http://hdl.handle.net/10144/11651 Search the Channel search http://fieldresearch.msf.org/msf/simple-search http://hdl.handle.net/10144/142210 Title: Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda.<br/><br/>Authors: De Beaudrap, Pierre; Nabasumba, Carolyn; Grandesso, Francesco; Turyakira, Eleanor; Schramm, Birgit; Boum, Yap; Etard, Jean-François<br/><br/>Abstract: Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection. http://hdl.handle.net/10144/141434 Title: Transmission of Plasmodium vivax in South-Western Uganda: Report of Three Cases in Pregnant Women<br/><br/>Authors: Dhorda, Mehul; Nyehangane, Dan; Rénia, Laurent; Piola, Patrice; Guerin, Philippe J; Snounou, Georges<br/><br/>Abstract: Plasmodium vivax is considered to be rare in the predominantly Duffy negative populations of Sub-Saharan Africa, as this red blood cell surface antigen is essential for invasion by the parasite. However, despite only very few reports of molecularly confirmed P. vivax from tropical Africa, serological evidence indicated that 13% of the persons sampled in Congo had been exposed to P. vivax. We identified P. vivax by microscopy in 8 smears from Ugandan pregnant women who had been enrolled in a longitudinal study of malaria in pregnancy. A nested polymerase chain reaction (PCR) protocol was used to detect and identify the Plasmodium parasites present. PCR analysis confirmed the presence of P. vivax for three of the women and analysis of all available samples from these women revealed clinically silent chronic low-grade vivax infections for two of them. The parasites in one woman carried pyrimethamine resistance-associated double non-synonymous mutations in the P. vivax dihydrofolate reductase gene. The three women found infected with P. vivax were Duffy positive as were nine of 68 women randomly selected from the cohort. The data presented from these three case reports is consistent with stable transmission of malaria in a predominantly Duffy negative African population. Given the substantial morbidity associated with vivax infection in non-African endemic areas, it will be important to investigate whether the distribution and prevalence of P. vivax have been underestimated in Sub-Saharan Africa. This is particularly important in the context of the drive to eliminate malaria and its morbidity. http://hdl.handle.net/10144/132506 Title: Low referral completion of rapid diagnostic test-negative patients in community-based treatment of malaria in Sierra Leone.<br/><br/>Authors: Thomson, Anna; Khogali, Mohammed; de Smet, Martin; Reid, Tony; Mukhtar, Ahmed; Peterson, Stefan; von Schreeb, Johan<br/><br/>Abstract: ABSTRACT: http://hdl.handle.net/10144/129969 Title: Free treatment, rapid diagnostic tests and malaria village workers can hasten the progress towards achieving the malaria related Millennium Development Goals: The MSF experience from Chad, Sierra-Leone and Mali.<br/><br/>Authors: Tayler-Smith K; Kociejowski A; de Lamotte N; Gerard S; Ponsar F; Philips M; Zachariah R http://hdl.handle.net/10144/120099 Title: Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial<br/><br/>Authors: Dondorp, Arjen M; Fanello, Caterina I; Hendriksen, Ilse C E; Gomes, Ermelinda; Seni, Amir; Chhaganlal, Kajal D; Bojang, Kalifa; Olaosebikan, Rasaq; Anunobi, Nkechinyere; Maitland, Kathryn; Kivaya, Esther; Agbenyega, Tsiri; Nguah, Samuel Blay; Evans, Jennifer; Gesase, Samwel; Kahabuka, Catherine; Mtove, George; Nadjm, Behzad; Deen, Jacqueline; Mwanga-Amumpaire, Juliet; Nansumba, Margaret; Karema, Corine; Umulisa, Noella; Uwimana, Aline; Mokuolu, Olugbenga A; Adedoyin, Olanrewaju T; Johnson, Wahab B R; Tshefu, Antoinette K; Onyamboko, Marie A; Sakulthaew, Tharisara; Ngum, Wirichada Pan; Silamut, Kamolrat; Stepniewska, Kasia; Woodrow, Charles J; Bethell, Delia; Wills, Bridget; Oneko, Martina; Peto, Tim E; von Seidlein, Lorenz; Day, Nicholas P J; White, Nicholas J; AQUAMAT group<br/><br/>Abstract: Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria. http://hdl.handle.net/10144/116337 Title: Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial<br/><br/>Authors: Piola, Patrice; Nabasumba, Carolyn; Turyakira, Eleanor; Dhorda, Mehul; Lindegardh, Niklas; Nyehangane, Dan; Snounou, Georges; Ashley, Elizabeth A; McGready, Rose; Nosten, Francois; Guerin, Philippe J<br/><br/>Abstract: BACKGROUND: Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on efficacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. METHODS: We did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confirmed by PCR. The non-inferiority margin was a difference in cure rate of 5%. Analysis of efficacy was for all randomised patients without study deviations that could have affected the efficacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508. FINDINGS: 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to follow-up and 25 were excluded from the analysis. At day 42, 137 (99·3%) of 138 patients taking artemether-lumefantrine and 122 (97·6%) of 125 taking quinine were cured-difference 1·7% (lower limit of 95% CI -0·9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group. INTERPRETATION: Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy. FUNDING: Médecins Sans Frontières and the European Commission. http://hdl.handle.net/10144/116353 Title: Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial<br/><br/>Authors: Smithuis, Frank; Kyaw, Moe Kyaw; Phe, Ohn; Win, Thein; Aung, Pyay Phyo; Oo, Aung Pyay Phyo; Naing, Arkar Linn; Nyo, Mya Yee; Myint, Naing Zaw Htun; Imwong, Mallika; Ashley, Elizabeth; Lee, Sue J; White, Nicholas J<br/><br/>Abstract: BACKGROUND: Artemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the addition of a single gametocytocidal dose of primaquine. METHODS: In an open-label randomised trial in clinics in Rakhine state, Kachin state, and Shan state in Myanmar (Burma) between Dec 30, 2008, and March 20, 2009, we compared the effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate-mefloquine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, artemether-lumefantrine) and loose artesunate-mefloquine in Burmese adults and children. Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection, who were older than 6 months, and who weighed more than 5 kg. Treatments were randomised in equal numbers within blocks of 50 and allocation was in sealed envelopes. All patients were also randomly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not. Patients were followed up for 63 days. Treatment groups were compared by analysis of variance and multiple logistic regression. The primary outcome was the 63 day recrudescence rate. This study is registered with clinicaltrials.gov, number NCT00902811. FINDINGS: 155 patients received artesunate-amodiaquine, 162 artemether-lumefantrine, 169 artesunate-mefloquine, 161 loose artesunate-mefloquine, and 161 dihydroartemisinin-piperaquine. By day 63 of follow-up, 14 patients (9·4%; 95% CI 5·7-15·3%) on artesunate-amodiaquine had recrudescent P falciparum infections, a rate significantly higher than for artemether-lumefantrine (two patients; 1·4%; 0·3-5·3; p=0·0013), fixed-dose artesunate-mefloquine (0 patients; 0-2·3; p<0·0001), loose artesunate-mefloquine (two patients; 1·3%; 0·3-5·3; p=0·0018), and dihydroartemisinin-piperaquine (two patients 1·3%; 0·3-5·2%; p=0·0012). Hazard ratios for re-infection (95% CI) after artesunate-amodiaquine were 3·2 (1·3-8·0) compared with the two artesunate-mefloquine groups (p=0·01), 2·6 (1·0-6-0) compared with artemether-lumefantrine (p=0·04), and 2·3 (0·9-6·0) compared with dihydroartemisinin-piperaquine (p=0·08). Mixed falciparum and vivax infections were common: 129 (16%) had a mixed infection at presentation and 330 (41%) patients had one or more episodes of Plasmodium vivax infection during follow-up. The addition of a single dose of primaquine (0·75 mg/kg) reduced P falciparum gametocyte carriage substantially: rate ratio 11·9 (95% CI 7·4-20·5). All regimens were well tolerated. Adverse events were reported by 599 patients, most commonly vomiting and dizziness. Other side-effects were less common and were not related to a specific treatment. INTERPRETATION: Artesunate-amodiaquine should not be used in Myanmar, because the other ACTs are substantially more effective. Artesunate-mefloquine provided the greatest post-treatment suppression of malaria. Adding a single dose of primaquine would substantially reduce transmission potential. Vivax malaria, not recurrent falciparum malaria, is the main complication after treatment of P falciparum infections in this region. FUNDING: Médecins sans Frontières (Holland) and the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme. http://hdl.handle.net/10144/95555 Title: Long-lasting insecticide-treated net usage in eastern Sierra Leone - the success of free distribution.<br/><br/>Authors: Gerstl, Sibylle; Dunkley, Sophie; Mukhtar, Ahmed; Maes, Peter; De Smet, Martin; Baker, Samuel; Maikere, Jacob<br/><br/>Abstract: Summary Objective Médecins Sans Frontières (MSF) runs a malaria control project in Bo and Pujehun districts (population 158 000) that includes the mass distribution, routine delivery and demonstration of correct use of free, long-lasting insecticide-treated nets (LLINs). In 2006/2007, around 65 000 LLINs were distributed. The aim of this follow-up study was to measure LLIN usage and ownership in the project area. Methods Heads of 900 randomly selected households in 30 clusters were interviewed, using a standardized questionnaire, about household use of LLINs. The condition of any LLIN was physically assessed. Results Of the 900 households reported, 83.4% owning at least one LLIN. Of the 16.6% without an LLIN, 91.9% had not participated in the MSF mass distribution. In 94.1% of the households reporting LLINs, the nets were observed hanging correctly over the beds. Of the 1135 hanging LLINs, 75.2% had no holes or 10 or fewer finger-size holes. The most common source of LLINs was MSF (75.2%). Of the 4997 household members, 67.2% reported sleeping under an LLIN the night before the study, including 76.8% of children under 5 years and 73.0% of pregnant women. Conclusion Our results show that MSF achieved good usage with freely distributed LLINs. It is one of the few areas where results almost achieve the new targets set in 2005 by Roll Back Malaria to have at least 80% of pregnant women and children under 5 years using LLINs by 2010. http://hdl.handle.net/10144/98691 Title: Successful introduction of artesunate combination therapy is not enough to fight malaria: results from an adherence study in Sierra Leone.<br/><br/>Authors: Gerstl, Sibylle; Dunkley, Sophie; Mukhtar, Ahmed; Baker, Samuel; Maikere, Jacob<br/><br/>Abstract: A study to measure adherence to artesunate and amodiaquine (AS+AQ) therapy in patients treated for uncomplicated malaria in community health centres (CHC) was conducted in Sierra Leone. Patients/caretakers were interviewed and remaining AS+AQ tablets at home after the last treatment dose were counted. Persons leaving CHCs with an AS+AQ prescription were also interviewed (exit interviews). In total, 118 patients were visited at home: 27 (22.9%) had one or more tablets left and were classed as certainly non-adherent; 34 (28.8%) were probably non-adherent [reported incorrect (n=27) or incomplete (n=7) intake]; and 57 (48.3%) were probably adherent. The main reasons for incomplete intake were sickness after one dose of AS+AQ, no food available for drug intake and forgetting to take them. For incorrect intake, reasons were vomiting after drug intake and incorrect instructions given by the CHC. Eighty-one percent of probably adherent patients reported following instructions given to them. In exit interviews, 82% of patients or caretakers of patients were able to repeat AS+AQ intake instructions correctly. Adherence to antimalarial treatment should not be taken for granted. Instructions on correct AS+AQ use should include discussion of disease symptoms as well as possible treatment side effects and how to manage them. Other factors are more difficult to influence, such as patients forgetting to take the treatment. http://hdl.handle.net/10144/91160 Title: Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone.<br/><br/>Authors: Gerstl, Sibylle; Dunkley, Sophie; Mukhtar, Ahmed; De Smet, Martin; Baker, Samuel; Maikere, Jacob<br/><br/>Abstract: ABSTRACT: BACKGROUND: Most malaria rapid diagnostic tests (RDTs) use HRP2 detection, including Paracheck-Pf(R), but their utility is limited by persistent false positivity after treatment. PLDH-based tests become negative more quickly, but sensitivity has been reported below the recommended standard of 90%. A new pLDH test, CareStartTM three-line P.f/PAN-pLDH, claims better sensitivity with continued rapid conversion to negative. The study aims were to 1) compare sensitivity and specificity of CareStartTM to Paracheck-Pf(R) to diagnose falciparum malaria in children under five years of age, 2) assess how quickly false-positive CareStartTM tests become negative and 3) evaluate ease of use and inter-reader agreement of both tests. METHODS: Participants were included if they were aged between two and 59 months, presenting to a Medecins Sans Frontieres community health centre in eastern Sierra Leone with suspected malaria defined as fever (axillary temperature > 37.5degreesC) and/or history of fever in the previous 72 hours and no signs of severe disease. The same capillary blood was used for the RDTs and the blood slide, the latter used as the gold standard reference. All positive participants were treated with supervised artesunate and amodiaquine treatment for three days. Participants with a persistent false-positive CareStartTM, but a negative blood slide on Day 2, were followed with repeated CareStartTM and blood slide tests every seven days until CareStartTM became negative or a maximum of 28 days. RESULTS: Sensitivity of CareStartTM was 99.4% (CI 96.8-100.0, 168/169) and of Paracheck-Pf(R), 98.8% (95% CI 95.8-99.8, 167/169). Specificity of CareStartTM was 96.0% (CI 91.9-98.4, 167/174) and of Paracheck-Pf(R), 74.7% (CI 67.6-81.0, 130/174) (p<0.001). Neither test showed any change in sensitivity with decreasing parasitaemia. Of the 155 eligible follow-up CareStartTM participants, 63.9% (99/155) had a false-positive test on day 2, 21.3% (33/155) on day 7, 5.8% (9/155) on day 14, 1.9% (3/155) on day 21 and 0.6% (1/155) on day 28. The median time for test negativity was seven days. CareStartTM was as easy to use and interpret as Paracheck-Pf(R) with excellent inter-reader agreement. CONCLUSIONS: Both RDTs were highly sensitive, met WHO standards for the detection of falciparum malaria monoinfections where parasitaemia was >100 parasites/mul and were easy to use. CareStartTM persistent false positivity decreased quickly after successful anti-malarial treatment, making it a good choice for a RDT for a hyperendemic falciparum malaria area.