Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections.

Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%-32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.

Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen.

BACKGROUND: The exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials. METHODS/PRINCIPAL FINDINGS: We conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d'Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline. CONCLUSIONS/SIGNIFICANCE: No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen. TRIAL REGISTRATION: NCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.

Prevalence and determinants of anaemia among pregnant women in a high malaria transmission setting: a cross-sectional study in rural Burkina Faso.

Introduction: anemia, the commonest nutritional deficiency disorder among pregnant women in sub-Saharan Africa, is associated with severe peripartum complications. Its regular monitoring is necessary to timely inform clinical and preventive decision-making. The aim of this study was to assess the prevalence and determinants of anemia among pregnant women in rural areas of Burkina Faso. Methods: between August 2019 and March 2020, a cross-sectional study was conducted to collect maternal sociodemographic, gynaeco-obstetric, and medical characteristics by face-to-face interview or by review of antenatal care books. In addition, maternal malaria was diagnosed by standard microscopy and the hemoglobin levels (Hb) measured by spectrophotometry. The proportion of anaemia (Hb<11.0 g/dL), moderate (7.0

Factors affecting African postdoctoral researcher capacity development within 'learn-by-doing' international research partnerships: findings from the 'Partnership for Increasing the Impact of Vector Control (PIIVeC)'.

INTRODUCTION: The Partnership to Increase the Impact of Vector Control sought to develop the research and leadership capacity of 10 African postdoctoral vectorborne disease scientists via a 'learn-by-doing' approach. We identified factors that either supported or hindered their development and, drawing on this information, determined key lessons for future programmes with similar objectives. METHODS: A longitudinal qualitative study encompassing focus group discussions and semistructured interviews conducted with the cohort of African postdoctoral fellows, programme leadership, supervisory and research support staff (N=28). Data analysis was informed by a general inductive approach. RESULTS: Numerous supportive and hindering factors were identified. Supportive factors were primarily structural or attitudinal in nature, whereas hindering factors were primarily operational or contextual. None of the supporting or hindering factors were specific to vectorborne disease research. Four key lessons for future programme implementation emerged, including: the value in exposing postdoctoral fellows to a diverse work-mix and training-mix to improve understanding of the broad skillset needed for scientific career advancement; recognising and managing the potentially competing interests of different partnership members to ensure everyone benefits from participation; ensuring equity of opportunity and rewarding engagement; and ensuring flexibility in support provision. CONCLUSION: Our study highlights numerous factors that may be readily incorporated into early career researcher capacity strengthening initiatives based on a learn-by-doing approach. Many of these factors are supported by a growing weight of evidence and would be appropriate to research capacity strengthening programmes both within and outside of a vectorborne disease context.

Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso.

In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.

Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis.

In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.

Correction: Performance of PfHRP2­RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso.

[This corrects the article DOI: 10.1007/s12639-023-01566-x.].

Performance of PfHRP2-RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso.

In this study, we evaluated the performance of a P. falciparum Histidine Rich Protein 2 (PfHRP2)-based rapid diagnostic test (RDT) used for malaria case detection (SD-Bioline malaria RDT P.f®) along with light microscopy (LM) against qPCR among children during the first year of life in a high and seasonal malaria transmission area in Burkina Faso. A total of 723 suspected malaria cases (including multiple episodes) that occurred among 414 children participating in a birth-cohort study were included in the present analysis. Factors including age at the time of malaria screening, transmission season and parasite densities were investigated for their potential influence in the performance of the RDT. Clinical malaria cases as detected by RDT, LM and qPCR were 63.8%, 41.5% and 49.8%, respectively. Compared with qPCR, RDT had a false-positive results rate of 26.7%, resulting in an overall accuracy of 79.9% with a sensitivity of 93%, a specificity of 66.1%, a Positive Predictive Value of 73.3% and a Negative Predictive Value of 91.6%. Its specificity differed significantly between high and low transmission seasons (53.7% vs 79.8%; P < 0.001) and decreased with increasing age (80.6-62%; P for trend = 0.024). The overall accuracy of LM was 91.1% and its performance was not significantly influenced by transmission season or age. These findings highlight the need to adapt malaria diagnostic tools recommendations to face the challenge of adequate malaria detection in this population group living in high burden and seasonal malaria transmission settings.

Creating a best practice template for participant communication plans in global health clinical studies.

BACKGROUND: Clinical trial participants have a right to be informed throughout the entire process of human subject research. As part of this pillar of research ethics, participants and other stakeholders should be made aware of research findings after a trial has been completed. Though participants have both a right, and a desire to be informed of research outcomes, studies show that they rarely receive communication about study findings. Our aim was (1) to understand what, if any, role communication plans play in current global health clinical research protocols and (2) to use our findings to develop a communication plan template tailored to clinical research carried out in low-and-middle-income countries (LMIC) while minimizing colonial assumptions. While the template was drafted in the LMIC context, the principles are universally applicable and should be considered best practices for all global health clinical trials. METHODS: We carried out a mixed-method study over a period of 6 months to understand the role of communication with study participants and other stakeholders in clinical trials. The semiquantitative analysis included mining publicly available clinical trial protocols for communication-related language. Qualitative interviews (n = 7) were used to gather knowledge and insight from clinical trial experts to inform the development of a communication plan template. RESULTS: None of the 48 mined clinical trial protocols included a communication plan. Of the 48, 21% (n = 21) protocols included communication-related language, and 10% (n = 5) described plans to share trial results with participants. CONCLUSION: The use of communication plans in global health clinical trials is lacking. To our knowledge, this is the first in-depth analysis of communication plans in clinical trials to date. We recommend that researchers utilize the developed communication plan template throughout the entire research process to ensure a human-centered approach to participant communication. This communication plan should apply to all phases of a research trial, with a particular emphasis on plans to share results in an accessible and engaging manner once the trial has been completed.

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.

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.

Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients.

BACKGROUND: Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes. METHODS: The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total, n=109) collected before treatment and at 12 h intervals after treatment. As a secondary objective, we investigated factors that may influence the effect of treatment on sexual conversion rates. FINDINGS: In the majority of infections from the African cohorts, but not from Vietnam, we observed increased expression of pfap2-g and other SRBs after treatment. Estimated parasite age at the time of treatment was negatively correlated with the increase in pfap2-g transcript levels, suggesting that younger parasites are less susceptible to stimulation of sexual conversion. INTERPRETATION: We observed enhanced expression of SRBs after ART-based treatment in many patients, which suggests that in natural malaria infections sexual conversion rates can be altered by treatment. ART-based treatment reduces the potential of a treated individual to transmit the disease, but we hypothesise that under some circumstances this reduction may be attenuated by ART-enhanced sexual conversion. FUNDING: Spanish Agencia Estatal de Investigación (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobalHealth-Erasmus Mundus (European Union).

Prevalence and risk factors of malaria among first antenatal care attendees in rural Burkina Faso.

BACKGROUND: The WHO recommends continuous surveillance of malaria in endemic countries to identify areas and populations most in need for targeted interventions. The aim of this study was to assess the prevalence of malaria and its associated factors among first antenatal care (ANC) attendees in rural Burkina Faso. METHODS: A cross-sectional survey was conducted between August 2019 and September 2020 at the Yako health district and included 1067 first ANC attendees. Sociodemographic, gyneco-obstetric, and medical characteristics were collected. Malaria was diagnosed by standard microscopy and hemoglobin level was measured by spectrophotometry. A multivariate logistic regression analysis was used to identify factors associated with malaria infection. RESULTS: Overall malaria infection prevalence was 16.1% (167/1039). Among malaria-positive women, the geometric mean parasite density was 1204 [95% confidence interval (CI) 934-1552] parasites/µL and the proportion of very low (1-199 parasites/µL), low (200-999 parasites/µL), medium (1000-9999 parasites/µL) and high (≥ 10,000 parasites/µL) parasite densities were 15.0%, 35.3%, 38.3% and 11.4%, respectively. Age < 20 years (adjusted odds ratio (aOR): 2.2; 95% CI 1.4-3.5), anemia (hemoglobin < 11 g/deciliter) (aOR: 3.4; 95% CI 2.2-5.5), the non-use of bed net (aOR: 1.8; 95% CI 1.1-2.8), and the absence of intermittent preventive treatment with sulfadoxine-pyrimethamine (aOR: 5.8; 95% CI 2.1-24.5) were positively associated with malaria infection. CONCLUSIONS: The study showed that one out of six pregnant women had a microscopy-detected P. falciparum malaria infection at their first ANC visit. Strengthening malaria prevention strategies during the first ANC visit is needed to prevent unfavorable birth outcomes.

Prospective observational study to evaluate the clinical and biological safety profile of pyronaridine-artesunate in a rural health district in Burkina Faso.

The assessment in real-life conditions of the safety and efficacy of new antimalarial drugs is of greatest interest. This study aimed to monitor and evaluate both clinical and biological safety of pyronaridine-artesunate (PA) in real-life conditions in Burkina Faso's health system. This was a single-arm, open-label study, where patients attending Nanoro health facilities with uncomplicated malaria were consented to be part of a cohort event monitoring (CEM). At inclusion (day-0), PA was administered orally once a day for 3 days. Patients spontaneous reported any clinical adverse events (AEs) occurring within 28 days following the treatment. Additionally, the study focused on AEs of special interest (AESI), namely clinical signs related to hepatotoxicity and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). A nested subset of patients with blood sample collection at day-0 and day-7 were monitored to investigate the effect of PA on biochemistry parameters. From September 2017 to October 2018, 2786 patients were treated with PA. About 97.8% (2720/2786) of patients did not report any AE. The most commonly reported events were respiratory, thoracic, and mediastinal disorders (8.3 per 1000), infections and infestations (7.9 per 1000), and gastrointestinal disorders (7.2 per 1000). No clinical or biological hepatotoxicity event related to PA was reported during the follow-up. Changes in biochemistry parameters remained within laboratory reference ranges. The study showed that PA is a well-tolerated drug and should be considered as a good option by malaria control programs in countries where existing first-line antimalarial drugs are continuously threatened by the emergence of drug resistance.

Assessment of Recovery Time, Worsening, and Death among Inpatients and Outpatients with COVID-19, Treated with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso.

OBJECTIVES: Our study aimed to assess the statistical relationship between the use of chloroquine phosphate or hydroxychloroquine plus azithromycin (CQ/HCQ + AZ) and virological recovery, disease worsening, and death among out- and inpatients with COVID-19 in Burkina Faso. METHODS AND DESIGNS: This was a retrospective observational study that compared outcomes in terms of time to recovery, worsening, and death in patients who received CQ/HCQ + AZ and those who did not using a multivariable Cox or Poisson model before and after propensity matching. RESULTS: Of the 863 patients included in the study, about 50% (432/863) were home-based follow-up patients and 50% were inpatients. Of these, 83.3% (746/863) received at least 1 dose of CQ/HCQ + AZ and 13.7% (118/863) did not. There were no significant differences in associated time to recovery for patients receiving any CQ/HCQ + AZ (adjusted HR 1.44; 95% CI 0.76-2.71). Similarly, there was no significant association between CQ/HCQ + AZ use and worsening (adjusted IRR 0.80; 95% CI 0.50-1.50). However, compared with the untreated group, the treated group had a lower risk of death (adjusted HR 0.20; 95% CI 0.10-0.44). CONCLUSIONS: The study provided valuable additional information on the use of CQ/HCQ in patients with COVID-19 and did not show any harmful outcomes of CQ/HCQ + AZ treatment.

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.

Low birth weight and its associated risk factors in a rural health district of Burkina Faso: a cross sectional study.

BACKGROUND: Low birth weight (LBW) is a major factor of neonate mortality that particularly affects developing countries. However, the scarcity of data to support decision making to reduce LBW occurrence is a major obstacle in sub-Saharan Africa. The aim of this research was to determine the prevalence and associated factors of LBW at the Yako health district in a rural area of Burkina Faso. METHODS: A cross sectional survey was conducted at four peripheral health centers among mothers and their newly delivered babies. The mothers' socio-demographic and obstetrical characteristics were collected by face-to-face interview or by review of antenatal care books. Maternal malaria was tested by standard microscopy and neonates' birth weights were documented. Multivariate logistic regression was used to determine factors associated with LBW. A p-value < 0.05 was considered statistically significant. RESULTS: Of 600 neonates examined, the prevalence of low birth weight was 11.0%. Adjustment for socio-demographic characteristic, medical conditions, obstetrical history, malaria prevention measures by multivariate logistic regression found that being a primigravid mother (aOR = 1.8, [95% CI: 1.1-3.0]), the presence of malaria infection (aOR = 1.9, [95% CI: 1.1-3.5]), the uptake of less than three doses of sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy (IPTp-SP) (aOR = 2.2, [95% CI: 1.3-3.9]), the presence of maternal fever at the time of delivery (aOR = 2.8, [95% CI: 1.5-5.3]) and being a female neonate (aOR = 1.9, [95% CI: 1.1-3.3]) were independently associated with an increased risk of LBW occurrence. The number of antenatal visits performed by the mother during her pregnancy did not provide any direct protection for low birth weight. CONCLUSION: The prevalence of LBW remained high in the study area. Maternal malaria, fever and low uptake of sulfadoxine-pyrimethamine doses were significantly associated with LBW and should be adequately addressed by public health interventions.

Safety of Chloroquine or Hydroxychloroquine Plus Azithromycin for the Treatment of COVID-19 Patients in Burkina Faso: An Observational Prospective Cohort Study.

INTRODUCTION: Though chloroquine derivatives are used in the treatment of coronavirus disease 2019 (COVID-19) in many countries worldwide, doubts remain about the safety and efficacy of these drugs, especially in African communities where published data are scarce. METHODS: We conducted an observational prospective cohort study from April 24 to September 03, 2020, in Burkina Faso to assess (as primary outcome) the clinical, biological, and cardiac (electrocardiographic) safety of chloroquine or hydroxychloroquine plus azithromycin administered to COVID-19 patients. The main secondary outcomes were all-cause mortality and median time of viral clearance. RESULTS: A total of 153 patients were enrolled and followed for 21 days. Among patients who took at least one dose of chloroquine or hydroxychloroquine (90.1% [138/153]), few clinical adverse events were reported and were mainly rash/pruritus, diarrhea, chest pain, and palpitations. No statistically significant increase in hepatic, renal, and hematological parameters or electrolyte disorders were reported. However, there was a significant increase in the QTc value without exceeding 500ms, especially in those who received chloroquine phosphate. Three adverse events of special interest classified as serious (known from chloroquine derivatives) were recorded namely pruritus, paresthesia, and drowsiness. One case of death occurred. The average onset of SARS-CoV-2 PCR negativity was estimated at 7.0 (95% CI: 5.0-10.0) days. CONCLUSION: Hydroxychloroquine appeared to be well tolerated in treated COVID-19 patients in Burkina Faso. In the absence of a robust methodological approach that could generate a high level of scientific evidence, our results could at least contribute to guide health decisions that should be made based on different sources of scientific evidence including those from our study.

Malaria and curable sexually transmitted and reproductive tract coinfection among pregnant women in rural Burkina Faso.

BACKGROUND: Malaria and sexually transmitted/reproductive tract infections (STI/RTI) are leading and preventable causes of low birthweight in sub-Saharan Africa. Reducing their impact on pregnancy outcomes requires efficient interventions that can be easily integrated into the antenatal care package. The paucity of data on malaria and STI/RTI coinfection, however, limits efforts to control these infections. This study aimed to determine the prevalence and associated factors of malaria and STI/RTI coinfection among pregnant women in rural Burkina Faso. METHODS: A cross-sectional survey was conducted among 402 pregnant women attending antenatal clinics at the Yako health district. Sociodemographic and behavioral data were collected, and pregnant women were tested for peripheral malaria by microscopy. Hemoglobin levels were also measured by spectrophotometry and curable bacterial STI/RTI were tested on cervico-vaginal swabs using rapid diagnostic test for chlamydia and syphilis, and Gram staining for bacterial vaginosis. A multivariate logistic regression model was used to assess the association of malaria and STI/RTI coinfection with the characteristics of included pregnant women. RESULTS: The prevalence of malaria and at least one STI/RTI coinfection was 12.9% (95% confidence interval, CI: [9.8-16.7]), malaria and bacterial vaginosis coinfection was 12.2% (95% CI: [9.3-15.9]), malaria and chlamydial coinfection was 1.6% (95% CI: [0.6-3.8]). No coinfection was reported for malaria and syphilis. The individual prevalence was 17.2%, 7.2%, 0.6%, 67.7% and 73.3%, respectively, for malaria infection, chlamydia, syphilis, bacterial vaginosis and STI/RTI combination. Only 10% of coinfections were symptomatic, and thus, 90% of women with coinfection would have been missed by the symptoms-based diagnostic approach. In the multivariate analysis, the first pregnancy (aOR = 2.4 [95% CI: 1.2-4.7]) was the only factor significantly associated with malaria and STI/RTI coinfection. Clinical symptoms were not associated with malaria and STI/RTI coinfection. CONCLUSION: The prevalence of malaria and curable STI/RTI coinfection was high among pregnant women. The poor performance of the clinical symptoms to predict coinfection suggests that alternative interventions are needed.

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.