souki, Mayida; Laguna, Francisco; León, José Rafael
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.
Cusimano, Alessia; Macaione, I; Fiorentino, E
Swallowing, voice disorders, throat discomfort and subjective neck discomfort are usually reported by patients with a known thyroid nodule and are correlated to nodular thyroid disease itself. Moreover, in endemic goitrous areas, total thyroidectomy (TT) is the most frequently performed surgical procedure. We are used to relate swallowing, voice and throat discomfort to the mechanical effects of nodular goiter or to thyroidectomy itself, but in both these cases the relationship between symptoms and the thyroid mass or its removal is not always clear or easily demonstrated. How can we explain the persistence of local neck symptoms after TT? And how can TT worsen the dysphagic or dysphonic disorders attributed to the goiter's effect over the surrounding structures? During these years, many articles have analyzed the relationship between the thyroid disease and the laryngopharyngeal reflux, finding more and more evidences of their consensuality, leading to important new management considerations and notable medico-legal implications; if the reason of local neck symptoms is not the thyroid disease, we have to study and specially cure the reflux disease, with specific test and drugs. Therefore, the aim of our study, relying on the published literature, was to investigate how, in demonstrated presence of reflux laryngopharyngitis in patients with nodular goiter and local neck symptoms before and after uncomplicated TT, the surgery could influence our anti-reflux mechanism analyzing the anatomical connection as well as the functional coordination; can we play a part in the post-operative persistence of swallowing and voice alterations and throat discomfort?
Aring, Ann M; Chan, Miriam M
Rhinosinusitis is one of the most common conditions for which patients seek medical care. Subtypes of rhinosinusitis include acute, subacute, recurrent acute, and chronic. Acute rhinosinusitis is further specified as bacterial or viral. Most cases of acute rhinosinusitis are caused by viral infections associated with the common cold. Symptomatic treatment with analgesics, decongestants, and saline nasal irrigation is appropriate in patients who present with nonsevere symptoms (e.g., mild pain, temperature less than 101°F [38.3°C]). Narrow-spectrum antibiotics, such as amoxicillin or trimethoprim/sulfamethoxazole, are recommended in patients with symptoms or signs of acute rhinosinusitis that do not improve after seven days, or that worsen at any time. Limited evidence supports the use of intranasal corticosteroids in patients with acute rhinosinusitis. Radiographic imaging is not recommended in the evaluation of uncomplicated acute rhinosinusitis. Computed tomography of the sinuses should not be used for routine evaluation, although it may be used to define anatomic abnormalities and evaluate patients with suspected complications of acute bacterial rhinosinusitis. Rare complications of acute bacterial rhinosinusitis include orbital, intracranial, and bony involvement. If symptoms persist or progress after maximal medical therapy, and if computed tomography shows evidence of sinus disease, referral to an otolaryngologist is warranted.
Comparative assessment of the clinical performance of chloroquine and sulphadoxine/pyrimethamine in the treatment of Plasmodium falciparum infection in Plateau State: an open randomised study of 109 children with acute uncomplicated malaria.
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.
Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima
BACKGROUND: In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin...... Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here...... investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the Plasmodium falciparum genes Pfdhfr, Pfdhps and Pfcrt before and a year after the introduction of SP. METHODS: Samples were collected during two cross sectional surveys in early 2002 and 2003...
A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire
Full Text Available Abstract Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination anti-malarial therapy, including artemisinins, has been advocated to improve efficacy and limit the spread of resistance. The fixed combination of oral artemether-lumefantrine (AL is highly effective and well-tolerated. Artemisinin/naphtoquine (AN is a fixed-dose ACT that has recently become available in Africa. The objectives of the study were to compare the efficacy and safety of AN and AL for the treatment of uncomplicated falciparum malaria in a high transmission-intensity site in Ivory Coast. Methods We enrolled 122 participants aged 6 months or more with uncomplicated falciparum malaria. Participants were randomized to receive either artemisinin/naphtoquine or artemether/lumefantrine with variable dose according to their weight. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. Results Among 125 participants enrolled, 123 (98.4% completed follow-up. Clinical evaluation of the 123 participants showed that cumulative PCR-uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4% for artemether/lumefantrine. Both artemisinin-based combinations effected rapid fever and parasite clearance. Interpretation These data suggest that Arco® could prove to be suitable for use as combination antimalarial therapy. Meanwhile, pharmacokinetic studies and further efficacy assessment should be conducted before its widespread use can be supported.
van Heteren, C F; Boekkooi, P F; Schiphorst, R H; Jongsma, H W; Nijhuis, J G
Testing of fetal habituation to repeated vibroacoustic stimulation might give additional information concerning the fetal condition and central nervous system (CNS) functioning in postterm pregnancies. This study is designed to investigate whether healthy postterm fetuses are able to habituate and if so, if the habituation pattern of postterm fetuses differs from that of term fetuses. Twenty women with an uncomplicated pregnancy beyond 41 weeks gestational age (GA) participated, and 37 women with a GA between 37 and 40 weeks served as controls. The vibroacoustic stimulus was repeatedly applied to the maternal abdomen above the fetal legs for a period of 1s every 30s. A fetal trunk movement within 1s of stimulus application was considered a positive response. Lack of response to four consecutive stimuli indicated habituation. The habituation rate is defined as the number of stimuli applied before the fetus stopped responding. Data were compared using Mann-Whitney U test. Of the 18 postterm fetuses in which the presence or absence of habituation could be established, 14 habituated and four persisted in responding. Twenty-six of the 32 term fetuses, in which the presence or absence of habituation could be established, habituated and six persisted in responding. The habituation rate varied widely in postterm (median of eight stimuli, quartile ranges of 6 and 18) as well as in term fetuses (median of 9.5 stimuli, quartile ranges of 6 and 15). There was no difference in median habituation rate between postterm and term fetuses. The ongoing maturation of the CNS in the last weeks of pregnancy appears not to be reflected in the fetal habituation pattern. Furthermore, the interfetal variability in habituation of healthy postterm fetuses is such that testing of habituation appears not to be suitable for the identification of the fetus at risk for an adverse neonatal outcome.
Dermatologists treat a variety of uncomplicated skin and skin structure infections (uSSSIs) such as folliculitis, impetigo, erysipelas, cellulitis, furuncles, carbuncles, and non-perirectal abscesses. Most uSSSIs are caused by Staphylococcus aureus and Streptococcus pyogenes. The new extended-spectrum cephalosporins (cefdinir, cefpodoxime) offer efficacy against most Gram-positive and Gram-negative pathogens. Despite recently published guidelines, many physicians do not prescribe cephalosporins for uSSSIs out of concern that these agents will produce a hypersensitivity reaction in patients allergic to penicillin. Although the rate of cephalosporin reaction in penicillin-allergic patients is often quoted as up to 10%, this rate does not take into account the 1% to 3% risk for allergy to cephalosporin alone and the nonspecific increased risk of penicillin-allergic patients to develop hypersensitivity to other drugs. When these additional risks are considered, the likelihood of a reaction in known penicillin-allergic patients, especially to most third-generation and extended spectrum cephalosporins, becomes less than 1%. Cephalosporins with side chains unlike those of penicillin or ampicillin side chains are less likely to result in an allergic reaction in penicillin or ampicillin-allergic patients than cephalosporins with similar side chains. Although both cefdinir and cefpodoxime are considered to carry a very low risk of cross reactivity with penicillin or ampicillin, the former demonstrates better activity against S. aureus. Among the late-generation cephalosporins, cefdinir is the most potent oral agent when tested against oxacillin-susceptible staphylococci, 4- to 16-fold more active than cefprozil and cephalexin, respectively.
Full Text Available Few epidemiologic studies have investigated predictors of uncomplicated peptic ulcer disease (PUD separately from predictors of complicated PUD.To analyze risk factors associated with uncomplicated PUD and medication use after diagnosis.Patients diagnosed with uncomplicated PUD (n = 3,914 were identified from The Health Improvement Network database among individuals aged 40-84 years during 1997-2005, with no previous history of PUD. Prescription records for the year after the date of diagnosis were reviewed and a nested case-control analysis was performed to calculate the odds ratios for the association of potential risk factors with PUD.Medications associated with developing uncomplicated PUD included current use of acetylsalicylic acid (ASA, nonsteroidal anti-inflammatory drugs (NSAIDs, paracetamol, selective serotonin reuptake inhibitors, antidepressants, antihypertensives or acid suppressants. Uncomplicated PUD was significantly associated with being a current or former smoker and having had a score of at least 3 on the Townsend deprivation index. Approximately 50% of patients who were users of ASA (19% of patients or chronic users of NSAIDs (7% of patients at diagnosis did not receive another prescription of the medication in the 60 days after diagnosis, and 30% were not represcribed therapy within a year. Among patients who were current users of ASA or chronic NSAIDs at the time of the PUD diagnosis and received a subsequent prescription for their ASA or NSAID during the following year, the vast majority (80-90% also received a proton pump inhibitor coprescription.Our results indicate that several risk factors for upper gastrointestinal bleeding are also predictors of uncomplicated PUD, and that some patients do not restart therapy with ASA or NSAIDs after a diagnosis of uncomplicated PUD. Further investigation is needed regarding the consequences for these patients in terms of increased cardiovascular burden due to discontinuation of
Alan Kang-Wai Mu
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.
Phuc, Bui Q; Caruana, Sonia R; Cowman, Alan F; Biggs, Beverley-Ann; Thanh, Ngo V; Tien, Nong T; Thuan, Le K
In 2002 an antimalarial drug resistance survey was carried out in a seasonally endemic area of Vietnam. Sulfadoxine/pyrimethamine (S/P) was the standard treatment recommended for uncomplicated Plasmodium falciparum malaria in that area at the time. Early or late treatment failure as defined by WHO was observed in 14.9% (7/47) of patients. Molecular analysis of treatment failure isolates identified that 5/6 carried two or more dhfr and dhps polymorphisms associated with S/P resistance. Chloroquine resistance-associated polymorphisms occurred in 38.5% (15/39) of the isolates. These results support the move to artemisinin-based combination therapy for malaria in Vietnam.
A-Elbasit, Ishraga E; Alifrangis, Michael; Khalil, Insaf F
BACKGROUND: The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. OBJECTIVE: To investigate...... the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. METHOD: Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR......-ELISA. RESULTS & CONCLUSION: Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six...
Jensen, Anja T R; Magistrado, Pamela; Sharp, Sarah
Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria...... in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA...... genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria....
Corredor, Vladimir; Murillo, Claribel; Echeverry, Diego F.; Benavides, Julie; Pearce, Richard J.; Roper, Cally; Guerra, Angela P.; Osorio, Lyda
The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in treating uncomplicated Plasmodium falciparum malaria is unevenly distributed in Colombia. The Andes mountain range separates regions in the west where malaria is endemic from those in the east and constitutes a barrier against gene flow and the dispersal of parasite populations. The distribution of dhfr and dhps genotypes of 146 P. falciparum samples from the eastern Amazon and Orinoco basins and Northwest and Southwest Pacific regions of Colombia was consistent with the documented levels of therapeutic efficacy of SP. The diversity of four dhfr- and dhps-linked microsatellites indicated that double- and triple-mutant alleles for both resistance loci have a single origin. Likewise, multilocus association genotypes, including two unlinked microsatellite loci, suggested that genetic exchanges between the eastern Orinoco and Northwest Pacific populations has taken place across the Andes, most probably via migration of infected people. PMID:20498318
Corredor, Vladimir; Murillo, Claribel; Echeverry, Diego F; Benavides, Julie; Pearce, Richard J; Roper, Cally; Guerra, Angela P; Osorio, Lyda
The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in treating uncomplicated Plasmodium falciparum malaria is unevenly distributed in Colombia. The Andes mountain range separates regions in the west where malaria is endemic from those in the east and constitutes a barrier against gene flow and the dispersal of parasite populations. The distribution of dhfr and dhps genotypes of 146 P. falciparum samples from the eastern Amazon and Orinoco basins and Northwest and Southwest Pacific regions of Colombia was consistent with the documented levels of therapeutic efficacy of SP. The diversity of four dhfr- and dhps-linked microsatellites indicated that double- and triple-mutant alleles for both resistance loci have a single origin. Likewise, multilocus association genotypes, including two unlinked microsatellite loci, suggested that genetic exchanges between the eastern Orinoco and Northwest Pacific populations has taken place across the Andes, most probably via migration of infected people.
Hviid, L; Kurtzhals, J A; Dodoo, D
Frequencies and absolute numbers of peripheral gamma/delta T cells have been reported to increase after episodes of Plasmodium falciparum malaria in adults with limited or no previous malaria exposure. In contrast, little is known about the gamma/delta T-cell response to malaria in children from...... areas where malaria is endemic, who bear the burden of malaria-related morbidity and mortality. We investigated the gamma/delta T-cell response in 19 Ghanaian children from an area of hyperendemic, seasonal malaria transmission. The children presented with cerebral malaria (n = 7), severe malarial...... anemia (n = 5), or uncomplicated malaria (n = 7) and were monitored from admission until 4 weeks later. We found no evidence of increased frequencies of gamma/delta T cells in any of the patient groups, whereas one adult expatriate studied in Ghana and three adults admitted to the hospital in Copenhagen...
malaria drugs. Dendrathema indicum/ Dunkufea plant used in the treatment of malaria in the northern part of Nigeria was evaluated for activity against Plasmodium falciparum. The crude ethanol extract of the plant, n-hexane, chloroform and ethyl ...
White, N J; Olliaro, P
Artemisinin and its derivatives are the most rapidly acting antimalarials known to-date and are well-tolerated. All derivatives in use today are produced by semi-synthesis from artemisinin: dihydroartemisinin is the product of the first step; more synthetic steps give rise to artesunate, artemether and arteether which are metabolised back to dihydroartemisinin in the body. Although their residence in the body after oral administration is very short (with half-lives of daily. By acting on ring stages, they clear peripheral parasitaemia more quickly than other antimalarial drugs and prevent the development into mature sequestering blood stages. They are effective against all human malaria parasites, notably multidrug-resistant Plasmodium falciparum. They have anti-transmission properties, too. So far, resistance to this class of compounds has not been reported. However, when used alone, they require long treatment courses (7 days). So, combination with long-half life drugs such as mefloquine appears to be the best approach to mutually protect both drugs against resistance. While reported in experimental animals, there is no evidence neurotoxicity in human beings. Whether such event could occur after continuous or discontinuous use is not clear.
Barber Bridget E; William Timothy; Grigg Matthew J; Yeo Tsin W; Anstey Nicholas M
Abstract Background In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy perfor...
Ansari, Hifzur Rahman
Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status.
Guiguemde, W. Armand; Shelat, Anang A.; Bouck, David; Duffy, Sandra; Crowther, Gregory J.; Davis, Paul H.; Smithson, David C.; Connelly, Michele; Clark, Julie; Zhu, Fangyi; Jiménez-Díaz, María B; Martinez, María S; Wilson, Emily B.; Tripathi, Abhai K.; Gut, Jiri; Sharlow, Elizabeth R.; Bathurst, Ian; El Mazouni, Farah; Fowble, Joseph W; Forquer, Isaac; McGinley, Paula L; Castro, Steve; Angulo-Barturen, Iñigo; Ferrer, Santiago; Rosenthal, Philip J.; DeRisi, Joseph L; Sullivan, David J.; Lazo, John S.; Roos, David S.; Riscoe, Michael K.; Phillips, Margaret A.; Rathod, Pradipsinh K.; Van Voorhis, Wesley C.; Avery, Vicky M; Guy, R. Kiplin
Malaria caused by Plasmodium falciparum is a catastrophic disease worldwide (880,000 deaths yearly). Vaccine development has proved difficult and resistance has emerged for most antimalarials. In order to discover new antimalarial chemotypes, we have employed a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library, many of which exhibited potent in vitro activity against drug resistant strains, and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in multiple organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Overall, our findings provide the scientific community with new starting points for malaria drug discovery. PMID:20485428
Rosalind E Howes
Full Text Available Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf. Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health
Howes, Rosalind E; Reiner, Robert C; Battle, Katherine E; Longbottom, Joshua; Mappin, Bonnie; Ordanovich, Dariya; Tatem, Andrew J; Drakeley, Chris; Gething, Peter W; Zimmerman, Peter A; Smith, David L; Hay, Simon I
Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well
Grobusch, M. P.; Hänscheid, T.; Zoller, T.; Jelinek, T.; Burchard, G. D.
In order to determine the reliability of two commercial tests for the rapid detection of plasmodial antigen in cases of infection with Plasmodium ovale and Plasmodium malariae, the products were evaluated in four centers and a search of the relevant literature was performed. The results of the
Penali, Louis Koné; Jansen, Frans Herwig
Malaria kills approximately 1.5 to 2.7 million people each year. Despite the introduction of artemisinin-based combination therapies (ACTs), the treatment of malaria is hampered by problems such as inadequate efficacy, recrudescence, early re-infection, low patient compliance, and high cost price of drugs. This study tested the hypothesis that the co-formulated fixed dose combination (FDC) artesunate/sulfamethoxypyrazine/pyrimethamine (As/SMP) administered as a 24-hour therapy with a dose interval of 12 hours is as efficacious and safe as the administration of the same drug over 3 days given with a dose interval of 24 hours, for the treatment of uncomplicated Plasmodium falciparum malaria in Ivory Coast. Two hundred and twenty-one patients presenting with uncomplicated P. falciparum malaria were randomly assigned to either one of the two dosing schemes. Treatment efficacy was assessed using the current 28-day World Health Organization protocol, success being determined by absence of recrudescence and parasitemia on day 28. Both treatment regimens were highly efficacious, with a success rate of 100% (111/111) for the 3-day therapy and 99% (109/110) for the 24-hour therapy. Only one patient in the 24-hour therapy group showed late treatment failure. No serious adverse events or significant laboratory abnormalities were seen. The 24-hour therapy is as well tolerated and efficacious as the same medicament administered over 3 days. This low cost and simplified three-pill treatment is certain to improve compliance.
Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau
Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed...... by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated...... positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased...
Artemisinins-based combination therapies (ACTs) are being recommended against uncomplicated malaria in endemic areas of Africa. However, in these areas data on their long term usefulness is limited. It has been demonstrated that ACTs resistance may be due to single nucleotide polymorphisms (SNPs) in the ...
Full Text Available Abstract Background Plasmodium falciparum is responsible for the most acute form of human malaria. Most recent studies demonstrate that it belongs to a monophyletic lineage specialized in the infection of great ape hosts. Several other Plasmodium species cause human malaria. They all belong to another distinct lineage of parasites which infect a wider range of primate species. All known mammalian malaria parasites appear to be monophyletic. Their clade includes the two previous distinct lineages of parasites of primates and great apes, one lineage of rodent parasites, and presumably Hepatocystis species. Plasmodium falciparum and great ape parasites are commonly thought to be the sister-group of all other mammal-infecting malaria parasites. However, some studies supported contradictory origins and found parasites of great apes to be closer to those of rodents, or to those of other primates. Results To distinguish between these mutually exclusive hypotheses on the origin of Plasmodium falciparum and its great ape infecting relatives, we performed a comprehensive phylogenetic analysis based on a data set of three mitochondrial genes from 33 to 84 malaria parasites. We showed that malarial mitochondrial genes have evolved slowly and are compositionally homogeneous. We estimated their phylogenetic relationships using Bayesian and maximum-likelihood methods. Inferred trees were checked for their robustness to the (i site selection, (ii assumptions of various probabilistic models, and (iii taxon sampling. Our results robustly support a common ancestry of rodent parasites and Plasmodium falciparum's relatives infecting great apes. Conclusions Our results refute the most common view of the origin of great ape malaria parasites, and instead demonstrate the robustness of a less well-established phylogenetic hypothesis, under which Plasmodium falciparum and its relatives infecting great apes are closely related to rodent parasites. This study sheds light
Blanquart, Samuel; Gascuel, Olivier
Plasmodium falciparum is responsible for the most acute form of human malaria. Most recent studies demonstrate that it belongs to a monophyletic lineage specialized in the infection of great ape hosts. Several other Plasmodium species cause human malaria. They all belong to another distinct lineage of parasites which infect a wider range of primate species. All known mammalian malaria parasites appear to be monophyletic. Their clade includes the two previous distinct lineages of parasites of primates and great apes, one lineage of rodent parasites, and presumably Hepatocystis species. Plasmodium falciparum and great ape parasites are commonly thought to be the sister-group of all other mammal-infecting malaria parasites. However, some studies supported contradictory origins and found parasites of great apes to be closer to those of rodents, or to those of other primates. To distinguish between these mutually exclusive hypotheses on the origin of Plasmodium falciparum and its great ape infecting relatives, we performed a comprehensive phylogenetic analysis based on a data set of three mitochondrial genes from 33 to 84 malaria parasites. We showed that malarial mitochondrial genes have evolved slowly and are compositionally homogeneous. We estimated their phylogenetic relationships using Bayesian and maximum-likelihood methods. Inferred trees were checked for their robustness to the (i) site selection, (ii) assumptions of various probabilistic models, and (iii) taxon sampling. Our results robustly support a common ancestry of rodent parasites and Plasmodium falciparum's relatives infecting great apes. Our results refute the most common view of the origin of great ape malaria parasites, and instead demonstrate the robustness of a less well-established phylogenetic hypothesis, under which Plasmodium falciparum and its relatives infecting great apes are closely related to rodent parasites. This study sheds light on the evolutionary history of Plasmodium falciparum, a
Background: Laparoscopic appendectomy is a feasible and safe alternative to open appendectomy for uncomplicated appendicitis. In the past decade several laparoscopic procedures have been described using one or more ports. We report our experience in treating acute appendicitis with one-port transumbilical ...
Full Text Available Symptoms and signs of acute pyelonephritis sometimes are subtle and emergency physicians attending overcrowded and busy institutions could easily miss the right diagnosis. The presence of a renal damage is decisive in the therapeutic choice. Aims of our study are: 1 to assess prevalence of renal damage in patients presenting to our ED with symptoms and signs of primary urinary tract infection (UTI; 2 to evaluate the reliability of such symptoms and signs in predicting a renal damage; 3 to assess accuracy of the contrast enhanced ultrasound (CEUS in the ED diagnosis of renal damage due to acute uncomplicated pyelonephritis. We studied 54 patients with suspected UTI. Each patient underwent clinical examination, routine blood and urine sampling and conventional renal ultrasound (US. 23 patients had confirmation of acute primary UTI, and performed renal magnetic resonance (MR to rule out renal parenchymal involvement. In 16 patients (69,6% one or more parenchymal lesions were visualized at MR, and diagnosis of acute uncomplicated pyelonephritis was confirmed (group A. The other 7 patients had a diagnosis of UTI without renal involvement (group B. Some of 23 patients presented with few atypical symptoms. Lumbar pain was the most frequent symptom (n = 21, without a statistically significant difference between group A and B (P 0,958; p = 0,328. No other symptom or sign has demonstrated statistically valid in predicting the renal involvement. Renal US was positive in only 3 patients of group A (18,7%. During this first part of our study, CEUS was performed in a limited number of patients (n = 8, and in 7 examinations data were concordant with MR. In conclusion, analysis of our preliminary data confirms that a distinction between patients with different extension of the UTI is not possible through the simple clinical examination and routine tests. CEUS is very promising and its routine employment in the ED could simplify the diagnostic practice in
Price, R; Nosten, F; Simpson, J A; Luxemburger, C; Phaipun, L; ter Kuile, F; van Vugt, M; Chongsuphajaisiddhi, T; White, N J
The factors affecting the development of patent Plasmodium falciparum gametocytemia were assessed in 5,682 patients entered prospectively into a series of antimalarial drug trials conducted in an area of low and seasonal transmission on the western border of Thailand. Of the 4,565 patients with admission thick smear assessments, 110 (2.4%) had gametocytemia. During the follow-up period 170 (3%) of all patients developed patent gametocytemia, which in 89% had developed by day 14 following treatment. In a multiple logistic regression model five factors were found to be independent risk factors at presentation for the development or persistence of gametocytemia during follow up; patent gametocytemia on admission (adjusted odds ratio [AOR] = 7.8, 95% confidence interval [CI] = 3.7-16, P < 0.001), anemia (hematocrit <30%) (AOR = 3.9, 95% CI = 2.3-6.5, P < 0.001), no coincident P. vivax malaria (AOR = 3.5, 95% CI = 1.04-11.5, P < 0.04), presentation with a recrudescent infection (AOR = 2.3, 95% CI = 1.3-4.1, P < 0.004), and a history of illness longer than two days (AOR = 3.3, 95% CI = 1.7-6.6, P < 0.001). Patients whose infections responded slowly to treatment or recrudesced subsequently were also more likely to carry gametocytes than those who responded rapidly or were cured (relative risks = 1.9, 95% CI = 1.3-2.7 and 2.8, 95% CI = 2.0-4.0, respectively; P < 0.001). These data provide further evidence of important epidemiologic interactions between P. falciparum and P. vivax, and drug resistance and transmission potential.
Jakobsen, P H; Morris-Jones, S D; Hviid, L
Plasma levels of antibodies against phosphatidylinositol (PI), phosphatidylcholine (PC) and cardiolipin (CL) were measured by enzyme-linked immunosorbent assay (ELISA) in patients from malaria endemic area of Sudan and The Gambia. Some Sudanese adults produced IgM antibodies against all three types...... of phospholipids (PL) during an acute Plasmodium falciparum infection. The anti-PL antibody titre returned to preinfection levels in most of the donors 30 days after the disease episode. IgG titres against PI, PC and CL were low. In Gambian children with malaria, IgM antibody titres against PI and PC were...... significantly higher in those with severe malaria than in those with mild malaria. These results show that a proportion of malaria patients produce anti-PL antibodies during infection and that titres of these antibodies are associated with the severity of disease....
The main presenting signs were pyrexia (84.5%), splenomegaly (38%) and hepatomegaly (14%). Malaria was the leading cause of paediatrics outpatient clinic attendance followed by acute respiratory infection and diarrhoeal disease. Though malaria occurred throughout the year, majority of the cases were seen during the ...
There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. Objective: To determine the population genomic diversity of Plasmodium falciparum in malaria patients attending Okelele Com- munity Healthcare Centre, Okelele, Ilorin, Kwara State. Methods: In this study, 50 Plasmodium ...
Jun 1, 2013 ... ABSTRACT. A study on relative abundance of Plasmodium species was conducted using blood film technique. For a 12 month period, 4037 positive blood films were exaqmined for a particular species of. Plasmodium. The result revealed that 3208 (79.46%) were Plasmodium falciparum, 157 (03.89%).
The emergence of possible resistant Plasmodium falciparum malaria to artemisinin known for its immense benefit in malaria chemotherapy is worrisome. We report a case of unresolving Plasmodium falciparum malaria to Artesunate treatment in a 29- year old man in Enugu Nigeria. Plasmodium falciparum count of Giemsa ...
Jaung, Rebekah; Robertson, Jason; Vather, Ryash; Rowbotham, David; Bissett, Ian P
Acute diverticulitis (AD) is one of the most common acute admission diagnoses for general surgery, and its prevalence is increasing, in part due to the ageing population. Currently, most patients who present to a tertiary hospital are admitted for a period of treatment and observation. Simple, safe and cost-effective strategies for improving our current treatment of this condition will be invaluable in providing the most appropriate management for individual patients and for reducing the health resources expended on hospital admissions and parenteral antibiotics. AD can be categorized as uncomplicated or complicated, these two subtypes have a very different clinical course. The management of uncomplicated AD has become increasingly conservative, with a focus on symptomatic relief and supportive management. Recent research has brought into question the need for extended hospital admission and questioned the current use of antibiotics. Anti-inflammatory agents that reduce local inflammation in uncomplicated AD may be a useful means of reducing damage caused by inflammation and aiding earlier resolution of the inflammatory response and associated symptoms. Mesalazine is an anti-inflammatory agent that has been trialled in uncomplicated AD. Mesalazine has been shown to improve time to resolution of endoscopic and histological evidence of inflammation following an episode of AD and also reduce the rate of recurrence. In this literature review, we provide an overview of recent advances in AD classification, pathophysiology and management, and examine the possibility of introducing the use of anti-inflammatory agents in the management of uncomplicated AD. © 2015 Royal Australasian College of Surgeons.
Full Text Available The risk factors associated with hyperparasitemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 1,048 children enrolled prospectively in seven antimalarial drug trials between July 1996 and September 2003 in a hyperendemic area of southwestern Nigeria. The outcomes of treatment of hyperparasitaemia, and gametocyte carriage following treatment were also evaluated. The children were assigned to one of seven treatment groups : chloroquine (CQ only ; pyrimethamine-sulfadoxine (PS only; amodiaquine (AQ only; CQ plus chlorpheniramine (CQCP; PS combined with CQ or AQ (COM; PS combined with probenecid (PPS; and halofantrine (HF. Hyperparasitaemia was found in 100 (9,5 % of the 1,048 children at enrolment (day 0. Following oral therapy, 1.2 % of all patients (i.e. 13 patients became hypeparasitaemic, which developed in all patients by day 1 of follow-up. In a multiple regression model, age ≤ 5 years, and a core temperature (oral or rectal ≥ 39.5°C were found to be independent risk factors for hyperparasitaemia at enrolment. Following therapy, the cure rate on day 14 was significantly lower in those treated with CQ compared to other treatment groups. Severe resistance (RIII response to treatment occurred significantly more frequently in those with hyperparasitaemia at enrolment than in those without, and was seen in five and one child with hyperparasitaemia who were treated with CQ and CQCP, respectively. Gametocyte carriage was insignificantly lower at enrolment and at all times following treatment in children with hyperparasitaemia than in age- and gender- matched children without hyperparasitaemia who received the same treatment. The results are discussed in the light of management of uncomplicated hyperparasitaemia in children in endemic settings.
Held, Jana; Supan, Christian; Salazar, Carmen L O; Tinto, Halidou; Bonkian, Léa N; Nahum, Alain; Moulero, Bancole; Sié, Ali; Coulibaly, Boubacar; Sirima, Sodiomon B; Siribie, Mohamadou; Otsyula, Nekoye; Otieno, Lucas; Abdallah, Ahmed M; Kimutai, Robert; Bouyou-Akotet, Marielle; Kombila, Maryvonne; Koiwai, Kimiko; Cantalloube, Cathy; Din-Bell, Chantal; Djeriou, Elhadj; Waitumbi, John; Mordmüller, Benjamin; Ter-Minassian, Daniel; Lell, Bertrand; Kremsner, Peter G
Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. Ferroquine is a new combination partner for fast-acting ACTs such as artesunate. We aimed to assess different doses of ferroquine in combination with artesunate against uncomplicated P falciparum malaria in a heterogeneous population in Africa. We did a phase 2, multicentre, parallel-group, double-blind, randomised, dose-ranging non-inferiority trial at eight African hospitals (two in Gabon, three in Burkina Faso, one in Benin, and two in Kenya). We recruited patients presenting with acute P falciparum monoinfection (1000-200,000 parasites per μL), and a central body temperature of at least 37·5°C or history of fever in the past 24 h. We assessed patients in two sequential cohorts: cohort 1 contained adults (bodyweight >50 kg) and adolescents (aged ≥14 years, >30 kg), and cohort 2 contained children (aged 2-13 years, 15-30 kg). We randomly assigned patients (1:1:1:1) to receive artesunate 4 mg/kg per day plus ferroquine 2 mg/kg, 4 mg/kg, or 6 mg/kg, given double-blind once per day for 3 days, or ferroquine monotherapy 4 mg/kg per day given single-blind (ie, allocation was only masked from the patient) once per day for 3 days. We did 14 patient visits (screening, 3 treatment days and 48 h post-treatment surveillance, a visit on day 7, then one follow-up visit per week until day 63). The primary endpoint was non-inferiority of treatment in terms of PCR-corrected cure rate against a reference value of 90%, with a 10% non-inferiority margin, assessed in patients treated without major protocol deviations for parasitologically confirmed malaria. We assessed safety in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00988507, and is closed. Between Oct 16, 2009, and Sept 22, 2010, we randomly assigned 326 eligible patients to treatment groups, with last follow-up visit on Dec 1, 2010. 284 patients
Cucunubá, Zulma Milena; Guerra, Angela Patricia; Rahirant, Sonia Judith; Rivera, Jorge Alonso; Cortés, Liliana Jazmín; Nicholls, Rubén Santiago
With the aim of determining the prevalence of asymptomatic Plasmodium spp. infection by thick smear and PCR and its association with demographic and epidemiological characteristics in the village of Nuevo Tay, Tierralta, Córdoba, Colombia, a cross-sectional population study was carried out, using random probabilistic sampling. Venous blood samples were taken from 212 people on day 0 for thick smear and PCR. Clinical follow-up and thick smears were carried out on days 14 and 28. The prevalence of Plasmodium spp. infection was 17.9% (38/212; 95% CI: 12.5-23.3%) and the prevalence of asymptomatic Plasmodiumspp. infection was 14.6% (31/212; 95% CI: 9.6-19.6%). Plasmodium vivax was found more frequently (20/31; 64.5%) than Plasmodium falciparum (9/31; 29%) and mixed infections (2/31; 6.5%). A significantly higher prevalence of asymptomatic infection was found in men (19.30%) than in women (9.18%) (prevalence ratio: 2.10; 95% CI: 1.01-4.34%; p = 0.02). People who developed symptoms had a significantly higher parasitemia on day 0 than those who remained asymptomatic, of 1,881.5 +/- 3,759 versus 79 +/- 106.9 (p = 0.008). PCR detected 50% more infections than the thick smears. The presence of asymptomatic Plasmodium spp. infection highlights the importance of carrying out active searches amongst asymptomatic populations residing in endemic areas.
Salazar-Castañon, Víctor H.; Legorreta-Herrera, Martha
More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response. PMID:25276830
Wilde, Elisabeth A; McCauley, Stephen R; Barnes, Amanda; Wu, Trevor C; Chu, Zili; Hunter, Jill V; Bigler, Erin D
Patients (n = 8) with uncomplicated mild traumatic brain injury (mTBI) underwent serial assessments (4) with diffusion tensor imaging (DTI) and neuropsychological testing within the first 8 days post-injury. Using a multi-case study design, we examined changes in brain parenchyma (via DTI-derived fractional anisotropy [FA], apparent diffusion coefficient [ADC], axial diffusivity [AD] and radial diffusivity [RD] in the left cingulum bundle) and in memory performance (via Hopkins Verbal Learning Test-Revised). Qualitative inspection of the results indicated that memory performance was transiently affected in most participants over the course of the week, with performance most negatively impacted on the second assessment (days 3-4 or 97-144 h post-injury), and then returning to within normal limits by 8 days post-injury. Alternatively, FA and other DTI metrics showed a more complex pattern, with the trajectory of some participants changing more prominently than others. For example, FA transiently increased in some participants over the study period, but the pattern was heterogeneous. Memory performance appeared to mirror changes in FA in certain cases, supporting a pathophysiological basis to memory impairment following mTBI. However, the pattern and the degree of symmetry between FA and memory performance was complex and did not always correspond. Serial imaging over the semi-acute recovery period may be important in reconciling conflicting findings in mTBI utilizing memory and/or DTI. Serial use of imaging modalities including DTI may aid understanding of underlying pathophysiological changes in the semi-acute post-injury period. Should a consistent pattern emerge that allows identification of patients at-risk for acute and/or persistent symptoms, such knowledge could guide development of therapeutic targets in mTBI and in understanding the most effective administration time window for these agents.
Full Text Available La apendicitis aguda es una causa típica de dolor abdominal agudo y la causa más frecuente de cirugía abdominal de urgencia. En las últimas dos décadas se ha publicado creciente evidencia sobre el uso de antibióticos como tratamiento exclusivo de la apendicitis aguda. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos nueve revisiones sistemáticas que en conjunto incluyen cinco estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de antibióticos para el tratamiento la apendicitis aguda no complicada podría tener menor efectividad que la apendicectomía y probablemente aumente las complicaciones mayores en comparación con la apendicectomía.
McGready, R; Stepniewska, K; Ward, S A; Cho, T; Gilveray, G; Looareesuwan, S; White, N J; Nosten, F
To determine the pharmacokinetic properties of dihydroartemisinin (DHA) following oral artesunate treatment in women with recrudescent multi-drug resistant falciparum malaria, in the second and third trimesters of pregnancy. Serial plasma concentrations of artesunate and DHA were measured in 24 women after the final dose of a 3 day treatment with artesunate (4 mg kg(-1) day(-1)) and atovaquone (20 mg kg(-1) day(-1)) plus proguanil (8 mg kg(-1) day(-1)), daily. Conventional non-compartmental modelling and a population one-compartment pharmacokinetic model were applied to the data. Artesunate was very rapidly eliminated. For DHA the median [90% range] estimate of oral clearance (CI/F) was 4.0 [0.8-20.7] l hour(-1) kg(-1), total apparent volume of distribution (Vd/f) was 3.4 [0.9-60.7] l/kg, and terminal elimination half-life was 1.0 [0.6-2.4] h. The kinetics of DHA are modified by pregnancy. The plasma levels of the active antimalarial metabolite DHA are lower than reported previously in non-pregnant adults. Dose-optimisation studies in pregnant women are needed.
P. C. Minneci
Full Text Available Актуальность. Имеющиеся доказательства позволяют считать, что консервативное лечение неосложненного аппендицита безопасно. Однако суммарная эффективность лечения детей определяется сочетанием медицинских исходов с ожиданиями как самих пациентов, так и членов их семьи.Цель исследования. Определить эффективность1 выбора пациентом между консервативным и хирургическим способами лечения неосложненного острого аппендицита у детей.Дизайн, условия и участники исследования. Прове дено проспективное когортное исследование среди детей и подростков в возрасте от 7 до 17 лет с острым неосложненным аппендицитом. Исследование проводили на базе отдельно взятой высокоспециализированной детской больницы скорой неотложной помощи в период с 1 октября 2012 по 6 марта 2013 г. Пациенты и члены их семей подтверждали свое участие в иссле- довании информированным согласием, выбирая между консервативным способом лечения и неотложной аппендэктомией.Вмешательства. Неотложная аппендэктомия так же, как и консервативное лечение, подразумевает наблюдение в стационаре в течение по крайней мере 24 ч с введением антибиотиков внутривенно и, при улучшении симптомов, завершение лечения курсом приема антибиотиков в течение 10 сут.Основные исходы. Основным (первичным исходом считали случаи (частоту консервативного лечения, не потребовавшие оперативного вмешательства в течение 1 года после включения в исследование. В качестве дополнительных (вторичных исходов анализировали частоту случаев осложненного аппендицита, число дней, в течение которых пациент имел ограничения жизнедеятельности (disability days, а также расходы на медицинские услуги в сравниваемых группах (консервативное лечение в сравнении с хирургическим.Результаты. В исследовании приняли участие 102 пациента; 65 пациентов/семей выбрали аппендэктомию [медиана возраста пациентов 12 лет; межквартильный размах — 9–13 лет; 45 (69% пациентов мужского пола], 37 пациентов/семей выбрали консервативное лечение [возраст 11 (10–14 лет; 24 (65% пациента мужского пола]. Исходные характеристики групп не различались. Основной исход исследования в группе консервативного лечения был достигнут в 89% случаев (95% ДИ 75–97 по истечении 30 сут (33 из 37 детей и в 76% (95% ДИ 59–88 — по истечении 1 года (28 из 37 детей. Частота случаев осложненного аппендицита составила 2,7% в группе консервативного лече- ния (1 из 37 детей и 12,3% — в группе с хирургическим вмешательством (8 из 65 детей; p = 0,150. По прошествии 1 года дети из группы консервативного лечения имели меньше дней ограничения жизнедеятельности, чем дети из группы с хирургическим вмешательством [Me 8 (5–18 и 21 (15–25 день, соответственно; p < 0,001]. Ниже в группе консервативного лечения были и расходы, связанные с лечением основного заболевания и уходом за пациентами [Me 4219 (2514–7795 и 5029 (4596–5482 долл. США, соответственно; p = 0,010].Выводы и клиническая значимость. При согласии семьи консервативное лечение является эффективным способом лечения детей с неосложненным острым аппендицитом, характеризуется меньшим риском осложнений при меньшей стоимости лечения по сравнению с хирургическим вмешательством.
Calderaro, Adriana; Piccolo, Giovanna; Gorrini, Chiara; Rossi, Sabina; Montecchini, Sara; Dell'Anna, Maria Loretana; De Conto, Flora; Medici, Maria Cristina; Chezzi, Carlo; Arcangeletti, Maria Cristina
Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy. In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria. These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria. Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed. Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of
Herman, C.M.; Kocan, R.M.
Until a little over a decade ago reports of Plasrnodium in geese, ducks, and swans were the result of examination of single blood smears from wild birds. One would gather from the earlier studies that Anatidae are infrequently infected. During the past decade we have conducted studies on prevalence of Plasmodium by an isodiagnosis technique, inoculating blood from wild birds into captive young geese, ducks, and other species of birds and determining the status of infection in the donors by examination of repetitive blood smears from the recipients. Examination by this technique of a series of adult Canada geese from the Seney National Wildlife Refuge in northern Michigan uncovered a prevalence of 60% during five successive years. Domestic geese were the primary recipients but we found that several other species of geese, ducks, and gulls were also susceptible. Similar studies on Canada geese from other areas (Maryland, New Jersey, New York, and southern Michigan) uncovered infection rates from zero to 27%. Following isolation of Plasmodlum in a single canvasback duck (Aythya valisineria) in southern Michigan by inoculation into a domestic duck, a series of 88 canvasbacks from Chesapeake Bay in Maryland this winter uncovered an infection rate of 27%. The most common parasite observed in both the geese and was as P. circumflexum.
Full Text Available Abstract Background Plasmodium knowlesi malaria causes severe disease in up to 10% of cases in Malaysian Borneo and has a mortality rate of 1 - 2%. However, laboratory markers with the ability to identify patients at risk of developing complications have not yet been assessed as they have for other species of Plasmodium. Methods A case control study was undertaken in two hospitals in Sarikei and Sibu, Malaysian Borneo. One hundred and ten patients with uncomplicated (n = 93 and severe (n = 17 P. knowlesi malaria were studied. Standardized pigment-containing neutrophil (PCN count, parasite density and platelet counts were determined and analysed by logistic regression and receiver operating characteristic (ROC analysis. Results The PCN count was strongly associated with risk of disease severity. Patients with high parasite density (≥ 35,000/μl or with thrombocytopaenia (≤ 45,000/μl were also more likely to develop complications (odds ratio (OR = 9.93 and OR = 5.27, respectively. The PCN count yielded the highest area under the ROC curve (AUC estimate among all markers of severity (AUC = 0.8561, 95% confidence interval: 0.7328, 0.9794. However, the difference between all parameter AUC estimates was not statistically significant (Wald test, p = 0.73. Conclusion Counting PCN is labour-intensive and not superior in predicting severity over parasitaemia and platelet counts. Parasite and platelet counts are simpler tests with an acceptable degree of precision. Any adult patient diagnosed with P. knowlesi malaria and having a parasite count ≥35,000/μl or ≥1% or a platelet count ≤45,000/μl can be regarded at risk of developing complications and should be managed according to current WHO guidelines for the treatment of severe malaria.
Fox, Annette; Than Manh Hung; Wertheim, Heiman; Le Nguyen Minh Hoa; Vincent, Angela; Lang, Bethan; Waters, Patrick; Nguyen Hong Ha; Nguyen Vu Trung; Farrar, Jeremy; Nguyen Van Kinh; Horby, Peter
Background The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam. Methods and Findings Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008?2010. Stand...
de Vries, P. J.; Tran, K. D.; Nguyen, X. K.; Le Nguyen, B.; Pham, T. Y.; Dao, D. D.; van Boxtel, C. J.; Kager, P. A.
The pharmacokinetics of artemisinin was studied in 11 Vietnamese patients with uncomplicated falciparum malaria after a single 500 mg oral dose. Curative treatment with mefloquine (15 mg/kg) was provided 24 hr after the artemisinin dose. Artemisinin concentrations were measured by high-performance
Giao, P. T.; Binh, T. Q.; Kager, P. A.; Long, H. P.; van Thang, N.; van Nam, N.; de Vries, P. J.
The efficacy of artemisinin monotherapy was studied in 227 patients with uncomplicated falciparum malaria. They all received artemisinin at t = 0 hr, t = 8 hr, and thereafter once daily; treatment was extended at random until they had taken either 5 days of artemisinin followed by 2 days of placebo
de Vries, P. J.; Bich, N. N.; van Thien, H.; Hung, L. N.; Anh, T. K.; Kager, P. A.; Heisterkamp, S. H.
Combinations of artemisinin and quinine for uncomplicated falciparum malaria were studied. A total of 268 patients were randomized to 7 days of quinine at 10 mg/kg of body weight three times a day (Q) or to artemisinin at 20 mg/kg of body weight followed by 3 (AQ3) or 5 (AQ5) days of quinine.
Pedersen, Benjamin; Ellebæk, Mark B.; Dorfelt, Allan
INTRODUCTION: The introduction of laparoscopic cholecystectomy was followed by a steep increase in the cholecystectomy rate, which has remained on an unchanged, high level. The main indication for cholecystectomy in Denmark in cases with uncomplicated gallbladder stones is socially debilitating p...
Knottnerus, Bart J.; Grigoryan, Larissa; Geerlings, Suzanne E.; Moll van Charante, Eric P.; Verheij, Theo J. M.; Kessels, Alphons G. H.; ter Riet, Gerben
The efficacies and adverse effects of different antibiotics for uncomplicated urinary tract infections (UTIs) have been studied by standard meta-analytic methods using pairwise direct comparisons of antimicrobial treatments: the effects of one treatment are compared to those of either another
Wakefield, Jerome C.; Schmitz, Mark F.
Purpose: To evaluate the claim, made repeatedly during "Diagnostic and Statistical Manual of Mental Disorders", Fifth Edition debates over eliminating the bereavement exclusion (BE), that ''uncomplicated'' depressive reactions have elevated suicidality like other major depressive disorder (MDD), so exclusions risk…
Sato, Tomonori; Fujita, Hitomi; Takahashi, Masahiro; Hatta, Masumitsu; Aoki, Hiroshi; Ishidoya, Shigeto
(Objectives) We report the clinical features about polymicrobial bacteria detection cases in the uncomplicated urinary tract infection of the premenopausal woman from the voided midstream urine culture. (Methods) We retrospectively reviewed the premenopausal woman from 18-49 years patients visited Sendai City Hospital from April, 2006 to December, 2014, diagnosed uncomplicated cystitis or uncomplicated pyelonephritis. We analyzed for 375 specimens from the voided midstream urine culture. (Results) Among 375 specimens, the urine culture-positive for uropathogens were 211 specimens. The monomicrobial bacterial were detected in 184 specimens (87.2%) and polymicrobial bacterial specimens were 27 specimens (12.8%). The most combination group was the caused bacteria and periurethral microorganisms in 20 specimens (74.1%). Then 6 periurethral microorganisms specimens (22.2%), the caused bacteria were only 1 specimen was overlapped (3.7%). The case of urinary tract infections recurrence or revealed voiding dysfunction that need periodic treatment were more prevalent in the polymicrobial than the monomicrobial group (22.2% vs 9.8%, p=0.043). (Conclusions) When polymicrobial bacteria were detected in uncomplicated urinary tract infection in premenopausal woman, it was confirmed that there were the most combinations of caused bacteria and periurethral microorganisms. In these cases, treatment intended for only the caused bacteria. A risk of the infection recurrence and voiding dysfunction were statistically significant higher rate in the polymicrobial bacteria detection cases, and it might be necessary to consider that search to complicated urinary tract infection.
Matthew T Aliota
Full Text Available Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG. Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness.Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria parasite infections.These results could have an
Degarege, Abraham; Degarege, Dawit; Veledar, Emir; Erko, Berhanu; Nacher, Mathieu; Beck-Sague, Consuelo M; Madhivanan, Purnima
It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA). A systematic review in according with PRISMA guidelines was conducted. All published articles available in PubMed, Embase, Cochrane library and CINAHL databases before May 20, 2015 were searched without any limits. Two reviewers independently screened, reviewed and assessed all the studies. Cochrane Q and Moran's I2 were used to assess heterogeneity and the Egger test was used to examine publication bias. The summary odds ratio (OR), summary regression co-efficient (β) and 95% confidence intervals (CI) were estimated using a random-effects model. Out of 2,920 citations screened, 12 articles (five cross-sectional, seven prospective cohort) were eligible to be included in the systematic review and 11 in the meta-analysis. The 12 studies involved 9,337 children in eight SSA countries. Eight studies compared the odds of asymptomatic/uncomplicated P. falciparum infection, two studies compared the incidence of uncomplicated P. falciparum infection, six studies compared P. falciparum density and four studies compared mean haemoglobin level between children infected and uninfected with S. haematobium or S. mansoni. Summary estimates of the eight studies based on 6,018 children showed a higher odds of asymptomatic/uncomplicated P. falciparum infection in children infected with S. mansoni or S. haematobium compared to those uninfected with Schistosoma (summary OR: 1.82; 95%CI: 1.41, 2.35; I2: 52.3%). The increase in odds of asymptomatic/uncomplicated P. falciparum infection among children infected with Schistosoma remained
Fay, Taryn B; Yeates, Keith Owen; Taylor, H Gerry; Bangert, Barbara; Dietrich, Ann; Nuss, Kathryn E; Rusin, Jerome; Wright, Martha
The occurrence of postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children may depend on cognitive reserve capacity. This prospective, longitudinal study examined whether the relationship between mild TBI and PCS is moderated by cognitive ability, which served as a proxy for cognitive reserve. Participants included 182 children with mild TBI and 99 children with orthopedic injuries (OI), ranging from 8 to 15 years of age when injured. Mild TBI were classified as complicated (n = 32) or uncomplicated (n = 150) depending on whether they were associated with trauma-related intracranial abnormalities on magnetic resonance imaging. PCS were assessed initially within 3 weeks of injury, and again at 1, 3, and 12 months post injury. The initial assessment also included standardized tests of children's cognitive skills and retrospective parent ratings of pre-injury symptoms. Hierarchical linear modeling indicated that ratings of PCS were moderated jointly by cognitive ability and injury severity. Children of lower cognitive ability with a complicated mild TBI were especially prone to cognitive symptoms across time according to parents and to high acute levels of PCS according to children's self-ratings. Cognitive reserve is an important moderator of the outcomes of mild TBI in children and adolescents.
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD, a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods Blood samples from children and adults participants (1 to 70 years old with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem® or artesunate plus mefloquine (Artequin™. A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A- allele of the gene mutation responsible for G6PD deficiency (G6PD*A-. 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%. The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups between G6PD deficiency (hemizygous, heterozygous, and homozygous and G6PD-normal participants
To describe the concept, models, and methods for the construction of estimates of joint probability of uncomplicated control of tumors in radiation oncology. Interpolations using this model can lead to the identification of more efficient treatment regimens for an individual patient. The requirement to find the treatment regimen that will maximize the joint probability of uncomplicated control of tumors suggests a new class of evolutionary experimental designs--Response Surface Methods--for clinical trials in radiation oncology. The software developed by Lesaffre and Molenberghs is used to construct bivariate probit models of the joint probability of uncomplicated control of cancer of the oropharynx from a set of 45 patients for each of whom the presence/absence of recurrent tumor (the binary event E1/E1) and the presence/absence of necrosis (the binary event E2/E2) of the normal tissues of the target volume is recorded, together with the treatment variables dose, time, and fractionation. The bivariate probit model can be used to select a treatment regime that will give a specified probability, say P(S) = 0.60, of uncomplicated control of tumor by interpolation within a set of treatment regimens with known outcomes of recurrence and necrosis. The bivariate probit model can be used to guide a sequence of clinical trials to find the maximum probability of uncomplicated control of tumor for patients in a given prognostic stratum using Response Surface Methods by extrapolation from an initial set of treatment regimens. The design of treatments for individual patients and the design of clinical trials might be improved by use of a bivariate probit model and Response Surface Methods.
Bi, Yan; Yu, Weiwei; Hu, Wenbiao; Lin, Hualiang; Guo, Yuming; Zhou, Xiao-Nong; Tong, Shilu
Background Malaria remains a public health problem in the remote and poor area of Yunnan Province, China. Yunnan faces an increasing risk of imported malaria infections from Mekong river neighboring countries. This study aimed to identify the high risk area of malaria transmission in Yunnan Province, and to estimate the effects of climatic variability on the transmission of Plasmodium vivax and Plasmodium falciparum in the identified area. Methods We identified spatial clusters of malaria cas...
Full Text Available Abstract Background Home-management of malaria (HMM strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL, presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs and administered unsupervised by parents or guardians at home. Methods An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5% patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%. The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10 compared with reinfections (205 ng/mL [114-390]; n = 92, or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046. Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home
del Portillo Hernando A
Full Text Available Abstract Background Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented. Methods Luciferase reporter plasmids harboring the upstream regions of the msp1, dhfr, and vir3 genes as well as the full-length intergenic regions of the vir23/24 and ef-1α genes of P. vivax were constructed and transiently transfected in P. falciparum. Results Only the constructs with the full-length intergenic regions of the vir23/24 and ef-1α genes were recognized by the P. falciparum transcription machinery albeit to values approximately two orders of magnitude lower than those reported by luc plasmids harbouring promoter regions from P. falciparum and Plasmodium berghei. A bioinformatics approach allowed the identification of a motif (GCATAT in the ef-1α intergenic region that is conserved in five Plasmodium species but is degenerate (GCANAN in P. vivax. Mutations of this motif in the P. berghei ef-1α promoter region decreased reporter expression indicating it is active in gene expression in Plasmodium. Conclusion Together, this data indicates that promoter regions of P. vivax are poorly or not recognized by the P. falciparum transcription machinery suggesting the existence of P. vivax-specific transcription regulatory elements.
Mayxay, Mayfong; Khanthavong, Maniphone; Chanthongthip, Odai; Imwong, Mallika; Lee, Sue J.; Stepniewska, Kasia; Soonthornsata, Bongkot; Pongvongsa, Tiengkham; Phompida, Samlane; Hongvanthong, Bouasy; Ringwald, Pascal; White, Nicholas J.; Newton, Paul N.
We conducted an open-label, randomized clinical trial to assess parasite clearance times (PCT) and the efficacy of 4 mg/kg (group 1, n = 22) and 2 mg/kg (group 2, n = 22) of oral artesunate for three days followed by artemether-lumefantrine in patients with uncomplicated Plasmodium falciparum malaria at Xepon Interdistrict Hospital, Savannakhet Province in southern Laos. Slides were read in duplicate. The overall mean (95% confidence interval; range) PCT in hours was 23.2 (21.2–25.3; 12–46) and 22.4 (20.3–24.5; 12–46) for the first and second microscopists, respectively (P = 0.57). Ten (23%) patients remained parasitemic on day 1 after treatment (4 [18%] in group 1 and 6 [27%] in group 2; P = 0.47). No patient had patent asexual parasitemia on the second and third days of treatment. The 42-day polymerase chain reaction–corrected cure rates were 100% in both treatment groups. Serious adverse events did not develop during or after treatment in any patients. In conclusion, no evidence of P. falciparum in vivo resistance to artesunate was found in southern Laos. PMID:22403308
Mangano, Valentina D; Luoni, Gaia; Rockett, Kirk A; Sirima, Bienvenu S; Konaté, Amadou; Forton, Julian; Clark, Taane; Bancone, Germana; Akha, Elham Sadighi; Kwiatkowski, Dominic P; Modiano, David
We describe the haplotypic structure of the Interferon Regulatory Factor-1 (IRF-1) locus in two West African ethnic groups, Fulani and Mossi, that differ in their susceptibility and immune response to Plasmodium falciparum malaria. Both populations showed significant associations between IRF-1 polymorphisms and carriage of P. falciparum infection, with different patterns of association that may reflect their different haplotypic architecture. Genetic variation at this locus does not therefore account for the Fulani-specific resistance to malaria while it could contribute to parasite clearance's ability in populations living in endemic areas. We then conducted a case-control study of three haplotype-tagging Single Nucleotide Polymorphisms (htSNPs) in 370 hospitalized malaria patients (160 severe and 210 uncomplicated) and 410 healthy population controls, all from the Mossi ethnic group. All 3 htSNPs showed correlation with blood infection levels in malaria patients, and the rs10065633 polymorphism was associated with severe disease (p=0.02). These findings provide the first evidence of the involvement in malaria susceptibility of a specific locus within the 5q31 region, previously shown to be linked with P. falciparum infection levels. PMID:18200030
The difficulty of identifying gametocyte carriers from the community is often limited due to financial and human resources constraints. The available alternative ... Plasmodium falciparum was the predominant parasite species and P. malariae being the only minor species, accounting for 0.9% of malaria cases. Clinical malaria ...
Resistance patterns of plasmodium falciparum malaria to chloroquine in Kampala, Uganda. ... Sixty three (65.6%) patients showed clinical improvement, 29 (30.2%) deteriorated and four (4.2%) had no change. Adequate parasitogical response was seen in 71 (74 %), moderate in four (4.2%) and poor in 21 (21.8%) patients.
Jamie M Orengo
Full Text Available Infection of erythrocytes with the Plasmodium parasite causes the pathologies associated with malaria, which result in at least one million deaths annually. The rupture of infected erythrocytes triggers an inflammatory response, which is induced by parasite-derived factors that still are not fully characterized. Induced secretion of inflammatory cytokines by these factors is considered a major cause of malaria pathogenesis. In particular, the inflammatory cytokine tumor necrosis factor (TNF is thought to mediate most of the life-threatening pathologies of the disease. Here we describe the molecular characterization of a novel pathway that results in the secretion of TNF by host cells. We found that erythrocytes infected by Plasmodium accumulate high concentrations of hypoxanthine and xanthine. Degradation of Plasmodium-derived hypoxanthine/xanthine results in the formation of uric acid, which triggers the secretion of TNF. Since uric acid is considered a "danger signal" released by dying cells to alert the immune system, Plasmodium appears to have co-evolved to exploit this warning system. Identifying the mechanisms used by the parasite to induce the host inflammatory response is essential to develop urgently needed therapies against this disease.
Boubidi, Said C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cecile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir
An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.
Oct 5, 2009 ... Kublin GJ, Dzinjalamala F, Kamwendo DD, Malkin ME, Cortese FJ,. Martino ML, Mukadam GAR, Molyneux EM, Winstanley AP,. Chimpeni P, Taylor ET, Plowe CP (2002). Molecular Markers for failure of Sulfadoxine-Pyrimethamine and Chlorproguanil-Dapsone treat- ment of Plasmodium falciparum malaria.
Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir
An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria. PMID:20113565
Boubidi, Sa?d C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, C?cile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir
An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.
This study reports malaria infection caused by the parasite Plasmodium falciparum in University of Ilorin Teaching Hospital (UITH), Ilorin, Kwara State, Nigeria. This study provides information on the infectivity rate of this parasite in dry season and the variation of laboratory diagnosed cases of malaria to clinically diagnosed ...
Studies were carried out to investigate how infections with Schistosoma haematobium influences Plasmodium parasitaemia level in school children in Ijebu East L.G.A. of Ogun State, south west Nigeria between August and November 2008. One hundred and thirty (130) primary school children, aged between 6 and 15 ...
Plasmodium parasitaemia was determined among pregnant women attending Ante-Natal Clinic at Military Hospital Port Harcourt, Rivers State, Nigeria using the Standard parasitological technique. Venous blood was collected from 200 pregnant women, both thick and thin blood films were made on clean greese-free glass ...
A total of forty six Local Chickens (Gallus gallus) were obtained from Wudil Market in Wudil Local Government Area in January 2009. The birds were screened for malaria parasite by making thick and thin blood films on slides. The slides were examined for the presence of plasmodium parasite (parasitaemia Value). Results ...
Plasmodium falciparum malaria is one of the most important parasitic diseases affecting sub-Saharan Africa, despite the availability of interventions. It exerts tremendous socio-economic and medical burden on the continent, particularly in under five children and pregnant women. In this review, we have attempted to ...
Background: Malaria is the primary cause of hospitalization in Côte d'Ivoire. Early treatment is one of the strategies to control this illness. However, the spread of resistance of Plasmodium falciparum to antimalarial drugs can seriously compromise this strategy. Objectives: The aim of this study was to assess the in vitro ...
Objective: To determine if there is a causal relationship between Plasmodium falciparum and clinical filariasis in individuals exposed to both infections. Methods: An onchocerciasis endemic community in Imo State, South East Nigeria was screened and persons showing overt clinical signs of onchocerciasis were selected ...
Müller, Mattia; Schlagenhauf, Patricia
Since the initial discovery of Plasmodium knowlesi in Malaysia, cases have been reported from several neighbouring countries. Tourism has also resulted in an increasing number of cases diagnosed in Europe, America, and Oceania. In this review we focus on the risk of the travel-associated acquisition of P. knowlesi malaria. A search of the literature in PubMed was carried out to identify articles and literature on the distribution of P. knowlesi infections in Southeast Asia and details of its acquisition and importation by travellers to other continents. The cut-off date for the search was December 1, 2013. Search words used were: "Plasmodium knowlesi", "Plasmodium knowlesi infections", "Plasmodium knowlesi travellers", "Plasmodium knowlesi prevalence", "Plasmodium knowlesi host", "Plasmodium knowlesi vector" "Plasmodium knowlesi RDT", and "Plasmodium knowlesi Malaysia". Traveller numbers to Malaysia were obtained from the Tourism Malaysia website. A total of 103 articles were found. Using a selection of these and others identified from the reference lists of the papers, we based our review on a total of 66 articles. P. knowlesi malaria appears to be the most common malaria species in Malaysian Borneo and is also widely distributed on the Malaysian mainland. Furthermore, locally transmitted cases of P. knowlesi malaria have been reported in Thailand, the Philippines, Vietnam, Singapore, Myanmar, Indonesian Borneo, and Cambodia. Two cases have been reported from non-endemic countries in Asia (Japan and Taiwan) in people with a history of travel to Malaysia and the Philippines. Twelve cases were imported to their home countries by travellers from other continents: two from the USA, two from the Netherlands, two from Germany, and one each from Spain, France, Sweden, Finland, Australia, and New Zealand. In most cases, the infection was associated with a trip to or near forested areas. The symptoms were fever (n=12), headache (n=6), chills (n=6), nausea (n=4), myalgia (n
Full Text Available Abstract Background A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN with a three-day regimen of dihydroartemisinin-piperaquine (DHP, the existing programme drug, in adults with uncomplicated symptomatic malaria. Methods This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR uncorrected and corrected. Results There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 ± 11.7 hours vs 25.5 ± 12.2 hours, p = 0.04. There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3–97.2 and 96.3% (95% Cl: 93.6–99.0 in AN, 96.3% (95% Cl: 93.5–99.0 and 97.3% (95% Cl: 95.0–99.6 in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality. Conclusion AN and DHP are confirmed very effective
Garred, Peter; Nielsen, Morten A; Kurtzhals, Jørgen
Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were...... associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe...... malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL...
Schousboe, Mette L; Rajakaruna, Rupika S; Salanti, Ali
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...... resistance across Sri Lanka. SUBJECTS AND METHODS: P. vivax-positive samples were collected from subjects presenting at government health facilities across nine of the major malaria endemic districts on the island. The samples were analysed for SNPs/haplotypes at codon 57, 58, 61 and 117 of the Pvdhfr gene...
Caruso, Anna Maria; Pane, Alessandro; Garau, Roberto; Atzori, Pietro; Podda, Marcello; Casuccio, Alessandra; Mascia, Luigi
An accurate diagnosis of acute appendicitis is important to avoid severe outcome or unnecessary surgery but management is controversial. The aim of study was to evaluate, in younger and older children, the efficacy of conservative management for uncomplicated appendicitis and the outcome of complicated forms underwent early surgery. Children with acute appendicitis were investigated by clinical, laboratory variables and abdominal ultrasound and divided in two groups: complicated and uncomplicated. Complicated appendicitis underwent early surgery; uncomplicated appendicitis started conservative treatment with antibiotic. If in the next 24-48h it was worsening, the conservative approach failed and patients underwent late surgery. A total of 362 pediatric patients were included. One hundred sixty-five underwent early appendectomy; 197 patients were at first treated conservatively: of these, 82 were operated within 24-48h for failure. The total percentage of operated patients was 68.2%. An elevated association was found between surgery and ultrasound. Conservative treatment for uncomplicated appendicitis had high percentage of success (58%). Complications in operated patients were infrequent. Our protocol was effective in order to decide which patients treat early surgically and which conservatively; specific red flags (age and onset) can identified patients at most risk of complications or conservative failure. treatment study. II. Copyright © 2016 Elsevier Inc. All rights reserved.
Sherer, D M; Onyeije, C I; Binder, D; Bernstein, P S; Divon, M Y
to assess perinatal outcome in post-term pregnancies in which fetal heart rate (FHR) monitoring revealed either uncomplicated baseline fetal tachycardia (> or = 160 bpm) or fetal bradycardia ( or = 41 weeks of gestation by strict dating criteria (last menstrual period consistent with ultrasound biometric parameters obtained prior to 20 weeks' gestation), normal fetal anatomy, intact membranes, and reactive nonstress test with no evidence of chorioamnionitis. Patients with fetal tachy or brady arrhythmias, FHR decelerations, or loss of short-term beat-to-beat variability were excluded. Baseline FHR was recorded retrospectively by an observer blinded to maternal and neonatal clinical outcome. For each case of uncomplicated baseline fetal tachycardia (> or = 160 bpm) or bradycardia ( 120 bpm and or = 160 bpm, and 76 fetuses (5.46%) exhibited baseline FHR postterm patients are not associated with an increase in the incidence of adverse perinatal outcome.
Clinical question In patients with uncomplicated abscesses receiving incision and drainage, does the addition of trimethoprim-sulfamethoxazole result in improved clinical resolution at 7 to 14 days after treatment when compared with placebo? Article chosen Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med 2016;374(9):823-32. The primary objective of this study was to compare the clinical cure rates at 7 to 14 days after the end of the treatment period among patients receiving either trimethoprim-sulfamethoxazole (TMP-SMX) or placebo. Secondary outcomes included composite cure; surgical drainage procedures; change in erythema size; presence of swelling, induration, or tenderness; invasive infections; skin infections at the same site and different sites; hospitalizations; similar infections in household contacts; days missed from normal activities; days missed from school or work; and days of analgesic use.
Plucinski, Mateusz M; Talundzic, Eldin; Morton, Lindsay; Dimbu, Pedro Rafael; Macaia, Aleixo Panzo; Fortes, Filomeno; Goldman, Ira; Lucchi, Naomi; Stennies, Gail; MacArthur, John R; Udhayakumar, Venkatachalam
The development of resistance to antimalarials is a major challenge for global malaria control. Artemisinin-based combination therapies, the newest class of antimalarials, are used worldwide but there have been reports of artemisinin resistance in Southeast Asia. In February through May 2013, we conducted open-label, nonrandomized therapeutic efficacy studies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in Zaire and Uíge Provinces in northern Angola. The parasitological and clinical responses to treatment in children with uncomplicated Plasmodium falciparum monoinfection were measured over 28 days, and the main outcome was a PCR-corrected adequate clinical and parasitological response (ACPR) proportion on day 28. Parasites from treatment failures were analyzed for the presence of putative molecular markers of resistance to lumefantrine and artemisinins, including the recently identified mutations in the K13 propeller gene. In the 320 children finishing the study, 25 treatment failures were observed: 24 in the AL arms and 1 in the DP arm. The PCR-corrected ACPR proportions on day 28 for AL were 88% (95% confidence interval [CI], 78 to 95%) in Zaire and 97% (91 to 100%) in Uíge. For DP, the proportions were 100% (95 to 100%) in Zaire, and 100% (96 to 100%) in Uíge. None of the treatment failures had molecular evidence of artemisinin resistance. In contrast, 91% of AL late-treatment failures had markers associated with lumefantrine resistance on the day of failure. The absence of molecular markers for artemisinin resistance and the observed efficacies of both drug combinations suggest no evidence of artemisinin resistance in northern Angola. There is evidence of increased lumefantrine resistance in Zaire, which should continue to be monitored. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Franck Prugnolle; Patrick Durand; Cécile Neel; Benjamin Ollomo; Francisco J. Ayala; Céline Arnathau; Lucie Etienne; Eitel Mpoudi-Ngole; Dieudonné Nkoghe; Eric Leroy; Eric Delaporte; Martine Peeters; François Renaud
.... Recently, Plasmodium gaboni, another closely related chimpanzee parasite, was discovered, suggesting that the diversity of Plasmodium circulating in great apes in Africa might have been underestimated...
Full Text Available Colonic diverticula are located predominantly on the right side in Asia and on the left side in Europe and the United States. Factors associated with uncomplicated colonic diverticulosis and its distribution pattern have been unknown. Our aims are to investigate the prevalence and risk factors for uncomplicated colonic diverticulosis. We conducted a prospective cross-sectional study in adults who underwent colonoscopy. Alcohol, alcohol related flushing, smoking, medications, and comorbidities were assessed by interview on the colonoscopy day. Alcohol consumption was categorized as nondrinker, light (1-180 g/week, moderate (181-360 g/week, and heavy (≥361 g/week. Smoking index was defined as the number of cigarettes per day multiplied by the number of smoking years and categorized as nonsmoker, <400, 400-799, and ≥800. A total of 2,164 consecutive patients were enrolled. Overall, 542 patients (25.1% had uncomplicated colonic diverticulosis located on the right side (50%, bilaterally (29%, and on the left side (21%. Univariate analysis revealed age, male, smoking index, alcohol consumption, aspirin use, anticoagulants use, corticosteroid use, hypertension, and atherosclerotic disease as factors significantly associated with diverticulosis. Alcohol related flushing was not associated with the disease. Multivariate analysis showed increasing age (P<0.01, increasing alcohol consumption (P<0.01 and smoking (P<0.01, and atherosclerotic disease (P<0.01 as significantly associated factors. Alcohol and smoking were associated with right-sided and bilateral diverticula. In conclusion, one in four Japanese adults have colonic diverticulosis (50% right-sided. Age, alcohol consumption, and smoking were found to be significant risk factors for uncomplicated colonic diverticulosis, particularly right-sided and bilateral.
Tarning, J; Zongo, I.; Somé, FA; Rouamba, N.; S. Parikh; Rosenthal, PJ; Hanpithakpong, W.; Jongrak, N; Day, NPJ; White, NJ; Nosten, F; Ouedraogo, J-B; Lindegardh, N.
Dihydroartemisinin-piperaquine is being increasingly used as a first-line artemisinin combination treatment for malaria. The aim of this study was to describe the pharmacokinetic and pharmacodynamic properties of piperaquine in 236 children with uncomplicated falciparum malaria in Burkina Faso. They received a standard body weight–based oral 3-day fixed-dose dihydroartemisinin-piperaquine regimen. Capillary plasma concentration–time profiles were characterized using nonlinear mixed-effects mo...
O. O. Sarukhanjan
Full Text Available ABSTRACT. Traumatic injury of spine vertebra in children is an actual problem of modern traumatology which is actively being discussed in literature. Recently, the frequency of such registered traumas has increased considerably. Primary diagnostics of uncomplicated traumas in spinal vertebra in children has considerable difficulties which are determined by objective reasons, and is characterized by a high percentage of mistakes. The clinical presentation, diagnostics and treatment of stable injuries of spinal vertebra in children need further studies.
Sanchez, Philip L.; Lancaster, Danny J.; Berg, S. William; Kerbs, Sharon B. J.; Harrison, William O.
Young men with uncomplicated gonococcal urethritis were treated with 1 gram of cefonicid given intramuscularly plus 1 gram of probenecid by mouth. Of 53 evaluable patients, 33 (62%) had penicillinase-producing Neisseria gonorrhoeae. All but one of these patients were cured. All men who had penicillin-sensitive infections were cured. Cefonicid was highly effective in the treatment of both penicillin-sensitive and penicillin-resistant N gonorrhoeae. Other than moderate pain at the site of injec...
Plasmodium. 67 68 3 Introduction 69 70 Malaria infection begins with the infection by Plasmodium ‘sporozoites’ of the liver. After 71 asexual...the Plasmodium mammalian cycle. Identifying parasite proteins that are required for liver infection can lead to novel drugs against malaria . For the...sporozoite infection and whose inhibition could be exploited to prevent the first step of a malaria infection. Thus, we have identified two potential
Nagata, Naoyoshi; Niikura, Ryota; Shimbo, Takuro; Kishida, Yoshihiro; Sekine, Katsunori; Tanaka, Shohei; Aoki, Tomonori; Watanabe, Kazuhiro; Akiyama, Junichi; Yanase, Mikio; Itoh, Toshiyuki; Mizokami, Masashi; Uemura, Naomi
Colonic diverticula are located predominantly on the right side in Asia and on the left side in Europe and the United States. Factors associated with uncomplicated colonic diverticulosis and its distribution pattern have been unknown. Our aims are to investigate the prevalence and risk factors for uncomplicated colonic diverticulosis. We conducted a prospective cross-sectional study in adults who underwent colonoscopy. Alcohol, alcohol related flushing, smoking, medications, and comorbidities were assessed by interview on the colonoscopy day. Alcohol consumption was categorized as nondrinker, light (1-180 g/week), moderate (181-360 g/week), and heavy (≥361 g/week). Smoking index was defined as the number of cigarettes per day multiplied by the number of smoking years and categorized as nonsmoker, diverticulosis located on the right side (50%), bilaterally (29%), and on the left side (21%). Univariate analysis revealed age, male, smoking index, alcohol consumption, aspirin use, anticoagulants use, corticosteroid use, hypertension, and atherosclerotic disease as factors significantly associated with diverticulosis. Alcohol related flushing was not associated with the disease. Multivariate analysis showed increasing age (Pdiverticulosis (50% right-sided). Age, alcohol consumption, and smoking were found to be significant risk factors for uncomplicated colonic diverticulosis, particularly right-sided and bilateral.
Choi, Soo Ran
To determine perinatal outcomes in uncomplicated term pregnancies with a borderline amniotic fluid index (AFI). A retrospective review was conducted of uncomplicated singleton pregnancies at term (>37 weeks). Borderline and normal AFI were defined as 5.1 ≤ AFI ≤ 8.0 cm and 8.1 ≤ AFI ≤ 24 cm, respectively. Adverse perinatal outcomes, cesarean delivery for non-reassuring fetal heart rate testing, meconium-stained amniotic fluid, a 5-min Apgar score of borderline and normal AFI groups. Borderline AFI was not significantly associated with cesarean delivery for non-reassuring fetal heart rate testing (p = 0.513), meconium-stained amniotic fluid (p = 0.641), admission to the NICU (p = 0.368), or a 5-min Apgar score of borderline group. Multiple logistic regression analysis showed that borderline AFI was not associated with cesarean delivery for non-reassuring fetal heart rate testing (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.27-1.91, p = 0.52). In uncomplicated term pregnancies, a borderline AFI does not increase the risk of adverse perinatal outcomes.
Comparative analysis of the safety and tolerability of fixed-dose artesunate/amodiaquine versus artemether/lumefantrine combinations for uncomplicated falciparum malaria in pregnancy: a randomized open label study
Full Text Available Osede I Iribhogbe,1 Igue Emmanuel,2 Marylove Odianosen2 1Department of Pharmacology and Therapeutics, 2Department of Human Physiology College of Medicine, Ambrose Alli University Ekpoma, Edo State, Nigeria Abstract: A comparative clinical study was conducted to evaluate the safety and tolerability of two commonly used fixed dose artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria in the second and third trimester of pregnancy. To achieve this, a total of 155 participants were recruited for the study. Eighty of these were drawn from pregnant women who came for routine antenatal care while 40 nonpregnant participants were recruited from apparently healthy females in the community. Eighty pregnant participants with uncomplicated P. falciparum malaria were randomized into artesunate/amodiaquine (AA and artemether/lumefantrine (AL treatment arms while 40 nonpregnant and 35 nonmalarious pregnant women were used as control. The interventional groups received standard fixed dose combinations of AA (100/270 mg daily or AL (20/120 mg twice daily for 3 days. Blood samples were collected on day 4 and patients were followed-up closely to ascertain the safety of the drugs. The study showed a significant (p<0.0001 elevation of alkaline phosphatase in the AA and AL group compared to the nonpregnant control and a significant (p<0.05 elevation of alanine transaminase and aspartate transaminase level in the AL combination group when compared with the AA group. The elevated hepatic enzymes were within the normal range for pregnancy and were not clinically significant. Adverse event rate was higher in the AA group (n=28 [70%] when compared to the AL group (n=4 [10%] although the drugs were well-tolerated in both treatment arms. In conclusion, the use of these combinations is safe in the second and third trimester of pregnancy. However, we recommend active pharmacovigilance and spontaneous drug reporting of the agents in
Shirakawa, Tomohiro; Gunji, Yukio-Pegio; Sato, Hiroshi; Tsubakino, Hiroto
The plasmodium of true slime mold Physarum polycephalum is a unicellular and multinuclear giant amoeba. Since the cellular organism has some computational abilities, it is attracting much attention in the field of information science. However, previous studies have mainly focused on the optimization behavior of the plasmodium for a single-modality stimulus, and there are few studies on how the organism adapts to multi-modal stimuli. We stimulated the plasmodium with mixture of attractant and repellent stimuli, and we observed bifurcation in the chemotactic behavior of the plasmodium.
Eriksen, J; Mwankusye, S; Mduma, S; Kitua, A; Swedberg, G; Tomson, G; Gustafsson, L L; Warsame, M
A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine.
Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima; Gómez-Olivé, Xavier; Rønn, Anita M; Thompson, Ricardo; Alifrangis, Michael
In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the Plasmodium falciparum genes Pfdhfr, Pfdhps and Pfcrt before and a year after the introduction of SP. Samples were collected during two cross sectional surveys in early 2002 and 2003 involving 796 and 692 children one year or older and adults randomly selected living in Maciana, an area located in Manhiça district, Southern Mozambique. Out of these, 171 and 173 P. falciparum positive samples were randomly selected to measure the frequency of resistance- related haplotypes in Pfdhfr, Pfdhps and Pfcrt based on results obtained by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The frequency of the SP-resistance associated Pfdhps double mutant (SGEAA) haplotype increased significantly from 14% to 35% (P drug, Coartem.
Aponte, Samanda; Guerra, Ángela Patricia; Álvarez-Larrotta, Catalina; Bernal, Sindy Durley; Restrepo, César; González, Camila; Yasnot, María Fernanda; Knudson-Ospina, Angélica
Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed. From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found. This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities.
Adelaide U.P. Hain
Full Text Available Autophagy is a catabolic process that normally utilizes the lysosome. The far-reaching implications of this system in disease are being increasingly understood. Studying autophagy is complicated by its role in cell survival and programmed cell death and the involvement of the canonical marker of autophagy, Atg8/LC3, in numerous non-autophagic roles. The malaria parasite, Plasmodium, has conserved certain aspects of the autophagic machinery but for what purpose has long remained a mystery. Major advances have recently been gained and suggest a role for Atg8 in apicoplast maintenance, degradation of heme inside the food vacuole, and possibly trafficking of proteins or organelles outside the parasite membrane. Autophagy may also participate in programmed cell death under drug treatment or as a selective tool to limit parasite load. We review the current findings and discuss discrepancies in the field of autophagy in the Plasmodium parasite.
Full Text Available A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.
Smith, Ryan C; Barillas-Mury, Carolina
Although the ability of mosquitoes to limit Plasmodium infection is well documented, many questions remain as to how malaria parasites are recognized and killed by the mosquito host. Recent evidence suggests that anti-Plasmodium immunity is multimodal, with different immune mechanisms regulating ookinete and oocyst survival. However, most experiments determine the number of mature oocysts, without considering that different immune mechanisms may target different developmental stages of the parasite. Complement-like proteins have emerged as important determinants of early immunity targeting the ookinete stage, yet the mechanisms by which the mosquito late-phase immune response limits oocyst survival are less understood. Here, we describe the known components of the mosquito immune system that limit oocyst development, and provide insight into their possible mechanisms of action. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Müller, Mattia; Schlagenhauf, Patricia
OBJECTIVES: Since the initial discovery of Plasmodium knowlesi in Malaysia, cases have been reported from several neighbouring countries. Tourism has also resulted in an increasing number of cases diagnosed in Europe, America, and Oceania. In this review we focus on the risk of the travel-associated acquisition of P. knowlesi malaria. METHODS: A search of the literature in PubMed was carried out to identify articles and literature on the distribution of P. knowlesi infections in Southeast ...
Price, R.; van Vugt, M.; Phaipun, L.; Luxemburger, C.; Simpson, J.; McGready, R.; ter Kuile, F.; Kham, A.; Chongsuphajaisiddhi, T.; White, N. J.; Nosten, F.
In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826
Surjadjaja, Claudia; Surya, Asik; Baird, J Kevin
Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. © The American Society of Tropical Medicine and Hygiene.
Ramharter, Michael; Oyakhirome, Sunny; Klein Klouwenberg, Peter; Adégnika, Ayola A; Agnandji, Sélidji T; Missinou, Michel A; Matsiégui, Pierre-Blaise; Mordmüller, Benjamin; Borrmann, Steffen; Kun, Jürgen F; Lell, Bertrand; Krishna, Sanjeev; Graninger, Wolfgang; Issifou, Saadou; Kremsner, Peter G
Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa. Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high. We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa. We conducted an open-label, randomized, controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days (artesunate, 2 mg/kg, and clindamycin, 7 mg/kg, per dose), compared with a standard quinine-clindamycin regimen given twice daily for 3 days (quinine, 15 mg/kg, and clindamycin, 7 mg/kg, per dose), for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3-12 years. The primary end point of the study was the polymerase chain reaction-corrected cure rate for the per-protocol population. The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the per-protocol analysis of cure rates at day 28 of follow-up (87% versus 94%). No serious adverse events were reported, and tolerability was good and was similar in both groups. Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group. Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high.
Daniela Camargos Costa
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.
Ressl, J; Jandová, R; Jebavý, P; Kasalický, J; Widimský, J
Left ventricular function was investigated at rest and during exercise by heart catheterization in 15 patients 3-5 months after acute myocardial infarction. The effect of 1 mg digoxin i.v. in ten patients was correlated to placebo (saline solution) in five patients. A significant decrease of the left ventricular enddiastolic pressure, increase of left ventricular systolic ejection fraction and a shift of the left ventricular function curve to left upwards was found after digoxin with no changes in the placebo group. This beneficial effect of acute digitalization in patients convalescing from uncomplicated myocardial infarction without clinical signs of manifest heart failure could have therapeutic implication.
Walker, Robin L; Chen, Guanmin; McAlister, Finlay A; Campbell, Norm R C; Hemmelgarn, Brenda R; Dixon, Elijah; Ghali, William; Rabi, Doreen; Tu, Karen; Jette, Nathalie; Quan, Hude
Hospitalizations for ambulatory care-sensitive conditions (ACSCs) represent an indirect measure of access and quality of community care. The purpose of this study was to examine the association between one ACSC, uncomplicated hypertension, and previous primary care physician (PCP) utilization. A cohort of patients with hypertension was identified using administrative databases in Alberta between fiscal years 1994 and 2008. We applied the Canadian Institute for Health Information's case definition to detect patients with uncomplicated hypertension as the most responsible reason for hospitalization and/or Emergency Department (ED) visit. We assessed hypertension-related and all-cause PCP visits. The overall adjusted rate of ACSC hospitalizations and ED visits for uncomplicated hypertension was 7.1 and 13.9 per 10,000 hypertensive patients, respectively. The likelihood of ACSC hospitalization for uncomplicated hypertension was associated with age, household income quintile, region of residence, and Charlson comorbidity status (all P hypertension increased from 4.8 per 10,000 hypertensive patients for those without hypertension-related PCP visits before diagnosis to 10.5 per 10,000 hypertensive patients for those with 5 or more hypertension-related PCP visits. The rate of ACSC hospitalizations and/or ED visits for uncomplicated hypertension increased as the number of hypertension-related PCP visits increased even after stratifying according to demographic and clinical characteristics. As the frequency of hypertension-related PCP visits increased, the rate of ACSC hospitalizations and/or ED visits for uncomplicated hypertension increased. This suggests that ACSC hospitalization for uncomplicated hypertension might not be a particularly good indicator for access to primary care. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Full Text Available Abstract Background Plasmodium falciparum exports proteins that remodel the erythrocyte membrane. One such protein, called Pf155/RESA (RESA1 contributes to parasite fitness, optimizing parasite survival during febrile episodes. Resa1 gene is a member of a small family comprising three highly related genes. Preliminary evidence led to a search for clues indicating the involvement of RESA2 protein in the pathophysiology of malaria. In the present study, cDNA sequence of resa2 gene was obtained from two different strains. The proportion of P. falciparum isolates having a non-stop T1526C mutation in resa2 gene was evaluated and the association of this genotype with severity of malaria was investigated. Methods Resa2 cDNAs of two different strains (a patient isolate and K1 culture adapted strain was obtained by RT-PCR and DNA sequencing was performed to confirm its gene structure. The proportion of isolates having a T1526C mutation was evaluated using a PCR-RFLP methodology on groups of severe malaria and uncomplicated patients recruited in 1991–1994 in Senegal and in 2009 in Benin. Results A unique ORF with an internal translation stop was found in the patient isolate (Genbank access number : JN183870, while the K1 strain harboured the T1526C mutation (Genbank access number : JN183869 which affects the internal stop codon and restores a full length coding sequence. About 14% of isolates obtained from Senegal and Benin harboured mutant T1526C parasites. Some isolates had both wild and mutant resa alleles. The analysis excluding those mixed isolates showed that the resa2 T1526C mutation was found more frequently in severe malaria cases than in uncomplicated cases (p = 0.008. The association of the presence of the mutant allele and parasitaemia >4% was shown in multivariate analysis (p = 0.03 in the group of Beninese children. Conclusions All T1526C mutant parasites theoretically have the ability to give rise to a full-length RESA2 protein
Full Text Available Abstract Background By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam. Methods From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS (2mg/kg/day versus 4 mg/kg/day for three days followed by dihydroartemisinin-piperaquine (DHA-PPQ and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time. Results 166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg, 2.72 (AS 4mg/kg, and 2.98 hours (DHA-PPQ (p=0.19. The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02. The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4% and late clinical failure occurred in one (2% of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR rates in the three groups were 94%, 100%, and 100% (p=0.04. Conclusions This study demonstrated faster P. falciparum parasite
Hien, Tran Tinh; Thuy-Nhien, Nguyen Thanh; Phu, Nguyen Hoan; Boni, Maciej F; Thanh, Ngo Viet; Nha-Ca, Nguyen Thuy; Thai, Le Hong; Thai, Cao Quang; Toi, Pham Van; Thuan, Phung Duc; Long, Le Thanh; Dong, Le Thanh; Merson, Laura; Dolecek, Christiane; Stepniewska, Kasia; Ringwald, Pascal; White, Nicholas J; Farrar, Jeremy; Wolbers, Marcel
By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam. From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS) (2mg/kg/day versus 4 mg/kg/day for three days) followed by dihydroartemisinin-piperaquine (DHA-PPQ) and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time. 166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2.72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4%) and late clinical failure occurred in one (2%) of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR) rates in the three groups were 94%, 100%, and 100% (p=0.04). This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but
Full Text Available Aim: In Benin, artemisinin-based combination therapy (ACT has been recommended as the first-line treatment for uncomplicated Plasmodium falciparum malaria since 2004. The emergence in Southeast Asia of parasites that are resistant to artemisinins poses a serious threat to global control of this disease. The presence of artemisinin resistance genotypes in parasite populations in Benin is currently unknown. The present study investigated the prevalence of relevant K13-propeller gene polymorphisms in parasite isolates from the north-western region of Benin. Method: Plasmodium falciparum isolates were collected from children with a confirmed diagnosis of malaria aged 6 months to 5 years in two towns, Cobly and Djougou, in the north-western part of Benin. The study was conducted during the rainy season from July to November 2014 in local health facilities. The K13-propeller gene was amplified in parasite isolates using nested PCR and subsequently sequenced. Results: A total of 108 children were recruited into the study. The efficiency of amplification reactions was 72% (78/108. The propeller domain of the K13 gene was successfully sequenced in 78 P. falciparum isolates; all of them were wild type with no polymorphisms detectable. Conclusion: The absence of mutations in the K13 gene indicates that P. falciparum parasite populations in the study area are still fully susceptible to artemisinins.
Plasmodium infection in man is caused by the bite of an infected female Anopheles mosquito. This results in the disease, malaria. Malaria has serious debilitating effects on man. It adversely affectsman's health, strength and productivity. Here, a review of Plasmodium infection in man including the life cycle transmisson, ...
Abstract. Background: Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. Objective: To ...
Objective: To determine how sensitive Plasmodium falciparum is to the major antimalarial drugs in Madagascar. Design: Assessment of Plasmodium falciparum isolates sensitivity to antimalarials, by use of the in-vitro radioisotope method. Setting: Ankazobe and Saharevo in the foothill areas; and Toamasina and Tolagnaro ...
Artemisinin derivatives constitute a key component of the present-day treatment for Plasmodium falciparum malaria. Resistance with artemisinins is generally associated with S769N point mutation in the sarco-endoplasmic reticulumdependant ATPase6 (SERCA ATPase6) gene of Plasmodium falciparum, few studies have ...
Background: Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. Objective: To determine ...
K. N. Mendis
Full Text Available The cytokine tumor necrosis factor and other as yet unidentified factor(s which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TFN levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheles serum TFN levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.
Full Text Available Cecal perforation is an uncommon phenomenon in a pediatric population. It has been linked to a number of underlying medical conditions, which may result in focal inflammation or relative ischemia including hematologic malignancy, infection, and inflammatory bowel disease. We present an otherwise healthy 16-year-old male diagnosed with acute uncomplicated appendicitis on ultrasound, who was found to have cecal perforation with normal appendix intraoperatively, ultimately requiring ileocectomy. With this report, we aim to present the numerous pathophysiologic etiologies of cecal perforation, and to promote a comprehensive differential diagnosis despite the clinical and radiologic findings consistent with uncomplicated appendicitis.
Dréanic, Johann; Sion, Elena; Dhooge, Marion; Dousset, Bertrand; Camus, Marine; Chaussade, Stanislas; Coriat, Romain
Acute diverticulitis is a common disease with increasing incidence. In most of cases, diagnosis is made at an uncomplicated stage offering a curative attempt under medical treatment and use of antibiotics. There is a risk of diverticulitis recurrence. Uncomplicated diverticulitis is opposed to complicated forms (perforation, abscess or fistula). Recent insights in the pathophysiology of diverticulitis, the natural history, and treatments have permitted to identify new treatment strategies. For example, the use of antibiotics tends to decrease; surgery is now less invasive, percutaneous drainage is preferred, peritoneal lavage is encouraged. Treatments of the diverticulitis are constantly evolving. In this review, we remind the pathophysiology and natural history, and summarize new recommendations for the medical and surgical treatment of acute diverticulitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Bagla, Prabhava; Sarria, Juan C; Riall, Taylor S
Various aspects of the management of acute calculous cholecystitis, including type and timing of surgery, role of antibiotics, and nonoperative management, remain controversial. This review focuses on recently published studies addressing the timing of cholecystectomy, use of cholecystostomy tubes, and role of antibiotics in this condition. In most cases, the diagnosis of acute cholecystitis can be initially confirmed with an abdominal ultrasound. Early laparoscopic cholecystectomy (within 24-72 h of symptom onset) is better than delayed surgery (>7 days) for most patients with grade I and II diseases. Percutaneous cholecystostomy and novel endoscopic gallbladder drainage interventions may be used as a temporizing measure or as definitive therapy in those who are too sick to undergo surgery. Studies are conflicting as to whether antibiotics are required for the treatment of uncomplicated cases. Cholecystectomy remains the only definitive therapy for acute cholecystitis. Current guidelines recommend treatment on the basis of disease severity at presentation. Antibiotics and a variety of minimally invasive nonsurgical interventions, although not definitive, play an adjunctive role in the management of the disease.
Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: a systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data
Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy...
Adam, Ishag; Magzoub, Mamoun; Osman, Maha E
BACKGROUND: Artemisinin-based combination therapy is increasingly being adopted as first-line antimalarial therapy. The choice of appropriate therapy depends on efficacy, cost, side effects, and simplicity of administration. METHODS: the efficacy of fixed co-formulated (f) artesunate...
Ibrahium, A M; Kheir, M M; Osman, M E
-SP but four (9.5%) of those given AS-AQ were initially considered to be late treatment and parasitological failures, with all other patients showing an adequate treatment response. The PCR-corrected frequencies of cure were 97.5% for AS-SP and 95.2% for AS-AQ (P>0.05). No gametocytaemias were observed during...... the follow-up and, although mild adverse effects (nausea, vomiting, abdominal pain, dizziness and/or rash) were detected in 14 patients, they occurred at the same frequency in each treatment arm. It therefore appears that the AS-SP and AS-AQ combinations were both effective and safe for the treatment...
Knutson, Doug; Braun, Chad
Acute bronchitis is one of the top 10 conditions for which patients seek medical care. Physicians show considerable variability in describing the signs and symptoms necessary to its diagnosis. Because acute bronchitis most often has a viral cause, symptomatic treatment with protussives, antitussives, or bronchodilators is appropriate. However, studies indicate that many physicians treat bronchitis with antibiotics. These drugs have generally been shown to be ineffective in patients with uncomplicated acute bronchitis. Furthermore, antibiotics often have detrimental side effects, and their overuse contributes to the increasing problem of antibiotic resistance. Patient satisfaction with the treatment of acute bronchitis is related to the quality of the physician-patient interaction rather than to prescription of an antibiotic.
Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki
Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.
Gerald, Noel; Mahajan, Babita; Kumar, Sanjai
Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. PMID:21317311
Ofori Michael F
Full Text Available Abstract Background Severe anaemia (SA, intravascular haemolysis (IVH and respiratory distress (RD are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. Methods The direct Coombs test (DCT and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ and the regulatory proteins [complement receptor 1 (CD35 and decay accelerating factor (CD55] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb levels and RD were investigated. Results Of the 484 samples tested, 131(27% were positive in DCT, out of which 115/131 (87.8% were positive for C3d alone while 16/131 (12.2% were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p Conclusion These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.
Ouedraogo, Dieu-Donné; Eti, Edmond; Daboiko, Jean-Claude; Simon, Frankz; Chuong, Van Tuan; Zué, Marcel Kouakou N
To study the epidemiologic and semiotic characteristics of uncomplicated sciatica in patients in a university hospital in Côte d'Ivoire. This retrospective study included 143 patients with an uncomplicated herniated disc hospitalized in the Cocody University Hospital from 1998 through 2002; patients were excluded if they were excessively sensitive to pain, had related motor deficits, cauda equina syndrome, or were resistant to medical treatment. Patients' average age was 42.5 years (range: 15-81), 58% were women, and mean body mass index (BMI) was 26.16. Ninety-nine (69.2%) reported relatively sedentary work. The disorder was characterized by an antalgic position (in 46.9%), an abnormal Schöber index in 117 (81.8%), the "bell sign" (in 63.6%) and a cough impulse in 58.7%. Lasègue's sign was homolateral at 114 (79.7%), and the average amplitude 42.2 degrees (range: 10 to 80). Paresis of 3/5 or higher was observed in 32 patients (22.4%). Radiography showed a disc disorder in 63% of cases; posterior osteoarthritis in 39.2% and a narrowed lumbar channel in 14 %. Computed tomography was performed for 56 patients and confirmed the presence of a hernia (median: 42,8%; paramedian: 48,2%; foraminal: 8,0%) of L4-l5 in 43 patients (77%); a large hernia, defined by a size greater than half of the rachidian channel, was found in eight (14,3%). After medical treatment, the course was favourable during this hospitalisation. Contrary to preconceived ideas, uncomplicated sciatica of black subjects has the same characteristics as in the white population.
Febir, Lawrence G; Asante, Kwaku Poku; Afari-Asiedu, Samuel; Abokyi, Livesy N; Kwarteng, Anthony; Ogutu, Bernhards; Gyapong, Margaret; Owusu-Agyei, Seth
Malaria accounts for many deaths and illnesses, mostly among young children and pregnant women in sub-Saharan Africa. An integrated approach is recommended to ensure effective malaria control. Socio-cultural factors continue to serve as determinants of malaria health-seeking behaviour. An INDEPTH effectiveness and safety study platform was established to unearth issues around the use of licensed and nationally recommended anti-malarials in real life settings. This study reports on treatment-seeking behaviour for uncomplicated malaria among community members. A qualitative study was conducted in the dry and rainy seasons in purposively selected communities in Kintampo north and south districts. This was based on distances to a health facility, ethnicity and availability of medicines at the sale outlets. Twenty-four focus group discussions were conducted among adult men, women care-takers of children less than 5 years and pregnant women. Ten INDEPTH interviews were also conducted among operators of medicine sale outlets and managers of health facilities. Fifty-one illnesses narrative interviews were conducted among adult men, women, women caretakers of children less than 5 years and pregnant women. Transcripts were transferred into Nvivo 8 software for data management and analysis. The artemisinin-based combinations that were commonly known and used were artesunate-amodiaquine and artemether-lumefantrine. Use of herbal preparation to treat diseases including uncomplicated malaria is rife in the communities. Drug stores were not the main source of artemisinin-based combination sales at time of the study. Monotherapies, pain killers and other medicines were purchased from these shops for malaria treatment. Dizziness, general body weakness and sleepiness were noted among respondents who used artemisinin-based combination therapy (ACT) in the past. There is no clear cut trajectory for management of uncomplicated malaria in the study area. Different approaches are adopted
Full Text Available Thirty cases of uncomplicated duodenal ulcer treated by anterior superficial lesser curvature seromyotomy and posterior truncal vagotomy were studied to evaluate the efficacy of this procedure. There was completeness of vagotomy in all the cases as shown by endoscopic Congo Red test. Twenty-seven cases were asymptomatic at 1-48 months (Mean 22.3 follow up, while 3 patients had controllable side effects such as dumping and diarrhoea. There was no mortality. This procedure is safe, effective and is a favourable alternative to highly selective vagotomy.
Milisavljević, Nemanja; Cvetković, Mirjana; Nikolić, Goran; Filipović, Branka; Milinić, Nikola
The association between celiac disease and eating disorders has been very rarely reported. This is the first report on celiac disease associated with bulimia in this part of Europe. An adult female patient with history of bulimia and one uncomplicated pregnancy was admitted to the Gastroenterology Department, due to long lasting dyspeptic symptoms, constipation, major weight loss and fatigue. After positive serological screening, the diagnosis of celiac disease was confirmed with histopathology examination of duodenal biopsy specimen. Complicated interactions between celiac disease and bulimia can make them difficult to diagnose and treat. It is important to consider the presence of celiac disease in patients with bulimia and gastrointestinal symptoms.
Vik, Ingvild; Bollestad, Marianne; Grude, Nils
BackgroundAlthough uncomplicated cystitis is often self-limiting, most such patients will be prescribed antibiotic treatment. We are investigating whether treatment of cystitis with an NSAID is as effective as an antibiotic in achieving symptomatic resolution.Methods/DesignThis is a randomized...... times a day or 200 mg mecillinam three times a day for three days. Allocation is conducted using block randomization. The primary outcome is the number of patients who feel cured by day four as recorded in a diary. Adverse events will be handled and reported in accordance with Good Clinical Practice...
Reid, Esther W; McNeill, Jenny A; Alderdice, Fiona A; Tully, Mark A; Holmes, Valerie A
to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia. a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing ≥ 4000 g (study group) or macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks. Copyright © 2014 Elsevier Ltd. All rights reserved.
Bisgaard, T; Støckel, M; Klarskov, B
fundoplication for gastro-oesophageal reflux disease. Patients were recommended to convalesce for 2 days after operation. Duration of convalescence, dysphagia, fatigue, nausea, vomiting and different pain components were registered daily during the first week and on days 10 and 30 after fundoplication. RESULTS...... or severe dysphagia during the study period. Fatigue scores were significantly increased for 6 days after surgery (P ... and dysphagia are significant problems after uncomplicated total laparoscopic fundoplication. The time taken off work and away from recreational activity exceeded the recommended 2 days of convalescence, justifying further efforts to optimize early clinical outcome after total laparoscopic fundoplication....
Karunaweera, Nadira; Wanasekara, Deepani; Chandrasekharan, Vishvanath; Mendis, Kamini; Carter, Richard
Background Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Methods Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Results Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum indicating that the parasite
Full Text Available Abstract Background Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Methods Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Results Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum
Karunaweera, Nadira; Wanasekara, Deepani; Chandrasekharan, Vishvanath; Mendis, Kamini; Carter, Richard
Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum indicating that the parasite activity involved may be
Full Text Available Acute bacterial sinusitis is a common infectious condition. Patients may initially present with an uncomplicated infection and later, despite appropriate initial antibiotic therapy, develop a potentially life-threatening complication. Interventions aimed at alleviating such unexpected events need be prompt and adequate. We describe a case of a patient who initially presented with signs and symptoms of acute sinusitis later to be diagnosed with a frontal epidural abscess.
Okonko, I. O.
Full Text Available This study reports the prevalence of malaria caused by plasmodium between genders in Abeokuta, the capital city of Ogun State located in the forest zone of southwestern Nigeria between January 2002 and December 2004. Blood film examination for malaria parasites in 708 patients; 366 males and 342 females. Microscopic examination of thick films techniques was employed for this study. Of the 708 (100% patients examined, 577 (81.5% were Plasmodium-positive. A high malaria parasite prevalence rate of 81.5% was noted in this study. Female subjects were more infected (42.4% than males (41.9% however, there was no significant difference in the sex of the subjects studied (p=0.05. A high malaria parasite prevalence rate of 86.9% was noted in samples collected in year 2003 than in other years studied. There was significant difference in the years under study (p=0.05. This study shows that a good percentage of people were infested by malaria Plasmodium. This could be attributed to lack of adequate accommodation and poor sanitary conditions in the area under study. Although several efforts have been made to effectively control the high incidence of malaria in Nigeria, these have been largely unsuccessful due to a number of reasons such as irrigated urban agriculture which can be the malaria vector’s breeding ground in the city, stagnant gutters and swamps in our environment where mosquitoes breed in millions, and lack of political will and commitment of the government in its disease management program, low awareness of the magnitude of malaria problem, poor health practices by individuals and communities and resistance to drugs. Therefore, future interventions in Nigeria should be directed toward controlling malaria in the context of a moderate transmission setting; thus, large-scale distribution of insecticide-treated nets or widespread use of indoor residual spraying may be less cost-effective than enhanced surveillance with effective case management or
LeBlanc, Danielle; Story, Robert; Gross, Eitan
Haemozoin crystals, produced by Plasmodium during its intra-erythrocytic asexual reproduction cycle, can generate UV light via the laser-induced, non-linear optical process of third harmonic generation (THG). In the current study the feasibility of using haemozoin, constitutively stored in the parasite's food vacuole, to kill the parasite by irradiation with a near IR laser was evaluated. Cultured Plasmodium parasites at different stages of development were irradiated with a pulsed NIR laser and the viability of parasites at each stage was evaluated from their corresponding growth curves using the continuous culture method. Additional testing for germicidal effects of haemozoin and NIR laser was performed by adding synthetic haemozoin crystals to Escherichia coli in suspension. Cell suspensions were then irradiated with the laser and small aliquots taken and spread on agar plates containing selective agents to determine cell viability (CFU). Parasites in the late-trophozoites form as well as trophozoites in early-stage of DNA synthesis were found to be the most sensitive to the treatment with -4-log reduction in viability after six passes through the laser beam; followed by parasites in ring phase (-2-log reduction). A -1-log reduction in E. coli viability was obtained following a 60 min irradiation regimen of the bacteria in the presence of 1 μM synthetic haemozoin and a -2-log reduction in the presence of 10 μM haemozoin. Minimal (≤ 15%) cell kill was observed in the presence of 10 μM haemin. Laser-induced third-harmonic generation by haemozoin can be used to inactivate Plasmodium. This result may have clinical implications for treating severe malaria symptoms by irradiating the patient's blood through the skin or through dialysis tubing with a NIR laser.
Full Text Available Abstract Background Haemozoin crystals, produced by Plasmodium during its intra-erythrocytic asexual reproduction cycle, can generate UV light via the laser-induced, non-linear optical process of third harmonic generation (THG. In the current study the feasibility of using haemozoin, constitutively stored in the parasite’s food vacuole, to kill the parasite by irradiation with a near IR laser was evaluated. Methods Cultured Plasmodium parasites at different stages of development were irradiated with a pulsed NIR laser and the viability of parasites at each stage was evaluated from their corresponding growth curves using the continuous culture method. Additional testing for germicidal effects of haemozoin and NIR laser was performed by adding synthetic haemozoin crystals to Escherichia coli in suspension. Cell suspensions were then irradiated with the laser and small aliquots taken and spread on agar plates containing selective agents to determine cell viability (CFU. Results Parasites in the late-trophozoites form as well as trophozoites in early-stage of DNA synthesis were found to be the most sensitive to the treatment with ~4-log reduction in viability after six passes through the laser beam; followed by parasites in ring phase (~2-log reduction. A ~1-log reduction in E. coli viability was obtained following a 60 min irradiation regimen of the bacteria in the presence of 1 μM synthetic haemozoin and a ~2-log reduction in the presence of 10 μM haemozoin. Minimal (≤15% cell kill was observed in the presence of 10 μM haemin. Conclusions Laser-induced third-harmonic generation by haemozoin can be used to inactivate Plasmodium. This result may have clinical implications for treating severe malaria symptoms by irradiating the patient’s blood through the skin or through dialysis tubing with a NIR laser.
Full Text Available Abstract Background The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection. Methods Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively and from immune adults (N = 30 living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α1, CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children. Results Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100% and asymptomatic children (92.3% but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively. The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α1. None of the
Okolie, E E; Onyezili, N I
The nuclei of Plasmodium yoelii nigeriensis contain an enzyme, ADP-ribosyltransferase, that will incorporate the ADP-ribose moiety of NAD+ into acid-insoluble product. The time, pH and temperature optima of this incorporation are 30 min, 8.5 and 25 degrees C respectively. Maximum stimulation of the enzyme activity is obtained with 1.0 mM-dithiothreitol or 2.0 mM-2-mercaptoethanol. Ca2+ and Mg2+ ions at optimum concentrations of 5 mM and 10 mM respectively stimulated the activity of the enzyme...
Andersen, S B; Paerregaard, A; Larsen, K
PURPOSE: Aim of the study was to describe changes in the epidemiology of acute appendicitis in Danish children between 0-19 years of age for the period 1996-2004. METHODS: The study was based on discharge diagnoses taken from the Danish National Patient Registry of all 28 274 patients with a diag......PURPOSE: Aim of the study was to describe changes in the epidemiology of acute appendicitis in Danish children between 0-19 years of age for the period 1996-2004. METHODS: The study was based on discharge diagnoses taken from the Danish National Patient Registry of all 28 274 patients...... with a diagnosis of acute uncomplicated or complicated appendicitis, and/or a registered procedure code of appendectomy. These data were computed together with data on the background population, and incidences were calculated. RESULTS: A significant decrease in the incidence of acute uncomplicated appendicitis...... was found for all age groups (range, 13-36%). The decrease was present for both sexes, but most prominent in girls. The incidence of complicated acute appendicitis decreased by 10%. CONCLUSION: The incidence of acute appendicitis is declining. The incidence of uncomplicated appendicitis appears...
The diagnostic approach of patients with suspected acute diverticulitis remains debated. On the one hand, a scoring system with the best predictive value in diagnosing acute diverticulitis has been developed in order to reduce the use of computed tomography (CT) scan, while, on the other hand, patients with a high probability of acute diverticulitis should benefit from CT scan from a clinical viewpoint, ensuring that they will receive the most appropriate treatment. The place and classification of CT scan for acute diverticulitis need to be reassessed. If the management of uncomplicated acute diverticulitis, abscess, and fecal peritonitis is now well codified, urgent surgical or medical treatment of hemodynamically stable patients presenting with intraperitoneal air or fluid without uncontrolled sepsis is still under discussion. Furthermore, the indications for laparoscopic lavage are not yet well established. It is known for years that episode(s) of acute uncomplicated diverticulitis may induce painful recurrent bowel symptoms, known as symptomatic uncomplicated diverticular disease and irritable bowel syndrome-like diverticular disease. These two clinical expressions of diverticular disease, that may darken quality of life, are treated medically aimed at symptom relief. The possible place of surgery should be discussed. Clinical and CT scan classifications should be separated entities. PMID:27574459
Full Text Available Patrick Ambrosetti Department of Surgery, Clinique Générale Beaulieu, Geneva, Switzerland Abstract: The diagnostic approach of patients with suspected acute diverticulitis remains debated. On the one hand, a scoring system with the best predictive value in diagnosing acute diverticulitis has been developed in order to reduce the use of computed tomography (CT scan, while, on the other hand, patients with a high probability of acute diverticulitis should benefit from CT scan from a clinical viewpoint, ensuring that they will receive the most appropriate treatment. The place and classification of CT scan for acute diverticulitis need to be reassessed. If the management of uncomplicated acute diverticulitis, abscess, and fecal peritonitis is now well codified, urgent surgical or medical treatment of hemodynamically stable patients presenting with intraperitoneal air or fluid without uncontrolled sepsis is still under discussion. Furthermore, the indications for laparoscopic lavage are not yet well established. It is known for years that episode(s of acute uncomplicated diverticulitis may induce painful recurrent bowel symptoms, known as symptomatic uncomplicated diverticular disease and irritable bowel syndrome-like diverticular disease. These two clinical expressions of diverticular disease, that may darken quality of life, are treated medically aimed at symptom relief. The possible place of surgery should be discussed. Clinical and CT scan classifications should be separated entities. Keywords: diverticulitis, urgent treatment, chronic symptoms, clinical and CT scan classifications
Otchwemah Rowland N
Full Text Available Abstract Background Both chloroquine (CQ and sulfadoxine-pyrimethamine (SP are failing drugs in much of sub-Saharan Africa. Previous findings suggest an association between resistance to CQ and to SP in vivo, in vitro, and on the molecular level. Methods In 126 Ghanaian children with uncomplicated malaria, associations between mutations conferring resistance in the Plasmodium falciparum dihydrofolate reductase (dhfr; SP and chloroquine resistance transporter (crt; CQ genes, concentrations of residual antimalarial drugs, and gametocyte carriage were examined. Results Mutant dhfr alleles and the CQ-resistance allele crt T76 were strongly associated with each other. Isolates exhibiting the dhfr triple mutation seven times more likely also contained crt T76 parasites as compared to isolates without the dhfr triple variant (P = 0.0001. Moreover, both, isolates with the dhfr triple mutation (adjusted OR, 3.2 (95%CI, 1.0–10.4 and with crt T76 (adjusted OR, 14.5 (1.4–150.8 were associated with an increased likelihood of pre-treatment gametocytaemia. However, crt T76 did not correlate with gametocytaemia following SP treatment and no selection of crt T76 in SP treatment failure isolates was observed. Conclusion These results confirm an association between CQ and SP resistance markers in isolates from northern Ghana. This could indicate accelerated development of resistance to SP if CQ resistance is already present, or vice versa. Considering the enhanced transmission potential as reflected by the increased proportion of isolates containing gametocytes when resistant parasites are present, co-resistance can be expected to spread in this area. However, the underlying mechanism leading to this constellation remains obscure.
Theander Thor G
Full Text Available Abstract Background In malaria endemic areas children may recover from malaria after chemotherapy in spite of harbouring genotypically drug-resistant Plasmodium falciparum. This phenomenon suggests that there is a synergy between drug treatment and acquired immunity. This hypothesis was examined in an area of moderately intense transmission of P. falciparum in Tanzania during a drug trail with sulphadoxine-pyrimethamine (SP or amodiaquine (AQ. Methods One hundred children with uncomplicated malaria were treated with either SP or AQ and followed for 28 days. Mutations in parasite genes related to SP and AQ-resistance as well as human sickle cell trait and alpha-thalassaemia were determined using PCR and sequence-specific oligonucleotide probes and enzyme-linked immunosorbent assay (SSOP-ELISA, and IgG antibody responses to a panel of P. falciparum antigens were assessed and related to treatment outcome. Results Parasitological or clinical treatment failure (TF was observed in 68% and 38% of children receiving SP or AQ, respectively. In those with adequate clinical and parasitological response (ACPR compared to children with TF, and for both treatment regimens, prevalence and levels of anti-Glutamate-rich Protein (GLURP-specific IgG antibodies were significantly higher (P Conclusion These findings suggest that GLURP-specific IgG antibodies in this setting contribute to clearance of drug-resistant infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy. The results should be confirmed in larger scale with greater sample size and with variation in transmission intensity.
Enevold, Anders; Nkya, Watoky M M M; Theisen, Michael; Vestergaard, Lasse S; Jensen, Anja Tr; Staalsoe, Trine; Theander, Thor G; Bygbjerg, Ib C; Alifrangis, Michael
In malaria endemic areas children may recover from malaria after chemotherapy in spite of harbouring genotypically drug-resistant Plasmodium falciparum. This phenomenon suggests that there is a synergy between drug treatment and acquired immunity. This hypothesis was examined in an area of moderately intense transmission of P. falciparum in Tanzania during a drug trail with sulphadoxine-pyrimethamine (SP) or amodiaquine (AQ). One hundred children with uncomplicated malaria were treated with either SP or AQ and followed for 28 days. Mutations in parasite genes related to SP and AQ-resistance as well as human sickle cell trait and alpha-thalassaemia were determined using PCR and sequence-specific oligonucleotide probes and enzyme-linked immunosorbent assay (SSOP-ELISA), and IgG antibody responses to a panel of P. falciparum antigens were assessed and related to treatment outcome. Parasitological or clinical treatment failure (TF) was observed in 68% and 38% of children receiving SP or AQ, respectively. In those with adequate clinical and parasitological response (ACPR) compared to children with TF, and for both treatment regimens, prevalence and levels of anti-Glutamate-rich Protein (GLURP)-specific IgG antibodies were significantly higher (P < 0.001), while prevalence of parasite haplotypes associated with SP and AQ resistance was lower (P = 0.02 and P = 0.07, respectively). Interestingly, anti-GLURP-IgG antibodies were more strongly associated with treatment outcome than parasite resistant haplotypes, while the IgG responses to none of the other 11 malaria antigens were not significantly associated with ACPR. These findings suggest that GLURP-specific IgG antibodies in this setting contribute to clearance of drug-resistant infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy. The results should be confirmed in larger scale with greater sample size and with variation in transmission intensity.
Délicat-Loembet, Lucresse; Rougeron, Virginie; Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck
African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.
Yang, Lily P H; Keam, Susan J
Topical retapamulin (Altabax, Altargo) is the first pleuromutilin antibacterial approved for the treatment of uncomplicated superficial skin infections caused by Staphylococcus aureus (excluding methicillin-resistant S. aureus [MRSA]) and Streptococcus pyogenes in patients aged > or = 9 months. In the EU, retapamulin is indicated for use in patients with impetigo or with infected small lacerations, abrasions, or sutured wounds (without abscesses); in the US, it is indicated for use in patients with impetigo. Retapamulin has a novel site of action on bacterial ribosomes. In clinical trials in patients with impetigo, topical retapamulin 1% ointment twice daily for 5 days (the approved regimen) was superior to placebo; treatment with retapamulin was noninferior to that with topical fusidic acid. In patients with secondarily infected traumatic lesions, treatment with retapamulin was noninferior to that with oral cephalexin, although the efficacy of retapamulin was reduced in patients with MRSA infections or superficial abscesses. Retapamulin was well tolerated in both pediatric and adult patients, and the majority of adverse events were of mild to moderate severity. Thus, the introduction of topical retapamulin 1% ointment extends the treatment options available in the management of impetigo and uncomplicated secondarily infected traumatic lesions.
Reddy, Vikram K; Girish, K; Lakshmi, Pandit; Vijendra, R; Kumar, Ajay; Harsha, R
Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.
Mohammed, Abdu O; Tewolde, Seltene; Estifanos, Dawit; Tekeste, Yohannes; Osman, Mohammed-Hamid
The aim of this study was to assess the efficacy of artesunate-amodiaquine (AS+AQ) which is the first-line treatment for uncomplicated falciparum malaria in Eritrea. The study was conducted from December 2014 to March 2015 in Ghindae Zonal Referral Hospital in Northern Red Sea Zone. Out of 481 patients screened, 103 were enrolled in the study. The therapeutic efficacy test was done as per the WHO protocol for a period of 28days of follow-up. The PCR-uncorrected treatment outcome was classified as adequate clinical and parasitological response (ACPR) in 95 patients, which meant the cure rate was 96.0 (95% CI: 89.7%-98.5%) after survival analysis. Therapeutic efficacy of AS+AQ still meets the WHO efficacy criteria for its continued use in the study area as the first-line drug against uncomplicated falciparum malaria. However, further studies are needed using correction with molecular markers to monitor therapeutic efficacy of antimalarial drugs in this area. Copyright © 2017 Elsevier B.V. All rights reserved.
Y. El Harrech
Full Text Available Objectives. We compared outcome and complications after uncomplicated ureteroscopic treatment of distal ureteral calculi with or without the use of ureteral stents. Materials and Methods. 117 patients, prospectively divided into three groups to receive a double j stent (group 1, 42 patients, ureteral stent (group 2, 37 patients, or no stent (group 3, 38 patients, underwent ureteroscopic treatment of distal ureteral calculi. Stone characteristics, operative time, postoperative pain, lower urinary tract symptoms (LUTS, analgesia need, rehospitalization, stone-free rate, and late postoperative complications were all studied. Results. There were no significant differences in preoperative data. There was no significant difference between the three groups regarding hematuria, fever, flank pain, urinary tract infection, and rehospitalisation. At 48 hours and 1 week, frequency/urgency and dysuria were significantly less in the nonstented group. When comparing group 1 and group 3, patients with double j stents had statistically significantly more bladder pain (P=0.003, frequency/urgency (P=0.002, dysuria (P=0.001, and need of analgesics (P=0.001. All patients who underwent imaging postoperatively were without evidence of obstruction or ureteral stricture. Conclusions. Uncomplicated ureteroscopy for distal ureteral calculi without intraoperative ureteral dilation can safely be performed without placement of a ureteral stent.
Full Text Available OBJETIVE: To describe the reattachment rate and visual acuity results of patients with uncomplicated rhegmatogenous retinal detachment who underwent segmental scleral buckle surgery. METHODS: Prospective case series of 100 patients with visual loss or symptoms (floaters and photopsia of less than 30 days' duration scheduled for surgery. No patient had a retinal break greater than 30°, a retinal detachment larger than 2 quadrants or proliferative vitreoretinopathy. RESULTS: The 1-week, 1-month, and 6-month anatomical success rates were 93%, 100%, and 100%, respectively. Seven patients underwent one additional retinal detachment surgery (pars plan vitrectomy after primary failure at 1-week follow-up. The preoperative, 1-month, and 6-month best correct visual acuity were 20/100, 20/80, and 20/50, respectively. The postoperative complications were: eyelid edema in 10% of the patients, transient ocular hypertension in 5%, macular pucker in 3%, transient diplopia in 3%, and hyphema (<0.5mm in 1%. CONCLUSION: In patients with uncomplicated retinal detachment, segmental scleral buckle showed a very good anatomical and functional success, with a few number of major complications.
Lasanianos, Nikolaos G; Lyras, Dimitrios N; Mouzopoulos, George; Tsutseos, Nikolaos; Garnavos, Christos
Subtalar dislocation is a rare injury, with the medial type occurring in the majority of cases. The period of postreduction immobilization is a matter of controversy. Most studies set the period of immobilization between 4 and 8 weeks. The hypothesis in this study is that a period of 2-3 weeks of immobilization in a cast, followed by early mobilization, could provide better functional results than longer periods of immobilization. During a period of 4 years, eight patients (six men, two women) with mean age of 37.2 years and uncomplicated medial subtalar dislocation were treated in our institution. Immediate reduction under sedation and cast immobilization was provided in all cases. Our rehabilitation protocol consisted of two completed weeks of immobilization and thereafter ankle range-of-motion exercises and partial weight-bearing mobilization. Patients were followed up for a mean period of 3 years. Clinical results were evaluated using the AOFAS Ankle-Hindfoot scale. All patients achieved almost normal ankle range of motion and good clinical outcome (mean AOFAS score 92.25). No radiographic evidence of arthritis or avascular necrosis of the talus was detected. Two patients complained of mild pain of the hindfoot. All patients returned to daily routine activities in about 2 months from injury. Immediate reduction and early mobilization could be key factors for uneventful recovery of uncomplicated medial subtalar dislocation. Multicenter clinical trials are needed for further validation of our initial results. III, prospective clinical series study.
SUMMARY Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection. PMID:23554413
Chu, Cindy S; White, Nicholas J
Relapses are important contributors to illness and morbidity in Plasmodium vivax and P. ovale infections. Relapse prevention (radical cure) with primaquine is required for optimal management, control and ultimately elimination of Plasmodium vivax malaria. A review was conducted with publications in English, French, Portuguese and Spanish using the search terms 'P. vivax' and 'relapse'. Hypnozoites causing relapses may be activated weeks or months after initial infection. Incidence and temporal patterns of relapse varies geographically. Relapses derive from parasites either genetically similar or different from the primary infection indicating that some derive from previous infections. Malaria illness itself may activate relapse. Primaquine is the only widely available treatment for radical cure. However, it is often not given because of uncertainty over the risks of primaquine induced haemolysis when G6PD deficiency testing is unavailable. Recommended dosing of primaquine for radical cure in East Asia and Oceania is 0.5 mg base/kg/day and elsewhere is 0.25 mg base/kg/day. Alternative treatments are under investigation. Expert commentary: Geographic heterogeneity in relapse patterns and chloroquine susceptibility of P. vivax, and G6PD deficiency epidemiology mean that radical treatment should be given much more than it is today. G6PD testing should be made widely available so primaquine can be given more safely.
Alonso-Morales, Alberto; González-López, Lorena; Cázares-Raga, Febe Elena; Cortés-Martínez, Leticia; Torres-Monzón, Jorge Aurelio; Gallegos-Pérez, José Luis; Rodríguez, Mario Henry; James, Anthony A; Hernández-Hernández, Fidel de la Cruz
Plasmodium gametogenesis within the mosquito midgut is a complex differentiation process involving signaling mediated by phosphorylation, which modulate metabolic routes and protein synthesis required to complete this development. However, the mechanisms leading to gametogenesis activation are poorly understood. We analyzed protein phosphorylation during Plasmodium berghei gametogenesis in vitro in serum-free medium using bidimensional electrophoresis (2-DE) combined with immunoblotting (IB) and antibodies specific to phosphorylated serine, threonine and tyrosine. Approximately 75 protein exhibited phosphorylation changes, of which 23 were identified by mass spectrometry. These included components of the cytoskeleton, heat shock proteins, and proteins involved in DNA synthesis and signaling pathways among others. Novel phosphorylation events support a role for these proteins during gametogenesis. The phosphorylation sites of six of the identified proteins, HSP70, WD40 repeat protein msi1, enolase, actin-1 and two isoforms of large subunit of ribonucleoside reductase were investigated using TiO2 phosphopeptides enrichment and tandem mass spectrometry. In addition, transient exposure to hydroxyurea, an inhibitor of ribonucleoside reductase, impaired male gametocytes exflagellation in a dose-dependent manner, and provides a resource for functional studies. Copyright © 2015 Elsevier Inc. All rights reserved.
Brutus, Laurent; Santalla, José; Schneider, Dominique; Avila, Juan Carlos; Deloron, Philippe
Plasmodium vivax is a major cause of illness in areas with low transmission of malaria in Latin America, Asia, and the Horn of Africa. However, pregnancy-associated malaria remains poorly characterized in such areas. Using a hospital-based survey of women giving birth and an antenatal survey, we assessed the prevalence rates of Plasmodium spp. infections in pregnant women in Bolivia, and evaluated the consequences of malaria during pregnancy on the health of mothers and newborns. P. vivax infection was detected in 7.9% of pregnant women attending antenatal visits, and placental infection occurred in 2.8% of deliveries; these rates did not vary with parity. Forty-two percent of all P. vivax malaria episodes were symptomatic. P. vivax-infected pregnant women were frequently anemic (6.5%) and delivered babies of reduced birthweight. P. vivax infections during pregnancy are clearly associated with serious adverse outcomes and should be considered in prevention strategies of pregnancy-associated malaria.
Full Text Available Abstract Background Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM, are not yet fully understood. Both endothelin-1 (ET-1 and C-type natriuretic peptide (CNP are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties. Methods Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA technique, in Gabonese children with severe falciparum malaria (SM, n = 50, with uncomplicated malaria (UM, n = 39 and healthy controls (HC, n = 25. Results Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p p p = 0.034, whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085. Conclusion In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.
Adam Mayyada B
Full Text Available Abstract Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases and healthy pregnant women (controls. Results The median (interquartile platelet counts were significantly lower in patients with malaria (N = 60 than in the controls (N = 60, 61, 000 (43,000–85,000 vs. 249,000 (204,000–300,000/μL, respectively, p P. falciparum malaria (N = 12 compared with those patients with uncomplicated P. falciparum malaria (N = 48, 68, 000 (33,000-88,000/μL vs. 61, 000 (45,000–85,000/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.
Ifeorah, Ifeanyi Kanayo; Brown, Biobele J; Sodeinde, Olugbemiro O
-g: Interferon-gamma, IgG: Immunoglobulin G, MP: Malaria parasite, NADP: Oxidised Nicotinamide Adenine Dinucleotide Phosphate, NADPH: Reduced Nicotinamide Adenine Dinucleotide Phosphate, PCV: Packed Cell Volume (haematocrit), P. falciparum: Plasmodium falciparum, PLDH: Plasmodium lactate dehydrogenase, PCR: Polymerase Chain Reaction, PPV: Positive predictive value, QBC: Quantitative Buffy Coat examination, TNF: Tumour necrosis factor, NPV: Negative predictive value, RDT: Rapid diagnostic test, SP: Sulphadoxine -Pyrimethamine, SMA: Severe malarial anaemia, UM: Uncomplicated malaria, USA:United States of America, VCAM-1: Vascular cell adhesion molecule, WBC: White Blood Cell, WHO: World Health Organization.
Ghosh, Anil K; Coppens, Isabelle; Gårdsvoll, Henrik
inhibits oocyst development of both Plasmodium berghei and Plasmodium falciparum, suggesting that enolase may act as an invasion ligand. Importantly, we demonstrate that surface enolase captures plasminogen from the mammalian blood meal via its lysine motif (DKSLVK) and that this interaction is essential...... for ookinete invasion. The results support the hypothesis that enolase on the surface of Plasmodium ookinetes plays a dual role in midgut invasion: by acting as a ligand that interacts with the midgut epithelium and, further, by capturing plasminogen, whose conversion to active plasmin promotes the invasion...
Amodiaquine-Artesunate versus Artemether-Lumefantrine against Uncomplicated Malaria in Children Less Than 14 Years in Ngaoundere, North Cameroon: Efficacy, Safety, and Baseline Drug Resistant Mutations in pfcrt, pfmdr1, and pfdhfr Genes
Innocent M. Ali
Full Text Available Background. In Cameroon, both Artesunate-amodiaquine (AS/AQ and artemether-lumefantrine (AL are used as first-line treatment against uncomplicated malaria in line with the WHO recommendations. We compared the efficacy and safety of both therapeutic combinations and determined the prevalence of drug resistance conferring mutations in three parasite genes. Methods. One hundred and fifty acute malaria patients between six months and 14 years of age were randomized to receive standard doses of either AS/AQ (73 or AL (77 and followedup for 28 days. Outcome of treatment was according to the standard WHO classification. DNA samples from pretreatment parasite isolates were used to determine the prevalence of resistant mutations in the pfcrt, pfmdr1, and dhfr genes. Results. Both drug combinations induced rapid clearance of parasites and malaria symptoms. PCR-corrected cure rates were 100% and 96.4% for AL. The combinations were well tolerated. Major haplotypes included CVIET (71%, CVMNT (25% for the pfcrt; SND (100% for the pfmdr1; IRN (79, 8%, NCS (8.8%, and mixed haplotype (11, 8% for the dhfr. Conclusion. Both AS/AQ and AL were highly effective and well tolerated for the treatment of uncomplicated falciparum malaria in Ngaoundere, Cameroon. High prevalence of mutant pfcrt alleles confirms earlier observations. Long-term monitoring of safety and efficacy and molecular markers is highly solicited.
Val, Fernando; Machado, Kim; Barbosa, Lisiane; Salinas, Jorge Luis; Siqueira, André Machado; Costa Alecrim, Maria Graças; Portillo, Hernando Del; Bassat, Quique; Monteiro, Wuelton Marcelo; Guimarães Lacerda, Marcus Vinícius
Malaria, a major global public health problem, is mainly caused by Plasmodium falciparum and Plasmodium vivax, and is responsible for nearly half a million deaths annually. Although P. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. However, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. A systematic search for articles reporting respiratory complications associated with vivax malaria was performed in Lilacs, Cochrane, Scielo, Web of Science, and Medline databases irrespective of publication date. Prevalence of acute respiratory distress syndrome (ARDS) and associated mortality among vivax patients were calculated from cross-sectional and longitudinal studies, whereas factors associated with mortality were calculated from data pooled from case reports and series of cases. A total of 101 studies were included (49 cross-sectional or longitudinal and 52 case reports or series of cases). Prevalence of ARDS was 2.8% and 2.2% in children and adults, respectively, with nearly 50% mortality. Moreover, female sex (P = 0.013), having any comorbidity (P = 0.036), lower body temperature (P = 0.032), lower hemoglobin (P = 0.043), and oxygen saturation (P = 0.053) values were significantly associated with mortality. Plasmodium vivax malaria respiratory complications included ARDS and were associated with high mortality. Demographics and clinical characteristics upon presentation to hospital were associated with mortality among patients with respiratory complications in vivax malaria. This study reaffirms the evidence of severe and fatal complications of P. vivax malaria and its associated respiratory complications.
Banerjee, Rajdeep; Khandelwal, Sanjay; Kozakai, Yukiko; Sahu, Bikash; Kumar, Sanjai
Several Plasmodium species exhibit a strong age-based preference for the red blood cells (RBC) they infect, which in turn is a major determinant of disease severity and pathogenesis. The molecular basis underlying this age constraint on the use of RBC and its influence on parasite burden is poorly understood. CD47 is a marker of self on most cells, including RBC, which, in conjunction with signal regulatory protein alpha (expressed on macrophages), prevents the clearance of cells by the immune system. In this report, we have investigated the role of CD47 on the growth and survival of nonlethal Plasmodium yoelii 17XNL (PyNL) malaria in C57BL/6 mice. By using a quantitative biotin-labeling procedure and a GFP-expressing parasite, we demonstrate that PyNL parasites preferentially infect high levels of CD47 (CD47(hi))-expressing young RBC. Importantly, C57BL/6 CD47(-/-) mice were highly resistant to PyNL infection and developed a 9.3-fold lower peak parasitemia than their wild-type (WT) counterparts. The enhanced resistance to malaria observed in CD47(-/-) mice was associated with a higher percentage of splenic F4/80(+) cells, and these cells had a higher percentage of phagocytized parasitized RBC than infected WT mice during the acute phase of infection, when parasitemia was rapidly rising. Furthermore, injection of CD47-neutralizing antibody caused a significant reduction in parasite burden in WT C57BL/6 mice. Together, these results strongly suggest that CD47(hi) young RBC may provide a shield to the malaria parasite from clearance by the phagocytic cells, which may be an immune escape mechanism used by Plasmodium parasites that preferentially infect young RBC.
MASON, DANIEL P.; McKENZIE, F. ELLIS
We present a mathematical model of the blood-stage dynamics of mixed Plasmodium vivax–Plasmodium falciparum malaria infections in humans. The model reproduces features of such infections found in nature and suggests several phenomena that may merit clinical attention, including the potential recrudescence of a long-standing, low-level P. falciparum infection following a P. vivax infection or relapse and the capacity of an existing P. vivax infection to reduce the peak parasitemia of a P. falciparum superinfection. We simulate the administration of anti-malarial drugs, and illustrate some potential complications in treating mixed-species malaria infections. Notably, our model indicates that when a mixed-species infection is misdiagnosed as a single-species P. vivax infection, treatment for P. vivax can lead to a surge in P. falciparum parasitemia. PMID:10497972
Taylor, K J; Van, T T H; MacDonald, S M; Meshnick, S R; Fernley, R T; Macreadie, I G; Smooker, P M
Translationally controlled tumour protein (TCTP) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. In this study, the potential of TCTP as a malaria vaccine was investigated in two trials. In the initial vaccine trial, Plasmodium falciparum TCTP (PfTCTP) was expressed in Saccharomyces cerevisiae and used to immunize BALB/c mice. Following challenge with Plasmodium yoelii YM, parasitemia was significantly reduced during the early stages of infection. In the second vaccine trial, the TCTP from P. yoelii and P. berghei was expressed in Escherichia coli and used in several mouse malaria models. A significant reduction in parasitemia in the early stages of infection was observed in BALB/c mice challenged with P. yoelii YM. A significantly reduced parasitemia at each day leading up to a delayed and reduced peak parasitemia was also observed in BALB/c mice challenged with the nonlethal Plasmodium chabaudi (P.c.) chabaudi AS. These results suggest that TCTP has an important role for parasite establishment and may be important for pathogenesis. © 2014 John Wiley & Sons Ltd.
Jeancolas, A-L; Conart, J-B; Tréchot, F; Berrod, J-P; Angioi-Duprez, K; Maalouf, T
Although the general increase in ambulatory surgery allows for a 20% reduction in costs of hospitalization, the necessity of a day 1 postoperative visit remains the main problem for elderly patients or those who reside at considerable distance. For these reasons, in 2014, we decided to only see patients with uncomplicated filtering surgery at D5 and D21 and to replace the D1 visit with a telephone call. The primary goal of our study was to analyze a population of patients undergoing uncomplicated filtering surgery who were not seen at D1 and to describe the frequency of postoperative complications, intraocular pressure results and therapeutic management at D5 and D21. This was a retrospective monocentric study in the department of ophthalmology. All patients (naïve of surgical treatment for glaucoma) underwent surgery for primary open-angle glaucoma in an ambulatory surgery unit between May 2014 and July 2016. A nurse made a phone call to the patients at day 1 and they responded to a standardized questionnaire. Depending upon their responses, the patients were seen quickly (day 5 and day 21. One hundred and forty-four eyes (126 patients) were included in our study. The mean preoperative IOP was 20.4±6.4mmHg. After the phone call, only five patients were examined before the first planned follow-up at day 5. For 3 of them, the examination revealed the presence of a hyphema, and their topical medication was changed. The other two patients had no treatment modifications. At day 5, the mean IOP was 10.6±5.9mmHg. Thirty-two eyes (22.2%) required a change in their medication at day 5. The mean IOP at day 21 was 12.9±4.6mmHg. Our success rate (IOPday 21 was 95.6%. The guidelines for filtering glaucoma surgery recommend examining the patient at day 1 (or at least before day 3), day 8, day 15 and day 30 or more frequently according to the case. We replaced the day 1 visit with a telephone call. We did not note a substantial rate of complications due to the elimination of
Mangham-Jefferies, Lindsay; Hanson, Kara; Mbacham, Wilfred; Onwujekwe, Obinna; Wiseman, Virginia
As agents for their patients, providers often make treatment decisions on behalf of patients, and their choices can affect health outcomes. However, providers operate within a network of relationships and are agents not only for their patients, but also other health sector actors, such as their employer, the Ministry of Health, and pharmaceutical suppliers. Providers' stated preferences for the treatment of uncomplicated malaria were examined to determine what factors predict their choice of treatment in the absence of information and institutional constraints, such as the stock of medicines or the patient's ability to pay. 518 providers working at non-profit health facilities and for-profit pharmacies and drug stores in Yaoundé and Bamenda in Cameroon and in Enugu State in Nigeria were surveyed between July and December 2009 to elicit the antimalarial they prefer to supply for uncomplicated malaria. Multilevel modelling was used to determine the effect of financial and non-financial incentives on their preference, while controlling for information and institutional constraints, and accounting for the clustering of providers within facilities and geographic areas. 69% of providers stated a preference for artemisinin-combination therapy (ACT), which is the recommended treatment for uncomplicated malaria in Cameroon and Nigeria. A preference for ACT was significantly associated with working at a for-profit facility, reporting that patients prefer ACT, and working at facilities that obtain antimalarials from drug company representatives. Preferences were similar among colleagues within a facility, and among providers working in the same locality. Knowing the government recommends ACT was a significant predictor, though having access to clinical guidelines was not sufficient. Providers are agents serving multiple principals and their preferences over alternative antimalarials were influenced by patients, drug company representatives, and other providers working at the
Bleidorn, Jutta; Kochen, Michael M; Schmiemann, Guido; Wegscheider, Karl; Hummers-Pradier, Eva
Study question Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications? Methods Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3×400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain. Study answer and limitations The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI. What this paper adds Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms. Funding, competing interests, data sharing German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of
Liew, Jonathan Wee Kent; Mahmud, Rohela; Tan, Lian Huat; Lau, Yee Ling
Plasmodium ovale is rare and not exactly known to be autochthonous in Malaysia. There are two distinct forms of the parasite, namely P. ovale curtisi (classic form) and P. ovale wallikeri (variant form...
Ibitokou, Samad; Oesterholt, Mayke; Brutus, Laurent
Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective...
Malaria prophylaxis during pregnancy is gradually being replaced with intermittent preventive treatment (IPT) using sulfadoxine - pyrimethamine (SP). This change in approach has been deemed necessary because of the high resistance to chloroquine by Plasmodium falciparum observed in malaria endemic zones.
Plasmodium falciparum invades erythrocytes as an essential part of their life cycle. While living inside erythrocytes, the parasite remodels the cell's intracellular organization as well as its outer surface. Late trophozoite-stage parasites and schizonts introduce numerous small protrusions...
Domingos Alves Meira
Full Text Available In August 1983 the Authors studied 36 patients with Plasmodium falciparum malaria and 14 normal individuals born in Humaita region who had never had malaria, had no spleen enlargement and had negative parasitemia as well as passive hemagglutination. Medical histories were obtained and complete physical examination were performed in all of them just as blood tests, parasite density and lymphocyte typing. The lymphocytes were separated and then frozen in liquid nitrogen for later typing by rosette formation. The patients were divided in two groups according to the presence (13 patients or abscence (23 patients of gametocytes before treatment. Severe malaria was predominant in the group without gametocytes. The results showed a decrease in the T-cell numbers in Plasmodium falciparum acute malaria patients both with or without gametocytes before the treatment, while B-cell numbers were normal only in the patients with gametocytes. These observations as like as those previously reported by the Authors, permit to associate the presence of gametocytes in peripheral blood and normal number of B-cells in patients with mild Plasmodium falciparum malaria.
Leung, Alexander K C; Wong, Alex H C
Acute otitis media is a common childhood infection. Prompt diagnosis and appropriate treatment are very important. To review in depth the epidemiology, pathophysiology, clinical manifestations, diagnosis, complications and particularly treatment of acute otitis media in children. A PubMed search was completed in Clinical Queries using the key term "acute otitis media". Patents were searched using the key term "acute otitis media" from www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com. Acute otitis media affects over 80% of children before their third birthday and 30 to 45% of these children have suffered two or more episodes. Streptococcus pneumoniae, nontypable Haemophilus influenzae, and Moraxella catarrhalis are the most frequently isolated middle-ear pathogens. The diagnosis is based on acute onset of symptoms such as otalgia and fever, middle ear inflammation such as erythema of the tympanic membrane, and middle ear effusion. The choice of treatment method depends on the age of the child, laterality, and the severity of the disease. Recent patents related to the management of acute otitis media are also retrieved and discussed. Antimicrobial treatment is recommended for all children less than two years of age, as well as in children ≥ two years of age who have a temperature ≥ 39oC; are toxic looking; have otalgia > 48 hours; have bilateral otitis media or otorrhea; have craniofacial abnormalities; are immunocompromised; or have uncertain access to follow-up. Amoxicillin is the drug of choice. Observation without antibiotic is an option in immunocompetent children ≥ two years of age who have an acute uncomplicated otitis media and non-severe illness if appropriate follow-up can be arranged. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the
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
Amanfo, Seth A; Mduluza, Takafira; Midzi, Nicholas; Cavanagh, David R; Mutapi, Francisca
Individuals living in malaria-endemic regions may be exposed to more than one Plasmodium species; there is paucity of data on the distribution of the different species of Plasmodium in affected populations, in part due to the diagnostic method of microscopy, which cannot easily differentiate between the species. Sero-epidemiological data can overcome some of the shortcomings of microscopy. The specificity of IgG antibodies to recombinant merozoite surface protein 1 (MSP-119) derived from four human Plasmodium species (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale) was investigated using competition enzyme-linked immunosorbent assay. Subsequently, these antigens were used to determine the exposure prevalence to the different Plasmodium species in serum samples of participants. One-hundred individuals, aged five-18 years, from each of the three Plasmodium meso-endemic Zimbabwean villages (Burma Valley, Mutoko, Chiredzi) were recruited in the study. The study demonstrated that the host serum reactivity to MSP-119 antigens was species-specific and that no cross-reactivity occurred. The overall prevalence of antibody response to MSP-119 antigens was 61 % in Burma Valley, 31 % in Mutoko and 32 % in Chiredzi. Single species IgG responses to MSP-119 were most frequent against P. falciparum, followed by P. malariae and P. ovale, with responses to P. vivax being the least prevalent. Interestingly, 78-87 and 50 % of sera with IgG responses to P. malariae and P. ovale MSP-119, respectively, also had IgG specific response for P. falciparum MSP-119 antigens, indicating that exposure to these species is a common occurrence in these populations. Single species IgG responses to the non-falciparum species were at a very low frequency, ranging between 0 and 13 % for P. malariae. There is evidence of a higher exposure to the non-falciparum parasite species than previously reported in Zimbabwe. The recombinant MSP-119 antigens could be used as
Loeki Enggar Fitri
Conclusions: It can be concluded that the average of plasma GSH and GSSG level, also plasma GSH/GSSG ratio in complicated malaria are not different from uncomplicated malaria. Although plasma concentration of albumin in both groups is below the normal range, there is an increase in complicated malaria that might be as compensation of oxidative stress.
Full Text Available Uncomplicated urinary tract infections (UTI in women are very common. Regular analysis of bacterial flora is important to formulate updated guidelines. The objective of this study is to determine and compare the microbiology of UTIs and their susceptibility patterns in a quaternary care hospital. In a seven-year review, the urine culture results of 480 female patients with uncomplicated UTIs were analyzed. Patients were divided into three groups according to their diagnosis and treatment characteristics: Group 1, cystitis at outpatient basis; group 2, cystitis at the Emergency Unit; and group 3, pyelonephritis. Group 1 included older patients, with a higher incidence of concomitant diabetes mellitus and recurrent UTIs. E. coli was the most common pathogen, responsible for 75.1% of cases, mainly for pyelonephritis (87.3%. Of the oral antimicrobials tested for cystitis, amoxicillin/clavulanate and nitrofurantoin had the highest susceptibility profiles (84.4% and 87.3%, respectively. For E. coli only, their susceptibility profiles were as high as 90.8% and 97.4%, respectively. For pyelonephritis treatment, fluoroquinoles had a susceptibility profile <90%, while ceftriaxone and gentamicin had susceptibility >90%. Uncomplicated UTI treatment is becoming more challenging because the susceptibility profiles of oral antimicrobials are increasingly resistant. In our environment, cystitis can still be managed with nitrofurantoin. Uncomplicated pyelonephritis should be managed with ceftriaxone or gentamicin.
BRUCE, M. C.; Macheso, A.; Galinski, M.R.; Barnwell, J W
Plasmodium malariae, a protozoan parasite that causes malaria in humans, has a global distribution in tropical and subtropical regions and is commonly found in sympatry with other Plasmodium species of humans. Little is known about the genetics or population structure of P. malariae. In the present study, we describe polymorphic genetic markers for P. malariae and present the first molecular epidemiological data for this parasite. Six microsatellite or minisatellite markers were validated usi...
Kyaw, Myat P; Nyunt, Myat H; Chit, Khin; Aye, Moe M; Aye, Kyin H; Aye, Moe M; Lindegardh, Niklas; Tarning, Joel; Imwong, Mallika; Jacob, Christopher G; Rasmussen, Charlotte; Perin, Jamie; Ringwald, Pascal; Nyunt, Myaing M
Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries. A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days) was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia), parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope), and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels. The median (range) parasite clearance half-life and time were 4.8 (2.1-9.7) and 60 (24-96) hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours) in approximately 1/3 of infections. Fourteen of 52 participants (26.9%) had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics. A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this
Myat P Kyaw
Full Text Available Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries.A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia, parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope, and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels.The median (range parasite clearance half-life and time were 4.8 (2.1-9.7 and 60 (24-96 hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours in approximately 1/3 of infections. Fourteen of 52 participants (26.9% had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics.A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread
Jiang, Lanhui; Li, Ka; Wu, Taixiang
Acute bronchitis is one of the most common diagnoses made by primary care physicians. It is traditionally treated with antibiotics (although the evidence for their effectiveness is weak, and modest at best) and other even less effective treatments. Chinese medicinal herbs have also been used as a treatment. This review aimed to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4) which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 19 September 19, 2011), EMBASE (1988 to 19 September 2011) and CNKI and the Chinese Biomedical Database (CBM) (1980 to 19 September, 2011). Randomised controlled trials (RCTs) comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis. At least two review authors independently extracted data and assessed trial quality. In this updated review, 74 studies involving 6877 participants were reported as RCTs by the study authors. None of them met the inclusion criteria for this review. Out of the 74 trials, we identified 39 as non-RCTs and 35 compared different Chinese herbal medicines in the intervention and control groups. There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. Trial design limitations of the individual studies meant that we could not draw any conclusions about the benefits of Chinese herbs for acute bronchitis. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence for these herbs, although adverse events were reported in some case reports.
Flávia Carolina F de Araujo
Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.
Sim, Jae Eun; Choi, Young-Chul; Kim, Won-Joo
Facial diplegia has diverse etiologies, including viral and bacterial infections such as diphtheria, syphilis and Lyme disease, and also protozoal infection in very rarely cases. A 20-year-old male patient was admitted to our hospital due to bilateral weakness of the upper and lower facial muscles. Examination revealed that the patient had a facial diplegia of the peripheral type. A peripheral blood smear demonstrated the presence of the asexual trophozoite stage of Plasmodium vivax with ring-form trophozoites, which led to a diagnosis of malaria. A serum work-up revealed increased IgG titers of antibodies to myelin-associated glycoprotein and ganglioside GD1b. The patient was administered antimalarial treatment, 1 week after which he showed signs of recovery. To our knowledge, this is the first case of facial diplegia after malaria infection, providing evidence that the mechanism underlying the condition is related to immune-mediated disease. Facial diplegia can manifest after P. vivax infection.
Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E
Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria. Copyright © 2015. Published by Elsevier Ltd.
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.
Fançony, Cláudia; Brito, Miguel; Gil, Jose Pedro
Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.
Full Text Available Abstract The protozoan Plasmodium falciparum has a complex life cycle in which asexual multiplication in the vertebrate host alternates with an obligate sexual reproduction in the anopheline mosquito. Apart from the apparent recombination advantages conferred by sex, P. falciparum has evolved a remarkable biology and adaptive phenotypes to insure its transmission despite the dangers of sex. This review mainly focuses on the current knowledge on commitment to sexual development, gametocytogenesis and the evolutionary significance of various aspects of gametocyte biology. It goes further than pure biology to look at the strategies used to improve successful transmission. Although gametocytes are inevitable stages for transmission and provide a potential target to fight malaria, they have received less attention than the pathogenic asexual stages. There is a need for research on gametocytes, which are a fascinating stage, responsible to a large extent for the success of P. falciparum.
Mendes, António M; Albuquerque, Inês S; Machado, Marta; Pissarra, Joana; Meireles, Patrícia; Prudêncio, Miguel
Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies. Copyright © 2017 Mendes et al.
Full Text Available Introduction. The association between celiac disease and eating disorders has been very rarely reported. This is the first report on celiac disease associated with bulimia in this part of Europe. Case report. An adult female patient with history of bulimia and one uncomplicated pregnancy was admitted to the Gastroenterology Department, due to long lasting dyspeptic symptoms, constipation, major weight loss and fatigue. After positive serological screening, the diagnosis of celiac disease was confirmed with histopathology examination of duodenal biopsy specimen. Conclusion. Complicated interactions between celiac disease and bulimia can make them difficult to diagnose and treat. It is important to consider the presence of celiac disease in patients with bulimia and gastrointestinal symptoms.
Uncomplicated, recurrent urinary tract infections (RUTIs) in heal-thy, premenopausal women are a common health complaint. This article discusses risk factors, diagnostic techniques, medical management, and referral information to help clinicians manage RUTIs in the primary care setting. This article cites research articles, systematic reviews, and current guidelines. The majority of RUTIs in healthy premenopausal women can be managed by using individualized plans of care. Referrals are usually not useful nor cost effective. This article discusses treatments based on increasing antimicrobial resistance and examines nonmicrobial options in RUTI prevention. This article serves as a foundation for guiding primary care providers in managing this common problem using current research and guidelines. ©2014 American Association of Nurse Practitioners.
Fenny, Ama P; Hansen, Kristian S; Enemark, Ulrika
INTRODUCTION: The National Health Insurance Act, 2003 (Act 650) established the National Health Insurance Scheme (NHIS) in Ghana with the aim of increasing access to health care and improving the quality of basic health care services for all citizens. The main objective is to assess the effect...... of health insurance on the quality of case management for patients with uncomplicated malaria, ascertaining any significant differences in treatment between insured and non-insured patients. METHOD: A structured questionnaire was used to collect data from 523 respondents diagnosed with malaria...... and prescribed malaria drugs from public and private health facilities in 3 districts across Ghana's three ecological zones. Collected information included initial examinations performed on patients (temperature, weight, age, blood pressure and pulse); observations of malaria symptoms by trained staff...
Channon Keith M
Full Text Available Abstract Aims Obese subjects with insulin resistance and hypertension have abnormal aortic elastic function, which may predispose them to the development of left ventricular dysfunction. We hypothesised that obesity, uncomplicated by other cardiovascular risk factors, is independently associated with aortic function. Methods and results We used magnetic resonance imaging to measure aortic compliance, distensibility and stiffness index in 27 obese subjects (BMI 33 kg/m2 without insulin resistance and with normal cholesterol and blood pressure, and 12 controls (BMI 23 kg/m2. Obesity was associated with reduced aortic compliance (0.9 ± 0.1 vs. 1.5 ± 0.2 mm2/mmHg in controls, p -1 × 10-3, p Conclusion Aortic elastic function is abnormal in obese subjects without other cardiovascular risk factors. These findings highlight the independent importance of obesity in the development of cardiovascular disease.
Rajahram, Giri S; Barber, Bridget E; William, Timothy; Menon, Jayaram; Anstey, Nicholas M; Yeo, Tsin W
The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported...
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.
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
Full Text Available Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear.The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions.P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours.Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.
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
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.
Kumar, Channaveerachari Naveen; Andrade, Chittaranjan; Murthy, Pratima
For important reasons, lorazepam (Ativan) and chlordiazepoxide (Librium) are both popular treatments for alcohol-withdrawal syndrome. Nevertheless, there is little literature directly comparing the two drugs. A formal comparison is desirable because of pharmacokinetic and other differences that could affect safety and efficacy considerations relevant to practice in developing countries. One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days. Double-blind assessments of withdrawal-symptom severity and impairing adverse events were obtained during treatment and for 4 days afterward. One chlordiazepoxide patient developed withdrawal delirium. Lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale. During withdrawal, irritability and dizziness were more common with lorazepam, and palpitations were more common with chlordiazepoxide. No difficulties in drug discontinuation or differences in impairing adverse events were observed with either drug. With the treatment schedule used in this study, lorazepam is as effective as the more traditional drug chlordiazepoxide in attenuating uncomplicated alcohol withdrawal. Lorazepam, therefore, could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic. The absence of clinically significant withdrawal complications with lorazepam in this large study contrasts with findings from previously published studies and suggests that higher doses of lorazepam than those formerly used may be necessary during alcohol withdrawal.
Full Text Available Background: Uncomplicated skin and skin structure infections (uSSSI are commonly encountered community-acquired infections and are typically confined to the superficial layers of the skin. Hence, they seldom lead to the destruction of skin structures. Aims: To evaluate the efficacy and tolerability of cefditoren pivoxil in uSSSI in Indian patients. Methods: One hundred and seventy-eight patients diagnosed with uncomplicated SSSI were enrolled in this randomized, comparative, multicentric study. Patients received either cefditoren pivoxil or cefdinir for ten days. Efficacy was assessed both clinically and microbiologically. Safety evaluation consisted of reporting of type, frequency, severity, and causal relationship of adverse events. Results: One hundred and fifty-one patients completed the study. Clinical and bacteriological efficacy of cefditoren pivoxil was comparable to that of cefdinir in the treatment of uSSSI. One hundred and five patients were eligible for per protocol (PP analysis of bacteriological outcome and clinical efficacy. Clinical cure or improvement was achieved in 98.00% patients treated with cefditoren pivoxil and 98.18% patients treated with cefdinir. In the modified Intent to Treat (mITT patient population, clinical cure or improvement was recorded in 97.33% patients treated with cefditoren pivoxil and 96.20% patients treated with cefdinir. Microbiological eradication (or presumed eradication was recorded in 88.00% patients treated with cefditoren pivoxil and 94.55% patients treated with cefdinir. The above differences in the outcome rates between the two drugs were not statistically significant. Six adverse events (AEs (two in cefditoren group and four in cefdinir group were reported in this study. Conclusion: Cefditoren pivoxil 200 mg b.i.d. was effective and well tolerated in the treatment of uSSSI.
Carolin Elizabeth George
Full Text Available Introduction: Uncomplicated but symptomatic urinary tract infections (UTIs are a common problem seen in practice. The study was undertaken to assess the most common pathogens responsible for uncomplicated symptomatic UTIs and the antimicrobial resistance pattern in a hospital in Bangalore. The study also explores the issue of antibiotic usage for these patients. Materials and Methods: The study was conducted in the Medicine department of a tertiary hospital in Bangalore. In all, 196 patients presented with symptoms of UTI. Bacterial growth was determined by standard microbiology techniques on freshly voided mid-steam urine samples collected from recruited patients. Patients′ demographic data, urine culture results, resistance rates to antimicrobial agents and prescribed empiric antimicrobial therapy were analyzed. Results: The prevalence of UTI was 32.1%; majority (67.9% of the symptomatic did not have UTI based on culture report. Gram-negative bacteria constituted the largest group with a prevalence of 84.1% (53/63, with Escherichia coli being the most common (70% uropathogen. Gram-negative isolates showed high level of sensitivity to amikacin (90.6% and nitrofurantoin (77.4%. Most of the gram-positive organisms were susceptible to nitrofurantoin (70% and gentamicin (50%. Uropathogens isolated demonstrated high resistance to cotrimoxazole, fluoroquinolones, and beta-lactam antibiotics. It was found out that 30.1% of the patients were wrongly managed of which 14.7% were over treated. Conclusion: UTI can be over diagnosed and over treated on the basis of clinical signs, symptoms and urine microscopy. In the era of emerging anti-microbial resistance, effective counseling and delay in antibiotic initiation or empirical therapy with a short course of nitrofurantoin is highly recommended. Empirical therapy guidelines should be updated periodically to reflect changes in antimicrobial resistance of uropathogens.
Dimitropoulos, Konstantinos; Bargiota, Alexandra; Mouzas, Odysseas; Melekos, Michael; Tzortzis, Vassilios; Koukoulis, Georgios
Current studies indicate that women with type 1 diabetes (T1DM) have a high prevalence of sexual disorders although data on the prevalence of sexual dysfunction are limited when sexual distress is included. The frequency and the possible correlates of distressful sexual disorders in a highly selected group of type 1 diabetic women. The sexual function, sexual distress, and general health status were assessed in 44 premenopausal women with uncomplicated T1DM and 47 healthy controls, using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the General Health Questionnaire-28 (GHQ-28). The impact of sexual distress on the frequency of female sexual dysfunction (FSD). The frequency of sexual disorders according to the FSFI was significantly higher in diabetic compared to control women (25% vs. 8.5%, respectively, P Diabetic women had significantly lower median (first to third quartile) total FSFI score compared to control group (30.55 [26.08-33.08] vs. 33.50 [30.70-34.30], P = 0.001). Desire, arousal, and satisfaction were the sexual domains significantly affected in the diabetic group. Diabetic women had significantly higher median (first to third quartile) FSDS score compared to control group (6.5 [2.3-15.8] vs. 4.0 [1.0-10.5] P = 0.043). FSD (combined pathological FSFI and FSDS scores) was present in higher proportion of diabetic women (15.9%) compared to controls (2.1%) (P = 0.020). GHQ-28 score was comparable between the groups. However, in the diabetic group, FSD was related with anxiety, depression, and low educational level. Diabetes-related factors were not associated with FSD. Pre-menopausal women with uncomplicated T1DM have significantly higher frequency of FSD compared to healthy controls, when the criterion of sexual distress is included. Psychosomatic and contextual factors implicated in sexual distress are correlates of FSD. © 2012 International Society for Sexual Medicine.
Ostri, Christoffer; Holfort, Stig K; Fich, Marianne S; Riise, Per
To compare automated refraction 1 week and 1 month after uncomplicated cataract surgery. In this prospective cohort study, we recruited patients in a 2-month period and included consecutive patients scheduled for bilateral small-incision phacoemulsification cataract surgery. The exclusion criteria were (i) corneal and/or retinal pathology that could lead to automated refraction miscalculation and (ii) surgery complications. Automated refraction was measured 1 week and 1 month after surgery. Ninety-five patients met the in- and exclusion criteria and completed follow-up. The mean refractive shift in spherical equivalent was -0.02 dioptre (D) between 1 week and 1 month after surgery and not statistical significant (p = 0.78, paired t-test). The magnitude of refractive shift in either myopic or hyperopic direction was neither correlated to age, preoperative corneal astigmatism, axial length nor phacoemulsification energy used during surgery (p > 0.05 for all variables, regression analysis). The refractive target was missed with 1.0 D or more in 11 (12%) patients. In this subgroup, the mean refractive shift in spherical equivalent was 0.49 D between 1 week and 1 month after surgery with a trend towards statistical significance (p = 0.07, paired t-test). There was no difference in age, preoperative corneal astigmatism, axial length or phacoemulsification energy used during surgery compared to the remainder of the patients (p > 0.05 for all variables, unpaired t-test). Automated refraction is stabile 1 week after uncomplicated cataract surgery, but there is a trend towards instability, if the refractive target is missed with 1.0 D or more. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Chloroquine is still a first-line antimalarial drug in uncomplicated falciparum malaria. Increasing resistance to chloroquine has been reported in many parts of Nigeria. Clinical and parasitological responses and classes of resistance to chloroquine in falciparum malaria in five communities in Delta region, southern Nigeria ...
Full Text Available BACKGROUND: In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2 into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria. METHODS AND FINDINGS: We measured plasma concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked immunosorbent assay, in 337 adult patients with falciparum malaria of varying severity hospitalised on the Thai-Burmese border. Based on in vitro production rates, we constructed a model to link this measure to the total parasite burden in the patient. The estimated geometric mean parasite burden was 7 x 10(11 (95% confidence interval [CI] 5.8 x 10(11 to 8.5 x 10(11 parasites per body, and was over six times higher in severe malaria (geometric mean 1.7 x 10(12, 95% CI 1.3 x 10(12 to 2.3 x 10(12 than in patients hospitalised without signs of severity (geometric mean 2.8 x 10(11, 95% CI 2.3 x 10(11 to 3.5 x 10(11; p < 0.001. Parasite burden was highest in patients who died (geometric mean 3.4 x 10(12, 95% CI 1.9 x 10(12 to 6.3 x 10(12; p = 0.03. The calculated number of sequestered parasites increased with disease severity and was higher in patients with late developmental stages of P. falciparum present on peripheral blood smears. Comparing model and laboratory estimates of the time of sequestration suggested that admission to hospital with uncomplicated malaria often follows schizogony-but in severe malaria is unrelated to stage of parasite development. CONCLUSION: Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in
Arjen M Dondorp
Full Text Available In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2 into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria.We measured plasma concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked immunosorbent assay, in 337 adult patients with falciparum malaria of varying severity hospitalised on the Thai-Burmese border. Based on in vitro production rates, we constructed a model to link this measure to the total parasite burden in the patient. The estimated geometric mean parasite burden was 7 x 10(11 (95% confidence interval [CI] 5.8 x 10(11 to 8.5 x 10(11 parasites per body, and was over six times higher in severe malaria (geometric mean 1.7 x 10(12, 95% CI 1.3 x 10(12 to 2.3 x 10(12 than in patients hospitalised without signs of severity (geometric mean 2.8 x 10(11, 95% CI 2.3 x 10(11 to 3.5 x 10(11; p < 0.001. Parasite burden was highest in patients who died (geometric mean 3.4 x 10(12, 95% CI 1.9 x 10(12 to 6.3 x 10(12; p = 0.03. The calculated number of sequestered parasites increased with disease severity and was higher in patients with late developmental stages of P. falciparum present on peripheral blood smears. Comparing model and laboratory estimates of the time of sequestration suggested that admission to hospital with uncomplicated malaria often follows schizogony-but in severe malaria is unrelated to stage of parasite development.Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in acute falciparum malaria. Severe malaria results
Farrow, Rachel E; Green, Judith; Katsimitsoulia, Zoe; Taylor, William R; Holder, Anthony A; Molloy, Justin E
Plasmodium falciparum is the most virulent causative agent of malaria in man accounting for 80% of all malarial infections and 90% of the one million annual deaths attributed to malaria. P. falciparum is a unicellular, Apicomplexan parasite, that spends part of its lifecycle in the mosquito and part in man and it has evolved a special form of motility that enables it to burrow into animal cells, a process termed "host cell invasion". The acute, life threatening, phase of malarial infection arises when the merozoite form of the parasite undergoes multiple cycles of red blood cell invasion and rapid proliferation. Here, we discuss the molecular machinery that enables malarial parasites to invade red blood cells and we focus particularly on the ATP-driven acto-myosin motor that powers invasion. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
van Gool, Tom; van Wolfswinkel, Marlies E; Koelewijn, Rob; van Thiel, Pieter P A M; Jacobs, Jan; van Hellemond, Jaap J; van Genderen, Perry J J
Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. In this study the Binax NOW Malaria Test, an easy-to-perform rapid diagnostic test, with Histidine Rich Protein-2 (HRP-2) and aldolase as diagnostic markers, was used for semi-quantitative assessment of parasitaemia of P. falciparum. In 257 patients with imported P. falciparum malaria, reactivity of aldolase increased with higher parasitaemia. In all patients with a parasitaemia above 50,000 asexual parasites/μl (> 1%) co-reactivity of HRP-2 and aldolase was observed. Absence of aldolase reactivity in the presence of HRP-2 wa