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Antiseptics, disinfectants, and hand hygiene products can act as reservoirs of Gram-negative bacteria causing healthcare-associated infections. This problem is rarely documented in low- and middle-income countries, particularly in sub-Saharan Africa. In a cross-sectional survey, we assessed the bacterial contamination of antiseptics, disinfectants, and hand hygiene products in two university hospitals in Burkina Faso and Benin. During ward visits and staff interviews, in-use products were cultured for the presence of Gram-negative bacteria. The growth of Gram-negative bacteria was absent or rare in alcohol-based products, povidone iodine, and Dakin solution. Contamination was highest (73.9% (51/69)) for liquid soap products (versus antiseptic/disinfectants (4.5%, 7/157) (p < 0.0001)), mostly used in high-risk areas and associated with high total bacterial counts (>10,000 colony-forming units/mL). Contaminating flora (105 isolates) included Enterobacterales and the Vibrio non-cholerae/Aeromonas group (17.1%) and non-fermentative Gram-negative rods (82.8%). Multidrug resistance was present among 9/16 Enterobacterales (Klebsiella and Enterobacter spp.) and 3/12 Acinetobacter spp., including carbapenem resistance (Acinetobacter baumannii: NDM, Pseudomonas stutzeri: VIM). The risk factors for contamination included the type of product (cleaning grade and in-house prepared liquid soap), use of recycled disposable containers and soft drink bottles, absence of labeling, topping-up of containers, dilution with tap water (pharmacy and ward), and poor-quality management (procurement, stock management, expiry dates, and period after opening).

Background Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. Methods For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. Findings We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49–1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47–1·17), stillbirth (aHR=0·71, 0·32–1·57), and major congenital anomalies (aHR=0·60, 0·13–2·87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92). Interpretation We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. Funding Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Background: The immunological shift occurring in pregnant women is crucial for the outcome of pregnancy. We conducted a study in pregnant women living in a malaria endemic area to determine the potential effect of gestational age on modulating the immune system by cortisol and prolactin production. Methods: Primigravidae and multigravidae with a gestational age between 16-20 weeks were included in the study and followed up to delivery and 6-7 weeks thereafter. Venous blood was collected at scheduled visit: Visit1 (V1; 16-20 weeks of amenorrhea), Visit2 (V2; 28 ±1 weeks of pregnancy), Visit3 (V3; 32 ±1 weeks of pregnancy), Visit4 (V4; delivery) and Visit5 (V5; 6-7 weeks after delivery). In addition, a cord blood sample was also collected at delivery. Nulliparous and primiparous/multiparous non-pregnant women were enrolled in the control group. Cortisol and prolactin plasma concentrations were measured using ichroma II and i-chamber apparatus. Light microscopy was used to detect Plasmodium falciparum infections. A linear mixed-effects regression (LMER) model was used to assess the association between the variation of cortisol titters and prolactin levels during the pregnancy and the post-partum. Results: Results showed that cortisol and prolactin levels in the peripheral blood were up-regulated during pregnancy. Concentrations of cortisol during follow-up was significantly higher in primigravidae than in multigravidae during the whole pregnancy (pConclusion: These results showed that the potential effects of cortisol and prolactin are related to gestational age. This could affect the susceptibility of pregnant women to infectious diseases such as malaria in endemic areas.

Background Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC-β-lactamase and carbapenemase producing Escherichia coli and Klebsiella pneumoniae have spread into environment worldwide posing a possible public health threat. However, the prevalence data in low- and middle-income countries are still scarce. The aim of this study was to assess the occurrence of ESBL, AmpC-β-lactamase and carbapenemase producing and multidrug-resistant E. coli and K. pneumoniae in wastewater collected from healthcare centers in Burkina Faso. Methodology Eighty-four (84) wastewater samples were collected from 5 healthcare centers and bacterial counts on ESBL ChromAgar were performed. E. coli and K. pneumoniae isolates were identified using API20E. ESBL production was confirmed using the double disc synergy test (DDST). AmpC-β-lactamase detection was performed on Muller Hinton (MH) agar supplemented with cloxacillin (4µg/l). Carbapenemase testing was carried out using O.K.N.V.I. RESIST-5 immunochromatography test. Result E. coli and/ or K. pneumoniae strains were isolated from 82 wastewater samples (97.6%). In total, 170 strains were isolated, E. coli more commonly (64%). Average concentrations of ESBL producing bacteria per hospital varied from 1.10x105 to 5.23x106 CFU/ml. Out of 170 presumptive ESBL producing isolates and 51 presumptive AmpC-β-lactamase producing isolates, 95% and 45% were confirmed, respectively. Carbapenemase production was detected in 10 isolates, 6 were NDM producers, 3 were OXA-48 producers and 1 was NDM and OXA-48 producer. All isolates were multidrug resistant and, furthermore, all of them were resistant to all β-lactams tested. Also, resistance to ESBL inhibitors was common, up to 66% E. coli and 62% in K. pneumoniae. Amikacin, fosfomycin and nitrofurantoin were the antibiotics for which least resistance was detected. Conclusion This study showed that wastewater from healthcare centers constitutes a reservoir of multidrug-resistant bacteria in Burkina Faso, including those capable of producing carbapenemases, which may disseminate into environment and further back to humans. Therefore, following the microbiological quality of the wastewaters released from healthcare centers is important to include in the future national AMR surveillance program.

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.

Background A trial in African children showed that combining seasonal vaccination with the RTS,S/AS01E vaccine with seasonal malaria chemoprevention reduced the incidence of uncomplicated and severe malaria compared with either intervention given alone. Here, we report on the anti-circumsporozoite antibody response to seasonal RTS,S/AS01E vaccination in children in this trial. Methods Sera from a randomly selected subset of children collected before and 1 month after 3 priming doses of RTS,S/AS01E and before and 1 month after 2 seasonal booster doses were tested for anti-circumsporozoite antibodies using enzyme-linked immunosorbent assay. The association between post-vaccination antibody titer and incidence of malaria was explored. Results A strong anti-circumsporozoite antibody response to 3 priming doses of RTS,S/AS01E was seen (geometric mean titer, 368.9 enzyme-linked immunosorbent assay units/mL), but titers fell prior to the first booster dose. A strong antibody response to an annual, pre-malaria transmission season booster dose was observed, but this was lower than after the primary vaccination series and lower after the second than after the first booster dose (ratio of geometric mean rise, 0.66; 95% confidence interval [CI], .57–.77). Children whose antibody response was in the upper tercile post-vaccination had a lower incidence of malaria during the following year than children in the lowest tercile (hazard ratio, 0.43; 95% CI, .28–.66). Conclusions Seasonal vaccination with RTS,S/AS01E induced a strong booster antibody response that was lower after the second than after the first booster dose. The diminished antibody response to the second booster dose was not associated with diminished efficacy. Clinical Trials Registration NCT03143218.

Background Malaria in pregnancy remains a major health threat in sub-Saharan Africa to both expectant mothers and their unborn children. To date, there have been very few studies focused on the out of pocket costs associated with seeking treatment for malaria during pregnancy. Methods A cross-sectional survey was undertaken in Burkina Faso and The Gambia to estimate the direct and indirect costs associated with outpatient consultations (OP) and inpatient admissions (IP). Direct costs were broken down into medical (admission fees, drug charges, and laboratory fees), and non-medical (transportation and food). Indirect costs reflected time lost due to illness. In total, 220 pregnant women in Burkina Faso and 263 in The Gambia were interviewed about their treatment seeking decisions, expenditure, time use and financial support associated with each malaria episode. Results In Burkina Faso 6.7% sought treatment elsewhere before their OP visits, and 27.1% before their IP visits. This compares to 1.3% for OP and 25.92% for IP in The Gambia. Once at the facility, the average direct costs (out of pocket) were 3.91US$ for an OP visit and 15.38US$ of an IP visit in Burkina Faso, and 0.80US$ for an OP visit and 9.19US$ for an IP visit in The Gambia. Inpatient direct costs were driven by drug costs (9.27US$) and transportation costs (2.72US$) in Burkina Faso and drug costs (3.44 US$) and food costs (3.44 US$) in The Gambia. Indirect costs of IP visits, valued as the opportunity cost of time lost due to the illness, were estimated at 11.85US$ in Burkina Faso and 4.07US$ in The Gambia. The difference across the two countries was mainly due to the longer time of hospitalization in Burkina Faso compared to The Gambia. In The Gambia, the vast majority of pregnant women reported receiving financial support from family members living abroad, most commonly siblings (65%). Conclusions High malaria treatment costs are incurred by pregnant women in Burkina Faso and The Gambia. Beyond the medical costs of fees and drugs, costs in terms of transport, food and time are significant drivers. The role of remittances, particularly their effect on accessing health care, needs further investigation.

Infectious diseases, including skin infections, have always been treated by plants and other natural products since ancient times. This study investigated the antimicrobial activity of nine medicinal plant species from Gonse Forest and Bangreweogo Park, Burkina Faso on seven microbial strains involved in skin infections. Sixty-eight organic and aqueous extracts from leaves, stem and root barks of the nine plants were tested on five bacterial and two fungal American Type Culture Collection (ATCC) strains using the disk diffusion and microdilution methods. Twenty-eight extracts (41.17%) from eight of the plants differently inhibited bacteria and fungi, the exception being Wissadula amplissima specie. Gram-positive Cocci (GPC) were the most sensitive to the extracts. Eleven extracts had a Minimum Inhibitory Concentration (MIC) lower than 1 mg/ml (MIC < 1 mg/ml). The extracts of Opilia celtidifolia gave the largest zones of inhibition ranging from 21.67 to 24.33 mm at 100 to 300 mg/ml on GPC and Candida albicans. Its MIC varied from 0.03 to 0.06 mg/ml on Streptococcus pyogenes, and from 0.07 to 0.24 mg/ml on Streptococcus agalactiae. Ethanolic extracts (80 and 96%) of Lawsonia inermis had MIC ranging from 0.29 to 9.37 mg/ml on the sensitive strains. The variable inhibitory activity displayed by the plants confirmed in part their traditional use in the treatment of some bacterial and fungal skin infections. Key words: Infectious diseases, inhibitory activity, plant extracts, minimal bactericidal concentration (MBC), minimum inhibitory concentration (MIC), skin infections.

Toussaint Rouamba,1,&ast; Houreratou Barry,2,&ast; Esperance Ouédraogo,1 Marc Christian Tahita,1 Nobila Valentin Yaméogo,3 Armel Poda,4 Arnaud Eric Diendéré,5 Abdoul-Salam Ouedraogo,4 Innocent Valea,1 Amariane M Koné,2 Cherileila Thiombiano,2 Isidore Traoré,2 Zekiba Tarnagda,1 Serge A Sawadogo,6 Zakaria Gansané,7 Yibar Kambiré,8 Idrissa Sanou,8 Fatou Barro-Traoré,8 Maxime K Drabo,1 Halidou Tinto1 On behalf of the CHLORAZ Study Group1Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso; 2Institut National de Santé Publique, Centre Muraz, Bobo-Dioulasso, Burkina Faso; 3Centre Hospitalier Universitaire Yalgado Ouédraogo, Ouagadougou, Burkina Faso; 4Centre Hospitalier Universitaire Sourou Sanon, Bobo-Dioulasso, Burkina Faso; 5Centre Hospitalier Universitaire de Bogodogo, Ouagadougou, Burkina Faso; 6Centre PrïmO Nelson Mandela (Promotion de la Recherche et de l’Innovation en Immunologie Médicale de Ouagadougou), Ouagadougou, Burkina Faso; 7Clinical Monitoring in Africa-Clinical Research Organization, Ouagadougou, Burkina Faso; 8Centre Hospitalier Universitaire de Tengandogo, Ouagadougou, Burkina Faso&ast;These authors contributed equally to this workCorrespondence: Toussaint RouambaInstitut de Recherche en Sciences de la Santé (CNRST-IRSS), 528, Avenue Kumda-Yoore, BP 218 Ouagadougou CMS 11, Ouagadougou, Nanoro, Burkina FasoTel +226 666 532 04Email rouambatoussaint@gmail.comIntroduction: 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.Keywords: SARS-CoV-2, chloroquine, hydroxychloroquine, azithromycin, safety, virus shedding

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

Objective:To explore the relationships between dental problems and underweight status among rural women in Burkina Faso by using nationally representative data.Design:This was a cross-sectional secondary study of primary data obtained by the 2013 WHO Stepwise Approach to Surveillance survey conducted in Burkina Faso. Descriptive and analytical analyses were performed using Student’s t test, ANOVA, the χ2 test, Fisher’s exact test and logistic regression.Setting:All thirteen Burkinabè regions were categorised using quartiles of urbanisation rates.Participants:The participants were 1730 rural women aged 25–64 years.Results:The prevalence of underweight was 16·0 %, and 24·1 % of participants experienced dental problems during the 12-month period. The women with dental problems were more frequently underweight (19·9 % and 14·7 %; P < 0·05) and had a lower mean BMI (21·1 ± 3·2 and 21·6 ± 3·7 kg/m2, P < 0·01) than those without dental problems. More risk factors for underweight were observed in less urbanised regions among elderly individuals (> 49 years old) and smokeless tobacco users. Age > 49 years, professions with inconsistent income, a lack of education, smokeless tobacco use and low BMI were factors that were significantly associated with dental problems, while residency in a low-urbanisation area was a protective factor.Conclusion:The prevalence of underweight in rural Burkinabè women is among the highest in sub-Saharan Africa, and women with dental problems are more frequently affected than those without dental problems. Public health measures for the prevention of these disorders should specifically target women aged over 49 years and smokeless tobacco users.

OBJECTIVES: Antibiotics efficacy is severely threatened due to emerging resistance worldwide, but there is a paucity of antibiotics efficacy data for the West African region in general. Therefore, this study aimed to determine the antibiotic susceptibility profile of bacterial isolated from febrile children under 5 years of age in Nanoro (Burkina Faso). METHODS: Blood, stool and urine samples were collected from 1099 febrile children attending peripheral health facilities and the referral hospital in Nanoro Health district. Bacterial isolates from these samples were assessed for their susceptibility against commonly used antibiotics by Kirby-Bauer method. RESULTS: In total, 141 bacterial isolates were recovered from 127 febrile children of which 65 from blood, 65 from stool and 11 from urine. Salmonella isolates were most frequently isolated and found to be highly resistant to ampicillin (70%; 56/80) and trimethoprim-sulphamethoxazole (65%; 52/80). Escherichia coli isolates showed a high resistance rate to trimethoprim-sulphamethoxazole (100%), ampicillin (100%), ciprofloxacin (71.4%; 10/14), amoxicillin-clavulanate (64.3%; 9/14), ceftriaxone (64.3%; 9/14) and gentamycin (50%; 7/14). Moreover, half of the E. coli isolates produced ß-lactamase suggesting multi-drug resistance against β-lactam as well as non-β-lactam antibiotics. Multi-drug resistance was observed in 54.6% (59/108) of the isolates, mainly Gram-negative bacteria. CONCLUSIONS: This study showed high resistance rates to common antibiotics used to treat bacterial infections in Nanoro. The work prompts the need to expand antibiotic resistance surveillance studies in Burkina Faso. ispartof: TROPICAL MEDICINE & INTERNATIONAL HEALTH vol:26 issue:10 pages:1220-1230 ispartof: location:England status: published

(1) Background: Malaria control has strongly benefited from the implementation of rapid diagnostic tests (RDTs). The malaria RDTs used in Burkina Faso, as per the recommendation of the National Malaria Control Program, are based on the detection of histidine-rich protein-2 (

International audience; OBJECTIVES: The overall death toll from COVID-19 in Africa is reported to be low but there is little individual-level evidence on the severity of the disease. This study examined the clinical spectrum and outcome of patients monitored in COVID-19 care centres (CCCs) in two West-African countries. METHODS: Burkina Faso and Guinea set up referral CCCs to hospitalise all symptomatic SARS-CoV-2 carriers, regardless of the severity of their symptoms. Data collected from hospitalised patients by November 2020 are presented. RESULT: A total of 1,805 patients (64% men, median age 41 years) were admitted with COVID-19. Symptoms lasted for a median of 7 days (IQR 4-11). During hospitalisation, 443 (25%) had a SpO2 < 94% at least once, 237 (13%) received oxygen and 266 (15%) took corticosteroids. Mortality was 5% overall, and 1%, 5% and 14% in patients aged

• Background: In Sub-Saharan Africa (SSA), febrile illnesses remain a major public health problem in children. However, the persistence of hrp2 antigen and the low sensitivity of pLDH RDT negatively affect antimalarials and antibiotics prescription practices. These limitations lead to poor management of febrile diseases and antimicrobial resistance (AMR). To improve the diagnosis of these febrile diseases and subsequent prescription of antimicrobials, it is hypothesized that the implementation of an algorithm including a two-step malaria RDT PfHRP2/pLDH supported by point-of-care (PoC) tests for bacterial infections could significantly improve the management of febrile diseases and thereby tackling AMR.• Methods: To assess the value of the proposed algorithm, an open-label randomized controlled trial with three arms, enrolling febrile children from 6 to 59 months is proposed.- In the control arm, febrile children will be managed according to the Integrated Management of Childhood Illnesses (IMCI), which is part of the standard of care in Burkina Faso. Treatment will be done according to national guidelines.- In RDTs decisional algorithm (RDT-DA) arm (intervention), the clinical examination based on IMIC will be supported by a two-step malaria RDT and bacterial infections RDTs. Prescription will be left to the discretion of the healthcare workers based on clinical examination and PoC test results- In e-algorithm arm (intervention), artificial intelligence integrating multiple layers of clinical information such as clinical examination, signs/symptoms and medical history, and biological information such as biomarkers (CRP and WBC) and pathogen specific PoC tests, and oximetry will be developed. The e-algorithm will serve to guide the diagnostic and management of febrile infections in children.In the 3 arms, the case report forms will be digitalized. A final follow-up visit (day 7) will be scheduled for all participants. Patients will be asked to come back to the health facilities before the scheduled visit if the symptoms persist or in case of health condition worsening.• Discussion: If successful, this study could contribute to improve the management of febrile diseases and reduce inappropriate use of antimicrobials. • Trial registration: The trial is registered at ClinicalTrial.gov, NCT05285657. Enrolment started on 4th March 2022 with long term outcome being assessed completely by 2023

Background Intermittent Preventive Treatment in pregnancy (IPTp) with Sulfadoxine-Pyrimethamine (SP) is an important malaria control strategy in sub-Saharan Africa. Indeed it overcomes the risk of misdiagnosis due to low peripheral parasitemia during pregnancy by treating women with SP on predetermined schedules. However, over time, the spread of Plasmodium resistant strains has threaten this strategy in many countries. As an alternative, the Intermittent Screening and Treatment for pregnancy (ISTp) aims at a monthly screening of pregnant women, preferably by using very sensitive tests such as ultrasensitive rapid diagnostic tests (us-RDT) and the treatment of positive cases with artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. Unlike IPTp-SP, ISTp prevents overuse of antimalarials limiting the drug pressure on parasites, an advantage which can be potentiated by using an ACT like Pyronaridine - Artesunate (Pyramax®) that is not yet used in pregnant women in the field. Methods This study aims to compare the non-inferiority of ISTp using us-RDTs and Pyramax® versus IPTp-SP on malaria in pregnancy through a randomized clinical trial performed in Kisenso, Kinshasa, the Democratic Republic of the Congo, a malaria perennial transmission area. Discussion The results will be essential for the National Malaria Control Program to update malaria prevention policy in pregnant women in the Democratic Republic of the Congo. Trial registration: ClinicalTrials.gov ID: NCT04783051

Malaria in endemic countries is often asymptomatic during pregnancy, but it has substantial consequences for both the mother and her unborn baby. During pregnancy, anaemia is an important consequence of malaria infection. In Burkina Faso, the intensity of malaria varies according to the season, albeit the prevalence of malaria and anaemia as well as their risk factors, during high and low malaria transmission seasons is underexplored at the household level., info:eu-repo/semantics/published

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

Maternal and newborn infections are a major contributor to mortality and morbidity globally. Lost-cost, effective and safe interventions are needed to address these. Based on promising findings, azithromycin has been identified as potentially effective antibiotic to reduce maternal and newborn infections in low- and middle-income countries (LMICs). However, robust randomized clinical trials in a range of settings are needed to confirm these findings as well as to understand the implications for antimicrobial resistance. To better understand the impact of azithromycin on maternal and newborn health, at least three clinical trials are being conducted to evaluate azithromycin in LMICs. We describe these trials, the importance of harmonizing study measures and the potential public health impact of azithromycin in LMICs.

Background Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali. Methods Between 2014 and 2016, 30 977 children aged 3–59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year. Poisson regression with gamma-distributed random effects, accounting for the household randomization and within-individual clustering of illness episodes, was used to compare incidence of prespecified outcomes between SMC+AZ versus SMC+placebo groups in fixed time strata post-treatment. The likelihood ratio test was used to assess evidence for a time-treatment group interaction. Results Relative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration (protective efficacy (PE): 24.2% [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], respectively, in the first 2 weeks postadministration. Protection against nonmalaria fevers with a skin condition persisted up to 28 days: PE: 46.3% [35.1; 55.6%]. Conclusions The benefits of AZ-MDA are broad-ranging but short-lived. To maximize impact, timing of AZ-MDA must address the challenge of targeting asynchronous morbidity and mortality peaks from different causes., Mass administration of azithromycin (AZ-MDA) alongside seasonal malaria chemoprevention in children in Burkina Faso and Mali has broad-ranging but short-lived benefits. To maximize impact, AZ-MDA must address the challenge of targeting asynchronous peaks in morbidity and mortality from different causes.

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.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.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).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.European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR Oxford Biomedical Research Centre.For the French translation of the abstract see Supplementary Materials section.

Single nucleotide polymorphisms occurring in the Plasmodium falciparum multidrug resistant gene 1 (pfmdr1) are known to be associated with aminoquinoline resistance and, therefore, represent key P. falciparum markers for monitoring resistance both in susceptible groups (children under 5 years old and pregnant women) and in the general population. This study aimed to determine prevalence and factors associated with the carriage of pfmdr1 N86Y, Y184F and D1246Y polymorphisms among pregnant women in a setting of high malaria transmission in Burkina Faso., info:eu-repo/semantics/published

Objective:To collect context-specific insights into maternal and child health and nutrition issues, and to explore potential solutions in Nanoro, Burkina Faso.Design:Eleven focus groups with men and women from eleven communities, facilitated by local researchers.Setting:The study took place in the Nanoro Health district, in the West-Central part of Burkina Faso.Participants:Eighty-six men (18–55 years) and women by age group: 18–25; 26–34 and 35–55 years, participated in the group discussions.Results:Participants described barriers to optimal nutrition of mothers and children related to a range of community factors, with gender inequality as central. Major themes in the discussions are related to poverty and challenges generated by socially and culturally determined gender roles. Sub-themes are women lacking access to food whilst pregnant and having limited access to health care and opportunities to generate income. Although communities believe that food donations should be implemented to overcome this, they also pointed out the need for enhancing their own food production, requiring improved agricultural technologies. Given the important role that women could play in reducing malnutrition, these communities felt they needed to be empowered to do so and supported by men. They also felt that this had to be carried out in the context of an enhanced health care system.Conclusions:Findings reported here highlight the importance of nutrition-sensitive interventions and women’s empowerment in improving maternal and child nutrition. There is a need to integrate a sustainable multi-sectorial approach which goes beyond food support.

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in Streptococcus pneumoniae. The emergence of resistance to AZ has also been observed when this antibiotic was combined with the antimalarials used for seasonal malaria chemoprevention (SMC). The development of antibiotic resistance, including resistance to AZ, is sometimes associated with the emergence of a bacterial clone that belongs to a specific serotype. We hypothesize that the increase in resistance of S. pneumoniae observed after 3 years of SMC with AZ might be associated with a change in the distribution of pneumococcal serotypes. Therefore, 698 randomly selected isolates from among the 1,468 isolates of S. pneumoniae obtained during carriage studies undertaken during an SMC plus AZ trial were serotyped. A polymerase chain reaction (PCR) multiplex assay using an algorithm adapted to the detection of the pneumococcal serotypes most prevalent in African countries was used for initial serotyping, and the Quellung technique was used to complement the PCR technique when necessary. Fifty-six serotypes were detected among the 698 isolates of S. pneumoniae. A swift appearance and disappearance of many serotypes was observed, but some serotypes including 6A, 19F, 19A, 23F, and 35B were persistent. The distribution of serotypes between isolates obtained from children who had received AZ or placebo was similar. An increase in AZ resistance was seen in several serotypes following exposure to AZ. Mass drug administration with AZ led to the emergence of resistance in pneumococci of several different serotypes and did not appear to be linked to the emergence of a single serotype.

Background: Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women. Methods: We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013. Findings: Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57–14·54, p Interpretation: Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation.

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., info:eu-repo/semantics/published

RTS,S/AS01E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01E when implemented in the Expan...

Mass administration of azithromycin has reduced mortality in children in sub-Saharan Africa but its mode of action is not well characterised. A recent trial found that azithromycin given alongside seasonal malaria chemoprevention was not associated with a reduction in mortality or hospital admissions in young children. We investigated the effect of azithromycin on the nutritional status of children enrolled in this study.A total of 19 578 children in Burkina Faso and Mali were randomised to receive either azithromycin or placebo alongside seasonal malaria chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine monthly for three malaria transmission seasons (2014-2016). After each transmission season, anthropometric measurements were collected from approximately 4000 randomly selected children (2000 per country) at a cross-sectional survey and used to derive nutritional status indicators. Binary and continuous outcomes between treatment arms were compared by Poisson and linear regression.Nutritional status among children was poor in both countries with evidence of acute and chronic malnutrition (24.9-33.3% stunted, 15.8-32.0% underweight, 7.2-26.4% wasted). There was a suggestion of improvement in nutritional status in Burkina Faso and deterioration in Mali over the study period. At the end of each malaria transmission season, nutritional status of children did not differ between treatment arms (seasonal malaria chemoprevention plus azithromycin or placebo) in either the intention-to-treat or per-protocol analyses (only children with at least three cycles of SMC in the current intervention year).The addition of azithromycin to seasonal malaria chemoprevention did not result in an improvement of nutritional outcomes in children in Burkina Faso and Mali.L'administration massive d'azithromycine a réduit la mortalité infantile en Afrique subsaharienne mais son mode d'action n'est pas bien caractérisé. Un essai récent a révélé que l'azithromycine administrée parallèlement à la chimioprévention du paludisme saisonnier n'était pas associée à une réduction de la mortalité ou des hospitalisations chez les jeunes enfants. Nous avons étudié l'effet de l'azithromycine sur l'état nutritionnel des enfants inscrits à cette étude. MÉTHODES: 19.578 enfants au Burkina Faso et au Mali ont été randomisés pour recevoir soit de l'azithromycine soit un placebo parallèlement à une chimioprévention du paludisme saisonnier avec du sulfadoxine-pyriméthamine plus de l’amodiaquine par mois pendant trois saisons de transmission du paludisme (2014-2016). Après chaque saison de transmission, des mesures anthropométriques ont été recueillies auprès d'environ 4.000 enfants sélectionnés au hasard (2.000 par pays) lors d'une enquête transversale et utilisées pour dériver des indicateurs de l'état nutritionnel. Les résultats binaires et continus entre les bras de traitement ont été comparés par la régression linéaire et de Poisson. RÉSULTATS: L'état nutritionnel des enfants était médiocre dans les deux pays avec des signes de malnutrition aiguë et chronique (24,9 à 33,3% de retard de croissance, 15,8 à 32,0% d'insuffisance pondérale, 7,2 à 26,4% d'émaciation). Il a été suggéré une amélioration de l'état nutritionnel au Burkina Faso et une détérioration au Mali au cours de la période d'étude. A la fin de chaque saison de transmission du paludisme, l'état nutritionnel des enfants ne différait pas entre les bras de traitement (chimioprévention contre le paludisme saisonnier plus azithromycine ou placebo) dans les analyses en intention de traiter ou selon le protocole (seulement les enfants avec au moins trois cycles de chimioprévention dans l’année d’intervention en cours).L'ajout d'azithromycine à la chimioprévention du paludisme saisonnier n'a pas entraîné d'amélioration des résultats nutritionnels chez les enfants au Burkina Faso et au Mali.

Background: Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. Methods: In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. Results: Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). Conclusion: These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1., SCOPUS: ar.j, info:eu-repo/semantics/published

Background This paper compared the anthropometric and blood pressure features between the adults who have ever and never been screened for hypertension prior to the first WHO’ Stepwise approach to Surveillance (STEPS) survey in Burkina Faso and assessed the associated factors with the uptake of the hypertension screening. Methods This was a secondary analysis using primary data from a cross-sectional study which were obtained from the 2013 STEPS survey conducted in Burkina Faso. We included 3831 men and women aged 25–64 years. Descriptive and analytical analyses were performed using Student’s t, and chi-square tests and logistic regression models respectively. Results Before the survey, 41.6% of participants have never been screened for hypertension, and comparatively to those who have ever been screened, they had significant lower means of weight, waist circumference and body mass index and lower prevalences of overweight/obesity and abdominal obesity. The prevalence of prehypertension was similar between in the two groups (41.6% in those who have never been screened vs 39.5%; p=0.19) whereas that of hypertension was lower in those who have never been screened (17.3% vs 20.8%; p=0.007). In addition to the important socio-demographic correlates in the logistic regression, the presence of both overweight/obesity (aOR=1.3; p=0.03) and abdominal obesity (aOR=1.3; p=0.002) were significantly associated with the uptake of hypertension screening. Conclusion Prehypertension and hypertension were also frequent in adults who had never been screened for hypertension and they usually had a slim-looking build, while the overweight/obesity and abdominal obesity status may motivate for the uptake of the hypertension screening.

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.

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.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.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).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.

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum parasite. Using protein microarrays, levels of IgG to 1,000 P. falciparum antigens were measured in 2,138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase 3 trial, sampled before and at four longitudinal visits after vaccination. One month post-vaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no pre-vaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (∼11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and re-increasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site and post-vaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.

Background Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. Methods The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. Results The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X22 = 69, P 22 = 54, P 22 = 61, P X22 = 22.8, P 21 = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX22 = 330, P Conclusion This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention.

BackgroundAlthough the association between malaria and anaemia is widely studied in patient cohorts, the population-representative causal effects of malaria on anaemia remain unknown. This study estimated the malaria-induced decrease in haemoglobin levels among young children in malaria-endemic Burkina Faso.MethodsThe study was based on pooled individual-level nationally representative health survey data (2010–2011, 2014, 2017–2018) from 17 599 children under 5 years of age. This data was used to estimate the effects of malaria on haemoglobin concentration, controlling for household fixed-effects, age, and sex in a series of regression analyses. The fixed-effects controlled for observed and unobserved confounding on the household level and allowed to determine the impact of malaria infection status on haemoglobin levels and anaemia prevalence. Furthermore, the diagnostic results from microscopy and rapid diagnostic tests were leveraged to provide a quasi-longitudinal perspective of acute and prolonged effects after malaria infection.ResultsThe prevalence of both malaria (survey prevalence ranging from 17.4% to 65.2%) and anaemia (survey prevalence ranging from 74% to 88.2%) was very high in the included surveys. Malaria was estimated to significantly reduce haemoglobin levels, with an overall effect of − 7.5 g/dL (95% CI − 8.5, − 6.5). Acute malaria resulted in a − 7.7 g/dL (95% CI − 8.8, − 6.6) decrease in haemoglobin levels. Recent malaria without current parasitaemia decreased haemoglobin concentration by − 7.1 g/dL (95% CI − 8.3, − 5.9). The in-sample predicted prevalence of severe anaemia was 9.4% among malaria positives, but only 2.2% among children without malaria.ConclusionMalaria infection has a strong detrimental effect on haemoglobin levels among young children in Burkina Faso. This effect seems to carry over even after acute infection, indicating prolonged haemoglobin reductions even after successful parasite-elimination. The quasi-experimental fixed-effect approach adds a population level perspective to existing clinical evidence.

A recent trial in Burkina Faso and Mali showed that combining seasonal RTS,S/AS01In Burkina Faso and Mali 5920 children were randomized to receive either SMC alone, RTS,S/AS01In 2017, compared to SMC alone, the combined intervention reduced the prevalence of wasting by approximately 12% [prevalence ratio (PR) = 0.88 (95% CI 0.75, 1.03)], and approximately 21% in 2018 [PR = 0.79 (95% CI 0.62, 1.01)]. Point estimates were similar for comparisons with RTS,S/AS01Despite a high burden of malnutrition and malaria in the study populations, and a major reduction in the incidence of malaria in children receiving both interventions, this had only a modest impact on nutritional status. Therefore, other interventions are needed to reduce the high burden of malnutrition in these areas.https://www.clinicaltrials.gov/ct2/show/NCT03143218 , registered 8th May 2017.

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.

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.

Antibiotic resistance is one of the greatest global threats to human health, but substantial gaps in antibiotic resistance data exist in West African countries. We explored the presence of antibiotic resistance genes (ARGs) in the hospital wastewater (HWW) of nine hospitals in Benin and Burkina Faso and, for comparison, four hospitals in Finland using shotgun metagenomic sequencing. The highest sum of the relative abundance of ARGs in the 68 HWW samples was detected in Benin and the lowest in Finland. HWW resistomes and mobilomes in Benin and Burkina Faso resembled more of each other than those in Finland. Different carbapenemases were detected in varying abundances, especially in HWW from Burkina Faso and Finland. TheblaGES genes, the most widespread carbapenemase genes in the Beninese HWW, were also found in water intended for hand-washing and in a puddle at the hospital yard in Benin.mcrwere detected in the HWW of all three countries, withmcr-5being the most commonmcrgene. These and othermcrgenes were observed in very high relative abundances, even in treated wastewater in Burkina Faso and in a street gutter in Benin. The results provide evidence for public health decision-makers for the dire need to increase wastewater treatment capacity, with particular attention to HWW.ImportanceThe global emergence and increased spread of antibiotic resistance threaten the effectiveness of antibiotics and, thus, the health of the entire population. Therefore, understanding the resistomes in different geographical locations is crucial in the global fight against the antibiotic crisis. However, this information is scarce in many low- and middle-income countries (LMICs), such as those in West Africa. In this study, we describe the resistomes of hospital wastewater in Benin and Burkina Faso and, as a comparison, in Finland. Our results help to understand the hitherto unrevealed resistance in Beninese and Burkinabe hospitals. Furthermore, the results emphasize the importance of wastewater management infrastructure design to minimize exposure events between humans, HWW, and the environment, preventing the circulation of resistant bacteria and ARGs between humans (hospitals and community) and the environment.

Background Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions. Methods Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS ( Results Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P P P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2–22 μg/ml, P 2, range 4.1–6.8 mg/kg), with low BIS (P = 0.36). Median serum transferrin receptor increased during the wet season (P P Conclusions Our analysis supports preventive treatment of malaria among adolescents 15–19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated.