Enhanced effect of seasonal malaria chemoprevention when coupled with nutrients supplementation for preventing malaria in children under 5 years old in Burkina Faso: a randomized open label trial.

BACKGROUND: In rural African settings, most of the children under the coverage of Seasonal Malaria Chemoprevention (SMC) are also undernourished at the time of SMC delivery, justifying the need for packaging malarial and nutritional interventions. This study aimed at assessing the impact of SMC by coupling the intervention with nutrients supplementation for preventing malaria in children less than 5 years old in Burkina Faso. METHODS: A randomized trial was carried out between July 2020 and June 2021 in the health district of Nanoro, Burkina Faso. Children (n = 1059) under SMC coverage were randomly assigned to one of the three study arms SMC + Vitamin A (SMC-A, n = 353) or SMC + Vitamin A + Zinc (SMC-AZc, n = 353) or SMC + Vitamin A + PlumpyDoz(tm) (SMC-APd, n = 353)-a medium quantity-lipid-based nutrient supplement (MQ-LNS). Children were followed up for one year that included an active follow-up period of 6 months with scheduled monthly home visits followed by 6 months passive follow-up. At each visit, capillary blood sample was collected for malaria diagnosis by rapid diagnosis test (RDT). RESULTS: Adding nutritional supplements to SMC had an effect on the incidence of malaria. A reduction of 23% (adjusted IRR = 0.77 (95%CI 0.61-0.97) in the odds of having uncomplicated malaria in SMC-APd arm but not with SMC-AZc arm adjusted IRR = 0.82 (95%CI 0.65-1.04) compare to control arm was observed. A reduction of 52%, adjusted IRR = 0.48 (95%CI 0.23-0.98) in the odds of having severe malaria was observed in SMC-APd arm compared to control arm. Besides the effect on malaria, this combined strategy had an effect on all-cause morbidity. More specifically, a reduction of morbidity odds of 24%, adjusted IRR = 0.76 (95%CI 0.60-0.94) in SMC-APd arm compared to control arm was observed. Unlike clinical episodes, no effect of nutrient supplementation on cross sectional asymptomatic infections was observed. CONCLUSION: Adding nutritional supplements to SMC significantly increases the impact of this intervention for preventing children from malaria and other childhood infections. TRIAL REGISTRATION: NCT04238845.

Baseline malarial and nutritional profile of children under seasonal malaria chemoprevention coverage in the health district of Nanoro, Burkina Faso.

Seasonal Malaria chemoprevention (SMC) is one of the large-scale life-saving malaria interventions initially recommended for the Sahel subregion, including Burkina Faso and recently extended to other parts of Africa. Initially, SMC was restricted to children 3 to 59 months old, but an extension to older children in some locations was recently recommended. Further characterization of SMC population profile beyond age criterion is necessary for understanding factors that could negatively impact the effectiveness of the intervention and to define complementary measures that could enhance its impact. Children were assessed through a cross-sectional survey during the first month of the 2020 SMC campaign (July-August 2020) as part of the SMC-NUT project in the health district of Nanoro. Parameters such as body temperature, weight, height, mid-upper arm circumference (MUAC) were assessed. In addition, blood sample was collected for malaria diagnosis by rapid diagnostic tests (RDT) and microscopy, and for haemoglobin measurement. A total of 1059 children were enrolled. RDT positivity rate (RPR) was 22.2%, while microscopy positivity rate (MPR) was 10.4%, with parasitaemia levels ranging from 40 to 70480/µL. RPR and MPR increased as patient age increased. Wasting was observed in 7.25% of children under SMC coverage while the prevalence of stunting and underweight was 48.79% and 23.38%, respectively. As the age of the children increased, an improvement in their nutritional status was observed. Finally, undernourished children had higher parasite densities than children with adequate nutritional status. In the health district of Nanoro, children who received Seasonal Malaria Chemoprevention (SMC) were mostly undernourished during the period of SMC delivery, suggesting the need for combining the SMC with synergistic interventions against malnutrition to achieve best impact.

Healthcare seeking outside healthcare facilities and antibiotic dispensing patterns in rural Burkina Faso: A mixed methods study.

OBJECTIVE: Optimising antibiotic use is important to limit increasing antibiotic resistance. In rural Burkina Faso, over-the-counter dispensing of antibiotics in community pharmacies and non-licensed medicine retail outlets facilitates self-medication. We investigated its extent, reasons and dispensing patterns. METHODS: In an exploratory mixed-method design conducted between October 2020 and December 2021, this study first explored illness perceptions, the range of healthcare providers in communities, antibiotics knowledge and reasons for seeking healthcare outside healthcare facilities. Second, frequencies of illness and healthcare utilisation in the last 3 months were quantitatively measured. RESULTS: Participants distinguished between natural and magico-religious illnesses, according to origins. For illnesses considered to be 'natural', healthcare was mainly sought at healthcare facilities, private pharmacies and informal drug outlets. For illnesses considered as magico-religious, traditional healers were mainly visited. Antibiotics were perceived in the community as medicines similar to painkillers. Healthcare-seeking outside healthcare facilities was reported by 660/1973 (33.5%) participants reporting symptoms, including 315 (47.7%) to informal vendors. Healthcare seeking outside facilities was less common for 0-4-year-olds (58/534, 10.9% vs. 379/850, 44.1% for ≥5-year-olds) and decreased with improving socio-economic status (108/237, 45.6% in the lowest quintile; 96/418, 23.0% in the highest). Reported reasons included financial limitation, and also proximity to informal drug vendors, long waiting times at healthcare facilities, and health professionals' non-empathetic attitudes towards their patients. CONCLUSION: This study highlights the need to facilitate and promote access to healthcare facilities through universal health insurance and patient-centred care including reducing patients' waiting time. Furthermore, community-level antibiotic stewardship programmes should include community pharmacies and informal vendors.

Effects of maternal antenatal treatment with two doses of azithromycin added to monthly sulfadoxine-pyrimethamine for the prevention of low birth weight in Burkina Faso: an open-label randomized controlled trial.

BACKGROUND: Exposure during pregnancy to malaria and sexually-transmitted infections is associated with adverse birth outcomes including low birth weight (LBW). This study aimed at assessing if the adjunction of two doses of azithromycin to sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy can reduce LBW. METHODS: A two parallel-groups, open-label randomized controlled trial involving pregnant women (16 to 35 years of age and 12 to 24 weeks of gestation as confirmed by last menstrual period or fundal height) was conducted in rural Burkina Faso. Women were assigned in a 1:1 ratio either to use azithromycin (1 g daily for 2 days) during the second and third trimesters of pregnancy plus monthly sulfadoxine-pyrimethamine (1500/75 mg) (SPAZ) (intervention) or to continue using a monthly sulfadoxine-pyrimethamine (1500/75 mg) (SP) (control). Primary outcome was a LBW (birth weight measured within 24 h after birth < 2500 g). Secondary outcomes including stillbirth, preterm birth or miscarriage are reported together with safety data. RESULTS: A total of 992 pregnant women underwent randomization (496 per group) and 898 (90.5%) valid birth weights were available (450 in SPAZ and 448 in SP). LBW incidence was 8.7% (39/450) in SPAZ and 9.4% (42/448) in controls (p-value = 0.79). Compared with controls, pregnant women with SPAZ showed a risk ratio (RR) of 1.16 (95% confidence interval (CI 0.64-2.08]) for preterm births, 0.75 (95% CI 0.17-3.35) for miscarriage and 0.64 (95% CI 0.25-1.64) for stillbirths. No treatment-related serious adverse events (SAEs) have been observed, and there was no significant difference in the number of SAEs (13.5% [67/496] in SPAZ, 16.7% [83/496] in SP, p-value = 0.18) or AEs (17.1% [85/496] in SPAZ, 18.8% [93/496] in SP, p-value = 0.56). CONCLUSION: Adequate prevention regimen with monthly sulfadoxine-pyrimethamine given to all pregnant women has been proved to reduce the risk of LBW in malaria endemic areas. Adding azithromycin to the regimen does not offer further benefits, as far as women receive a malaria prevention regimen early enough during pregnancy. Trial registration Pan African Clinical Trial Registry ( https://pactr.samrc.ac.za/Search.aspx ): PACTR201808177464681. Registered 21 August 2018.

Impact and operational feasibility of adding malaria infection screening using an ultrasensitive RDT for placental and fetal outcomes in an area of high IPTP-SP coverage in Burkina Faso: the ASSER MALARIA pilot study protocol.

BACKGROUND: Malaria infection during pregnancy (MIP) is not only deleterious to the woman, but it also puts her fetus at increased risk of adverse outcomes, such as preterm delivery, low birth weight, and intrauterine growth retardation. Additionally, all-cause mortality during the first year of life in babies born to women with malaria during pregnancy is also increased. Many interventions such as IPTp-SP and long-lasting insecticidal nets have proven to be efficient at reducing malaria in pregnancy burden but adherence to recommended policies remains poor. In sub-Saharan Africa, malaria in pregnancy is often asymptomatic and many malaria infections may be missed due to the inadequate performance of the current rapid diagnostic test to detect low-level parasitemias. Therefore, additional strategies such as intermittent screening with ultrasensitive rapid diagnostic tests and treatment with an effective artemisinin-based combination therapy in addition to IPTp-SP could reduce placental malaria, peripheral malaria infection at delivery, and low birth weight. METHODS: This pilot 2-group randomized open trial with a nested qualitative social behavioral will be carried out in Nanoro district in which 340 pregnant women will be recruited. Pregnant women will be randomized into two groups and followed on a monthly basis until delivery. In the intervention group, monthly screening using ultrasensitive rapid diagnostic tests and treatment of those found to be infected with dihydroartemisinin-piperaquine will be performed. In addition, a reminder will be sent to increase the uptake of IPTp-SP doses per woman. During scheduled and unscheduled visits, malaria infection, hemoglobin level, and other clinical outcomes will be assessed and compared by the group. The primary feasibility outcome will evaluate the study site's capacity to enroll participants and the women's perception and acceptability of the intervention. The primary clinical outcome will be the prevalence of placental malaria at delivery. DISCUSSION: The present protocol aims to evaluate the feasibility on a large-scale and also to demonstrate the impact and the operational feasibility of additional screening with ultrasensitive rapid diagnostic tests and treatment with DHA-PQ on placental malaria, low birth weight, and peripheral malaria infection at delivery in a high-burden setting in Burkina Faso. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04147546 (14 October 2019).

Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial.

BACKGROUND: Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at 12 months following administration of a booster vaccination. METHODS: This double-blind phase 1/2b randomised controlled trial was done in children aged 5-17 months in Nanoro, Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either 5 µg R21/25 µg Matrix-M, 5 µg R21/50 µg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity or receipt of other investigational products. A random allocation list was generated by an independent statistician by use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster vaccination. The population in which the efficacy analyses were done comprised all participants who received the primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of additional booster vaccine doses and longer-term safety. FINDINGS: Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 µg R21 adjuvanted with 25 µg Matrix-M, 137 received 5 µg R21 adjuvanted with 50 µg Matrix-M, and 140 received the control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in the high adjuvant dose (50 µg) group, similar to previous findings at 1 year after the primary series of vaccinations. Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman's ρ -0·32 [95% CI -0·45 to -0·19]; p=0·0001) and second year of follow-up (-0·20 [-0·34 to -0·06]; p=0·02). INTERPRETATION: A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these participants and the value of further booster vaccinations. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR Oxford Biomedical Research Centre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Changing Dietary Habits: The Impact of Urbanization and Rising Socio-Economic Status in Families from Burkina Faso in Sub-Saharan Africa.

(1) Background: Sub-Saharan Africa is experiencing the fastest urbanization worldwide. People in rural areas still have a traditional and rural lifestyle, whereas the Westernization of diet and lifestyle is already evident in urban areas. This study describes dietary habits of families in Burkina Faso living at different levels of urbanization. (2) Methods: Data on lifestyle, socio-economic conditions, health status and anthropometry were collected from 30 families living in rural villages, a small town and the capital city. A food frequency questionnaire and a 24 h recall diary were used to estimate dietary habits and macronutrients intake. (3) Results: The urban cohort showed a more diversified diet, with a higher intake of animal protein and, especially in children, a higher consumption of simple sugars. Fiber intake was significantly higher in the rural and semi-urbanized cohorts. As expected, overweight and obesity gradually increased with the level of urbanization. In semi-urbanized and urban families, we observed coexistence of under- and over-nutrition, whereas in rural families, a portion of children were wasted and stunted, and adults were underweight. (4) Conclusions: These three cohorts represent a model of the effect on diet of rural-to-urban migration. Rural diet and traditional habits are replaced by a Western-oriented diet when families move to urbanized areas. This dietary transition and increased socio-economic status in newly developing urban areas have a major impact on disease epidemiology, resembling the past evolution in Western countries.

Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial.

BACKGROUND: Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS: This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION: The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention.

[Polymorphisms in Plasmodium falciparum parasites and mutations in the resistance genes Pfcrt and Pfmdr1 in Nanoro area, Burkina Faso]. / Polymorphisme de Plasmodium falciparum et mutations des gènes de résistance Pfcrt et Pfmdr1 dans la zone de Nanoro, Burkina Faso.

INTRODUCTION: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. METHODS: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. RESULTS: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. CONCLUSION: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs.

Patterns of child mortality in rural area of Burkina Faso: evidence from the Nanoro health and demographic surveillance system (HDSS).

BACKGROUND: Half of global child deaths occur in sub-Saharan Africa. Understanding child mortality patterns and risk factors will help inform interventions to reduce this heavy toll. The Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso was described previously, but patterns and potential drivers of heterogeneity in child mortality in the district had not been studied. Similar studies in other districts indicated proximity to health facilities as a risk factor, usually without distinction between facility types. METHODS: Using Nanoro HDSS data from 2009 to 2013, we estimated the association between under-5 mortality and proximity to inpatient and outpatient health facilities, seasonality of death, age group, and standard demographic risk factors. RESULTS: Living in homes 40-60 min and > 60 min travel time from an inpatient facility was associated with 1.52 (95% CI: 1.13-2.06) and 1.74 (95% CI: 1.27-2.40) greater hazard of under-5 mortality, respectively, than living in homes < 20 min from an inpatient facility. No such association was found for outpatient facilities. The wet season (July-November) was associated with 1.28 (95% CI: 1.07, 1.53) higher under-5 mortality than the dry season (December-June), likely reflecting the malaria season. CONCLUSIONS: Our results emphasize the importance of geographical proximity to health care, distinguish between inpatient and outpatient facilities, and also show a seasonal effect, probably driven by malaria.

Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial.

BACKGROUND: Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy. METHODS: In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 µg R21 plus 25 µg MM, group 2 received 5 µg R21 plus 50 µg MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724. FINDINGS: From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered 1 year later. INTERPRETATION: R21/MM appears safe and very immunogenic in African children, and shows promising high-level efficacy. FUNDING: The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre.

Assessment of a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy'Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT).

BACKGROUND: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage. METHODS: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. DISCUSSION: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845.

Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density.

BACKGROUND: Multi-genotype malaria infections are frequent in endemic area, and people commonly harbour several genetically distinct Plasmodium falciparum variants. The influence of genetic multiplicity and whether some specific genetic variants are more or less likely to invest into gametocyte production is not clearly understood. This study explored host and parasite-related risk factors for gametocyte carriage, and the extent to which some specific P. falciparum genetic variants are associated with gametocyte carriage. METHODS: Gametocytes and asexual forms were detected by light microscopy on thick smears collected between 2010 and 2012 in Nanoro, Burkina Faso. Merozoite surface protein 1 and 2 were genotyped by nested PCR on clinical samples. Associations between gametocyte carriage and factors, including multiplicity of infection, parasite density, patient age, gender, haemoglobin (Hb) level, and body temperature were assessed. The relationship between the presence of a particular msp1 and msp2 genetic variants and gametocyte carriage was also explored. RESULTS: Of the 724 samples positive to P. falciparum and successfully genotyped, gametocytes were found in 48 samples (6.63%). There was no effect of patient gender, age and body temperature on gametocyte carriage. However, the probability of gametocyte carriage significantly increased with increasing values of multiplicity of infection (MOI). Furthermore, there was a negative association between parasite density and gametocyte carriage. MOI decreased with parasite density in gametocyte-negative patients, but increased in gametocyte carriers. The probability of gametocyte carriage decreased with Hb level. Finally, the genetic composition of the infection influenced gametocyte carriage. In particular, the presence of RO33 increased the odds of developing gametocytes by 2 while the other allelic families K1, MAD20, FC27, and 3D7 had no significant impact on the occurrence of gametocytes in infected patients. CONCLUSION: This study provides insight into potential factors influencing gametocyte production in symptomatic patients. The findings contribute to enhance understanding of risk factors associated with gametocyte carriage in humans. Trial registration NCT01232530.

Malaria and curable sexually transmitted infections in pregnant women: A two-years observational study in rural Burkina Faso.

BACKGROUND: Malaria and curable sexually transmitted infections (STI) are the most common curable infections known to have a severe impact on pregnancy outcomes in sub-Saharan Africa. This study aims to assess the marginal and joint prevalence of symptomatic cases of malaria and STI in pregnant women living in rural settings of Burkina Faso and their associated factors, after more than a decade of the introduction of intermittent preventive treatment (IPT-SP). METHODS: We carried out an observational study in two health districts in rural Burkina, namely Nanoro and Yako. Routine data were collected during antenatal and delivery visits for all women who delivered in the year 2016 and 2017. Logistic regression models were used to assess factors associated with infections. RESULTS: We collected data from 31639 pregnant women attending health facilities. Malaria, curable STI and their coinfections were diagnosed in 7747 (24.5%; 95%CI: 24.0-25.0%), 1269 (4.0%; 95%CI: 3.8-4.2%) and 388 (1.2%; 95%CI: 1.1-1.4%) women, respectively. In multivariate logistic regression, malaria occurrence was significantly higher in pregnant women < 20 years (Adjusted OR = 2.36; 95% CI: 2.07-2.69) than in women ≥30 years. The prevalence of curable STI was also significantly higher in students (Adjusted OR = 1.93; 95% CI: 1.26-2.95) and compensated workers (Adjusted OR = 1.52; 95% CI: 1.01-2.17) than in uncompensated workers. Women who received no IPT-SP had higher prevalence of malaria (Adjusted OR = 3.33; 95%CI: 3.00-3.70), curable STI (Adjusted OR = 1.96 95%CI: 1.60-2.39) and coinfections (Adjusted OR = 2.11; 95% CI: 1.50-2.95) compared to women who received SP. CONCLUSION: Malaria and curable STI remain highly prevalent in rural settings of Burkina Faso, with young pregnant women and women who received no IPT-SP being the most affected. Prevention must be reinforced to improve maternal and infant health.

Red blood cell homeostasis in children and adults with and without asymptomatic malaria infection in Burkina Faso.

Asymptomatic malaria infections may affect red blood cell (RBC) homeostasis. Reports indicate a role for chronic hemolysis and splenomegaly, however, the underlying processes are incompletely understood. New hematology analysers provide parameters for a more comprehensive analysis of RBC hemostasis. Complete blood counts were analysed in subjects from all age groups (n = 1118) living in a malaria hyperendemic area and cytokines and iron biomarkers were also measured. Subjects were divided into age groups (<2 years, 2-4, 5-14 and ≥15 years old) and clinical categories (smear-negative healthy subjects, asymptomatic malaria and clinical malaria). We found that hemoglobin levels were similar in smear-negative healthy children and asymptomatic malaria children but significantly lower in clinical malaria with a maximum difference of 2.2 g/dl in children <2 years decreasing to 0.1 g/dl in those aged ≥15 years. Delta-He, presenting different hemoglobinization of reticulocytes and RBC, levels were lower in asymptomatic and clinial malaria, indicating a recent effect of malaria on erythropoiesis. Reticulocyte counts and reticulocyte production index (RPI), indicating the erythropoietic capacity of the bone marrow, were higher in young children with malaria compared to smear-negative subjects. A negative correlation between reticulocyte counts and Hb levels was found in asymptomatic malaria (ρ = -0.32, p<0.001) unlike in clinical malaria (ρ = -0.008, p = 0.92). Free-Hb levels, indicating hemolysis, were only higher in clinical malaria. Phagocytozing monocytes, indicating erythophagocytosis, were highest in clinical malaria, followed by asymptomatic malaria and smear-negative subjects. Circulating cytokines and iron biomarkers (hepcidin, ferritin) showed similar patterns. Pro/anti-inflammatory (IL-6/IL-10) ratio was higher in clinical than asymptomatic malaria. Cytokine production capacity of ex-vivo whole blood stimulation with LPS was lower in children with asymptomatic malaria compared to smear-negative healthy children. Bone marrow response can compensate the increased red blood cell loss in asymptomatic malaria, unlike in clinical malaria, possibly because of limited level and length of inflammation. Trial registration: Prospective diagnostic study: ClinicalTrials.gov identifier: NCT02669823. Explorative cross-sectional field study: ClinicalTrials.gov identifier: NCT03176719.

Clinical management and mortality among COVID-19 cases in sub-Saharan Africa: A retrospective study from Burkina Faso and simulated case analysis.

BACKGROUND: Absolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies. METHODS: Data from deceased cases reported across SSA through 10 May 2020 and from hospitalized cases in Burkina Faso through 15 April 2020 were analyzed. Demographic, epidemiological and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Centre Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was probabilistically derived using distributions of age, sex and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses. RESULTS: Across SSA, deceased cases for which demographic data were available were predominantly male (63/103, 61.2%) and aged >50 years (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32). Hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy were significantly higher than for those receiving oxygen, such as due to disruptions to standard care (OR 2.07; 95% CI 1.56-2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI 0.24-0.93). CONCLUSIONS: Investment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted until data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.

Determinants of Plasmodium falciparum multiplicity of infection and genetic diversity in Burkina Faso.

BACKGROUND: Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso. METHODS: Blood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction. RESULTS: In the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation. CONCLUSIONS: In high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.

Adolescent Fertility Is Lower than Expected in Rural Areas: Results from 10 African HDSS.

The adolescent birth rate (ABR) is an important indicator of maternal health, adolescent sexual health, and gender equity; it remains high in sub-Saharan Africa. While Demographic and Health Surveys (DHS) are the main source of ABR estimates, Health and Demographic Surveillance Systems (HDSS) also produce ABRs. Studies are lacking, however, to assess the ease of access and accuracy of HDSS ABR measures. In this paper, we use birth and exposure data from 10 HDSS in six African countries to compute local ABRs and compare these rates to DHS regional rates where the HDSS sites are located, standardizing by education and place of residence. In rural HDSS sites, the ABR measure is on average 44 percent lower than the DHS measure, after controlling for education and place of residence. Strong temporary migration of childless young women out of rural areas and different capacities in capturing temporarily absent women in the DHS and HDSS could explain this discrepancy. Further comparisons based on more strictly similar populations and measures seem warranted.

Optimal Approach and Strategies to Strengthen Pharmacovigilance in Sub-Saharan Africa: A Cohort Study of Patients Treated with First-Line Artemisinin-Based Combination Therapies in the Nanoro Health and Demographic Surveillance System, Burkina Faso.

BACKGROUND AND PURPOSE: Resource-limited countries face challenges in setting up effective pharmacovigilance systems. This study aimed to monitor the occurrence of adverse events (AEs) after the use of artemisinin-based combination therapies (ACTs), identify potential drivers of reporting suspected adverse drug reactions (ADRs) and monitor AEs among women who were inadvertently exposed to ACTs in the first trimester of pregnancy. PATIENTS AND METHODS: We conducted a prospective observational study from May 2010 to July 2012 in Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso. The HDSS area was divided into active and passive surveillance areas to monitor AEs among patients (regardless of age or sex) who received a first-line ACT (artemether-lumefantrine or artesunate-amodiaquine). In the active surveillance area, patients were followed up for 28 days, while in the passive surveillance area, patients were encouraged to return voluntarily to the health facility to report any occurrence of AEs until day 28 after drug intake. We assessed the crude incidence rates of AEs in both cohorts and performed Cox regression with mixed random effects to identify potential drivers of ADR occurrence. RESULTS: In total, 3170 participants were included in the study. Of these, 40.3% had reported at least one AE, with 39.6% and 44.4% from active and passive surveillance groups, respectively. The types of ADRs were similar in both groups. The most frequent reported ADRs were anorexia, weakness, cough, dizziness and pruritus. One case of abortion and eight cases of death were reported, but none of them was related to the ACT. The variance in random factors showed a high variability of ADR occurrence between patients in both groups, whereas variability between health facilities was low in the active surveillance group and high in passive surveillance group. Taking more than two concomitant medications was associated with high hazard in ADR occurrence, whereas the rainy season was associated with low hazard. CONCLUSION: This study showed that both passive and active surveillance approaches were useful tools. The HDSS allowed us to capture a few cases of exposure during the first trimester of pregnancy. The passive surveillance approach, which is more likely to be implemented by malaria control programs, seems to be more relevant in the Sub-Saharan African context.

The changing epidemiology of hepatitis B and C infections in Nanoro, rural Burkina Faso: a random sampling survey.

BACKGROUND: This study sought to provide up-to-date hepatitis B (HBV) and C (HCV) seroprevalence in rural Burkina Faso decade after hepatitis B vaccine was introduced in the national immunization scheduled for children. METHODS: In 2018, a community-based, random sampling strategy with probability proportional to population size was conducted in Nanoro to investigate the prevalence of viral hepatitis in children and their mothers. Sociodemographic, vaccination history and risk factors were assessed by interview and health books. HBsAg rapid tests were done by finger prick and Dried Blood Spots (DBS) were collected for hepatitis seromarkers by chemiluminescence enzyme immunoassay. Positive samples underwent confirmatory PCR and phylogenetic analysis. RESULTS: Data were presented on 240 mother-child pairs. HBsAg Prevalence was 0.8% in children and 6.3% in mothers. Hepatitis B core antibody positivity was 89.2% in mothers, 59.2% in children and was associated with age, sex and scarification. Hepatitis B surface antibodies prevalence was 37.5% in children and 5.8% in mothers. Good vaccination coverage was limited by home delivery. Phylogenetic analysis of HBV strains based on full genome sequences (n = 7) and s-fragment sequences (n = 6) revealed genotype A, E, and recombinant A3/E. Viral genome homology was reported in one mother-child pair. Anti-HCV prevalence was 5.4% in mothers, 2.1% in children and strains belonged to genotype 2. CONCLUSIONS: In Nanoro, HBsAg prevalence was low in children, intermediate in mothers and mother-to-child transmission persists. Home delivery was a limiting factor of Hepatitis B vaccination coverage. HBV genotype E was predominant and genotype A3/E is reported for the first time in Burkina Faso.