Escherichia coli from urine samples of pregnant women as an indicator for antimicrobial resistance in the community: a field study from rural Burkina Faso.

BACKGROUND: In low- and middle-income countries, surveillance of antimicrobial resistance (AMR) is mostly hospital-based and, in view of poor access to clinical microbiology, biased to more resistant pathogens. We aimed to assess AMR among Escherichia coli isolates obtained from urine cultures of pregnant women as an indicator for community AMR and compared the AMR results with those from E. coli isolates obtained from febrile patients in previously published clinical surveillance studies conducted within the same population in Nanoro, rural Burkina Faso. We furthermore explored feasibility of adding urine culture to standard antenatal care in a rural sub-Saharan African setting. METHODS: Between October 2016-September 2018, midstream urine samples collected as part of routine antenatal care in Nanoro district were cultured by a dipslide method and screened for antibiotic residues. Significant growth was defined as a pure culture of Enterobacterales at counts of ≥ 104 colony forming units/ml. RESULTS: Significant growth was observed in 202/5934 (3.4%) cultures; E. coli represented 155 (76.7%) of isolates. Among E. coli isolates, resistance rates to ampicillin, cotrimoxazole and ciprofloxacin were respectively 65.8%, 64.4% 16.2%, compared to 89.5%, 89.5% and 62.5% among E. coli from clinical isolates (n = 48 of which 45 from blood cultures). Proportions of extended spectrum beta-lactamase producers and multidrug resistance were 3.2% and 5.2% among E. coli isolates from urine in pregnant women versus 35.4%, and 60.4% respectively among clinical isolates. CONCLUSIONS: The E. coli isolates obtained from healthy pregnant women had significantly lower AMR rates compared to clinical E. coli isolates, probably reflecting the lower antibiotic pressure in the pregnant women population. Adding urine culture to the routine urine analysis (dipstick) of antenatal care was feasible. The dipslide culture method was affordable and user-friendly and allowed on-site inoculation and easy transport; challenges were contamination (midstream urine sampling) and the semi-quantitative reading. Provided confirmation of the present findings in other settings, E. coli from urine samples in pregnant women may be a potential indicator for benchmarking, comparing, and monitoring community AMR rates across populations over different countries and regions.

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.

Mucosal lactoferrin response to genital tract infections is associated with iron and nutritional biomarkers in young Burkinabé women.

BACKGROUND/OBJECTIVES: The iron-binding affinity of vaginal lactoferrin (Lf) reduces iron available to genital pathogens. We describe host reproductive, nutritional, infection and iron biomarker profiles affecting vaginal Lf concentration in young nulliparous and primigravid women in Burkina Faso. SUBJECTS/METHODS: Vaginal eluates from women who had participated in a randomized, controlled periconceptional iron supplementation trial were used to measure Lf using a competitive double-sandwich ELISA. For this analysis samples from both trial arms were combined and pregnant and non-pregnant cohorts compared. Following randomization Lf was measured after 18 months (end assessment) for women remaining non-pregnant, and at two antenatal visits for those becoming pregnant. Associations between log Lf levels and demographic, anthropometric, infection and iron biomarker variables were assessed using linear mixed models. RESULTS: Lf samples were available for 712 non-pregnant women at end assessment and for 303 women seen at an antenatal visit. Lf concentrations of pregnant women were comparable to those of non-pregnant, sexually active women. Lf concentration increased with mid-upper-arm circumference, (P = 0.047), body mass index (P = 0.018), Trichomonas vaginalis (P < 0.001) infection, bacterial vaginosis (P < 0.001), serum C-reactive protein (P = 0.048) and microbiota community state types III/IV. Adjusted Lf concentration was positively associated with serum hepcidin (P = 0.047), serum ferritin (P = 0.018) and total body iron stores (P = 0.042). There was evidence that some women maintained persistently high or low Lf concentrations from before, and through, pregnancy. CONCLUSION: Lf concentrations increased with genital infection, higher BMI, MUAC, body iron stores and hepcidin, suggesting nutritional and iron status influence homeostatic mechanisms controlling vaginal Lf responses.

Interleukin-10 and soluble tumor necrosis factor receptor II are potential biomarkers of Plasmodium falciparum infections in pregnant women: a case-control study from Nanoro, Burkina Faso.

BACKGROUND: Diagnosis of malaria in pregnancy is problematic due to the low sensitivity of conventional diagnostic tests (rapid diagnostic test and microscopy), which is exacerbated due to low peripheral parasite densities, and lack of clinical symptoms. In this study, six potential biomarkers to support malaria diagnosis in pregnancy were evaluated. METHODS: Blood samples were collected from pregnant women at antenatal clinic visits and at delivery. Microscopy and real-time PCR were performed for malaria diagnosis and biomarker analyses were performed by ELISA (interleukin 10, IL-10; tumor necrosis factor-α, TNF-α; soluble tumor necrosis factor receptor II, sTNF-RII; soluble fms-like tyrosine kinase 1, sFlt-1; leptin and apolipoprotein B, Apo-B). A placental biopsy was collected at delivery to determine placental malaria. RESULTS: IL-10 and sTNF-RII were significantly higher at all time-points in malaria-infected women (p < 0.001). Both markers were also positively associated with parasite density (p < 0.001 and p = 0.003 for IL-10 and sTNF-RII respectively). IL-10 levels at delivery, but not during pregnancy, were negatively associated with birth weight. A prediction model was created using IL-10 and sTNF-RII cut-off points. For primigravidae the model had a sensitivity of 88.9% (95%CI 45.7-98.7%) and specificity of 83.3% (95% CI 57.1-94.9%) for diagnosing malaria during pregnancy. For secundi- and multigravidae the sensitivity (81.8% and 56.5% respectively) was lower, while specificity (100.0% and 94.3% respectively) was relatively high. Sub-microscopic infections were detected in 2 out of 3 secundi- and 5 out of 12 multigravidae. CONCLUSIONS: The combination of biomarkers IL-10 and sTNF-RII have the potential to support malaria diagnosis in pregnancy. Additional markers may be needed to increase sensitivity and specificity, this is of particular importance in populations with sub-microscopic infections or in whom other inflammatory diseases are prevalent.

H3Africa AWI-Gen Collaborative Centre: a resource to study the interplay between genomic and environmental risk factors for cardiometabolic diseases in four sub-Saharan African countries.

Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40-60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

"There is iron and iron " Burkinabè women's perceptions of iron supplementation: a qualitative study.

Most pregnant women in Burkina Faso are iron deficient and many are anemic. This study assessed women's understanding of anemia and the role of iron in preventing and treating this condition. A qualitative study was conducted within a randomized controlled trial of weekly iron supplementation in a rural malaria endemic area. Focus groups with women of similar age, parity, and marital status took place in 12 of 24 study villages. Two additional focus groups were conducted with female field workers. Tape-recorded transcripts were translated into French and analyzed using Framework analysis. Anemia, for which no Mooré term or traditional treatment for anemia was evident, was described in terms of blood volume. Moderate blood loss (diminished blood) could be easily replaced by eating well and was not considered serious. Massive blood loss (finished blood) was a rare, life-threatening illness. Iron tablets could increase blood volume and help women withstand massive blood loss at delivery, but for the latter, transfusion was indicated. Women had no knowledge of iron's role and did not readily concede that iron supplements contained elemental iron. Neither adolescents nor field workers were convinced of the benefits of supplementing non-pregnant adolescents, who were incorrectly considered to be at low risk of anemia. Young women's knowledge of anemia did not provide an adequate explanatory framework to motivate anemia prevention. Improving information on the role of iron is especially important for adolescent girls who may be incorrectly considered at low risk of anemia as they have not yet experienced pregnancy.

Selective arterial embolization of life-threatening renal hemorrhage in four patients after partial nephrectomy.

PURPOSE: Partial nephrectomy (PN) is an accepted alternative to radical nephrectomy for nephron sparing surgery to treat renal tumors. Although complications are relatively rare after PN, they may include renal hemorrhage that can be massive and life threatening. Artery embolization can have a major role in the management of these cases and to avoid radical nephrectomy. MATERIALS AND METHODS: We report four consecutive patients with massive hemorrhage after PN, treated by arterial embolization and review the literature to discuss the clinical presentation, imaging evaluation and clinical outcome. All patients developed arteriovenous fistula and one a pseudoaneurysm. RESULTS: After selective catheterization and identification of the bleeding site, we used microcoils as embolization material. Immediate technical and clinical success was achieved in all cases. CONCLUSION: Superselective artery embolization of renal hemorrhage is a simple, safe and efficient procedure. It has a high clinical success and should be considered as an alternative to nephrectomy, minimizing the morbidity and preserving renal tissue.

Direct blood PCR in combination with nucleic acid lateral flow immunoassay for detection of Plasmodium species in settings where malaria is endemic.

Declining malaria transmission and known difficulties with current diagnostic tools for malaria, such as microscopy and rapid diagnostic tests (RDTs) in particular at low parasite densities, still warrant the search for sensitive diagnostic tests. Molecular tests need substantial simplification before implementation in clinical settings in countries where malaria is endemic. Direct blood PCR (db-PCR), circumventing DNA extraction, to detect Plasmodium was developed and adapted to be visualized by nucleic acid lateral flow immunoassay (NALFIA). The assay was evaluated in the laboratory against samples from confirmed Sudanese patients (n = 51), returning travelers (n = 214), samples from the Dutch Blood Bank (n = 100), and in the field in Burkina Faso (n = 283) and Thailand (n = 381) on suspected malaria cases and compared to RDT and microscopy. The sensitivity and specificity of db-PCR-NALFIA compared to the initial diagnosis in the laboratory were 94.4% (95% confidence interval [CI] = 0.909 to 0.969) and 97.4% (95% CI = 0.909 to 0.969), respectively. In Burkina Faso, the sensitivity was 94.8% (95% CI = 0.88.7 to 97.9%), and the specificity was 82.4% (95% CI = 75.4 to 87.7%) compared to microscopy and 93.3% (95% CI = 87.4 to 96.7%) and 91.4% (95% CI = 85.2 to 95.3%) compared to RDT. In Thailand, the sensitivity and specificity were 93.4% (CI = 86.4 to 97.1%) and 90.9 (95% CI = 86.7 to 93.9%), respectively, compared to microscopy and 95.6% (95% CI = 88.5 to 98.6%) and 87.1% (95% CI = 82.5 to 90.6) compared to RDT. db-PCR-NALFIA is highly sensitive and specific for easy and rapid detection of Plasmodium parasites and can be easily used in countries where malaria is endemic. The inability of the device to discriminate Plasmodium species requires further investigation.

In vitro and in vivo antiplasmodial activity of 'saye', an herbal remedy used in Burkina Faso traditional medicine.

'Saye', a traditional medicine used in Burkina Faso, which consists of extracts of Cochlospermum planchonii (rhizome), Cassia alata (leaf) and Phyllanthus amarus (whole plant), showed a significant effect against Plasmodium falciparum and Plasmodium berghei parasites grown in vivo (IC(50) = 80.11 +/- 3.40 microg/mL; ED(50) = 112.78 +/- 32.32 mg/kg). In vitro the activity was lower.

[In vivo sensitivity of Plasmodium faciparum to chloroquine and sulfadoxine pyrimethamine in the Bobo Dioulasso region (1998-2001): risk factors associated with treatments failures to the two drugs]. / Sensibilité in vivo de Plasmodium falciparum à la chloroquine et à la sulfadoxine-pyrimethamine dans la région de Bobo Dioulasso (1998-2001): étude des facteurs de risque associés aux échecs thérapeutiques de ces deux médicaments.

The therapeutic efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was determined over a 4 year period (1998-2001) in Bobo Dioulasso, Burkina Faso, with an analysis of the risk factors associated to treatment failures to the 2 drugs. In total, 2008 children (6 months-15 years old) attending in 4 health centres (1 urban and 3 rural) were included in the study. Children were alternatively allocated to either CQ or SP The WHO 14-days in vivo field test was carried out. PCV was measured at day 0 and 14. CQ treatment failure was 24.4% (229/940), most of them being late failures. Between 1998 and 2001 a significant increase in CQ treatment failure (p < 0.001) was observed. SP showed a good efficacy with a total treatment failure of 4.4% (33/749). However; a significant increase of resistance to this drug (p=0.001) was also observed between 1998 and 2001. Among children with anaemia at day 0.85% (23/27) were no more anaemic by day 14 in the SP group, while in the CQ group the proportion was lower; 69% (27/39). However the difference between the two drugs was not significant (p > 0.1). Univariate analysis showed that the site, the age of children, the time of recruitment and the parasitaemia were significantly associated with CQ treatment failure. In the multivariate analysis these 4 variables remain significantly and independently associated with the risk of CQ treatment failure. After adjusting for the effect of the 3 other factors, the risk of treatment failure was reduced by half in rural area compared to urban area as well as in children of 5-15 years of age compared to those under 5. The risk of treatment failure was significantly increased in 2000-2001 (OR = 1.66, p < 0.05) as compared to the 2 previous years (1998-1999). It was also twice higher in children with parasitaemia > or = 16,000/microl than in those having a lower parasitaemia. For SP we have not observed such connexions with the univariate and multivariate analysis.

Chloroquine and sulphadoxine-pyrimethamine efficacy for uncomplicated malaria treatment and haematological recovery in children in Bobo-Dioulasso, Burkina Faso during a 3-year period 1998-2000.

We determined the parasitological resistance and the clinical failure to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) by the WHO 14-day in vivo test over three consecutive years in 948 children aged 6-59 months with uncomplicated malaria attending four health centres in the province of Houet, Burkina Faso. Children were alternatively allocated to either CQ or SP. Packed cell volume (PCV) was measured at days 0 and 14. Parasitological resistance (RI, RII and RIII) to CQ was 18% (83 of 455) and to SP <1% (two of 308). Clinical failure with CQ was 12% (53 of 455) with no evidence of increase over time. Only one case of clinical failure was detected among the children treated with SP. The prevalence of anaemia (PCV <25%) was about 40% at day 0 and had decreased substantially by day 14 in both groups. However, in children treated with SP the prevalence of anaemia at day 14 was significantly lower than in those treated with CQ:RR = 3.15 (95% CI: 1.33-7.42, P = 0.008). CQ and SP are still efficacious for the treatment of uncomplicated malaria in children, at least in this area of Burkina Faso. However, the prevalences of CQ resistance reported from other areas of the country are worrying because of its potential spread. Regular surveillance of resistance to commonly used antimalarial drugs should continue.

[In vitro susceptibility of 232 isolates of Plasmodium falciparum to antimalarials in Burkina Faso (West Africa)]. / Etude de la sensibilité in vitro de 232 isolats de Plasmodium falciparum aux antipaludéens au Burkina Faso (Afrique de l'Ouest).

Plasmodium falciparum in vitro susceptibility to chloroquine, quinine, mefloquine and halofantrine was investigated in patients living in Bobo-Dioulasso (Burkina Faso, West Africa). Our study was carried out from July to November 1997 at the Malaria Chemoresistance Reference Centre, Centre MurazIOCCGE. Inclusion criteria were: presence of a single infection by R falciparum with a parasite count > or =4000 infected red cells/mm3. The susceptibility to drugs was measured after an incubation period of 48 hours at 37 degrees C, under 5% CO2. (3H) Hypoxanthine was added to the medium to monitor parasite growth. 134 isolates of P. falciparum were tested against chloroquine; 24.6% (33/134) were resistant. We have also documented 11.2% (15/133) of resistant isolates to halofantrine. All the tested isolates were susceptible to quinine (n=135) and mefloquine (n=136). A significant positive correlation was found between the following IC50 values: chloroquine-quinine, quinine-mefloquine and mefloquine-halofantrine. Our study shows no significant increase of the prevalence of chloroquine-resistant strains of P. falciparum in our study area; as well as the persistence of resistance to halofantrine with regard to previous publications in the subject.

[The simplified isotopic microtest: a method for studying the drug resistance in vitro of Plasmodium falciparum to antimalarial drugs]. / Le microtest isotopique simplifié: une méthode pour l'étude de la chimio-résistance in vitro de Plasmodium falciparum aux antipaludiques.

We evaluated the efficiency of the simplified version of the isotopic microtest (simplified test) and compared it to that of the complete version (standard test), for determining the susceptibility of local strains of Plasmodium falciparum to chloroquine, quinine, mefloquine and halofantrine. The study was carried out from July to November 1996, at the MURAZ Center, Bobo-Dioulasso, Burkina Faso. The inclusion criteria were: single infection with P. falciparum, with a parasite count of at least 4,000 infected red blood cells per mm3. Susceptibility to each drug was determined after incubation for 48 hours at 37

In vitro sensitivity of Plasmodium falciparum to halofantrine compared with chloroquine, quinine and mefloquine in the region of Bobo-Dioulasso, Burkina Faso (West Africa).

The in vitro sensitivity of P. falciparum drug-resistant isolates was evaluated in the region of Bobo-Dioulasso during the 1995 and 1996 rainy seasons. Two routinely used antimalarials (chloroquine and quinine) and two new antimalarials (mefloquine and halofantrine) were assessed using 24-hour in vitro cultures with tritiated hypoxanthine and a parasite density > or = 4,000/microl of blood. The proportion of chloroquine-resistant isolates was 20% in 1995 and 19% in 1996, whilst in 1996, the proportion of isolates resistant to halofantrine was greater than in 1995 (9.6% versus 1%). No significant differences were seen in the mean IC50 values in relation to the susceptibility of chloroquine-resistant or chloroquine-sensitive isolates to mefloquine and halofantrine. In the case of quinine, the mean IC50 values were significantly higher in chloroquine-resistant isolates than in chloroquine-sensitive ones. A significant positive correlation was found between the following IC50 values: chloroquine versus quinine, quinine versus mefloquine and mefloquine versus halofantrine.