WorldWideScience

Sample records for surviving severe malaria

  1. Severe malaria in Europe

    DEFF Research Database (Denmark)

    Kurth, Florian; Develoux, Michel; Mechain, Matthieu

    2017-01-01

    BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. METHODS: The European Network for Tropical Medicine and Travel Health (Trop......Net) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre...... for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. RESULTS: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections...

  2. Survival and haematological recovery of children with severe malaria transfused in accordance to WHO guidelines in Kilifi, Kenya

    Directory of Open Access Journals (Sweden)

    Idro Richard

    2008-12-01

    Full Text Available Abstract Background Severe anaemia requiring emergency blood transfusion is a common complication of malaria in children. To ensure access for urgent blood transfusion, the World Health Organization has developed clear guidelines with haemoglobin thresholds prevent unwarranted transfusion,. Few studies have reported outcome and haematological recovery of children with severe malaria where transfusion practice complies with WHO recommendations. Methods A prospective observational study of survivors of severe and complicated malaria transfused in accordance with WHO guidelines. Children were invited for review at one month post-discharge. Non-attendees were traced in the community to ascertain survival. Results Outcome was assessed in 213 survivors. Those transfused were younger, had a higher base deficit, mean lactate levels and a higher prevalence of respiratory distress. As expected mean admission haemoglobin (Hb was significantly lower amongst transfused [5.0 g/dL SD: 1.9] compared to non-transfused children [8.3 g/dL SD: 1.7] (p Conclusion This data supports the policy of rational use of blood transfusion, as proposed in the WHO guidelines, for children with anaemia in areas where access to emergency transfusion is not guaranteed. We have provided empirical data indicating that transfusion does not influence superior recovery in haemoglobin concentrations and therefore cannot be justified on this basis alone. This may help resolve the disparity between international policy and current clinical practice. Effective anti-malarial treatment at discharge may prevent reoccurrence of anaemia.

  3. Cognition, behaviour and academic skills after cognitive rehabilitation in Ugandan children surviving severe malaria: a randomised trial

    Directory of Open Access Journals (Sweden)

    John Chandy C

    2011-08-01

    Full Text Available Abstract Background Infection with severe malaria in African children is associated with not only a high mortality but also a high risk of cognitive deficits. There is evidence that interventions done a few years after the illness are effective but nothing is known about those done immediately after the illness. We designed a study in which children who had suffered from severe malaria three months earlier were enrolled into a cognitive intervention program and assessed for the immediate benefit in cognitive, academic and behavioral outcomes. Methods This parallel group randomised study was carried out in Kampala City, Uganda between February 2008 and October 2010. Sixty-one Ugandan children aged 5 to 12 years with severe malaria were assessed for cognition (using the Kaufman Assessment Battery for Children, second edition and the Test of Variables of Attention, academic skills (Wide Range Achievement Test, third edition and psychopathologic behaviour (Child Behaviour Checklist three months after an episode of severe malaria. Twenty-eight were randomised to sixteen sessions of computerised cognitive rehabilitation training lasting eight weeks and 33 to a non-treatment group. Post-intervention assessments were done a month after conclusion of the intervention. Analysis of covariance was used to detect any differences between the two groups after post-intervention assessment, adjusting for age, sex, weight for age z score, quality of the home environment, time between admission and post-intervention testing and pre-intervention score. The primary outcome was improvement in attention scores for the intervention group. This trial is registered with Current Controlled Trials, number ISRCTN53183087. Results Significant intervention effects were observed in the intervention group for learning mean score (SE, [93.89 (4.00 vs 106.38 (4.32, P = 0.04] but for working memory the intervention group performed poorly [27.42 (0.66 vs 25.34 (0.73, P = 0.04]. No

  4. Intravenous artesunate for severe malaria in travelers, Europe

    DEFF Research Database (Denmark)

    Zoller, Thomas; Junghanss, Thomas; Kapaun, Annette

    2011-01-01

    Multicenter trials in Southeast Asia have shown better survival rates among patients with severe malaria, particularly those with high parasitemia levels, treated with intravenous (IV) artesunate than among those treated with quinine. In Europe, quinine is still the primary treatment for severe...... malaria. We conducted a retrospective analysis for 25 travelers with severe malaria who returned from malaria-endemic regions and were treated at 7 centers in Europe. All patients survived. Treatment with IV artesunate rapidly reduced parasitemia levels. In 6 patients at 5 treatment centers, a self...... of malaria patients in Europe. Patients should be monitored for signs of hemolysis, especially after parasitologic cure....

  5. CLINICAL ASPECTS OF UNCOMPLICATED AND SEVERE MALARIA

    Directory of Open Access Journals (Sweden)

    Alessandro Bartoloni

    2012-05-01

    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.

  6. Oxidative stress in children with severe malaria.

    Science.gov (United States)

    Narsaria, Nidhi; Mohanty, C; Das, B K; Mishra, S P; Prasad, Rajniti

    2012-04-01

    Fifty cases of severe malaria were studied for their oxidant and antioxidant status. Severe anemia (54%) was the most common presentation followed by hyperpyrexia, cerebral malaria and jaundice. Plasma malondialdehyde, protein carbonyl, nitrite, ascorbic acid and copper levels were significantly raised in cases as compared with controls (p children with severe malaria (p < 0.001). Plasma zinc was increased in cases but difference is not statistically significant. Significantly decreased level of nitrites and increased value of glutathione was found in patients with hemoglobinuria and jaundice, respectively. The significantly elevated malondialdehyde and protein carbonyl levels reflect the increased oxidative stress, whereas decreased levels of glutathione and superoxide dismutase point toward utilization of the antioxidants in severe malaria. Thus, changes in oxidants and antioxidants observed suggest the production of reactive oxygen species and their possible role in pathogenesis of severe malaria.

  7. Adjunctive therapy for cerebral malaria and other severe forms of Plasmodium falciparum malaria

    OpenAIRE

    John, Chandy C; Kutamba, Elizabeth; Mugarura, Keith; Opoka, Robert O

    2010-01-01

    Severe malaria due to Plasmodium falciparum causes more than 800,000 deaths every year. Primary therapy with quinine or artesunate is generally effective in controlling P. falciparum parasitemia, but mortality from cerebral malaria and other forms of severe malaria remains unacceptably high. Long-term cognitive impairment is also common in children with cerebral malaria. Of the numerous adjunctive therapies for cerebral malaria and severe malaria studied over the past five decades, only one (...

  8. Predictive score of uncomplicated falciparum malaria patients turning to severe malaria

    OpenAIRE

    Tangpukdee, Noppadon; Krudsood, Srivicha; Thanachartwet, Vipa; Duangdee, Chatnapa; Paksala, Siriphan; Chonsawat, Putza; Srivilairit, Siripan; Looareesuwan, Sornchai; Wilairatana, Polrat

    2007-01-01

    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...

  9. Intravenous artesunate reduces parasite clearance time, duration of intensive care, and hospital treatment in patients with severe malaria in Europe

    DEFF Research Database (Denmark)

    Kurth, Florian; Develoux, Michel; Mechain, Matthieu

    2015-01-01

    Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive...... care unit and hospital treatment in European patients with imported severe malaria....

  10. Spontaneous peripheral gangrene following severe cerebral malaria

    African Journals Online (AJOL)

    She gave a history of sudden onset of a severe febrile illness during July 1998, nine weeks prior to her arrival in Addis Ababa. She had attended her local local Health Centre where she had been admitted and treated for cerebral malaria. Unfortunately, no records of the laboratory findings or treatment given were available.

  11. Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.

    Science.gov (United States)

    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

    2015-11-18

    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.

  12. Preparing for future efficacy trials of severe malaria vaccines.

    Science.gov (United States)

    Gonçalves, Bronner P; Prevots, D Rebecca; Kabyemela, Edward; Fried, Michal; Duffy, Patrick E

    2016-04-07

    Severe malaria is a major cause of mortality in children, but comprises only a small proportion of Plasmodium falciparum infections in naturally exposed populations. The evaluation of vaccines that prevent severe falciparum disease will require clinical trials whose primary efficacy endpoint will be severe malaria risk during follow-up. Here, we show that such trials are feasible with fewer than 1000 participants in areas with intense malaria transmission during the age interval when severe malaria incidence peaks. Published by Elsevier Ltd.

  13. Predictors of childhood severe malaria in a densely populated area ...

    African Journals Online (AJOL)

    Hemoglobin and blood glucose levels decreased significantly in severe malaria patients compared with uncomplicated malaria patients or controls (P < 0.001). On the contrary ... Low levels of haemoglobin and glycemia, as well as high levels of transaminases and CRP has been identified as predictor of malaria severity.

  14. Prevalence and Severity of Malaria Parasitemia among Children ...

    African Journals Online (AJOL)

    Background: Malaria is one of the most serious and complex health problems in Sub Saharan Africa. Anemia in Children with malaria may require blood transfusion and has been be associated with high mortality rates. Aim: The aim of this study is to evaluate the prevalence, pattern, and severity of malaria parasitemia ...

  15. Spontaneous peripheral gangrene following severe cerebral malaria

    African Journals Online (AJOL)

    ... phalanges of the right index and middle fingers and the distal phalanges of the great, second and middle toes of the right foot following cerebral malaria. Until now, there has been only five such cases of peripheral gangrene associated with 'cerebral' malaria reported in literature and all these were all from Southeast Asia.

  16. Severe falciparum malaria associated with massive pulmonary ...

    African Journals Online (AJOL)

    Microthrombotic complications are the best described; however, a number of cases of thrombosis involving larger vessels have been published in the literature. Herein, we describe the case of a woman with malaria associated with massive pulmonary embolism. Keywords: Falciparum, malaria, pulmonary embolism ...

  17. Predictors of mortality in Gambian children with severe malaria anaemia

    NARCIS (Netherlands)

    Bojang, K. A.; van Hensbroek, M. B.; Palmer, A.; Banya, W. A.; Jaffar, S.; Greenwood, B. M.

    1997-01-01

    Severe malaria anaemia is a frequent cause of admission to hospital in tropical Africa and about 10% of children with this condition die. To determine ways in which mortality might be reduced we have studied risk factors for a fatal outcome in 173 children with severe malaria anaemia who were

  18. Imported malaria : improving assessment of severity and complications

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies)

    2017-01-01

    markdownabstractThe aim of this thesis is to answer several questions raised while caring for patients with imported malaria in Rotterdam. The challenge in the care for patients with imported malaria lies in the fact that most hospitals in non-endemic countries have little experience in

  19. Pattern of severe and complicated malaria in children Admitted to ...

    African Journals Online (AJOL)

    also found to be less common in partially immunised population that lives in stable malarious area, particularly in those beyond 6 years of age. Severe and complicated malaria should be diagnosed early and managed accordingly if one or more of the signs of complication are observed in patient with P. falciparum malaria.

  20. Clinical pattern of severe Plasmodium falciparum malaria in Sudan in an area characterized by seasonal and unstable malaria transmission

    DEFF Research Database (Denmark)

    Giha, H A; Elghazali, G; A-Elgadir, T M E

    2005-01-01

    A hospital-based study was carried out in Gedarif town, eastern Sudan, an area of markedly unstable malaria transmission. Among the 2488 diagnosed malaria patients, 4.4% fulfilled the WHO criteria for severe malaria, and seven died of cerebral malaria. The predominant complication was severe...

  1. Copeptin does not accurately predict disease severity in imported malaria

    Directory of Open Access Journals (Sweden)

    van Wolfswinkel Marlies E

    2012-01-01

    Full Text Available Abstract Background Copeptin has recently been identified to be a stable surrogate marker for the unstable hormone arginine vasopressin (AVP. Copeptin has been shown to correlate with disease severity in leptospirosis and bacterial sepsis. Hyponatraemia is common in severe imported malaria and dysregulation of AVP release has been hypothesized as an underlying pathophysiological mechanism. The aim of the present study was to evaluate the performance of copeptin as a predictor of disease severity in imported malaria. Methods Copeptin was measured in stored serum samples of 204 patients with imported malaria that were admitted to our Institute for Tropical Diseases in Rotterdam in the period 1999-2010. The occurrence of WHO defined severe malaria was the primary end-point. The diagnostic performance of copeptin was compared to that of previously evaluated biomarkers C-reactive protein, procalcitonin, lactate and sodium. Results Of the 204 patients (141 Plasmodium falciparum, 63 non-falciparum infection, 25 had severe malaria. The Area Under the ROC curve of copeptin for severe disease (0.66 [95% confidence interval 0.59-0.72] was comparable to that of lactate, sodium and procalcitonin. C-reactive protein (0.84 [95% CI 0.79-0.89] had a significantly better performance as a biomarker for severe malaria than the other biomarkers. Conclusions C-reactive protein but not copeptin was found to be an accurate predictor for disease severity in imported malaria. The applicability of copeptin as a marker for severe malaria in clinical practice is limited to exclusion of severe malaria.

  2. Retinopathy in severe malaria in Ghanaian children - overlap between fundus changes in cerebral and non-cerebral malaria

    DEFF Research Database (Denmark)

    Essuman, Vera A; Ntim-Amponsah, Christine T; Astrup, Birgitte S

    2010-01-01

    diagnostic tool. This study was designed to determine the diagnostic usefulness of retinopathy on ophthalmoscopy in severe malaria syndromes: Cerebral malaria (CM) and non-cerebral severe malaria (non-CM), i.e. malaria with respiratory distress (RD) and malaria with severe anaemia (SA), in Ghanaian children......-CM syndromes. However, the high prevalence of any retinopathy in the latter suggests that the brain and the retina may be suffering from ischaemia in both CM and non-CM....

  3. Antigens for a Vaccine that Prevents Severe Malaria

    National Research Council Canada - National Science Library

    Duffy, Patrick E

    2008-01-01

    .... The long-term objective of this project is to identify and prepare the malaria parasite forms causing severe anemia and then apply functional genomics and bioformatics tools to identify 15 to 30...

  4. Composition of the gut microbiota modulates the severity of malaria

    National Research Council Canada - National Science Library

    Nicolas F. Villarino; Gary R. LeCleir; Joshua E. Denny; Stephen P. Dearth; Christopher L. Harding; Sarah S. Sloan; Jennifer L. Gribble; Shawn R. Campagna; Steven W. Wilhelm; Nathan W. Schmidt

    2016-01-01

    ... with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria...

  5. Severe falciparum malaria associated with massive pulmonary ...

    African Journals Online (AJOL)

    E-mail: Jeremy.schwartz@yale.edu. Abstract. Falciparum malaria is known to cause alterations in the coagulation cascade, including disseminated intravascular coagulation. Microthrombotic complications are the best described; however, a number of cases of thrombosis involving larger vessels have been published in the ...

  6. The role of EPCR in the pathogenesis of severe malaria

    DEFF Research Database (Denmark)

    Mosnier, Laurent O; Lavstsen, Thomas

    2016-01-01

    Of the five Plasmodium species that infect humans, infection with P. falciparum is the most lethal, causing severe malaria syndromes, that result in over half a million annual deaths. With parasites becoming increasingly resistant to artemisinin there is an urgent need for new preventative...... and therapeutic options, for which understanding of the mechanisms that cause death and disability in malaria is essential. The recent discoveries that certain variants of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on infected erythrocytes are intimately linked to the precipitation of severe...... malaria syndromes and that these PfEMP1 variants contain EPCR binding domains provides new opportunities to improve our understanding of the molecular mechanisms responsible for the pathogenesis of severe malaria. EPCR is known for its essential role in the protein C (PC) system and for its ability...

  7. The role of EPCR in the pathogenesis of severe malaria.

    Science.gov (United States)

    Mosnier, Laurent O; Lavstsen, Thomas

    2016-05-01

    Of the five Plasmodium species that infect humans, infection with P. falciparum is the most lethal, causing severe malaria syndromes, that result in over half a million annual deaths. With parasites becoming increasingly resistant to artemisinin there is an urgent need for new preventative and therapeutic options, for which understanding of the mechanisms that cause death and disability in malaria is essential. The recent discoveries that certain variants of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on infected erythrocytes are intimately linked to the precipitation of severe malaria syndromes and that these PfEMP1 variants contain EPCR binding domains provides new opportunities to improve our understanding of the molecular mechanisms responsible for the pathogenesis of severe malaria. EPCR is known for its essential role in the protein C (PC) system and for its ability to support the cytoprotective effects of activated protein C (APC) that result in vascular and tissue protective effects in many organ systems of the body, including the brain, lung, kidney, and liver. Observations that binding of PfEMP1 to EPCR results in an acquired functional PC system deficiency support the new paradigm that EPCR plays a central role in the pathogenesis of severe malaria. Thus, targeting of the PfEMP1-EPCR interaction and restoring the functionality of the PC system may provide new strategies for the development of novel adjuvant therapies for severe malaria. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Severe congenital malaria acquired in utero.

    Science.gov (United States)

    Poespoprodjo, Jeanne R; Hasanuddin, Afdal; Fobia, Wendelina; Sugiarto, Paulus; Kenangalem, Enny; Lampah, Daniel A; Tjitra, Emiliana; Price, Ric N; Anstey, Nicholas M

    2010-04-01

    Vertical transmission of Plasmodium falciparum is under-recognized and usually associated with asymptomatic low-level parasitemia at birth. We report symptomatic congenital malaria presenting as a neonatal sepsis syndrome. The presence at birth of a high asexual parasitemia, gametocytemia, and splenomegaly indicated in utero rather than intrapartum transmission. The neonate was successfully treated with intravenous artesunate followed by oral dihydroartemisinin-piperaquine, without apparent adverse effects.

  9. A review of malarial retinopathy in severe malaria

    Directory of Open Access Journals (Sweden)

    H. L. Sithole

    2011-12-01

    Full Text Available The ocular manifestations of severe malaria in patients with cerebral malaria (CM include retinal whitening, vessel discolouration, retinal haemorrhages and papilloedema. A large prospective study of Malawian children with CM found that the severity of retinal signs, including the number of retinal haemorrhages, was related to the outcome and length of coma in survivors of malaria. In a smaller number of Kenyan children with cerebral malaria, retinal haemorrhages were associated with deep coma and severe anaemia. A study on the effect of malarial retinopathy on vision found no detectable effect on visual acuity (VA but where malaria isaggravated by failure to receive treatment this may possibly affect VA. The failure to receive treatment may be directly linked to the socio-economic status (SES of those affected and this may occur in the KwaZulu-Natal, Mpumalanga and Limpopo provinces of South Africa where malaria is endemic. This suggests the need for effective health education and health promotion amongst those affected by malaria especially in severely affected provinces of South Africa. Also, in view of the direct ocular consequences of severe malaria, optometrists should engage communities in health education and health promotion. This is particularly relevant because in some communities, a large majority of those suffering from malarial infections do not visit formal health facilities for treatment. In so doing, optometrists in South Africa will be contributing positively to the Millennium Development Goals which seek, amongst others, to reduce unwarranted sources of morbidity worldwide. (S Afr Optom 2011 70(3 129-135 

  10. Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria.

    Science.gov (United States)

    Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2017-04-01

    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.

  11. Clinical manifestations and outcomes of severe malaria among ...

    African Journals Online (AJOL)

    clinical manifestations and outcomes of severe malaria in children admitted to district hospital in. Rungwe and Kyela in south-western Tanzania. A total of 1371 children were selected as screening group of which 409 (29.8%) were tested positive for malaria. Mean age of the children was 2.7. (95%CI= 2.5, 2.8) years and the ...

  12. [Imported severe falciparum malaria in France in 2000-2011: epidemiological trends and the need for new treatments].

    Science.gov (United States)

    Danis, Martin; Thellier, Marc; Jauréguiberry, Stéphane; Bricaire, François; Buffet, Pierre

    2013-03-01

    In France malaria is monitored by the Centre National de Référence (CNR) du Paludisme (French National Malaria Reference Centre). The annual incidence of imported malaria currently ranges from 4 800 to 3 500 cases and has fallen gradually since 2000. However, the proportion of patients with severe P. falciparum malaria is increasing (2.5% in 2000, 7% in 2011), particularly among French residents from sub-Saharan Africa who neglect preventive measures. Overall mortality remains stable at 0.4%, but survival is improving in severe cases. The survival rate is higher among patients of African origin than among Europeans. Nonetheless, between 10 and 20 patients die of malaria every year in France. Two large controlled trials published in 2005 and 2010 showed that IV artesunate, a new treatment for severe falciparum malaria, is associated with a 22-38% absolute reduction in mortality relative to quinine. Artesunate is not licensed in Europe but has been available in France since May 2011 through a named-patient program controlled by the French Agency for Drug Safety [ANSM]. The first 99 patients treated with artesunate up to September 2012 experienced satisfactory efficacy and tolerability. Delayed, sometimes persistent anemia was observed in 13 patients, a rate similar to that noted in recent reports on imported malaria in Europe. This unexpected adverse effect requires further investigation. IV artesunate is now recommended as the first-line treatment for severe falciparum malaria in France.

  13. Surviving severe traumatic brain injury in Denmark

    DEFF Research Database (Denmark)

    Odgaard, Lene; Poulsen, Ingrid; Kammersgaard, Lars Peter

    2015-01-01

    PURPOSE: To identify all hospitalized patients surviving severe traumatic brain injury (TBI) in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS: Patients surviving severe TBI were identified from...... severe TBI were admitted to HS-rehabilitation. Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark...

  14. Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children

    Directory of Open Access Journals (Sweden)

    Tugumisirize Joshua

    2010-04-01

    Full Text Available Abstract Background Cerebral malaria is the most severe neurological complication of falciparum malaria and a leading cause of death and neuro-disability in sub-Saharan Africa. This study aimed to describe functional deficits and behaviour problems in children who survived cerebral malaria with severe neurological sequelae and identify patterns of brain injury. Findings Records of children attending a specialist child neurology clinic in Uganda with severe neurological sequelae following cerebral malaria between January 2007 and December 2008 were examined to describe deficits in gross motor function, speech, vision and hearing, behaviour problems or epilepsy. Deficits were classified according to the time of development and whether their distribution suggested a focal or generalized injury. Any resolution during the observation period was also documented. Thirty children with probable exposure to cerebral malaria attended the clinic. Referral information was inadequate to exclude other diagnoses in 7 children and these were excluded. In the remaining 23 patients, the commonest severe deficits were spastic motor weakness (14, loss of speech (14, hearing deficit (9, behaviour problems (11, epilepsy (12, blindness (12 and severe cognitive impairment (9. Behaviour problems included hyperactivity, impulsiveness and inattentiveness as in attention deficit hyperactivity disorder (ADHD and conduct disorders with aggressive, self injurious or destructive behaviour. Two patterns were observed; a immediate onset deficits present on discharge and b late onset deficits. Some deficits e.g. blindness, resolved within 6 months while others e.g. speech, showed little improvement over the 6-months follow-up. Conclusions In addition to previously described neurological and cognitive sequelae, severe behaviour problems may follow cerebral malaria in children. The observed differences in patterns of sequelae may be due to different pathogenic mechanisms, brain

  15. Copeptin does not accurately predict disease severity in imported malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); Y.B. de Rijke (Yolanda); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: Copeptin has recently been identified to be a stable surrogate marker for the unstable hormone arginine vasopressin (AVP). Copeptin has been shown to correlate with disease severity in leptospirosis and bacterial sepsis. Hyponatraemia is common in severe imported malaria and

  16. Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia

    DEFF Research Database (Denmark)

    Kempaiah, Prakasha; Dokladny, Karol; Karim, Zachary

    2016-01-01

    Severe malarial anemia [SMA, hemoglobin (Hb) cause of global morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized...... by decreased HSPA1A, a heat shock protein (Hsp) 70 coding gene. Hsp70 is a ubiquitous chaperone that regulates Nuclear Factor-kappa B (NF-κB) signaling and production of pro-inflammatory cytokines known to be important in malaria pathogenesis (e.g., IL-1β, IL-6 and TNF-α). Since the role of host Hsp70...... in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to non-severe malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70...

  17. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Helegbe, Gideon K; Goka, Bamenla Q; Kurtzhals, Jørgen

    2007-01-01

    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......55)] 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...... malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement...

  18. Defining childhood severe falciparum malaria for intervention studies.

    Directory of Open Access Journals (Sweden)

    Philip Bejon

    2007-08-01

    Full Text Available Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no "gold standard" individual test for severe malaria, malaria-attributable fractions (MAFs can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints.A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor, lower respiratory tract infection (clinician's final diagnosis, meningitis (on cerebrospinal fluid [CSF] examination, and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%-86.1% without excluding these conditions, 89% (95% CI 88.4%-90.2% after exclusions, and 95% (95% CI 94.0%-95.5% when a threshold of 2,500 parasites/mul was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%-83%.The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician's diagnosis, bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition.

  19. Retinopathy of vivax malaria in adults and its relation with severity parameters

    OpenAIRE

    Kochar, Anju; Kalra, Paavan; SB, Vijeth; Ukirade, Vinayak; Chahar, Anita; Kochar, Dhanpat Kumar; Kochar, Sanjay Kumar

    2016-01-01

    Malarial retinopathy is a set of retinal signs in severe malaria due to falciparum malaria. With increased recognition of severe manifestations of vivax malaria, a systematic study to evaluate retinal changes in vivax malaria could elaborate our knowledge about this neglected entity. This observational study included retinal examination of 104 adult patients (>14��years) with varying severity of vivax malaria admitted to a tertiary care center during peak seasons of 2012 and 2013. Thirty-eigh...

  20. Composition of the gut microbiota modulates the severity of malaria.

    Science.gov (United States)

    Villarino, Nicolas F; LeCleir, Gary R; Denny, Joshua E; Dearth, Stephen P; Harding, Christopher L; Sloan, Sarah S; Gribble, Jennifer L; Campagna, Shawn R; Wilhelm, Steven W; Schmidt, Nathan W

    2016-02-23

    Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.

  1. Severe and complicated malaria in KwaZulu-Natal

    African Journals Online (AJOL)

    severe anaemia (5). Multivariate analysis using a logistic regression model showed a high parasite .... logistic regression model showed high parasite loads and cerebral malaria (relative risks of 11.9 and 51.8 .... high parasite density, although the reverse was not true. This finding implies that the level of parasitaemia is not ...

  2. Acute kidney injury in children with severe malaria | Okpere | African ...

    African Journals Online (AJOL)

    The estimated glomerular filtration rate (eGFR) was calculated using the modified Schwartz equation. Results: AKI occurred in 32 of 960 patients with severe malaria giving a prevalence of 3.3%. They were aged 8 months to 9 years with majority (84.4%) less than 60 months. There were more males with a male: female ratio ...

  3. Cytokine profiles at birth predict malaria severity during infancy.

    Directory of Open Access Journals (Sweden)

    Edward Kabyemela

    Full Text Available BACKGROUND: Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood. METHODS AND FINDINGS: Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10 were measured at birth (cord blood; N=783 and during subsequent routine follow-up visits (peripheral blood for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear and clinical assessments every 2-4 weeks, and at the time of any illness. Cord blood levels of all cytokines were positively correlated with each other (Spearman's rank correlation. Cord levels of IL-1β and TNF-α (but not other cytokines correlated with levels of the same cytokine measured at routine visits during early life (P < 0.05. Higher cord levels of IL-1β but not TNF-α were associated with lower parasite densities during infancy (P=0.003; Generalized Estimating Equation (GEE method, with an average ~40% reduction versus children with low cord IL-1β levels, and with decreased risk of severe malaria during follow-up (Cox regression: adjusted hazard ratio (95% CI 0.60 (0.39-0.92, P = 0.02. CONCLUSION: IL-1β levels at birth are related to future IL-1β levels as well as the risk of severe malaria in early life. The effect on severe malaria risk may be due in part to the effect of inflammatory cytokines to control parasite density.

  4. Incidence of Severe Malaria Syndromes and Status of Immune Responses among Khat Chewer Malaria Patients in Ethiopia.

    Directory of Open Access Journals (Sweden)

    Tsige Ketema

    Full Text Available Although more emphasis has been given to the genetic and environmental factors that determine host vulnerability to malaria, other factors that might have a crucial role in burdening the disease have not been evaluated yet. Therefore, this study was designed to assess the effect of khat chewing on the incidence of severe malaria syndromes and immune responses during malaria infection in an area where the two problems co-exist. Clinical, physical, demographic, hematological, biochemical and immunological data were collected from Plasmodium falciparum mono-infected malaria patients (age ≥ 10 years seeking medication in Halaba Kulito and Jimma Health Centers. In addition, incidences of severe malaria symptoms were assessed. The data were analyzed using SPSS (version 20 software. Prevalence of current khat chewer malaria patients was 57.38% (95%CI =53-61.56%. Malaria symptoms such as hyperpyrexia, prostration and hyperparasitemia were significantly lower (P0.05, IgG3 antibody was significantly higher (P<0.001 among khat chewer malaria patients. Moreover, IgM, IgG, IgG1and IgG3 antibodies had significant negative association (P<0.001 with parasite burden and clinical manifestations of severe malaria symptoms, but not with severe anemia and hypoglycemia. Additionally, a significant increment (P<0.05 in CD4+ T-lymphocyte population was observed among khat users. Khat might be an important risk factor for incidence of some severe malaria complications. Nevertheless, it can enhance induction of humoral immune response and CD4+ T-lymphocyte population during malaria infection. This calls for further investigation on the effect of khat on parasite or antigen-specifc protective malaria immunity and analysis of cytokines released upon malaria infection among khat chewers.

  5. Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Quaye, I K; Ekuban, F A; Goka, B Q

    2000-01-01

    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...

  6. Initial treatment of severe malaria in children is inadequate – a study ...

    African Journals Online (AJOL)

    sectional study investigating characteristics of children admitted for severe malaria, confirmed with a positive thick blood smear. Results. A total of 309 ... In 85% of the malaria-infected children, quinine, artemisinin-based combination therapies ...

  7. Stunting may determine the severity of malaria-associated anemia in African children

    NARCIS (Netherlands)

    Verhoef, H.; West, C.E.; Veenemans, J.; Beguin, Y.; Kok, F.J.

    2002-01-01

    OBJECTIVE: Evidence from previous studies that malnourished children are protected against malaria is controversial. In individuals repeatedly exposed to malaria, immunity may develop first against severe disease, then against pyrogens, and last, against parasites. If this is true, this would

  8. Severe imported malaria in children in France. A national retrospective study from 1996 to 2005.

    Science.gov (United States)

    Mornand, Pierre; Verret, Catherine; Minodier, Philippe; Faye, Albert; Thellier, Marc; Imbert, Patrick

    2017-01-01

    Malaria is a leading cause of imported febrile illnesses in pediatric travelers, but few studies have addressed severe imported pediatric malaria. We aimed to determine the risk factors and the features of imported pediatric severe malaria. We conducted a retrospective, descriptive study using the French National Reference Center for Imported Malaria database, in children aged 0-15 years who were hospitalized with a falciparum malaria from January 1st 1996 to December 31th 2005. Uncomplicated and severe cases of falciparum malaria were compared to identify risk factors for severe cases. In the hospitals that reported more than five severe cases during the study period, we evaluated severe cases for prognostic factors and assessed the accuracy WHO criteria for predicting severity. Given the rarity of deaths, adverse outcomes were defined as requiring major therapeutic procedures (MTPs)-e.g., sedation, mechanical ventilation, nasal oxygen therapy, blood transfusions, hemodialysis, fluid resuscitation-or pediatric intensive care unit (PICU) admission. Of 4150 pediatric malaria cases included in the study, 3299 were uncomplicated and 851 (20.5%) were severe. Only one death was recorded during this period. Predictors for severe falciparum malaria were: age malaria cases, a stay in a Sahelian region, lack of chemoprophylaxis, age malaria reliably predicted adverse outcomes. In our study, the threshold of parasitemia most predictive of a poor outcome was 8%. In imported pediatric malaria, children younger than 2 years deserve particular attention. The main WHO 2000 criteria for severity are accurate, except for the threshold of hyperparasitemia, which should be revised.

  9. Studying Different Clinical Syndromes Of Paediatric Severe Malaria Using Plasma Proteomics

    KAUST Repository

    Ramaprasad, Abhinay

    2012-08-01

    Background- Severe Plasmodium falciparum malaria remains one of the major causes of childhood morbidity and mortality in Africa. Severe malaria manifests itself as three main clinical syndromes-impaired consciousness (cerebral malaria), respiratory distress and severe malarial anaemia. Cerebral malaria and respiratory distress are major contributors to malaria mortality but their pathophysiology remains unclear. Motivation/Objectives- Most children with severe malaria die within the first 24 hours of admission to a hospital because of their pathophysiological conditions. Thus, along with anti-malarial drugs, various adjuvant therapies such as fluid bolus (for hypovolaemia) and anticonvulsants (for seizures) are given to alleviate the sick child’s condition. But these therapies can sometimes have adverse effects. Hence, a clear understanding of severe malaria pathophysiology is essential for making an informed decision regarding adjuvant therapies. Methodology- We used mass spectrometry-based shotgun proteomics to study plasma samples from Gambian children with severe malaria. We compared the proteomic profiles of different severe malaria syndromes and generated hypotheses regarding the underlying disease mechanisms. Results/Conclusions- The main challenges of studying the severe malaria syndromes using proteomics were the high complexity and variability among the samples. We hypothesized that hepatic injury and nitric oxide play roles in the pathophysiology of cerebral malaria and respiratory distress.

  10. Clinical Factors for Severity of Plasmodium falciparum Malaria in Hospitalized Adults in Thailand

    OpenAIRE

    Patrick Sagaki; Vipa Thanachartwet; Varunee Desakorn; Duangjai Sahassananda; Supat Chamnanchanunt; Wirongrong Chierakul; Punnee Pitisuttithum; Prajej Ruangkanchanasetr

    2013-01-01

    Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malar...

  11. Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria

    DEFF Research Database (Denmark)

    Zhang, Qingfeng; Siegel, T Nicolai; Martins, Rafael M

    2014-01-01

    malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin......RNase II and upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally......, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality....

  12. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Ofori Michael F

    2007-12-01

    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.

  13. Malaria.

    Science.gov (United States)

    Fletcher, Tom E; Beeching, N J

    2013-09-01

    Malaria is a life-threatening disease, with its largest impact being due to Plasmodium falciparum infection in Africa. Military populations continue to be at a high risk of malaria and reported case series have frequently revealed poor compliance with preventative measures. The symptoms of malaria are non-specific and its management depends on awareness of the diagnosis and early recognition and treatment. This is aided by new and simple rapid diagnostic tests, but these should not replace the examination of blood films if these are available. Artemisinin combination therapy provides a more rapid and dependable cure of uncomplicated P falciparum infection, with artesunate now being the drug of choice in severe infection.

  14. Survival of severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Lai, Mary Y Y; Cheng, Peter K C; Lim, Wilina W L

    2005-10-01

    The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.

  15. [A severe form of falciparum malaria associated with staphylococcal endocarditis].

    Science.gov (United States)

    Mikic, D; Djokic, M; Bojic, I; Pavlovic, M; Balint, B; Vucinic, Z; Maksic, Dj

    2001-01-01

    A case is presented of a patient, aged 56 years, with severe form of imported malaria caused by Plasmodia falciparum. Hyperparasitemia of erythrocytes > 30% was registered, and during the course of the disease CNS dysfunction, severe anemia, acute renal failure, disseminated intravenous coagulation with manifest hemorrhagic syndrome, icterus, enterocolitis, pneumonia and staphylococcal endocarditis were developed Due to hyperparasitemia and numerous complications, antimalarial drugs such as quinidine (1,200 mg/day) and artemether (160 mg/day) were administered parenterally. Infected erythrocytes were exchanged with 2.5 litres of healthy erythrocytes suspension. Hemodialysis was also performed as well as nine-week antistaphylococcal therapy. During the treatment preparation of deplasmated blood, concentrated thrombocytes, fresh frozen plasma, cryoprecipitates, human albumins and immunoglobulins were applied, along with the correction of electrolytic dysbalance, administration of diuretic, cardiotonic, antiarrhythmic, anxiolytic, antipsychotic and antidepressive drugs. Two months after the admission the patient was released from the Clinic in good condition, with normal clinical-laboratory findings.

  16. Retinopathy of vivax malaria in adults and its relation with severity parameters.

    Science.gov (United States)

    Kochar, Anju; Kalra, Paavan; Sb, Vijeth; Ukirade, Vinayak; Chahar, Anita; Kochar, Dhanpat Kumar; Kochar, Sanjay Kumar

    2016-01-01

    Malarial retinopathy is a set of retinal signs in severe malaria due to falciparum malaria. With increased recognition of severe manifestations of vivax malaria, a systematic study to evaluate retinal changes in vivax malaria could elaborate our knowledge about this neglected entity. This observational study included retinal examination of 104 adult patients (>14 years) with varying severity of vivax malaria admitted to a tertiary care center during peak seasons of 2012 and 2013. Thirty-eight percent of severe cases had a retinal sign as compared to 6% of non-severe cases (p sign (p signs was significantly associated with anemia and jaundice. No statistical association was noted for retinal signs to be present in either renal dysfunction or altered thrombocytes count. The most common signs were arteriovenous changes, present in eight cases (19%) of severe malaria and three cases (5%) of non-severe malaria. Retinal hemorrhage was present in five cases (12%) of severe malaria and no case of non-severe malaria. Both superficial and deep hemorrhages were seen including white-centered hemorrhages. Other signs included cotton wool spots, hard exudates, blurred disk margins with spontaneous venous pulsations and bilateral disk edema. A correlation between retinal signs and severity parameters was drawn from the study. This is the first systemic study to evaluate the retinal changes in vivax malaria. Larger prospective studies should be done for further knowledge regarding retinal changes in vivax malaria, especially severe disease. Apart from its clinical significance, it might lead to a better understanding of the pathogenesis of the systemic disease of vivax malaria.

  17. Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital.

    Science.gov (United States)

    Bassat, Quique; Guinovart, Caterina; Sigaúque, Betuel; Mandomando, Inácio; Aide, Pedro; Sacarlal, Jahit; Nhampossa, Tacilta; Bardají, Azucena; Morais, Luís; Machevo, Sonia; Letang, Emilio; Macete, Eusébio; Aponte, John J; Roca, Anna; Menéndez, Clara; Alonso, Pedro L

    2009-09-01

    To describe the prevalence, aetiology and prognostic implications of coexisting invasive bacterial disease in children admitted with severe malaria in a rural Mozambican Hospital. Retrospective study of data systematically collected from June 2003 to May 2007 in a rural Mozambican hospital, from all children younger than 5 years admitted with severe malaria. Seven thousand and forty-three children were admitted with a diagnosis of malaria. 25.2% fulfilled the criteria for severe malaria. 5.4% of the children with severe malaria and valid blood culture results had a concomitant bacteraemia. Case fatality rates of severe malaria cases rose steeply when bacteraemia was also present (from 4.0% to 22.0%, P Staphilococcus aureus and non-typhoid Salmonella (NTS) were the most frequently isolated microorganisms among severe malaria cases. Their frequency and associated case fatality rates (CFR) varied according to age and to syndromic presentation. Streptococcus pneumoniae had a relatively low CFR, but was consistently associated with severe malaria syndromes, or anaemia severity groups. No clear-cut relationship between malarial anaemia and NTS bacteraemia was found. The coexistence of malaria and invasive bacterial infections is a frequent and life-threatening condition in many endemic African settings. In Mozambique, S. pneumoniae is the leading pathogen in this interaction, possibly as a consequence of the high HIV prevalence in the area. Measures directed at reducing the burden of both those infections are urgently needed to reduce child mortality in Africa.

  18. SEVERE MALARIA IN SUDANESE CHILDREN: CLINICAL ASPECTS AND PROGNOSIS IN HOSPITILIZED PATIENTS

    Science.gov (United States)

    Zeidan, Zeidan A.; Kojal, Elkhir M.; Habour, Ali B.; Nowary, Kamal A.; Mohammed, Fatih H.; Awadelkareem, Mohammed A.

    2005-01-01

    Objective: To asssess the epidemiology, clinical presentations, disease mangement, outcome and risk factors associatted with severe malaria in children in four hospitals in Sudan. Methods: Follow-up prospective design was used to fulfil the objectives of the study in four hospitals: Omdurman paediatrics hospital, located in the capital (Khartoum) compared to Madani, Gadarif and Sennar hospitals located in other states. The results: Total admission of severe malaria was 543 children representing 21% of all paediatric admissions, and 12% of malaria outpatient cases. Median age of children with severe malaria was 48 months. 93% of children with severe malaria died before the age of 9 years. Case fatlality rate was 2.6%. The risk of dying because of delay was four times more than when there was no delay , 95% CI (1.5 – 14.3). Other risks of death were severe malaria associated with coma, inability to sit or eat and hyperpyrexia. Omdurman hospital in Khartoum State in the capital, had the highest case management performance percentage compared to other regional hospitals. Conclusions: In view of this, it can be argued that deaths due to severe malaria could be reduced by improving health management and planning with the redistribution of resources (including consultants) at the central and regional levels and the conduct of proper training programs on the management of severe malaria at all levels. Raising the awareness of parents about seeking treatment for malaria early in order to avoid unnecessary deaths is vital. PMID:23012090

  19. Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage

    OpenAIRE

    Kihara, Michael; Carter, Julie A; Holding, Penny A; Vargha-Khadem, Faraneh; Scott, Rod C; Idro, Richard; Fegan, Greg W; de Haan, Michelle; Neville, Brian GR; Newton, Charles RJC

    2009-01-01

    Abstract Background Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. Methods An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males)...

  20. Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children.

    Directory of Open Access Journals (Sweden)

    Kathrin Schuldt

    Full Text Available BACKGROUND: Two recent reports have identified the Endothelial Protein C Receptor (EPCR as a key molecule implicated in severe malaria pathology. First, it was shown that EPCR in the human microvasculature mediates sequestration of Plasmodium falciparum-infected erythrocytes. Second, microvascular thrombosis, one of the major processes causing cerebral malaria, was linked to a reduction in EPCR expression in cerebral endothelial layers. It was speculated that genetic variation affecting EPCR functionality could influence susceptibility to severe malaria phenotypes, rendering PROCR, the gene encoding EPCR, a promising candidate for an association study. METHODS: Here, we performed an association study including high-resolution variant discovery of rare and frequent genetic variants in the PROCR gene. The study group, which previously has proven to be a valuable tool for studying the genetics of malaria, comprised 1,905 severe malaria cases aged 1-156 months and 1,866 apparently healthy children aged 2-161 months from the Ashanti Region in Ghana, West Africa, where malaria is highly endemic. Association of genetic variation with severe malaria phenotypes was examined on the basis of single variants, reconstructed haplotypes, and rare variant analyses. RESULTS: A total of 41 genetic variants were detected in regulatory and coding regions of PROCR, 17 of which were previously unknown genetic variants. In association tests, none of the single variants, haplotypes or rare variants showed evidence for an association with severe malaria, cerebral malaria, or severe malaria anemia. CONCLUSION: Here we present the first analysis of genetic variation in the PROCR gene in the context of severe malaria in African subjects and show that genetic variation in the PROCR gene in our study population does not influence susceptibility to major severe malaria phenotypes.

  1. Cardiovascular involvement in severe malaria: A prospective study in Ranchi, Jharkhand

    OpenAIRE

    Hemant Narayan Ray; Darshit Doshi; Appu Rajan; Singh, Amit K.; S B Singh; Das, M. K.

    2017-01-01

    Background & objectives: Malaria is considered as the most important parasitic disease of humans, causing seri- ous illness that can be fatal, if not diagnosed and treated immediately. It is a multisystem disorder affecting nearly every system of the body. The aim of the present study was to evaluate the involvement of cardiovascular system in severe malaria using non-invasive methods. Methods: This prospective study was conducted on patients of severe malaria who were admitted between Ju...

  2. Survival After Severe Rhabdomyolysis Following Monensin Ingestion.

    Science.gov (United States)

    Blain, Michela; Garrard, Alexander; Poppenga, Robert; Chen, Betty; Valento, Matthew; Halliday Gittinger, Melissa

    2017-09-01

    Monensin is a veterinary antibiotic with a narrow therapeutic window that has led to lethal intoxication in many animal species. Only two prior cases of human toxicity have been reported, both fatal. We present the first case of survival from severe toxicity following monensin ingestion. A 58-year-old man presented with 8 days of vomiting and abdominal pain. Due to delusions of central nervous system toxoplasmosis, he ingested 300 mg of monensin. His laboratory studies revealed severe rhabdomyolysis without renal dysfunction. Total creatine kinase (CK) peaked above 100,000 U/L. His CK decreased to 5192 U/L after 15 days of aggressive hydration and sodium bicarbonate therapy. His ejection fraction on echocardiogram decreased from 69 to 56%. Reports on acute clinical effects after human exposure to monensin are limited. Ingestion is known to cause skeletal and cardiac muscle rhabdomyolysis and necrosis. Animal studies demonstrate that monensin's toxicity is due to increases in intracellular sodium concentrations and Ca2+ release. To date, no effective antidotal treatment has been described. Monensin is a veterinary medication not approved for human use by the US Food and Drug Administration. Though poorly studied in humans, this case demonstrates the severe harm that may occur following ingestion.

  3. Severe Malaria in Neonates Masquerading as Septicaemia | Ojukwu ...

    African Journals Online (AJOL)

    Background: Malaria was once thought to be rare in the neonatal period, especially in neonates of semi-immune mothers in holoendemic areas. As a result, ill neonates admitted to newborn special care units are often presumed to have neonatal sepsis. Consequently, blood films for malaria parasites are not routinely ...

  4. Treatment of imported severe malaria with artesunate instead of quinine--more evidence needed?

    NARCIS (Netherlands)

    Cramer, J.P.; López-Vélez, R.; Burchard, G.D.; Grobusch, M.P.; de Vries, P.J.

    2011-01-01

    Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions

  5. IL4-589C/T polymorphism and IgE levels in severe malaria.

    Science.gov (United States)

    Verra, Federica; Luoni, Gaia; Calissano, Carlo; Troye-Blomberg, Marita; Perlmann, Peter; Perlmann, Hedvig; Arcà, Bruno; Sirima, Bienvenu Sodiomon; Konaté, Amadou; Coluzzi, Mario; Kwiatkowski, Dominic; Modiano, David

    2004-04-01

    Previous studies identified an allelic variant of the IL4 promoter region (IL4-589T) that appears to enhance the transcriptional activity of IL4, and is associated with increased IgE levels. Total serum IgE levels are elevated in malaria endemic regions, and higher in children with severe malaria. Here, we investigated the relationship of the IL4-589C/T polymorphism with severity of the disease in a case-control study of severe malaria in Burkina Faso, West Africa. No association between the IL4-589T and severe malaria was observed. No difference in Plasmodium falciparum-specific IgE was detected between severe and uncomplicated malaria patients. Among children with severe malaria, total IgE levels were significantly elevated in those carrying the IL4-589T allele (P = 0.018). In children with uncomplicated malaria, no significant difference was found. These results raise the possibility that there is a relationship between susceptibility to severe malaria, IgE production and genetic variation in the IL4 region, which merits further investigation in other epidemiological settings. Copyright 2004 Elsevier B.V.

  6. Minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during Plasmodium berghei ANKA infection.

    Science.gov (United States)

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash

    2017-02-01

    Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study. Infected mice were treated with an intra-peritoneal dose of minocycline hydrochloride, 45mg/kg daily for ten days that led to parasite clearance in blood, brain, liver and spleen on 7th day post-infection; and the mice survived until experiment ended (90days) without parasite recrudescence. Evans blue extravasation assay showed that blood-brain barrier integrity was maintained by minocycline. The tumor necrosis factor-alpha protein level and caspase activity, which is related to CM pathogenesis, was significantly reduced in the minocycline-treated group. Fluoro-Jade® C and hematoxylin-eosin staining of the brains of minocycline group revealed a decrease in degenerating neurons and absence of hemorrhages respectively. Minocycline treatment led to decrease in gene expressions of inflammatory mediators like interferon-gamma, CXCL10, CCL5, CCL2; receptors CXCR3 and CCR2; and hence decrease in T-cell-mediated cerebral inflammation. We also proved that this reduction in gene expressions is irrespective of the anti-parasitic property of minocycline. The distinct ability of minocycline to modulate gene expressions of CXCL10 and CXCR3 makes it effective than doxycycline, a tetracycline used as chemoprophylaxis. Our study shows that minocycline is highly effective in conferring neuroprotection during ECM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Feeding and survival of the malaria vector Anopheles gambiae on plants growing in Kenia

    NARCIS (Netherlands)

    Impoinvil, D.E.; Kongere, J.O.; Foster, W.A.; Njiru, B.N.; Killeen, G.F.; Githure, J.I.; Beier, J.C.; Hassanali, A.; Knols, B.G.J.

    2004-01-01

    The propensity of the malaria vector mosquito Anopheles gambiae Giles (Diptera: Culicidae) to ingest sugars from various plants, and subsequent survival rates, were assessed with laboratory-reared males and females offered eight species of plants commonly cultivated and/or growing wild in western

  8. Egg hatching, larval movement and larval survival of the malaria vector Anopheles gambiae in desiccating habitats

    NARCIS (Netherlands)

    Koenraadt, C.J.M.; Paaijmans, K.P.; Githeko, A.K.; Knols, B.G.J.; Takken, W.

    2003-01-01

    Background - Although the effects of rainfall on the population dynamics of the malaria vector Anopheles gambiae have been studied in great detail, the effects of dry periods on its survival remain less clear. Methods - The effects of drying conditions were simulated by creating desiccated habitats,

  9. Duodenal perforation in a 12-month old child with severe malaria ...

    African Journals Online (AJOL)

    Peptic ulcer disease (PUD) in children remains rare and difficult to diagnose before the onset of complications. We report on a case of a 12-month child with perforated duodenal ulcer, association with malaria. The severity of the febrile presentation and the positive laboratory confirmation of malaria delayed the diagnosis of ...

  10. Outcome of severe malaria in children in two district hospitals in ...

    African Journals Online (AJOL)

    Malaria is a major endemic parasitic disease and remains the main cause of morbidity and mortality in sub-Saharan Africa. Children less than 5 years old carry the largest part of this burden with 3000 deaths daily. Case management of severe malaria is a main problem in Cameroon. The regime proposed by the WHO ...

  11. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral malaria from uncomplicated malaria

    Directory of Open Access Journals (Sweden)

    Tangpukdee Noppadon

    2009-12-01

    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.

  12. Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographical Approach.

    Science.gov (United States)

    Wassmer, Samuel C; Taylor, Terrie E; Rathod, Pradipsinh K; Mishra, Saroj K; Mohanty, Sanjib; Arevalo-Herrera, Myriam; Duraisingh, Manoj T; Smith, Joseph D

    2015-09-01

    More than a century after the discovery of Plasmodium spp. parasites, the pathogenesis of severe malaria is still not well understood. The majority of malaria cases are caused by Plasmodium falciparum and Plasmodium vivax, which differ in virulence, red blood cell tropism, cytoadhesion of infected erythrocytes, and dormant liver hypnozoite stages. Cerebral malaria coma is one of the most severe manifestations of P. falciparum infection. Insights into its complex pathophysiology are emerging through a combination of autopsy, neuroimaging, parasite binding, and endothelial characterizations. Nevertheless, important questions remain regarding why some patients develop life-threatening conditions while the majority of P. falciparum-infected individuals do not, and why clinical presentations differ between children and adults. For P. vivax, there is renewed recognition of severe malaria, but an understanding of the factors influencing disease severity is limited and remains an important research topic. Shedding light on the underlying disease mechanisms will be necessary to implement effective diagnostic tools for identifying and classifying severe malaria syndromes and developing new therapeutic approaches for severe disease. This review highlights progress and outstanding questions in severe malaria pathophysiology and summarizes key areas of pathogenesis research within the International Centers of Excellence for Malaria Research program. © The American Society of Tropical Medicine and Hygiene.

  13. Possible association of the Plasmodium falciparum T1526C resa2 gene mutation with severe malaria

    Directory of Open Access Journals (Sweden)

    Durand Rémy

    2012-04-01

    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

  14. Case Report: Severe and Complicated Cynomolgi Malaria in a Rhesus Macaque Resulted in Similar Histopathological Changes as Those Seen in Human Malaria.

    Science.gov (United States)

    J Joyner, Chester; Consortium, The MaHPIC; Wood, Jennifer S; Moreno, Alberto; Garcia, Anapatricia; Galinski, Mary R

    2017-08-01

    Histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. Animal models of malaria are critical to complement such studies. Here, the histopathological changes observed in a rhesus macaque with severe and complicated Plasmodium cynomolgi malaria are reported. The animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. The macaque was given subcurative antimalarial treatment, fluid support, and a blood transfusion to treat the clinical complications, but at the time of transfusion, kidney function was compromised. These interventions did not restore kidney function, and the animal was euthanized due to irreversible renal failure. Gross pathological and histological examinations revealed that the lungs, kidneys, liver, spleen, and bone marrow exhibited abnormalities similar to those described in patients with malaria. Overall, this case report illustrates the similarities in the pathophysiological complications that can occur in human malaria and cynomolgi malaria in rhesus macaques.

  15. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

    Science.gov (United States)

    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  16. Interdisciplinary Ugandan perspectives on computerized intervention implementation for child survivors of severe malaria: A qualitative analysis.

    Science.gov (United States)

    Finn, Katherine; Lori, Jody; Lee, Maurgan; Giordani, Bruno

    2018-02-01

    Severe malaria (SM) is the leading cause of pediatric cognitive impairment in sub-Saharan Africa. Computerized Cognitive Rehabilitation Therapy (CCRT), a promising intervention for children suffering from SM related cognitive delay, targets areas impacted by the disease (memory, attention, and executive function), but has yet to be implemented for daily use. This paper explores the perspectives of Ugandan professionals regarding CCRT implementation in the academic setting of Uganda. A qualitative descriptive approach was taken to conduct interviews with Ugandan professionals directly or indirectly aware of an ongoing CCRT intervention trial. Eight individuals were consented and interviewed. Responses were analyzed thematically. Question topics included knowledge of malaria and CCRT, perspectives on implementation feasibility, and experience engaging in a global collaborative research endeavor. Facilitators included perceived value and environment. Potential barriers were geography and resource availability. Perceived value is seen, expected, and/or hoped for outcomes by adults involved in the child's development. Environment speaks to the internal environment of the CCRT program as well as the external environment of the school setting. Geography presents as a barrier due to the difficulty of accessing CCRT in rural settings. Resource availability was a consistently identified barrier to implementation including aspects of technological, financial, and understanding deficits leading to difficulties in CCRT dissemination. Results demonstrate optimism and hope of Ugandan professionals for CCRT in children who have survived SM. Professionals identify and prioritize needs for implementation uniquely, pointing to the value in interdisciplinary collaboration to ensure effective implementation of CCRT. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Haemoglobinuria among children with severe malaria attending tertiary care in Ibadan, Nigeria

    Directory of Open Access Journals (Sweden)

    Ajetunmobi Wasiu A

    2012-10-01

    Full Text Available Abstract Background Haemoglobinuria is one of the manifestations of severe malaria and results from severe intravascular haemolysis. Glucose-6-phosphate dehydrogenase (G6PD deficiency has been implicated in its aetiology. Haemoglobinuria may be associated with severe anaemia and, less frequently, acute renal failure. Methods A prospective case-control study was carried out to determine the incidence of haemoglobinuria as confirmed by dipstick urinalysis, microscopy and spectrophotometric measurement, among children with severe malaria. A total of 251 children presenting at the Children’s Emergency Ward with severe malaria were recruited over a period of 21 months. The G6PD status and the outcomes of severe malaria in children with and without haemoglobinuria was studied with respect to renal failure, the recurrence of haemoglobinuria and blood pressure changes over a three-month follow-up period. Results It was found that the incidence of haemoglobinuria among children with severe malaria is 19.1%. Children Conclusions Haemoglobinuria was a prominent feature of severe malaria and it was significantly associated with jaundice at presentation. Haemoglobinuria was commoner in older children than younger children but not related to sex. G6PD deficiency was not an independent predictor of the occurrence or outcome of haemoglobinuria. Blood pressure was not affected by haemoglobinuria on admission nor during follow-up.

  18. Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S; Theander, T G

    1994-01-01

    . Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of IL-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6...... antigen. We conclude that soluble IL-2R is a useful marker of disease severity independently of the association with levels of parasitaemia, and that functional regulation of different lymphocyte subsets occurs during acute malaria episodes....

  19. PPARγ agonists improve survival and neurocognitive outcomes in experimental cerebral malaria and induce neuroprotective pathways in human malaria.

    Directory of Open Access Journals (Sweden)

    Lena Serghides

    2014-03-01

    Full Text Available Cerebral malaria (CM is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors. Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone. PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models. Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM. Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF and nerve growth factor (NGF in the brains of infected mice. Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy. In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF. These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM.

  20. Severe malaria in children: a proposal for clinical grading

    African Journals Online (AJOL)

    Results. A total of 8 PCFs were identified in 155 children with SM; impaired consciousness, prostration, convulsions and .... tion, defined as inability of the conscious patient to sit, drink or eat/breastfeed when he/she would otherwise be able to; (iii) respiratory distress, ... The evolution of malaria diagnostic technology recently.

  1. Haemoglobin genotype of children with severe malaria seen at the ...

    African Journals Online (AJOL)

    Prof Ezechukwu

    2011-10-23

    Oct 23, 2011 ... Abstract: Introduction: Types of haemoglobin (Hb) genotype have been found to be crucial to the rate of red blood cell parasite invasion, multiplication, and destruction as well as outcome of malaria disease. In a bid to provide more informa- tion on the relationship between Hb genotype and level of ...

  2. Malaria.

    Science.gov (United States)

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  3. Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Nicolas Argy

    Full Text Available Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known.From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants.Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host.Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden.

  4. Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria.

    Science.gov (United States)

    Argy, Nicolas; Kendjo, Eric; Augé-Courtoi, Claire; Cojean, Sandrine; Clain, Jérôme; Houzé, Pascal; Thellier, Marc; Hubert, Veronique; Deloron, Philippe; Houzé, Sandrine

    2017-01-01

    Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known. From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology) associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants). Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host. Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden.

  5. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa.

    Science.gov (United States)

    Snow, R W; Omumbo, J A; Lowe, B; Molyneux, C S; Obiero, J O; Palmer, A; Weber, M W; Pinder, M; Nahlen, B; Obonyo, C; Newbold, C; Gupta, S; Marsh, K

    1997-06-07

    Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted. We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory-tract infections (ARI) as a comparison. 3556 malaria admissions were recorded for the five sites. Marked differences were observed in age, clinical spectrum and rates of severe malaria between the five sites. Paradoxically, the risks of severe disease in childhood were lowest among populations with the highest transmission intensities, and the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. For severe malaria, for example, admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3.9, 25.8, 25.9, 16.7, and 18.0 in the five communities; the forces of infection estimated for those communities (new infections per infant per month) were 0.001, 0.034, 0.050, 0.093, and 0.176, respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing transmission intensity. We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate. In

  6. Severe imported malaria in an intensive care unit: a review of 59 cases

    Directory of Open Access Journals (Sweden)

    Santos Lurdes C

    2012-03-01

    Full Text Available Abstract Background In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU. Methods Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011 and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS, malaria score for adults (MSA, simplified acute physiology score (SAPSII and a score based on WHO's malaria severe criteria were applied. Statistical analysis was performed using StataV12. Results Fifty nine patients were included in the study, all but three were adults; 47 (79,6% were male; parasitaemia on admission, quantified in 48/59 (81.3% patients, was equal or greater than 2% in 47 of them (97.9%; the most common complications were thrombocytopaenia in 54 (91.5% patients, associated with disseminated intravascular coagulation (DIC in seven (11.8%, renal failure in 31 (52.5% patients, 18 of which (30.5% oliguric, shock in 29 (49.1% patients, liver dysfunction in 27 (45.7% patients, acidaemia in 23 (38.9% patients, cerebral dysfunction in 22 (37.2% patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2% patients, hypoglycaemia in 18 (30.5% patients; 29 (49.1% patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were

  7. New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance.

    Science.gov (United States)

    Price, Ric N; Douglas, Nicholas M; Anstey, Nicholas M

    2009-10-01

    Unlike Plasmodium falciparum, Plasmodium vivax rarely causes severe disease in healthy travellers or in temperate endemic regions and has been regarded as readily treatable with chloroquine. However, in tropical areas, recent reports have highlighted severe and fatal disease associated with P. vivax infection. We review the evidence for severe disease and the spread of drug-resistant P. vivax and speculate how these maybe related. Studies from Indonesia, Papua New Guinea, Thailand and India have shown that 21-27% of patients with severe malaria have P. vivax monoinfection. The clinical spectrum of these cases is broad with an overall mortality of 0.8-1.6%. Major manifestations include severe anaemia and respiratory distress, with infants being particularly vulnerable. Most reports of severe and fatal vivax malaria come from endemic regions where populations have limited access to healthcare, a high prevalence of comorbidity and where drug-resistant P. vivax strains and partially effective primaquine regimens significantly undermine the radical cure and control of this relapsing infection. The mechanisms underlying severe disease in vivax malaria remain poorly defined. Severe, fatal and multidrug-resistant vivax malaria challenge our perception of P. vivax as a benign disease. Strategies to understand and address these phenomena are needed urgently if the global elimination of malaria is to succeed.

  8. Cardiovascular involvement in severe malaria: A prospective study in Ranchi, Jharkhand.

    Science.gov (United States)

    Ray, Hemant Narayan; Doshi, Darshit; Rajan, Appu; Singh, Amit K; Singh, S B; Das, M K

    2017-01-01

    Malaria is considered as the most important parasitic disease of humans, causing seri- ous illness that can be fatal, if not diagnosed and treated immediately. It is a multisystem disorder affecting nearly every system of the body. The aim of the present study was to evaluate the involvement of cardiovascular system in severe malaria using non-invasive methods. This prospective study was conducted on patients of severe malaria who were admitted between June and November 2015 in the Department of Medicine, Rajendra Institute of Medical Sciences and Hospital, Ranchi, Jharkhand, India. A total of 27 cases (18 males and 9 females; age ranging between 15 and 70 yr) of severe malaria (P. falciparum 24; P. vivax 1; mixed 2) were diagnosed by microscopic examination of peripheral blood smear and bivalent rapid diagnostic test (RDT) kit. The assessment of cardiovascular system was done by clinical examination, chest X-ray, ECG and transthoracic echocardiography. In all, 7 (26%) patients were found to be suffering from circulatory failure, out of which one was P. vivax case and rest were cases of P. falciparum infection with high parasite density. One patient died due to cardiovascular collapse. ECG revealed sinus bradycardia [Heart rate (HR): 40-60] in 7% of the cases, extreme tachycardia (HR: 120-150) in 3.7% of cases and premature arterial ectopic with tachycardia in 3.7% of patients (p malaria. The present study indicated involvement of cardiovascular system in severe malaria as evidenced from ECG and echocardiography. The study also revealed that cardiovascular instabilities are common in falciparum malaria, but can also be observed in vivax malaria.

  9. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Wang, Christian W.; Mkumbaye, Sixbert I.

    2016-01-01

    Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding hum...... the hypothesis that the CIDRα1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction....... endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full......-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support...

  10. Acute Renal Failure in Patients with Severe Falciparum Malaria: Using the WHO 2006 and RIFLE Criteria.

    Science.gov (United States)

    Thanachartwet, Vipa; Desakorn, Varunee; Sahassananda, Duangjai; Kyaw Win, Ko Ko Yazar; Supaporn, Thanom

    2013-01-01

    There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF) in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients). The requirement for RRT was 45.2% (52 patients) and the in-hospital mortality was 31.9% (36 patients). Using the RIFLE criteria, 73.9% (190 patients) had acute kidney injury (AKI). The requirement for RRT was 11.6% (5 patients) in patients with RIFLE-I and 44.9% (48 patients) in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (P < 0.05) and the in-hospital mortality (P < 0.05) were significantly higher in ARF patients with severe falciparum malaria using both criteria. In conclusion, the RIFLE criteria could be used for diagnosing AKI and predicting outcomes in patients with severe malaria similar to the WHO 2006 criteria.

  11. Acute Renal Failure in Patients with Severe Falciparum Malaria: Using the WHO 2006 and RIFLE Criteria

    Directory of Open Access Journals (Sweden)

    Vipa Thanachartwet

    2013-01-01

    Full Text Available There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients. The requirement for RRT was 45.2% (52 patients and the in-hospital mortality was 31.9% (36 patients. Using the RIFLE criteria, 73.9% (190 patients had acute kidney injury (AKI. The requirement for RRT was 11.6% (5 patients in patients with RIFLE-I and 44.9% (48 patients in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (P<0.05 and the in-hospital mortality (P<0.05 were significantly higher in ARF patients with severe falciparum malaria using both criteria. In conclusion, the RIFLE criteria could be used for diagnosing AKI and predicting outcomes in patients with severe malaria similar to the WHO 2006 criteria.

  12. Determinants of variant surface antigen antibody response in severe Plasmodium falciparum malaria in an area of low and unstable malaria transmission

    DEFF Research Database (Denmark)

    A-Elgadir, T M E; Theander, T G; Elghazali, G

    2006-01-01

    The variant surface antigens (VSA) of infected erythrocytes are important pathogenic markers, a set of variants (VSA(SM)), were assumed to be associated with severe malaria (SM), while SM constitutes clinically diverse forms, such as, severe malarial anemia (SMA) and cerebral malaria (CM). This s......The variant surface antigens (VSA) of infected erythrocytes are important pathogenic markers, a set of variants (VSA(SM)), were assumed to be associated with severe malaria (SM), while SM constitutes clinically diverse forms, such as, severe malarial anemia (SMA) and cerebral malaria (CM...... range of isolates had a higher level of VSA Ab against the recognized isolates (correlation coefficient, 0.727, PSMA (P....001). Parasites obtained from patients with SMA or from children were better recognized than isolates obtained from patients with uncomplicated malaria or from adults, P

  13. Low larval vector survival explains unstable malaria in the Western Kenya higlands

    NARCIS (Netherlands)

    Koenraadt, C.J.M.; Paaijmans, K.P.; Schneider, P.; Githeko, A.K.; Takken, W.

    2006-01-01

    Several highland areas in eastern Africa have recently suffered from serious malaria epidemics. Some models predict that, in the short term, these areas will experience more epidemics as a result of global warming. However, the various processes underlying these changes are poorly understood. We

  14. [Prognostic value of clinical and parasitological signs for severe malaria in patients from Colombia].

    Science.gov (United States)

    Tobón-Castaño, Alberto; Giraldo-Castro, Cecilia; Blair, Silvia

    2012-03-01

    Early recognition of danger signs in patients with malaria can reduce complications and deaths, but little is known about their prognostic value for severe malaria, especially in areas of low transmission and unstable malaria. To assess the prognostic value for severity of different clinical and parasitological signs in patients with malaria. A prospective cohort of patients from five municipalities in Colombia with diagnosis of Plasmodium falciparum or P. vivax malaria in whom the association between clinical and parasitological signs with complicated malaria was studied. A predictive model with 47.4% sensitivity, 92.8% specificity, 63.2% positive predictive value and 87.1% negative predictive value was obtained which includes jaundice, dark urine, hyperpyrexia and signs of dehydration. To impact the morbidity of complicated proposed a strategy is proposed for the early recognition of danger signs by non-medical personnel, which could be complemented by other elements of health care, such as providing adequate and appropriate antimalarial treatment. Diagnostic criteria for moderate complication are also proposed.

  15. Evaluation of severe malaria case management in Mazowe District, Zimbabwe, 2014.

    Science.gov (United States)

    Makumbe, Bargley; Tshuma, Cremence; Shambira, Gerald; Mungati, More; Gombe, Notion Tafara; Bangure, Donewell; Juru, Tsitsi Patience; Tshimanga, Mufuta

    2017-01-01

    Malaria is a preventable and curable disease. Mazowe district had been experiencing a lower malaria transmission rate in comparison to other districts in the Mashonaland Central province but it experienced a huge outbreak in the 2013-2014 rainy seasons with a case fatality rate (CFR) of 0.21%. This CFR was the highest in the province and it was twice as much as the national CFR (0.12%) for the same period. We evaluated severe malaria case management in Mazowe district to determine if practice is as per standard treatment guidelines. A descriptive cross sectional study was conducted in Mazowe district using the Logical Framework approach. District Health Executives (DHE) members, nurses and severe malaria case notes were purposively and conveniently selected into the study. Key informant Interviews and review of case notes were carried out. All data were analysed using Epi Info 3.5.1.to calculate means and frequencies. Permission to conduct the study was obtained from the Mashonaland Central Provincial Medical Directorate (PMD) Institutional Ethical Review Board (IRB). The median age in years of the cases was 16 (Q1=7.3; Q3=30.8) and up to 58.1% of the cases were female. Inputs including staff, medicines and medical and laboratory equipment for severe case management were inadequate in the district. Only 60% of severe cases were diagnosed using blood slides and up to 95.6% of cases presented with one or more of the clinical signs of severe malaria. All severe cases were treated using correct anti-malarial and analgesic doses. Patient monitoring was not done as per prerequisite intervals and up to 5% of cases died. The health workers had above average knowledge on severe malaria. Severe malaria case management inputs were inadequate in the district. For many cases, the district did not follow complicated malaria treatment guidelines for diagnosis, treatment and monitoring. Untrained staff needs training in Severe Malaria Case Management and monitoring of commodity

  16. Malaria

    Science.gov (United States)

    ... deadly type occurs in Africa south of the Sahara Desert. Malaria symptoms include chills, flu-like symptoms, fever, vomiting, diarrhea, and jaundice. A blood test can diagnose it. It can be life-threatening. However, you can treat malaria with drugs. ...

  17. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.

    Science.gov (United States)

    Menendez, C; Kahigwa, E; Hirt, R; Vounatsou, P; Aponte, J J; Font, F; Acosta, C J; Schellenberg, D M; Galindo, C M; Kimario, J; Urassa, H; Brabin, B; Smith, T A; Kitua, A Y; Tanner, M; Alonso, P L

    1997-09-20

    Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility. 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys. The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]). Malaria

  18. Acute traumatic coagulopathy decreased actual survival rate when compared with predicted survival rate in severe trauma.

    Science.gov (United States)

    Kim, Su Jin; Lee, Sung Woo; Han, Gap Su; Moon, Sung Woo; Choi, Sung Hyuck; Hong, Yun Sik

    2012-11-01

    To determine whether acute traumatic coagulopathy (ATC) should be combined with the trauma and injury severity score (TRISS) to predict outcome in severe trauma patients and investigate effects of the change in coagulation state during early resuscitation on the actual survival rate. This was a retrospective study. Significant variables that affected 28-day mortality were analysed using multivariate logistic regression. Study patients were classified into three groups: no coagulopathy, mild coagulopathy or severe coagulopathy. Concordance between actual and predicted survival rates were compared for each group. The predicted survival rate was calculated using the TRISS method. The study also determined whether changes in the coagulation state during inhospital resuscitation affected the relationship between actual and predicted survival in patients who had rechecked coagulation profile within 12 h after presentation. Data from a total of 336 patients were analysed. At presentation, 20.8% of the study patients had mild coagulopathy, whereas 7.7% had severe coagulopathy. Age, injury severity score, revised trauma score and presence of ATC at presentation were independently associated with 28-day mortality. Actual survival was significantly lower than predicted survival in the mild and severe coagulopathy groups. Aggravation of coagulation state from normal or mild to severe coagulopathy or persistent severe coagulopathy during inhospital resuscitation mainly contributed to the discrepancy between actual and predicted survival. ATC decreased actual survival more than expected. ATC should be combined with TRISS to predict trauma outcome in severely injured patients. Improvement in coagulopathy during resuscitation may reduce the incidence of preventable death after trauma.

  19. CD36 T188G gene polymorphism and severe falciparum malaria in India.

    Science.gov (United States)

    Das, A; Das, T K; Sahu, U; Das, B P; Kar, S K; Ranjit, M R

    2009-07-01

    Sequestration of parasitized erythrocytes (PE) in the microvasculature contributes directly to the virulence and severe pathology of Plasmodium falciparum malaria. The scavenger receptor CD36 appears to play an important role in PE adherence. Recently several mutations in the CD36 gene have been found to be associated with variability in susceptibility to P. falciparum infection in different ethnic populations. We investigated the possible association of T188G CD36 gene polymorphism with severe clinical manifestations of malaria in 95 adult patients with severe malaria admitted to SCB Medical College Hospital, Cuttack, Orissa, India ('severe' group) and 95 ethnically matched controls attending outpatient clinics at primary health centres ('mild' group). The frequency of the wild-type (T188T) allele of the CD36 gene was 0.91 in the 'severe' group and 0.78 in the 'mild' group of patients, while mutant (T188G) allele frequency was 0.09 in the severe group and 0.22 in the mild group. The Hardy-Weinberg equation indicates that the mutant allele is under selection pressure and disease association analysis shows that the presence of the heterozygote mutant allele renders protection against severe malaria (chi(2)=10.67, odds ratio=3.51, 95% CI 1.67-7.36).

  20. Survival after severe self poisoning with sodium valproate.

    OpenAIRE

    Lakhani, M; McMurdo, M E

    1986-01-01

    A 48 year old patient deliberately poisoned herself with 25 g of sodium valproate and survived with supportive measures only. This case contradicts the experience of those who advocate aggressive management of such severe overdoses.

  1. Inhaled nitric oxide for the adjunctive therapy of severe malaria: Protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lavery James V

    2011-07-01

    Full Text Available Abstract Background Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2 has recently been shown to function as a key regulator. Nitric oxide (NO is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates. Methods/Design This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy, among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae. Discussion Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa. Trial Registration ClinicalTrials.gov Identifier: NCT01255215

  2. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goel, Suchi; Palmkvist, Mia; Moll, Kirsten

    2015-01-01

    Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs......—preferentially of blood group A—to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population....

  3. Increased levels of inflammatory mediators in children with severe Plasmodium falciparum malaria with respiratory distress

    DEFF Research Database (Denmark)

    Awandare, Gordon A; Goka, Bamenla; Boeuf, Philippe

    2006-01-01

    circulating levels of mediators of inflammation--including the cytokines tumor necrosis factor (TNF)- alpha and interleukin (IL)-10; the chemokines macrophage inflammatory protein (MIP)-1 alpha , MIP-1 beta , and IL-8; and the immune activation marker neopterin--in children with RD, severe malarial anemia......BACKGROUND: Respiratory distress (RD), a symptom of underlying metabolic acidosis, has been identified as a major risk factor for mortality in children with severe malaria in Africa, yet the molecular mediators involved in the pathogenesis of RD have not been identified. METHODS: We studied...... (SMA), cerebral malaria (CM), and uncomplicated malaria (UM). RESULTS: Children with RD had significantly higher plasma levels of TNF- alpha , IL-10, and neopterin and a significantly higher TNF- alpha : IL-10 ratio than those without RD. In addition, the results demonstrated that, relative to UM, CM...

  4. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children

    DEFF Research Database (Denmark)

    Gyan, B A; Goka, B; Cvetkovic, J T

    2004-01-01

    Immunoglobulin E has been associated with severe malaria suggesting a regulatory role for interleukin (IL)-4 and/or IgE in the pathogenesis of severe malaria. We have investigated possible associations between polymorphisms in the IL-4 repeat region (intron 3) and promoter regions (IL-4 +33CT...... groups. Carriers of IL-4 +33T/-590T with cerebral malaria had elevated total IgE compared to non-carriers (P = 0.03). Our data suggest that IL-4 and/or IgE play a regulatory role in the pathogenesis of severe or complicated malaria....

  5. Artesunate: investigational drug for the treatment of severe falciparum malaria in Hawai'i.

    Science.gov (United States)

    Callender, David M; Hsue, Gunther

    2011-04-01

    There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai'i. A 49-year-old man presented to Tripler Army Medical Center, Hawai'i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria.

  6. Artesunate: Investigational Drug for the Treatment of Severe Falciparum Malaria in Hawai‘i

    Science.gov (United States)

    Hsue, Gunther

    2011-01-01

    Introduction There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai‘i. Case Report A 49-year-old man presented to Tripler Army Medical Center, Hawai‘i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. Discussion Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria. PMID:21785506

  7. Severe anaemia in children living in a malaria endemic area of Kenya.

    Science.gov (United States)

    Newton, C R; Warn, P A; Winstanley, P A; Peshu, N; Snow, R W; Pasvol, G; Marsh, K

    1997-02-01

    Severe anaemia is an important cause of morbidity and mortality in African children, but the causes, particularly falciparum malaria, are difficult to determine. We assessed the contribution of falciparum malaria to anaemia in Kenyan children by clinical examination and measurement of parasitaemia and haemoglobin (Hb) concentration in 559 children in the community and in 2412 children admitted to Kilifi district hospital during a 2-year period. We also attempted to characterize severe malarial anaemia by examining the causes and pathophysiology of anaemia in 101 children admitted with Hb concentration anaemia admitted to hospital. There was no difference in the frequency of haemolysis or dyserythropoiesis in the children with malarial anaemia and those with anaemia from other causes, such as iron deficiency or sickle cell disease. The mortality rate in the children with severe malarial anaemia was 8.6% compared with 3.6% in children with severe anaemia due to other causes. Falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.

  8. Malaria Control Interventions Contributed to Declines in Malaria Parasitemia, Severe Anemia, and All-Cause Mortality in Children Less Than 5 Years of Age in Malawi, 2000-2010.

    Science.gov (United States)

    Hershey, Christine L; Florey, Lia S; Ali, Doreen; Bennett, Adam; Luhanga, Misheck; Mathanga, Don P; Salgado, S René; Nielsen, Carrie F; Troell, Peter; Jenda, Gomezgani; Yé, Yazoume; Bhattarai, Achuyt

    2017-09-01

    Malaria control intervention coverage increased nationwide in Malawi during 2000-2010. Trends in intervention coverage were assessed against trends in malaria parasite prevalence, severe anemia (hemoglobin cause mortality in children under 5 years of age (ACCM) using nationally representative household surveys. Associations between insecticide-treated net (ITN) ownership, malaria morbidity, and ACCM were also assessed. Household ITN ownership increased from 27.4% (95% confidence interval [CI] = 25.9-29.0) in 2004 to 56.8% (95% CI = 55.6-58.1) in 2010. Similarly intermittent preventive treatment during pregnancy coverage increased from 28.2% (95% CI = 26.7-29.8) in 2000 to 55.0% (95% CI = 53.4-56.6) in 2010. Malaria parasite prevalence decreased significantly from 60.5% (95% CI = 53.0-68.0) in 2001 to 20.4% (95% CI = 15.7-25.1) in 2009 in children aged 6-35 months. Severe anemia prevalence decreased from 20.4% (95% CI: 17.3-24.0) in 2004 to 13.1% (95% CI = 11.0-15.4) in 2010 in children aged 6-23 months. ACCM decreased 41%, from 188.6 deaths per 1,000 live births (95% CI = 179.1-198.0) during 1996-2000, to 112.1 deaths per 1,000 live births (95% CI = 105.8-118.5) during 2006-2010. When controlling for other covariates in random effects logistic regression models, household ITN ownership was protective against malaria parasitemia in children (odds ratio [OR] = 0.81, 95% CI = 0.72-0.92) and severe anemia (OR = 0.82, 95% CI = 0.72-0.94). After considering the magnitude of changes in malaria intervention coverage and nonmalaria factors, and given the contribution of malaria to all-cause mortality in malaria-endemic countries, the substantial increase in malaria control interventions likely improved child survival in Malawi during 2000-2010.

  9. The Survival Strategies of Malaria Parasite in the Red Blood Cell and Host Cell Polymorphisms

    Directory of Open Access Journals (Sweden)

    Gunanidhi Dhangadamajhi

    2010-01-01

    Full Text Available Parasite growth within the erythrocyte causes dramatic alterations of host cell which on one hand facilitates nutrients acquisition from extracellular environment and on other hand contributes to the symptoms of severe malaria. The current paper focuses on interactions between the Plasmodium parasite and its metabolically highly reduced host cell, the natural selection of numerous polymorphisms in the genes encoding hemoglobin and other erythrocyte proteins.

  10. Clinical manifestations and outcomes of severe malaria among ...

    African Journals Online (AJOL)

    50.9%) compensated shock (30.6%), prostration (29.1%) and symptomatic severe anaemia (14.9%). The case fatality rate (CFR) was 4.6% and the cure rate (CR) was 95.4%. Children with suspected severe acidosis and symptomatic severe ...

  11. Pattern and Trend of Severe and Malaria Morbidity Over Five Years ...

    African Journals Online (AJOL)

    Pattern and Trend of Severe and Malaria Morbidity Over Five Years in JImma Zone, Southwest Ethiopia. Lelisa Sena, Wondimu Tesgera. Abstract. No abstract - Available on PDF. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online.

  12. A novel carbon monoxide-releasing molecule fully protects mice from severe malaria.

    Science.gov (United States)

    Pena, Ana C; Penacho, Nuno; Mancio-Silva, Liliana; Neres, Rita; Seixas, João D; Fernandes, Afonso C; Romão, Carlos C; Mota, Maria M; Bernardes, Gonçalo J L; Pamplona, Ana

    2012-03-01

    Severe forms of malaria infection, such as cerebral malaria (CM) and acute lung injury (ALI), are mainly caused by the apicomplexan parasite Plasmodium falciparum. Primary therapy with quinine or artemisinin derivatives is generally effective in controlling P. falciparum parasitemia, but mortality from CM and other forms of severe malaria remains unacceptably high. Herein, we report the design and synthesis of a novel carbon monoxide-releasing molecule (CO-RM; ALF492) that fully protects mice against experimental CM (ECM) and ALI. ALF492 enables controlled CO delivery in vivo without affecting oxygen transport by hemoglobin, the major limitation in CO inhalation therapy. The protective effect is CO dependent and induces the expression of heme oxygenase-1, which contributes to the observed protection. Importantly, when used in combination with the antimalarial drug artesunate, ALF492 is an effective adjunctive and adjuvant treatment for ECM, conferring protection after the onset of severe disease. This study paves the way for the potential use of CO-RMs, such as ALF492, as adjunctive/adjuvant treatment in severe forms of malaria infection.

  13. Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Adabayeri, V; Goka, B Q

    1998-01-01

    BACKGROUND: Severe anaemia is a major complication of malaria but little is known about its pathogenesis. Experimental models have implicated tumour necrosis factor (TNF) in induction of bone-marrow suppression and eythrophagocytosis. Conversely, interleukin 10 (IL-10), which mediates feed...

  14. Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children

    DEFF Research Database (Denmark)

    Murungi, Linda M; Sondén, Klara; Llewellyn, David

    2016-01-01

    Severe malaria (SM) is a life-threatening complication of infection with Plasmodium falciparum Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging...... the development of vaccines to protect against SM....

  15. Severe malaria is associated with parasite binding to endothelial protein C receptor

    DEFF Research Database (Denmark)

    Turner, Louise; Lavstsen, Thomas; Berger, Sanne S

    2013-01-01

    . falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins...

  16. The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria.

    Science.gov (United States)

    Newton, Paul N; Barnes, Karen I; Smith, Peter J; Evans, Alicia C; Chierakul, Wirongrong; Ruangveerayuth, Ronatrai; White, Nicholas J

    2006-12-01

    Intravenous artesunate is commonly used in the emergency treatment of patients with severe falciparum malaria in Asia. The choice of doses used has been empirical. To inform dosage recommendations we assessed the pharmacokinetics of intravenous artesunate after the first dose. As part of a clinical trial of artesunate in adults with severe falciparum malaria in western Thailand, we assayed plasma concentrations of artesunate and the principal biologically active metabolite dihydroartemisinin (DHA) in 17 patients given an initial dose of 2.4 mg/kg body weight of intravenous artesunate. Drug levels were measured using high performance liquid chromatography with mass spectroscopy-electrospray ionisation detection. Median (range) observed DHA Cmax was 2128 (513-5789) nmol/L, elimination half-life was 0.34 (0.14-0.87) h, and the time to the last detectable DHA was 2 h. The large inter-individual variability (10 fold) in DHA Cmax and AUC in patients with potentially lethal, severe malaria, suggests that 2.4 mg/kg should be the minimum daily dose in severe malaria.

  17. Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, Annemarie R.; van Genderen, Perry J.; Visser, Leo G.; Bierman, Wouter F. W.; Clerinx, Jan; van Veldhuizen, Cees K. W.; de Vries, Peter J.

    2012-01-01

    Background: Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient

  18. Cost-efficacy of managing severe malaria in children in two district ...

    African Journals Online (AJOL)

    Most children (95.9%) were completely cured, 2.0% died and there were no neurological deficits over one month follow-up. We estimate the cost of hospital management of each episode of severe malaria at 26 000 – 36 000 F CFA and the overall direct costs (before and during hospitalisation) at 27 000 – 39 000 F CFA.

  19. A Review of Plasmodium coatneyi-Macaque Models of Severe Malaria.

    Science.gov (United States)

    Lombardini, E D; Gettayacamin, M; Turner, G D H; Brown, A E

    2015-11-01

    Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease. © The Author(s) 2015.

  20. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena

    2008-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has - besides of its well known...... with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...... expression in brain tissue was measured by real time PCR. RESULTS: Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect...

  1. Artemisinin derivatives versus quinine in treating severe malaria in children: a systematic review

    Directory of Open Access Journals (Sweden)

    de Frey Albie

    2008-10-01

    Full Text Available Abstract Background The efficacy of intravenous quinine, which is the mainstay for treating severe malaria in children, is decreasing in South East Asia and Africa. Artemisinin derivatives are a potential alternative to quinine. However, their efficacy compared to quinine in treating severe malaria in children is not clearly understood. The objective of this review was to assess the efficacy of parenteral artemisinin derivatives versus parenteral quinine in treating severe malaria in children. Methods All randomized controlled studies comparing parenteral artemisinin derivatives with parenteral quinine in treating severe malaria in children were included in the review. Data bases searched were: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007, MEDLINE (1966 to February 2008, EMBASE (1980 to February 2008, and LILACS (1982 to February 2008. Dichotomous variables were compared using risk ratios (RR and the continuous data using weighted mean difference (WMD. Results Twelve trials were included (1,524 subjects. There was no difference in mortality between artemisinin derivatives and quinine (RR = 0.90, 95% CI 0.73 to 1.12. The artemisinin derivatives resolved coma faster than quinine (WMD = -4.61, 95% CI: -7.21 to -2.00, fixed effect model, but when trials with adequate concealment only were considered this differences disappeared. There was no statistically significant difference between the two groups in parasite clearance time, fever clearance time, incidence of neurological sequelae and 28th day cure rate. One trial reported significantly more local reactions at the injection site with intramuscular quinine compared to artemether. None of the trials was adequately powered to demonstrate equivalence. Conclusion There was no evidence that treatment of children with severe malaria with parenteral artemisinin derivatives was associated with lower mortality or long-term morbidity compared to parenteral quinine

  2. Effect of quinine and artesunate combination therapy on platelet count of children with severe malaria.

    Science.gov (United States)

    Gupta, Parul; Narang, Manish; Gomber, Sunil; Saha, Rumpa

    2017-05-01

    There are several case reports of quinine-induced thrombocytopenia but no clinical trials to ascertain its incidence and significance in severe malaria. The primary objective was to assess the effect of quinine on the platelet count in children with severe malaria and to compare it with artesunate combination therapy (ACT), and the secondary objective was to assess outcome of treatment with quinine and ACT. An open-labelled, randomised, controlled trial was undertaken in 100 children aged 6 months to 12 years who were diagnosed with malaria by microscopy and/or rapid diagnostic test kits with at least one WHO clinical or laboratory criterion for severe malaria. All subjects were commenced on either quinine or ACT. Clindamycin was added to artesunate as a combination drug (ACT). It was also given to patients on quinine to avoid its confounding effect on the results. Platelet counts were undertaken every 24 hours for 7 consecutive days, temperature and coma score (Blantyre coma score ≥3 in children 4 years) was recorded 6-hourly and peripheral smears were taken 12-hourly until two consecutively negative smears were obtained. The primary outcome was a fall in the platelet count by ≥20% from the time of drug initiation until day 7. The secondary outcome was comparison of the efficacy, parasite clearance time, fever clearance time, coma recovery time and adverse effects of quinine vs ACT. 30.4% patients in the quinine group (n = 48) had ≥20% fall in platelet count and 10.8% of patients in the ACT group (n = 46) (P = 0.02). Despite the fall in platelet count, there was no bleeding. The efficacy of ACT was significantly better than quinine but the other treatment outcomes showed insignificant difference. Quinine should be used with caution in patients with severe malaria because of the potential risk of quinine-induced thrombocytopenia.

  3. Severe imported falciparum malaria: a cohort study in 400 critically ill adults.

    Directory of Open Access Journals (Sweden)

    Fabrice Bruneel

    Full Text Available BACKGROUND: Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit. METHODOLOGY AND PRINCIPAL FINDINGS: Retrospective review of severe Plasmodium falciparum malaria episodes according to the 2000 World Health Organization definition and requiring admission to the intensive care unit. Data were collected from medical charts using standardised case-report forms, in 45 French intensive care units in 2000-2006. Risk factors for in-hospital mortality were identified by univariate and multivariate analyses. Data from 400 adults admitted to the intensive care unit were analysed, representing the largest series of severe imported malaria to date. Median age was 45 years; 60% of patients were white, 96% acquired the disease in sub-Saharan Africa, and 65% had not taken antimalarial chemoprophylaxis. Curative quinine treatment was used in 97% of patients. Intensive care unit mortality was 10.5% (42 deaths. By multivariate analysis, three variables at intensive care unit admission were independently associated with hospital death: older age (per 10-year increment, odds ratio [OR], 1.72; 95% confidence interval [95%CI], 1.28-2.32; P = 0.0004, Glasgow Coma Scale score (per 1-point decrease, OR, 1.32; 95%CI, 1.20-1.45; P<0.0001, and higher parasitemia (per 5% increment, OR, 1.41; 95%CI, 1.22-1.62; P<0.0001. CONCLUSIONS AND SIGNIFICANCE: In a large population of adults treated in a non-endemic industrialized country, severe malaria still carried a high mortality rate. Our data, including predictors of death, can probably be generalized to other non-endemic countries where high-quality healthcare is available.

  4. Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia.

    Science.gov (United States)

    Maude, Richard J; Silamut, Kamolrat; Plewes, Katherine; Charunwatthana, Prakaykaew; Ho, May; Abul Faiz, M; Rahman, Ridwanur; Hossain, Md Amir; Hassan, Mahtab U; Bin Yunus, Emran; Hoque, Gofranul; Islam, Faridul; Ghose, Aniruddha; Hanson, Josh; Schlatter, Joel; Lacey, Rachel; Eastaugh, Alison; Tarning, Joel; Lee, Sue J; White, Nicholas J; Chotivanich, Kesinee; Day, Nicholas P J; Dondorp, Arjen M

    2014-01-01

    Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine. Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate. Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0-28 025) parasites/µL × hour in patients treated with levamisole and 5489 (IQR, 192-25 848) parasites/µL × hour in controls (P = .25). The "sequestration ratios" at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P > .40). The median time to normalization of plasma lactate (levamisole vs 28 (IQR, 12-36) hours without levamisole (P = .15). There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole.

  5. Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria.

    Science.gov (United States)

    Barber, Bridget E; Grigg, Matthew J; William, Timothy; Piera, Kim A; Boyle, Michelle J; Yeo, Tsin W; Anstey, Nicholas M

    2017-06-15

    In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [rs] = 0.36; P malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

  6. The interaction between malaria and human immunodeficiency virus infection in severely anaemic Malawian children: a prospective longitudinal study.

    Science.gov (United States)

    Kyeyune, Francis X; Calis, Job C J; Phiri, Kamija S; Faragher, Brian; Kachala, David; Brabin, Bernard J; van Hensbroek, Michaël Boele

    2014-06-01

    Malaria and human immunodeficiency virus (HIV) infection are co-prevalent in sub-Saharan Africa and cause severe anaemia in children. Interactions between these infections occur in adults, although these are less clear in children. The aim of study was to determine their interaction in a cohort of severely anaemic children. Severely anaemic Malawian children were enrolled, tested for HIV and malaria, transfused and followed for 18 months for malaria incidence. Antiretrovirals were not widely available in Malawi during the study period. Of 381 children (haemoglobin <5 g/dl), 357 consented for HIV testing, 12.6% were HIV-infected, and 59.5% had malaria parasitaemia. At enrolment, HIV-infected children had similar malaria parasitaemia prevalence (59.1% vs. 58.7%; P = 0.96) and parasite density (geometric mean [parasites/μl] 6903 vs. 12417; P = 0.18) as HIV-negative children. There were no differences in mean CD4%, or prevalence of severe immunosuppression, between those with and without malaria parasitaemia. Plasma viral load correlated negatively with log parasitaemia (r = -0.78; P = 0.01). During follow-up, HIV-infected children did not experience more frequent parasitaemias or symptomatic malaria episodes. Adjusted risk estimates (95% CI) for malaria parasitaemia in HIV-infected children at 6 and 18 months follow-up were 0.39 (0.13-1.14) and 0.40 (0.11-1.51), respectively. Severely anaemic HIV-infected children showed no increased susceptibility to asymptomatic or symptomatic malaria during or following their anaemic episode, although all experienced lower parasite prevalence during follow-up. This contrasts with data in adults and may relate to the malaria immunity of young children which is insufficiently developed to be impaired by HIV. The negative correlation between viral load and malaria parasitaemia remains unexplained. © 2014 John Wiley & Sons Ltd.

  7. Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage

    Directory of Open Access Journals (Sweden)

    Fegan Greg W

    2009-12-01

    Full Text Available Abstract Background Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. Methods An everyday memory battery was administered on 152 children with cerebral malaria (CM (mean age, 7 y 4 months [SD 13 months]; 77 males 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males with malaria plus complex seizures (MS and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males unexposed to either condition. Results CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures. Discussion The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia that are strongly associated with impaired everyday memory.

  8. Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage.

    Science.gov (United States)

    Kihara, Michael; Carter, Julie A; Holding, Penny A; Vargha-Khadem, Faraneh; Scott, Rod C; Idro, Richard; Fegan, Greg W; de Haan, Michelle; Neville, Brian G R; Newton, Charles R J C

    2009-12-01

    Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males) 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males) with malaria plus complex seizures (MS) and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males) unexposed to either condition. CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures. The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia) that are strongly associated with impaired everyday memory.

  9. Hypoxemia predicts death from severe falciparum malaria among ...

    African Journals Online (AJOL)

    Background: Oxygen saturation is a good marker for disease severity in emergency care. However, studies have not considered its use in identifying individuals infected with Plasmodium falciparum at risk of deaths. Objective: To investigate the prevalence and predictive value of hypoxaemia for deaths in under-5s with ...

  10. Clinical Profile of Plasmodium vivax Malaria in Children and Study of Severity Parameters in relation to Mortality: A Tertiary Care Centre Perspective in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Manju Kumari

    2014-01-01

    Full Text Available Background. While research on P. vivax is scarce because it is considered benign, it has become evident with implementation of molecular diagnosis that it can also cause multiple organ dysfunction and severe life-threatening disease. Objective. To study clinical presentations and complications of P. vivax malaria and mortality correlation to severity parameters as defined by WHO criteria for severe malaria. Materials and methods. This study was conducted in a tertiary care centre in Mumbai. Confirmed P. vivax cases were enrolled and studied for their clinical profile, and WHO severity parameters were tested for their frequency and association to mortality. Result. The most common presentation was fever followed by pallor. 26% of the cases satisfied one or more criteria of WHO severity parameters. 2 cases died; both had pulmonary edema and bleeding. The major predictor of mortality among these predefined severity criteria was pulmonary edema/ARDS. Patients with severe anemia, circulatory collapse, and repeated generalized convulsion had 100% survival rate. Leukopenia was present in 10% of the cases. Both cases with mortality had leukopenia. Conclusion. P. vivax monoinfection tends to have severe complications in children. There is a need to review severity criteria for P. vivax malaria.

  11. Prognostic value of clinical and parasitological signs for severe malaria in patients from Colombia Utilidad pronóstica para malaria grave de signos clínicos y parasitológicos en pacientes de Colombia

    National Research Council Canada - National Science Library

    Silvia Blair-Trujillo; Alberto Tobón-Castaño; Cecilia Giraldo-Castro

    2011-01-01

    Introduction. Early recognition of danger signs in patients with malaria can reduce complications and deaths, but little is known about its prognostic value for severe malaria, especially in areas of low...

  12. The association between cognition and academic performance in Ugandan children surviving malaria with neurological involvement.

    Science.gov (United States)

    Bangirana, Paul; Menk, Jeremiah; John, Chandy C; Boivin, Michael J; Hodges, James S

    2013-01-01

    The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This study's objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement. 62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention) and academic performance (reading, spelling, arithmetic) three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA) and structural equation models (SEM) were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance. In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, pWorking memory, visual spatial ability and learning were the best predictors of academic performance. Academic performance is strongly associated with the latent variable labelled "cognitive ability" which captures most of the variation in the individual specific cognitive outcome measures. Working memory, visual spatial skills, and learning together stood out as the best combination to predict academic performance.

  13. Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.

    Directory of Open Access Journals (Sweden)

    Sarah Auburn

    2010-04-01

    Full Text Available With the functional demonstration of a role in erythrocyte invasion by Plasmodium falciparum parasites, implications in the aetiology of common conditions that prevail in individuals of African origin, and a wealth of pharmacological knowledge, the stimulatory G protein (Gs signal transduction pathway presents an exciting target for anti-malarial drug intervention. Having previously demonstrated a role for the G-alpha-s gene, GNAS, in severe malaria disease, we sought to identify other important components of the Gs pathway. Using meta-analysis across case-control and family trio (affected child and parental controls studies of severe malaria from The Gambia and Malawi, we sought evidence of association in six Gs pathway candidate genes: adenosine receptor 2A (ADORA2A and 2B (ADORA2B, beta-adrenergic receptor kinase 1 (ADRBK1, adenylyl cyclase 9 (ADCY9, G protein beta subunit 3 (GNB3, and regulator of G protein signalling 2 (RGS2. Our study amassed a total of 2278 cases and 2364 controls. Allele-based models of association were investigated in all genes, and genotype and haplotype-based models were investigated where significant allelic associations were identified. Although no significant associations were observed in the other genes, several were identified in ADORA2A. The most significant association was observed at the rs9624472 locus, where the G allele (approximately 20% frequency appeared to confer enhanced risk to severe malaria [OR = 1.22 (1.09-1.37; P = 0.001]. Further investigation of the ADORA2A gene region is required to validate the associations identified here, and to identify and functionally characterize the responsible causal variant(s. Our results provide further evidence supporting a role of the Gs signal transduction pathway in the regulation of severe malaria, and request further exploration of this pathway in future studies.

  14. Prevalence of hypoglycemia among severe malaria children in a rural African population

    Directory of Open Access Journals (Sweden)

    Osonuga OA

    2017-09-01

    Full Text Available Objective: To determine the prevalence of hypoglycemia in severe malaria children in a rural African community. Methods: Thirty two children who fulfilled the inclusion criteria were recruited for the study from two hospitals with intensive care facilities. Blood sugar levels of the patients were monitored serially at admission and then every 4 hours (after admission for 24 hours using a glucometer; taking values <2.2 mmol/L as hypoglycemia. The children received intensive care according to WHO guidelines for severe malaria. Results: Fifteen out of 32 children recruited (representing 46.9% had hypoglycemia with about 60% under 5 years of age. The mean age of the children was (4.49暲2.89 years. The pre-correction and average post correction blood glucose levels were (2.04暲0.13 mmol/L and (3.18暲0.23 mmol/L, respectively. Conclusions: The result has demonstrated that about 1 in 2 children with severe malaria may suffer from hypoglycemia in an African rural environment hence there is a need for at least three-point glucose estimation (at recruitment, 4 hours following correction and the end of the 24 hours.

  15. Obesity and Diabetes as Risk Factors for Severe Plasmodium falciparum Malaria: Results From a Swedish Nationwide Study.

    Science.gov (United States)

    Wyss, Katja; Wångdahl, Andreas; Vesterlund, Maria; Hammar, Ulf; Dashti, Saduddin; Naucler, Pontus; Färnert, Anna

    2017-09-15

    Noncommunicable diseases and obesity are increasing in prevalence globally, also in populations at risk of malaria. We sought to investigate if comorbidity, in terms of chronic diseases and obesity, is associated with severe Plasmodium falciparum malaria. We performed a retrospective observational study in adults (≥18 years of age) diagnosed with malaria in Sweden between January 1995 and May 2015. We identified cases through the surveillance database at the Public Health Agency of Sweden and reviewed clinical data from 18 hospitals. Multivariable logistic regression was used to assess associations between comorbidities and severe malaria. Among 937 adults (median age, 37 years; 66.5% were male), patients with severe malaria had higher prevalence of chronic diseases (28/92 [30.4%]) compared with nonsevere cases (151/845 [17.9%]) (P = .004). Charlson comorbidity score ≥1 was associated with severe malaria (adjusted odds ratio [aOR], 2.63 [95% confidence interval {CI}, 1.45-4.77), as was diabetes among individual diagnoses (aOR, 2.98 [95% CI, 1.25-7.09]). Median body mass index was higher among severe (29.3 kg/m2) than nonsevere cases (24.7 kg/m2) (P Obesity was strongly associated with severe malaria, both independently (aOR, 5.58 [95% CI, 2.03-15.36]) and in combination with an additional metabolic risk factor (hypertension, dyslipidemia, or diabetes) (aOR, 6.54 [95% CI, 1.87-22.88]). The associations were observed among nonimmune travelers as well as immigrants from endemic areas. Comorbidities, specifically obesity and diabetes, are previously unidentified risk factors for severe malaria in adults diagnosed with P. falciparum. Noncommunicable diseases should be considered in the acute management and prevention of malaria.

  16. Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria

    DEFF Research Database (Denmark)

    Duffy, Michael F; Noviyanti, Rintis; Tsuboi, Takafumi

    2016-01-01

    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...

  17. Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Turner, Louise; Saguti, Fredy

    2012-01-01

    The clinical outcome of Plasmodium falciparum infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of P. falciparum infections is associated with the type of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed...... amplifying var subtype-specific loci covering most var/PfEMP1 subtypes. In addition, we characterized the near-full-length sequence of the most prominently expressed var genes in three patients diagnosed with severe anemia and/or cerebral malaria. The combined analysis showed that severe malaria syndromes......, including severe anemia and cerebral malaria, are associated with high transcript levels of PfEMP1 domain cassette 8-encoding var genes. Transcript levels of group A var genes, including genes encoding domain cassette 13, were also significantly higher in patients with severe syndromes compared with those...

  18. Interaction of malaria with a common form of severe thalassemia in an Asian population.

    Science.gov (United States)

    O'Donnell, A; Premawardhena, A; Arambepola, M; Samaranayake, R; Allen, S J; Peto, T E A; Fisher, C A; Cook, J; Corran, P H; Olivieri, Nancy F; Weatherall, D J

    2009-11-03

    In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and beta thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE beta thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE beta thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE beta thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE beta thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs.

  19. Deep brain stimulation improves survival in severe Parkinson's disease.

    Science.gov (United States)

    Ngoga, Desire; Mitchell, Rosalind; Kausar, Jamilla; Hodson, James; Harries, Anwen; Pall, Hardev

    2014-01-01

    Levodopa and other dopaminergic treatments have not had the expected effect on survival in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor function, motor fluctuations, health-related quality of life, and to reduce medication usage and drug-induced dyskinesia in patients with severe PD refractory to medical therapy. Little however, has been described on the impact of STN-DBS on the survival of these patients. We aim in this study to examine the impact of STN-DBS on the survival of patients with severe PD. Patients who were eligible for STN-DBS were given the choice of undergoing surgery or continuing on medical treatment. Those who exercised patient choice and preferred to continue with medical treatment formed a control population. All eligible patients seen in a 10-year period are included in this study. Our primary outcome measure is a difference in mortality between the two groups with a secondary measure of admission rates to residential (nursing home) care. 106 patients underwent STN-DBS, and 41 patients exercised patient choice and declined the procedure. The two groups were matched for age, gender, ethnicity, duration of disease, rates of pre-existing depression and Levodopa equivalent doses of anti-Parkinson's medications taken. Patients undergoing STN-DBS had significantly longer survival and were significantly less likely to be admitted to a residential care home than those managed purely medically. The statistical significance of these findings persisted after adjusting for potential confounding factors (survival: p=0.002, HR 0.29 (0.13 to 0.64) (residential care home admission: OR: 0.1 (95% CI 0.0 to 0.3; padvanced PD. The effect of potential bias factors is examined. The survival advantage may arise for several postulated reasons, ranging from improvement in axial functions, such as swallowing, to some as yet unrecognised benefit of reduction in dopaminergic medication. These

  20. Lack of Association of CD55 Receptor Genetic Variants and Severe Malaria in Ghanaian Children

    Directory of Open Access Journals (Sweden)

    Kathrin Schuldt

    2017-03-01

    Full Text Available In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.

  1. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Victoria Ryg-Cornejo

    2016-01-01

    Full Text Available Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.

  2. Early home treatment of childhood fevers with ineffective antimalarials is deleterious in the outcome of severe malaria

    Directory of Open Access Journals (Sweden)

    Olumese Peter E

    2008-07-01

    Full Text Available Abstract Background Early diagnosis and prompt treatment including appropriate home-based treatment of malaria is a major strategy for malaria control. A major determinant of clinical outcome in case management is compliance and adherence to effective antimalarial regimen. Home-based malaria treatment with inappropriate medicines is ineffective and there is insufficient evidence on how this contributes to the outcome of severe malaria. This study evaluated the effects of pre-hospital antimalarial drugs use on the presentation and outcome of severe malaria in children in Ibadan, Nigeria. Methods Two hundred and sixty-eight children with a median age of 30 months comprising 114 children with cerebral malaria and 154 with severe malarial anaemia (as defined by WHO were prospectively enrolled. Data on socio-demographic data, treatments given at home, clinical course and outcome of admission were collected and analysed. Results A total of 168 children had treatment with an antimalarial treatment at home before presenting at the hospital when there was no improvement. There were no significant differences in the haematocrit levels, parasite counts and nutritional status of the pre-hospital treated and untreated groups. The most commonly used antimalarial medicine was chloroquine. Treatment policy was revised to Artemesinin-based Combination Therapy (ACT in 2005 as a response to unacceptable levels of therapeutic failures with chloroquine, however chloroquine use remains high. The risk of presenting as cerebral malaria was 1.63 times higher with pre-hospital use of chloroquine for treatment of malaria, with a four-fold increase in the risk of mortality. Controlling for other confounding factors including age and clinical severity, pre-hospital treatment with chloroquine was an independent predictor of mortality. Conclusion This study showed that, home treatment with chloroquine significantly impacts on the outcome of severe malaria. This finding

  3. Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor.

    Directory of Open Access Journals (Sweden)

    Alfredo Mayor

    Full Text Available INTRODUCTION: Severe malaria has been attributed partly to the sequestration of Plasmodium falciparum-infected erythrocytes (IEs in the microvasculature of vital host organs. Identification of P. falciparum cytoadherence phenotypes that are associated with severe malaria may lead to the development of novel strategies against life-threatening malaria. METHODS AND FINDINGS: Forty-six P. falciparum isolates from Mozambican children under 5 years of age with severe malaria (cases were examined and compared to 46 isolates from sex and age matched Mozambican children with uncomplicated malaria (controls. Cytoadherence properties such as platelet-mediated clumping, rosetting and adhesion to purified receptors (CD36, ICAM1 and gC1qR, were compared between these matched pairs by non-parametric tests. The most common clinical presentation associated with severe malaria was prostration. Compared to matched controls, prevalence of platelet-mediated clumping was higher in cases (P = .019, in children presenting with prostration (P = .049 and in children with severe anaemia (P = .025. Prevalence of rosetting and gC1qR adhesion were also higher in isolates from cases with severe anemia and multiple seizures, respectively (P = .045 in both cases, than in controls. CONCLUSIONS: These data indicate a role for platelet-mediated clumping, rosetting and adhesion to gC1qR in the pathogenesis of severe malaria. Inhibition of these cytoadherence phenotypes may reduce the occurrence or improve the prognosis of severe malaria outcomes.

  4. In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children

    DEFF Research Database (Denmark)

    Staalsoe, Trine; Nielsen, Morten A; Vestergaard, Lasse S

    2003-01-01

    . Parasites isolated from young children with severe malaria (SM) tend to express a limited and conserved set of VSA (VSASM) that are both stronger and more commonly recognized by IgG in the plasma of malaria-exposed individuals than VSA (VSAUM) expressed by parasites causing uncomplicated malaria (UM...... and epidemiologically diverse areas of endemic parasite transmission. The described selection method appears a useful tool in the identification of genes encoding VSA involved in severe and life-threatening P. falciparum malaria....

  5. Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity

    Directory of Open Access Journals (Sweden)

    Ruangweerayut Ronnatrai

    2010-09-01

    Full Text Available Abstract Background Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GTn repeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription as well as polymorphism of TNF were investigated. Methods Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated Plasmodium falciparum malaria (UM and 80 cases with Plasmodium vivax malaria (VM, and 77 cases with severe or cerebral malaria (SM for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3% Thai, 243 (50.0% Burmese and 120 (24.7% Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand. Results The number of (GTn repeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S, medium (M and long (L GTn repeats. The genotype of (GTn repeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed. Conclusions Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria

  6. Developing and Testing a High-Fidelity Simulation Scenario for an Uncommon Life-Threatening Disease: Severe Malaria

    Directory of Open Access Journals (Sweden)

    Andrew Kestler

    2011-01-01

    Full Text Available Background. Severe malaria is prevalent globally, yet it is an uncommon disease posing a challenge to education in nonendemic countries. High-fidelity simulation (sim may be well suited to teaching its management. Objective. To develop and evaluate a teaching tool for severe malaria, using sim. Methods. A severe malaria sim scenario was developed based on 5 learning objectives. Sim sessions, conducted at an academic center, utilized METI ECS mannequin. After sim, participants received standardized debriefing and completed a test assessing learning and a survey assessing views on sim efficacy. Results. 29 participants included 3rd year medical students (65%, 3rd year EM residents (28%, and EM nurses (7%. Participants scored average 85% on questions related to learning objectives. 93% felt that sim was effective or very effective in teaching severe malaria, and 83% rated it most effective. All respondents felt that sim increased their knowledge on malaria. Conclusion. Sim is an effective tool for teaching severe malaria in and may be superior to other modalities.

  7. Sublingual sugar for hypoglycaemia in children with severe malaria: A pilot clinical study

    Directory of Open Access Journals (Sweden)

    Giani Sergio

    2008-11-01

    Full Text Available Abstract Background Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Methods Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations = 3.3 mmol/l (60 mg/dl within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late, maximal BGC gain (CGmax, and treatment delay. Results There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3–40. Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5–63.4. Conclusion Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.

  8. Nutritional status of children in a malaria meso endemic area: cross sectional study on prevalence, intensity, predictors, influence on malaria parasitaemia and anaemia severity.

    Science.gov (United States)

    Sumbele, Irene Ule Ngole; Bopda, Orelien S Mtopi; Kimbi, Helen Kuokuo; Ning, Teh Rene; Nkuo-Akenji, Theresa

    2015-11-05

    The contradictory results on the interaction between nutritional status and malaria warrants further investigation in various epidemiological settings, to assert the antagonistic or synergistic relationship. This study examines the prevalence, severity and predictors of malnutrition and its influence on malaria parasitaemia and anaemia severity in children in the Mount Cameroon area. A cross-sectional study involving 454 children ≤ 14 years was carried out from February to May 2013 in Muea community. Anthropometric measures of malnutrition (z-scores anaemia, malaria parasitaemia and predictors respectively. The overall prevalence of malnutrition was 22.8 %, with stunting being the most common form (17.1 %), followed by underweight (8.2 %) and wasting (5.5 %). Stunting was significantly higher (P anaemia as well as severities were significantly higher (P = 0.04 and P = 0.001 respectively) in those malnourished. The presence of stunting in the community significantly augmented the prevalence and clinical presentation of Plasmodium infection. Malnutrition enhanced the severity of anaemia in malaria parasite negative children hence, their health and growth potential needs to be improved upon.

  9. Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes

    DEFF Research Database (Denmark)

    Jensen, Anja T R; Magistrado, Pamela; Sharp, Sarah

    2004-01-01

    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....

  10. Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults

    LENUS (Irish Health Repository)

    Byakika-Kibwika, Pauline

    2012-04-27

    AbstractBackgroundSevere malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria.MethodsFourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg\\/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134).ResultsAll study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8–24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020–164000) ng\\/mL, terminal elimination half-life (T1\\/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290–111256) ng·h\\/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670–9530) ng\\/mL, with Tmax of 0.14 (0.6 – 6.07) hours and T1\\/2 of 1.31 (0.8–2.8) hours. Dihydroartemisinin AUC was 3492 (2183–6338) ng·h\\/mL. None of the participants reported adverse events.ConclusionsPlasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.

  11. Factors associated with severe malaria among children below ten years in Mutasa and Nyanga districts, Zimbabwe, 2014-2015.

    Science.gov (United States)

    Mutsigiri-Murewanhema, Faith; Mafaune, Patron Trish; Shambira, Gerald; Juru, Tsitsi; Bangure, Donewell; Mungati, More; Gombe, Notion Tafara; Tshimanga, Mufuta

    2017-01-01

    Severe malaria is a rare life threatening illness. Only a small proportion of patients with clinical malaria progress to this medical emergency. On reviewing 61 malaria death investigation forms submitted to the provincial office in 2014, 22(36%) were children below ten years who succumbed to severe malaria. Mutasa and Nyanga Districts reported 73% of these deaths. This study was conducted to determine factors associated with severe malaria so as to come up with evidence based interventions to prevent severe malaria and associated mortality. A 1:2 unmatched case control study was conducted. A case was defined as a child 10 years and below, who was admitted at Hauna (Mutasa) or Nyanga District Hospitals between September 2014 and May 2015 with a primary diagnosis of severe malaria. Controls were children of similar age with uncomplicated malaria. Permission to conduct the study was sought and granted by the Medical Research Council of Zimbabwe (Approval number B/874), Joint Research Ethics Committee, Health Studies Office and the Manicaland Directorate Institutional Review Board. Written informed consent was sought from all caregivers of enrolled children. Interviewer administered questionnaires were used to ascertain exposures. A total of 52 cases and 104 controls were enrolled into the study. The median age of cases was 4 years (Q1=3, Q3=9) and 6 years for controls (Q1=3, Q3=8). The Case Fatality Rate among cases was 28.8%. The independent risk factors for severe malaria were; distance >10km to the nearest health facility [Adjusted Odds Ratio (aOR)=14.35, 95% CI=1.30, 158.81], duration of symptoms before seeking medical care >2 days [aOR=9.03, 95% CI=2.21, 36.93], having comorbidities [aOR=5.38, 95% CI=1.90, 15.19], staying in a house under construction [aOR=4.51, 95%CI=1.80, 11.32] and duration of illness before receiving antimalarial medicines >24 hours [aOR=3.82, 95% CI=1.44, 10.12]. Owning at least one ITN in the household [aOR=0.32, 95% CI=0.11, 0.95] and

  12. HLA-A2 Supertype-Restricted Cell-Mediated Immunity by Peripheral Blood Mononuclear Cells Derived from Malian Children with Severe or Uncomplicated Plasmodium falciparum Malaria and Healthy Controls

    National Research Council Canada - National Science Library

    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

    2005-01-01

    ...) 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...

  13. G6PD A- deficiency and severe malaria in The Gambia: heterozygote advantage and possible homozygote disadvantage.

    Science.gov (United States)

    Sirugo, Giorgio; Predazzi, Irene M; Bartlett, Jacquelaine; Tacconelli, Alessandra; Walther, Michael; Williams, Scott M

    2014-05-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is frequent in Africa, because it confers resistance to Plasmodium falciparum malaria; however, the nature of the protection and the genotypes associated with it have been controversial. In 1972, Bienzle and others described protection from malaria in West African females heterozygous for G6PD A-. They determined that G6PD A- heterozygotes had lower parasite counts than A- homozygotes, hemizygous males, and normal individuals. However, other studies have reached different conclusions about the protective genotypes. DNA samples from 135 children with severe malaria and 146 children with mild malaria from The Gambia were genotyped for the G6PD A- mutation that is most frequent among Gambians (G6PD 968 T->C); there was a marked deficiency of heterozygotes and an excess of homozygotes with severe malaria, producing a strong deviation from Hardy-Weinberg equilibrium. Our results support the protective effect in G6PD A- heterozygous females and suggest that homozygotes might be more susceptible to severe malaria attacks.

  14. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria.

    Directory of Open Access Journals (Sweden)

    Aldiouma Guindo

    2007-03-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A- form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection.We conducted large case-control studies of the A- form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies.The A- form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females

  15. Association of cytokine and Toll-like receptor gene polymorphisms with severe malaria in three regions of Cameroon.

    Directory of Open Access Journals (Sweden)

    Tobias O Apinjoh

    Full Text Available P. falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical human genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity that would be invaluable for vaccine development. We investigated the effect of single nucleotide polymorphisms (SNPs on malaria pathology in a case- control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Twenty nine polymorphisms in cytokine and toll-like receptor (TLR genes as well as the sickle cell trait (HbS were assayed on the Sequenom iPLEX platform. Our results confirm the known protective effect of HbS against severe malaria and also reveal a protective effect of SNPs in interleukin-10 (IL10 cerebral malaria and hyperpyrexia. Furthermore, IL17RE rs708567 GA and hHbS rs334 AT individuals were associated with protection from uncomplicated malaria and anaemia respectively in this study. Meanwhile, individuals with the hHbS rs334 TT, IL10 rs3024500 AA, and IL17RD rs6780995 GA genotypes were more susceptible to severe malarial anaemia, cerebral malaria, and hyperpyrexia respectively. Taken together, our results suggest that polymorphisms in some immune response genes may have important implications for the susceptibility to severe malaria in Cameroonians. Moreover using uncomplicated malaria may allow us to identify novel pathways in the early development of the disease.

  16. The association between cognition and academic performance in Ugandan children surviving malaria with neurological involvement.

    Directory of Open Access Journals (Sweden)

    Paul Bangirana

    Full Text Available The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This study's objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement.62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention and academic performance (reading, spelling, arithmetic three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA and structural equation models (SEM were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance.In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, p<0.01 and Spelling (0.46, 0.13 to 0.78, p<0.01, Visual Spatial Skills was associated with Arithmetic (0.15, 0.03 to 0.26, p<0.05, and Learning was associated with Reading (0.06, 0.00 to 0.11, p<0.05. One latent cognitive factor was identified using EFA. The SEM found a strong association between this latent cognitive ability and each academic performance measure (P<0.0001. Working memory, visual spatial ability and learning were the best predictors of academic performance.Academic performance is strongly associated with the latent variable labelled "cognitive ability" which captures most of the variation in the individual specific

  17. Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

    Directory of Open Access Journals (Sweden)

    Adem Patricia

    2010-01-01

    Full Text Available Abstract Background Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further

  18. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Morten A; Staalsoe, Trine; Kurtzhals, Jørgen

    2002-01-01

    of immunity, as disease-causing parasites appear to be those not controlled by preexisting VSA-specific Abs. In this work we report that VSA expressed by parasites from young Ghanaian children with P. falciparum malaria were commonly and strongly recognized by plasma Abs from healthy children in the same area...... to limit the risk of severe disease by discriminating against the expression of VSA likely to cause life-threatening complications, such as cerebral malaria and severe anemia. Such VSA seem to be preferred by parasites infecting a nonimmune host, suggesting that VSA expression and switching are not random......In areas of endemic parasite transmission, protective immunity to Plasmodium falciparum malaria is acquired over several years with numerous disease episodes. Acquisition of Abs to parasite-encoded variant surface Ags (VSA) on the infected erythrocyte membrane is important in the development...

  19. [Case management and diagnosis of severe malaria in adults and the application of national guidelines in Burkina Faso].

    Science.gov (United States)

    Yaméogo, T M; Kyelem, C G; Ouédraogo, S M; Diallo, O J; Moyenga, L; Poda, G E A; Guiguemdé, T R

    2011-10-01

    The purpose of this study was to assess the application of national guidelines on the diagnosis and treatment of severe malaria in adults in Burkina Faso. We conducted a retrospective study of medical records of the patients admitted for severe malaria in the emergency service of the regional hospital of Fada N'Gourma in the east of Burkina Faso in the year 2008; 165 records were chosen by simple random sampling. We reported all the severe clinical and biological signs of malaria and its treatment. We compared them with the criteria of severe malaria diagnosis and its treatment according to the national guidelines. The mean age of patients was 38 ± 16.2 and male to female ratio was 0.96. The most frequent period of admissions was between July and October. Fever or recent past of fever was reported in 142 cases (86.1%). According to the two criteria for severe malaria (means existing of at least one of the severe signs associated and positive parasitemia with Falciparum plasmodium), we noted that only 74 cases had at least one of the severe signs (44.8%) which were: anemia (51.3%), cardiovascular collapse (7.9%), jaundice (7.3%), dyspnea (6.7%), impairment of consciousness (5.5%), prostration (5.5%), renal failure (4.8%), hypoglycemia (2.4%), hemorrhage (1.8%) and seizures (1.2%). The biological signs were not systematically searched. Parasitological exam was conducted in 91 cases (55.1%). Only 18 were positive (19.8%). In total, only 18 cases (10.9%) met the guidelines' criteria of severe malaria. The other cases were over-diagnosed; note that the investigation was not complete for 74 of these cases (50.3%). Among the 165 cases, the treatment was appropriate in 146 (88.5%) and 19 cases (11.5%) didn't receive treatment for malaria. So much we observed an over diagnosis of severe malaria in adults that we can suggest an under diagnosis of the disease due to the lack of biological investigations.

  20. [Children hospitalized with severe malaria in Kinshasa (Democratic Republic of the Congo): Household characteristics and factors associated with mortality].

    Science.gov (United States)

    Ilunga-Ilunga, F; Levêque, A; Donnen, P; Dramaix, M

    2015-01-01

    Malaria is a major health problem in tropical Africa. In DRC, little is known about the characteristics of households of children with severe malaria or the factors associated with its lethality, especially relative to hospital status. This study of 9 hospitals of the city-province of Kinshasa studied 1350 children younger than 15 years and hospitalized for severe malaria from January to November 2011. More than three quarters of children admitted to public (state) and church hospitals were from poor households and with uneducated mothers (P 2 (OR = 3.5), z-score of weight-for-age ≤-2 (OR = 3.5), delay in seeking medical care (OR = 4.9), body temperature ≥40°C (OR = 2.9), respiratory distress (OR = 1.9) and home rental (versus ownership) a tenant (OR = 2.8), and anorexia was a protective factor (odds ratio = 0.5). Severe cases of malaria are rife in poor households and periurban residential areas. Orienting prevention, control, and care- according to the vulnerability of affected households and providing early treatment are imperative if we are to reduce mortality from malaria.

  1. Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis.

    Science.gov (United States)

    Sypniewska, Paulina; Duda, Jose F; Locatelli, Isabella; Althaus, Clotilde Rambaud; Althaus, Fabrice; Genton, Blaise

    2017-08-03

    The criteria for defining severe malaria have evolved over the last 20 years. We aimed to assess the strength of association of death with features currently characterizing severe malaria through a systematic review and meta-analysis. Electronic databases (Medline, Embase, Cochrane Database of Systematic Reviews, Thomson Reuters Web of Knowledge) were searched to identify publications including African children with severe malaria. PRISMA guidelines were followed. Selection was based on design (epidemiological, clinical and treatment studies), setting (Africa), participants (children malaria), outcome (survival/death rate), and prognostic indicators (clinical and laboratory features). Quality assessment was performed following the criteria of the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Odds ratios (ORs) were calculated for each study and prognostic indicator, and, when a test was assessed in at least two studies, pooled estimates of ORs were computed using fixed- or random-effects meta-analysis. A total of 601 articles were identified and screened and 30 publications were retained. Features with the highest pooled ORs were renal failure (5.96, 95% CI 2.93-12.11), coma score (4.83, 95% CI 3.11-7.5), hypoglycemia (4.59, 95% CI 2.68-7.89), shock (4.31, 95% CI 2.15-8.64), and deep breathing (3.8, 95% CI 3.29-4.39). Only half of the criteria had an OR > 2. Features with the lowest pooled ORs were impaired consciousness (0.58, 95% CI 0.25-1.37), severe anemia (0.76, 95% CI 0.5- 1.13), and prostration (1.12, 95% CI 0.45-2.82). The findings of this meta-analysis show that the strength of association between the criteria defining severe malaria and death is quite variable for each clinical and/or laboratory feature (OR ranging from 0.58 to 5.96). This ranking allowed the identification of features weakly associated with death, such as impaired consciousness and prostration, which could assist to improve case definition, and thus optimize

  2. Adherence to national guidelines for the diagnosis and management of severe malaria: a nationwide, cross-sectional survey in Malawi, 2012.

    Science.gov (United States)

    Shah, Monica P; Briggs-Hagen, Melissa; Chinkhumba, Jobiba; Bauleni, Andy; Chalira, Alfred; Moyo, Dubulao; Dodoli, Wilfred; Luhanga, Misheck; Sande, John; Ali, Doreen; Gutman, Julie; Mathanga, Don P; Lindblade, Kim A

    2016-07-19

    Severe malaria has a case fatality rate of 10-20 %; however, few studies have addressed the quality of severe malaria case management. This study evaluated the diagnostic and treatment practices of malaria patients admitted to inpatient health facilities (HF) in Malawi. In July-August 2012, a nationwide, cross-sectional survey of severe malaria management was conducted in 36 HFs selected with equal probability from all eligible public sector HFs in Malawi. Patient records from all admissions during October 2011 and April 2012 (low and high season, respectively) were screened for an admission diagnosis of malaria or prescription of any anti-malarial. Eligible records were stratified by age (malaria was defined by admission diagnosis or documentation of at least one sign or symptom of severe malaria. Treatment with intravenous (IV) quinine or artesunate was considered correct. Patients without documentation of severe malaria were analysed as uncomplicated malaria patients; treatment with an artemisinin-based combination therapy (ACT) or oral quinine based on malaria test results was considered correct. All analyses accounted for HF level clustering and sampling weights. The analysis included 906 records from 35 HFs. Among these, 42 % (95 % confidence interval [CI] 35-49) had a severe malaria admission diagnosis and 50 % (95 % CI 44-57) had at least one severe malaria sign or symptom documented. Severe malaria patients defined by admission diagnosis (93, 95 % CI 86-99) were more likely to be treated correctly compared to patients defined by a severe sign (82, 95 % CI 75-89) (p malaria patients, 26 % (95 % CI 18-35) were correctly treated and 53 % (95 % CI 42-64) were adequately treated with IV quinine alone or in combination with an ACT or oral quinine. A majority of patients diagnosed with severe malaria received the recommended IV therapy in accordance with national treatment guidelines. However, the inconsistencies between diagnosis of severe malaria

  3. Neurocognitive domains affected by cerebral malaria and severe malarial anemia in children.

    Science.gov (United States)

    Bangirana, Paul; Opoka, Robert O; Boivin, Michael J; Idro, Richard; Hodges, James S; John, Chandy C

    2016-02-01

    This study assessed the effects of cerebral malaria (CM) and severe malarial anemia (SMA) on individual neurocognitive domains. Eighty children with CM, 86 with SMA, and 61 community children (CC) were assessed for gross motor skills, fine motor skills, visual reception, receptive language, and expressive language a week after discharge (CM or SMA) or at enrolment (CC), and 6 and 12 months later. At 12-months follow-up, children with CM had significantly lower scores than CC for all outcomes. Children with SMA had significantly lower scores than CC for visual reception, receptive language, and expressive language, and scores that were lower but did not reach significance for gross and fine motor skills. Children with CM had significantly lower scores than children with SMA for fine motor skills. Children with SMA and CM have long-term impairment in multiple neurocognitive domains. Fine motor skills may be affected more profoundly in CM than SMA.

  4. Resolution pattern of jaundice among children presenting with severe malaria in rural South-West Nigeria.

    Science.gov (United States)

    Osonuga, O A; Osonuga, A; Osonuga, A A; Osonuga, I O

    2012-07-01

    To compare the pattern of jaundice resolution among children with severe malaria treated with quinine and artemether. Thirty two children who fulfilled the inclusion criteria were recruited for the study from two hospitals with intensive care facilities. They were divided into two groups; 'Q' and 'A', receiving quinine and artemether, respectively. Jaundice was assessed by clinical examination. Sixteen out of 32 children recruited (representing 50%) presented with jaundice on the day of recruitment. The mean age was (7.00°C2.56) years. On day 3, four patients in 'A' and six patients in 'Q' had jaundice. By day 7, no child had jaundice. The study has shown that both drugs resolve jaundice although artemether relatively resolves it faster by the third day.

  5. A study protocol for a randomised open-label clinical trial of artesunate-mefloquine versus chloroquine in patients with non-severe Plasmodium knowlesi malaria in Sabah, Malaysia (ACT KNOW trial).

    Science.gov (United States)

    Grigg, M J; William, T; Dhanaraj, P; Menon, J; Barber, B E; von Seidlein, L; Rajahram, G; Price, R N; Anstey, N M; Yeo, T W

    2014-08-19

    Malaria due to Plasmodium knowlesi is reported throughout South-East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates every 24 h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits. P. knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or P. vivax, with a high proportion of the latter two species being chloroquine-resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all Plasmodium species. ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24 h between treatment arms (clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (α 0.05) to determine the primary end point using intention-to-treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis. This study has been approved by relevant institutional ethics committees in Malaysia and Australia. Results will be disseminated to inform

  6. Comparative pharmacokinetics of intramuscular artesunate and artemether in patients with severe falciparum malaria.

    Science.gov (United States)

    Hien, T T; Davis, T M E; Chuong, L V; Ilett, K F; Sinh, D X T; Phu, N H; Agus, C; Chiswell, G M; White, N J; Farrar, J

    2004-11-01

    The first-dose pharmacokinetic properties of intramuscular (i.m.) artesunate (ARTS; 2.4 mg/kg immediately [stat], followed by 1.2 mg/kg i.m. daily) and artemether (ARM; 3.2 mg/kg i.m. stat, followed by 1.6 mg/kg i.m. daily) were compared in Vietnamese adults with severe falciparum malaria. A total of 19 patients were studied; 9 received ARTS, and 10 received ARM. ARTS was absorbed very rapidly; concentrations in plasma peaked between 1,362 and 8,388 nmol/liter (median, 5,710 nmol/liter) within 20 min of injection and then declined with a median (range) half-life (t(1/2)) of 30 (3 to 67) min. ARTS was hydrolyzed rapidly and completely to the biologically active metabolite dihydroartemisinin (DHA). Peak DHA concentrations in plasma ranged between 1,718 and 7,080 nmol/liter (median, 3,060 nmol/liter) and declined with a t(1/2) of 52 (26 to 69) min. In contrast, ARM was slowly and erratically absorbed. The absorption profile appeared biphasic. Maximum ARM concentrations in plasma ranged between 67 nmol/liter (a value close to the 50% inhibitory concentration for some Plasmodium falciparum isolates) and 1,631 nmol/liter (median, 574 nmol/liter) and occurred at a median (range) of 10 (1.5 to 24) h. There was relatively little conversion to DHA. After i.m. injection in cases of severe malaria, absorption of the water-soluble ARTS is rapid and extensive, whereas the oil-based ARM is slowly and erratically absorbed, with relatively little conversion to the more active DHA. On the basis of this pharmacological study, parenteral ARTS is preferable to ARM as an initial antimalarial therapy, particularly in the most seriously ill patients. These findings should be formally assessed by a randomized clinical trial.

  7. Major burden of severe anemia from non-falciparum malaria species in Southern Papua: a hospital-based surveillance study.

    Science.gov (United States)

    Douglas, Nicholas M; Lampah, Daniel A; Kenangalem, Enny; Simpson, Julie A; Poespoprodjo, Jeanne R; Sugiarto, Paulus; Anstey, Nicholas M; Price, Ric N

    2013-12-01

    The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia. Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81-9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16-9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44-9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49-9.57]); p-value for all comparisons malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99-3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00-2.23), 1.87 (95% CI 1.74-2.01), and 2.18 (95% CI 1.76-2.67), respectively, pcause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity.

  8. Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters.

    Science.gov (United States)

    Milner, Danny A; Pochet, Nathalie; Krupka, Malkie; Williams, Chris; Seydel, Karl; Taylor, Terrie E; Van de Peer, Yves; Regev, Aviv; Wirth, Dyann; Daily, Johanna P; Mesirov, Jill P

    2012-01-01

    In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking. We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system. The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome.

  9. Severe malaria--analysis of prognostic symptoms and signs in 169 patients treated in Gdynia in 1991-2005.

    Science.gov (United States)

    Goljan, Jolanta; Nahorski, Wacław Leszek; Wroczyńska, Agnieszka; Felczak-Korzybska, Iwona; Pietkiewicz, Halina

    2006-01-01

    In the period 1991-2005, 169 patients with the diagnosis of malaria were hospitalized in the Department of Tropical and Parasitic Diseases, Institute of Maritime and Tropical Medicine in Gdynia (from 2003--the Academic Centre of Maritime and Tropical Medicine, Medical University of Gdańsk). All the cases were analysed for severity, occurrence of complications and permanent sequelae of the disease. According to the criteria set by the WHO (5), malaria was classified as severe in 36 cases. All of them were Plasmodium falciparum infections or mixed infections: P. f. and another species of the parasite. Patients in this group developed a number of complications, inter alia shock, acute respiratory distress syndrome (ARDS), acute renal failure, blackwater fever, severe anemia, disseminated intravascular coagulation, myocarditis, consciousness disorders of varied degree, acute transient psychoses, and exacerbation of ischemic heart disease. In one case of a pregnant woman, necrosis of the fetus occurred in the course of disease in the 4th month of pregnancy. Moreover, meningoencephalitis was diagnosed in two patients--in one of them concurrently with symptoms and signs of malaria, while in the other one-3 weeks after the symptoms subsided. In 6 patients, permanent sequelae of the disease developed and in 4 patients the disease was fatal. The cause of death was multi-organ failure, with the first sign of poor prognosis being rapidly progressing renal failure resistant to treatment in three men; in one case death resulted from cerebral malaria. In cases of suspected malaria, relapsing malaria or in mixed infections, molecular testing was a valuable complementary tool of diagnosis, which helped in beginning the appropriate treatment.

  10. Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters.

    Directory of Open Access Journals (Sweden)

    Danny A Milner

    Full Text Available In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking.We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system.The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome.

  11. Comparison of Cox and Gray's survival models in severe sepsis

    DEFF Research Database (Denmark)

    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate.......Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  12. Malária grave importada: relato de caso Severe imported malaria: case report

    Directory of Open Access Journals (Sweden)

    Alessandra Alves

    2007-06-01

    intensivo rápidos, pois o atraso aumenta a morbimortalidade do paciente.BACKGROUND AND OBJECTIVES: Malaria is still considered a major global health problem. The severity form of the disease is caused, mainly by P. falciparum and may occur together with cerebral, kidney, pulmonary, hematologic, circulatory and hepatic complications. This report is about a patient with a case of severe imported malaria. CASE REPORT: A 30-years-old man, mulatto, Philippine, sailor, coming from a ship arriving from Nigeria, with a history of abdominal pain on the right hypochondrium, jaundice, fever, decreased in the consciousness. Lab tests made upon his admission showed hyperbilirubinemia at a level of 50 mg/dL, severe metabolic acidosis, thrombocytopenia, creatinine levels of 5.6 mg/dL and leukocytosis with deviation through metamyelocytes. The APACHE II score was 37, with death estimated risk of 88%. During his stay at the hospital, P. Falciparum Malaria was diagnosed through the thick drop test. And, even with the adequate anti-malaria therapy, the patient’s condition evolved to an acute renal failure requiring hemodialis; acute respiratory distress syndrome (ARDS; septic shock, and hematological disorders, forming a multiple organ dysfunction syndrome (MODS. After being discharged from the hospital, the patient did not present any cerebral, pulmonary or kidney sequel. CONCLUSIONS: From the criteria described in medical literature to define critical malaria, the patient fulfilled the following: acute renal failure, ARDS, metabolic acidosis, altered level of consciousness, macroscopic hemoglobinuria, hyperparasitism and hyperbilirubinemia, related to a lethality rate of over 10%, depending on early treatment and available resources. Severe malaria requires fast diagnosis allied to a quick access to an intensive care treatment, since any delay increases the morbid-mortality of the disease.

  13. Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania

    DEFF Research Database (Denmark)

    Hansson, Helle Holm; Turner, Louise; Møller, Line

    2015-01-01

    in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria. CONCLUSION: Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming...

  14. Using the PfEMP1 head structure binding motif to deal a blow at severe malaria.

    Directory of Open Access Journals (Sweden)

    Manuel E Patarroyo

    Full Text Available Plasmodium falciparum (Pf malaria causes 200 million cases worldwide, 8 million being severe and complicated leading to ∼1 million deaths and ∼100,000 abortions annually. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1 has been implicated in cytoadherence and infected erythrocyte rosette formation, associated with cerebral malaria; chondroitin sulphate-A attachment and infected erythrocyte sequestration related to pregnancy-associated malaria and other severe forms of disease. An endothelial cell high activity binding peptide is described in several of this ∼300 kDa hypervariable protein's domains displaying a conserved motif (GACxPxRRxxLC; it established H-bonds with other binding peptides to mediate red blood cell group A and chondroitin sulphate attachment. This motif (when properly modified induced PfEMP1-specific strain-transcending, fully-protective immunity for the first time in experimental challenge in Aotus monkeys, opening the way forward for a long sought-after vaccine against severe malaria.

  15. The reliability of the physical examination to guide fluid therapy in adults with severe falciparum malaria: an observational study

    NARCIS (Netherlands)

    Hanson, Josh; Lam, Sophia W. K.; Alam, Shamsul; Pattnaik, Rajyabardhan; Mahanta, Kishore C.; Uddin Hasan, Mahatab; Mohanty, Sanjib; Mishra, Saroj; Cohen, Sophie; Day, Nicholas; White, Nicholas; Dondorp, Arjen

    2013-01-01

    Adults with severe malaria frequently require intravenous fluid therapy to restore their circulating volume. However, fluid must be delivered judiciously as both under- and over-hydration increase the risk of complications and, potentially, death. As most patients will be cared for in a

  16. The Clinical Pattern and Complications of Severe Malaria in Parts of ...

    African Journals Online (AJOL)

    The medical records of all cases of malaria admitted to Aboh Mbaise General Hospital, Imo State, Nigeria over a three year period( from 2005 to 2007) were analyzed in retrospect. During the study period, 246 patients were diagnosed with malaria. The history of fever was generally present and in 78.8% of the cases it was ...

  17. Diagnosis, prognosis and treatment of severe falciparum malaria in African children

    NARCIS (Netherlands)

    Hendriksen, I.C.E.

    2012-01-01

    De behandeling van Afrikaanse kinderen tegen malaria met artesunaat in plaats van kinine vermindert de sterfte met 22,5 procent. Bovendien heeft artesunaat minder bijwerkingen en is het makkelijker toe te dienen. Bijna een miljoen Afrikaanse kinderen sterven jaarlijks aan malaria. Ilse Hendriksen

  18. Manual blood exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals with imported severe Plasmodium falciparum malaria

    NARCIS (Netherlands)

    A.R. Kreeftmeijer-Vegter (Annemarie); M.M. de Melo (Mariana ); P.J. de Vries (Peter); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2013-01-01

    textabstractBackground: Exchange transfusion (ET) has remained a controversial adjunct therapy for the treatment of severe malaria. In order to assess the relative contribution of ET to parasite clearance in severe malaria, all patients receiving ET as an adjunct treatment to parenteral quinine or

  19. Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria

    DEFF Research Database (Denmark)

    Shabani, Estela; Hanisch, Benjamin; Opoka, Robert O.

    2017-01-01

    Background: Expression of group A and the A-like subset of group B Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying...... and especially CM as discriminated by retinopathy. Methods: We performed qRT-PCR targeting the different subsets of these var genes on samples from Ugandan children with CM (n = 98, of whom 50 had malarial retinopathy [RP] and 47 did not [RN]), severe malarial anemia (SMA, n = 47), and asymptomatic parasitemia...

  20. Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria.

    Science.gov (United States)

    Campos, A C; Brant, F; Miranda, A S; Machado, F S; Teixeira, A L

    2015-03-19

    Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Women survive severe famines and epidemics better than men

    DEFF Research Database (Denmark)

    Zarulli, Virginia; Barthold Jones, Julia; Oksuzyan, Anna

    Women live longer than men almost everywhere. Research provides evidence for both biological and behavioral factors modulating this gender gap, leaving open the question of what are its fundamental determinants. An unexplored source of information is when men and women experience extremely high...... better than men. In all populations they had lower mortality and, with the exception of one slave population, they lived longer. Infant ages contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality better than newborn boys. Our...... results lend support to the hypothesis that the gender survival gap has deep biological roots....

  2. Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice

    Directory of Open Access Journals (Sweden)

    Grau Georges E

    2007-12-01

    Full Text Available Abstract Background Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R and CM-susceptible (CM-S mice, upon infection by Plasmodium berghei ANKA (PbA. We investigated mouse transcriptional responses at early and late stages of infection by use of cDNA microarrays. Results Through a rigorous statistical approach with multiple testing corrections, we showed that PbA significantly altered brain gene expression in CM-R (BALB/c, and in CM-S (CBA/J and C57BL/6 mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation indicates that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In addition, our data suggest that cerebral malaria and Alzheimer's disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of β-amyloid proteins in brains of CM-S mice, but not of CM-R mice. Conclusion Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies.

  3. [Imported severe malaria in adults: a retrospective study of ten cases admitted to intensive care units in Casablanca].

    Science.gov (United States)

    Charra, B; Sodqi, M; Sandali, O; Nejmi, H; Hachimi, A; Ezzouine, H; Benslama, A; Himmich, H; Motaouakkil, S

    2007-03-01

    We report a retrospective study in the medical intensive care unit of the Casablanca Ibn-Rochd University hospital. All patients over 14 years of age with falciparum malaria, who were admitted to ICUs between 1996 and 2001, were included. The main epidemiological features, criteria of admission, treatment, and outcome were investigated. Ten patients were included for severe imported malaria. The mean age was 32+/-4 years. All patients had acquired falciparum malaria in sub-Saharan Africa. Chemoprophylaxis was inadequate in all patients. The mean time from symptom onset to treatment initiation was 9+/-2 days. Criteria of admission were impaired consciousness (7), acute renal failure (4), and respiratory distress (3). The most worrying factors were the severity of consciousness disorders, the acute respiratory distress syndrome, the metabolic acidosis, and the refractory shock. All patients presented with nosocomial respiratory infection related to Gram-negative bacilli, in the evolution. All patients received quinine therapy with loading dose and symptomatic treatment. Five patients died. The lethality of severe imported malaria is still high despite optimal management in ICUs. Improving chemoprophylaxis and an earlier diagnosis may reduce significantly the mortality rate.

  4. Post-treatment haemolysis in severe imported malaria after intravenous artesunate: case report of three patients with hyperparasitaemia

    Directory of Open Access Journals (Sweden)

    Rolling Thierry

    2012-05-01

    Full Text Available Abstract Parenteral artesunate has been shown to be a superior treatment option compared to parenteral quinine in adults and children with severe malaria. Little evidence, however, is available on long-term safety. Recently, cases of late-onset haemolysis after parenteral treatment with artesunate have been reported in European travellers with imported Plasmodium falciparum malaria. Therefore, an extended follow-up of adult patients treated for severe imported malaria was started in August 2011 at the University Medical Center Hamburg-Eppendorf. Until January 2012, three patients with hyperparasitaemia (range: 14-21% were included for analysis. In all three patients, delayed haemolysis was detected in the second week after the first dose of intravenous artesunate. Reticulocyte production index remained inadequately low in the 7 – 14 days following the first dose of artesunate despite rapid parasite clearance. Post-treatment haemolysis after parenteral artesunate may be of clinical relevance in particular in imported severe malaria characterized by high parasite levels. Extended follow-up of at least 30 days including controls of haematological parameters after artesunate treatment seems to be indicated. Further investigations are needed to assess frequency and pathophysiological background of this complication.

  5. Cytoadhesion to gC1qR through Plasmodium falciparum erythrocyte membrane protein 1 in severe malaria

    DEFF Research Database (Denmark)

    Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau

    2016-01-01

    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...

  6. Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study

    Science.gov (United States)

    Douglas, Nicholas M.; Lampah, Daniel A.; Kenangalem, Enny; Simpson, Julie A.; Poespoprodjo, Jeanne R.; Sugiarto, Paulus; Anstey, Nicholas M.; Price, Ric N.

    2013-01-01

    Background The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia. Methods and Findings Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons anemia (hemoglobin anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, panemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; panemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria

  7. Prevalence and Severity of Malaria Parasitemia among Children Requiring Emergency Blood Transfusion in a Tertiary Hospital in Imo State, Nigeria.

    Science.gov (United States)

    Austin, Nir; Adikaibe, Eab; Ethelbert, Oo; Chioma, Ue; Ekene, Nu

    2014-07-01

    Malaria is one of the most serious and complex health problems in Sub Saharan Africa. Anemia in Children with malaria may require blood transfusion and has been be associated with high mortality rates. The aim of this study is to evaluate the prevalence, pattern, and severity of malaria parasitemia among children 6 months to 14 years old, requiring blood transfusion. This is a cross-sectional study carried out at the children emergency unit of the Imo state University Teaching Hospital South East Nigeria. Data were analyzed using SPSS version 21, Chicago Il, USA. A total of 409 children were recruited into the study. The overall rate of malaria parasitemia was 83.1% (340/409) lower in males 81.6% (228/276) than in females 86.3% (112/133). The peak of parasitemia is similar in both sexes (5-9 years). Most of the children had medium levels of parasitemia, which decreased with increasing age. The proportion of children transfused also decreased with increasing age. At medium and high levels of parasitemia; in children below 5 years, 92.8% (132/142) were transfused while in 5 years and above only 79.6% (39/49) of the children were transfused. At medium level parasitemia the proportion of children transfused was significantly higher than those not transfused (P transfusion. Targeted measures toward primary prevention of malaria in children should be intensified as this will not only reduce morbidity and mortality of malaria, but will reduce the economic burden of the disease in Semi-rural and rural dwellers in Sub Saharan Africa.

  8. Clinical features of severe malaria associated with death: a 13-year observational study in the Gambia.

    Directory of Open Access Journals (Sweden)

    Muminatou Jallow

    Full Text Available Severe malaria (SM is a major cause of death in sub-Saharan Africa. Identification of both specific and sensitive clinical features to predict death is needed to improve clinical management.A 13-year observational study was conducted from 1997 through 2009 of 2,901 children with SM enrolled at the Royal Victoria Teaching Hospital in The Gambia to identify sensitive and specific predictors of poor outcome in Gambian children with severe malaria between the ages 4 months to 14 years. We have measured the sensitivity and specificity of clinical features that predict death or development of neurological sequelae.Impaired consciousness (odds ratio {OR} 4.4 [95% confidence interval {CI}, 2.7-7.3], respiratory distress (OR 2.4 [95%CI, 1.7-3.2], hypoglycemia (OR 1.7 [95%CI, 1.2-2.3], jaundice (OR 1.9 [95%CI, 1.2-2.9] and renal failure (OR 11.1 [95%CI, 3.3-36.5] were independently associated with death in children with SM. The clinical features that showed the highest sensitivity and specificity to predict death were respiratory distress (area under the curve 0.63 [95%CI, 0.60-0.65] and impaired consciousness (AUC 0.61[95%CI, 0.59-0.63], which were comparable to the ability of hyperlactatemia (blood lactate>5 mM to predict death (AUC 0.64 [95%CI, 0.55-0.72]. A Blantyre coma score (BCS of 2 or less had a sensitivity of 74% and specificity of 67% to predict death (AUC 0.70 [95% C.I. 0.68-0.72], and sensitivity and specificity of 74% and 69%, respectively to predict development of neurological sequelae (AUC 0.72 [95% CI, 0.67-0.76].The specificity of this BCS threshold to identify children at risk of dying improved in children less than 3 years of age (AUC 0.74, [95% C.I 0.71-0.76].The BCS is a quantitative predictor of death. A BCS of 2 or less is the most sensitive and specific clinical feature to predict death or development of neurological sequelae in children with SM.

  9. Development of Delayed Hemolytic Anemia After Treatment with Oral Artemether-Lumefantrine in Two Patients with Severe Falciparum Malaria.

    Science.gov (United States)

    Tsuchido, Yasuhiro; Nakamura-Uchiyama, Fukumi; Toyoda, Kasumi; Iwagami, Moritoshi; Tochitani, Kentaro; Shinohara, Koh; Hishiya, Naokuni; Ogawa, Taku; Uno, Kenji; Kasahara, Kei; Ouji, Yukiteru; Kano, Shigeyuki; Mikasa, Keiichi; Shimizu, Tsunehiro; Yoshikawa, Masahide; Maruyama, Haruhiko

    2017-05-01

    AbstractRecently, reports of delayed hemolytic anemia after treatment with artemisinin and its derivatives have emerged. Here we report two cases of delayed hemolytic anemia in a patient with severe falciparum malaria after treatment with oral artemether-lumefantrine (AL). The first patient, a 20-year-old Japanese male student, was diagnosed with falciparum malaria and was administered AL. As having a high parasitemia rate (20.6%) was the only severe malaria criterion met in this case and his general condition was stable, we continued with AL treatment. Despite disappearance of malarial parasites after 4 days of AL administration, a persistent fever remained. On days 13 and 16, a diagnosis of hemolytic anemia was made (lactate dehydrogenase [LDH]: 1,466 U/L, hemoglobin [Hb]: 7.2 g/dL). A blood smear at that time revealed no parasites. He recovered naturally from delayed hemolysis. The second patient, a 27-year-old Japanese female student, was diagnosed with falciparum malaria (parasitemia: 4.5%) and treated initially with oral quinine hydrochloride and doxycycline. The following day, parasitemia increased to 7.9% and oral AL was initiated. She was discharged on day 4 after achieving parasite clearance and afebrility. However, on day 5, fever (body temperature > 38°C) recurred, and on day 11, a diagnosis of hemolytic anemia was made (LDH: 712 U/L, Hb: 8.8 g/dL). A follow-up confirmed that her condition improved gradually. AL treatment of severe malaria can cause delayed hemolytic anemia. Patients should be followed up for up to 4 weeks to detect signs of hemolysis and provide appropriate symptomatic treatment.

  10. [Long circulating nanocapsules: interest in the treatment of severe malaria with halofantrine].

    Science.gov (United States)

    Legrand, P; Mosqueira, V; Loiseau, P; Bories, C; Barratt, G

    2003-05-01

    The aim of the work was to develop a new submicronic delivery system that can be used with poorly water soluble drugs for which sustained circulating concentrations are necessary. This system consists of oily core surrounded by a shell made of a copolymer of poly (D,L-lactid) and poly (ethylene glycol). Covalent coupling between the hydrophylic poly (ethylene glycol) and poly (D,L lactid) and high molecular weight of the poly (ethylene glycol) chains yield long circulating particles after intra-venous administration in mice. Halofantrine, a very effective drug administrated for the treatment of severe malaria caused by Plasmodium, for which no injectable preparation exists. Results showed that percentage of loading, yield of encapsulation and physical stability were more favourable with surface modified nanocapsules. Release of halofantrine was clearly related to partition between oil and external medium. Serum proteins in the medium, increased halofantrine release from nanocapsules and poly (ethylene glycol) grafted nanocapsules reduced this phenomenum. The pharmacokinetics of the free drug was modified to maintain it in blood circulation. It is important to note that high plasma concentrations of halofantrine were correlated with higher activity against parasites in mice infected with Plasmodium berghei.

  11. Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria

    Czech Academy of Sciences Publication Activity Database

    Francischetti, I.M.B.; Oliveira, C. J.; Ostera, G. R.; Yager, S. B.; Debierre-Grockiego, F.; Carregaro, V.; Jaramillo-Gutierrez, G.; Hume, J. C. C.; Jiang, L.; Moretz, S. E.; Lin, Ch. K.; Ribeiro, J.M.C.; Long, C. A.; Vickers, B. K.; Schwarz, R. T.; Seydel, K. B.; Iacobelli, M.; Ackerman, H. C.; Srinivasan, P.; Gomes, R. B.; Wang, X.; Monteiro, R.Q.; Kotsyfakis, Michalis; Sa-Nunes, A.; Waisberg, M.

    2012-01-01

    Roč. 32, č. 3 (2012), s. 786-798 ISSN 1079-5642 Institutional research plan: CEZ:AV0Z60220518 Keywords : anticoagulants * blood coagulation * endothelium * microcirculation * vascular biology * malaria * defibrotide * inflammation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.338, year: 2012

  12. Paradoxical sleep deprivation impairs mouse survival after infection with malaria parasites.

    Science.gov (United States)

    Lungato, Lisandro; Gazarini, Marcos L; Paredes-Gamero, Edgar J; Tufik, Sergio; D'Almeida, Vânia

    2015-04-28

    Parasitic diseases like malaria are a major public health problem in many countries and disrupted sleep patterns are an increasingly common part of modern life. The aim of this study was to assess the effects of paradoxical sleep deprivation (PSD) and sleep rebound (RB) on malarial parasite infection in mice. After PSD, one group was immediately infected with parasites (PSD). The two other PSD rebound groups were allowed to sleep normally for either 24 h (24 h RB) or 48 h (48 h RB). After the recovery periods, mice were inoculated with parasites. The PSD group was the most affected by parasites presenting the higher death rate (0.02), higher number of infected cells (p body weight (p body weight (p malaria parasites; only 48 hours of recovery sleep was sufficient to return the mice infection response to baseline values.

  13. Altered platelet indices as potential markers of severe and complicated malaria caused by Plasmodium vivax: a cross-sectional descriptive study.

    Science.gov (United States)

    Leal-Santos, Fábio A; Silva, Soraya B R; Crepaldi, Natasha P; Nery, Andréia F; Martin, Thamires O G; Alves-Junior, Eduardo R; Fontes, Cor J F

    2013-12-27

    This study described altered platelet indices in patients with acute malaria caused by Plasmodium vivax and determined whether these alterations are associated with warning signs of severe and complicated malaria. A total of 186 patients attending the Malaria Clinic at the University Hospital from the Federal University of Mato Grosso, Brazil, between 2008 and 2013 were included in this study. After parasitological confirmation of exclusive infection by P. vivax, blood cell counts and platelet indices were determined. Disease gravity was evaluated on the basis of classic signs of Plasmodium falciparum severe malaria, including severe anemia, or by changes in serum levels of glucose, bilirubin, aminotransferases and creatinine at the time of the patient's admission. Patients with a longer duration of symptoms or those identified as primo infected were considered potential candidates for evolution into the severe form of malaria. The mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) values exhibited significant variability. A significant inverse relationship was observed between parasitaemia and PCT. Patients with warning signs for evolution into severe disease, with primo infection, or presenting with symptoms for over three days had the highest MPV and PDW. The adjusted analyses showed the presence of warning signs for the development of severe and complicated malaria remained independently linked to elevated MPV and PDW. Altered platelet indices should be analysed as potential markers for the severity of malaria caused by P. vivax. Future studies with appropriate methodology for prognostic evaluation could confirm the potential use of these indices in clinical practice.

  14. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  15. DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.

    Directory of Open Access Journals (Sweden)

    Marion Avril

    Full Text Available During blood stage infection, Plasmodium falciparum infected erythrocytes (IE bind to host blood vessels. This virulence determinant enables parasites to evade spleen-dependent killing mechanisms, but paradoxically in some cases may reduce parasite fitness by killing the host. Adhesion of infected erythrocytes is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1, a family of polymorphic adhesion proteins encoded by var genes. Whereas cerebral binding and severe malaria are associated with parasites expressing DC8 and DC13 var genes, relatively little is known about the non-brain endothelial selection on severe malaria adhesive types. In this study, we selected P. falciparum-IEs on diverse endothelial cell types and demonstrate that DC8 and DC13 var genes were consistently among the major var transcripts selected on non-brain endothelial cells (lung, heart, bone marrow. To investigate the molecular basis for this avid endothelial binding activity, recombinant proteins were expressed from the predominant upregulated DC8 transcript, IT4var19. In-depth binding comparisons revealed that multiple extracellular domains from this protein bound brain and non-brain endothelial cells, and individual domains largely did not discriminate between different endothelial cell types. Additionally, we found that recombinant DC8 and DC13 CIDR1 domains exhibited a widespread endothelial binding activity and could compete for DC8-IE binding to brain endothelial cells, suggesting they may bind the same host receptor. Our findings provide new insights into the interaction of severe malaria adhesive types and host blood vessels and support the hypothesis that parasites causing severe malaria express PfEMP1 variants with a superior ability to adhere to diverse endothelial cell types, and may therefore endow these parasites with a growth and transmission advantage.

  16. Prognostic value of clinical and parasitological signs for severe malaria in patients from Colombia Utilidad pronóstica para malaria grave de signos clínicos y parasitológicos en pacientes de Colombia

    Directory of Open Access Journals (Sweden)

    Silvia Blair-Trujillo

    2011-07-01

    Full Text Available Introduction. Early recognition of danger signs in patients with malaria can reduce complications and deaths, but little is known about its prognostic value for severe malaria, especially in areas of low transmission and unstable malaria.
    Objective. Assess the prognostic value for gravity that has different clinical and parasitological signs in patients with malaria.
    Materials and methods. A prospective cohort of patients from five municipalities in Colombia with diagnosis of malaria by Plasmodium falciparum or P. vivax, in whom was studied the association between clinical and parasitological signs with complicated malaria. Results. Was obtained a predictive model with a 47,4% sensitivity, 92,8% specificity, 63,2% positive predictive value and 87,1% negative predictive value, that includes jaundice, dark urine, hyperpyrexia and signs of dehydration.
    Conclusions. To impact the complicated cases caused by malaria it is proposed a strategy for the early recognition of danger signs by non-medical personnel, which could be accompanied by other elements of the healthcare, such as providing an adequate and appropriate antimalarial treatment. Also are proposed diagnostic criteria for moderate complications.
    Introducción. El reconocimiento temprano de signos de peligro en los pacientes con malaria puede reducir las complicaciones y muertes, sin embargo se conoce poco acerca de su valor pronóstico para malaria complicada, especialmente en zonas de transmisión baja e inestable de malaria.
    Objetivo. Estimar el valor pronóstico de gravedad que tienen diversos signos clínicos y parasitológicos en pacientes con malaria.
    Materiales y métodos. Cohorte prospectiva con pacientes de cinco municipios de Colombia con diagnóstico de malaria por Plasmodium falciparum y P. vivax, en quienes se estudió la asociación entre signos clínicos y parasitológicos con malaria complicada.
    Resultados. Se obtuvo un modelo predictivo con

  17. INFLUENCE OF SICKLE CELL GENE ON THE ALLELIC DIVERSITY AT THE MSP-1 LOCUS OF PLASMODIUM FALCIPARUM IN ADULT PATIENTS WITH SEVERE MALARIA

    OpenAIRE

    Dilip Kumar Patel; Ranjeet Singh Mashon; Prasanta Purohit; Siris Patel; Satyabrata Meher; Snehadhini Dehury; Chhatray Marndi; Kishalaya Das; Bipin Kishore Kullu; Padmalaya Das

    2015-01-01

    Although several studies have supported that sickle cell trait (HbAS) protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of the sickle gene on the parasitic diversity of P. falciparum population in severe symptomatic malaria. This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum m...

  18. The reliability of the physical examination to guide fluid therapy in adults with severe falciparum malaria: an observational study.

    Science.gov (United States)

    Hanson, Josh; Lam, Sophia W K; Alam, Shamsul; Pattnaik, Rajyabardhan; Mahanta, Kishore C; Uddin Hasan, Mahatab; Mohanty, Sanjib; Mishra, Saroj; Cohen, Sophie; Day, Nicholas; White, Nicholas; Dondorp, Arjen

    2013-10-01

    Adults with severe malaria frequently require intravenous fluid therapy to restore their circulating volume. However, fluid must be delivered judiciously as both under- and over-hydration increase the risk of complications and, potentially, death. As most patients will be cared for in a resource-poor setting, management guidelines necessarily recommend that physical examination should guide fluid resuscitation. However, the reliability of this strategy is uncertain. To determine the ability of physical examination to identify hypovolaemia, volume responsiveness, and pulmonary oedema, clinical signs and invasive measures of volume status were collected independently during an observational study of 28 adults with severe malaria. The physical examination defined volume status poorly. Jugular venous pressure (JVP) did not correlate with intravascular volume as determined by global end diastolic volume index (GEDVI; r(s) = 0.07, p = 0.19), neither did dry mucous membranes (p = 0.85), or dry axillae (p = 0.09). GEDVI was actually higher in patients with decreased tissue turgor (p physical examination correlate poorly with true volume status in adults with severe malaria and must be used with caution to guide fluid therapy. Clinicaltrials.gov identifier: NCT00692627.

  19. Population pharmacokinetics of intramuscular artesunate in African children with severe malaria: implications for a practical dosing regimen.

    Science.gov (United States)

    Hendriksen, I C E; Mtove, G; Kent, A; Gesase, S; Reyburn, H; Lemnge, M M; Lindegardh, N; Day, N P J; von Seidlein, L; White, N J; Dondorp, A M; Tarning, J

    2013-05-01

    Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model.

  20. Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three African populations.

    Directory of Open Access Journals (Sweden)

    Valentina D Mangano

    Full Text Available Interferon Regulatory Factor 1 (IRF-1 is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi. No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria.

  1. Lack of Association of Interferon Regulatory Factor 1 with Severe Malaria in Affected Child-Parental Trio Studies across Three African Populations

    Science.gov (United States)

    Mangano, Valentina D.; Clark, Taane G.; Green, Angela; Richardson, Anna; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Griffiths, Michael J.; Newton, Charles; Peshu, Norbert; Williams, Thomas N.; Marsh, Kevin; Molyneux, Malcolm E.; Taylor, Terrie E.; Modiano, David; Kwiatkowski, Dominic P.; Rockett, Kirk A.

    2009-01-01

    Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria. PMID:19145247

  2. A randomized pilot study of L-arginine infusion in severe falciparum malaria: preliminary safety, efficacy and pharmacokinetics.

    Directory of Open Access Journals (Sweden)

    Tsin W Yeo

    Full Text Available Decreased nitric oxide (NO and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed.In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study, patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT] were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM.Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP and diastolic blood pressure (DBP or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n = 4 showed L-arginine concentrations 40% lower than predicted from models developed in MSM.In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine.ClinicalTrials.gov NCT00616304.

  3. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency

    NARCIS (Netherlands)

    Diekman, E.F.; Koning, T.J. de; Verhoeven-Duif, N.M.; Rovers, M.M.; Hasselt, P.M. van

    2014-01-01

    IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

  4. Survival and Psychomotor Development With Early Betaine Treatment in Patients With Severe Methylenetetrahydrofolate Reductase Deficiency

    NARCIS (Netherlands)

    Diekman, Eugene F.; de Koning, Tom J.; Verhoeven-Duif, Nanda M.; Rovers, Maroeska M.; van Hasselt, Peter M.

    IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

  5. Survival trends and predictors of mortality in severe pelvic trauma

    DEFF Research Database (Denmark)

    Pohlemann, Tim; Stengel, Dirk; Tosounidis, Georgios

    2011-01-01

    STUDY OBJECTIVE: To determine longitudinal trends in mortality, and the contribution of specific injury characteristics and treatment modalities to the risk of a fatal outcome after severe and complex pelvic trauma. METHODS: We studied 5048 patients with pelvic ring fractures enrolled in the German...... Pelvic Trauma Registry Initiative between 1991 and 1993, 1998 and 2000, and 2004 and 2006. Complete datasets were available for 5014 cases, including 508 complex injuries, defined as unstable fractures with severe peri-pelvic soft tissue and organ laceration. Multivariable mixed-effects logistic...... with this type of injury was 18% (95% CI 9-32%) in 2006. CONCLUSION: In contrast to an overall decline in trauma mortality, complex pelvic ring injuries remain associated with a significant risk of death. Awareness of this potentially life-threatening condition should be increased amongst trauma care...

  6. Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement.

    Directory of Open Access Journals (Sweden)

    Ilse C E Hendriksen

    Full Text Available In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2 is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria.Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054. In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209, acidosis (p<0.0001, and severe anaemia (p<0.0001. Admission geometric mean (95%CI plasma PfHRP2 was 1,611 (1,350-1,922 ng/mL in fatal cases (n = 381 versus 1,046 (991-1,104 ng/mL in survivors (n = 3,445, p<0.0001, without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10 plasma PfHRP2 and risk of death. Mortality increased 20% per log(10 increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009. A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018 in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82. A limitation of the study is that some

  7. Endocan is useful biomarker of survival and severity in sepsis.

    Science.gov (United States)

    Mihajlovic, Dunja M; Lendak, Dajana F; Brkic, Snezana V; Draskovic, Biljana G; Mitic, Gorana P; Novakov Mikic, Aleksandra S; Cebovic, Tatjana N

    2014-05-01

    Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined. 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test. Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (pAPACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure. Results of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

    Science.gov (United States)

    Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy Me; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris Ca; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

    2017-01-09

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

  9. Rapid antigen detection tests for malaria diagnosis in severely ill Papua New Guinean children: a comparative study using Bayesian latent class models.

    Directory of Open Access Journals (Sweden)

    Laurens Manning

    Full Text Available BACKGROUND: Although rapid diagnostic tests (RDTs have practical advantages over light microscopy (LM and good sensitivity in severe falciparum malaria in Africa, their utility where severe non-falciparum malaria occurs is unknown. LM, RDTs and polymerase chain reaction (PCR-based methods have limitations, and thus conventional comparative malaria diagnostic studies employ imperfect gold standards. We assessed whether, using Bayesian latent class models (LCMs which do not require a reference method, RDTs could safely direct initial anti-infective therapy in severe ill children from an area of hyperendemic transmission of both Plasmodium falciparum and P. vivax. METHODS AND FINDINGS: We studied 797 Papua New Guinean children hospitalized with well-characterized severe illness for whom LM, RDT and nested PCR (nPCR results were available. For any severe malaria, the estimated prevalence was 47.5% with RDTs exhibiting similar sensitivity and negative predictive value (NPV to nPCR (≥96.0%. LM was the least sensitive test (87.4% and had the lowest NPV (89.7%, but had the highest specificity (99.1% and positive predictive value (98.9%. For severe falciparum malaria (prevalence 42.9%, the findings were similar. For non-falciparum severe malaria (prevalence 6.9%, no test had the WHO-recommended sensitivity and specificity of >95% and >90%, respectively. RDTs were the least sensitive (69.6% and had the lowest NPV (96.7%. CONCLUSIONS: RDTs appear a valuable point-of-care test that is at least equivalent to LM in diagnosing severe falciparum malaria in this epidemiologic situation. None of the tests had the required sensitivity/specificity for severe non-falciparum malaria but the number of false-negative RDTs in this group was small.

  10. Initial treatment of severe malaria in children is inadequate – a study ...

    African Journals Online (AJOL)

    In 60% of the subjects, some form of treatment had been administered at home, and 33% had consulted a primary health facility. In 85% of the malaria-infected children, quinine, artemisinin-based combination therapies (ACTs) and amodiaquine were respectively administered to 32%, 30% and 23% of the children.

  11. Severe malaria not responsive to artemisinin derivatives in man returning from Angola to Vietnam.

    Science.gov (United States)

    Van Hong, Nguyen; Amambua-Ngwa, Alfred; Tuan, Nguyen Quang; Cuong, Do Duy; Giang, Nguyen Thi Huong; Van Dung, Nguyen; Tinh, Ta Thi; Van Tien, Nguyen; Phuc, Bui Quang; Duong, Tran Thanh; Rosanas-Urgell, Anna; D'Alessandro, Umberto; Van Geertruyden, Jean-Pierre; Erhart, Annette

    2014-07-01

    Resistance to artemisinin derivatives, the most potent antimalarial drugs currently used, has emerged in Southeast Asia and threatens to spread to Africa. We report a case of malaria in a man who returned to Vietnam after 3 years in Angola that did not respond to intravenous artesunate and clindamycin or an oral artemisinin-based combination.

  12. Zinc levels and malaria severity in children below five years in Dar ...

    African Journals Online (AJOL)

    Introduction: Interventions which will decrease the morbidity and mortality related to Malaria are still being sought in order to improve the state of children in developing countries. Zinc is recognized to improve child health by improving immunity growth, weight and reducing episodes of infectious disease. The relation of Zinc ...

  13. Plasmodium genome in blood donors at risk for malaria after several years of residence in Italy.

    Science.gov (United States)

    Assennato, Sonny Michael; Berzuini, Alessandra; Foglieni, Barbara; Spreafico, Marta; Allain, Jean-Pierre; Prati, Daniele

    2014-10-01

    At present, the main risk of transfusion-transmitted malaria (TTM) in nonendemic countries is chronic, asymptomatic immigrants from malaria-endemic areas. Semi-immune donors may carry undetected parasitemia. This study examines Plasmodium infection in at-risk blood donors in Northern Italy. Plasma samples from 97 candidate donors and 80 controls were tested for malarial antibodies using a commercial enzyme immunoassay. The conserved 18S rRNA and the mitochondrial genes of Plasmodium were amplified to detect and quantify parasite genomes (copies/mL). Plasmodium species were identified with a species-specific nested polymerase chain reaction. Parasitemic samples were further tested by amplification of polymorphic repetitive regions in MSP-1 Block 2, MSP-2 Block 3, and glutamate-rich protein (GLURP) confirmed by sequencing. Three of 83 seropositive (3.6%) and one of 14 seronegative at-risk candidate donors carried Plasmodium genome (4 × 10(3) -8.5 × 10(4) copies/mL): two P. falciparum, one P. malariae (seronegative sample), and one coinfection with P. malariae and P. ovale. Alleles of MSP-1 (MAD20 and K1), MSP-2 (3D7 and FC27), and GLURP were amplified from Sample 261. In Sample 282 only one allele in MSP-2 (FC27) and GLURP was amplified. No alleles were detected in Samples 283 and 331. Immigrants from endemic countries might carry infectious Plasmodium after 2 to 5 years of continuous residence in Italy. Serologic screening may miss donors carrying P. malariae. Permanent exclusion or screening for both antibodies and genome are needed to prevent TTM. © 2014 AABB.

  14. Hypoxemia predicts death from severe falciparum malaria among children under 5 years of age in Nigeria: the need for pulse oximetry in case management.

    Science.gov (United States)

    Orimadegun, Adebola; Ogunbosi, Babatunde; Orimadegun, Bose

    2014-06-01

    Oxygen saturation is a good marker for disease severity in emergency care. However, studies have not considered its use in identifying individuals infected with Plasmodium falciparum at risk of deaths. To investigate the prevalence and predictive value of hypoxaemia for deaths in under-5s with severe falciparum malaria infection. Oxygen saturation was prospectively measured alongside other indicators of disease severity in 369 under-5s admitted to a tertiary hospital in Nigeria. Participants were children in whom falciparum malaria parasitaemia was confirmed with blood film microscopy in the presence of any of the World Health Organization-defined life-threatening features for malaria. Overall mortality rate was 8.1%. Of the 16 indicators of the disease severity assessed, hypoxaemia (OR=7.54; 95% CI=2.80, 20.29), co-morbidity with pneumonia (OR=19.27; 95% CI=2.87, 29.59), metabolic acidosis (OR=6.21; 95% CI=2.21, 17.47) and hypoglycaemia (OR=19.71; 95% CI=2.61, 25.47) were independent predictors of death. Cerebral malaria, male gender, wasting, hypokalaemia, hyponatriaemia, azotaemia and renal impairment were significantly associated with death in univariate analysis but not logistic regression model. Hypoxaemia predicts deaths in Nigerian children with severe malaria, irrespective of other features. Efforts should always be made to measure oxygen saturation as part of the treatments for severe malaria in children.

  15. Protective efficacy of malaria case management and intermittent preventive treatment for preventing malaria mortality in children: a systematic review for the Lives Saved Tool

    Directory of Open Access Journals (Sweden)

    Steketee Richard W

    2011-04-01

    Full Text Available Abstract Background The Lives Saved Tool (LiST model was developed to estimate the impact of the scale-up of child survival interventions on child mortality. New advances in antimalarials have improved their efficacy of treating uncomplicated and severe malaria. Artemisinin-based combination therapies (ACTs for uncomplicated Plasmodium falciparum malaria and parenteral or rectal artemisinin or quinine for severe malaria syndromes have been shown to be very effective for the treatment of malaria in children. These interventions are now being considered for inclusion in the LiST model. However, for obvious ethical reasons, their protective efficacy (PE compared to placebo is unknown and their impact on reducing malaria-attributable mortality has not been quantified. Methods We performed systematic literature reviews of published studies in P. falciparum endemic settings to determine the protective efficacy (PE of ACT treatment against malaria deaths among children with uncomplicated malaria, as well as the PE of effective case management including parenteral quinine against malaria deaths among all hospitalized children. As no randomized placebo-controlled trials of malaria treatment have been conducted, we used multiple data sources to ascertain estimates of PE, including a previously performed Delphi estimate for treatment of uncomplicated malaria. Results Based on multiple data sources, we estimate the PE of ACT treatment of uncomplicated P. falciparum malaria on reducing malaria mortality in children 1–23 months to be 99% (range: 94-100%, and in children 24-59 months to be 97% (range: 86-99%. We estimate the PE of treatment of severe P. falciparum malaria with effective case management including intravenous quinine on reducing malaria mortality in children 1-59 months to be 82% (range: 63-94% compared to no treatment. Conclusions This systematic review quantifies the PE of ACT used for treating uncomplicated malaria and effective case

  16. Severe Flooding and Malaria Transmission in the Western Ugandan Highlands: Implications for Disease Control in an Era of Global Climate Change.

    Science.gov (United States)

    Boyce, Ross; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar; Metlay, Joshua P; Band, Lawrence; Siedner, Mark J

    2016-11-01

     There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will influence malaria transmission in highland areas of East Africa.  We used a differences-in-differences, quasi-experimental design to examine spatial variability in the incidence rate of laboratory-confirmed malaria cases and malaria-related hospitalizations between villages (1) at high versus low elevations, (2) with versus without rivers, and (3) upstream versus downstream before and after severe flooding that occurred in Kasese District, Western Region, Uganda, in May 2013.  During the study period, 7596 diagnostic tests were performed, and 1285 patients were admitted with a diagnosis of malaria. We observed that extreme flooding resulted in an increase of approximately 30% in the risk of an individual having a positive result of a malaria diagnostic test in the postflood period in villages bordering a flood-affected river, compared with villages farther from a river, with a larger relative impact on upstream versus downstream villages (adjusted rate ratio, 1.91 vs 1.33).  Extreme precipitation such as the flooding described here may pose significant challenges to malaria control programs and will demand timely responses to mitigate deleterious impacts on human health. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Rapid reemergence of T cells into peripheral circulation following treatment of severe and uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Goka, B Q

    1997-01-01

    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...

  18. TLR9 polymorphisms in African populations: no association with severe malaria, but evidence of cis-variants acting on gene expression

    Directory of Open Access Journals (Sweden)

    Pinder Margaret

    2009-03-01

    Full Text Available Abstract Background During malaria infection the Toll-like receptor 9 (TLR9 is activated through induction with plasmodium DNA or another malaria motif not yet identified. Although TLR9 activation by malaria parasites is well reported, the implication to the susceptibility to severe malaria is not clear. The aim of this study was to assess the contribution of genetic variation at TLR9 to severe malaria. Methods This study explores the contribution of TLR9 genetic variants to severe malaria using two approaches. First, an association study of four common single nucleotide polymorphisms was performed on both family- and population-based studies from Malawian and Gambian populations (n>6000 individual. Subsequently, it was assessed whether TLR9 expression is affected by cis-acting variants and if these variants could be mapped. For this work, an allele specific expression (ASE assay on a panel of HapMap cell lines was carried out. Results No convincing association was found with polymorphisms in TLR9 for malaria severity, in either Gambian or Malawian populations, using both case-control and family based study designs. Using an allele specific expression assay it was observed that TLR9 expression is affected by cis-acting variants, these results were replicated in a second experiment using biological replicates. Conclusion By using the largest cohorts analysed to date, as well as a standardized phenotype definition and study design, no association of TLR9 genetic variants with severe malaria was found. This analysis considered all common variants in the region, but it is remains possible that there are rare variants with association signals. This report also shows that TLR9 expression is potentially modulated through cis-regulatory variants, which may lead to differential inflammatory responses to infection between individuals.

  19. Surviving severe traumatic brain injury in Denmark: incidence and predictors of highly specialized rehabilitation

    Directory of Open Access Journals (Sweden)

    Odgaard L

    2015-03-01

    Full Text Available Lene Odgaard,1 Ingrid Poulsen,2 Lars Peter Kammersgaard,2 Søren Paaske Johnsen,3 Jørgen Feldbæk Nielsen,1 1Hammel Neurorehabilitation Center and University Research Clinic, Aarhus University, Aarhus, Denmark; 2Department of Neurorehabilitation, TBI and Research Unit on Brain injury rehabilitation (RUBRIC, Glostrup Hospital, Copenhagen University, Copenhagen, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Purpose: To identify all hospitalized patients surviving severe traumatic brain injury (TBI in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation. Patients and methods: Patients surviving severe TBI were identified from The Danish National Patient Registry and The Danish Head Trauma Database. Overall incidence rates of surviving severe TBI and incidence rates of admission to HS-rehabilitation after severe TBI were estimated and compared. Patient-related predictors of no admission to HS-rehabilitation among patients surviving severe TBI were identified using multivariable logistic regression. Results: The average incidence rate of surviving severe TBI was 2.3 per 100,000 person years. Incidence rates of HS-rehabilitation were generally stable around 2.0 per 100,000 person years. Overall, 84% of all patients surviving severe TBI were admitted to HS-rehabilitation. Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI. Conclusion: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark and the majority of the patients were admitted to HS-rehabilitation. However, potential inequity in access to HS-rehabilitation may still be present despite a health care system based on equal access for all citizens. Keywords: database, health care disparities, registries, validity 

  20. Effect of severity of disability on survival in north east England cerebral palsy cohort.

    Science.gov (United States)

    Hutton, J L; Colver, A F; Mackie, P C

    2000-12-01

    To investigate the effect of motor and cognitive disabilities on the survival of people on the North of England Collaborative Cerebral Palsy Survey, and compare this with other published results. The cerebral palsy cohort consists of 1960-1990 births in Northumberland, Newcastle, and North Tyneside health districts. Survival and cause of death were analysed in relation to data on birth, disabilities, and a unique measure of the impact of disability. Disability strongly influences survival. More than a third of those with a severe disability die before age 30. Fewer than a third of deaths are attributed to cerebral palsy on death certificates. Of those with severe cognitive disability, 63% live to age 35 (58% with severe ambulatory disability and 53% with severe manual disability), whereas at least 98% without severe disabilities live to age 35. The Lifestyle Assessment Score (LAS) allows a finer categorisation of impact of disability, and is strongly associated with survival: a ten point increase in LAS is associated with a doubling of the hazard rate. People who had LAS of at least 70, and had survived to age 5 have a 39% chance of dying before age 35. The majority of people with cerebral palsy attain adulthood. There appears to be more variation in survival rates associated with severe disability between regions of England, than between north east England, British Columbia, and California. Instantaneous risks of dying vary widely between England and California. This variation is not obviously attributable to differing rates of severe disability.

  1. Feasibility and acceptability of injectable artesunate for the treatment of severe malaria in the Democratic Republic of Congo.

    Science.gov (United States)

    Ntuku, Henry M T; Ferrari, Gianfrancesco; Burri, Christian; Tshefu, Antoinette K; Kalemwa, Didier M; Lengeler, Christian

    2016-01-08

    The Democratic Republic of the Congo (DRC) changed its national policy for the treatment of severe malaria in both children and adults in 2012 from intravenous quinine to injectable artesunate. The country is now planning to deploy nationwide injectable artesunate as the preferred treatment for the management of severe malaria. To support this process, the feasibility and acceptability of the use of injectable artesunate in the context of the DRC was assessed, from the perspective of both health care providers and patients/caretakers. Questionnaires and observations were used to collect information from health care providers and patients/caretakers in eight health facilities in the Province of Kinshasa and in the Province of Bas-Congo. A total of 31 health care providers and 134 patients/care takers were interviewed. Seventy five percent (75%) of health care providers found it less difficult to prepare injectable artesunate compared to quinine. None of them encountered problems during preparation and administration of injectable artesunate. The large majority of care providers (93%) and patients/caretakers (93%) answered that injectable artesunate took less time than quinine to cure the symptoms of the patients. 26 (84%) health care providers reported that the personnel workload had diminished with the use of injectable artesunate. 7 (22.6%) health workers reported adverse drug reactions, of which a decrease in the haemoglobin rate was the most common (71.4%). All care providers and the vast majority of patients/caretakers (96%, N = 128) were either satisfied or very satisfied with injectable artesunate. These findings show that the use of injectable artesunate for the treatment of severe malaria is feasible and acceptable in the context of DRC, with appropriate training of care providers. Both care providers and patients/caretakers perceived injectable artesunate to be effective and safe, thus promoting acceptability.

  2. STATUS HEMATOLOGI PENDERITA MALARIA SEREBRAL

    Directory of Open Access Journals (Sweden)

    Nurhayati Nurhayati

    2009-05-01

    Full Text Available AbstrakMalaria masih merupakan masalah kesehatan masyarakat dunia. Berdasarkan klasifikasi klinis, malaria dibedakan atas malaria berat dan malaria tanpa komplikasi. Malaria serebral merupakan komplikasi terberat dari malaria falsiparum.Telah dilakukan penelitian seksi silang terhadap penderita malaria falciparum yang dirawat inap di Bangsal Penyakit Dalam RS. Perjan. Dr. M. Djamil Padang dari bulan Juni 2002 sampai Juni 2006. Pada penelitian ini didapatkan jumlah sampel sebanyak 60 orang, terdiri dari 16 orang penderita malaria serebral dan 44 orang penderita malaria tanpa komplikasi.Data penelitian menunjukan terdapat perbedaan bermakna nilai hematokrit (p<0,05 dan jumlah leukosit (p<0,05 antara penderita malaria serebral dengan penderita malaria tanpa komplikasi. Dan terdapat korelasi positif antara nilai hemoglobin dengan hematokrit (r=0,864; p<0,05 pada penderita malaria falsiparum.Kata kunci: malaria serebral, malaria tanpa komplikasi, malaria falsiparumAbstract Malaria is still a problem of health of world society. Based on the clinical classification, are distinguished on severe malaria and uncomplicated malaria. Cerebral malaria is the worst complication of falciparum malaria. Cross section of the research done at the Hospital Dr. M. Djamil Padang againts medical record of malaria patients who are hospitalized in the Internal Medicine from June 2002 until June 2004. In this study, a total sample of 60 people, consisting of 16 cerebral malaria and 44 uncomplicated malaria. Data showed there were significant differences for hematocrit values (p <0.05 and total leukocytes values (p <0.05 between cerebral malaria and uncomplicated malaria patients. There is a positive correlation between hemoglobin with hematocrit values (r = 0.864; p <0.05 of falciparum malaria patients. Keywords: cerebral malaria, uncomplicated malaria, falciparum malaria

  3. Geographical concentration of falciparum malaria treated in the UK and delay to treatment with artesunate in severe cases: an observational study

    OpenAIRE

    Broderick, C; Friend, P; Smith, V.; Blaze, M; Gothard, P; Chiodini, PL; Whitty, CJM

    2012-01-01

    Objectives: To quantify geographical concentration of falciparum malaria cases in the UK at a hospital level. To assess potential delay-to-treatment associated with hub-and-spoke distribution of artesunate in severe cases. Design: Observational study using national and hospital data. Setting and participants: 3520 patients notified to the Malaria Reference Laboratory 2008-2010, 34 patients treated with intravenous artesunate from a tropical diseases centre 2002-2010. Main outcome measures: Ge...

  4. Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

    Science.gov (United States)

    Cabrales, Pedro; Zanini, Graziela M.; Meays, Diana; Frangos, John A.; Carvalho, Leonardo J.M.

    2010-01-01

    Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably, vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM. PMID:20110412

  5. Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

    Science.gov (United States)

    Thellier, Marc; Ndour, Papa Alioune; Ader, Flavie; Roussel, Camille; Sonneville, Romain; Mayaux, Julien; Matheron, Sophie; Angoulvant, Adela; Wyplosz, Benjamin; Rapp, Christophe; Pistone, Thierry; Lebrun-Vignes, Bénédicte; Kendjo, Eric; Danis, Martin; Houzé, Sandrine; Bricaire, François; Mazier, Dominique; Buffet, Pierre; Caumes, Eric

    2015-01-01

    Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate. PMID:25898007

  6. Influence of Sickle Cell Gene on the Allelic Diversity at the msp-1 locus of Plasmodium falciparum in Adult Patients with Severe Malaria.

    Science.gov (United States)

    Patel, Dilip Kumar; Mashon, Ranjeet Singh; Purohit, Prasanta; Meher, Satyabrata; Dehury, Snehadhini; Marndi, Chhatray; Das, Kishalaya; Kullu, Bipin Kishore; Patel, Siris; Das, Padmalaya

    2015-01-01

    Although several studies have supported that sickle cell trait (HbAS) protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of the sickle gene on the parasitic diversity of P. falciparum population in severe symptomatic malaria. This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum malaria. The study was carried out in 166 adults hospitalized subjects with severe falciparum malaria at Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, Odisha, India. They were divided into three groups on the basis of hemoglobin variants HbAA (n=104), HbAS (n=30) and HbSS (n=32). The msp-1 loci were genotyped using a PCR-based methodology. The parasite densities were significantly high in HbAA compared to HbAS and HbSS. The multiplicity of infection (MOI) and multi-clonality for msp-1 were significantly low in HbSS and HbAS compared to HbAA. The prevalence of K1 (pSickle gene was found to reduce both the parasite densities and diversity of P. falciparum in adults with severe malaria.

  7. CD36 selection of 3D7 Plasmodium falciparum associated with severe childhood malaria results in reduced VAR4 expression

    Directory of Open Access Journals (Sweden)

    Hviid Lars

    2008-10-01

    Full Text Available Abstract Background A subset of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1SM is involved in the cytoadherence of P. falciparum-infected red blood cells (iRBC contributing to the pathogenesis of severe disease among young children in malaria endemic areas. The PfEMP1SM are encoded by group A var genes that are composed of a more constrained range of amino acid sequences than groups B and C var genes encoding PfEMP1UM associated with uncomplicated malaria. Also, unlike var genes from groups B and C, those from group A do not have sequences consistent with CD36 binding – a major cytoadhesion phenotype of P. falciparum isolates. Methods A 3D7 PfEMP1SM sub-line (3D7SM expressing VAR4 (PFD1235w/MAL8P1.207 was selected for binding to CD36. The protein expression of this parasite line was monitored by surface staining of iRBC using VAR4-specific antibodies. The serological phenotype of the 3D7SM parasites was determined by flow cytometry using malaria semi-immune and immune plasma and transcription of the 59 var genes in 3D7 were analysed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR using var-specific primers. Results A selection-induced increased adhesion of 3D7SM iRBC to CD36 resulted in a reduced var4 transcription and VAR4 surface expression. Conclusion VAR4 is not involved in CD36 adhesion. The current findings are consistent with the notion that CD36 adhesion is not associated with particular virulent parasite phenotypes, such as those believed to be exhibited by VAR4 expressing parasites.

  8. falciparum malaria?

    African Journals Online (AJOL)

    destruction by the reticulo-endothelial system.'·. Skudowitz er al. '7 have shown that thrombocytopenia in falciparum malaria is the result of excessive splenic pool- ing as well as decreased platelet survival. Unfortunately, platelet counts could not be measured in our study. In patients with systemic lupus erythemarosus a ...

  9. Relationship between child survival and malaria transmission: an analysis of the malaria transmission intensity and mortality burden across Africa (MTIMBA) project data in Rufiji demographic surveillance system, Tanzania.

    Science.gov (United States)

    Rumisha, Susan F; Smith, Thomas A; Masanja, Honorati; Abdulla, Salim; Vounatsou, Penelope

    2014-03-28

    The precise nature of the relationship between malaria mortality and levels of transmission is unclear. Due to methodological limitations, earlier efforts to assess the linkage have lead to inconclusive results. The malaria transmission intensity and mortality burden across Africa (MTIMBA) project initiated by the INDEPTH Network collected longitudinally entomological data within a number of sites in sub-Saharan Africa to study this relationship. This work linked the MTIMBA entomology database with the routinely collected vital events within the Rufiji Demographic Surveillance System to analyse the transmission-mortality relation in the region. Bayesian Bernoulli spatio-temporal Cox proportional hazards models with village clustering, adjusted for age and insecticide-treated nets (ITNs), were fitted to assess the relation between mortality and malaria transmission measured by entomology inoculation rate (EIR). EIR was predicted at household locations using transmission models and it was incorporated in the model as a covariate with measure of uncertainty. Effects of covariates estimated by the model are reported as hazard ratios (HR) with 95% Bayesian confidence interval (BCI) and spatial and temporal parameters are presented. Separate analysis was carried out for neonates, infants and children 1-4 years of age. No significant relation between all-cause mortality and intensity of malaria transmission was indicated at any age in childhood. However, a strong age effect was shown. Comparing effects of ITN and EIR on mortality at different age categories, a decrease in protective efficacy of ITN was observed (i.e. neonates: HR = 0.65; 95% BCI:0.39-1.05; infants: HR = 0.72; 95% BCI:0.48-1.07; children 1-4 years: HR = 0.88; 95% BCI:0.62-1.23) and reduction on the effect of malaria transmission exposure was detected (i.e. neonates: HR = 1.15; 95% BCI:0.95-1.36; infants: HR = 1.13; 95% BCI:0.98-1.25; children 1-4 years: HR = 1.04; 95% BCI:0.89-1.18). A very strong spatial

  10. Clinical presentation of severe malaria due plasmodiun falciparum. casecontrol study in Tumaco and Turbo (Colombia. Clínica de la malaria complicada debida a P. falciparum Estudio de casos y controles en Tumaco y Turbo (Colombia

    Directory of Open Access Journals (Sweden)

    Jaime Carmona Fonseca

    2006-04-01

    Full Text Available Background: Latin American studies on severe falciparum malaria are scarce, therefore, the pattern of complications of the region is uknown. Objectives. To identify characterize severe malaria in patients from Tumaco (Nariño and Turbo (Antioquia in Colombia. Methods. The 2000 World Health Organization criteria for complicated malaria were applied in a cases and controls study. Results. 64 cases (P falciparum complicated malaria and 135 controls (P falciparum uncomplicated malaria were included. The time of evolution of the disease (mean 5.6 days in cases and 5.9 in the controls and the frequency of most symptoms were similar in both groups (p>0.05. However, respiratory distress and jaundice was more frequent in the cases (p<0.05. The mean glycemia and creatinina values were similar in both groups; hemoglobin and platelet count were lower in the cases (p<0.05 when compared to controls. On the other hand, blood ureic nitrogen, aspartatoaminotransferase, and total and direct bilirrubin were lower in controls (p<0.05. The frequency of complications in the cases was as follows: hyperparasitaemia 48%, liver dysfunction 44%, acute respiratory distress syndrome 9%, kidney failure 6%, severe thrombocytopenia 5%, severe anemia 3%, cerebral malaria 3% and severe hipoglycemia 2%. The WHO criteria for severe malaria were compared with others and the implications are discussed. Antecedentes y problema: son muy pocos los estudios latinoamericanos sobre malaria por Plasmodium falciparum (P falciparum complicada y se requiere estudiarla para identificar un patrón propio. OBJETIVOS. Identificar las complicaciones presentes en pacientes de Tumaco (Nariño y Turbo (Antioquia en Colombia, con malaria por P falciparum. MÉTODOS. Diseño de casos y controles. Se aplicaron los criterios diagnósticos de complicación OMS-2000 (Organización Mundial de la Salud. RESULTADOS. Se captaron 64 casos (con malaria por P. falciparum complicada y 135 controles (con malaria por

  11. Impact of chronic obstructive pulmonary disease on survival and symptoms of severe aortic valve stenosis

    DEFF Research Database (Denmark)

    Poulsen, Mikael K; Dahl, Jordi S; Kjeldsen, Bo J

    2015-01-01

    severe comorbidities, including chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Since the beginning of our TAVI program in March 2008, data on all 131 TAVI patients were prospectively and consecutively collected in this registry with complete follow-up. COPD was present in 37...... patients. By January 2012 survival data were collected from the Danish Civil Registration System. Median follow-up duration was 559 days. RESULTS: Overall survival and survival from cardiac death was equivalent in both patients with and without COPD (p = 0.98 and p = 0.26) in the follow-up period. Further...

  12. Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

    Science.gov (United States)

    Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

    2014-01-01

    Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR) are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm), was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture. PMID:25226036

  13. Interact to survive: Phyllobacterium brassicacearum improves Arabidopsis tolerance to severe water deficit and growth recovery.

    Directory of Open Access Journals (Sweden)

    Justine Bresson

    Full Text Available Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm, was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture.

  14. Artemisia vulgaris L. ethanolic leaf extract reverses thrombocytopenia/thrombocytosis and averts end-stage disease of experimental severe Plasmodium berghei murine malaria.

    Science.gov (United States)

    Bamunuarachchi, Gayan S; Ratnasooriya, Wanigasekara D; Premakumara, Sirimal; Udagama, Preethi V

    2014-12-01

    Artemisinin isolated from Artemisia annua is the most potent antimalarial against chloroquine resistant Plasmodium falciparum malaria. We previously reported that the ethanolic leaf extract of Artemisia vulgaris, an invasive weed and the only Artemisia species in Sri Lanka, possess both potent and safe antimalarial activity (in terms of antiparasitic properties) in a P. berghei murine malaria model. We report here a prototype study that investigated antidisease activities of A. vulgaris ethanolic leaf extract (AVELE) in a P. berghei ANKA murine malaria model that elicit pathogenesis similar to falciparum malaria. Profound thrombocytosis and thrombocytopenia in mice were detected in early-stage (Day 3), and at a later stage of infection (Day 6), respectively. Plasmodium berghei infected mice, 7 or 8 days post-infection reached end-stage disease with rapid drop in body temperature and usually die within 24 h, as a consequence of cerebral malaria. Three doses of the AVELE (500, 750 and 1000 mg/kg) were used to assess antidisease activity of A. vulgaris in terms of survival, effects on thrombocyte related pathology and end-stage disease, antipyretic activity, and antinociception, using standard methodology. The 1000 mg/kg dose of AVELE significantly increased survival, reversed the profound thrombocytopenia/ thrombocytosis (p ≤0.01), altered the end-stage disease (p ≤0.05), and manifested significant antipyretic and antinociceptive (p ≤0.05) activities. We conclude that a crude ethanolic leaf extract of A. vulgaris, showed potent antimalarial properties, in terms of antidisease activities; antipyretic activity, peripheral and central antinociception, increased survival, averted end-stage disease and reversed thrombocytopenia/thrombocytosis.

  15. Distinct roles for FOXP3 and FOXP3 CD4 T cells in regulating cellular immunity to uncomplicated and severe Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Michael Walther

    2009-04-01

    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.

  16. Characteristics of Travel-Related Severe Plasmodium vivax and Plasmodium falciparum Malaria in Individuals Hospitalized at a Tertiary Referral Center in Lima, Peru.

    Science.gov (United States)

    Llanos-Chea, Fiorella; Martínez, Dalila; Rosas, Angel; Samalvides, Frine; Vinetz, Joseph M; Llanos-Cuentas, Alejandro

    2015-12-01

    Severe Plasmodium falciparum malaria is uncommon in South America. Lima, Peru, while not endemic for malaria, is home to specialized centers for infectious diseases that admit and manage patients with severe malaria (SM), all of whom contracted infection during travel. This retrospective study describes severe travel-related malaria in individuals admitted to one tertiary care referral hospital in Lima, Peru; severity was classified based on criteria published by the World Health Organization in 2000. Data were abstracted from medical records of patients with SM admitted to Hospital Nacional Cayetano Heredia from 2006 to 2011. Of 33 SM cases with complete clinical data, the mean age was 39 years and the male/female ratio was 2.8. Most cases were contracted in known endemic regions within Peru: Amazonia (47%), the central jungle (18%), and the northern coast (12%); cases were also found in five (15%) travelers returning from Africa. Plasmodium vivax was most commonly identified (71%) among the severe infections, followed by P. falciparum (18%); mixed infections composed 11% of the group. Among the criteria of severity, jaundice was most common (58%), followed by severe thrombocytopenia (47%), hyperpyrexia (32%), and shock (15%). Plasmodium vivax mono-infection predominated as the etiology of SM in cases acquired in Peru. © The American Society of Tropical Medicine and Hygiene.

  17. Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites

    DEFF Research Database (Denmark)

    Sleebs, Brad E; Lopaticki, Sash; Marapana, Danushka S

    2014-01-01

    The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmep......The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease...... PEXEL cleavage occurs cotranslationaly, similar to signal peptidase. Treatment of P. falciparum-infected erythrocytes with the inhibitor caused dose-dependent inhibition of PEXEL processing as well as protein export, including impaired display of the major virulence adhesin, PfEMP1, on the erythrocyte...

  18. Clinical manifestations and outcomes of severe malaria among children admitted at Rungwe and Kyela district hospitals in south-western Tanzania.

    Science.gov (United States)

    Kalinga, Akili; Mayige, Mary; Kagaruki, Gibson; Shao, Amani; Mwakyusa, Brighton; Jacob, Frank; Mwesiga, Charles

    2012-01-01

    Malaria remains as an important public health and a major cause of childhood death and paediatric hospital admission in sub-Saharan Africa. This prospective hospital based cross sectional study was conducted from April 2007 to April 2008. The main objective was to assess clinical manifestations and outcomes of severe malaria in children admitted to district hospital in Rungwe and Kyela in south-western Tanzania. A total of 1371 children were selected as screening group of which 409 (29.8%) were tested positive for malaria. Mean age of the children was 2.7 (95%CI= 2.5, 2.8) years and the majority (86%) were under five years of age. The proportion of children severe malaria in Rungwe was significantly higher than that of Kyela by 21.3% (P=0.002). The common symptoms of severe malaria during admission were convulsions (50.9%) compensated shock (30.6%), prostration (29.1%) and symptomatic severe anaemia (14.9%). The case fatality rate (CFR) was 4.6% and the cure rate (CR) was 95.4%. Children with suspected severe acidosis and symptomatic severe anemia were 4.8 (95%CI=1.6, 14.6) and 5.5 (95%CI 1.1, 28.2), respectively, more likely to die compared to those without these symptoms. The proportion of deaths among children presenting ≥5 symptoms was 32.1% higher than among those presenting one symptom (OR =0.50, 95%CI 0.125-2.000; P=0.000). Convulsions and compensated shock were the leading symptoms at admission. Suspected severe acidosis and symptomatic severe anemia were the predictors of mortality for children. In order to reduce mortality among admitted children with severe malaria there is a need for health providers to deploy strategic management of fatal prognostic factors. In conclusion, convulsion and compensated shock were the leading symptoms among children at admission and that suspected severe acidosis and symptomatic severe anemia were the predictors of mortality. It is therefore important to emphasis early diagnosis and prompt treatment of severe cases of

  19. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    Science.gov (United States)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  20. Eleven years of malaria surveillance in a Sudanese village highlights unexpected variation in individual disease susceptibility and outbreak severity

    DEFF Research Database (Denmark)

    Creasey, A; Giha, H; Hamad, A A

    2004-01-01

    An analysis is presented of continuous data collected over 11 years based on 1,902,600 person/days of observation on the malaria experience of the people of Daraweesh, a village in eastern Sudan. Malaria transmission is hypo-endemic: the acquisition of clinical immunity with age is not as obvious...... as in more holo-endemic areas and malaria remained a problem in all age groups throughout the study. However, this population, who are of Fulani origin, showed a distinctly variable level of disease susceptibility. Thirty-two percent of the village never reported malaria symptoms or required malaria...... an interesting question for malaria modelling in this, and in other low transmission zones, such as the burgeoning urban areas of modern Africa....

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

    National Research Council Canada - National Science Library

    Santos-Ciminera, Patricia D

    2005-01-01

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

  2. "The Impact of Malaria Eradication on Fertility"

    OpenAIRE

    Adrienne M. Lucas

    2011-01-01

    The malaria eradication campaign that started in Sri Lanka in the late 1940s virtually eliminated malaria transmission on the island. I use the pre-eradication differences in malaria endemicity within Sri Lanka to identify the effect of malaria eradication on fertility and child survival. Malaria eradication increased the number of live births through increasing age specific fertility and causing an earlier first birth. The effect of malaria on the transition time to higher order births is in...

  3. Pathogenesis of Plasmodium berghei ANKA infection in the gerbil (Meriones unguiculatus as an experimental model for severe malaria

    Directory of Open Access Journals (Sweden)

    Junaid Quazim Olawale

    2017-01-01

    Full Text Available Background: As the quest to eradicate malaria continues, there remains a need to gain further understanding of the disease, particularly with regard to pathogenesis. This is facilitated, apart from in vitro and clinical studies, mainly via in vivo mouse model studies. However, there are few studies that have used gerbils (Meriones unguiculatus as animal models. Thus, this study is aimed at characterizing the effects of Plasmodium berghei ANKA (PbA infection in gerbils, as well as the underlying pathogenesis. Methods: Gerbils, 5-7 weeks old were infected by PbA via intraperitoneal injection of 1 × 106 (0.2 mL infected red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red blood cell count and body temperature changes in both control and infected groups were monitored over a duration of 13 days. RNA was extracted from the brain, spleen and whole blood to assess the immune response to PbA infection. Organs including the brain, spleen, heart, liver, kidneys and lungs were removed aseptically for histopathology. Results: Gerbils were susceptible to PbA infection, showing significant decreases in the hemoglobin concentration, RBC counts, body weights and body temperature, over the course of the infection. There were no neurological signs observed. Both pro-inflammatory (IFNγ and TNF and anti-inflammatory (IL-10 cytokines were significantly elevated. Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were observed in the organs, using routine light microscopy and in situ hybridization. Conclusion: Gerbils may serve as a good model for severe malaria to further understand its pathogenesis.

  4. Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1

    DEFF Research Database (Denmark)

    Petersen, Jens E V; Mkumbaye, Sixbert I; Vaaben, Anna V

    2016-01-01

    Membrane Protein 1 (PfEMP1) containing Cysteine Rich Inter Domain Region α1 (CIDRα1) domains predicted to bind Endothelial Protein C receptor (EPCR). ADAM17 levels were not associated with expression of var genes encoding different PfEMP1 types when controlling for age. These data are the first to report...... ADAM17 plasma levels in malaria-exposed individuals, and support the notion that parasite sequestration mediated by EPCR-binding PfEMP1 is associated with endothelial activation and pathology in severe paediatric malaria....

  5. CD36 selection of 3D7 Plasmodium falciparum associated with severe childhood malaria results in reduced VAR4 expression

    DEFF Research Database (Denmark)

    Magistrado, Pamela; Staalsoe, Trine; Theander, Thor

    2008-01-01

    ABSTRACT: BACKGROUND: A subset of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1SM) is involved in the cytoadherence of P. falciparum-infected red blood cells (iRBC) contributing to the pathogenesis of severe disease among young children in malaria endemic areas. The PfEMP1SM...

  6. IgE- and IgG mediated severe anaphylactic platelet transfusion reaction in a known case of cerebral malaria

    Directory of Open Access Journals (Sweden)

    B Shanthi

    2013-01-01

    Full Text Available Background: Allergic reactions occur commonly in transfusion practice. However, severe anaphylactic reactions are rare; anti-IgA (IgA: Immunoglobulin A in IgA-deficient patients is one of the well-illustrated and reported causes for such reactions. However, IgE-mediated hypersensitivity reaction through blood component transfusion may be caused in parasitic hyperimmunization for IgG and IgE antibodies. Case Report: We have evaluated here a severe anaphylactic transfusion reaction retrospectively in an 18year-old male, a known case of cerebral malaria, developed after platelet transfusions. The examination and investigations revealed classical signs and symptoms of anaphylaxis along with a significant rise in the serum IgE antibody level and IgG by hemagglutination method. Initial mild allergic reaction was followed by severe anaphylactic reaction after the second transfusion of platelets. Conclusion: Based on these results, screening of patients and donors with mild allergic reactions to IgE antibodies may help in understanding the pathogenesis as well as in planning for preventive desensitization and measures for safe transfusion.

  7. Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi in southern Tanzania: evaluation of impact on survival

    Directory of Open Access Journals (Sweden)

    Schellenberg Joanna

    2011-12-01

    Full Text Available Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12 or not (n = 12. Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P P = 0.31. Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

  8. Aortic valve replacement associated with survival in severe regurgitation and low ejection fraction.

    Science.gov (United States)

    Fiedler, Amy G; Bhambhani, Vijeta; Laikhter, Elizabeth; Picard, Michael H; Wasfy, Meagan M; Tolis, George; Melnitchouk, Serguei; Sundt, Thoralf M; Wasfy, Jason H

    2017-11-01

    Although guidelines support aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular ejection fraction (LVEF) <50%, severe left ventricular dysfunction (LVEF <35%) is thought to confer high surgical risk. We sought to determine if a survival benefit exists with AVR compared with medical management in this high-risk, relatively rare population. A large institutional echocardiography database was queried to identify patients with severe AR and LVEF <35%. Manual chart review was performed. Due to small sample size and population heterogeneity, corrected group prognosis method was applied, which calculates the adjusted survival curve for each individual using fitted Cox proportional hazard model. Average survival adjusted for comorbidities and age was then calculated using the weighted average of the individual survival curves. Initially, 2 54 614 echocardiograms were considered, representing 1 45 785 unique patients, of which 40 patients met inclusion criteria. Of those, 18 (45.0%) underwent AVR and 22 (55.0%) were managed medically. Absolute mortality was 27.8% in the AVR group and 91.2% in the medical management group. After multivariate adjustment, end-stage renal disease (HR=17.633, p=0.0335) and peripheral arterial disease (HR=6.050, p=0.0180) were associated with higher mortality. AVR was associated with lower mortality (HR=0.143, p=0.0490). Mean follow-up time of the study cohort was 6.58 years, and mean survival for patients undergoing AVR was 6.31 years. Even after adjustment for clinical characteristics and patient age, AVR is associated with higher survival for patients with low LVEF and severe AR. Although treatment selection bias cannot be completely eliminated by this analysis, these results provide some evidence that surgery may be associated with prolonged survival in this high-risk patient group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All

  9. Recognition, perceptions and treatment practices for severe malaria in rural Tanzania: implications for accessing rectal artesunate as a pre-referral.

    Directory of Open Access Journals (Sweden)

    Marian Warsame

    Full Text Available OBJECTIVES: Preparatory to a community trial investigating how best to deliver rectal artesunate as pre-referral treatment for severe malaria; local understanding, perceptions of signs/symptoms of severe malaria and treatment-seeking patterns for and barriers to seeking biomedical treatment were investigated. METHODOLOGY/PRINCIPAL FINDINGS: 19 key informant interviews, 12 in-depth interviews and 14 focus group discussions targeting care-givers, opinion leaders, and formal and informal health care providers were conducted. Monthly fever episodes and danger signs or symptoms associated with severe malaria among under-fives were recorded. Respondents recognized convulsions, altered consciousness and coma, and were aware of their risks if not treated. But, these symptoms were perceived to be caused by supernatural forces, and traditional healers were identified as primary care providers. With some delay, mothers eventually visited a health facility when convulsions were part of the illness, despite pressures against this. Although vomiting and failure to eat/suck/drink were associated with malaria, they were not considered as indicators of danger signs unless combined with another more severe symptom. Study communities were familiar with rectal application of medicines. CONCLUSIONS/SIGNIFICANCE: Communities' recognition and awareness of major symptoms of severe malaria could encourage action, but perceptions of their causes and poor discrimination of other danger signs - vomiting and failure to feed - might impede early treatment. An effective health education targeting parents/guardians, decision-makers/advisors, and formal and informal care providers might be a prerequisite for successful introduction of rectal artemisinins as an emergency treatment. Role of traditional healers in delivering such medication to the community should be explored.

  10. INFLUENCE OF SICKLE CELL GENE ON THE ALLELIC DIVERSITY AT THE MSP-1 LOCUS OF PLASMODIUM FALCIPARUM IN ADULT PATIENTS WITH SEVERE MALARIA

    Directory of Open Access Journals (Sweden)

    Dilip Kumar Patel

    2015-08-01

    Full Text Available Although several studies have supported that sickle cell trait (HbAS protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of sickle gene on parasitic diversity of P. falciparum population in severe symptomatic malaria.  This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum malaria. The study was carried out in 166 adult hospitalized subjects with severe falciparum malaria at Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, Odisha, India . They were divided into three groups on the basis of hemoglobin variants HbAA (n=104, HbAS (n=30 and HbSS (n=32. The msp-1 loci was genotyped using a PCR based methodology. The parasite densities were significantly high in HbAA compared to HbAS and HbSS. The multiplicity of infection (MOI and multiclonicity for msp-1 were significantly low in HbSS and HbAS compared to HbAA. The prevalence of K1 (p<0 .0001 and MAD20 (p=0.0003 alleles were significantly high in HbAA. The RO33 allele was detected at a higher frequency in HbSS and HbAS, compared to K1 and MAD20. Sickle gene was found to reduce both the parasite densities and diversity of P. falciparum in adults with severe malaria.

  11. South American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids.

    Directory of Open Access Journals (Sweden)

    Sean M Griffing

    Full Text Available Malaria has reemerged in many regions where once it was nearly eliminated. Yet the source of these parasites, the process of repopulation, their population structure, and dynamics are ill defined. Peru was one of malaria eradication's successes, where Plasmodium falciparum was nearly eliminated for two decades. It reemerged in the 1990s. In the new era of malaria elimination, Peruvian P. falciparum is a model of malaria reinvasion. We investigated its population structure and drug resistance profiles. We hypothesized that only populations adapted to local ecological niches could expand and repopulate and originated as vestigial populations or recent introductions. We investigated the genetic structure (using microsatellites and drug resistant genotypes of 220 parasites collected from patients immediately after peak epidemic expansion (1999-2000 from seven sites across the country. The majority of parasites could be grouped into five clonal lineages by networks and AMOVA. The distribution of clonal lineages and their drug sensitivity profiles suggested geographic structure. In 2001, artesunate combination therapy was introduced in Peru. We tested 62 parasites collected in 2006-2007 for changes in genetic structure. Clonal lineages had recombined under selection for the fittest parasites. Our findings illustrate that local adaptations in the post-eradication era have contributed to clonal lineage expansion. Within the shifting confluence of drug policy and malaria incidence, populations continue to evolve through genetic outcrossing influenced by antimalarial selection pressure. Understanding the population substructure of P. falciparum has implications for vaccine, drug, and epidemiologic studies, including monitoring malaria during and after the elimination phase.

  12. Blood transfusions for severe malaria-related anemia in Africa: a decision analysis

    NARCIS (Netherlands)

    C.O. Obonyo; E.W. Steyerberg (Ewout); A.J. Oloo; J.D.F. Habbema (Dik)

    1998-01-01

    textabstractSevere childhood malarial anemia is commonly treated using blood transfusion. Although transfusion may decrease short-term mortality, the risk of human immunodeficiency virus (HIV) transmission is considerable in Africa. We constructed a decision tree to

  13. Forecasting paediatric malaria admissions on the Kenya Coast using rainfall.

    Science.gov (United States)

    Karuri, Stella Wanjugu; Snow, Robert W

    2016-01-01

    Malaria is a vector-borne disease which, despite recent scaled-up efforts to achieve control in Africa, continues to pose a major threat to child survival. The disease is caused by the protozoan parasite Plasmodium and requires mosquitoes and humans for transmission. Rainfall is a major factor in seasonal and secular patterns of malaria transmission along the East African coast. The goal of the study was to develop a model to reliably forecast incidences of paediatric malaria admissions to Kilifi District Hospital (KDH). In this article, we apply several statistical models to look at the temporal association between monthly paediatric malaria hospital admissions, rainfall, and Indian Ocean sea surface temperatures. Trend and seasonally adjusted, marginal and multivariate, time-series models for hospital admissions were applied to a unique data set to examine the role of climate, seasonality, and long-term anomalies in predicting malaria hospital admission rates and whether these might become more or less predictable with increasing vector control. The proportion of paediatric admissions to KDH that have malaria as a cause of admission can be forecast by a model which depends on the proportion of malaria admissions in the previous 2 months. This model is improved by incorporating either the previous month's Indian Ocean Dipole information or the previous 2 months' rainfall. Surveillance data can help build time-series prediction models which can be used to anticipate seasonal variations in clinical burdens of malaria in stable transmission areas and aid the timing of malaria vector control.

  14. Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

    Science.gov (United States)

    Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

    2017-02-01

    Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p = .0001) and thienopyridine treatment (27% vs. 3%; p = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © AlphaMed Press 2017.

  15. Factors associated with severe disease from malaria, pneumonia and diarrhea among children in rural Tanzania – A hospital-based cross-sectional study

    Directory of Open Access Journals (Sweden)

    Kahabuka Catherine

    2012-09-01

    Full Text Available Abstract Background Mild cases of malaria, pneumonia and diarrhea are readily treatable with complete recovery and with inexpensive and widely available first-line drugs. However, treatment is complicated and expensive, and mortality is higher when children present to the hospital with severe forms of these illnesses. We studied how care seeking behaviours and other factors contributed to severity of malaria, pneumonia and diarrhoea among children less than five years in rural Tanzania. Methods We interviewed consecutive care-takers of children diagnosed with malaria, pneumonia and/or diarrhea at Korogwe and Muheza district hospitals, in north-eastern Tanzania, between July 2009 and January 2010, and compared characteristics of children presenting with severe and those with non-severe disease. Results A total of 293 children with severe and 190 with non-severe disease were studied. We found persistent associations between severity of disease and caretaker’s lack of formal education (OR 6.6; 95% confidence interval (CI 2.7-15.8 compared to those with post-primary education, middle compared to high socio-economic status (OR 1.9; 95% CI 1.2-3.2, having 4 or more children compared to having one child (OR 2.5; 95% CI 1.4-4.5, having utilized a nearer primary health care (PHC facility for the same illness compared to having not (OR 5.2; 95% CI 3.0-9.1, and having purchased the first treatment other than paracetamol from local or drug shops compared to when the treatment was obtained from the public hospitals for the first time (OR 3.2; 95% CI 1.9-5.2. The old officially abandoned first line anti-malaria drug Sulfadoxin-pyrimethamine (SP was found to still be in use for the treatment of malaria and was significantly associated with childrens’ presentation to the hospital with severe malaria (OR 12.5; 95% CI 1.6-108.0. Conclusions Our results indicate that caretakers with no formal education, with lower SES and with many children can be target

  16. Socioeconomic and environment determinants as predictors of severe malaria in children under 5 years of age admitted in two hospitals in Koudougou district, Burkina Faso: a cross sectional study.

    Science.gov (United States)

    Zoungrana, Amadou; Chou, Yiing-Jenq; Pu, Christy

    2014-11-01

    Burkina Faso has a high incidence and death rate of severe malaria, especially for children under 5 years of age. Although the malaria elimination program is a high-priority public health project, finding an effective strategy for managing the problem is a major challenge. Understanding the various factors that contribute to the severity of malaria is essential in designing an effective strategy. In this study, parental and environmental factors associated with severe malaria in Burkinabè children were investigated in two hospitals in Koudougou Health District, Burkina Faso. Between July and September 2012, a cross-sectional study was used to test 510 children under 5 years of age (mean age: 23.5 months) admitted with suspected malaria. Each child was screened using a blood smear to identify whether he or she had severe malaria based on the criteria established by the World Health Organization (WHO). When a child was diagnosed with malaria, either severe or not severe, the parents were interviewed by a trained interviewer using a structured questionnaire. A logistic regression was used to identify the determinants of severe malaria and associated deaths. Of the 510 children having malaria, 201 (39.4%) had severe malaria. Most of the patients (54.9%) lived in rural areas. The main factors associated with severe malaria were low education level of the father, low socioeconomic status [odds ratio (OR)=4.11, 95% confidence interval (CI)=1.44-11.75], delayed treatment [OR=4.53, 95% CI=1.76-11.65], treating children at home as a typical practice when the child has a fever [OR=3.24, 95% CI=1.40-7.51], living in rural area [OR=6.66, 95% CI=3.36-13.22], and living beside a water gathering pond (OR=1.67, 95% CI=1.02-2.74]. Parental and environmental context associated with severe malaria for children under 5 years of age remains a serious public health problem that affects malaria outcomes in resource-limited areas. Promotion of early care is urgently required. Parents

  17. Optimal freezing and thawing for the survival of peripheral nerves in severed rabbit limbs.

    Science.gov (United States)

    Zhu, Zexing; Qiao, Lin; Zhao, Yandong; Zhang, Shuming

    2014-01-01

    This study aimed to investigate the optimal freezing and thawing procedures for the survival of peripheral nerves in severed rabbit limbs. Twenty New Zealand White rabbits were randomized into four groups: normal control, slow-freezing fast-thawing, slow-freezing slow-thawing, fast-freezing fast-thawing, with five animals in each group. The hind limbs of the rabbits were severed at 1 cm above the knee joint. The severed limbs were cryopreserved with various freezing and thawing procedures. The sciatic nerves were harvested and trypsinized into single nerve fibers for morphological evaluation. The cell viability of the nerve fibers was examined by staining with Calcein-AM and propidium iodide. The fluorescent intensity of the nerve fibers was measured with a laser scanning confocal microscope. The morphology of the nerve fibers in the slow-freezing fast-thawing group was very similar with that of the normal control group, with only mild demyelination. The slow-freezing fast-thawing group and slow-freezing slow-thawing group showed severely damaged nerve fibers. The fluorescent intensities of the nerve fibers was significantly different among the four groups, with a decreasing order of normal control, slow-freezing fast-thawing, slow-freezing slow-thawing, and fast-freezing fast-thawing (P freezing fast thawing has the minimal effects on the survival of nerve fibers in severed rabbit limbs.

  18. Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: a cohort study.

    Science.gov (United States)

    Downs, Jenny; Torode, Ian; Wong, Kingsley; Ellaway, Carolyn; Elliott, Elizabeth J; Izatt, Maree T; Askin, Geoffrey N; Mcphee, Bruce I; Cundy, Peter; Leonard, Helen

    2016-06-01

    Scoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12-0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06-0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16-1.03; p=0.06). With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome. © 2015 Mac Keith Press.

  19. Non-typhi salmonella in children with severe malaria | Oundo | East ...

    African Journals Online (AJOL)

    19,118 (7.3%) and 342/1,820 (19%) respectively. Non-typhi salmonella consisted of 260/1,395 (18.6%) of the positive blood cultures and 92/324 (28.4%) of the stool cultures out of which a total of 101 NTS occurred in children with severe ...

  20. Levels of serum zinc and severity of malaria in under-fives: any ...

    African Journals Online (AJOL)

    Background: It remains uncertain why some individuals infected with Plasmodium falciparum develop severe disease while others do not. This may be due to differences in immunological status of the individuals. Zinc levels may play some roles in the immune competence of such individuals as manifested in its effects on ...

  1. Assessing Survival and Grading the Severity of Complications in Octogenarians Undergoing Pulmonary Lobectomy

    Directory of Open Access Journals (Sweden)

    Andrew Feczko

    2017-01-01

    Full Text Available Introduction. Octogenarians are at increased risk for complications after lung resection. With alternatives such as radiation, understanding the risks of surgery and associated survival are valuable. Data grading the severity of complications and long-term survival in this population is lacking. We reviewed our experience with lobectomy in octogenarians, grading complications using a validated thoracic morbidity and mortality schema. Methods. We retrospectively reviewed consecutive patients aged ≥80 undergoing lobectomy between 2004 and 2012. Demographics, clinical/pathologic stage, complications, recurrence, and mortality were collected. Complications were graded by the Seely thoracic morbidity and mortality model. Results. 45 patients (mean age 82.2 years were analyzed. The majority of patients (28/45, 62% were clinical stage IA/IB. 62% (28/45 of patients experienced a complication. Only 15.6% (7/45 were considered significantly morbid (≥ grade IIIB per the Seely model. Perioperative mortality was 2% and half of patients were living at a follow-up of 53 months. Overall five-year survival was 52%. Conclusions. In carefully selected octogenarians, lobectomy carries a 15.6% rate of significantly morbid complications with encouraging overall survival. These data provide the basis for a more complete discussion with patients regarding lobectomy for lung cancer.

  2. Prediction of the survival and functional ability of severe stroke patients after ICU therapeutic intervention

    Directory of Open Access Journals (Sweden)

    Aoun-Bacha Zeina

    2008-06-01

    Full Text Available Abstract Background This study evaluated the benefits and impact of ICU therapeutic interventions on the survival and functional ability of severe cerebrovascular accident (CVA patients. Methods Sixty-two ICU patients suffering from severe ischemic/haemorrhagic stroke were evaluated for CVA severity using APACHE II and the Glasgow coma scale (GCS. Survival was determined using Kaplan-Meier survival tables and survival prediction factors were determined by Cox multivariate analysis. Functional ability was assessed using the stroke impact scale (SIS-16 and Karnofsky score. Risk factors, life support techniques and neurosurgical interventions were recorded. One year post-CVA dependency was investigated using multivariate analysis based on linear regression. Results The study cohort constituted 6% of all CVA (37.8% haemorrhagic/62.2% ischemic admissions. Patient mean(SD age was 65.8(12.3 years with a 1:1 male: female ratio. During the study period 16 patients had died within the ICU and seven in the year following hospital release. The mean(SD APACHE II score at hospital admission was 14.9(6.0 and ICU mean duration of stay was 11.2(15.4 days. Mechanical ventilation was required in 37.1% of cases. Risk ratios were; GCS at admission 0.8(0.14, (p = 0.024, APACHE II 1.11(0.11, (p = 0.05 and duration of mechanical ventilation 1.07(0.07, (p = 0.046. Linear coefficients were: type of CVA – haemorrhagic versus ischemic: -18.95(4.58 (p = 0.007, GCS at hospital admission: -6.83(1.08, (p = 0.001, and duration of hospital stay -0.38(0.14, (p = 0.40. Conclusion To ensure a better prognosis CVA patients require ICU therapeutic interventions. However, as we have shown, where tests can determine the worst affected patients with a poor vital and functional outcome should treatment be withheld?

  3. [Survival analysis for patients with severe motor and intellectual disabilities following tracheotomy].

    Science.gov (United States)

    Maruyama, Koichi; Kurahashi, Hirokazu; Suzuki, Motomasa; Miura, Kiyokuni; Kumagai, Toshiyuki

    2012-01-01

    To investigate the survival rate and causes of death in patients with severe motor and intellectual disabilities (SMIDs) that necessitated tracheotomy, we retrospectively analyzed 90 patients who underwent tracheotomy between 1990 and 2009. Indications for tracheotomy in these patients were upper airway obstruction (44 patients), recurrent aspiration pneumonia (28 patients), retained secretions (23 patients), prolonged mechanical ventilation (18 patients), chronic respiratory failure (9 patients), central respiratory failure (5 patients), and gastroesophageal reflux (8 patients). Most of the patients underwent tracheotomy at the age of 0-5 years or 10-19 years. As of April 1, 2010, 28 patients had died. The survival rate was 0.91 at 1 year, 0.74 at 5 years, 0.59 at 10 years, 0.54 at 15 years, and 0.40 at 19 years after tracheotomy. Massive tracheal bleeding due to development of tracheo-innominate artery fistulas occurred in 5 patients, and 4 of them died. They were thirteen years of age or older when they underwent tracheotomy, and developed fistulas after 2 weeks or later. In contrast, 7 patients at high risk for fistula formation, including those that had developed severe tracheomalacia associated with granulation or warning hemorrhages, underwent preventive resection of the innominate artery, and all of them had survived. It is important to regularly evaluate patients with SMIDs who have undergone tracheotomy by using bronchofiberscopy to identify risk factors for tracheoinnominate artery fistulas, a preventable cause of death.

  4. Kompliceret malaria

    DEFF Research Database (Denmark)

    Rønn, A M; Bygbjerg, Ib Christian; Jacobsen, E

    1989-01-01

    An increasing number of cases of malaria, imported to Denmark, are caused by Plasmodium falciparum and severe and complicated cases are more often seen. In the Department of Infectious Diseases, Rigshospitalet, 23 out of 32 cases, hospitalized from 1.1-30.6.1988, i.e. 72%, were caused by P...

  5. Malaria og graviditet

    DEFF Research Database (Denmark)

    Hoffmann, A L; Rønn, A M; Langhoff-Roos, J

    1992-01-01

    In regions where malaria is endemism, the disease is a recognised cause of complications of pregnancy such as spontaneous abortion, premature delivery, intrauterine growth retardation and foetal death. Malaria is seldom seen in pregnant women in Denmark but, during the past two years, the authors...... the patients but also their practitioners were unaware that malaria can occur several years after exposure. Three out of the four patients had employed malaria prophylaxis. As resistance to malarial prophylactics in current use is increasing steadily, chemoprophylaxis should be supplemented by mechanical...... protection against malaria and insect repellents. As a rule, malaria is treated with chloroquine. In cases of Falciparum malaria in whom chloroquine resistance is suspected, treatment with mefloquine may be employed although this should only be employed in cases of dire necessity in pregnant patients during...

  6. Differing Causes of Lactic Acidosis and Deep Breathing in Cerebral Malaria and Severe Malarial Anemia May Explain Differences in Acidosis-Related Mortality.

    Science.gov (United States)

    Brand, Nathan R; Opoka, Robert O; Hamre, Karen E S; John, Chandy C

    Lactic acidosis (LA) is a marker for mortality in severe malaria, but the mechanisms that lead to LA in the different types of severe malaria and the extent to which LA-associated mortality differs by type of severe malaria are not well described. We assessed the frequency of LA in children admitted to Mulago Hospital, Kampala, Uganda with cerebral malaria (CM, n = 193) or severe malarial anemia (SMA, n = 216). LA was compared to mortality and measures of parasite biomass and sequestration (P. falciparum histidine-rich protein-2 (PfHRP2) concentration, platelet count), and to a measure of systemic tissue oxygen delivery (hemoglobin level). LA was more frequent in children with SMA than CM (SMA, 47.7%, CM, 34.2%, P = 0.006), but mortality was higher in children with CM (13.0%) than SMA (0.5%, P<0.0001). In CM, LA was associated with increased PfHRP2 concentration and decreased platelet count but was not associated with hemoglobin level. In contrast, in SMA, LA was associated with a decreased hemoglobin level, but was not associated with PfHRP2 concentration or platelet count. LA was related to mortality only in CM. In multivariable regression analysis of the effect PfHRP2 and hemoglobin levels on LA and DB, only PfHRP2 level increased risk of LA and DB in CM, while in SMA, elevated hemoglobin strongly decreased risk of LA and DB, and PfHRP2 level modestly increased risk of LA. The study findings suggest that LA in CM is due primarily to parasite sequestration, which currently has no effective adjunctive therapy, while LA in SMA is due primarily to anemia, which is rapidly corrected with blood transfusion. Differing etiologies of LA in CM and SMA may explain why LA is associated with mortality in CM but not SMA.

  7. Pediatric Triage in a Severe Pandemic: Maximizing Survival by Establishing Triage Thresholds.

    Science.gov (United States)

    Gall, Christine; Wetzel, Randall; Kolker, Alexander; Kanter, Robert K; Toltzis, Philip

    2016-09-01

    To develop and validate an algorithm to guide selection of patients for pediatric critical care admission during a severe pandemic when Crisis Standards of Care are implemented. Retrospective observational study using secondary data. Children admitted to VPS-participating PICUs between 2009-2012. A total of 111,174 randomly selected nonelective cases from the Virtual PICU Systems database were used to estimate each patient's probability of death and duration of ventilation employing previously derived predictive equations. Using real and projected statistics for the State of Ohio as an example, triage thresholds were established for casualty volumes ranging from 5,000 to 10,000 for a modeled pandemic with peak duration of 6 weeks and 280 pediatric intensive care beds. The goal was to simultaneously maximize casualty survival and bed occupancy. Discrete Event Simulation was used to determine triage thresholds for probability of death and duration of ventilation as a function of casualty volume and the total number of available beds. Simulation was employed to compare survival between the proposed triage algorithm and a first come first served distribution of scarce resources. Population survival was greater using the triage thresholds compared with a first come first served strategy. In this model, for five, six, seven, eight, and 10 thousand casualties, the triage algorithm increased the number of lives saved by 284, 386, 547, 746, and 1,089, respectively, compared with first come first served (all p triage thresholds based on probability of death and duration of mechanical ventilation determined from actual critically ill children's data demonstrated superior population survival during a simulated overwhelming pandemic.

  8. Use of the Behavior Rating Inventory of Executive Function and Child Behavior Checklist in Ugandan Children with HIV or a History of Severe Malaria.

    Science.gov (United States)

    Familiar, Itziar; Ruisenor-Escudero, Horacio; Giordani, Bruno; Bangirana, Paul; Nakasujja, Noeline; Opoka, Robert; Boivin, Michael

    2015-05-01

    To assess the structural overlap between the Behavior Rating Inventory of Executive Function (BRIEF) and Achenbach Child Behavior Checklist (CBCL) among children in Uganda. Caregiver ratings for the BRIEF and CBCL were obtained for 2 independent samples of school-aged children: 106 children (5-12 years old, 50% males) with a history of severe malaria and on 144 HIV-infected children (5-12 years old, 58% males) in Uganda. Exploratory factor analysis was used to evaluate the factor structure of the 8 subscales for the BRIEF and the 8 scales of the CBCL to determine correlation. Overall, children in the severe malaria group had higher (increased symptom) BRIEF and CBCL scores than those in the HIV-infected group. Three factors that provided a reasonable fit to the data and could be characterized as 3 specific domains were identified: (1) Metacognition, which consisted of the scales in the BRIEF Metacognition domain, (2) Behavioral Adjustment, which comprised of the scales in the BRIEF Behavioral Regulation domain and the Externalizing Symptoms scales in the CBCL, and (3) Emotional Adjustment, which mainly consisted of the Internalizing Symptoms scales in the CBCL. The BRIEF Behavior Regulation and CBCL Externalizing Symptoms scales, however, did overlap in terms of assessing similar behavior symptoms. These findings were consistent across the severe malaria and HIV-infected samples of children. The BRIEF and CBCL instruments offer distinct, yet complementary, assessments of behavior in clinical pediatric populations in the Ugandan context, supporting the use of these measures for similar research settings.

  9. Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?

    Directory of Open Access Journals (Sweden)

    Nagelkerke Nicolas

    2008-08-01

    Full Text Available Abstract Background The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of α+-thalassemia, which is protective against malaria. However, it also causes an excessive mortality amongst the offspring due to an increase in homozygosis of recessive lethal alleles. The aim of this study was to explore the overall effects of inbreeding on the fitness of a population infested with malaria. Methods In a stochastic computer model of population growth, the sizes of inbred and outbred populations were compared. The model has been previously validated producing results for inbred populations that have agreed with analytical predictions. Survival likelihoods for different α+-thalassemia genotypes were obtained from the odds of severe forms of disease from a field study. Survivals were further estimated for different values of mortality from malaria. Results Inbreeding increases the frequency of α+-thalassemia allele and the loss of life due to homozygosis of recessive lethal alleles; both are proportional to the coefficient of inbreeding and the frequency of alleles in population. Inbreeding-mediated decrease in mortality from malaria (produced via enhanced α+-thalassemia frequency mitigates inbreeding-related increases in fatality (produced via increased homozygosity of recessive lethals. When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population. Conclusion Consanguineous marriages may increase the overall fitness of populations with endemic malaria.

  10. Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria.

    Science.gov (United States)

    Plewes, Katherine; Soontarawirat, Ingfar; Ghose, Aniruddha; Bancone, Germana; Kingston, Hugh W F; Herdman, M Trent; Leopold, Stije J; Ishioka, Haruhiko; Faiz, Md Abul; Anstey, Nicholas M; Day, Nicholas P J; Hossain, Md Amir; Imwong, Mallika; Dondorp, Arjen M; Woodrow, Charles J

    2017-03-29

    Control of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh. G6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations. One male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants. In line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of

  11. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  12. Paracetamol versus placebo in treatment of non-severe malaria in children in Guinea-Bissau: a randomized controlled trial

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik; Ursing, Johan; Rodrigues, Amabelia

    2011-01-01

    The current guidelines for treatment of malaria include paracetamol to children with fever. No convincing evidence for the beneficial effects of this practice exists. Studies show that time to parasite clearance is significantly longer in children treated with paracetamol, which questions...

  13. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria.

    Science.gov (United States)

    Martins, Yuri C; Clemmer, Leah; Orjuela-Sánchez, Pamela; Zanini, Graziela M; Ong, Peng Kai; Frangos, John A; Carvalho, Leonardo J M

    2013-04-24

    Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM. However, the dose and administration route used is associated with cardiovascular side effects such as hypotension and bradycardia in humans and mice, which could preclude its potential use as adjunctive treatment in HCM. In the present study, alternative delivery systems for nimodipine during late-stage ECM in association with artesunate were searched to define optimal protocols to achieve maximum efficacy in increasing survival in rescue therapy while causing the least cardiac side effects. The baseline electrocardiogram (ECG) and arterial pressure characteristics of uninfected control animals and of mice with ECM and its response upon rescue treatment with artesunate associated or not with nimodipine is also analysed. Nimodipine, given at 0.5 mg/kg/day via a slow and continuous delivery system by osmotic pumps, increases survival of mice with ECM when used as adjunctive treatment to artesunate. Mice with ECM showed hypotension and ECG changes, including bradycardia and increases in PR, QRS, QTc and ST interval duration. ECM mice also show increased QTc dispersion, heart rate variability (HRV), RMSSD, low frequency (LF) and high frequency (HF) bands of the power spectrum. Both sympathetic and parasympathetic inputs to the heart were increased, but there was a predominance of sympathetic tone as demonstrated by an increased LF/HF ratio. Nimodipine potentiated bradycardia when given by bolus injection, but not when via osmotic pumps. In addition, nimodipine shortened PR duration and improved HRV, RMSSD, LF and HF powers in mice with ECM. In addition, nimodipine did not increased

  14. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  15. Effect of continuous hemofiltration on internal environment and survival rate of severe heatstroke dogs with shock

    Directory of Open Access Journals (Sweden)

    Guang-ming CHEN

    2011-08-01

    Full Text Available Objective To explore the effect of continuous hemofiltration(CHF on internal environment and survival rate of severe heatstroke dogs with shock.Methods Sixteen healthy male dogs were randomly divided into heatshock group(HS group,n=8 and continuous hemofiltration group(CHF group,n=8.Severe heatstroke model was established by applying high temperature to whole body,and then the animals were removed from the heating cabin as soon as they presented manifestations of shock.Dogs of HS group were put into an ordinary environment,while dogs of CHF group received CHF treatment.The core temperature(Tc,mean arterial pressure(MAP,blood gas analysis,serum electrolytes and survival rate of dogs in two groups were observed.Results The time from heat exposure to shock was 107.0±28.5min and 111.4±22.2min in HS group and CHF group respectively(t=-0.354,P=0.729.The Tc in CHF group declined to normal level 15 to 30 minitues after CHF treatment,while the Tc in HS group remained at a level higher than that before heat exposure at 90min after shock.The Tc of two groups showed significant difference at each time point after shock(P < 0.01.The MAP of both groups was obviously lowered than that before heatstroke.The MAP of CHF group raised gradually 30 min after treatment,while the MAP of HS group rose very slowly,and it was significantly lower than that of CHF group at each time point after 45min(P < 0.05,P < 0.01.All the dogs in both groups manifested hyperventilation and respiratory alkalosis when shock appeared.After shock,respiratory alkalosis in HS group gradually became metabolic acidosis,with some animals manifested combined metabolic and respiratory acidosis because of respiratory decompensation,while the blood gas levels in CHF group recovered to normal gradually.The blood gas levels of two groups showed significant difference at each time point after shock(P < 0.05,P < 0.01.Hypernatremia,hyperchloraemia and hyperpotassaemia were found in all animals of both

  16. Severe malaria in Battambang Referral Hospital, an area of multidrug resistance in Western-Cambodia: a retrospective analysis of cases from 2006–2009

    Science.gov (United States)

    2013-01-01

    Background Despite recent malaria containment and control efforts leading to reduced incidence, Cambodia remains endemic for both Plasmodium vivax and multidrug-resistant Plasmodium falciparum malaria. Little has been reported in the peer-reviewed literature regarding the burden of severe malaria (SM) in Cambodia. Methods Medical records for all patients admitted to the Battambang Referral Hospital (BRH) with an admitting or discharge diagnosis of SM from 2006 to 2009 (suspected SM cases) were reviewed. Those meeting the case definition of SM according to retrospective chart review and investigator assessment of probable cases, based on published national guidelines available at the time, were analysed for trends in demographics, mortality and referral patterns. Results Of the 537 suspected SM cases at BRH during the study period, 393 (73%) met published WHO criteria for SM infection. Despite limited diagnostic and treatment facilities, overall mortality was 14%, with 7% mortality in children 14 and under, but 19% in adults (60% of cases). Cerebral malaria with coma was relatively rare (17%), but mortality was disproportionately high at 35%. Mean time to hospital presentation was five days (range one to 30 days) after onset of symptoms. While patients with delays in presentation had worse outcomes, there was no excess mortality based on treatment referral times, distance travelled or residence in artemisinin-resistance containment (ARC) Zone 1 compared to Zone 2. Conclusions Despite limitations in diagnosis and treatment, and multiple confounding co-morbidities, mortality rates at BRH were similar to reports from other countries in the region. Interventions to improve access to early diagnosis and effective treatment, combined with modest improvements in intensive care, are likely to reduce mortality further. Patients referred from Zone 1 did not have excess mortality compared to Zone 2 ARC areas. A steep decrease in SM cases and deaths observed in the first half

  17. Malaria Research

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Malaria Go to Information for Researchers ► Malaria is a ... for the disease. Why Is the Study of Malaria a Priority for NIAID? Roughly 3.2 billion ...

  18. A spatial individual-based model predicting a great impact of copious sugar sources and resting sites on survival of Anopheles gambiae and malaria parasite transmission.

    Science.gov (United States)

    Zhu, Lin; Qualls, Whitney A; Marshall, John M; Arheart, Kris L; DeAngelis, Donald L; McManus, John W; Traore, Sekou F; Doumbia, Seydou; Schlein, Yosef; Müller, Günter C; Beier, John C

    2015-02-05

    Agent-based modelling (ABM) has been used to simulate mosquito life cycles and to evaluate vector control applications. However, most models lack sugar-feeding and resting behaviours or are based on mathematical equations lacking individual level randomness and spatial components of mosquito life. Here, a spatial individual-based model (IBM) incorporating sugar-feeding and resting behaviours of the malaria vector Anopheles gambiae was developed to estimate the impact of environmental sugar sources and resting sites on survival and biting behaviour. A spatial IBM containing An. gambiae mosquitoes and humans, as well as the village environment of houses, sugar sources, resting sites and larval habitat sites was developed. Anopheles gambiae behaviour rules were attributed at each step of the IBM: resting, host seeking, sugar feeding and breeding. Each step represented one second of time, and each simulation was set to run for 60 days and repeated 50 times. Scenarios of different densities and spatial distributions of sugar sources and outdoor resting sites were simulated and compared. When the number of natural sugar sources was increased from 0 to 100 while the number of resting sites was held constant, mean daily survival rate increased from 2.5% to 85.1% for males and from 2.5% to 94.5% for females, mean human biting rate increased from 0 to 0.94 bites per human per day, and mean daily abundance increased from 1 to 477 for males and from 1 to 1,428 for females. When the number of outdoor resting sites was increased from 0 to 50 while the number of sugar sources was held constant, mean daily survival rate increased from 77.3% to 84.3% for males and from 86.7% to 93.9% for females, mean human biting rate increased from 0 to 0.52 bites per human per day, and mean daily abundance increased from 62 to 349 for males and from 257 to 1120 for females. All increases were significant (P malaria parasite transmission.

  19. Effects of a new outdoor mosquito control device, the mosquito landing box, on densities and survival of the malaria vector, Anopheles arabiensis, inside controlled semi-field settings.

    Science.gov (United States)

    Mmbando, Arnold S; Okumu, Fredros O; Mgando, Joseph P; Sumaye, Robert D; Matowo, Nancy S; Madumla, Edith; Kaindoa, Emmanuel; Kiware, Samson S; Lwetoijera, Dickson W

    2015-12-09

    The significance of malaria transmission occurring outdoors has risen even in areas where indoor interventions such as long-lasting insecticidal nets and indoor residual spraying are common. The actual contamination rates and effectiveness of recently developed outdoor mosquito control device, the mosquito landing box (MLB), on densities and daily survival of host-seeking laboratory Anopheles arabiensis, which readily bites humans outdoors was demonstrated. Experiments were conducted in large semi-field systems (SFS) with human volunteers inside, to mimic natural ecosystems, and using MLBs baited with natural or synthetic human odours and carbon dioxide. The MLBs were dusted with 10% pyriproxyfen (PPF) or entomopathogenic fungi (Metarhizium anisopliae) spores to mark mosquitoes physically contacting the devices. Each night, 400 laboratory-reared An. arabiensis females were released in one SFS chamber with two MLBs, and another chamber without MLBs (control). Mosquitoes were individually recaptured while attempting to bite volunteers inside SFS or by aspiration from SFS walls. Mosquitoes from chambers with PPF-treated MLBs and respective controls were individually dipped in water-filled cups containing ten conspecific third-instar larvae, whose subsequent development was monitored. Mosquitoes recaptured from chambers with fungi-treated MLBs were observed for fungal hyphal growth on their cadavers. Separately, effects on daily survival were determined by exposing An. arabiensis in chambers having MLBs treated with 5% pirimiphos methyl compared to chambers without MLBs (control), after which the mosquitoes were recaptured and monitored individually until they died. Up to 63% (152/240) and 43% (92/210) of mosquitoes recaptured inside treatment chambers were contaminated with pyriproxyfen and M. anisopliae, respectively, compared to 8% (19/240) and 0% (0/164) in controls. The mean number of larvae emerging from cups in which adults from chambers with PPF-treated MLBs

  20. Case Report Frequent malaria illness episodes in two Malawian ...

    African Journals Online (AJOL)

    cotrimoxazole preventative therapy (CPT) and insecticide- treated bed net use is highly effective in preventing malaria in persons living with HIV.5,6 CPT provides a survival benefit to patients with HIV infection by preventing severe bacterial and parasitic infections, although its exact role for patients on successful ART in ...

  1. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.

    Science.gov (United States)

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi

    2016-01-11

    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.

  2. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice

    Science.gov (United States)

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi

    2016-01-01

    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

  3. The Malaria System MicroApp: A New, Mobile Device-Based Tool for Malaria Diagnosis.

    Science.gov (United States)

    Oliveira, Allisson Dantas; Prats, Clara; Espasa, Mateu; Zarzuela Serrat, Francesc; Montañola Sales, Cristina; Silgado, Aroa; Codina, Daniel Lopez; Arruda, Mercia Eliane; I Prat, Jordi Gomez; Albuquerque, Jones

    2017-04-25

    Malaria is a public health problem that affects remote areas worldwide. Climate change has contributed to the problem by allowing for the survival of Anopheles in previously uninhabited areas. As such, several groups have made developing news systems for the automated diagnosis of malaria a priority. The objective of this study was to develop a new, automated, mobile device-based diagnostic system for malaria. The system uses Giemsa-stained peripheral blood samples combined with light microscopy to identify the Plasmodium falciparum species in the ring stage of development. The system uses image processing and artificial intelligence techniques as well as a known face detection algorithm to identify Plasmodium parasites. The algorithm is based on integral image and haar-like features concepts, and makes use of weak classifiers with adaptive boosting learning. The search scope of the learning algorithm is reduced in the preprocessing step by removing the background around blood cells. As a proof of concept experiment, the tool was used on 555 malaria-positive and 777 malaria-negative previously-made slides. The accuracy of the system was, on average, 91%, meaning that for every 100 parasite-infected samples, 91 were identified correctly. Accessibility barriers of low-resource countries can be addressed with low-cost diagnostic tools. Our system, developed for mobile devices (mobile phones and tablets), addresses this by enabling access to health centers in remote communities, and importantly, not depending on extensive malaria expertise or expensive diagnostic detection equipment.

  4. Malaria control in rural Malawi

    NARCIS (Netherlands)

    Malenga, Tumaini; Kabaghe, Alinune Nathanael; Manda-Taylor, Lucinda; Kadama, Asante; McCann, Robert S.; Phiri, Kamija Samuel; Vugt, van Michèle; Berg, van den Henk

    2017-01-01

    Background: Interventions to reduce malaria burden are effective if communities use them appropriately and consistently. Several tools have been suggested to promote uptake and use of malaria control interventions. Community workshops on malaria, using the 'Health Animator' approach, are a potential

  5. Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

    Directory of Open Access Journals (Sweden)

    Pasque Michael K

    2007-01-01

    Full Text Available Abstract Objective Patients with severe left ventricular (LV dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+ in the post -operative period was compared to those without ICD (ICD-. Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5% patients received an ICD with a median of 2 (+/-2 years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT. There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

  6. MALARIA AMONG CHILDREN (1)

    African Journals Online (AJOL)

    BACKGROUND: Malaria is the most important parasitic disease of humans affecting more than half of the world population, majority of ... of this study was to describe patterns and trend of severe and complicated malaria cases, which could partly measure impact of .... Core body temperature >40°C. Hyperbilirubinemia.

  7. Malaria: uncomplicated, caused by Plasmodium falciparum

    OpenAIRE

    Taylor-Robinson, David; Jones, Katharine; Garner, Paul; Sinclair, David

    2008-01-01

    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...

  8. Fats & Fakes : Towards improved control of malaria

    NARCIS (Netherlands)

    Visser, B.J.

    2017-01-01

    Effective malaria control reduced the malaria burden worldwide tremendously. Simultaneously, the epidemiology of malaria is changing and has become more complex. To continue the progress of the last decade, this thesis addressed several areas of importance in the field of malaria. Since effective

  9. Economic evaluation of artesunate and three quinine regimens in the treatment of severe malaria in children at the Ebolowa Regional Hospital-Cameroon: a cost analysis.

    Science.gov (United States)

    Maka, Daniel Ethe; Chiabi, Andreas; Obadeyi, Bolaji; Mah, Evelyn; Nguefack, Séraphin; Nana, Pamela; Mbacham, Wilfred; Mbonda, Elie

    2016-12-07

    Severe malaria is a leading cause of morbidity and mortality in under-fives in sub-Saharan Africa. Recently quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. Artesunate has been shown to be cost-effective in African children, but whether these findings are transferable to Cameroonian children remains to be explored. To conduct a cost-analysis of four different regimens used in the treatment from the perspective of the healthcare payer. An economic evaluation alongside a randomized comparative study was conducted in children aged 3 months to 15 years, admitted at the Ebolowa Regional Hospital with severe malaria due to Plasmodium falciparum. Patients were randomized to receive one of the four treatment alternatives. Group 1 (ARTES) received parenteral artesunate at 2.4 mg/kg at H0, H12, H24 and then once daily; Group 2 (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 h later by an 8-hourly maintenance dose of 8.3 mg/kg quinine base; Group 3 (QNLD3) received 8.3 mg/kg quinine base every 8 h, and Group 4 (QNLD2) received 12.5 mg/kg quinine base every 12 h. The main outcome measure for effectiveness of treatment was the parasite reduction rate. Based on a healthcare perspective, an evaluation of direct medical costs was done, including costs of anti-malarials, nursing care materials, adjuvant treatment, laboratory investigations, hospitalisation and professional fees. Guided by a cost minimalization approach, the relative costs of these treatment alternatives was compared and reported. Overall cost was higher for ARTES group at $65.14 (95% CI $57.68-72.60) than for quinine groups ($52.49-$62.40), but the difference was not statistically significant. Cost of the anti-malarial drug was significantly higher for artesunate-treated patients than for quinine-treated patients, whereas cost of hospitalization was significantly lower for artesunate-treated patients than for quinine

  10. G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria

    Science.gov (United States)

    Satyagraha, Ari Winasti; Sadhewa, Arkasha; Baramuli, Vanessa; Elvira, Rosalie; Ridenour, Chase; Elyazar, Iqbal; Noviyanti, Rintis; Coutrier, Farah Novita; Harahap, Alida Roswita; Baird, J. Kevin

    2015-01-01

    Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (PG6PD deficiency (PG6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm. PMID:25746733

  11. Defining falciparum malaria attributable sever febrile illness in moderate to high transmission settings based on plasma PfHRP2 concentration

    NARCIS (Netherlands)

    Hendriksen, I.C.E.; White, L.J.; Veenemans, J.; Verhoef, J.C.M.

    2013-01-01

    Background. In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of

  12. Effect of severity of disability on survival in north east England cerebral palsy cohort

    OpenAIRE

    Hutton, J; Colver, A; Mackie, P; ROSENBLOOM, L.

    2000-01-01

    AIMS—To investigate the effect of motor and cognitive disabilities on the survival of people on the North of England Collaborative Cerebral Palsy Survey, and compare this with other published results.
METHODS—The cerebral palsy cohort consists of 1960-1990 births in Northumberland, Newcastle, and North Tyneside health districts. Survival and cause of death were analysed in relation to data on birth, disabilities, and a unique measure of the impact of disability.
RESULTS—D...

  13. Efficacy of Proveblue (Methylene Blue) in an Experimental Cerebral Malaria Murine Model

    OpenAIRE

    Dormoi, Jérome; Briolant, Sébastien; Desgrouas, Camille; Pradines, Bruno

    2013-01-01

    Although 100% of untreated mice infected with Plasmodium berghei died with specific signs of cerebral malaria and 100% of mice treated with 3 mg/kg dihydroartemisinin, the active metabolite of artesunate, which is used as the first-line treatment for severe malaria, also died but showed no specific signs of cerebral malaria, 78% of mice treated with 10 mg/kg Proveblue (methylene blue) and 78% of mice treated with a combination of 3 mg dihydroartemisinin and 10 mg/kg Proveblue survived and sho...

  14. Glucose production and gluconeogenesis in adults with uncomplicated falciparum malaria

    NARCIS (Netherlands)

    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.

    1997-01-01

    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

  15. Advances in Molecular Diagnosis of Malaria.

    Science.gov (United States)

    Zheng, Zhi; Cheng, Zhibin

    Malaria is a mosquito-borne disease caused by five species of Plasmodium parasites. Accurate diagnosis of malaria plays an essential part in malaria control. With traditional diagnostic methodologies, malaria control programs have achieved remarkable success during the past decade, and are now heading toward malaria elimination in many areas. This new situation, however, calls for novel diagnostics with improved sensitivity, throughput, and reduced cost for active screening of malaria parasites, as all transfected individuals have to be identified in order to block transmission. In this chapter, we provide a brief introduction of malaria, the requirement of diagnostic advances in the age of malaria elimination, and a comprehensive overview of the currently available molecular malaria diagnostics, ranging from well-known tests to platforms in early stages of evaluation. We also discussed several practical issues for the application of molecular tests in malaria identification. © 2017 Elsevier Inc. All rights reserved.

  16. Severe nutritional risk predicts decreased long-term survival in geriatric patients undergoing pancreaticoduodenectomy for benign disease.

    Science.gov (United States)

    Sanford, Dominic E; Sanford, Angela M; Fields, Ryan C; Hawkins, William G; Strasberg, Steven M; Linehan, David C

    2014-12-01

    Weight loss and malnutrition are poorly tolerated by geriatric patients, and pancreaticoduodenectomy (PD) can result in chronic malabsorption and weight loss. We sought to determine how preoperative severe nutritional risk (SNR), as defined by the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society Best Practice Guidelines, affects long-term survival after PD for benign disease among geriatric and nongeriatric patients. All patients undergoing PD for nonmalignant conditions at a single center between 1995 and 2013 were followed for survival, excluding patients who died within 90 days of surgery. Survival of geriatric (age ≥65 years) and nongeriatric (age patients with and without SNR was compared using Kaplan Meier methods. Cox regression was performed. There were 320 patients who underwent PD for benign disease. Over the course of the study, the proportion of geriatric patients undergoing PD for benign conditions increased from 25% to 46%. In addition to being older, geriatric patients undergoing PD for benign disease were significantly more likely to have coronary artery disease (CAD) and hypertension. Geriatric patients with preoperative SNR had significantly decreased long-term survival after PD for benign disease (p patients dead at 5 years compared with 1 in 14 patients without SNR. Survival was not significantly different among nongeriatric patients with and without SNR. In geriatric patients, age, CAD, and SNR were significantly associated with decreased survival on both univariate and multivariate analysis. Severe nutritional risk can be a useful predictor of long-term survival in geriatric patients undergoing PD, and could improve patient risk stratification preoperatively. Nonoperative management should be strongly considered in geriatric patients with SNR, when malignancy is not suspected. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Extracorporeal life support with left ventricular decompression-improved survival in severe cardiogenic shock: results from a retrospective study.

    Science.gov (United States)

    Schmack, Bastian; Seppelt, Philipp; Weymann, Alexander; Alt, Christina; Farag, Mina; Arif, Rawa; Doesch, Andreas O; Raake, Philip W; Kallenbach, Klaus; Mansur, Ashham; Popov, Aron-Frederik; Karck, Matthias; Ruhparwar, Arjang

    2017-01-01

    Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression. Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 20, 41.7%) or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial. Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival. ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.

  18. Hyperparasitaemia during bouts of malaria in French Guiana.

    Science.gov (United States)

    Carme, Bernard; Demar, Magalie

    2013-01-16

    High circulating parasite load is one of the WHO criteria for severe falciparum malaria. During a period of 11 years (2000-2010), the frequency of hyperparasitaemia (HP) (≥4% infected erythrocytes) during bouts of malaria due to Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae in patients referred to Cayenne General Hospital (CGH) in French Guiana and the frequency of their admission to the Intensive Care Unit (ICU) were evaluated. A mean of 1,150 malaria cases were referred to the Parasitology Laboratory of CGH each year over the last decade. During this period, malaria diagnostic (microscopy) and parasitaemia evaluation have remained unchanged: determination of the parasitized erythrocytes percentage with asexual forms on thin blood smears for all cases of parasitaemia exceeding 0.1%. Patients admitted to the ICU can be counted by origin of the request for malaria testing. All the data collected retrospectively were anonymized in a standardized case report form and in database. Between 2000 and 2010, 12,254 bouts of malaria were confirmed at the Parasitology Laboratory of CHG: P. vivax: 56.2%, P. falciparum: 39.5%, co-infection with both species: 3.4%, P. malariae: 0.9%. HP was observed in 262 cases, at a frequency of 4.9% for P. falciparum and only 0.041% for P. vivax, with no recorded cases for P. malariae. The need for intensive care was correlated with P. falciparum parasite load: 12.3% of cases for parasitaemia of 4-9%, 21.2% for parasitaemia 10-19%, 50% for parasitaemia 20-29% and 77.8% for parasitaemia ≥30% (n=9). The patient with the highest parasitaemia (75% infected erythrocytes with asexual form) presented a major concomitant lupus flare-up treated with corticoids. He survived without obvious sequelae. In French Guiana during bouts of malaria, HP was observed at a frequency of ~ 5% for P. falciparum and two orders of magnitude less frequent for P. vivax. HP is a severity criterion for falciparum malaria in this endemic area. However

  19. Determining utility values related to malaria and malaria chemoprophylaxis

    Directory of Open Access Journals (Sweden)

    Coyle Doug

    2010-04-01

    Full Text Available Abstract Background Chemoprophylaxis for travellers' malaria is problematic. Decision modeling may help determine optimal prevention strategies for travellers' malaria. Such models can fully assess effect of drug use and disease on quality of life, and help travellers make informed values based decisions. Such models require utility values reflecting societal preferences over different health states of relevance. To date, there are no published utility values relating to clinical malaria or chemoprophylaxis adverse events. Methods Utility estimates for health states related to falciparum malaria, sequelae and drug-related adverse events were obtained using a self-administered visual analogue scale in 20 individuals. Utility values for health states related to clinical malaria were obtained from a survey of 11 malaria experts questioned about length of hospital stay or equivalent disability with simple and severe travellers' malaria. Results The general public (potential travellers, were more tolerant of taking prophylaxis if associated with no or mild AEs and least tolerant of mild sequelae from malaria and severe drug related events. The rating value reported for taking no prophylaxis was quite variable. Tropical medicine specialists estimated a mean hospital stay 3.23 days (range 0.5-4.5 days for simple and 6.36 days (range 4.5 - 7 days for severe malaria. Conclusions This study provides a benchmark for important utility value estimates for modeling malaria and drug-related outcomes in non-immune travellers.

  20. Malaria biology and disease pathogenesis: insights for new treatments

    Science.gov (United States)

    Miller, Louis H; Ackerman, Hans C; Su, Xin-zhuan; Wellems, Thomas E

    2016-01-01

    Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival. PMID:23389616

  1. Association between Fcγ receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya.

    Science.gov (United States)

    Munde, Elly O; Okeyo, Winnie A; Raballah, Evans; Anyona, Samuel B; Were, Tom; Ong'echa, John M; Perkins, Douglas J; Ouma, Collins

    2017-04-20

    Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (FcγRs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. FcγR polymorphisms influence binding affinity to IgGs and consequently, can influence clinical malaria outcomes. Specifically, variations in FcγRIIA -131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 modulate immune responses through altered binding preferences to IgGs and immune complexes. Differential binding, in turn, changes ability of immune cells to respond to infection through production of inflammatory mediators during P. falciparum infection. We determined the association between haplotypes of FcγRIIA-131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 variants and severe malarial anemia (SMA; hemoglobin malaria in a holoendemic transmission region of western Kenya. FcγRIIA-131Arg/His and FcγRIIIA-176F/V genotypes were determined using TaqMan® SNP genotyping, while FcγRIIIBNA1/NA2 genotypes were determined using restriction fragment length polymorphism. Hematological and parasitological indices were measured in all study participants. Carriage of FcγRIIA-131Arg/FcγRIIIA-176F/FcγRIIIBNA2 haplotype was associated with susceptibility to SMA (OR = 1.70; 95% CI; 1.02-2.93; P = 0.036), while the FcγRIIA-131His/ FcγRIIIA-176F/ FcγRIIIB NA1 haplotype was marginally associated with enhanced susceptibility to SMA (OR: 1.80, 95% CI; 0.98-3.30, P = 0.057) and higher levels of parasitemia (P = 0.009). Individual genotypes of FcγRIIA-131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 were not associated with susceptibility to SMA. The study revealed that haplotypes of FcγRs are important in conditioning susceptibility to SMA in immune-naive children from P. falciparum holoendemic region of western Kenya.

  2. Chloroquine resistant malaria in neonates.

    Science.gov (United States)

    Khichi, Qasim Khan; Channar, Mohammad Saleem; Wairraich, Mohammad Ihsan; Butt, Ahsan

    2005-01-01

    To analyze the clinical presentation, treatment given, and outcome of patients suffering from congenital and acquired malaria in neonatal period. Analytical study. Paediatrics Ward-2, QAMC/BVH, Bahawalpur for 02 years from October 2001 to October 2003. The study included 45 cases of neonatal malaria. Thirty cases of malaria, admitted during first ten days of life, diagnosed as congenital malaria, were kept in group A, while 15 cases admitted in the ward from the age of 11 to 28 days, labeled as acquired malaria, were named group B. The clinical features at the time of presentation were noted in each group from the charts having positive malarial parasite (M.P.) on thick and thin slides. The diagnosed cases were treated with the standard dose of chloroquine sulphate. Those patients who improved clinically as well as revealed no parasite on follow-up were labeled as chloroquine sensitive. On the other hand, patients showing poor clinical response with persistence of the parasites in the blood or initially disappearing but later again having a clinical disease with positive M.P. on follow-up, were labeled as chloroquine resistant. They were treated with quinine sulphate. Outcome was compared in both the groups regarding the pattern of chloroquine resistance and death/ survival. Data was collected on which Fischer's exact test of significance was performed to know the level of significance. P-value of < 0.05 was taken as statistically significant. Low birth weight, severe hemolytic anemia with history of fever in the mother were main features in group A while in group B fever, anaemia and history of blood transfusion were marked features. In group A 76.66% were caused by Plasmodium (P.) falciparum. While in group B 60% were caused by Plasmodium vivax. In group A 26.66% were chloroquine resistant while 33.65% were chloroquine resistant in group B. The mortality was 16.66% in group A and 13.33% in group B. Intrauterine growth retardation, hemolytic jaundice and history

  3. The Severity of Plasmodium falciparum infection is associated with transcript levels of var genes encoding endothelial protein C receptor-binding P. falciparum erythrocyte membrane protein 1

    DEFF Research Database (Denmark)

    Mkumbaye, Sixbert I; Wang, Christian W; Lyimo, Eric

    2017-01-01

    importance of different subtypes of CIDRα1 domains, we compared Pfemp1 transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria (n = 42), children with mild malaria not requiring hospitalization (n = 10), and children...... the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDRα1 subtypes....

  4. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.

    Science.gov (United States)

    Gadalla, Shahinaz M; Wang, Tao; Haagenson, Michael; Spellman, Stephen R; Lee, Stephanie J; Williams, Kirsten M; Wong, Jason Y; De Vivo, Immaculata; Savage, Sharon A

    2015-02-10

    Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity. To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia. The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013. Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution. Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up. Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P = .009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence

  5. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer

    Science.gov (United States)

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-01-01

    Abstract Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. PMID:27043677

  6. (quinine) and to prevent malaria (mefloquine

    African Journals Online (AJOL)

    . Quinine is the main treatment for severe malaria in Comoros and Madagascar. Mefloquine and cycloguanil-based antimalarial drugs are recommended for the prevention of malaria, particularly for travellers.'·' Very few in vivo or in vitro.

  7. Embolization of severe arterioportal shunts in the patients with hepatocellular carcinoma : safety and influence on patient survival

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Deok Hee; Yoon, Hyun Ki; Song, Ho Young; Kim, Gab Choul; Hwang, Jae Cheol; Sung, Kyu Bo [Asan Medical Center, Ulsan Univ. College of Medicine, Ulsan (Korea, Republic of)

    1999-12-01

    To evaluate the safety and the influence of embolization of severe arterioportal shunts, and the effect of the procedure on the survival rate of patients with hepatocellular carcinoma combined with portal vein tumor thrombosis. This study involved a total of 54 patients with hepatocellular carcinoma in whom hepatic arteriography revealed severe arterioportal shunt. From among this total, 34 patients (embolization group) underwent chemoinfusion after shunt embolization, while 19 (control group) underwent chemoinfusion only. The embolic materials included PVA particles and /or Gelfoam pieces. The frequency of postem-bolization symptoms (Chi-squared test) and changes in laboratory values (paired t-test) were compared between the two groups, and shunt improvement was also evaluated. Patient survival was tested using the Kaplan-Meier method. Fever and RUQ pain were more frequent in the embolization group (p<0.001). The complications of embolization included severe postembolization syndrome (n=1), acute hepatic failure (n=2), hepatic infarction (n=1), and sepsis (n=1). There were no significant changes in laboratory values. Among the 28 patients (24 of embolization group and four of control group) who underwent follow-up angiography, arterioportal shunt became less severe or disappeared in ten of the embolization group. For the embolization and control groups, the mean survival interval was 29.5{+-}5.4 weeks and 10.3{+-}3.1 weeks (p=0.0002), respectively. The best results were seen in the PVA particle group (p=0.01). The embolization of severe arterioportal shunts is relatively safe and increases patient survival rate.

  8. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while hypoglyc......In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while...

  9. [Malaria in Algerian Sahara].

    Science.gov (United States)

    Hammadi, D; Boubidi, S C; Chaib, S E; Saber, A; Khechache, Y; Gasmi, M; Harrat, Z

    2009-08-01

    Thanks to the malaria eradication campaign launched in Algeria in 1968, the number of malaria cases fell down significantly from 95,424 cases in 1960 to 30 cases in 1978. At that time the northern part of the country was declared free of Plasmodium falciparum. Only few cases belonging to P. vivax persisted in residual foci in the middle part of the country. In the beginning of the eighties, the south of the country was marked by an increase of imported malaria cases. The resurgence of the disease in the oases coincided with the opening of the Trans-Saharan road and the booming trade with the neighbouring southern countries. Several authors insisted on the risk of introduction of malaria or its exotic potential vectors in Algeria via this new road. Now, the totality of malaria autochthonous cases in Algeria are located in the south of the country where 300 cases were declared during the period (1980-2007). The recent outbreak recorded in 2007 at the borders with Mall and the introduction of Anopheles gambiae into the Algerian territory show the vulnerability of this area to malaria which is probably emphasized by the local environmental changes. The authors assess the evolution of malaria in the Sahara region and draw up the distribution of the anopheles in this area.

  10. Continuous Renal Replacement Therapy Improves Survival in Severely Burned Military Casualties With Acute Kidney Injury

    National Research Council Canada - National Science Library

    Chung, Kevin K; Juncos, , Luis A; Wolf, Steven E; Mann, Elizabeth E; Renz, Evan M; White, Christopher E; Barillo, David J; Clark, Richard A; Jones, John A; Edgecombe, Harcourt P

    2007-01-01

    .... We wondered whether early use of continuous renal replacement therapy (CRRT) changes outcomes in severely burned military casualties with predetermined criteria for acute kidney injury. Methods...

  11. Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors.

    Science.gov (United States)

    Grossman, Stuart A; Ellsworth, Susannah; Campian, Jian; Wild, Aaron T; Herman, Joseph M; Laheru, Dan; Brock, Malcolm; Balmanoukian, Ani; Ye, Xiaobu

    2015-10-01

    The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival. Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed. The data set included 297 patients with newly diagnosed malignant glioma (N=96), resected pancreatic cancer (N=53), unresectable pancreatic cancer (N=101), and non-small cell lung cancer (N=47). Pretreatment lymphocyte counts were normal in 83% of the patient population, and no patient had severe baseline lymphopenia. Two months after initiating chemoradiation, 43% developed severe and persistent lymphopenia (P=.001). An increased risk for death was attributable to TRL in each cancer cohort (gliomas: hazard rate [HR], 1.8; 95% CI, 1.13-2.87; resected pancreas: HR, 2.2; 95% CI, 1.17-4.12; unresected pancreas: HR, 2.9; 95% CI, 1.53-5.42; and lung: HR, 1.7; 95% CI, 0.8-3.61) and in the entire study population regardless of pathologic findings (HR, 2.1; 95% CI, 1.54-2.78; P<.0001). Severe TRL was observed in more than 40% of patients 2 months after initiating chemoradiation, regardless of histology or chemotherapy regimen, and was independently associated with shorter survival from tumor progression. Increased attention and research should be focused on the cause, prevention, and reversal of this unintended consequence of cancer treatment that seems to be related to survival in patients with solid tumors. Copyright © 2015 by the National Comprehensive Cancer Network.

  12. Disseminated intravascular coagulation in malaria: A case report ...

    African Journals Online (AJOL)

    Disseminated intravascular coagulation (DIC) is seen in <5% of patients with severe Plasmodium falciparum malaria and is more common in cerebral malaria. Here, we report the diagnosis and management of a case of severe P. falciparum malaria with DIC. Keywords: Cerebral malaria, cytokine storm, DIC, heparin ...

  13. Extracorporeal life support with left ventricular decompression—improved survival in severe cardiogenic shock: results from a retrospective study

    Directory of Open Access Journals (Sweden)

    Bastian Schmack

    2017-09-01

    Full Text Available Objective Extracorporeal life support (ECLS is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression. Methods Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years, who received either central ECLS with (n = 20, 41.7% or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS integrated left ventricular vent in our retrospective single centre trial. Results Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14, bridge to transplant in 10.4% (n = 5 and bridge to recovery in 8.3% (n = 4. Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034. Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent. Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival. Conclusion ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.

  14. Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre.

    Science.gov (United States)

    Daniel, C R; Shu, X; Ye, Y; Gu, J; Raju, G S; Kopetz, S; Wu, X

    2016-01-12

    In contrast to the consistent evidence for obesity and colorectal cancer (CRC) risk, the impact of obesity in CRC patients is less clear. In a well-characterised cohort of CRC patients, we prospectively evaluated class I and class II obesity with survival outcomes. The CRC patients (N=634) were followed from the date of diagnosis until disease progression/first recurrence (progression-free survival (PFS)) or death (overall survival (OS)). Body mass index (BMI) was calculated from reported usual weight prior to diagnosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in models adjusted for clinicopathologic, treatment, and lifestyle factors. Over a median follow-up of 4 years, 208 (33%) patients died and 235 (37%) recurred or progressed. Class II obesity, as compared with either overweight or normal weight, was associated with an increased risk of death (HR and 95% CI: 1.55 (0.97-2.48) and 1.65 (1.02-2.68), respectively), but no clear association was observed with PFS. In analyses restricted to patients who presented as stages I-III, who reported stable weight, or who were aged obesity was associated with a significant two- to five-fold increased risk of death. In CRC patients evaluated at a large cancer centre, severely obese patients experienced worse survival outcomes independent of many other factors.

  15. Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: Implications for the development of severe anemia

    Directory of Open Access Journals (Sweden)

    Odera Michael M

    2008-08-01

    Full Text Available Abstract Background Severe anemia due to Plasmodium falciparum malaria is a major cause of mortality among young children in western Kenya. The factors that lead to the age-specific incidence of this anemia are unknown. Previous studies have shown an age-related expression of red cell complement regulatory proteins, which protect erythrocytes from autologous complement attack and destruction. Our primary objective was to determine whether in a malaria-endemic area red cells with low levels of complement regulatory proteins are at increased risk for complement (C3b deposition in vivo. Secondarily, we studied the relationship between red cell complement regulatory protein levels and hemoglobin levels. Methods Three hundred and forty-two life-long residents of a malaria-holoendemic region of western Kenya were enrolled in a cross-sectional study and stratified by age. We measured red cell C3b, CR1, CD55, and immune complex binding capacity by flow cytometry. Individuals who were positive for malaria were treated and blood was collected when they were free of parasitemia. Analysis of variance was used to identify independent variables associated with the %C3b-positive red cells and the hemoglobin level. Results Individuals between the ages of 6 and 36 months had the lowest red cell CR1, highest %C3b-positive red cells, and highest parasite density. Malaria prevalence also reached its peak within this age group. Among children ≤ 24 months of age the %C3b-positive red cells was usually higher in individuals who were treated for malaria than in uninfected individuals with similarly low red cell CR1 and CD55. The variables that most strongly influenced the %C3b-positive red cells were age, malaria status, and red cell CD55 level. Although it did not reach statistical significance, red cell CR1 was more important than red cell CD55 among individuals treated for malaria. The variables that most strongly influenced the hemoglobin level were age, the %C3b

  16. Bioinformatics approaches to malaria

    DEFF Research Database (Denmark)

    Hansen, Daniel Aaen

    Malaria is a life threatening disease found in tropical and subtropical regions of the world. Each year it kills 781 000 individuals; most of them are children under the age of five in sub-Saharan Africa. The most severe form of malaria in humans is caused by the parasite Plasmodium falciparum......, which is the subject of the first part of this thesis. The PfEMP1 protein which is encoded by the highly variablevargene family is important in the pathogenesis and immune evasion of malaria parasites. We analyzed and classified these genes based on the upstream sequence in seven......Plasmodium falciparumclones. We show that the amount of nucleotide diversity is just as big within each clone as it is between the clones. DNA methylation is an important epigenetic mark in many eukaryotic species. We are studying DNA methylation in the malaria parasitePlasmodium falciparum. The work is still in progress...

  17. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Wang, Christian W.; Mkumbaye, Sixbert I.

    2016-01-01

    Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding hum...

  18. Use of evidence based practices to improve survival without severe morbidity for very preterm infants

    DEFF Research Database (Denmark)

    Zeitlin, Jennifer; Manktelow, Bradley N; Piedvache, Aurelie

    2016-01-01

    population based observational study. SETTING: 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. PARTICIPANTS: 7336 infants born between 24+0 and 31+6 weeks' gestation in 2011...... of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. RESULTS: Only 58.3% (n=4275) of infants received all evidence based practices...... ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. CONCLUSIONS: More...

  19. Predictive value of the Status Epilepticus Severity Score (STESS) and its components for long-term survival

    DEFF Research Database (Denmark)

    Aukland, Preben; Lando, Martin; Vilholm, Ole

    2016-01-01

    with lower odds ratios. When looking only at patients that survived the acute phase of treatment, only the STESS components "level of consciousness" (at admission), "coma" as worst seizure type, and "age" reached a statistical significant association with mortality. In these patients, STESS with a cut......BACKGROUND: The "Status Epilepticus Severity Score" (STESS) is the most important clinical score to predict in-hospital mortality of patients with status epilepticus (SE), but its prognostic relevance for long-term survival is unknown. This study therefore examined if STESS and its components...... retain their prognostic relevance beyond acute treatment. METHODS: One hundred twenty-five non-anoxic patients with SE were retrospectively identified in two hospitals between 2008 and 2014 (39.2 % refractory SE). Patients' treatment, demographic data, date of death, aetiology of SE, and the components...

  20. Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

    DEFF Research Database (Denmark)

    Egeberg, A; Ottosen, M B; Gniadecki, R

    2018-01-01

    originators with biosimilars (i.e. Enbrel with Benepali, and Remicade with Remsima). METHODS: The DERMBIO registry contains data on all Danish patients with moderate-to-severe plaque psoriasis treated with biologics. We examined patients treated between January 1(st) , 2007 and March 31(st) , 2017. We used...

  1. Floral resource limitation severely reduces butterfly survival, condition and flight activity in simplified agricultural landscapes.

    Science.gov (United States)

    Lebeau, Julie; Wesselingh, Renate A; Van Dyck, Hans

    2016-02-01

    Agricultural intensification has a strong negative impact on farmland biodiversity (including flower-visiting insects), but understanding the mechanisms involved in this requires experimental work. We document the impact of nectar limitation on the performance of a flower-visiting insect, the meadow brown butterfly Maniola jurtina. We conducted two types of experiments: a field experiment in agricultural landscapes with grasslands of different management intensity and an experiment in outdoor flight cages in which the nectar supply was simulated. For the field experiment, we introduced an array of nectar resources in intensively managed, nectar-poor meadows and in extensively managed, flower-rich grasslands and counted flower visitors. Despite higher butterfly abundance in the extensive meadows, our introduced nectar sources were more frequently visited in intensive meadows, indicating the lack of floral resources. The 48-h confinement under nectar-poor conditions in the flight cages had a strong negative effect on body condition, flight activity and lifetime survival compared to butterflies under nectar-rich conditions. Female lifespan was reduced by 22% and male lifespan even by 43%. Agricultural landscapes that provide limited amounts of floral nectar, and no high-quality, preferred nectar sources relative to the needs of the flower-visiting species, may create ecological sinks. Regards an insect's performance, the simple presence of nectar is not necessarily functionally adequate. The effectiveness of agri-environmental schemes for flower-visiting insects (e.g. flower strips) could be improved based on ecological and evolutionary insights on the effects of specific nectar quantities and qualities.

  2. Pulmonary Vascular Distensibility Predicts Pulmonary Hypertension Severity, Exercise Capacity, and Survival in Heart Failure.

    Science.gov (United States)

    Malhotra, Rajeev; Dhakal, Bishnu P; Eisman, Aaron S; Pappagianopoulos, Paul P; Dress, Ashley; Weiner, Rory B; Baggish, Aaron L; Semigran, Marc J; Lewis, Gregory D

    2016-06-01

    Pulmonary vascular (PV) distensibility, defined as the percent increase in pulmonary vessel diameter per mm Hg increase in pressure, permits the pulmonary vessels to increase in size to accommodate increased blood flow. We hypothesized that PV distensibility is abnormally low in patients with heart failure (HF) and serves as an important determinant of right ventricular performance and exercise capacity. Patients with HF with preserved ejection fraction (n=48), HF with reduced ejection fraction (n=55), pulmonary arterial hypertension without left heart failure (n=18), and control subjects (n=30) underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and first-pass radionuclide ventriculography. PV distensibility was derived from 1257 matched measurements (mean±SD, 8.3±2.8 per subject) of pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output. PV distensibility was lowest in the pulmonary arterial hypertension group (0.40±0.24% per mm Hg) and intermediate in the HF with preserved ejection fraction and HF with reduced ejection fraction groups (0.92±0.39 and 0.84±0.33% per mm Hg, respectively) compared to the control group (1.39±0.32% per mm Hg, Phypertension and is closely related to RV systolic function during exercise, maximal exercise capacity, and survival. Furthermore, PV distensibility is modifiable with selective pulmonary vasodilator therapy and may represent an important target for therapy in selected HF patients with pulmonary hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790. © 2016 American Heart Association, Inc.

  3. Lactate Clearance Predicts Survival Among Patients in the Emergency Department with Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Sundeep R. Bhat

    2015-12-01

    Full Text Available Introduction: Lactate clearance has been implicated as a predictor of mortality among emergency department (ED patients with severe sepsis or septic shock. We aimed to validate prior studies showing that lactate clearance during the ED stay is associated with decreased mortality. Methods: Retrospective dual-centered cross-sectional study using patients identified in the YaleNew Haven Hospital Emergency Medicine sepsis registry with severe sepsis or septic shock who had initial lactate levels measured in the ED and upon arrival (<24 hours to the hospital floor. Lactate clearance was calculated as percent of serum lactate change from ED to floor measurement. We compared mortality and hospital interventions between patients who cleared lactate and those who did not. Results: 207 patients (110 male; 63.17±17.9 years were included. Two reviewers extracted data with 95% agreement. One hundred thirty-six patients (65.7% had severe sepsis and 71 patients (34.3% had septic shock. There were 171 patients in the clearance group and 36 patients in the non-clearance group. The 28-day mortality rates were 15.2% in the lactate clearance group and 36.1% in the non-clearance group (p<0.01. Vasopressor support was initiated more often in the nonclearance group (61.1% than in the clearance group (36.8%, p<0.01 and mechanical ventilation was used in 66.7% of the non-clearance group and 36.3% of the clearance group (p=0.001. Conclusion: Patients who do not clear their lactate in the ED have significantly higher mortality than those with decreasing lactate levels. Our results are confirmatory of other literature supporting that lactate clearance may be used to stratify mortality-risk among patients with severe sepsis or septic shock.

  4. Major clinical events, signs and severity assessment scores related to actual survival in patients who died from primary biliary cirrhosis. A long-term historical cohort study

    NARCIS (Netherlands)

    van Dam, GM; Gips, CH; Reisman, Y; Maas, KW; Purmer, IM; Huizenga, [No Value; Verbaan, BW

    1999-01-01

    BACKGROUND/AIMS: One of the prognostic methods for survival in primary biliary cirrhosis (PBC) is the Mayo model, with a time-scale limited to 7 years. The aim of our study was to assess how major clinical events, signs, several severity assessment methods and Mayo survival probabilities fit in with

  5. Associations between several aspects of heifer development and dairy cow survivability to second lactation.

    Science.gov (United States)

    Bach, A

    2011-02-01

    A data set from 7,768 Holstein heifers born between 2004 and 2006, including growth rates from birth until first calving; age and body weight at insemination; and incidence of diarrhea, navel infections, and bovine respiratory disease (BRD) was used to evaluate potential associations between these factors and the odds of completing the first lactation. All heifers were raised in a contract heifer operation (Rancho Las Nieves, Mallen, Spain) and returned to their herds of origin (133 herds in total) before calving. Dates of death were provided by the Subdirección General de Explotaciones y Sistemas de Trazabilidad de los Recursos Agrícolas y Ganaderos from the Ministry of Environment, and Rural and Marine Areas of the Spanish government. At the time of analysis, 2,571 (33.1%) animals out of the 7,768 considered had died. In total, 655 (8.4%) heifers did not finish first lactation, and 31.5% of these left the herd within the first 50 DIM. Also, 4.8% of heifers aborted and were rebred. Data were analyzed using a mixed-effects logistic regression and survival analysis for dichotomous variables and a mixed-effects model for continuous ones. Incidence of diarrhea or navel infection was not associated with the chances of finishing the first lactation. Heifers that completed first lactation had a lesser average age at first calving (724 ± 2 d) than those that did not (737 ± 3 d). Heifers that reached second lactation grew (0.8 ± 0.04 kg/d) more between 12 and 65 d of age than those that did not (0.7 ± 0.04 kg/d). As conception rate decreased, chances of leaving the herd before completing the first lactation increased. The number of AI services needed per conception as a nulliparous heifer was negatively associated with survivorship to second lactation. Heifers that experienced an abortion were 2.73 ± 0.52 times more likely to leave the herd before completing the first lactation (but also calved with a much older age at first calving). Heifers that experienced 4 or

  6. Climate and health: observation and modeling of malaria in the Ferlo (Senegal).

    Science.gov (United States)

    Diouf, Ibrahima; Deme, Abdoulaye; Ndione, Jacques-André; Gaye, Amadou Thierno; Rodríguez-Fonseca, Belén; Cissé, Moustapha

    2013-01-01

    The aim of this work, undertaken in the framework of QWeCI (Quantifying Weather and Climate Impacts on health in the developing countries) project, is to study how climate variability could influence malaria seasonal incidence. It will also assess the evolution of vector-borne diseases such as malaria by simulation analysis of climate models according to various climate scenarios for the next years. Climate variability seems to be determinant for the risk of malaria development (Freeman and Bradley, 1996 [1], Lindsay and Birley, 1996 [2], Kuhn et al., 2005 [3]). Climate can impact on the epidemiology of malaria by several mechanisms, directly, via the development rates and survival of both pathogens and vectors, and indirectly, through changes in vegetation and land surface characteristics such as the variability of breeding sites like ponds. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  7. Mitral Regurgitation Severity and Left Ventricular Systolic Dimension Predict Survival in Young Cavalier King Charles Spaniels

    DEFF Research Database (Denmark)

    Reimann, M J; Møller, J E; Häggström, J

    2017-01-01

    BACKGROUND: Development and progression of myxomatous mitral valve disease (MMVD) in dogs are difficult to predict. Identification at a young age of dogs at high risk of adverse outcome in the future is desirable. HYPOTHESIS/OBJECTIVES: To study the predictive value of selected clinical...... was assessed by telephone interview with owners. The value of variables for predicting mortality was investigated by Cox proportional hazard and Kaplan-Meier analyses. RESULTS: Presence of moderate to severe mitral regurgitation (MR) (hazard ratio (HR) = 3.03, 95% confidence interval (95% CI) = 1.48-6.23, P...

  8. Echocardiographic parameters and survival in Chagas heart disease with severe systolic dysfunction.

    Science.gov (United States)

    Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

    2014-03-01

    Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.

  9. Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Rassi, Daniela do Carmo, E-mail: dani.rassi@hotmail.com [Faculdade de Medicina e Hospital das Clínicas da Universidade Federal de Goiás (UFG), Goiânia, GO (Brazil); Vieira, Marcelo Luiz Campos [Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil); Arruda, Ana Lúcia Martins [Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil); Hotta, Viviane Tiemi [Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil); Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador [Faculdade de Medicina e Hospital das Clínicas da Universidade Federal de Goiás (UFG), Goiânia, GO (Brazil)

    2014-03-15

    Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m{sup 2} were associated with a significant increase in mortality (log rank p < 0.0001). The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.

  10. Malaria infection and socioeconomic status of some residents of Port ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: The study investigated the prevalence of malaria and socioeconomic status of subjects in part of Port Harcourt ... Keywords: Malaria infection, prevalence, Parasite intensity, Socio-economic status,. Malaria is one of the most severe ..... of effective vaccine for malaria prevention and development of unacceptable ...

  11. Relative Susceptibilities of ABO Blood Groups to Plasmodium falciparum Malaria in Ghana

    Directory of Open Access Journals (Sweden)

    Richmond Afoakwah

    2016-01-01

    Full Text Available The clinical outcome of falciparum malaria in endemic areas is influenced by erythrocyte polymorphisms including the ABO blood groups. Studies have reported association of ABO blood group to resistance, susceptibility, and severity of P. falciparum malaria infection. Individuals with blood group “A” have been found to be highly susceptible to falciparum malaria whereas blood group “O” is said to confer protection against complicated cases. We analyzed samples from 293 young children less than six years old with malaria in the Korle-Bu Teaching Hospital in Accra, Ghana. It was observed that group O was present in about 16.1% of complicated cases weighed against 40.9% of uncomplicated controls. Individuals with complicated malaria were about twice likely to be of blood groups A and B compared to group O (A versus O, OR = 1.90, 95% CI = 1.59–2.26, P<0.0001; B versus O, OR = 1.82. 95% CI = 1.57–2.23, P<0.0001. Blood group O participants with complicated diseases had low parasitaemia compared to the other blood groups (P<0.0001. This may give blood group O individuals a survival advantage over the other groups in complicated malaria as suggested. Participants with complicated falciparum malaria were generally anaemic and younger than those with uncomplicated disease.

  12. Cerebral malaria Malaria cerebral

    Directory of Open Access Journals (Sweden)

    Silvia Blair Trujillo

    2003-03-01

    Full Text Available Is the most common complication of P. falciparum malaria; nearly 90% of people who have suffered CM can recover without neurological problems. Currently there are four hypotheses that explain pathogenesis of CM: cytoadherence and sequestering of parasitized red blood cells to cerebral capillaries; rosette formation and parasitized red blood cells agglutination; production of cytokines and activation of second messengers and opening of the blood-brain barrier. However the main question remains to be answered; how the host-parasite interaction in the vascular space interferes transiently with cerebral function? Recently, the beta amyloid precursor peptide has been employed as marker of neural injury in CM. It is expected that the beta amyloid precursor peptide will help to understand the pathogenesis of CM in complicated patients of endemic areas of Colombia. La malaria Cerebral (MC es la complicación más frecuente de la malaria por P. falciparum; aproximadamente el 90% de las personas que la han padecido se recuperan completamente sin secuelas neurológicas. Aún no se conoce con claridad su patogénesis pero se han postulado cuatro hipótesis o mecanismos posibles: 1 citoadherencia y secuestro de glóbulos rojos parasitados en la microvasculatura cerebral; 2 formación de rosetas y aglutinación de glóbulos rojos parasitados; 3 producción de citoquinas y activación de segundos mensajeros y, 4 apertura de la barrera hematoencefálica. Sin embargo, queda un interrogante sin resolver aún: ¿qué proceso se lleva a cabo para que el parásito, desde el espacio microvascular, pueda interferir transitoriamente con la función cerebral? Recientemente se ha utilizado el precursor de la proteína b-Amiloide como un marcador de daño neuronal en MC; este precursor será de gran ayuda en futuras investigaciones realizadas en nuestro medio que aporten información para comprender la patogénesis de la MC.

  13. Malaria Matters

    Centers for Disease Control (CDC) Podcasts

    2008-04-18

    This podcast gives an overview of malaria, including prevention and treatment, and what CDC is doing to help control and prevent malaria globally.  Created: 4/18/2008 by National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED).   Date Released: 4/18/2008.

  14. Murine malaria is associated with significant hearing impairment

    Directory of Open Access Journals (Sweden)

    Stephan Kurt

    2010-06-01

    Full Text Available Abstract Background Plasmodium falciparum malaria has been suspected to cause hearing loss. Developmental, cognitive and language disorders have been observed in children, surviving cerebral malaria. This prospective study aims to evaluate whether malaria influences hearing in mice. Methods Twenty mice were included in a standardized murine cerebral malaria model. Auditory evoked brainstem responses were assessed before infection and at the peak of the illness. Results A significant hearing impairment could be demonstrated in mice with malaria, especially the cerebral form. The control group did not show any alterations. No therapy was used. Conclusion This suggests that malaria itself leads to a hearing impairment in mice.

  15. Introduction of the resection severity index as independent risk factor limiting survival after resection of colorectal liver metastases.

    Science.gov (United States)

    Gwiasda, Jill; Schrem, Harald; Kaltenborn, Alexander; Mahlmann, Jan; Mix, Heiko; Lehner, Frank; Kayser, Nicolas; Klempnauer, Jürgen; Kulik, Ulf

    2017-12-01

    The purpose of this study is to evaluate the influence of the recently introduced resection severity index (RSI) in patients with liver resection for hepatocellular carcinoma on survival after resection of colorectal liver metastases. The RSI quantifies pre-operatively the liver cellular damage, liver synthetic function and loss of organ parenchyma. All consecutive patients who underwent liver resection for metastases of colorectal cancer (CLM) between 2000 and 2015 were included in this study. Risk factors limiting survival were analyzed using univariable and multivariable Cox regression analyses. The median survival after liver resection for CLM was 3.0 years. Significant independent risk factors for mortality were the RSI (p = 0.029; hazard ratio (HR): 1.088, 95%-confidence interval (95%-CI): 1.009-1.174), age at resection in years (p = 0.001; HR: 1.017, 95%-CI: 1.007-1.027), pre-operative hemoglobin level (p = 0.041; HR: 0.932, 95%-CI: 0.891-0.997), the cecum as location of primary CRC (p < 0.001; HR: 2.023, 95%-CI: 1.403-2.833), adjuvant chemotherapy (p < 0.001; HR: 1.506, 95%-CI: 1.212-1.878), local relapse of the primary tumor (p = 0.027; HR: 1.591, 95%-CI: 1.057-2.297), the units of intra-operatively transfused packed red blood cells (p < 0.001; HR: 1.068, 95%-CI: 1.033-1.104), the size of the largest metastasis (p = 0.002; HR: 1.005, 95%-CI: 1.002-1.008) and the metastasis' distance to the resection margin (p = 0.014; HR: 0.984, 95%-CI: 0.972-0.997). The RSI is an independent prognostic factor for survival after liver resection for CLM. Besides the extent of liver resection certain primary tumor characteristics have to be taken into account to ensure long-term survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. [Malaria: an update].

    Science.gov (United States)

    Scotto, Gaetano

    2010-12-01

    More than 100 years have passed since the discovery of its aetiological agent, but malaria is still the first cause of morbidity and mortality in the world. After the initial illusory successes of the fight against the infection, malarial infection is currently in a phase of expansion due to the sum of several contributory factors: the rise of anophelism related to the failure of eradication campaigns in endemic areas, due to environmental, structural and economic causes; the spread of stocks of chloroquine-resistant Plasmodium falciparum in such areas; the increase in travel for work and tourism, and the flows of populations due to wars, political issues, or just survival. In this paper we inspected all the aspects of the infection, from historical aspects - in which there was sometimes a mingling of history and legend - to those more properly defined as scientific. We seek to point out less well-known details, both about the vector and the clinical-epidemiological aspects concerning the populations in endemic areas, semi-immune subjects and foreigners. We also underline the importance both of prophylaxis and treatment of infection in travellers in high-risk areas, in the light of pharmacological resistance developed by the parasite and of the new usable molecules.

  17. Coculture of autologous limbal and conjunctival epithelial cells to treat severe ocular surface disorders: Long-term survival analysis

    Science.gov (United States)

    Subramaniam, Sandhya V; Sejpal, Kunjal; Fatima, Anees; Gaddipati, Subhash; Vemuganti, Geeta K; Sangwan, Virender S

    2013-01-01

    Background: Cultivated limbal epithelium for reconstruction of corneal surface is a well-established procedure; however, it is not adequate for damage which also extensively involves the conjunctiva. In severe cases of ocular surface damage that warrant additional conjunctival transplantation apart from cultivated limbal stem cell transplantation, we describe the long-term survival of a novel method of cocultivating autologous limbal and conjunctival epithelium on a single substrate. Materials and Methods: Forty eyes of 39 patients with severe limbal stem cell deficiency and conjunctival scarring or symblepharon underwent transplantation of autologous cocultivated epithelium on human amniotic membrane. A ring barrier was used to segregate the central limbal and peripheral conjunctival epithelia in vitro. Patients were followed up at regular intervals to assess stability of the ocular surface, defined by absence of conjunctivalization into the central 4 mm of the cornea and absence of diffuse fluorescein staining. Penetrating keratoplasty (PKP) was subsequently performed, where indicated, in patients with surface stability. Results: The cumulative survival probability was 60% at 1 year and 45% at 4 years by Kaplan–Meier analysis (mean follow-up duration: 33 ± 29 months, range: 1–87 months). Best-corrected visual acuity improved to greater than 20/200 in 38% eyes at the last follow-up, compared with 5% eyes before surgery. Immunohistochemistry in five of the corneal buttons excised for PKP showed an epithelial phenotype similar to cornea in all five. Conclusions: Synchronous use of cultured limbal and conjunctival epithelium offers a feasible alternative and a simpler one-step surgical approach to treat severe ocular surface disorders involving limbus and conjunctiva. PMID:23552358

  18. Case report Malaria: A cerebral approach | Court | Continuing ...

    African Journals Online (AJOL)

    An increasing number of patients with severe complicated Plasmodium falciparum malaria are presenting to South African hospitals, having travelled through malariaendemic countries from Central and East Africa. This report concerns an immigrant from Pakistan who developed severe cerebral malaria.

  19. Sustainable malaria control: transdisciplinary approaches for translational applications

    Directory of Open Access Journals (Sweden)

    Birkholtz Lyn-Marie

    2012-12-01

    Full Text Available Abstract With the adoption of the Global Malaria Action Plan, several countries are moving from malaria control towards elimination and eradication. However, the sustainability of some of the approaches taken may be questionable. Here, an overview of malaria control and elimination strategies is provided and the sustainability of each in context of vector- and parasite control is assessed. From this, it can be concluded that transdisciplinary approaches are essential for sustained malaria control and elimination in malaria-endemic communities.

  20. Sustainable malaria control: transdisciplinary approaches for translational applications.

    Science.gov (United States)

    Birkholtz, Lyn-Marie; Bornman, Riana; Focke, Walter; Mutero, Clifford; de Jager, Christiaan

    2012-12-26

    With the adoption of the Global Malaria Action Plan, several countries are moving from malaria control towards elimination and eradication. However, the sustainability of some of the approaches taken may be questionable. Here, an overview of malaria control and elimination strategies is provided and the sustainability of each in context of vector- and parasite control is assessed. From this, it can be concluded that transdisciplinary approaches are essential for sustained malaria control and elimination in malaria-endemic communities.

  1. Relation of nutritional status, immunity, hemoglobinopathy and falciparum malaria infection

    OpenAIRE

    Nyakeriga, Alice

    2005-01-01

    The interaction between nutritional status and malaria disease is complex and often controversial. Nutritional deficiencies (macro- or micro-nutrient) are thought to lead to malnutrition with subsequent susceptibility to malaria infection. On the other hand severe malaria or repeated malaria infections lead to malnutrition. While the cause and effect are difficult to attribute, micronutrient deficiencies such as iron deficiency and malaria infection often co-exist and show complex interaction...

  2. Transfected HEK293 Cells Expressing Functional Recombinant Intercellular Adhesion Molecule 1 (ICAM-1) - A Receptor Associated with Severe Plasmodium falciparum Malaria

    DEFF Research Database (Denmark)

    Bengtsson, Anja; Joergensen, Louise; Barbati, Zachary R

    2013-01-01

    . Additionally, ICAM-1 acts as receptor for pathogens like human rhinovirus and Plasmodium falciparum malaria parasites. A group of related P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains, the DBLβ, mediates ICAM-1 binding of P. falciparum-infected erythrocytes. This ICAM‑1-binding phenotype has...... been suggested to be involved in the development of cerebral malaria. However, more studies identifying cross-reactive antibody and ICAM-1-binding epitopes and the establishment of a clinical link between DBLβ expression and e.g. cerebral malaria are needed before the DBLβ domains can be put forward...... as vaccine candidates and go into clinical trials. Such studies require availability of functional recombinant ICAM-1 in large quantities. In this study, we compared recombinant ICAM-1 expressed in HEK293 and COS-7 cells with mouse myeloma NS0 ICAM-1 purchased from a commercial vendor in terms of protein...

  3. Malaria Treatment (United States)

    Science.gov (United States)

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria Treatment (United States) Recommend on Facebook Tweet Share Compartir Treatment of Malaria: Guidelines For Clinicians (United States) Download PDF version ...

  4. Malaria and Travelers

    Science.gov (United States)

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria and Travelers Recommend on Facebook Tweet Share Compartir ... may be at risk for infection. Determine if malaria transmission occurs at the destinations Obtain a detailed ...

  5. Tacrolimus prevents murine cerebral malaria.

    Science.gov (United States)

    Bao, Lam Quoc; Nhi, Dang My; Huy, Nguyen Tien; Hamano, Shinjiro; Hirayama, Kenji

    2017-02-01

    Tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. Tacrolimus is also reported to inhibit Plasmodium falciparum growth in vitro. Here, we report that tacrolimus prevented the death from cerebral malaria of Plasmodium berghei ANKA-infected C57BL/6J mice, but not their death from malaria due to the high parasitaemia and severe anaemia. The mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malaria earlier than tacrolimus-treated littermates. Tacrolimus attenuated the infiltration of mononuclear cells including pathogenic CD8+ T cells into the brain. It appears to prevent murine cerebral malaria through the inhibition of cerebral infiltration of CD8+ T cells. © 2016 John Wiley & Sons Ltd.

  6. Malaria Facts

    Science.gov (United States)

    ... 216 million clinical episodes, and 445,000 deaths. Biology, Pathology, Epidemiology Among the malaria species that infect ... Cinchona spp., South America, 17th century). Get Email Updates To receive email updates about this page, enter ...

  7. Transfected HEK293 cells expressing functional recombinant intercellular adhesion molecule 1 (ICAM-1)--a receptor associated with severe Plasmodium falciparum malaria.

    Science.gov (United States)

    Bengtsson, Anja; Joergensen, Louise; Barbati, Zachary R; Craig, Alister; Hviid, Lars; Jensen, Anja T R

    2013-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is a membrane-bound glycoprotein expressed on endothelial cells and cells of the immune system. Human ICAM-1 mediates adhesion and migration of leucocytes, and is implicated in inflammatory pathologies, autoimmune diseases and in many cancer processes. Additionally, ICAM-1 acts as receptor for pathogens like human rhinovirus and Plasmodium falciparum malaria parasites. A group of related P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains, the DBLβ, mediates ICAM-1 binding of P. falciparum-infected erythrocytes. This ICAM‑1-binding phenotype has been suggested to be involved in the development of cerebral malaria. However, more studies identifying cross-reactive antibody and ICAM-1-binding epitopes and the establishment of a clinical link between DBLβ expression and e.g. cerebral malaria are needed before the DBLβ domains can be put forward as vaccine candidates and go into clinical trials. Such studies require availability of functional recombinant ICAM-1 in large quantities. In this study, we compared recombinant ICAM-1 expressed in HEK293 and COS-7 cells with mouse myeloma NS0 ICAM-1 purchased from a commercial vendor in terms of protein purity, yield, fold, ability to bind DBLβ, and relative cost. We present a HEK293 cell-based, high-yield expression and purification scheme for producing inexpensive, functional ICAM‑1. ICAM-1 expressed in HEK293 is applicable to malaria research and can also be useful in other research fields.

  8. Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study

    NARCIS (Netherlands)

    Gichohi-Wainaina, W.N.; Boonstra, A.; Feskens, E.J.M.; Demir, A.Y.; Veenemans, J.; Verhoef, H.

    2015-01-01

    Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates

  9. Internationally comparable diagnosis-specific survival probabilities for calculation of the ICD-10-based Injury Severity Score

    DEFF Research Database (Denmark)

    Gedeborg, R.; Warner, M.; Chen, L. H.

    2014-01-01

    BACKGROUND: The International Statistical Classification of Diseases, 10th Revision (ICD-10) -based Injury Severity Score (ICISS) performs well but requires diagnosis-specific survival probabilities (DSPs), which are empirically derived, for its calculation. The objective was to examine if DSPs b...... based on data pooled from several countries could increase accuracy, precision, utility, and international comparability of DSPs and ICISS. METHODS: Australia, Argentina, Austria, Canada, Denmark, New Zealand, and Sweden provided ICD-10-coded injury hospital discharge data, including in......-hospital mortality status. Data from the seven countries were pooled using four different methods to create an international collaborative effort ICISS (ICE-ICISS). The ability of the ICISS to predict mortality using the country-specific DSPs and the pooled DSPs was estimated and compared. RESULTS: The pooled DSPs...... generated empirically derived DSPs. These pooled DSPs facilitate international comparisons and enables the use of ICISS in all settings where ICD-10 hospital discharge diagnoses are available. The modest reduction in performance of the ICE-ICISS compared with the country-specific scores is unlikely...

  10. High-Throughput Testing of Antibody-Dependent Binding Inhibition of Placental Malaria Parasites

    DEFF Research Database (Denmark)

    Nielsen, Morten A; Salanti, Ali

    2015-01-01

    The particular virulence of Plasmodium falciparum manifests in diverse severe malaria syndromes as cerebral malaria, severe anemia and placental malaria. The cause of both the severity and the diversity of infection outcome, is the ability of the infected erythrocyte (IE) to bind a range......-throughput assay used in the preclinical and clinical development of a VAR2CSA based vaccine against placental malaria....

  11. Utility of health facility-based malaria data for malaria surveillance.

    Directory of Open Access Journals (Sweden)

    Yaw A Afrane

    Full Text Available BACKGROUND: Currently, intensive malaria control programs are being implemented in Africa to reduce the malaria burden. Clinical malaria data from hospitals are valuable for monitoring trends in malaria morbidity and for evaluating the impacts of these interventions. However, the reliability of hospital-based data for true malaria incidence is often questioned because of diagnosis accuracy issues and variation in access to healthcare facilities among sub-groups of the population. This study investigated how diagnosis and treatment practices of malaria cases in hospitals affect reliability of hospital malaria data. METHODOLOGY/PRINCIPAL FINDINGS: The study was undertaken in health facilities in western Kenya. A total of 3,569 blood smears were analyzed after being collected from patients who were requested by clinicians to go to the hospital's laboratory for malaria testing. We applied several quality control measures for clinical malaria diagnosis. We compared our slide reading results with those from the hospital technicians. Among the 3,390 patients whose diagnoses were analyzed, only 36% had clinical malaria defined as presence of any level of parasitaemia and fever. Sensitivity and specificity of clinicians' diagnoses were 60.1% (95% CI: 61.1-67.5 and 75.0% (95% CI: 30.8-35.7, respectively. Among the 980 patients presumptively treated with an anti-malarial by the clinicians without laboratory diagnosis, only 47% had clinical malaria. CONCLUSIONS/SIGNIFICANCE: These findings revealed substantial over-prescription of anti-malarials and misdiagnosis of clinical malaria. More than half of the febrile cases were not truly clinical malaria, but were wrongly diagnosed and treated as such. Deficiency in malaria diagnosis makes health facility data unreliable for monitoring trends in malaria morbidity and for evaluating impacts of malaria interventions. Improving malaria diagnosis should be a top priority in rural African health centers.

  12. Survival trends and predictors of mortality in severe pelvic trauma: estimates from the German Pelvic Trauma Registry Initiative.

    Science.gov (United States)

    Pohlemann, Tim; Stengel, Dirk; Tosounidis, Georgios; Reilmann, Heinrich; Stuby, Fabian; Stöckle, Uli; Seekamp, Andreas; Schmal, Hagen; Thannheimer, Andreas; Holmenschlager, Francis; Gänsslen, Axel; Rommens, Pol Maria; Fuchs, Thomas; Baumgärtel, Friedel; Marintschev, Ivan; Krischak, Gert; Wunder, Stephan; Tscherne, Harald; Culemann, Ulf

    2011-10-01

    To determine longitudinal trends in mortality, and the contribution of specific injury characteristics and treatment modalities to the risk of a fatal outcome after severe and complex pelvic trauma. We studied 5048 patients with pelvic ring fractures enrolled in the German Pelvic Trauma Registry Initiative between 1991 and 1993, 1998 and 2000, and 2004 and 2006. Complete datasets were available for 5014 cases, including 508 complex injuries, defined as unstable fractures with severe peri-pelvic soft tissue and organ laceration. Multivariable mixed-effects logistic regression analysis was employed to evaluate the impact of demographic, injury- and treatment-associated variables on all-cause in-hospital mortality. All-cause in-hospital mortality declined from 8% (39/466) in 1991 to 5% (33/638) in 2006. Controlling for age, Injury Severity Score, pelvic vessel injury, the need for emergency laparotomy, and application of a pelvic clamp, the odds ratio (OR) per annum was 0.94 (95% confidence interval [CI] 0.91-0.96). However, the risk of death did not decrease significantly in patients with complex injuries (OR 0.98, 95% CI 0.93-1.03). Raw mortality associated with this type of injury was 18% (95% CI 9-32%) in 2006. In contrast to an overall decline in trauma mortality, complex pelvic ring injuries remain associated with a significant risk of death. Awareness of this potentially life-threatening condition should be increased amongst trauma care professionals, and early management protocols need to be implemented to improve the survival prognosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. MALARIA IN PREGNANCY

    Directory of Open Access Journals (Sweden)

    Ebako Ndip Takem

    2013-01-01

    Full Text Available Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired in the past decade on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP include low maternal age, low gravidity, and low gestational age. The effects of MIP include maternal anaemia, low birth weight (LBW, preterm delivery and increased infant mortality. P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA, that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery, anaemia, and high cytokines levels have been implicated.       Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections, respectively. Compared to microscopy, RDTs have a lower sensitivity. Insecticide treated nets (ITN and intermittent preventive treatment in pregnancy (IPTp are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28-47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria, a combination of quinine + clyndamycin is recommended in all trimesters, while artesunate+ clindamycin or any other ACT known to be effective in the region are recommended in the second and third trimesters. For severe

  14. Influence of plasmodium Falciparum malaria on sickle cell Vaso ...

    African Journals Online (AJOL)

    . Malaria infection is thought to influence the occurrence and severity of crisis in sickle cell patients. Objective To investigate the relationship between malaria infection and vasoocclusive crisis in sickle cell disease patients. Methods In order to ...

  15. The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria

    DEFF Research Database (Denmark)

    Shabani, Estela; Opoka, Robert O; Bangirana, Paul

    2016-01-01

    deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC). The rs867186-GG genotype was more frequent in CC (4.1%) than SM (0.6%, P = 0.002). The rs867186-G variant was associated with increased sEPCR levels and sEPCR was lower in children with SM than...

  16. Global challenges of malaria risk - perspectives from Transfusion-transmitted malaria

    OpenAIRE

    Owusu-Ofori, Alex; Owusu-Ofori, Shirley; Bates, Imelda

    2017-01-01

    Malaria is a protozoan disease that is transmitted by the Anopheles mosquito. It can however be transmitted by blood transfusion if the blood donor is parasitaemic. Of the five species of Plasmodium that causes malaria, P. falciparum causes the most severe form of malaria. Nearly half of the world’s population is at risk of malaria. Mortality due to malaria has reduced by 48% from 839,000 deaths in 2000 to 438,000 deaths in 2015. This is largely due to a combination of two approaches, vector ...

  17. Inhibiting the Mammalian target of rapamycin blocks the development of experimental cerebral malaria.

    Science.gov (United States)

    Gordon, Emile B; Hart, Geoffrey T; Tran, Tuan M; Waisberg, Michael; Akkaya, Munir; Skinner, Jeff; Zinöcker, Severin; Pena, Mirna; Yazew, Takele; Qi, Chen-Feng; Miller, Louis H; Pierce, Susan K

    2015-06-02

    Malaria is an infectious disease caused by parasites of several Plasmodium spp. Cerebral malaria (CM) is a common form of severe malaria resulting in nearly 700,000 deaths each year in Africa alone. At present, there is no adjunctive therapy for CM. Although the mechanisms underlying the pathogenesis of CM are incompletely understood, it is likely that both intrinsic features of the parasite and the human host's immune response contribute to disease. The kinase mammalian target of rapamycin (mTOR) is a central regulator of immune responses, and drugs that inhibit the mTOR pathway have been shown to be antiparasitic. In a mouse model of CM, experimental CM (ECM), we show that the mTOR inhibitor rapamycin protects against ECM when administered within the first 4 days of infection. Treatment with rapamycin increased survival, blocked breakdown of the blood-brain barrier and brain hemorrhaging, decreased the influx of both CD4(+) and CD8(+) T cells into the brain and the accumulation of parasitized red blood cells in the brain. Rapamycin induced marked transcriptional changes in the brains of infected mice, and analysis of transcription profiles predicted that rapamycin blocked leukocyte trafficking to and proliferation in the brain. Remarkably, animals were protected against ECM even though rapamycin treatment significantly increased the inflammatory response induced by infection in both the brain and spleen. These results open a new avenue for the development of highly selective adjunctive therapies for CM by targeting pathways that regulate host and parasite metabolism. Malaria is a highly prevalent infectious disease caused by parasites of several Plasmodium spp. Malaria is usually uncomplicated and resolves with time; however, in about 1% of cases, almost exclusively among young children, malaria becomes severe and life threatening, resulting in nearly 700,000 deaths each year in Africa alone. Among the most severe complications of Plasmodium falciparum infection

  18. Neonatal malaria complicated by hypoglycaemia and ...

    African Journals Online (AJOL)

    There is no established and widely accepted guidelines for clinical management of severe neonatal malaria. The aim of this paper is to raise the alertness of physicians regarding the occurrence of severe malaria in the neonatal period and to describe the treatment modality we adopted (in the absence of an internationally ...

  19. Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria

    Directory of Open Access Journals (Sweden)

    Dkhil Mohamed A

    2009-04-01

    Full Text Available Abstract Background To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/c mice succumbing to infection with Plasmodium chabaudi were compared to those surviving after vaccination. Methods Mice were vaccinated with host cell plasma membranes isolated from P. chabaudi-infected erythrocytes. Hepatic and splenic capacity to trap particulate material was determined after injection of fluorescent polystyrol beads. Hepatic gene expression was measured using real-time RT-PCR and Northern blotting. Results Survival of BALB/c mice was raised from 0% to 80% and peak parasitaemia was decreased by about 30% by vaccination. Vaccination boosted particle trapping capacity of the liver during crisis when splenic trapping is minimal due to spleen 'closing'. It also attenuated malaria-induced inflammation, thus diminishing severe damages and hence liver failure. Vaccination increased hepatic IFN-γ production but mitigated acute phase response. Vaccination has a complex influence on infection-induced changes in expression of hepatic nuclear receptors (CAR, FXR, RXR, and PXR and of the metabolic enzymes Sult2a and Cyp7a1. Although vaccination decreased CAR mRNA levels and prevented Cyp7a1 suppression by the CAR ligand 1,2-bis [2-(3,5-dichloropyridyloxy]benzene (TCPOBOP on day 8 p.i., Sult2a-induction by TCPOBOP was restored. Conclusion These data support the view that the liver is an essential effector site for a vaccine against blood stage malaria: vaccination attenuates malaria-induced inflammation thus improving hepatic metabolic activity and particle trapping activity of the liver.

  20. Molecular basis of human cerebral malaria development

    OpenAIRE

    Wah, Saw Thu; Hananantachai, Hathairad; Kerdpin, Usanee; Plabplueng, Chotiros; Prachayasittikul, Virapong; Nuchnoi, Pornlada

    2016-01-01

    Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, m...

  1. Hyposplenism revealed by Plasmodium malariae infection

    OpenAIRE

    Hommel, Benjamin; Galloula, Alexandre; Simon, Anne; Buffet, Pierre

    2013-01-01

    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...

  2. Unreported births and deaths, a severe obstacle for improved neonatal survival in low-income countries; a population based study

    Directory of Open Access Journals (Sweden)

    Wallin Lars

    2008-03-01

    Full Text Available Abstract Background In order to improve child survival there is a need to target neonatal mortality. In this pursuit, valid local and national statistics on child health are essential. We analyze to what extent births and neonatal deaths are unreported in a low-income country and discuss the consequences at local and international levels for efforts to save newborn lives. Methods Information on all births and neonatal deaths in Quang Ninh province in Northern Vietnam in 2005 was ascertained by systematic inventory through group interviews with key informants, questionnaires and examination of health facility records. Health care staff at 187 Community Health Centers (CHC and 18 hospitals, in addition to 1372 Village Health Workers (VHW, were included in the study. Results were compared with the official reports of the Provincial Health Bureau. Results The neonatal mortality rate (NMR was 16/1000 (284 neonatal deaths/17 519 births, as compared to the official rate of 4.2/1000. The NMR varied between 44/1000 and 10/1000 in the different districts of the province. The under-reporting was mainly attributable to a dysfunctional reporting system and the fact that families, not the health system, were made responsible to register births and deaths. This under-reporting has severe consequences at local, national and international levels. At a local level, it results in a lack of awareness of the magnitude and differentials in NMR, leading to an indifference towards the problem. At a national and international level the perceived low mortality rate is manifested in a lack of investments in perinatal health programs. Conclusion This example of a faulty health information system is reportedly not unique in low and middle income countries where needs for neonatal health reforms are greatest. Improving reporting systems on births and neonatal deaths is a matter of human rights and a prerequisite for reducing neonatal mortality in order to reach the fourth

  3. Malaria prevention and treatment

    African Journals Online (AJOL)

    malaria parasites into the blood. Four species of malaria parasites can infect humans and cause illness; only P. falci- parum malaria is potentially life-threat- ening. Most of the malaria found in Af- rica is of the falciparum species - this is the most dangerous species of malaria. Symptoms may develop as soon as seven days ...

  4. Estimating individual exposure to malaria using local prevalence of malaria infection in the field.

    Directory of Open Access Journals (Sweden)

    Ally Olotu

    Full Text Available BACKGROUND: Heterogeneity in malaria exposure complicates survival analyses of vaccine efficacy trials and confounds the association between immune correlates of protection and malaria infection in longitudinal studies. Analysis may be facilitated by taking into account the variability in individual exposure levels, but it is unclear how exposure can be estimated at an individual level. METHOD AND FINDINGS: We studied three cohorts (Chonyi, Junju and Ngerenya in Kilifi District, Kenya to assess measures of malaria exposure. Prospective data were available on malaria episodes, geospatial coordinates, proximity to infected and uninfected individuals and residence in predefined malaria hotspots for 2,425 individuals. Antibody levels to the malaria antigens AMA1 and MSP1(142 were available for 291 children from Junju. We calculated distance-weighted local prevalence of malaria infection within 1 km radius as a marker of individual's malaria exposure. We used multivariable modified Poisson regression model to assess the discriminatory power of these markers for malaria infection (i.e. asymptomatic parasitaemia or clinical malaria. The area under the receiver operating characteristic (ROC curve was used to assess the discriminatory power of the models. Local malaria prevalence within 1 km radius and AMA1 and MSP1(142 antibodies levels were independently associated with malaria infection. Weighted local malaria prevalence had an area under ROC curve of 0.72 (95%CI: 0.66-0.73, 0.71 (95%CI: 0.69-0.73 and 0.82 (95%CI: 0.80-0.83 among cohorts in Chonyi, Junju and Ngerenya respectively. In a small subset of children from Junju, a model incorporating weighted local malaria prevalence with AMA1 and MSP1(142 antibody levels provided an AUC of 0.83 (95%CI: 0.79-0.88. CONCLUSION: We have proposed an approach to estimating the intensity of an individual's malaria exposure in the field. The weighted local malaria prevalence can be used as individual marker of

  5. Estimating individual exposure to malaria using local prevalence of malaria infection in the field.

    Science.gov (United States)

    Olotu, Ally; Fegan, Gregory; Wambua, Juliana; Nyangweso, George; Ogada, Edna; Drakeley, Chris; Marsh, Kevin; Bejon, Philip

    2012-01-01

    Heterogeneity in malaria exposure complicates survival analyses of vaccine efficacy trials and confounds the association between immune correlates of protection and malaria infection in longitudinal studies. Analysis may be facilitated by taking into account the variability in individual exposure levels, but it is unclear how exposure can be estimated at an individual level. We studied three cohorts (Chonyi, Junju and Ngerenya) in Kilifi District, Kenya to assess measures of malaria exposure. Prospective data were available on malaria episodes, geospatial coordinates, proximity to infected and uninfected individuals and residence in predefined malaria hotspots for 2,425 individuals. Antibody levels to the malaria antigens AMA1 and MSP1(142) were available for 291 children from Junju. We calculated distance-weighted local prevalence of malaria infection within 1 km radius as a marker of individual's malaria exposure. We used multivariable modified Poisson regression model to assess the discriminatory power of these markers for malaria infection (i.e. asymptomatic parasitaemia or clinical malaria). The area under the receiver operating characteristic (ROC) curve was used to assess the discriminatory power of the models. Local malaria prevalence within 1 km radius and AMA1 and MSP1(142) antibodies levels were independently associated with malaria infection. Weighted local malaria prevalence had an area under ROC curve of 0.72 (95%CI: 0.66-0.73), 0.71 (95%CI: 0.69-0.73) and 0.82 (95%CI: 0.80-0.83) among cohorts in Chonyi, Junju and Ngerenya respectively. In a small subset of children from Junju, a model incorporating weighted local malaria prevalence with AMA1 and MSP1(142) antibody levels provided an AUC of 0.83 (95%CI: 0.79-0.88). We have proposed an approach to estimating the intensity of an individual's malaria exposure in the field. The weighted local malaria prevalence can be used as individual marker of malaria exposure in malaria vaccine trials and longitudinal

  6. Malaria in rural Mozambique. Part II: children admitted to hospital

    Directory of Open Access Journals (Sweden)

    Macete Eusébio

    2008-02-01

    Full Text Available Abstract Background Characterization of severe malaria cases on arrival to hospital may lead to early recognition and improved management. Minimum community based-incidence rates (MCBIRs complement hospital data, describing the malaria burden in the community. Methods A retrospective analysis of all admitted malaria cases to a Mozambican rural hospital between June 2003 and May 2005 was conducted. Prevalence and case fatality rates (CFR for each sign and symptom were calculated. Logistic regression was used to identify variables which were independent risk factors for death. MCBIRs for malaria and severe malaria were calculated using data from the Demographic Surveillance System. Results Almost half of the 8,311 patients admitted during the study period had malaria and 13,2% had severe malaria. Children under two years accounted for almost 60% of all malaria cases. CFR for malaria was 1.6% and for severe malaria 4.4%. Almost 19% of all paediatric hospital deaths were due to malaria. Prostration (55.0%, respiratory distress (41.1% and severe anaemia (17.3% were the most prevalent signs among severe malaria cases. Severe anaemia and inability to look for mother's breast were independent risk factors for death in infants younger than eight months. For children aged eight months to four years, the risk factors were malnutrition, hypoglycaemia, chest indrawing, inability to sit and a history of vomiting. MCBIRs for severe malaria cases were highest in children aged six months to two years of age. MCBIRs for severe malaria per 1,000 child years at risk for the whole study period were 27 in infants, 23 in children aged 1 to Conclusion Malaria remains the number one cause of admission in this area of rural Mozambique, predominantly affecting young children, which are also at higher risk of dying. Measures envisaged to protect children during their first two years of life are likely to have a greater impact than at any other age.

  7. Ethical aspects of malaria control and research.

    Science.gov (United States)

    Jamrozik, Euzebiusz; de la Fuente-Núñez, Vânia; Reis, Andreas; Ringwald, Pascal; Selgelid, Michael J

    2015-12-22

    Malaria currently causes more harm to human beings than any other parasitic disease, and disproportionally affects low-income populations. The ethical issues raised by efforts to control or eliminate malaria have received little explicit analysis, in comparison with other major diseases of poverty. While some ethical issues associated with malaria are similar to those that have been the subject of debate in the context of other infectious diseases, malaria also raises distinct ethical issues in virtue of its unique history, epidemiology, and biology. This paper provides preliminary ethical analyses of the especially salient issues of: (i) global health justice, (ii) universal access to malaria control initiatives, (iii) multidrug resistance, including artemisinin-based combination therapy (ACT) resistance, (iv) mandatory screening, (v) mass drug administration, (vi) benefits and risks of primaquine, and (vii) malaria in the context of blood donation and transfusion. Several ethical issues are also raised by past, present and future malaria research initiatives, in particular: (i) controlled infection studies, (ii) human landing catches, (iii) transmission-blocking vaccines, and (iv) genetically-modified mosquitoes. This article maps the terrain of these major ethical issues surrounding malaria control and elimination. Its objective is to motivate further research and discussion of ethical issues associated with malaria--and to assist health workers, researchers, and policy makers in pursuit of ethically sound malaria control practice and policy.

  8. Coadaptation and malaria control

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    2007-06-01

    Full Text Available Malaria emerges from a disequilibrium of the system 'human-plasmodium-mosquito' (HPM. If the equilibrium is maintained, malaria does not ensue and the result is asymptomatic plasmodium infection. The relationships among the components of the system involve coadaptive linkages that lead to equilibrium. A vast body of evidence supports this assumption, including the strategies involved in the relationships between plasmodium and human and mosquito immune systems, and the emergence of resistance of plasmodia to antimalarial drugs and of mosquitoes to insecticides. Coadaptive strategies for malaria control are based on the following principles: (1 the system HPM is composed of three highly complex and dynamic components, whose interplay involves coadaptive linkages that tend to maintain the equilibrium of the system; (2 human and mosquito immune systems play a central role in the coadaptive interplay with plasmodium, and hence, in the mainten-ance of the system's equilibrium; the under- or overfunction of human immune system may result in malaria and influence its severity; (3 coadaptation depends on genetic and epigenetic phenomena occurring at the interfaces of the components of the system, and may involve exchange of infectrons (genes or gene fragments between the partners; (4 plasmodia and mosquitoes have been submitted to selective pressures, leading to adaptation, for an extremely long while and are, therefore, endowed with the capacity to circumvent both natural (immunity and artificial (drugs, insecticides, vaccines measures aiming at destroying them; (5 since malaria represents disequilibrium of the system HPM, its control should aim at maintaining or restoring this equilibrium; (6 the disequilibrium of integrated systems involves the disequilibrium of their components, therefore the maintenance or restoration of the system's equilibrium depend on the adoption of integrated and coordinated measures acting on all components, that means

  9. Evaluation of Students' Conceptual Understanding of Malaria

    Science.gov (United States)

    Poh-Ai Cheong, Irene; Treagust, David; Kyeleve, Iorhemen J.; Oh, Peck-Yoke

    2010-12-01

    In this study, a two-tier diagnostic test for understanding malaria was developed and administered to 314 Bruneian students in Year 12 and in a nursing diploma course. The validity, reliability, difficulty level, discriminant indices, and reading ability of the test were examined and found to be acceptable in terms of measuring students' understanding and identifying alternative conceptions with respect to malaria. Results showed that students' understanding of malaria was high for content, low for reasons, and limited and superficial for both content and reasons. The instrument revealed several common alternative conceptual understandings students' hold about malaria. The MalariaTT2 instrument developed could be used in classroom lessons for challenging alternative conceptions and enhancing conceptions of malaria.

  10. Molecular basis of human cerebral malaria development.

    Science.gov (United States)

    Wah, Saw Thu; Hananantachai, Hathairad; Kerdpin, Usanee; Plabplueng, Chotiros; Prachayasittikul, Virapong; Nuchnoi, Pornlada

    2016-01-01

    Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention. Therefore, understanding of the underlying complex molecular basis of cerebral malaria is important for the design of strategy for cerebral malaria treatment and control.

  11. T-cell responses in malaria

    DEFF Research Database (Denmark)

    Hviid, L; Jakobsen, P H; Abu-Zeid, Y A

    1992-01-01

    Malaria is caused by infection with protozoan parasites of the genus Plasmodium. It remains one of the most severe health problems in tropical regions of the world, and the rapid spread of resistance to drugs and insecticides has stimulated intensive research aimed at the development of a malaria...... vaccine. Despite this, no efficient operative vaccine is currently available. A large amount of information on T-cell responses to malaria antigens has been accumulated, concerning antigens derived from all stages of the parasite life cycle. The present review summarizes some of that information......, and discusses factors affecting the responses of T cells to malaria antigens....

  12. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts.

    Science.gov (United States)

    Vafaei, Ali; Ranjkesh, Bahram; Lovschall, Henrik; Erfanparast, Leila; Jafarabadi, Mohammad A; Oskouei, Sina Ghertasi; Isidor, Flemming

    2016-01-01

    The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the primary maxillary canine on each side: either a glass fiber post or a metallic post in reversed orientation and teeth restored with light-cured composite. Survival rate of each technique was evaluated at predetermined follow-ups and data were analyzed with McNemar's test (α = 0.05). The difference in survival of restorations retained by two types of posts was not statistically significant in clinical and radiographical evaluations after 6, 12, and 18 months. The survival rate of reversed-orientated metal and glass fiber posts after 18 months was 81.1 and 67.6% respectively (p = 0.14). Reversed-orientated metal post did not show lower clinical survival compared with glass fiber posts in 18-month follow-up. Hence, reversed-orientated metal post can be considered as a potential method to obtain retention for composite restorations in severely decayed primary anterior teeth. How to cite this article: Vafaei A, Ranjkesh B, L0vschall H, Erfanparast L, Jafarabadi MA, Oskouei SG, Isidor F. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts. Int J Clin Pediatr Dent 2016;9(2):109-113.

  13. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts

    Science.gov (United States)

    Ranjkesh, Bahram; Lovschall, Henrik; Erfanparast, Leila; Jafarabadi, Mohammad A; Oskouei, Sina Ghertasi; Isidor, Flemming

    2016-01-01

    ABSTRACT Aim: The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. Materials and methods: A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the primary maxillary canine on each side: either a glass fiber post or a metallic post in reversed orientation and teeth restored with light-cured composite. Survival rate of each technique was evaluated at predetermined follow-ups and data were analyzed with McNemar’s test (α = 0.05). Results: The difference in survival of restorations retained by two types of posts was not statistically significant in clinical and radiographical evaluations after 6, 12, and 18 months. The survival rate of reversed-orientated metal and glass fiber posts after 18 months was 81.1 and 67.6% respectively (p = 0.14). Conclusion: Reversed-orientated metal post did not show lower clinical survival compared with glass fiber posts in 18-month follow-up. Hence, reversed-orientated metal post can be considered as a potential method to obtain retention for composite restorations in severely decayed primary anterior teeth. How to cite this article: Vafaei A, Ranjkesh B, L0vschall H, Erfanparast L, Jafarabadi MA, Oskouei SG, Isidor F. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts. Int J Clin Pediatr Dent 2016;9(2):109-113. PMID:27365929

  14. Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression

    DEFF Research Database (Denmark)

    Tuikue Ndam, Nicaise; Bischoff, Emmanuel; Proux, Caroline

    2008-01-01

    BACKGROUND: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances...

  15. Kidney function status in Nigerian human malaria patients | Anionye ...

    African Journals Online (AJOL)

    Malaria is now known to affect over 500 million persons worldwide, killing about 1 to 3 million of them annually. Plasmodium falciparum is the species mostly implicated in the causation of severe malaria. This study was carried out to investigate the kidney function status of malaria patients in Benin metropolis, Southern ...

  16. Assessment of Home Management of Malaria by Caregivers in a ...

    African Journals Online (AJOL)

    Saharan Africa. Home-based management of malaria (HMM) is promoted as a major strategy of reducing malaria mortality and severe morbidity, in line with the Millennium Development Goal 6. This study assessed the treatment of malaria at home in ...

  17. Prevalence of malaria and human blood factors among patients in ...

    African Journals Online (AJOL)

    Background: Malaria has been and is still a major protozoan disease affecting the human population. Erythrocyte polymorphisms (mainly in blood groups and genotypes) influence the susceptibility to severe malaria. Aim: This study is aimed at assessing the prevalence malaria in relation to human blood factor and to ...

  18. Knowledge, Perception and Control Practices of Malaria Vector ...

    African Journals Online (AJOL)

    Malaria remains one of the most devastating public health scourges especially in the tropics. Several studies have documented the prevalence of malaria among different vulnerable groups; however, an understanding of the communities' knowledge, perceptions and practices relating to malaria is crucial to the success of ...

  19. malaria parasitaemia among pregnant women in a rural community

    African Journals Online (AJOL)

    Daniel Owu

    Introduction: Malaria infection caused by Plasmodium falciparum is a major cause of fever and anaemia in pregnant women resident in hyper endemic areas of. Africa. Basically, this is as a result of reduced immunity to malaria in pregnancy (Klufio, 1992), making the pregnant women prone to severe malaria attack and ...

  20. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts

    OpenAIRE

    Vafaei, Ali; Ranjkesh, Bahram; Lovschall, Henrik; Erfanparast, Leila; Jafarabadi, Mohammad A; Oskouei, Sina Ghertasi; Isidor, Flemming

    2016-01-01

    ABSTRACT Aim: The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. Materials and methods: A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the prim...

  1. Symmetrical peripheral gangrene: A rare complication of plasmodium falciparum malaria

    OpenAIRE

    Rana, Atul; Singh, DP; Kaur, Gurdeep; Verma, SK; Mahur, Hemant

    2015-01-01

    Malaria, the most important of the parasitic diseases of humans, is transmitted in 108 countries containing 3 billion people and causes nearly 1 million deaths each year. With the re-emergence of malaria various life-threatening complications of malaria have been observed. Unarousable coma/cerebral malaria, severe normochromic, normocytic anemia, renal failure, pulmonary edema/adult respiratory distress syndrome, hypoglycemia, hypotension/shock, bleeding/disseminated intravascular coagulation...

  2. Multi-year optimization of malaria intervention: a mathematical model

    OpenAIRE

    Dudley, Harry J.; Goenka, Abhishek; Orellana, Cesar J.; Susan E. Martonosi

    2016-01-01

    Background Malaria is a mosquito-borne, lethal disease that affects millions and kills hundreds of thousands of people each year, mostly children. There is an increasing need for models of malaria control. In this paper, a model is developed for allocating malaria interventions across geographic regions and time, subject to budget constraints, with the aim of minimizing the number of person-days of malaria infection. Methods The model considers a range of several conditions: climatic characte...

  3. Malaria in Pregnancy: Morbidities and Management | Yakasai ...

    African Journals Online (AJOL)

    Malaria infection during pregnancy remains an important public health concern especially in the tropics with substantial risk for the mother, her fetus and the neonate. More than 25 million African women in malaria endemic areas get pregnant and are at risk of infection with Plasmodium falciparum. Several pregnancy ...

  4. Ocular complications of malaria treatment | Nwosu | Nigerian ...

    African Journals Online (AJOL)

    Malaria is endemic in Nigeria. With the emergence of chloroquine resistance various modes of treatment including parenteral quinine are employed with consequent untoward effects. This article reports two cases of severe ocular toxicity, including mimicry of intracranial space‑occupying lesion, from treatment of malaria ...

  5. Cerebral Malaria Complicated by Blindness, Deafness and ...

    African Journals Online (AJOL)

    Introduction. Malaria is a parasitic disease affecting about 1 billion people globally and causing about 1.24 million deaths annually especially in the developing countries.[1,2] About. 1% of the patients with Plasmodium falciparum develop severe manifestations culminating in multi-organ failure.[3]. Cerebral malaria is one of ...

  6. Fetal Tracheal Occlusion for Severe Pulmonary Hypoplasia in Isolated Congenital Diaphragmatic Hernia: A Systematic Review and Meta-analysis of Survival.

    Science.gov (United States)

    Al-Maary, Jamila; Eastwood, Mary P; Russo, Francesca Maria; Deprest, Jan A; Keijzer, Richard

    2016-12-01

    To evaluate fetal survival after tracheal occlusion in fetuses with severe pulmonary hypoplasia and isolated congenital diaphragmatic hernia (CDH). Despite recent advances in neonatal intensive care, CDH still has a high mortality and morbidity. Fetoscopic endoluminal tracheal occlusion (FETO) stimulates lung growth and improves gas exchange in animal models of CDH, but the effects in humans are still under investigation. We searched Pubmed, Cochrane, EMBASE, and Scopus databases for clinical studies on tracheal occlusion and CDH. All studies comparing FETO and a contemporary control group were included. The primary outcome was survival, with the need for oxygen on discharge the secondary outcome. Meta-analysis of outcome measures was performed and odds ratios, relative risk ratios, and 95% confidence intervals were estimated with a fixed-effects model and were reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Between 1997 and 2015, five eligible studies describing 211 patients were included (101 control and 110 FETO). All studies selected isolated severe CDH fetuses with a lung-to-head ratio 1.0 or less and liver herniation into the thoracic cavity. FETO favored survival outcome (odds ratio 13.32; 95% confidence interval, 5.40-32.87). Meta-analysis of the secondary outcome oxygen need at discharge could not be calculated, because it was not reported in all included studies. FETO improves survival in isolated CDH with severe pulmonary hypoplasia compared with the standard perinatal management.

  7. Increased Severe Trauma Patient Volume is Associated With Survival Benefit and Reduced Total Health Care Costs: A Retrospective Observational Study Using a Japanese Nationwide Administrative Database.

    Science.gov (United States)

    Endo, Akira; Shiraishi, Atsushi; Fushimi, Kiyohide; Murata, Kiyoshi; Otomo, Yasuhiro

    2017-06-07

    The aim of this study was to evaluate the associations of severe trauma patient volume with survival benefit and health care costs. The effect of trauma patient volume on survival benefit is inconclusive, and reports on its effects on health care costs are scarce. We conducted a retrospective observational study, including trauma patients who were transferred to government-approved tertiary emergency hospitals, or hospitals with an intensive care unit that provided an equivalent quality of care, using a Japanese nationwide administrative database. We categorized hospitals according to their annual severe trauma patient volumes [1 to 50 (reference), 51 to 100, 101 to 150, 151 to 200, and ≥201]. We evaluated the associations of volume categories with in-hospital survival and total cost per admission using a mixed-effects model adjusting for patient severity and hospital characteristics. A total of 116,329 patients from 559 hospitals were analyzed. Significantly increased in-hospital survival rates were observed in the second, third, fourth, and highest volume categories compared with the reference category [94.2% in the highest volume category vs 88.8% in the reference category, adjusted odds ratio (95% confidence interval, 95% CI) = 1.75 (1.49-2.07)]. Furthermore, significantly lower costs (in US dollars) were observed in the second and fourth categories [mean (standard deviation) for fourth vs reference = $17,800 ($17,378) vs $20,540 ($32,412), adjusted difference (95% CI) = -$2559 (-$3896 to -$1221)]. Hospitals with high volumes of severe trauma patients were significantly associated with a survival benefit and lower total cost per admission.

  8. Effect of Recipient Age and Stem Cell Source on the Association between Donor Telomere Length and Survival after Allogeneic Unrelated Hematopoietic Cell Transplantation for Severe Aplastic Anemia.

    Science.gov (United States)

    Gadalla, Shahinaz M; Wang, Tao; Dagnall, Casey; Haagenson, Michael; Spellman, Stephen R; Hicks, Belynda; Jones, Kristine; Katki, Hormuzd A; Lee, Stephanie J; Savage, Sharon A

    2016-12-01

    We previously showed an association between donor leukocyte relative telomere length (RTL) and post-hematopoietic cell transplantation (HCT) survival in patients with severe aplastic anemia (SAA) who received bone marrow grafts at ages survival, but further analysis identified differences by recipient age and stem cell source as the likely explanation. In patients survival benefit only in <40-year-old patients receiving bone marrow graft (HR comparing longest and middle RTL tertiles with shortest = .69; 95% CI, .50 to .95, P = .02). The study suggested that the association between donor RTL and post-HCT outcomes in recipients with SAA may vary by recipient age and stem cell source. A larger study is needed to account for multiple comparisons and to further test the generalizability of our findings. Published by Elsevier Inc.

  9. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR Variants in a Thai Population.

    Directory of Open Access Journals (Sweden)

    Rebekah van Bruggen

    Full Text Available Pyruvate kinase (PKLR is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41 is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

  10. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population.

    Science.gov (United States)

    van Bruggen, Rebekah; Gualtieri, Christian; Iliescu, Alexandra; Louicharoen Cheepsunthorn, Chalisa; Mungkalasut, Punchalee; Trape, Jean-François; Modiano, David; Sirima, Bienvenu Sodiomon; Singhasivanon, Pratap; Lathrop, Mark; Sakuntabhai, Anavaj; Bureau, Jean-François; Gros, Philippe

    2015-01-01

    Pyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q) was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41) is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q) affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

  11. Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases

    Science.gov (United States)

    Wunsch, Ewa; Krawczyk, Marcin; Milkiewicz, Malgorzata; Trottier, Jocelyn; Barbier, Olivier; Neurath, Markus F.; Lammert, Frank; Kremer, Andreas E.; Milkiewicz, Piotr

    2016-01-01

    Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1–60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival. PMID:27506882

  12. EDITORIAL MALARIA DIAGNOSIS Malaria remains the most ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-02

    Mar 2, 2005 ... Malaria remains the most significant parasitic disease affecting man. Prompt and accurate diagnosis of malaria is the key to cost effective management (1). Since the identification of Plasmodium parasites in human blood in 1880, the diagnosis of malaria has remained a hot bed of scientific discussion.

  13. Decoding the Role of Glycans in Malaria

    Directory of Open Access Journals (Sweden)

    Pollyanna S. Gomes

    2017-06-01

    Full Text Available Complications arising from malaria are a concern for public health authorities worldwide, since the annual caseload in humans usually exceeds millions. Of more than 160 species of Plasmodium, only 4 infect humans, with the most severe cases ascribed to Plasmodium falciparum and the most prevalent to Plasmodium vivax. Over the past 70 years, since World War II, when the first antimalarial drugs were widely used, many efforts have been made to combat this disease, including vectorial control, new drug discoveries and genetic and molecular approaches. Molecular approaches, such as glycobiology, may lead to new therapeutic targets (both in the host and the parasites, since all interactions are mediated by carbohydrates or glycan moieties decorating both cellular surfaces from parasite and host cells. In this review, we address the carbohydrate-mediated glycobiology that directly affects Plasmodium survival or host resistance.

  14. Malaria (For Parents)

    Science.gov (United States)

    ... in others. Proper treatment can cure malaria. What Causes Malaria? Malaria is caused by parasites carried by mosquitoes. ... seen a lot, doctors often treat people for malaria who have a fever with no obvious cause without getting lab tests to prove the person ...

  15. The ¿/d T-cell response to Plasmodium falciparum malaria in a population in which malaria is endemic

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Dodoo, D

    1996-01-01

    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...

  16. Climate, environment and transmission of malaria.

    Science.gov (United States)

    Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Zaramella, Marco; Caputo, Annamaria; Garavelli, Pietro Luigi

    2016-06-01

    Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political

  17. Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil

    Directory of Open Access Journals (Sweden)

    Pedro Renata S

    2012-07-01

    Full Text Available Abstract Background Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions. Methods An observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence. Results Twenty-one relapses (39.6% of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p  Conclusions A known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines.

  18. KINET: a social marketing programme of treated nets and net treatment for malaria control in Tanzania, with evaluation of child health and long-term survival.

    Science.gov (United States)

    Schellenberg, J R; Abdulla, S; Minja, H; Nathan, R; Mukasa, O; Marchant, T; Mponda, H; Kikumbih, N; Lyimo, E; Manchester, T; Tanner, M; Lengeler, C

    1999-01-01

    We present a large-scale social marketing programme of insecticide-treated nets in 2 rural districts in southwestern Tanzania (population 350,000) and describe how the long-term child health and survival impact will be assessed. Formative and market research were conducted in order to understand community perceptions, knowledge, attitudes and practice with respect to the products to be socially marketed. We identified Zuia Mbu (Kiswahili for 'prevent mosquitoes') as a suitable brand name for both treated nets and single-dose insecticide treatment sachets. A mix of public and private sales outlets is used for distribution. In the first stage of a stepped introduction 31 net agents were appointed and trained in 18 villages: 15 were shop owners, 14 were village leaders, 1 was a parish priest and 1 a health worker. For net treatment 37 young people were appointed in the same villages and trained as agents. Further institutions in both districts such as hospitals, development projects and employers were also involved in distribution. Promotion for both products was intense and used a variety of channels. A total of 22,410 nets and 8072 treatments were sold during the first year: 18 months after launching, 46% of 312 families with children aged under 5 years reported that their children were sleeping under treated nets. A strong evaluation component in over 50,000 people allows assessment of the long-term effects of insecticide-treated nets on child health and survival, anaemia in pregnancy, and the costs of the intervention. This evaluation is based on cross-sectional surveys, and case-control and cohort studies.

  19. [Malaria in Poland in 2009].

    Science.gov (United States)

    Stepiń, Małgorzata

    2011-01-01

    In Poland in 2009 were reported 22 malaria cases confirmed according to the EU case definition for the purposes of routine surveillance system. All of them were imported, including 1 case of recrudescence, 86% from Africa. In 18 cases P falciparum etiology was confirmed and in 2--P vivax, in 1--P ovale and 1 P malariae. Most cases occurred in the age group 21-40 years, there were 21 cases in males and 1 in female. Common reasons for travel to endemic countries were work-related visits (14 cases) and tourism (6 cases), one person who visited the family and in one case unknown reason for travel. Three persons used chemoprophylaxis during their travel but only one of them appropriately, relevant information was missing in 5 cases. Clinical course was severe in 7 cases of P falciparum malaria and medium-severe in one case. In 2009, there were no malaria deaths in Poland. Education on the prevention of malaria and pretravel health advising is still greatly needed.

  20. [Malaria in Poland in 2010].

    Science.gov (United States)

    Stepień, Małgorzata

    2012-01-01

    The objective of this study was to describe the epidemiology of imported malaria in Poland in 2010 in comparison to previous years. The study included malaria cases that were collected and registered by the State Sanitary Inspection in 2010 in Poland. Data reported was verified, processed and published by National Institute of Public Health - National Institute of Hygiene. All cases were laboratory confirmed by blood film, polymerase chain reaction or rapid diagnostic tests outlined by the EU case definition. Differences in the distribution of demographic, parasitological and clinical characteristics, and incidence were analyzed. In 2010, a total of 35 confirmed malaria cases were notified in Poland, 13 more than 2009. All cases were imported, 49% from Africa, including 1 case with relapsing malaria caused by P. vivax and 2 cases of recrudescence falciparum malaria following failure of treatment. The number of cases acquired in Asia (37% of the total), mainly from India and Indonesia, was significantly higher than observed in previous years. Among cases with species-specific diagnosis 19 (63%) were caused by P. falciparum, 9 (30%) by P. vivax, one by P. ovale and one by P. malariae. The median age of all cases was 42 years (range 9 months to 71 years), males comprised 69% of patients, females 31%, three patients were Indian citizens temporarily in Poland. Common reasons for travel to endemic countries were tourism (57%), work-related visits (37%), one person visited family and in one case the reason for travel was unknown. Sixteen travelers took chemoprophylaxis, but only three of them appropriately (adherence to the recommended drug regimen, continuation upon return and use of appropriate medicines). In 2010, there were no deaths due to malaria and clinical course of disease was severe in 7 cases. When compared with 2009, there was a marked increase in the number of imported malaria cases in Poland, however the total number of notified cases remained low. Serious

  1. The complexities of malaria disease manifestations with a focus on asymptomatic malaria

    Science.gov (United States)

    2012-01-01

    Malaria is a serious parasitic disease in the developing world, causing high morbidity and mortality. The pathogenesis of malaria is complex, and the clinical presentation of disease ranges from severe and complicated, to mild and uncomplicated, to asymptomatic malaria. Despite a wealth of studies on the clinical severity of disease, asymptomatic malaria infections are still poorly understood. Asymptomatic malaria remains a challenge for malaria control programs as it significantly influences transmission dynamics. A thorough understanding of the interaction between hosts and parasites in the development of different clinical outcomes is required. In this review, the problems and obstacles to the study and control of asymptomatic malaria are discussed. The human and parasite factors associated with differential clinical outcomes are described and the management and treatment strategies for the control of the disease are outlined. Further, the crucial gaps in the knowledge of asymptomatic malaria that should be the focus of future research towards development of more effective malaria control strategies are highlighted. PMID:22289302

  2. Malaria in Poland in 2013.

    Science.gov (United States)

    Stępień, Małgorzata

    2015-01-01

    Evaluation of the epidemiological situation of imported malaria in Poland in 2013 compared to the data from previous years. The assessment was performed based on the results of the analysis of individual reports sent to the NIPH-NIH by sanitary-epidemiological stations and aggregated data published in the annual bulletins "Infectious diseases and poisonings in Poland". Cases were registered according to the case definition criteria applicable in the EU countries. In 2013, a total of 36 imported malaria cases were registered in Poland, 15 more than in 2012. No deaths were recorded. As much as 80% of all cases were imported from African countries, of whom the majority came from Nigeria, 14% from Asia and 6% from South America. Concurrent infection with dengue virus was confirmed in one person coming back from Philippines. Plasmodium species was determined in 35 of 36 cases by blood film or PCR test. Invasion with P. falciparum and P. vivax was found in 23 (66%) and 9 (26%) cases, respectively. There was also one case of each of the following: P. ovale, P. malariae and mixed invasion. As in previous years, in most cases, the invasion was associated with tourist trips (47%) or work-related travels (36%). Immigrants or students visiting the country of origin accounted for 11% of patients, in two cases (6%) purpose of the journey was not determined. As many as 7 patients used chemoprophylaxis, including two persons who took drugs in compliance with the recommendations. Despite a significant increase in the number of cases compared to previous years, the total number of imported malaria remains low. Persistent large number of delays in the diagnosis and a high percentage of severe malaria cases indicate the need to raise doctors awareness of the possibility of malaria incidence. Travelers should be also constantly reminded of the need to inform their GPs about the stay in the malaria endemic areas in the event of fever after returning.

  3. The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis.

    Science.gov (United States)

    Lorente, Leonardo; Martín, Mar; Plasencia, Fátima; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan María; Jiménez, Alejandro; Páramo, José Antonio; Orbe, Josune; Rodríguez, José A; Salido, Eduardo

    2013-05-25

    Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study. This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFα, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman's rank correlation coefficient or Spearman's rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission. Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P=0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio=2.08; 95% confidence interval=1.06 to 4.09; P=0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (χ2=5.77; P=0.016). We found an association between TIMP-1 levels and levels of MMP-9 (ρ=-0.19; P=0.002), MMP-10 (ρ=0.55; Ppolymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic

  4. The impact of coronary artery disease severity on late survival after combined aortic valve replacement and coronary artery bypass grafting - experience of a single cardiac surgery center.

    Science.gov (United States)

    Perek, Bartłomiej; Misterski, Marcin; Stachowiak, Wojciech; Buczkowski, Piotr; Stefaniak, Sebastian; Puślecki, Mateusz; Urbanowicz, Tomasz; Budniak, Wiktor; Jemielity, Marek

    2014-12-01

    The severity of coronary artery disease (CAD) may have an impact on the outcomes of patients (pts) after aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). The aim of the study was to analyze survival after simultaneous AVR and CABG with respect to CAD severity. The study involved 143 consecutive pts (40 women and 103 men) with a mean age of 65.1 ± 7.7 years treated between 2006 and 2009. The indication for surgery was aortic stenosis accompanied by left main or three-vessel disease (group A; n = 43) and by single- or two-vessel disease (group B; n = 100). In-hospital and late mortality were analyzed. Post-discharge survival was estimated using the Kaplan-Meier method. Moreover, selected preoperative clinical and echocardiographic data as well as intraoperative variables were compared between the groups. In-hospital mortality was 4.7% in group A and 3.0% in group B (NS). The 12-month and 48-month survival probability rates were 0.88 ± 0.05 and 0.83 ± 0.06 in group A, and 0.97 ± 0.01 and 0.92 ± 0.03 in group B, respectively (p < 0.05). Patients in group A and B differed (p < 0.05) with respect to the preoperative prevalence of arterial hypertension (65.1% vs. 42.0%) and atrial fibrillation (18.6% vs. 6.0%) as well as with regard to the rate of complete revascularization (20.9% vs. 85.0%, group A and B, respectively). Coronary artery disease severity impacts long-term survival after combined AVR and CABG. Patients with left main or three-vessel disease more often undergo incomplete surgical revascularization, and this fact may be one of the predictors of an unfavorable outcome.

  5. The impact of coronary artery disease severity on late survival after combined aortic valve replacement and coronary artery bypass grafting – experience of a single cardiac surgery center

    Science.gov (United States)

    Misterski, Marcin; Stachowiak, Wojciech; Buczkowski, Piotr; Stefaniak, Sebastian; Puślecki, Mateusz; Urbanowicz, Tomasz; Budniak, Wiktor; Jemielity, Marek

    2014-01-01

    Introduction The severity of coronary artery disease (CAD) may have an impact on the outcomes of patients (pts) after aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). Aim The aim of the study was to analyze survival after simultaneous AVR and CABG with respect to CAD severity. Material and methods The study involved 143 consecutive pts (40 women and 103 men) with a mean age of 65.1 ± 7.7 years treated between 2006 and 2009. The indication for surgery was aortic stenosis accompanied by left main or three-vessel disease (group A; n = 43) and by single- or two-vessel disease (group B; n = 100). In-hospital and late mortality were analyzed. Post-discharge survival was estimated using the Kaplan-Meier method. Moreover, selected preoperative clinical and echocardiographic data as well as intraoperative variables were compared between the groups. Results In-hospital mortality was 4.7% in group A and 3.0% in group B (NS). The 12-month and 48-month survival probability rates were 0.88 ± 0.05 and 0.83 ± 0.06 in group A, and 0.97 ± 0.01 and 0.92 ± 0.03 in group B, respectively (p < 0.05). Patients in group A and B differed (p < 0.05) with respect to the preoperative prevalence of arterial hypertension (65.1% vs. 42.0%) and atrial fibrillation (18.6% vs. 6.0%) as well as with regard to the rate of complete revascularization (20.9% vs. 85.0%, group A and B, respectively). Conclusions Coronary artery disease severity impacts long-term survival after combined AVR and CABG. Patients with left main or three-vessel disease more often undergo incomplete surgical revascularization, and this fact may be one of the predictors of an unfavorable outcome. PMID:26336450

  6. Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999–2010

    Science.gov (United States)

    Smithson, Paul; Florey, Lia; Salgado, S. Rene; Hershey, Christine L.; Masanja, Honorati; Bhattarai, Achuyt; Mwita, Alex; McElroy, Peter D.

    2015-01-01

    Background Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period. Methods Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM. Results Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains. Conclusion Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival. PMID:26536354

  7. Malaria in the Greater Mekong Subregion: heterogeneity and complexity.

    Science.gov (United States)

    Cui, Liwang; Yan, Guiyun; Sattabongkot, Jetsumon; Cao, Yaming; Chen, Bin; Chen, Xiaoguang; Fan, Qi; Fang, Qiang; Jongwutiwes, Somchai; Parker, Daniel; Sirichaisinthop, Jeeraphat; Kyaw, Myat Phone; Su, Xin-zhuan; Yang, Henglin; Yang, Zhaoqing; Wang, Baomin; Xu, Jianwei; Zheng, Bin; Zhong, Daibin; Zhou, Guofa

    2012-03-01

    The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by 'border malaria' and 'forest malaria' with high transmission occurring along international borders and in forests or forest fringes, respectively. 'Border malaria' is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and Plasmodium vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is severely

  8. Malaria-induced immune thrombocytopenia

    DEFF Research Database (Denmark)

    Sørensen, P G; Mickley, H; Schmidt, K G

    1984-01-01

    On return from Liberia, a previously healthy 36-year-old man showed signs of malaria accompanied by severe haemolysis and slight thrombocytopenia. We found evidence of a platelet-associated IgG being responsible for the thrombocytopenia, inasmuch as the direct platelet suspension immunofluorescen...

  9. Ocular complications of malaria treatment

    African Journals Online (AJOL)

    2011-10-08

    Oct 8, 2011 ... Malaria is endemic in Nigeria. With the emergence of chloroquine resistance various modes of treatment including parenteral quinine are employed with consequent untoward effects. This article reports two cases of severe ocular toxicity, including mimicry of intracranial space-occupying lesion, from ...

  10. Neonatal Malaria in the Gambia

    African Journals Online (AJOL)

    Uche

    Department of ... mechanisms such as the milk diet of the infant being deficient ... this protection may not be complete and that symptomatic malaria in the newborn period can occur, and that such babies may present with severe disease. 13-23.

  11. [Pulmonary manifestations associated with malaria].

    Science.gov (United States)

    Hovette, P; Camara, P; Burgel, P R; Mbaye, P S; Sane, M; Klotz, F

    1998-12-01

    Pulmonary manifestations are frequently observed in children, pregnant women and travellers with malaria. The pathophysiology of these pulmonary manifestations is poorly understood but would appear to be secondary to an interaction between the parasitized red cells and the pulmonary capillary endothelium. Bronchitis and pneumonia do not directly compromise outcome but, left unrecognized, the delay in diagnosis and treatment may be fatal. Acute respiratory distress in children is the first cause of overmortality, coming before neurological involvement. The acute respiratory distress caused by severe malaria has no specific characteristics. Iatrogenic complications and pulmonary superinfections must be differentiated. The prevention of pulmonary manifestations associated with malaria can easily be accomplished by limiting water intake and carefully monitoring urinary output and weight. Treatment is the same as for acute flare-ups in combination with symptomatic respiratory treatment when required.

  12. Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats.

    Science.gov (United States)

    Ackland, Gareth L; Yao, Song T; Rudiger, Alain; Dyson, Alex; Stidwill, Ray; Poputnikov, Dmitry; Singer, Mervyn; Gourine, Alexander V

    2010-02-01

    To explore the hypothesis that beta-1 adrenoreceptor blockade may be protective through the attenuation of sympathetic hyperactivity and catecholaminergic inflammatory effects on cardiac and hepatic function. Prospective, randomized, controlled study. Animal laboratory in a university medical center. Male adult Wistar rats. Peripheral beta1-adrenoceptor blockade through daily intraperitoneal injection (metoprolol, 100 mg x kg(-1); atenolol, 6 mg x kg(-1)) or central nervous system beta1-adrenoceptor blockade (intracerebroventricular metoprolol, 25 microg) to achieve approximately 20% heart rate reduction in rats for 2 days before or after the induction of lethal endotoxemia, cecal ligation and puncture, or fecal peritonitis. Peripheral beta1-adrenoceptor blockade established for 2 days before lethal endotoxemia markedly improved survival in both metoprolol-treated (n = 16; log rank test, p = .002) and atenolol-treated (n = 15; p = .03) rats. Overall mortality in cecal ligation and puncture was similar between metoprolol (40%; n = 10) and saline (50%; n = 10) pretreatment (p = .56), but the median time to death was increased by 33 hrs in metoprolol-treated rats (p = .03). Metoprolol pretreatment reduced hepatic expression of proinflammatory cytokines and lowered plasma interleukin-6 (both p inflammatory and cardioprotective effects, with mortality reduction if commenced before a septic insult. Its role in sepsis should be explored further.

  13. Deep intronic variation in splicing regulatory element of the ERCC8 gene associated with severe but long-term survival Cockayne syndrome.

    Science.gov (United States)

    Schalk, Audrey; Greff, Géraldine; Drouot, Nathalie; Obringer, Cathy; Dollfus, Hélène; Laugel, Vincent; Chelly, Jamel; Calmels, Nadège

    2018-02-08

    Cockayne syndrome is an autosomal recessive multisystem disorder characterized by intellectual disability, microcephaly, severe growth failure, sensory impairment, peripheral neuropathy, and cutaneous sensitivity. This rare disease is linked to disease-causing variations in the ERCC6 (CSB) and ERCC8 (CSA) genes. Various degrees of severity have been described according to age at onset and survival, without any clear genotype-phenotype correlation. All types of nucleotide changes have been observed in CS genes, including splice variations mainly affecting the splice site consensus sequences. We report here the case of two brothers from a consanguineous family presenting a severe but long-term survival phenotype of Cockayne syndrome. We identified in the patients a homozygous deep intronic nucleotide variation causing the insertion of a cryptic exon in the ERCC8 (CSA) transcript, by modifying intronic regulatory elements important for exon definition. The pathogenesis of the nucleotide variant NG_009289.1(NM_000082.3):c.173+1119G>C was validated in vitro with a reporter minigene system. To our knowledge, these are the first Cockayne patients described with this kind of disease-causing variation, though molecular mechanism underlying early onset symptoms and unexpected slow raise of progression of the disease remain to be elucidated.

  14. [Inclusion of prehospital mortality statistics in severe trauma registries: a study of the influence of inclusion on trauma lethality rates and survival prediction].

    Science.gov (United States)

    Fortún Moral, Mariano; Ali Ali, Bismil; Montes Fernández, Luisa M; Rey Pecharroman, José Miguel; Teijeira Álvarez, Rafael; Belzunegui Otano, Tomás

    2016-06-01

    To compare the frequency and characteristics of prehospital and hospital deaths and assess whether injury severity and age can predict mortality when prehospital deaths are included or excluded from total mortality. Descriptive analysis of a retrospective cohort of 918 patients with multiple injuries attended by emergency medical services in Navarre, Spain, in 2010-2013. We analyzed prehospital and hospital deaths by cause of injuries and developed and compared the precision of logistic regression models to predict mortality. Most deaths occurred before arrival at a hospital. Three quarters of prehospital deaths occurred in patients under the age of 65 years. When prehospital deaths were included in the analysis, the lethality rate after traffic accidents rose from 16% to 42%; lethality from firearm injuries rose from 13% to 70%. When the model using the new injury severity score and age as independent variables was asked to predict survival with and without data for deaths at the scene or during transfer to a hospital, the model's performance differed only slightly. Most deaths from injuries occur before patients reach a hospital. The main characteristics of prehospital and hospital deaths differ. Including data for prehospital deaths in regression models does not change survival prediction based on injury severity and age.

  15. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

    Science.gov (United States)

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-08-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. Distribution of the 729 women with EC according to BMI was BMI obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

  16. Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Josh Hanson

    Full Text Available BACKGROUND: Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. METHODS: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. RESULTS: If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI 97.8-99.9 and for survival to discharge 96.9% (95% CI 94.3-98.5. In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100 and to discharge was 98.5% (95% CI 94.8-99.8. CONCLUSIONS: Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.

  17. Rapid Clinical Assessment to Facilitate the Triage of Adults with Falciparum Malaria, a Retrospective Analysis

    Science.gov (United States)

    Hanson, Josh; Lee, Sue J.; Mohanty, Sanjib; Faiz, M. Abul; Anstey, Nicholas M.; Price, Ric N.; Charunwatthana, Prakaykaew; Yunus, Emran Bin; Mishra, Saroj K.; Tjitra, Emiliana; Rahman, Ridwanur; Nosten, Francois; Htut, Ye; Maude, Richard J.; Thi Hong Chau, Tran; Phu, Nguyen Hoan; Hien, Tran Tinh; White, Nicholas J.; Day, Nicholas P. J.; Dondorp, Arjen M.

    2014-01-01

    Background Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. Methods We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. Results If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm’s positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8–99.9) and for survival to discharge 96.9% (95% CI 94.3–98.5). In the 712 patients receiving artesunate, the algorithm’s positive predictive value for survival to 48 hours was 100% (95% CI 97.3–100) and to discharge was 98.5% (95% CI 94.8–99.8). Conclusions Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data. PMID:24489828

  18. Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study.

    Science.gov (United States)

    Zhang, Ruyang; Wang, Zhaoxi; Tejera, Paula; Frank, Angela J; Wei, Yongyue; Su, Li; Zhu, Zhaozhong; Guo, Yichen; Chen, Feng; Bajwa, Ednan K; Thompson, B Taylor; Christiani, David C

    2017-03-01

    To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis. Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively. Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48-3.39, P = 1.24 × 10-4 (derivation); HR = 2.16, 95% CI 1.33-3.51, P = 1.95 × 10-3 (validation); and HR = 2.00, 95% CI 1.47-2.72, P = 1.10 × 10-5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16-2.48, P = 6.62 × 10-3 (derivation); HR = 1.78, 95% CI 1.15-2.75, P = 9.80 × 10-3 (validation); and HR = 1.59, 95% CI 1.20-2.10, P = 1.22 × 10-3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04-2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03-2.02, P = 0.0313). Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.

  19. Malaria Surveillance - United States, 2014.

    Science.gov (United States)

    Mace, Kimberly E; Arguin, Paul M

    2017-05-26

    . Less than 1.0% of patients were infected with two species. The infecting species was unreported or undetermined in 11.7% of cases. CDC provided diagnostic assistance for 14.2% of confirmed cases and tested 12.0% of P. falciparum specimens for antimalarial resistance markers. Of patients who reported purpose of travel, 57.5% were visiting friends and relatives (VFR). Among U.S. residents for whom information on chemoprophylaxis use and travel region was known, 7.8% reported that they initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were among pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died. CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers (although some loci for chloroquine and mefloquine were untestable for up to nine samples). Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) and improve the ability of CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this effort to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult CDC

  20. Extended Survival of Several Microorganisms and Relevant Amino Acid Biomarkers under Simulated Martian Surface Conditions as a Function of Burial Depth

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Adam [Indiana University; Pratt, L.M. [Indiana University; Vishnivetskaya, Tatiana A [ORNL; Pfiffner, S. M. [University of Tennessee, Knoxville (UTK); Bryan, R. A. [Yeshiva University, New York; Dadachova, E. [Yeshiva University, New York; Whyte, L G [McGill University, Montreal, Quebec; Radtke, K. [McGill University, Montreal, Quebec; Chan, E. [Princeton University; Tronick, S. [Princeton University; Borgonie, G. [Ghent University, Belgium; Mancinelli, R. [SETI Institute; Rothschild, L. [NASA Ames Research Center; Rogoff, D. [NASA Ames Research Center; Horikawa, D. D. [NASA Ames Research Center; Onstott, T. C. [Princeton University

    2011-01-01

    Recent orbital and landed missions have provided substantial evidence for ancient liquid water on the martian surface as well as evidence of more recent sedimentary deposits formed by water and/or ice. These observations raise serious questions regarding an independent origin and evolution of life on Mars. Future missions seek to identify signs of extinct martian biota in the form of biomarkers or morphological characteristics, but the inherent danger of spacecraft-borne terrestrial life makes the possibility of forward contamination a serious threat not only to the life detection experiments, but also to any extant martian ecosystem. A variety of cold and desiccation-tolerant organisms were exposed to 40 days of simulated martian surface conditions while embedded within several centimeters of regolith simulant in order to ascertain the plausibility of such organisms survival as a function of environmental parameters and burial depth. Relevant amino acid biomarkers associated with terrestrial life were also analyzed in order to understand the feasibility of detecting chemical evidence for previous biological activity. Results indicate that stresses due to desiccation and oxidation were the primary deterrent to organism survival, and that the effects of UV-associated damage, diurnal temperature variations, and reactive atmospheric species were minimal. Organisms with resistance to desiccation and radiation environments showed increased levels of survival after the experiment compared to organisms characterized as psychrotolerant. Amino acid analysis indicated the presence of an oxidation mechanism that migrated downward through the samples during the course of the experiment and likely represents the formation of various oxidizing species at mineral surfaces as water vapor diffused through the regolith. Current sterilization protocols may specifically select for organisms best adapted to survival at the martian surface, namely species that show tolerance to radical

  1. Delayed mortality effects cut the malaria transmission potential of insecticide-resistant mosquitoes.

    Science.gov (United States)

    Viana, Mafalda; Hughes, Angela; Matthiopoulos, Jason; Ranson, Hilary; Ferguson, Heather M

    2016-08-09

    Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance.

  2. De behandeling van malaria

    NARCIS (Netherlands)

    Kager, P. A.; Zijlmans, C. W.; Boele van Hensbroek, M.; Wetsteyn, J. C.

    1997-01-01

    The diagnosis of malaria should include the species involved and in case of P. falciparum infection the parasitaemia index: the percentage of the infected red cells. P. vivax, ovale and malariae infection are treated with chloroquine, in case of P. vivax and ovale malaria followed by primaquine.

  3. Falciparum Malaria Infection in a Case of Sickle Cell Trait; Unbalancing the Balanced Polymorphism

    OpenAIRE

    Amale, Amar; Acharya, Sourya; Shukla, Samarth; Dubey, Sameeksha

    2012-01-01

    Suffers of Sickle cell trait are protected against plasmodium falciparum malaria because of the law of balanced polymorphism. We present a case of sickle cell trait infected with severe falciparum malaria unbalancing of balanced polymorphism.

  4. Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians?

    Science.gov (United States)

    Sangare, Modibo; Dicko, Ilo; Guinto, Cheick Oumar; Sissoko, Adama; Dembele, Kekouta; Coulibaly, Youlouza; Coulibaly, Siaka Y; Landoure, Guida; Diallo, Abdallah; Dolo, Mamadou; Dolo, Housseini; Maiga, Boubacar; Traore, Moussa; Karembe, Mamadou; Traore, Kadiatou; Toure, Amadou; Sylla, Mariam; Togora, Arouna; Coulibaly, Souleymane; Traore, Sékou Fantamady; Hendrickson, Brant; Bricceno, Katherine; Schindler, Alice B; Kokkinis, Angela; Meilleur, Katherine G; Sangho, Hammadoun Ali; Diakite, Brehima; Kassogue, Yaya; Coulibaly, Yaya Ibrahim; Burnett, Barrington; Maiga, Youssoufa; Doumbia, Seydou; Fischbeck, Kenneth H

    2016-06-01

    Spinal muscular atrophy (SMA) and sporadic amyotrophic lateral sclerosis (SALS) are both motor neuron disorders. SMA results from the deletion of the survival motor neuron ( SMN ) 1 gene. High or low SMN1 copy number and the absence of SMN2 have been reported as risk factors for the development or severity of SALS. To investigate the role of SMN gene copy number in the onset and severity of SALS in Malians. We determined the SMN1 and SMN2 copy number in genomic DNA samples from 391 Malian adult volunteers, 120 Yoruba from Nigeria, 120 Luyha from Kenya and 74 U.S. Caucasians using a Taqman quantitative PCR assay. We evaluated the SALS risk based on the estimated SMA protein level using the Veldink formula ( SMN1 copy number + 0.2 ∗  SMN2 copy number). We also characterized the disease natural history in 15 ALS patients at the teaching hospital of Point G, Bamako, Mali. We found that 131 of 391 (33.5%) had an estimated SMN protein expression of ≤ 2.2; 60 out of 391 (15.3%) had an estimated SMN protein expression < 2 and would be at risk of ALS and the disease onset was as early as 16 years old. All 15 patients were male and some were physically handicapped within 1-2 years in the disease course. Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

  5. Reduction in serum sphingosine 1-phosphate concentration in malaria.

    Directory of Open Access Journals (Sweden)

    Chuchard Punsawad

    Full Text Available Sphingosine 1-phosphate (S1P is a lipid mediator formed by the metabolism of sphingomyelin which is involved in the endothelial permeability and inflammation. Although the plasma S1P concentration is reportedly decreased in patients with cerebral malaria, the role of S1P in malaria is still unclear. The purpose of this study was to examine the impact of malaria on circulating S1P concentration and its relationship with clinical data in malaria patients. Serum S1P levels were measured in 29 patients with P. vivax, 30 patients with uncomplicated P. falciparum, and 13 patients with complicated P. falciparum malaria on admission and on day 7, compared with healthy subjects (n = 18 as control group. The lowest level of serum S1P concentration was found in the complicated P. falciparum malaria group, compared with P. vivax, uncomplicated P. falciparum patients and healthy controls (all p < 0.001. In addition, serum S1P level was positively correlated with platelet count, hemoglobin and hematocrit levels in malaria patients. In conclusions, low levels of S1P are associated with the severity of malaria, and are correlated with thrombocytopenia and anemia. These findings highlight a role of S1P in the severity of malaria and support the use of S1P and its analogue as a novel adjuvant therapy for malaria complications.

  6. Malaria, anaemia and antimalarial drug resistance in African children

    NARCIS (Netherlands)

    Obonyo, C.O.

    2006-01-01

    Malaria-associated anaemia is a potentially preventable cause of severe morbidity and mortality in children < 5years of age, in areas of high malaria transmission in sub-Saharan Africa. In a cross-sectional study of 3586 children, 80% were anaemic (haemoglobin [Hb]<11g/dL) and 3% had severe anaemia

  7. Glucose production and gluconeogenesis in adults with cerebral malaria

    NARCIS (Netherlands)

    van Thien, H.; Ackermans, M. T.; Dekker, E.; Thanh Chien, V. O.; Le, T.; Endert, E.; Kager, P. A.; Romijn, J. A.; Sauerwein, H. P.

    2001-01-01

    Hypoglycaemia is an important complication in severe malaria, ascribed to an inhibition of gluconeogenesis. However, the only data available suggested that in severe malaria, total glucose production is increased. We measured glucose production and gluconeogenesis after an overnight fast in all

  8. Malaria in a returning traveler from Jamaica.

    Science.gov (United States)

    Kavanaugh, Michael; Bavaro, Mary

    2014-06-01

    Malaria in Jamaica is a real, but uncommon entity and poses a health risk to our Department of Defense personnel, which should not be overlooked in returning travelers. Malaria in Jamaica was actually considered eradicated in the 1960s, but there has been a reemergence attributed to the combination of Haitian nationals as well as endemic Anopheles mosquitoes in the Kingston area. Our facility recently admitted a 33-year-old Marine who had two Emergency Department visits before being evaluated for malaria. He had returned from Kingston 14 days before presentation, which included fever, night sweats, and headache followed by a period of malaise prior to the next paroxysm. He was found to have a 1.5% parasitemia with Malaria falciparum that borders on severe malaria. Fortunately, he was treated effectively with atovaquone/proguanil and had a favorable outcome. The Center for Disease Control acknowledges that malaria is present in Jamaica, but only recommends mosquito avoidance without prophylaxis. This case emphasizes the need to consider malaria in differential diagnosis in Jamaica as well as in any returning travelers with fever because of broad global travel. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  9. Malaria in Children.

    Science.gov (United States)

    Cohee, Lauren M; Laufer, Miriam K

    2017-08-01

    Malaria is a leading cause of morbidity and mortality in endemic areas, leading to an estimated 438,000 deaths in 2015. Malaria is also an important health threat to travelers to endemic countries and should be considered in evaluation of any traveler returning from a malaria-endemic area who develops fever. Considering the diagnosis of malaria in patients with potential exposure is critical. Prompt provision of effective treatment limits the complications of malaria and can be life-saving. Understanding Plasmodium species variation, epidemiology, and drug-resistance patterns in the geographic area where infection was acquired is important for determining treatment choices. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Imported Plasmodium falciparum malaria in HIV-infected patients: A report of two cases

    OpenAIRE

    García-Bujalance Silvia; Francisco Carolina; Rubio José M; Arribas José R; Gutierrez Avelino

    2012-01-01

    Abstract As HIV becomes a chronic infection, an increasing number of HIV-infected patients are travelling to malaria-endemic areas. Association of malaria with HIV/AIDS can be clinically severe. Severe falciparum malaria is a medical emergency that is associated with a high mortality, even when treated in an Intensive Care Unit. This article describes two cases of HIV-positive patients, who returned from malaria-endemic areas and presented a parasitaemia > 5% of erythrocytes and clinical sign...

  11. Malaria: Epidemiology and Diagnostic

    Directory of Open Access Journals (Sweden)

    Lukman Hakim

    2011-12-01

    Full Text Available Malaria is an infectious disease caused by Plasmodium spp, are naturally trans­mitted by the mosquito Anopheles spp. Malaria transmission occurs because of interaction between the agent, the definitive host and intermediate hosts (humans. Therefore, the trans­mission of malaria is injluenced by the presence and fluctuations in vector populations (i.e transmitting mosquito Anopheles spp.Malaria diagnosis consists of clinical diagnosis and diagnosis based on laboratory examina­tion. Clinical diagnosis or clinical malaria diagnosis was presumptive diagnosis of malaria based on clinical examination of patients with symptoms include fever (periodical, heat, level of consciousness, dizziness, etc. as well as specific local typical symptoms. Experiences of medical personnel who perform precise diagnosis will determine whether or not the diag­nosis, so that clinical diagnosis cannot be the main reference in the treatment of malaria be­cause of high error rates.

  12. [Malaria tropica and pregnancy].

    Science.gov (United States)

    Broermann, L; Heidenreich, W

    1992-10-01

    The authors report on a female patient of 26 years of age suffering from malaria tropica infection in her 36th week of pregnancy with fatal outcome. The newborn (after performance of Caesarean section) was infected connatally. Although infections with malaria are rare in Europe today--especially during pregnancy--there is a probability of rising incidence on account of increasing international tourism. Therapeutic problems are expected to multiply due to the resistance of Plasmodia to antiparasitary medication. Additionally pregnancy involves the risk of a more severe course of the disease in the mother. Pregnant women should be discouraged from travelling to countries with malarial risk because of the likelihood of a high rate of abortion, danger of intrauterine retardation, increased incidence of premature deliveries and risk of connatal infection of the newborn. If such warnings cannot be heeded, the persons concerned must be given all relevant information on conventional preventive measures in accordance with WHO recommendations and drug prophylaxis as recommended by a hospital or institution dealing with tropical diseases according to updated standards. The measures to be taken must be adapted to the individual risk of exposure of the patient.

  13. Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected].

    Directory of Open Access Journals (Sweden)

    Weera Mahavanakul

    Full Text Available The Surviving Sepsis Campaign (SSC guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting.We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53% of who died within 28 days. One third of patients were treated in intensive care units (ICUs. Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis.It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.

  14. Diagnosis of Plasmodium falciparum malaria in children using the ...

    African Journals Online (AJOL)

    Results: The results showed that the diagnosis of falciparum malaria was achieved within eight minutes using the ICT-Malaria P f Ò test kit. The sensitivity of the test kit was 69.6 percent while the specificity was 98.4 percent. However, among patients with severe malaria, the ICT had a sensitivity of 90.3 percent. The test kit ...

  15. Uncovering the role of IFNAR1 in Experimental Cerebral malaria

    OpenAIRE

    Ball, Elisabeth Ann

    2013-01-01

    Dissertation presented the Ph.D degree in Biology Cerebral malaria is a severe and fatal form of clinical Plasmodium falciparum infection, resulting in brain injury from a damaging cascade of vascular, inflammatory and immunological host responses. However progression to cerebral malaria can be modified by host genetic factors. This thesis work extensively reveals the role of Interferon type I receptor (IFNAR1) in the development of Experimental cerebral malaria, through ...

  16. [Malaria in Poland in 2007].

    Science.gov (United States)

    Rosińska, Magdalena

    2009-01-01

    In Poland in 2007 there were 11 malaria cases confirmed according to the European Union cases definition reported through the routine surveillance system. All of them were imported, 82% from Africa, including 2 cases of relapse. Invasion with Plasmodium falciparum was diagnosed in 7 cases, mixed invasion in 2 cases and P. vivax- in one case. The majority of cases were in the age group 35-45 (8 cases) and were males (10 cases). Common reasons for travel to endemic countries were work-related (5 cases) and tourism or family visits (4 cases). Approximately half of the cases for whom the information was available used malaria chemoprophylaxis during their travel. Clinical course was severe in one case of P. falciparum malaria and the person died of the disease. The decreasing trend in malaria incidence in Poland is likely related to incomplete reporting as tourist and professional travel to endemic areas has not decreased and there is no indication of wider use ofchemoprophylaxis.

  17. Malaria in the Greater Mekong Subregion: Heterogeneity and Complexity

    Science.gov (United States)

    Cui, Liwang; Yan, Guiyun; Sattabongkot, Jetsumon; Cao, Yaming; Chen, Bin; Chen, Xiaoguang; Fan, Qi; Fang, Qiang; Jongwutiwes, Somchai; Parker, Daniel; Sirichaisinthop, Jeeraphat; Kyaw, Myat Phone; Su, Xin-zhuan; Yang, Henglin; Yang, Zhaoqing; Wang, Baomin; Xu, Jianwei; Zheng, Bin; Zhong, Daibin; Zhou, Guofa

    2011-01-01

    The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by ‘border malaria’ and ‘forest malaria’ with high transmission occurring along international borders and in forests or forest fringes, respectively. ‘Border malaria’ is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and P. vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is

  18. Prevalence of Malaria Plasmodium in Abeokuta, Nigeria

    Directory of Open Access Journals (Sweden)

    Okonko, I. O.

    2009-01-01

    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

  19. Malaria in South Asia: Prevalence and control

    Science.gov (United States)

    Kumar, Ashwani; Chery, Laura; Biswas, Chinmoy; Dubhashi, Nagesh; Dutta, Prafulla; Dua, Virendra Kumar; Kacchap, Mridula; Kakati, Sanjeeb; Khandeparkar, Anar; Kour, Dalip; Mahajanj, Satish N.; Maji, Ardhendu; Majumder, Partha; Mohanta, Jagadish; Mohapatra, Pradyumna K.; Narayanasamy, Krishnamoorthy; Roy, Krishnangshu; Shastri, Jayanthi; Valecha, Neena; Vikash, Rana; Wani, Reena; White, John; Rathod, Pradipsinh K

    2013-01-01

    The “Malaria Evolution in South Asia” (MESA) program project is an International Center of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. This US–India collaborative program will study the origin of genetic diversity of malaria parasites and their selection on the Indian subcontinent. This knowledge should contribute to a better understanding of unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. In this first of two reviews, we highlight malaria prevalence in India. In particular, we draw attention to variations in distribution of different human-parasites and different vectors, variation in drug resistance traits, and multiple forms of clinical presentations. Uneven malaria severity in India is often attributed to large discrepancies in health care accessibility as well as human migrations within the country and across neighboring borders. Poor access to health care goes hand in hand with poor reporting from some of the same areas, combining to possibly distort disease prevalence and death from malaria in some parts of India. Corrections are underway in the form of increased resources for disease control, greater engagement of village-level health workers for early diagnosis and treatment, and possibly new public–private partnerships activities accompanying traditional national malaria control programs in the most severely affected areas. A second accompanying review raises the possibility that, beyond uneven health care, evolutionary pressures may alter malaria parasites in ways that contribute to severe disease in India, particularly in the NE corridor of India bordering Myanmar Narayanasamy et al., 2012. PMID:22248528

  20. Viral and bacterial causes of severe acute respiratory illness among children aged less than 5 years in a high malaria prevalence area of western Kenya, 2007-2010.

    Science.gov (United States)

    Feikin, Daniel R; Njenga, M Kariuki; Bigogo, Godfrey; Aura, Barrack; Aol, George; Audi, Allan; Jagero, Geoffrey; Muluare, Peter O; Gikunju, Stella; Nderitu, Leonard; Winchell, Jonas M; Schneider, Eileen; Erdman, Dean D; Oberste, M Steven; Katz, Mark A; Breiman, Robert F

    2013-01-01

    Few comprehensive data exist on the etiology of severe acute respiratory illness (SARI) among African children. From March 1, 2007 to February 28, 2010, we collected blood for culture and nasopharyngeal and oropharyngeal swabs for real-time quantitative polymerase chain reaction for 10 viruses and 3 atypical bacteria among children aged causes and pneumococcus the most likely bacterial cause. Contemporaneous controls are important for interpreting upper respiratory tract specimens.

  1. Respiratory Virus-Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition.

    Science.gov (United States)

    Peterson, Ingrid; Bar-Zeev, Naor; Kennedy, Neil; Ho, Antonia; Newberry, Laura; SanJoaquin, Miguel A; Menyere, Mavis; Alaerts, Maaike; Mapurisa, Gugulethu; Chilombe, Moses; Mambule, Ivan; Lalloo, David G; Anderson, Suzanne T; Katangwe, Thembi; Cunliffe, Nigel; Nagelkerke, Nico; McMorrow, Meredith; Widdowson, Marc-Allain; French, Neil; Everett, Dean; Heyderman, Robert S

    2016-12-01

     We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering.  From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection.  Hospital-attended influenza virus-positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged infected children aged 5-9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4-3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3-3.0) and rainy season (aRR, 2.4; 95% CI, 1.6-3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs.  Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. KEMUNGKINAN MALARIA PRIMATA SEBAGAI MASALAH ZOONOSIS

    Directory of Open Access Journals (Sweden)

    Shinta Shinta

    2012-09-01

    Full Text Available Until today, four species of Plasmodium are pedicular to inan {Plasmodium falciparum, P. vivax, P. malariae, and P. ovale and at least five species are common in simian: Plasmodium inue, P. cynomolgy, P. knowlesi, P. brasilianum and P. simium. There is little doubts that simian Plasmodium can infect man, it is known as zoonosis. Number of cases of zoonosis infection of simian Plasmodium have been reported from several countries; P. knowlesi (1965, in America, P. simium (1966 in Brazilia, P. inui (1971 in Pahang Malaysia, P. cynomolgi (1973 in America and P. Brazilianum in Sao Paulo (1966, 1995. While pro and contra about zoonotic malaria still not clearly discussed, the new cases have occurred. This give an indication that this zoor >tic malaria will probably be in Indonesia where human, primate, Plasmodium (agents and vector live in the same ecosystem. This paper will discuss the simian Plasmodium and its possibility to be a zoonotic malaria.

  3. Sri Lanka Malaria Maps

    Directory of Open Access Journals (Sweden)

    van der Hoek Wim

    2003-07-01

    Full Text Available Abstract Background Despite a relatively good national case reporting system in Sri Lanka, detailed maps of malaria distribution have not been publicly available. Methods In this study, monthly records over the period 1995 – 2000 of microscopically confirmed malaria parasite positive blood film readings, at sub-district spatial resolution, were used to produce maps of malaria distribution across the island. Also, annual malaria trends at district resolution were displayed for the period 1995 – 2002. Results The maps show that Plasmodium vivax malaria incidence has a marked variation in distribution over the island. The incidence of Plasmodium falciparum malaria follows a similar spatial pattern but is generally much lower than that of P. vivax. In the north, malaria shows one seasonal peak in the beginning of the year, whereas towards the south a second peak around June is more pronounced. Conclusion This paper provides the first publicly available maps of both P. vivax and P. falciparum malaria incidence distribution on the island of Sri Lanka at sub-district resolution, which may be useful to health professionals, travellers and travel medicine professionals in their assessment of malaria risk in Sri Lanka. As incidence of malaria changes over time, regular updates of these maps are necessary.

  4. Malaria drives T cells to exhaustion

    Directory of Open Access Journals (Sweden)

    Michelle N Wykes

    2014-05-01

    Full Text Available Malaria is a significant global burden but after >30 years of effort there is no vaccine on the market. While the complex life cycle of the parasite presents several challenges, many years of research have also identified several mechanisms of immune evasion by Plasmodium spp.. Recent research on malaria, has investigated the Programmed cell death-1 (PD-1 pathway which mediates exhaustion of T cells, characterized by poor effector functions and recall responses and in some cases loss of the cells by apoptosis. Such studies have shown exhaustion of CD4+ T cells and an unappreciated role for CD8+ T cells in promoting sterile immunity against blood stage malaria. This is because PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8+ T cells, thus masking their role in protection. The role of T cell exhaustion during malaria provides an explanation for the absence of sterile immunity following the clearance of acute disease which will be relevant to future malaria-vaccine design and suggests the need for novel therapeutic solutions. This review will thus examine the role of PD-1-mediated T cell exhaustion in preventing lasting immunity against malaria.

  5. Survival status and predictors of mortality among severely acute malnourished children <5 years of age admitted to stabilization centers in Gedeo Zone: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Girum T

    2017-01-01

    Full Text Available Tadele Girum,1 Mesfin Kote,2 Befikadu Tariku,2 Henok Bekele3 1Department of Public Health, College of Medicine and Health Sciences, Wolkite University, Wolkite, 2Department of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, 3Department of Planning, Adare Hospital, Southern Region Health Bureau, Hawassa, Ethiopia Abstract: Despite the existence of standard protocol, many stabilization centers (SCs continue to experience high mortality of children receiving treatment for severe acute malnutrition. Assessing treatment outcomes and identifying predictors may help to overcome this problem. Therefore, a 30-month retrospective cohort study was conducted among 545 randomly selected medical records of children <5 years of age admitted to SCs in Gedeo Zone. Data was entered by Epi Info version 7 and analyzed by STATA version 11. Cox proportional hazards model was built by forward stepwise procedure and compared by the likelihood ratio test and Harrell’s concordance, and fitness was checked by Cox–Snell residual plot. During follow-up, 51 (9.3% children had died, and 414 (76% and 26 (4.8% children had recovered and defaulted (missed follow-up for 2 consecutive days, respectively. The survival rates at the end of the first, second and third weeks were 95.3%, 90% and 85%, respectively, and the overall mean survival time was 79.6 days. Age <24 months (adjusted hazard ratio [AHR] =2.841, 95% confidence interval [CI] =1.101–7.329, altered pulse rate (AHR =3.926, 95% CI =1.579–9.763, altered temperature (AHR =7.173, 95% CI =3.05–16.867, shock (AHR =3.805, 95% CI =1.829–7.919, anemia (AHR =2.618, 95% CI =1.148–5.97, nasogastric tube feeding (AHR =3.181, 95% CI =1.18–8.575, hypoglycemia (AHR =2.74, 95% CI =1.279–5.87 and treatment at hospital stabilization center (AHR =4.772, 95% CI =1.638–13.9 were independent predictors of mortality. The treatment outcomes and incidence of death

  6. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium.

    Science.gov (United States)

    Faust, Christina; Dobson, Andrew P

    2015-12-01

    Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence-absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  7. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

    Directory of Open Access Journals (Sweden)

    Christina Faust

    2015-12-01

    Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  8. Malaria complicated by gangrene: a case presentation and review

    Directory of Open Access Journals (Sweden)

    Faraj Omar Alkizim

    2011-11-01

    Full Text Available Symmetrical peripheral gangrene (SPG is an extremely rare complication of malaria. It occurs acutely and progresses rapidly to cause irreversible necrosis of tissue following which debridement or amputation is inevitable. We present a case of malaria complicated by SPG. A 54-year old male developed SPG two days after he was diagnosed with severe malaria and treated with intravenous quinine. Despite intervention quad-amputation was necessary as the gangrene had involved all four limbs. SPG secondary to malaria is caused by obstruction of arterioles following sequestration of parasite infected erythrocytes. This is extremely rare, hence almost never anticipated during management of malaria patients. Furthermore due to its rapid progression, it is almost always detected at an advanced irreversible stage. Physicians managing malaria should therefore be vigilant, and look out for SPG, as its prognosis is dependent on correct and timely intervention.

  9. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study

    National Research Council Canada - National Science Library

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-01-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS...

  10. Congenital Malaria in China

    Science.gov (United States)

    Liu, Xue; Culleton, Richard; Tao, Li; Xia, Hui; Gao, Qi

    2014-01-01

    Abstract Background Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. Methods/Principal Findings Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured

  11. Epidemiological and clinical profile of paediatric malaria: a cross sectional study performed on febrile children in five epidemiological strata of malaria in Cameroon.

    Science.gov (United States)

    Kwenti, Tebit Emmanuel; Kwenti, Tayong Dizzle Bita; Latz, Andreas; Njunda, Longdoh Anna; Nkuo-Akenji, Theresa

    2017-07-17

    In the wake of a decline in global malaria, it is imperative to describe the epidemiology of malaria in a country to inform control policies. The purpose of this study was to describe the epidemiological and clinical profile of paediatric malaria in five epidemiological strata of malaria in Cameroon including: the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata, and the Coastal (C) strata. This study involved 1609 febrile children (≤15 years) recruited using reference hospitals in the five epidemiological strata. Baseline characteristics were determined; blood glucose level was measured by a glucometer, malaria parasitaemia was assessed by Giemsa microscopy, and complete blood count was performed using an automated hematology analyser. Severe malaria was assessed and categorized based on WHO criteria. An overall prevalence of 15.0% (95% CI: 13.3-16.9) for malaria was observed in this study. Malaria prevalence was significantly higher in children between 60 and 119 months (p malaria (SM) attack in this study was 29.3%; SM was significantly higher in children below 60 months (p malaria anaemia and impaired consciousness. The majority (73.2%) of SM cases were in group 1 of the WHO classification of severe malaria (i.e. the most severe form). The malaria case-fatality rate was 5.8%; this was higher in Ngaoundere (HIP strata) (p = 0.034). In this study, malaria prevalence decreased steadily northward, from the C strata in the South to the SS strata in the North of Cameroon, meanwhile the mortality rate associated with malaria increased in the same direction. On the contrary, the rate of severe malaria attack was similar across the different epidemiological strata. Immunoepidemiological studies will be required to shed more light on the observed trends.

  12. HIPOGLIKEMIA PADA SEORANG PENDERITA MALARIA

    Directory of Open Access Journals (Sweden)

    P. N. Harianto

    2012-09-01

    Full Text Available Hypoglycemia is a serious and often fatal complication of severe malaria. This condition has been reported in many parts of the world including from Thailand (1983 and from Indonesia by Hoffman (1988 and Harianto (1990. Two main causes that can lead to development of this condition are quinine administration and the severity of the malaria condition itself. A case study is presented about development of prolonged hypoglycemia after quinine administration. A 41 years old male was hospitalized with 4 days history of fever, headache vomiting and icterus. On examination he was found to be in good mental status, had a normal blood pressure, and a body temperature of 40°C. He also had icterus and hepatomegaly. Laboratory examination on admission showed malaria slide positive forRfalciparum ring 30-40, with parasite count of 3% (+ on day I. CBC showed: WBC of 21,700/mm3 and platelet count of 40,000/mm3. Blood chemistry showed glucose level of 77 mm %, serum bilirubin of 29.34 mg % (direct 21.87 mg % SGOT 31 u/l, SGPT 20 u/l, serum ureum 167 mg %, creatinine of 3.36 mg %, serum Na 123 m Eq/L and K 3.99 Eq/L. Urinalysis was normal except for specific gravity of 1.07. After diagnosis of bilious malaria was confirmed, the patient was given i.v. quinine 500 mg diluted in 500 ml 5% dextrose, infused over 4 hours and repeated every 8 hours. On day IVi.v. quinine was switched to oral preparation of 600 mg given bid and the next day quinine was changed to oral chloroquine. The day after admission (30 hours after quinine administration, blood glucose dropped to 21 mg %, 16-46 mg % on day III, and to less than 10 mg % on day IV. It gradulty returned to normal afterwards. Administration of 10% dextrose and boluses of 40% glucose were able to keep the patient in good clinical condition and prevent death. Malaria slide improved on day III, became negative by day IV and serum bilirubin also decreased on follow up. Hypoglycemia should be expected in severe malaria

  13. Malaria control in the African Region: perceptions and viewspoints on proceedings of the Africa Leaders Malaria Alliance (ALMA).

    Science.gov (United States)

    Sambo, Luis Gomes; Ki-Zerbo, Georges; Kirigia, Joses Muthuri

    2011-06-13

    In 2009 a total of 153,408 malaria deaths were reported in Africa. Eleven countries showed a reduction of more than 50% in either confirmed malaria cases or malaria admissions and deaths in recent years. However, many African countries are not on track to achieve the malaria component of the Millennium Development Goal (MDG) 6. The African Leaders Malaria Alliance (ALMA) working session at the 15th African Union Summit discussed the bottlenecks to achieving MDG 6 (specifically halting and beginning to reverse the incidence of malaria by 2015), success factors, and what countries needed to do to accelerate achievement of the MDG. The purpose of this article is to reflect on the proceedings of the ALMA working session. Working methods of the session included speeches and statements by invited speakers and high-level panel discussions. The main bottlenecks identified related to the capacity of the health systems to deliver quality care and accessibility issues; need for strong, decentralized malaria-control programmes with linkages with other health and development sectors, the civil society and private sector entities; benefits of co-implementation of malaria control programmes with child survival or other public health interventions; systematic application of integrated promotive, preventive, diagnostic and case management interventions with full community participation; adapting approaches to local political, socio-cultural and administrative environments.The following prerequisites for success were identified: a clear vision and effective leadership of national malaria control programmes; high level political commitment to ensure adequate capacity in expertise, skill mix and number of managers, technicians and service providers; national ownership, intersectoral collaboration and accountability, as well as strong civil society and private sector involvement; functional epidemiological surveillance systems; and levering of African Union and regional economic

  14. Malaria control in the African Region: perceptions and viewspoints on proceedings of the Africa Leaders Malaria Alliance (ALMA

    Directory of Open Access Journals (Sweden)

    Sambo Luis

    2011-06-01

    Full Text Available Abstract Background In 2009 a total of 153,408 malaria deaths were reported in Africa. Eleven countries showed a reduction of more than 50% in either confirmed malaria cases or malaria admissions and deaths in recent years. However, many African countries are not on track to achieve the malaria component of the Millennium Development Goal (MDG 6. The African Leaders Malaria Alliance (ALMA working session at the 15th African Union Summit discussed the bottlenecks to achieving MDG 6 (specifically halting and beginning to reverse the incidence of malaria by 2015, success factors, and what countries needed to do to accelerate achievement of the MDG. The purpose of this article is to reflect on the proceedings of the ALMA working session. Methods Working methods of the session included speeches and statements by invited speakers and high-level panel discussions. Discussion The main bottlenecks identified related to the capacity of the health systems to deliver quality care and accessibility issues; need for strong, decentralized malaria-control programmes with linkages with other health and development sectors, the civil society and private sector entities; benefits of co-implementation of malaria control programmes with child survival or other public health interventions; systematic application of integrated promotive, preventive, diagnostic and case management interventions with full community participation; adapting approaches to local political, socio-cultural and administrative environments. The following prerequisites for success were identified: a clear vision and effective leadership of national malaria control programmes; high level political commitment to ensure adequate capacity in expertise, skill mix and number of managers, technicians and service providers; national ownership, intersectoral collaboration and accountability, as well as strong civil society and private sector involvement; functional epidemiological surveillance systems

  15. HIV AND MALARIA

    Directory of Open Access Journals (Sweden)

    Ririek Parwitasari

    2014-01-01

    Full Text Available IV/AIDS is a global problem involving industrialized and developing country including Indonesia. Malaria has killed millions ofhuman beings almost 3 million people each year, whereas since 1999, nearly 36 million people in the world infected with HIV and 3 million more have died (Kakilaya, 2006. HIV infection increases the risk and aggravate malaria. In Africa in the area of malaria transmission intensities high and low, HIVaggravate malaria and improve case fatality at any age (Eline 2006. HIVis an RNA viruses whose hallmark is the reverse transcriptation ofits genomic. Malaria is a protozoan disease transmitted by the bite ofinfected anopheles mosquito. Infection malaria can stimulate HIV replication and may cause faster progression ofHIV disease.

  16. Malaria rapid diagnostic tests: a revolution and a challenge for the ...

    African Journals Online (AJOL)

    Febrile patients in malaria-endemic areas need rapid and accurate diagnosis to ensure prompt access to antimalarial treatment to avoid severe disease. As most fevers in malaria-endemic areas of South Africa are not caused by malaria, and symptom-based diagnosis is highly nonspecific, rapid demonstration of the ...

  17. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: 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. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with

  18. Malaria and Tropical Travel

    Centers for Disease Control (CDC) Podcasts

    2008-05-15

    Malaria is a serious mosquito-borne disease that can lead to death. This podcast discusses malaria risk when traveling to tropical areas, as well as how to protect yourself and your family from malaria infection.  Created: 5/15/2008 by National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED).   Date Released: 5/29/2008.

  19. A review of malaria transmission dynamics in forest ecosystems

    Science.gov (United States)

    2014-01-01

    Malaria continues to be a major health problem in more than 100 endemic countries located primarily in tropical and sub-tropical regions around the world. Malaria transmission is a dynamic process and involves many interlinked factors, from uncontrollable natural environmental conditions to man-made disturbances to nature. Almost half of the population at risk of malaria lives in forest areas. Forests are hot beds of malaria transmission as they provide conditions such as vegetation cover, temperature, rainfall and humidity conditions that are conducive to distribution and survival of malaria vectors. Forests often lack infrastructure and harbor tribes with distinct genetic traits, socio-cultural beliefs and practices that greatly influence malaria transmission dynamics. Here we summarize the various topographical, entomological, parasitological, human ecological and socio-economic factors, which are crucial and shape malaria transmission in forested areas. An in-depth understanding and synthesis of the intricate relationship of these parameters in achieving better malaria control in various types of forest ecosystems is emphasized. PMID:24912923

  20. The Transcriptional Response of Neurotrophins and Their Tyrosine Kinase Receptors in Lumbar Sensorimotor Circuits to Spinal Cord Contusion is Affected by Injury Severity and Survival Time

    Science.gov (United States)

    Hougland, M. Tyler; Harrison, Benjamin J.; Magnuson, David S. K.; Rouchka, Eric C.; Petruska, Jeffrey C.

    2013-01-01

    Traumatic spinal cord injury (SCI) results in changes to the anatomical, neurochemical, and physiological properties of cells in the central and peripheral nervous system. Neurotrophins, acting by binding to their cognate Trk receptors on target cell membranes, contribute to modulation of anatomical, neurochemical, and physiological properties of neurons in sensorimotor circuits in both the intact and injured spinal cord. Neurotrophin signaling is associated with many post-SCI changes including maladaptive plasticity leading to pain and autonomic dysreflexia, but also therapeutic approaches such as training-induced locomotor improvement. Here we characterize expression of mRNA for neurotrophins and Trk receptors in lumbar dorsal root ganglia (DRG) and spinal cord after two different severities of mid-thoracic injury and at 6 and 12 weeks post-SCI. There was complex regulation that differed with tissue, injury severity, and survival time, including reversals of regulation between 6 and 12 weeks, and the data suggest that natural regulation of neurotrophins in the spinal cord may continue for months after birth. Our assessments determined that a coordination of gene expression emerged at the 12-week post-SCI time point and bioinformatic analyses address possible mechanisms. These data can inform studies meant to determine the role of the neurotrophin signaling system in post-SCI function and plasticity, and studies using this signaling system as a therapeutic approach. PMID:23316162

  1. Vaccines against malaria.

    Science.gov (United States)

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  3. Annual Frequency of Malaria Attack in Different Haemoglobin ...

    African Journals Online (AJOL)

    GREG F. FOMBO

    The high frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency gene in malaria endemic regions is believed to be ... hosts through reduction of severe malarial anaemia, density parasitaemia and clinical malarial symptoms while having less effect ..... Molecular Monitoring of Malaria Vaccine Trial. Trends in.

  4. Experimental human challenge infections can accelerate clinical malaria vaccine development

    NARCIS (Netherlands)

    Sauerwein, R.W.; Roestenberg, M.; Moorthy, V.S.

    2011-01-01

    Malaria is one of the most frequently occurring infectious diseases worldwide, with almost 1 million deaths and an estimated 243 million clinical cases annually. Several candidate malaria vaccines have reached Phase IIb clinical trials, but results have often been disappointing. As an alternative to

  5. Ethical dilemmas in malaria vector research in Africa: Making the ...

    African Journals Online (AJOL)

    Malaria vector research presents several dilemmas relating to the various ways in which humans are used in the malaria vector research enterprise. A review of the past and present practices reveals much about the prevailing attitudes and assumptions with regard to the ethical conduct of research involving humans.

  6. Serum ferritin levels in children with malaria anaemia in Ibadan

    African Journals Online (AJOL)

    Dr. J. T. Ekanem

    manifestation of acute severe malaria in southwestern Nigeria is anaemia. Pathogenic mechanisms such as haemolysis, impaired erythropoiesis6, and possibly iron sequestration and iron deficiency7 could contribute to the anaemia, and serum ferritin levels have been shown to increase with increasing malaria density8,9.

  7. Plasmodium falciparum malaria in children at a tertiary teaching ...

    African Journals Online (AJOL)

    raoul

    2011-09-06

    Sep 6, 2011 ... study was done to determine the association between ABO phenotypes and the severity of P. falciparum malaria in children. Methods: ... falciparum malaria, and their mean haemoglobin was 4.49 g/dl (SD ±1.69). .... Tube 1 - 1 volume anti-A serum and 1 volume 5% patient's red cell suspension in saline.

  8. Parasitaemia and haematological changes in malaria-infected ...

    African Journals Online (AJOL)

    The health burden posed by malaria infection worldwide cannot be overemphasised.[1,2] To date, malaria has represented one of the most severe causes of morbidity among refugee populations worldwide. The United Nations High Commissioner for Refugees reported that this disease affects more than a million cross- ...

  9. Asymptomatic malaria and associated factors among blood donors ...

    African Journals Online (AJOL)

    Background: Blood transfusion saves life of patients with severe anaemia. However, blood transfusion can transmit blood-borne parasites. Despite malaria being endemic in Tanzania, there is limited information on asymptomatic malaria among blood donors. This study determined the prevalence and associated factors of ...

  10. Exclusive Breastfeeding and Malaria in Early Infancy: Experience ...

    African Journals Online (AJOL)

    Malaria is a leading cause of morbidity and mortality in African children including infants while the roles of exclusive breastfeeding in the prevention of infections and protection against several common childhood morbidities are widely acknowledged. To study the role of exclusive breastfeeding on the incidence of malaria in ...

  11. Review Article: Morphological Changes in Malaria | Buhari | African ...

    African Journals Online (AJOL)

    Malaria remains a global health problem. Several organs of the body are affected by the Plasmodium species which parasitized erythrocytes. The small blood vessels of all the major organs of the body are usually filled with parasitized red cells and this represents the major morphological changes seen in malaria.

  12. Review Article: Malaria Vaccine: The Pros and Cons | Saleh ...

    African Journals Online (AJOL)

    Other relevant websites like PATH, Malaria Vaccine Initiative and Global Fund were also visited to source for information. The key words employed were: malaria, vaccine, anopheles mosquito, insecticide treated bed-nets, pyrethroids and Plasmodium. several studies have underscored the need to develop an effective ...

  13. Hyposplenism revealed by Plasmodium malariae infection.

    Science.gov (United States)

    Hommel, Benjamin; Galloula, Alexandre; Simon, Anne; Buffet, Pierre

    2013-08-02

    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.

  14. [Malaria in Poland in 2008].

    Science.gov (United States)

    Stepień, Małgorzata

    2010-01-01

    There were 22 malaria cases confirmed according to the European Union cases definition registered in Poland in 2008. All of them were imported, 13 cases (59%) from Africa, 3 from Asia, 5 from Oceania and 1 from South America. Invasion with Plasmodium falciparum was confirmed in 14 cases, P. vivax in 4 cases, mixed invasion in 2 cases and in 2 cases species of Plasmodium was undetermined. There were 13 cases in males and 9 in females. Age at onset ranged from 23 to 58 years and majority of cases were in the age group 25-40. Common reason for travel to endemic countries were tourism (11 cases) and work-related visits (7 cases). Clinical course was severe in 6 cases of P. falciparum malaria and 1 person died because of the disease. Nine cases used chemoprophylaxis during their travel but only one of them appropriately, relevant information was missing in 6 cases.

  15. [Malaria in Poland in 2006].

    Science.gov (United States)

    Rosińska, Magdalena

    2008-01-01

    There were 19 cases of malaria meeting European Union case definition for confirmed case registered in Poland in 2006. All of them were imported, including 1 case of relapse: 17 from Africa, 1 from Asia and 1 from Oceania. Species of Plasmodium was determined for 12 cases (68%): P. falciparum in 12 cases and P. vivax in one. There were 15 cases in males and 4 in females. Age at onset ranged from 17 to 59 years and a considerable number of cases occurred in persons 50 years old or older (5.26%). Common reasons for travel to endemic countries included tourism or family visits (10 cases) and professional or missionary travel (5 cases). Only four cases used chemoprophylaxis and the relevant information was missing in 4 cases. In two cases of malaria caused by Pl. falciparum the clinical course was severe and one of them died.

  16. Development of replication-deficient adenovirus malaria vaccines.

    Science.gov (United States)

    Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

    2017-03-01

    Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

  17. Falciparum malaria associated changes in biochemical indices in children

    Directory of Open Access Journals (Sweden)

    Augusta Chinyere Nsonwu-Anyanwu

    2017-01-01

    Full Text Available Metabolic disturbances associated with fluid and electrolyte imbalance, and changes in the synthetic functions of the liver are common complications of malaria and are dependent on the degree of parasitemia. Packed cell volume (PCV, random blood glucose (RBG, total bilirubin (TB, total proteins (TP, albumin, serum electrolytes [sodium (Na+, potassium (K+, chloride (Cl-, bicarbonate (HCO3-, calcium (Ca2+, magnesium (Mg2+] and anion gap (AG were determined in fifty children with malaria aged between 1-15 years and thirty age matched apparently healthy children without malaria, using colorimetric and flame photometric methods. Data was analyzed using t-test at p < 0.05. The PCV, RBG, Na+, Mg2+, AG and TP were significantly lower and Ca2+ and TB higher in children with malaria compared to children without malaria. The serum Na+, K+, AG, TP and albumin were significantly lower and Ca2+, HCO3- and TB higher in children with severe malaria compared to those with mild malaria. Malaria and high parasite density is associated with perturbations in homeostasis of proteins and electrolytes and these may be implicated in the deleterious consequences associated with malaria in children. [J Med Allied Sci 2017; 7(1.000: 29-33

  18. Severe falciparum malaria associated with massive pulmonary ...

    African Journals Online (AJOL)

    day history of weakness and progressive depressed mental status. Labored breathing and rigors then developed, though no fevers were recorded. She smoked cigarettes and was known to have ischemic heart disease for which she had previously been treated with aspirin, carvedilol and captopril. On examination, her ...

  19. Severe malaria | Maartens | Continuing Medical Education

    African Journals Online (AJOL)

    Infection with Plasmodium falciparum induces changes in red blood cells that cause them to adhere to each other and to the endothelium. These changes in the red cells reduce their deformability. Red cells become sequestered in the microcirculation (Fig. 1) where maturation of the parasite occurs prior to haemolysis and ...

  20. Bacteraemia in cerebral malaria

    NARCIS (Netherlands)

    Enwere, G.; van Hensbroek, M. B.; Adegbola, R.; Palmer, A.; Onyiora, E.; Weber, M.; Greenwood, B.

    1998-01-01

    As part of a treatment trial of cerebral malaria, blood cultures were done in 276 Gambian children, aged between 1 and 9 years, with cerebral malaria. Fourteen (5%) of these were positive. The organisms isolated were Staphylococcus aureus (6), coliforms (4), Pseudomonas spp. (2), Salmonella spp. (1)

  1. Changing the Malaria Environment

    African Journals Online (AJOL)

    tega

    Changing the Malaria Environment. On Friday, 21st ... that malaria exerts a great burden in Africa, but even the World Health Organization (WHO) acknowledges the difficulty of counting ... Although selectivity and resistance also limits the deployment of biological control mechanisms, they represent local technologies.

  2. Malaria at Johannesburg Hospital

    African Journals Online (AJOL)

    AGE GROUPS. There were 43 positive blood smears from 32 male and 11 female patients (median age 30 years; range 3 - 66 years). The incidence of malaria in the different age groups is shown in. Table I. Over the last 10 - 15 years the deterioration in the incidence of malaria in Mrica has been partly due to the increasing ...

  3. Fighting malaria without DDT

    International Development Research Centre (IDRC) Digital Library (Canada)

    Nancy Minogue

    The women are part of a successful Mexican initiative that is fighting malaria on many fronts. Through community involve- ment in control strategies, improved surveillance and treatment, and the use of new household spraying techniques, Mexico has dramatically reduced malaria transmission. In 2001 there were just 4,996 ...

  4. Advances in the management of cerebral malaria in adults

    DEFF Research Database (Denmark)

    Mishra, Saroj K; Wiese, Lothar

    2009-01-01

    PURPOSE OF REVIEW: Cerebral malaria continues to be a substantial cause of death and disability worldwide. Although many studies deal with cerebral malaria in children, only very few pertain to adults. Presence of multiorgan failure makes the prognosis poor. Various mechanisms in the pathogenesis...... of cerebral malaria and the role of adjuvant therapy will be discussed. RECENT FINDINGS: Artemisinin-based therapies have improved antiparasitic treatment, but in-hospital mortality still remains high, as do neurological sequelae. Several recent studies have given new insights in the pathophysiology...... of cerebral malaria particularly the role of immune mechanisms in disease progression. Recent findings have identified several potential candidates for adjuvant neuroprotective treatment. Recombinant human erythropoietin has shown beneficial effect in experimental cerebral malaria and will soon enter...

  5. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S D; Hviid, L

    1993-01-01

    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....

  6. Quality of life of survivors from severe sepsis and septic shock may be similar to that of others who survive critical illness

    Science.gov (United States)

    Granja, Cristina; Dias, Cláudia; Costa-Pereira, Altamiro; Sarmento, António

    2004-01-01

    Introduction The objective of the present study was to compare the health-related quality of life (HR-QoL) of survivors from severe sepsis and septic shock with HR-QoL in others who survived critical illness not involving sepsis. Methods From March 1997 to March 2001, adult patients in an eight-bed medical/surgical intensive care unit (ICU) of a tertiary care hospital admitted with severe sepsis or septic shock (sepsis group; n = 305) were enrolled and compared with patients admitted without sepsis (control group; n = 392). Patients younger than 18 years (n = 48) and those whose ICU stay was 1 day or less (n = 453) were excluded. In addition, patients exhibiting nonsevere sepsis on admission were excluded (n = 87). Finally, patients who developed nonsevere sepsis or severe sepsis/septic shock after admission were also excluded (n = 88). Results In-hospital mortality rates were 34% in the sepsis group and 26% in the control group. There were no differences in sex, age, main activity (work status), and previous health state between groups. Survivors in the sepsis group had a significantly higher Acute Physiology and Chronic Health Evaluation II score on admission (17 versus 12) and stayed significantly longer in the ICU. A follow-up appointment was held 6 months after ICU discharge, and an EQ-5D (EuroQol five-dimension) questionnaire was administered. A total of 104 sepsis survivors and 133 survivors in the control group answered the EQ-5D questionnaire. Sepsis survivors reported significantly fewer problems only in the anxiety/depression dimension. Although there were no significant differences in the other dimensions of the EQ-5D, there was a trend towards fewer problems being reported by sepsis survivors. Conclusion Evaluation using the EQ-5D at 6 months after ICU discharge indicated that survivors from severe sepsis and septic shock have a similar HR-QoL to that of survivors from critical illness admitted without sepsis. PMID:15025783

  7. Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease.

    Directory of Open Access Journals (Sweden)

    Louise Kuhn

    2009-06-01

    Full Text Available We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention or to continued breastfeeding (control. Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98. Children of women with less severe disease during pregnancy (not eligible for ART had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06-6.36 compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it who weaned early had better outcomes (p-value interaction = 0.002. In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65-9.39 increase in HIV infection or death among infants of mothers with less severe disease.Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding

  8. Serum autotaxin is a parameter for the severity of liver cirrhosis and overall survival in patients with liver cirrhosis--a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Thomas Pleli

    Full Text Available Autotaxin (ATX and its product lysophosphatidic acid (LPA are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.Patients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry.270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001. Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease score and LPA levels (r = 0.493, P = 0.027. Patients with hepatic encephalopathy (P = 0.006, esophageal varices (P = 0.002 and portal hypertensive gastropathy (P = 0.008 had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365-0.905, P = 0.017.Serum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.

  9. Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

    Directory of Open Access Journals (Sweden)

    Adam Mayyada B

    2012-08-01

    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.

  10. MALARIA DI PURWOREJO

    Directory of Open Access Journals (Sweden)

    Harijani A. Marwoto

    2012-10-01

    Full Text Available Dalam 5 tahun terakhir banyak l