Impact of Intrapartum Azithromycin on the Carriage and Antibiotic Resistance of Escherichia coli and Klebsiella pneumoniae in Mothers and their Newborns: a sub-study of a Randomized Double-Blind Trial Conducted in The Gambia and Burkina Faso.

BACKGROUND: Limited data exists on effects of intrapartum azithromycin on prevalence of carriage and antibiotic resistance of Enterobacterales. METHODS: We conducted a randomized trial in Gambia and Burkina Faso where women received intrapartum azithromycin (2g) or placebo. We determined impact of treatment on prevalence of carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae by analysing rectal swabs (RS), nasopharyngeal swabs (NPS), breast milk and recto-vaginal swabs (RVS). Bacteria were isolated microbiologically; antibiotic susceptibility was confirmed with an E-test. Prevalence ratios (PR) with 95% confidence intervals (CI's) were used for comparison between arms. RESULTS: In infants, E. coli carriage in RS was lower in the intervention than placebo arm at days 6 (63.0% vs. 75.2%, PR, 0.84; CI, 0.75-0.95) and 28 (52.7% vs. 70.4%, 0.75; 0.64-0.87) post-intervention. Prevalence of azithromycin-resistant E. coli was higher in the azithromycin arm at days 6 (13.4% vs. 3.6%, 3.75; 1.83-7.69) and 28 (16.4% vs. 9.6%, 1.71; 1.05-2.79). For K. pneumoniae, carriage in RS was higher in the intervention than placebo arm at days 6 (49.6% vs. 37.2%, 1.33; 1.08-1.64) and 28 (53.6% vs. 32.9%, 1.63; 1.31-2.03). Prevalence of azithromycin-resistant K. pneumoniae was higher in the azithromycin arm at day 28 (7.3% vs. 2.1%, 3.49; 1.30-9.37). No differences were observed for other sample types. CONCLUSION: Intrapartum azithromycin decreased E. coli carriage but increased both K. pneumoniae carriage and azithromycin resistance in both bacteria. These data need to be considered together with efficacy results to balance the potential short- and long-term impact of the intervention. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov: NCT03199547.

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

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

Effect of Intrapartum Azithromycin vs Placebo on Neonatal Sepsis and Death: A Randomized Clinical Trial.

Importance: Neonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden. Objective: To evaluate the efficacy of intrapartum azithromycin to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial enrolled and followed up birthing parents and their infants at 10 health facilities in The Gambia and Burkina Faso, West Africa, between October 2017 and May 2021. Interventions: Participants were assigned at random to receive oral azithromycin (2 g) or placebo (ratio 1:1) during labor. Main Outcomes and Measures: The primary outcome was a composite of neonatal sepsis or mortality, with the former defined based on microbiologic or clinical criteria. Secondary outcomes were neonatal infections (skin, umbilical, eye and ear infections), malaria, and fever; postpartum infections (puerperal sepsis, mastitis), fever, and malaria; and use of antibiotics during 4-week follow-up. Results: The trial randomized 11 983 persons in labor (median age, 29.9 years). Overall, 225 newborns (1.9% of 11 783 live births) met the primary end point. The incidence of neonatal mortality or sepsis was similar in the azithromycin and placebo groups (2.0% [115/5889] vs 1.9% [110/5894]; risk difference [RD], 0.09 [95% CI, -0.39 to 0.57]), as was the incidence of neonatal mortality (0.8% vs 0.8%; RD, 0.04 [95% CI, -0.27 to 0.35]) and neonatal sepsis (1.3% vs 1.3%; RD, 0.02 [95% CI, -0.38 to 0.43]). Newborns in the azithromycin group compared with the placebo group had lower incidence of skin infections (0.8% vs 1.7%; RD, -0.90 [95% CI, -1.30 to -0.49]) and need for antibiotics (6.2% vs 7.8%; RD, -1.58 [95% CI, -2.49 to -0.67]). Postpartum parents in the azithromycin group had lower incidence of mastitis (0.3% vs 0.5%; RD, -0.24 [95% CI, -0.47 to -0.01]) and puerperal fever (0.1% vs 0.3%; RD, -0.19 [95% CI, -0.36 to -0.01]). Conclusions and Relevance: Azithromycin administered orally during labor did not reduce neonatal sepsis or mortality. These results do not support routine introduction of oral intrapartum azithromycin for this purpose. Trial Registration: ClinicalTrials.gov Identifier: NCT03199547.

Socioeconomic inequalities in curative healthcare-seeking for children under five before and after the free healthcare initiative in Sierra Leone: analysis of population-based survey data.

BACKGROUND: Socioeconomic inequalities between and within countries lead to disparities in the use of health services. These disparities could lead to child mortality in children under 5 years by depriving them of healthcare. Therefore, initiatives to remove healthcare fees such as the Free Healthcare Initiative (FHCI) adopted in Sierra Leone can contribute to reducing these inequities in healthcare-seeking for children. This study aimed to assess the socioeconomic inequalities in healthcare-seeking for children under 5 years of age before and after the implementation of the FHCI. METHODS: Data were included on 1207, 2815, 1633, and 1476 children under 5 years of age with fever from the 2008, 2013, 2016, and 2019 nationwide surveys, respectively. Concentration curves were drawn for the period before (2008) and after (2013-2019) the implementation of the FHCI to assess socioeconomic inequalities in healthcare-seeking. Finally, Erreyger's corrected concentration indices were calculated to understand the magnitude of these inequalities. RESULTS: Before the implementation of the FHCI, there were inequalities in healthcare-seeking for children under five (Erreyger's corrected concentration index (CI) = 0.168, standard error (SE) = 0.049; p < 0.001) in favor of the wealthy households. These inequalities decreased after the implementation of the FHCI (CI = 0.061, SE = 0.033; p = 0.06 in 2013, CI = 0.039, SE = 0.04; p = 0.32 in 2016, and CI = - 0.0005, SE = 0.362; p = 0.98 in 2019). Furthermore, before the implementation of the FHCI, a significant pro-rich inequality in the districts of Kenema (CI = 0.117, SE = 0.168, p = 0.021), Kono (CI = 0.175, SE = 0.078, p = 0.028) and Western Area Urban (CI = 0.070, SE = 0.032, p = 0.031) has been observed. After the implementation of the FHCI in 2019, these disparities were reduced, 11 of the 14 districts had a CI around the value of equality, and only in 2 districts the pro-rich inequality were significant (Western Area Urban (CI = 0.035, SE = 0.016, p = 0.039) and Western Area Rural (CI = 0.066, SE = 0.030, p = 0.027)). CONCLUSION: The results of this study demonstrated that socio-economic inequalities in healthcare-seeking for children have been considerably reduced after the FHCI in Sierra Leone. To further reduce these inequalities, policy actions can focus on the increase of availability of health services in the districts where the healthcare-seeking remained pro-rich.

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

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

Safety Profile of Drug Use During Pregnancy at Peripheral Health Centres in Burkina Faso: A Prospective Observational Cohort Study.

PURPOSE: Safety data of many drugs used during pregnancy remain scarce. This is especially true in developing countries characterised by the absence of a robust pharmacovigilance system, high prevalence of different tropical diseases affecting patients and potential for drug-drug interactions. This study aimed to assess the safety profile of drugs used in women at high risk of malaria during pregnancy and delivery in Burkina Faso's health facilities. It also aimed to assess factors associated with the use of potentially risky drugs over the entire course of pregnancy. METHODS: We enrolled pregnant women from their first antenatal care visit and followed them up until delivery, and collected data on drug use. Based on United States Food and Drug Administration (FDA) or Australian Therapeutic Goods Administration (TGA) drug risk classification, drugs were classified into three groups: 'probably safe', 'potentially risky' or 'unclassified'. A modified classification was built to take into account national malaria policy treatment guidelines and World Health Organization Malaria Treatment Guidelines recommending malaria chemoprophylaxis during pregnancy. RESULTS: Out of 2371 pregnant women enrolled, 56.7% used at least one medication during the entire course of the pregnancy (excluding sulphadoxine-pyrimethamine and iron-folic acid). A total of 101 different types of medications were used by study participants and 36.6, 49.5 and 13.9% were, respectively, classified as 'probably safe', 'potentially risky' and 'unclassified'. Antimalarials and antibiotics were the most frequently used drugs. Around 39% of women used a least one medication classified as potentially risky. However, this proportion dropped to 26% with the modified classification. Living in urban areas and attending the first antenatal care within their first trimester of pregnancy (longer health surveillance) were associated with using 'potentially risky' medications. CONCLUSION: This study provides rare and valuable information on the current use of drugs among pregnant women in Burkina Faso. Many pregnant women used medications classified as potentially risky. Our findings suggest the need for rational drug prescription and community education to reduce hazardous drug exposure during pregnancy.