Increasing the uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) through seasonal malaria chemoprevention channel delivery: protocol of a multicenter cluster randomized implementation trial in Mali and Burkina Faso.

BACKGROUND: The uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) remains unacceptably low, with more than two-thirds of pregnant women in sub-Saharan Africa still not accessing the three or more doses recommended by the World Health Organisation (WHO). In contrast, the coverage of Seasonal Malaria Chemoprevention (SMC), a more recent strategy recommended by the WHO for malaria prevention in children under five years living in Sahelian countries with seasonal transmission, including Mali and Burkina-Faso, is high (up to 90%). We hypothesized that IPTp-SP delivery to pregnant women through SMC alongside antenatal care (ANC) will increase IPTp-SP coverage, boost ANC attendance, and increase public health impact. This protocol describes the approach to assess acceptability, feasibility, effectiveness, and cost-effectiveness of the integrated strategy. METHODS AND ANALYSIS: This is a multicentre, cluster-randomized, implementation trial of IPTp-SP delivery through ANC + SMC vs ANC alone in 40 health facilities and their catchment populations (20 clusters per arm). The intervention will consist of monthly administration of IPTp-SP through four monthly rounds of SMC during the malaria transmission season (July to October), for two consecutive years. Effectiveness of the strategy to increase coverage of three or more doses of IPTp-SP (IPTp3 +) will be assessed using household surveys and ANC exit interviews. Statistical analysis of IPT3 + and four or more ANC uptake will use a generalized linear mixed model. Feasibility and acceptability will be assessed through in-depth interviews and focus group discussions with health workers, pregnant women, and women with a child < 12 months. DISCUSSION: This multicentre cluster randomized implementation trial powered to detect a 45% and 22% increase in IPTp-SP3 + uptake in Mali and Burkina-Faso, respectively, will generate evidence on the feasibility, acceptability, effectiveness, and cost-effectiveness of IPTp-SP delivered through the ANC + SMC channel. The intervention is designed to facilitate scalability and translation into policy by leveraging existing resources, while strengthening local capacities in research, health, and community institutions. Findings will inform the local national malaria control policies. TRIAL REGISTRATION: Retrospectively registered on August 11th, 2022; registration # PACTR202208844472053. Protocol v4.0 dated September 04, 2023. Trail sponsor: University of Sciences Techniques and Technologies of Bamako (USTTB), Mali.

Age-modified factors associated with placental malaria in rural Burkina Faso.

BACKGROUND: Malaria in pregnancy can result in placental infection with fetal implications. This study aimed at assessing placental malaria (PM) prevalence and its associated factors in a cohort of pregnant women with peripheral malaria and their offspring. METHOD: The data were collected in the framework of a clinical trial on treatments for malaria in pregnant women . Placental malaria (PM) was diagnosed by histopathological detection of parasites and/or malaria pigment on placenta biopsies taken at delivery. Factors associated with PM were assessed using logistic regression. RESULTS: Out of 745 biopsies examined, PM was diagnosed in 86.8 % of women. Acute, chronic and past PM were retrieved in 11 (1.5 %), 170 (22.8 %), and 466 (62.6 %) women, respectively. A modifying effect was observed in the association of gravidity or anemia at the study start with pooled PM (presence of parasites and/or malaria pigment). In women under 30, gravidity ≤ 2 was associated with an increased prevalence of pooled PM but in women aged 30 years or more, gravidity was no more associated with pooled PM (OR 6.81, 95 % CI 3.18 - 14.60; and OR 0.52, 95 % CI 0.10 - 2.76, respectively). Anemia was associated with pooled PM in women under 30 (OR 1.96, 95 % CI 1.03 - 3.72) but not in women aged 30 years or more (OR 0.68, 95 % CI 0.31 - 1.49). Similarly, the association of gravidity with past-chronic PM depended also on age. A higher prevalence of active PM was observed in women under 30 presenting with symptomatic malaria (OR 3.79, 95 % CI 1.55 - 9.27), while there was no significant increase in the prevalence of active PM (presence of parasites only) in women with symptomatic malaria when aged 30 years or more (OR 0.42, 95 % CI 0.10 - 1.75). In women with chronic PM, the prevalence of low birth weight or prematurity was the highest (31.2 %) as compared with past PM or no PM. CONCLUSION: Despite the rapid diagnosis and efficacious treatment of peripheral infection, the prevalence of placental malaria remained high in women with P. falciparum peripheral infection in Nanoro, especially in younger women This underlines the importance of preventive measures in this specific group.

Association of malaria and curable sexually transmitted infections with pregnancy outcomes in rural Burkina Faso.

BACKGROUND: Malaria and curable sexually transmitted infections (STIs) are severe infections associated with poor pregnancy outcomes in sub-Saharan countries. These infections are responsible for low birth weight, preterm birth, and miscarriage. In Burkina Faso, many interventions recommended by the World Health Organization were implemented to control the impact of these infections. After decades of intervention, we assessed the impact of these infections on pregnancy outcomes in rural setting of Burkina Faso. METHODS: Antenatal care and delivery data of pregnant women attending health facilities in 2016 and 2017 were collected in two rural districts namely Nanoro and Yako, in Burkina Faso. Regression models with likelihood ratio test were used to assess the association between infections and pregnancy outcomes. RESULTS: During the two years, 31639 pregnant women received antenatal care. Malaria without STI, STI without malaria, and their coinfections were reported for 7359 (23.3%), 881 (2.8 %), and 388 (1.2%) women, respectively. Low birth weight, miscarriage, and stillbirth were observed in 2754 (10.5 %), 547 (2.0 %), and 373 (1.3 %) women, respectively. Our data did not show an association between low birth weight and malaria [Adjusted OR: 0.91 (0.78 - 1.07)], STIs [Adjusted OR: 0.74 (0.51 - 1.07)] and coinfection [Adjusted OR: 1.15 (0.75 - 1.78)]. Low birth weight was strongly associated with primigravidae [Adjusted OR: 3.53 (3.12 - 4.00)]. Both miscarriage and stillbirth were associated with malaria [Adjusted OR: 1.31 (1.07 - 1.59)], curable STI [Adjusted OR: 1.65 (1.06 - 2.59)], and coinfection [Adjusted OR: 2.00 (1.13 - 3.52)]. CONCLUSION: Poor pregnancy outcomes remained frequent in rural Burkina Faso. Malaria, curable STIs, and their coinfections were associated with both miscarriage and stillbirth in rural Burkina. More effort should be done to reduce the proportion of pregnancies lost associated with these curable infections by targeting interventions in primigravidae women.

[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.

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.

Fetal biometry assessment with Intergrowth 21st's and Salomon's equations in rural Burkina Faso.

BACKGROUND: Ultrasound scanning during the 2nd or the 3rd trimester of pregnancy for fetal size disturbances screening is heavily dependent of the choice of the reference chart. This study aimed to assess the agreement of Salomon and the Intergrowth 21st equations in evaluating fetal biometric measurements in a rural area of Burkina Faso, and to measure the effect of changing a reference chart. METHODS: Data collected in Nazoanga, Burkina Faso, between October 2010 and October 2012, during a clinical trial evaluating the safety and efficacy of several antimalarial treatments in pregnant women were analyzed. We included singleton pregnancies at 16-36 weeks gestation as determined by ultrasound measurements of fetal bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). Expected mean and standard deviation at a given gestational age was computed using equations from Salomon references and using Intergrowth 21st standard. Then, z-scores were calculated and used subsequently to compare Salomon references with Intergrowth 21st standards. RESULTS: The analysis included 276 singleton pregnancies. Agreement was poor except for HC: mean difference - 0.01, limits of agreement - 0.60 and 0.59. When AC was used as a surrogate of fetal size, switching from the reference of Salomon to the standards of Intergrowth 21st increased ten times the proportion of fetuses above the 90th percentile: 2.9 and 31.2%, respectively. Mean differences were larger in the third trimester than in the second trimester. However, agreement remained good for HC in both trimesters. Difference in the proportion of AC measurements above the 90th percentile using Salomon and Intergrowth 21st equations was greater in the second trimester (2.6 and 36.3%, respectively) than in the third trimester (3.5 and 19.8%, respectively). The greatest difference between the two charts was observed in the number of FL measurements classified as large in the second trimester (6.8 and 54.2%, using Salomon and Intergrowth 21st equations, respectively). CONCLUSION: The agreement between Intergrowth 21st and Salomon equations is poor apart from HC. This would imply different clinical decision regarding the management of the pregnancy.

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.

Gender differences in sociodemographic and behavioural factors associated with BMI in an adult population in rural Burkina Faso - an AWI-Gen sub-study.

BACKGROUND: The global health transition is linked with an increased burden of non-communicable diseases with cardiovascular diseases leading the epidemic. In sub-Saharan Africa (SSA), the prevalence of obesity has increased during the past decades and there is a need to investigate the associated driving factors. In Burkina Faso obesity remains low, especially in rural areas. In this study we recruited middle-aged adults, as part of a larger study on genetic and environmental contributions to cardiometabolic disease among Africans. OBJECTIVES: To investigate the distribution of BMI and prevalence of obesity in a cross-sectional population-based study and to determine the sociodemographic and behavioural correlates with BMI. METHODS: Participants (N = 2,076) were recruited from the Nanoro Health and Demographic Surveillance System area and were aged 40-60 years. We applied hierarchical modelling to identify factors associated with BMI and structural equation modelling to identify mediated effects of sociodemographic and behavioural variables on BMI. RESULTS: Data are presented on 2,076 participants (49.9% female). Men had significantly higher BMI than women with medians of 21.1 (19.2 - 23.4) vs 19.8 (18.1 - 21.6) (p < 0.001), and there were significantly more underweight women compared to men (31.0% vs 17.4%) (p < 0.001). More men were overweight and obese than women (11.9% vs 5.2% and 2.2% vs 1.4%). Socioeconomic status was the major contributor to increased BMI for men, and education was the main contributor in women. Tobacco smoking and chewing, and problematic alcohol consumption were associated with a decrease in BMI in men and women. CONCLUSION: Overweight and obesity are relatively low among adults in rural Burkina Faso, and men had a higher median BMI than women. Behavioural factors, including tobacco use and alcohol consumption, contributed to a decrease in BMI, whereas socioeconomic status and education (which were both generally low in this community) contributed to an increase in BMI.

The impact of clinical research activities on communities in rural Africa: the development of the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso.

BACKGROUND: The opportunities for developing new drugs and vaccines for malaria control look brighter now than ten years ago. However, there are few places in sub-Saharan Africa with the necessary infrastructure and expertise to support such research in compliance to international standards of clinical research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) was founded in 2008 to provide a much-needed GCP-compliant clinical trial platform for an imminent large-scale Phase 3 malaria vaccine trial. A dynamic approach was used that entailed developing the required infrastructure and human resources, while engaging local communities in the process as key stakeholders. This provided a better understanding and ownership of the research activities by the local population. CASE DESCRIPTION: Within five years (2008-2013), the CRUN set up a fully and well-equipped GCP-compliant clinical trial research facility, which enabled to attract 25 grants. The research team grew from ten health workers prior to 2008 to 254 in 2013. A Health and Demographic Surveillance System (HDSS), which covers a total population of about 60,000 people in 24 villages was set up in the district. The local community contributed to the development of the facility through the leadership of the king and the mayor of Nanoro. As a result of their active advocacy, the government extended the national electrical grid to the new research center, and later to the entire village. This produced a positive impact on the community's quality of life. The quality of health care improved substantially, due to the creation of more elaborate clinical laboratory services and the acquisition of state-of-the-art equipment. CONCLUSION: Involving the community in the key steps of establishing the centre provided the foundation for what was to become the CRUN success story. This experience demonstrates that when clinical trials research sites are carefully developed and implemented, they can have a positive and powerful impact on local communities in resource-poor settings, well beyond the task of generating expected study data.

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.

BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).