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.

What are the trends in seeking health care for fever in children under-five in Sierra Leone? evidence from four population-based studies before and after the free health care initiative.

BACKGROUND: In 2010, the government of Sierra Leone implemented the Free Health Care Initiative (FHCI) in the country with the objective of reducing the high maternal, infant, and child mortality rates and improving general health indicators. The objective of this study was to assess the trends in the prevalence of health care-seeking and to identify the determinants of healthcare service utilization by caregivers of children younger than five years. METHODS: The analysis of health-care-seeking behavior was done using data from four population-based surveys in Sierra Leone before (2008) and after (2013, 2016, 2019) the FHCI was implemented. Care-seeking behavior was assessed with regard to caregivers seeking care for children under-five in the two weeks prior to each survey. We compared the percentages of healthcare-seeking behavior change and identify factors associated with healthcare-seeking using a modified Poisson regression model with generalized estimating equations. RESULTS: In 2008, a total of 1208 children with fever were recorded, compared with 2823 children in 2013, 1633 in 2016, and 1464 in 2019. Care-seeking for children with fever was lowest in 2008 (51%; 95% CI (46.4-55.5)) than in 2013 (71.5%; 95% CI (68.4-74.5)), 2016 (70.3%; 95% CI (66.6-73.8)), and 2019 (74.6%; 95% CI (71.6-77.3)) (p < 0.001). Care-seeking in 2013, 2016 and 2019 was at least 1.4 time higher than in 2008 (p < 0.001) after adjusting for mother's age, wealth, religion, education level, household head and the child's age. Care-seeking was lowest for children older than 12 months, mothers older than 35 years, children living in the poorest households, and in the northern region. A trend was observed for the sex of the household head. The level of care-seeking was lowest when the household head was a man. CONCLUSIONS: The increase in healthcare-seeking for children under-five with fever followed the introduction of the FHCI in Sierra Leone. Care-seeking for fever varied by the child's age, caregiver's age, household wealth, the sex of the household head and region. Maintaining the FHCI with adequate strategies to address other barriers beyond financial ones is essential to reduce disparities between age groups, regions and, households.

Using the first nationwide survey on non-communicable disease risk factors and different definitions to evaluate the prevalence of metabolic syndrome in Burkina Faso.

BACKGROUND: The burden of cardiovascular diseases is rising in the developing world including Sub-Saharan Africa. The rapid rise of cardiovascular disease burden is in part due to undetected and uncontrolled cardiovascular risk factors. The clustering of metabolic syndrome (MetS) components is associated with a high risk of cardiovascular diseases. This complex biochemical disorder is still poorly studied in western Africa. In this study, we aimed to determine the prevalence of metabolic syndrome and its determinants among the adult population in Burkina Faso. METHODS: We performed a secondary analysis of the data from the first national survey on non-communicable diseases risk factors using the World Health Organization (WHO) Stepwise approach. We included 4019 study participants aged 25 to 64 years. The metabolic syndrome prevalence was estimated using six different definitions. RESULTS: The mean age was 38.6±11.1 years. Women represented 52.4% and three quarters (75%) lived in rural areas. The overall prevalence of metabolic syndrome according to the different definitions was 1.6% (95%CI:1.1-2.2) for the American College of Endocrinology, 1.8% (95%CI: 1.3-2.4) for the WHO, 4.3% (95%CI:3.5-5.2) for the National Cholesterol Education Program Adult Treatment Panel III, 6.2% (95%CI: 5.1-7.6) for the AAH/NHBI, 9.6%(95%CI: 8.1-11.3) for the International Diabetes Federation and 10.9% (95%: 9.2-12.7) for the Joint Interim Statement. The metabolic syndrome components with the highest prevalence were low High density lipoprotein (63.3%), abdominal obesity (22.3%) and hypertension (20.6%). People living in urban areas and those with older age have higher prevalence of metabolic syndrome regardless of the definition used. CONCLUSION: Our findings suggest various levels of prevalence of MetS according to the definition used. Identifying the most appropriate criteria for MetS among the adult population is important to early detect and treat this syndrome and its components at the primary health care level to control the rising burden of cardiovascular diseases in the context of ongoing epidemiological transition in the country.

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.

Infection Manager System (IMS) as a new hemocytometry-based bacteremia detection tool: A diagnostic accuracy study in a malaria-endemic area of Burkina Faso.

BACKGROUND: New hemocytometric parameters can be used to differentiate causes of acute febrile illness (AFI). We evaluated a software algorithm-Infection Manager System (IMS)-which uses hemocytometric data generated by Sysmex hematology analyzers, for its accuracy to detect bacteremia in AFI patients with and without malaria in Burkina Faso. Secondary aims included comparing the accuracy of IMS with C-reactive protein (CRP) and procalcitonin (PCT). METHODS: In a prospective observational study, patients of ≥ three-month-old (range 3 months- 90 years) presenting with AFI were enrolled. IMS, blood culture and malaria diagnostics were done upon inclusion and additional diagnostics on clinical indication. CRP, PCT, viral multiplex PCR on nasopharyngeal swabs and bacterial- and malaria PCR were batch-tested retrospectively. Diagnostic classification was done retrospectively using all available data except IMS, CRP and PCT results. FINDINGS: A diagnosis was affirmed in 549/914 (60.1%) patients and included malaria (n = 191) bacteremia (n = 69), viral infections (n = 145), and malaria-bacteremia co-infections (n = 47). The overall sensitivity, specificity, and negative predictive value (NPV) of IMS for detection of bacteremia in patients of ≥ 5 years were 97.0% (95% CI: 89.8-99.6), 68.2% (95% CI: 55.6-79.1) and 95.7% (95% CI: 85.5-99.5) respectively, compared to 93.9% (95% CI: 85.2-98.3), 39.4% (95% CI: 27.6-52.2), and 86.7% (95% CI: 69.3-96.2) for CRP at ≥20mg/L. The sensitivity, specificity and NPV of PCT at 0.5 ng/ml were lower at respectively 72.7% (95% CI: 60.4-83.0), 50.0% (95% CI: 37.4-62.6) and 64.7% (95% CI: 50.1-77.6) The diagnostic accuracy of IMS was lower among malaria cases and patients <5 years but remained equal to- or higher than the accuracy of CRP. INTERPRETATION: IMS is a new diagnostic tool to differentiate causes of AFI. Its high NPV for bacteremia has the potential to improve antibiotic dispensing practices in healthcare facilities with hematology analyzers. Future studies are needed to evaluate whether IMS, combined with malaria diagnostics, may be used to rationalize antimicrobial prescription in malaria endemic areas. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02669823) https://clinicaltrials.gov/ct2/show/NCT02669823.

The XN-30 hematology analyzer for rapid sensitive detection of malaria: a diagnostic accuracy study.

BACKGROUND: Accurate and timely diagnosis of malaria is essential for disease management and surveillance. Thin and thick blood smear microscopy and malaria rapid diagnostic tests (RDTs) are standard malaria diagnostics, but both methods have limitations. The novel automated hematology analyzer XN-30 provides standard complete blood counts (CBC) as well as quantification of malaria parasitemia at the price of a CBC. This study assessed the accuracy of XN-30 for malaria detection in a controlled human malaria infection (CHMI) study and a phase 3 diagnostic accuracy study in Burkina Faso. METHODS: Sixteen healthy, malaria-naive CHMI participants were challenged with five Plasmodium falciparum-infected mosquitoes. Blood was sampled daily for XN-30, blood smear microscopy, and malaria qPCR. The accuracy study included patients aged > 3 months presenting with acute febrile illness. XN-30, microscopy, and rapid diagnostic tests (HRP-2/pLDH) were performed on site; qPCR was done in retrospect. The malaria reference standard was microscopy, and results were corrected for sub-microscopic cases. RESULTS: All CHMI participants became parasitemic by qPCR and XN-30 with a strong correlation for parasite density (R2 = 0.91; p < .0001). The XN-30 accurately monitored treatment and allowed detection of recrudescence. Out of 908 patients in the accuracy study, 241 had microscopic malaria (density 24-491,802 parasites/µL). The sensitivity and specificity of XN-30 compared to microscopy were 98.7% and 99.4% (PPV = 98.7%, NPV = 99.4%). Results were corrected for qPCR-confirmed sub-microscopic cases. Three microscopy-confirmed cases were not detected by XN-30. However, XN-30 detected 19/134 (14.2%) qPCR-confirmed cases missed by microscopy. Among qPCR-confirmed cases, XN-30 had a higher sensitivity (70.9% versus 66.4%; p = .0009) and similar specificity (99.6% versus 100%; p = .5) as microscopy. The accuracy of XN-30 for microscopic malaria was equal to or higher than HRP-2 and pLDH RDTs, respectively. CONCLUSIONS: The XN-30 is a novel, automated hematology analyzer that combines standard hemocytometry with rapid, objective, and robust malaria detection and quantification, ensuring prompt treatment of malaria and malaria anemia and follow-up of treatment response. TRIAL REGISTRATION: Both trials were registered on clinicaltrials.gov with respective identifiers NCT02836002 (CHMI trial) and NCT02669823 (diagnostic accuracy study).

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.