Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non-inferiority trial.

BACKGROUND: Artemisinin-based combination regimens are widely advocated for malarial treatment, but other effective regimens might be cheaper and more readily available. Our aim was to compare the risk of recurrent parasitaemia in patients given artemether-lumefantrine with that in those given amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated malaria. METHODS: We enrolled 521 patients aged 6 months or older with uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina Faso. Patients were randomly assigned to receive standard doses of either artemether-lumefantrine (261) or amodiaquine plus sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. The study is registered at controlled-trials.gov with the identifier ISRCTN54261005. FINDINGS: Of enrolled patients, 478 (92%) completed the 28-day study. The risk of recurrent symptomatic malaria was lowest in the group given amodiaquine plus sulfadoxine-pyrimethamine (1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were due to new infections. Recrudescences were four late treatment failures with artemether-lumefantrine and one early treatment failure with amodiaquine plus sulfadoxine-pyrimethamine. Both regimens were safe and well tolerated, with pruritus more common with amodiaquine plus sulfadoxine-pyrimethamine than with artemether-lumefantrine. Each regimen selected for new isolates with mutations that have been associated with decreased drug susceptibility. INTERPRETATION: Amodiaquine plus sulfadoxine-pyrimethamine was more effective than was artemether-lumefantrine for the treatment of uncomplicated malaria. For regions of Africa where amodiaquine plus sulfadoxine-pyrimethamine continues to be effective, this less expensive and more available regimen should be considered as an alternative to blanket recommendations for artemisinin-based combination treatment for malaria

Prevalence of the dhfr and dhps Mutations among Pregnant Women in Rural Burkina Faso Five Years after the Introduction of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine.

BACKGROUND: The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine-pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso. METHODS: From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene. RESULTS: The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NRNI and the triple mutations IRNI was 35.7% (91/255) and 11.4% (29/255), respectively. CONCLUSION: Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso

An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso.

BACKGROUND: A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. METHODS: Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. RESULTS: Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. CONCLUSION: Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy

Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso.

BACKGROUND: Ex vivo assays are usually carried out on parasite isolates collected from patients with uncomplicated Plasmodium falciparum malaria, from which pregnant women are usually excluded as they are often asymptomatic and with relatively low parasite densities. Nevertheless, P. falciparum parasites infecting pregnant women selectively sequester in the placenta and may have a different drug sensitivity profile compared to those infecting other patients. The drug sensitivity profile of P. falciparum isolates from infected pregnant women recruited in a treatment efficacy trial conducted in Burkina Faso was determined in an ex vivo study. METHODS: The study was conducted between October 2010 and December 2012. Plasmodium falciparum isolates were collected before treatment and at the time of any recurrent infection whose parasite density was at least 100/µl. A histidine-rich protein-2 assay was used to assess their susceptibility to a panel of seven anti-malarial drugs. The concentration of anti-malarial drug inhibiting 50% of the parasite maturation to schizonts (IC(50)) for each drug was determined with the IC Estimator version 1.2. RESULTS: The prevalence of resistant isolates was 23.5% for chloroquine, 9.2% for mefloquine, 8.0% for monodesethylamodiaquine, and 4.4% for quinine. Dihydroartemisinin, mefloquine, lumefantrine, and monodesethylamodiaquine had the lowest mean IC(50) ranging between 1.1 and 1.5 nM respectively. The geometric mean IC(50) of the tested drugs did not differ between chloroquine-sensitive and resistant parasites, with the exception of quinine, for which the IC(50) was higher for chloroquine-resistant isolates. The pairwise comparison between the IC(50) of the tested drugs showed a positive and significant correlation between dihydroartemisinin and both mefloquine and chloroquine, between chloroquine and lumefantrine and between monodesethylamodiaquine and mefloquine. CONCLUSION: These ex vivo results suggest that treatment with the currently available artemisinin-based combinations is efficacious for the treatment of malaria in pregnancy in Burkina Faso. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00852423

How equitable is bed net ownership and utilisation in Tanzania? A practical application of the principles of horizontal and vertical equity

BACKGROUND: Studies show that the burden of malaria remains huge particularly in low-income settings. Although effective malaria control measures such as insecticide-treated nets (ITNs) have been promoted, relatively little is known about their equity dimension. Understanding variations in their use in low-income settings is important for scaling up malaria control programmes particularly ITNs. The objective of this paper is to measure the extent and causes of inequalities in the ownership and utilisation of bed nets across socioeconomic groups (SEGs) and age groups in Tanga District, north-eastern Tanzania. METHODS: A questionnaire was administered to heads of 1,603 households from rural and urban areas. Households were categorized into SEGs using both an asset-based wealth index and education level of the household head. Concentration indices and regression-based measures of inequality were computed to analyse both vertical and horizontal inequalities in ownership and utilisation of bed nets. Focus Group Discussions (FGDs) were used to explore community perspectives on the causes of inequalities. RESULTS: Use of ITNs remained appallingly low compared to the RBM target of 80% coverage. Inequalities in ownership of ITNs and all nets combined were significantly pro-rich and were much more pronounced in rural areas. FGDs revealed that lack of money was the key factor for not using ITNs followed by negative perceptions about the effect of insecticides on the health of users. Household SES, living within the urban areas and being under-five were positively associated with bed net ownership and/or utilisation. CONCLUSION: The results highlight the need for mass distribution of ITN; a community-wide programme to treat all untreated nets and to promote the use of Long-Lasting Insecticidal nets (LLINs) or longer-lasting treatment of nets. The rural population and under-fives should be targeted through highly subsidized schemes and mass distribution of free nets. Public campaigns are also needed to encourage people to use treated nets and mitigate negative perceptions about insecticides

Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy.

International audienceCryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine during pregnancy in Burkina Faso: effect of adding a third dose to the standard two-dose regimen on low birth weight, anaemia and pregnancy outcomes

Abstract Background Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) is being implemented in most malaria endemic countries as a standard two-doses regimen as it reduces the risk of low birth weight (LBW) and the prevalence of maternal anaemia. Nevertheless, where the risk of infection close to delivery is high because of intense transmission, a third IPTp-SP dose may further reduce the negative effects of malaria on pregnancy outcome. Methods Pregnant women in the 2nd or 3rd trimester were randomized to receive either 2 (SP2) or 3 doses (SP3) of SP. Trained field workers paid home visits to the women for drug administration according to a predefined drug delivery schedule. Women were encouraged to attend their scheduled ANC visits and to deliver at the health facilities where the new-born was weighed. The prevalence of LBW ( Results Data from 1274 singleton pregnancies were analysed (641 in the SP3 and 633 in the SP2 group). The uptake of the intervention appeared to be low. Though the prevalence of LBW in both intervention groups was similar (adjusted Incident Rate Ratio, AIRR = 0.92, 95%CI: 0.69-1.24) in the ITT analysis, the risk of severe anaemia was significantly lower in the SP3 group compared to the SP2 group (AIRR = 0.38, 95%CI: 0.16 - 0.90). The PP analysis showed a trend of reduced risk of LBW, severe anaemia and premature delivery in the SP3 group, albeit the difference between two and three IPTp-SP did not reach statistical significance. Conclusion The risk of LBW and severe anaemia tended to be lower in the SP3 group, though this was not statistically significant, probably due to the low uptake of the intervention which reduced the power of the study. Further studies are needed for establishing whether a third SP dose has a real benefit in preventing the negative effects of malaria in pregnancy in settings where transmission is markedly seasonal.</p

Clinical signs and symptoms cannot reliably predict **Plasmodium falciparum** malaria infection in pregnant women living in an area of high seasonal transmission

BACKGROUND: Malaria in pregnancy is a major public health problem in endemic countries. Though the signs and symptoms of malaria among pregnant women have been already described, clinical presentation may vary according to intensity of transmission and local perceptions. Therefore, determining common signs and symptoms among pregnant women with a malaria infection may be extremely useful to identify those in need of further investigation by rapid diagnostic test or microscopy. METHODS: Six hundred pregnant women attending the maternity clinic of Nanoro District Hospital, Burkina Faso were recruited, 200 with suspected clinical malaria and 400 as controls. Cases were matched with controls by gestational age and parity. Signs and symptoms were collected and a blood sample taken for rapid diagnostic test, microscopy and haemoglobin measurement. A multivariate model was used to assess the predictive value of signs and symptoms for malaria infection. RESULTS: The overall prevalence of malaria was 42.6% (256/600) while anaemia was found in 60.8% (365/600) of the women. Nearly half (49%) of the cases and 39.5% of the controls had a malaria infection (p = 0.03). The most common signs and symptoms among the cases were fever (36%,72/200), history of fever (29%,58/200) and headache (52%,104/200). The positive predictive value for fever was 53% (95% CI:41–64), history of fever 58% (95% CI:37–63) and headache 51% (95% CI:41–61). CONCLUSION: Signs and symptoms suggestive of malaria are frequent among pregnant women living in areas of intense transmission. Common malaria symptoms are not strong predictors of infection. For a better management of malaria in pregnancy, active screening to detect and treat malaria infection early should be performed on all pregnant women attending a health facility