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Background Malaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region. Methods Two cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis. Results A total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine–pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14–0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39–0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31–4.91, p = 0.006). Conclusions The prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.

Background In the current context of tailoring interventions to maximize impact, it is important that current data of clinical epidemiology guide public health programmes and health workers in the management of severe disease. This study aimed at describing the burden of severe malaria at hospital level in two areas with distinct malaria transmission intensity. Methods A hospital-based surveillance was established in two regional hospitals located in two areas exposed to different malaria transmission. Data on paediatric severe malaria admissions were recorded using standardized methods from August 2017 to August 2018 with an interruption during the dry season from April to June 2018. Results In total, 921 children with severe malaria cases were enrolled in the study. The mean age was 33.9 (± 1.3) and 36.8 (± 1.6) months in lower malaria transmission (LMT) and higher malaria transmission (HMT) areas (p = 0.15), respectively. The geometric mean of asexual P. falciparum density was significantly higher in the LMT area compared to the HMT area: 22,861 trophozoites/µL (95% CI 17,009.2–30,726.8) vs 11,291.9 trophozoites/µL (95% CI 8577.9–14,864.5). Among enrolled cases, coma was present in 70 (9.2%) participants. 196 patients (21.8%) presented with two or more convulsions episodes prior to admission. Severe anaemia was present in 448 children (49.2%). Other clinical features recorded included 184 (19.9%) cases of lethargy, 99 (10.7%) children with incoercible vomiting, 80 (8.9%) patients with haemoglobinuria, 43 (4.8%) children with severe hypoglycaemia, 37 (4.0%) cases where child was unable to drink/suck, 11 (1.2%) cases of patients with circulatory collapse/shock, and 8 cases (0.9%) of abnormal bleeding (epistaxis). The adjusted odds of presenting with coma, respiratory distress, haemoglobinuria, circulatory collapse/shock and hypoglycaemia were significantly higher (respectively 6.5 (95%CI 3.4–12.1); 1.8 (95%CI 1.0–3.2); 2.7 (95%CI 1.6–4.3); 5.9 (95%CI 1.3–27.9); 1.9 (95%CI 1.0–3.6)) in children living in the HMT area compared to those residing in the LMT area. Overall, forty-four children died during hospitalization (case fatality rate 5.0%) with the highest fatalities in children admitted with respiratory distress (26.0%) and those with hypoglycaemia (25.0%). Conclusion The study showed that children in the HMT area have a higher risk of presenting with coma, shock/dehydration, haemoglobinuria, hypoglycaemia, and respiratory distress. Case-fatality rate is higher among patients with respiratory distress or hypoglycaemia. Hospital surveillance provides a reliable and sustainable means to monitor the clinical presentation of severe malaria and tailor the training needs and resources allocation for case management.

While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the gametocyte sex ratio contribution to this process still remains a relevant research question. The present review discusses the biology of sex determination in P. falciparum, the underlying host and parasite factors, the sex specific susceptibility to drugs, the effect of sex ratio dynamics on malaria parasite transmission and the development of gametocyte sex specific diagnosis tools. Despite the inherent differences across several studies and approaches, the emerging picture highlights a potentially relevant contribution of the P. falciparum gametocyte sex ratio in the modulation of malaria parasite transmission. The increasing availability of molecular methods to measure gametocyte sex ratio will enable evaluation of important parameters, such as the impact of drug treatment on gametocyte sex ratio in vitro and in vivo as well as the changes of gametocyte sex ratios in natural infections, key steps towards elucidating how these parameters affect parasite infectiousness to the mosquito vectors.

Here we address the issue of the possible interplay between host genetic variation and the risk of acquiring Plasmodium falciparum drug-resistant strains. The involvement of human genetic variation as a possible co-factor in the selection and spread of P. falciparum drug resistance is a new tool in the study of malaria and possibly of other infectious diseases. The driving hypothesis of this approach is that parasite drug resistance could be affected both by ethnicity and human variability in the genes encoding for enzymes that metabolise antimalarials (cytochrome P450 liver enzymes). Understanding if parasite drug sensitivity is influenced and possibly modulated by human diversity can contribute to a better knowledge and control of the spread of drug resistance. So far, few studies have addressed this strategic issue. To explore this hypothesis we carried out an association analysis on 506 human/P. falciparum DNA samples from adult asymptomatic subjects belonging to three sympatric ethnic groups of Burkina Faso, an area of hyperendemic malaria in West Africa. Here we report that the prevalence of chloroquine-resistant infections (pfcrt 76T and/or pfmdr1 86Y) differs among sympatric ethnic groups, being higher in Mossi and Rimaibe compared to Fulani (OR: 2.24; 1.27-3.92; P = 0.007). Moreover, the human CYP2C8*2 variant, known to determine a poor drug metaboliser phenotype, is associated with P. falciparum chloroquine-resistant infections (OR: 1.66; 1.13-2.43; P = 0.008). The results strongly suggest that human genetic variation affects the dynamics of selection of parasite drug-resistance. We strongly believe that these observations are of general interest and may have important implications in public health.

Background Rapid diagnostic tests (RDTs) are immune chromatographic tests targeting antigens of one or more Plasmodium species and offer the potential to extend accurate malaria diagnosis in endemic areas. In this study, the performance of Plasmodium falciparum-specific histidine-rich protein-2 (PfHRP-2) RDT in the detection of asymptomatic carriers from a hyperendemic region of Burkina Faso was compared with microscopy to gain further insight on its relevance in community-based interventions. Methods The performance of HRP-2 test was evaluated in terms of sensitivity, specificity, positive and negative predictive values, discordant values, likelihood ratios, accuracy, and precision using microscopy as the 'gold standard’. This analysis was carried out in a controlled, parallel, cluster-randomized (18 clusters; 1:1) study in children and adults. The effect of systematic treatment of P. falciparum asymptomatic carriers during three consecutive monthly community screening campaigns on the incidence of symptomatic malaria episodes over a 12-month period was compared with no treatment of asymptomatic carriers. Results Sensitivity of HRP-2 test in asymptomatic carriers was higher in campaign 1 (92.4%) when compared to campaign 2 (84.0%) and campaign 3 (77.8%). The sensitivity of HRP-2 test increased as parasite density increased across all the age groups. Highest sensitivity (≥97.0%) was recorded at parasite densities of 1,000-4,999/μl, except for children aged 10 to 14 years. The specificity of HRP-2 test was comparable across age groups and highest in campaign 3 (95.9%). The negative predictive values were high across the three campaigns (≥92.7%) while the positive predictive values ranged from 23.2 to 73.8%. False-positive and false-negative rates were high in campaign 1 and campaign 3, respectively. Conclusion The performance of HRP-2 test in detecting asymptomatic carriers of P. falciparum varied by age and parasite density. Although the use of HRP-2 test is beneficial for the diagnosis of acute malaria, its low sensitivity in screening asymptomatic carriers may limit its utility in pre-elimination interventional settings. The use of a practical and more sensitive test such as loop-mediated isothermal amplification in combination with a cost effective HRP-2 test may be worth exploring in such settings.

Background Artesunate (AS) plus amodiaquine (AQ) is one artemisinin-based combination (ACT) recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested. Methods A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design) and safety of fixed (F) dose AS (25 mg)/AQ (67.5 mg) to loose (L) AS (50 mg) + AQ (153 mg) in 750, P. falciparum-infected children from Burkina Faso aged 6 months to 5 years. Dosing was by age. Primary efficacy endpoint was Day (D) 28, PCR-corrected, parasitological cure rate. Recipients of rescue treatment were counted as failures and new infections as cured. Documented, common toxicity criteria (CTC) graded adverse events (AEs) defined safety. Results Recruited and evaluable children numbered 750 (375/arm) and 682 (90.9%), respectively. There were 8 (AS/AQ) and 6 (AS+AQ) early treatment failures and one D7 failure (AS+AQ). Sixteen (AS/AQ) and 12 (AS+AQ) patients had recurrent parasitaemia (PCR new infections 10 and 6, respectively). Fourteen patients per arm required rescue treatment for vomiting/spitting out study drugs. Efficacy rates were 92.1% in both arms: AS/AQ = 315/342 (95% CI: 88.7–94.7) vs. AS+AQ = 313/340 (95% CI: 88.6–94.7). Non-inferiority was demonstrated at two-sided α = 0.05: Δ (AS+AQ – AS/AQ) = 0.0% (95% CI: -4.1% to 4.0%). D28, Kaplan Meier PCR-corrected cure rates (all randomized children) were similar: 93.7% (AS/AQ) vs. 93.2% (AS+AQ) Δ = -0.5 (95% CI -4.2 to 3.0%). By D2, both arms had rapid parasite (F & L, 97.8% aparasitaemic) and fever (97.2% [F], 96.0% [L] afebrile) clearances. Both treatments were well tolerated. Drug-induced vomiting numbered 8/375 (2.1%) and 6/375 (1.6%) in the fixed and loose arms, respectively (p = 0.59). One patient developed asymptomatic, CTC grade 4 hepatitis (AST 1052, ALT 936). Technical difficulties precluded the assessment and risk of neutropaenia for all patients. Conclusion Fixed dose AS/AQ was efficacious and well tolerated. These data support the use of this new fixed dose combination for treating P. falciparum malaria with continued safety monitoring. Trial registration Current Controlled Trials ISRCTN07576538

Background Malaria can be caused by five Plasmodium species. Due to their higher prevalence, much of the research concentrates on Plasmodium falciparum and Plasmodium vivax. In Burkina Faso, where P. falciparum co-exists with Plasmodium malariae and Plasmodium ovale, there is not much data about the prevalence of the latter two species across human population. Moreover, interactions between co-infecting Plasmodium species are not documented. The aim of the current research is to determine species-specific prevalence and temporal distribution. The potential interactions between co-infecting Plasmodium species amongst the child-aged population in Burkina Faso are also discussed. Methods The study took place in the Sudanese savannah zone in Burkina Faso in a rural village, Laye. Surveys were conducted during the wet season across four years, 2007 to 2010. Volunteers aged three to 15 years with parental signed consent were enrolled. Ten children per week were screened for any history of pain, fever. Parasitological data were obtained by blood slide processing. Results Three sympatric Plasmodium species were recorded during this study with an average prevalence of 70.7%. Species temporal distribution showed an increase of P. malariae parasite prevalence from 0.9% in 2007 to 13.2% in 2010. Within a season, P. falciparum occurred in the overall study period while P. malariae and P. ovale were highly prevalent after the rainy part of this period. Species-specific infection analysis showed that in a comparison of mono-infections, P. malariae gametocyte prevalence and median density were higher than those of P. falciparum (88.9% vs 34.5% and 124.0 vs 40.0 gametocytes/μl, respectively). Likewise, in P. falciparum co-infections with P. malariae or P. ovale, gametocyte prevalence was also higher than in P. falciparum mono-infection. However, in P. falciparum mixed infection with P. malariae, P. falciparum gametocyte prevalence and median density as well as asexual form density decreased compared to P. falciparum mono-infection while for P. malariae mono-infection, only asexual form density significantly vary. Conclusion These data revealed high gametocyte prevalence in other Plasmodium species than P. falciparum with a significant variation of P. malariae gametocyte carriers and gametocyte density across years. Molecular tools and entomological studies are needed to highly assess species-specific contribution to malaria transmission.

Background In malaria-endemic countries, large proportions of infected individuals are asymptomatic, constituting a reservoir of parasites for infection of newly hatched mosquitoes. This study evaluated the impact of screening and treatment of asymptomatic carriers of Plasmodium falciparum. Methods Eighteen villages were randomized (1:1) to study arms and inhabitants participated in four community screening campaigns: three before the rainy season ~1 month apart, and the fourth after the rains at ~12 months. On day 1 of campaigns 1–3, asymptomatic carriers in the intervention arm were identified by rapid diagnostic test and treated with artemether-lumefantrine. Outcomes were symptomatic malaria with parasite density >5,000/μL per person-year in children 5,000/μL per person-year in children

Background Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.

Background The weekly chemoprophylaxis of malaria during pregnancy with chloroquine (CQ) has become problematic with the increasing resistance of Plasmodium falciparum to this drug. There was a need to test the benefits of new strategies over the classical chemoprophylaxis. This study was conducted to provide data to the National Malarial Control Programme for an evidence-based policy change decision making process. It compares the efficacy of two IPT regimens, using chloroquine (CQ) or sulphadoxine/pyrimethamine (SP), with the classical chemoprophylaxis regimen using CQ in reducing the adverse outcomes of malaria infection, for the mother and the foetus. Methods Pregnant women attending the first antenatal care visit were randomly assigned to one of the three treatment regimens. They were subsequently followed up till delivery. Maternal, placental and cord blood samples were obtained upon delivery to check for P. falciparum infection. Results A total of 648 pregnant women were enrolled in the study. Delivery outcome were available for 423 of them. Peripheral maternal P. falciparum infection at delivery was found in 25.8% of the women. The proportion of women with maternal infection was significantly lower in the IPTp/SP group than in the CQ group (P << 0.000). The prevalence of placental malaria was 18.8% in the CWC/CQ group; 15.9% in the IPTp/CQ group and 10.6% in the IPTp/SP group. The incidence of LBW (weigth < 2,500 g) was significantly higher among infants of mothers in the CWC/CQ group (23.9%) as compared with those of mothers in the IPTp/CQ (15.6%) and IPTp/SP (11.6%) groups (p = 0.02) Conclusion Intermittent preventive treatment with SP has shown clear superiority in reducing adverse outcomes at delivery, as compared with intermittent preventive treatment with CQ and classical chemoprophylaxis with CQ.

Background The clinical presentation of malaria, considered as the result of a complex interaction between parasite and human genetics, is described to be different between rural and urban areas. The analysis of the Plasmodium falciparum genetic diversity in children with uncomplicated malaria, living in these two different areas, may help to understand the effect of urbanization on the distribution of P. falciparum genotypes. Methods Isolates collected from 75 and 89 children with uncomplicated malaria infection living in a rural and an urban area of Burkina Faso, respectively, were analysed by a nested PCR amplification of msp1 and msp2 genes to compare P. falciparum diversity. Results The K1 allelic family was widespread in children living in the two sites, compared to other msp1 allelic families (frequency >90%). The MAD 20 allelic family of msp1 was more prevalent (p = 0.0001) in the urban (85.3%) than the rural area (63.2%). In the urban area, the 3D7 alleles of msp2 were more prevalent compared to FC27 alleles, with a high frequency for the 3D7 300bp allele (>30%). The multiplicity of infection was in the range of one to six in the urban area and of one to seven in the rural area. There was no difference in the frequency of multiple infections (p = 0.6): 96.0% (95% C.I: 91.6–100) in urban versus 93.1% (95%C.I: 87.6–98.6) in rural areas. The complexity of infection increased with age [p = 0.04 (rural area), p = 0.06 (urban area)]. Conclusion Urban-rural area differences were observed in some allelic families (MAD20, FC27, 3D7), suggesting a probable impact of urbanization on genetic variability of P. falciparum. This should be taken into account in the implementation of malaria control measures.

Malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-Saharan African countries. This cross-sectional study (NCT01954264) was conducted between October and November, 2013, corresponding to the high malaria transmission season, in four sites with Health and Demographic Surveillance Systems (DSS) [two sites with moderate-to-high malaria endemicity in Burkina Faso (Nouna and Sapone) and two sites with low malaria endemicity in Senegal (Keur Soce and Niakhar)]. Children (N = 2421) were randomly selected from the DSS lists of the study sites and were stratified into two age groups (6 months–4 years and 5–9 years). A blood sample was collected from each child to evaluate parasite prevalence of Plasmodium falciparum and other Plasmodium species and gametocyte density by microscopy, and rapid diagnosis test in the event of fever within 24 h. Case report forms were used to evaluate malaria control measures and other factors. Plasmodium falciparum was identified in 707 (29.2%) children, with a higher prevalence in Burkina Faso than Senegal (57.5 vs 0.9% of children). In Burkina Faso, prevalence was 57.7% in Nouna and 41.9% in Sapone in the 6 months–4 years age group, and 75.4% in Nouna and 70.1% in Sapone in the 5–9 years age group. Infections with other Plasmodium species were rare and only detected in Burkina Faso. While mosquito nets were used by 88.6–97.0 and 64.7–80.2% of children in Burkina Faso and Senegal, other malaria control measures evaluated at individual level were uncommon. In Burkina Faso, exploratory analyses suggested that use of malaria treatment or any other medication within 14 days, and use of insecticide spray within 7 days decreased the prevalence of malaria infection; older age, rural residence, natural floor, grass/palm roof, and unavailability of electricity in the house were factors associated with increased malaria occurrence. Plasmodium falciparum infection prevalence in children younger than 10 years was 57.5% in Burkina Faso and 0.9% in Senegal, and variability was observed, among others, by age, study site and malaria control measures.