Ex vivo drug susceptibility and resistance mediating genetic polymorphisms of Plasmodium falciparum in Bobo-Dioulasso, Burkina Faso.

Malaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether-lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria chemoprevention with monthly sulfadoxine-pyrimethamine plus amodiaquine in children during the transmission season. Monitoring the activities of available antimalarial drugs is a high priority. We assessed the ex vivo susceptibility of Plasmodium falciparum to 11 drugs in isolates from patients presenting with uncomplicated malaria in Bobo-Dioulasso in 2021 and 2022. IC50 values were derived using a standard 72 h growth inhibition assay. Parasite DNA was sequenced to characterize known drug resistance-mediating polymorphisms. Isolates were generally susceptible, with IC50 values in the low-nM range, to chloroquine (median IC5010 nM, IQR 7.9-24), monodesethylamodiaquine (22, 14-46) piperaquine (6.1, 3.6-9.2), pyronaridine (3.0, 1.3-5.5), quinine (50, 30-75), mefloquine (7.1, 3.7-10), lumefantrine (7.1, 4.5-12), dihydroartemisinin (3.7, 2.2-5.5), and atovaquone (0.2, 0.1-0.3) and mostly resistant to cycloguanil (850, 543-1,290) and pyrimethamine (33,200, 18,400-54,200), although a small number of outliers were seen. Considering genetic markers of resistance to aminoquinolines, most samples had wild-type PfCRT K76T (87%) and PfMDR1 N86Y (95%) sequences. For markers of resistance to antifolates, established PfDHFR and PfDHPS mutations were highly prevalent, the PfDHPS A613S mutation was seen in 19% of samples, and key markers of high-level resistance (PfDHFR I164L; PfDHPS K540E) were absent or rare (A581G). Mutations in the PfK13 propeller domain known to mediate artemisinin partial resistance were not detected. Overall, our results suggest excellent susceptibilities to drugs now used to treat malaria and moderate, but stable, resistance to antifolates used to prevent malaria.

Implementation of the WHO core components of an infection prevention and control programme in two sub-saharan African acute health-care facilities: a mixed methods study.

BACKGROUND: The coronavirus pandemic again highlighted the need for robust health care facility infection prevention and control (IPC) programmes. WHO guidelines on the core components (CCs) of IPC programmes provides guidance for facilities, but their implementation can be difficult to achieve in resource-limited settings. We aimed to gather evidence on an initial WHO IPC implementation experience using a mixed methods approach. METHODS: A five-day training on the WHO IPC CCs was conducted at two reference acute health care facilities in the Democratic Republic of Congo and Burkina Faso. This was accompanied by a three-part mixed-methods evaluation consisting of a: (1) baseline and follow-up survey of participants' knowledge, attitudes and practices (KAP), (2) qualitative assessment of plenary discussion transcripts and (3) deployment of the WHO IPC assessment framework (IPCAF) tool. Results were analysed descriptively and with a qualitative inductive thematic approach. RESULTS: Twenty-two and twenty-four participants were trained at each facility, respectively. Baseline and follow-up KAP results suggested increases in knowledge related to the necessity of a dedicated IPC focal person and annual evaluations of IPC training although lack of recognition on the importance of including hospital leadership in IPC training and hand hygiene monitoring recommendations remained. Most participants reported rarely attending IPC meetings or participating in IPC action planning although attitudes shifted towards stronger agreement with the feeling of IPC responsibility and importance of an IPC team. A reocurring theme in plenary discussions was related to limited resources as a barrier to IPC implementation, namely lack of reliable water access. However, participants recognised the importance of IPC improvement efforts such as practical IPC training methods or the use of data to improve quality of care. The facilities' IPCAF scores reflected a 'basic/intermediate' IPC implementation level. CONCLUSIONS: The training and mixed methods evaluation revealed initial IPC implementation experiences that could be used to inform stepwise approaches to facility IPC improvement in resource-limited settings. Implementation strategies should consider both global standards such as the WHO IPC CCs and specific local contexts. The early involvement of all relevant stakeholders and parallel efforts to advocate for sufficient resources and health system infrastructure are critical.

Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study.

BACKGROUND: Strong surveillance systems with wide geographic coverage are needed to detect and respond to reports of antimalarial drug resistance on the African continent. We aimed to assess the utility and feasibility of using blood-fed mosquitos (xenomonitoring) to conduct rapid surveillance of molecular markers associated with resistance in human populations. METHODS: We conducted three cross-sectional surveys in two rainy seasons and the interim dry season in southwest Burkina Faso between Oct 10, 2018, and Sept 17, 2019. We collected human blood samples and blood-fed mosquitos residing in household clusters across seven village sectors. Samples were assessed for Plasmodium falciparum with ultrasensitive quantitative PCR, genotyped for two markers of reduced drug susceptibility, pfmdr1 256A>T (Asn86Tyr) and pfcrt 227A>C (Lys76Thr), and sequenced for four markers of clonality. We assessed statistical equivalence using a 10% margin of equivalence. FINDINGS: We identified 551 infections in 1483 human blood samples (mean multiplicity of infection [MOI] 1·94, SD 1·47) and 346 infections in 2151 mosquito blood meals (mean MOI 2·2, SD 1·67). The frequency of pfmdr1 Asn86Tyr was 4% in survey 1, 2% in survey 2, and 12% in survey 3 in human samples, and 3% in survey 1, 0% in survey 2, and 8% in survey 3 in mosquito blood meals, and inter-host frequencies were statistically equivalent in surveys 1 and 2 (p<0·0001) but not Survey 3 (p=0·062) within a tolerability of 0·10. The frequency of pfcrt Lys76Thr was 16% in survey 1, 55% in survey 2, and 11% in survey 3 in humans and 40% in survey 1, 72% in survey 2, and 13% in survey 3 in mosquitos, and inter-host frequencies were equivalent in survey 3 only (p=0·032) within a tolerability of 0·10. In simulations, multiple but not preferential feeding behaviour in mosquitos reduced the accuracy of frequency estimates between hosts, particularly for markers circulating at higher frequencies. INTERPRETATION: Molecular markers in mosquito blood meals and in humans exhibited similar temporal trends but frequencies were not statistically equivalent in all scenarios. More work is needed to determine empirical and pragmatic thresholds of difference. Xenomonitoring might be an efficient tool to provide rapid information on emerging antimalarial resistance in regions with insufficient surveillance. FUNDING: National Institute of Allergy and Infectious Diseases. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Repeat Ivermectin Mass Drug Administrations for Malaria Control II: Protocol for a Double-blind, Cluster-Randomized, Placebo-Controlled Trial for the Integrated Control of Malaria.

BACKGROUND: The gains made against malaria have stagnated since 2015, threatened further by increasing resistance to insecticides and antimalarials. Improvement in malaria control necessitates a multipronged strategy, which includes the development of novel tools. One such tool is mass drug administration (MDA) with endectocides, primarily ivermectin, which has shown promise in reducing malaria transmission through lethal and sublethal impacts on the mosquito vector. OBJECTIVE: The primary objective of the study is to assess the impact of repeated ivermectin MDA on malaria incidence in children aged ≤10 years. METHODS: Repeat Ivermectin MDA for Malaria Control II is a double-blind, placebo-controlled, cluster-randomized, and parallel-group trial conducted in a setting with intense seasonal malaria transmission in Southwest Burkina Faso. The study included 14 discrete villages: 7 (50%) randomized to receive standard measures (seasonal malaria chemoprevention [SMC] and bed net use for children aged 3 to 59 months) and placebo, and 7 (50%) randomized to receive standard measures and monthly ivermectin MDA at 300 µg/kg for 3 consecutive days, provided under supervision to all eligible village inhabitants, over 2 successive rainy seasons. Nonpregnant individuals >90 cm in height were eligible for ivermectin MDA, and cotreatment with ivermectin and SMC was not permitted. The primary outcome is malaria incidence in children aged ≤10 years, as assessed by active case surveillance. The secondary safety outcome of repeated ivermectin MDA was assessed through active and passive adverse event monitoring. RESULTS: The trial intervention was conducted from July to November in 2019 and 2020, with additional sampling of humans and mosquitoes occurring through February 2022 to assess postintervention changes in transmission patterns. Additional human and entomological assessments were performed over the 2 years in a subset of households from 6 cross-sectional villages. A subset of individuals underwent additional sampling in 2020 to characterize ivermectin pharmacokinetics and pharmacodynamics. Analysis and unblinding will commence once the database has been completed, cleaned, and locked. CONCLUSIONS: Our trial represents the first study to directly assess the impact of a novel approach for malaria control, ivermectin MDA as a mosquitocidal agent, layered into existing standard-of-care interventions. The study was designed to leverage the current SMC deployment infrastructure and will provide evidence regarding the additional benefit of ivermectin MDA in reducing malaria incidence in children. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT03967054; https://clinicaltrials.gov/ct2/show/NCT03967054 and Pan African Clinical Trials Registry PACT201907479787308; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8219. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41197.

Quantifying and characterizing hourly human exposure to malaria vectors bites to address residual malaria transmission during dry and rainy seasons in rural Southwest Burkina Faso.

BACKGROUND: To sustain the efficacy of malaria vector control, the World Health Organization (WHO) recommends the combination of effective tools. Before designing and implementing additional strategies in any setting, it is critical to monitor or predict when and where transmission occurs. However, to date, very few studies have quantified the behavioural interactions between humans and Anopheles vectors in Africa. Here, we characterized residual transmission in a rural area of Burkina Faso where long lasting insecticidal nets (LLIN) are widely used. METHODS: We analysed data on both human and malaria vectors behaviours from 27 villages to measure hourly human exposure to vector bites in dry and rainy seasons using a mathematical model. We estimated the protective efficacy of LLINs and characterised where (indoors vs. outdoors) and when both LLIN users and non-users were exposed to vector bites. RESULTS: The percentage of the population who declared sleeping under a LLIN the previous night was very high regardless of the season, with an average LLIN use ranging from 92.43 to 99.89%. The use of LLIN provided > 80% protection against exposure to vector bites. The proportion of exposure for LLIN users was 29-57% after 05:00 and 0.05-12% before 20:00. More than 80% of exposure occurred indoors for LLIN users and the estimate reached 90% for children under 5 years old in the dry cold season. CONCLUSIONS: LLINs are predicted to provide considerable protection against exposure to malaria vector bites in the rural area of Diébougou. Nevertheless, LLIN users are still exposed to vector bites which occurred mostly indoors in late morning. Therefore, complementary strategies targeting indoor biting vectors in combination with LLIN are expected to be the most efficient to control residual malaria transmission in this area.

[Central Post-Stroke Pain at the Tingandogo University Teaching Hospital of Ouagadougou (Burkina Faso): Frequency, Clinical Profile, Quality of Life of Patients and Associated Factors]. / La Douleur Centrale Post Accident Vasculaire Cérébral au Chu Tingandogo de Ouagadougou (Burkina Faso): Fréquence, Profil Clinique, Qualité de Vie des Patients et Facteurs Associés.

Objective: Few studies have been done on central post-stroke pain (CPSP) in Sub-Saharan Africa, while taking it into account would improve the quality of life of stroke survivors. The purpose of this study was to determine the prevalence of CPSP, to describe its clinical profile, to assess the quality of life of patients and to identify the factors associated with its occurrence, from a prospective hospital series in Ouagadougou, Burkina Faso. Methodology: It was a prospective, descriptive and analytical longitudinal follow-up study, conducted from January 2015 to March 2020, at the Tingandogo University Hospital, in Ouagadougou, Burkina Faso. The study involved all patients over the age of 16, consecutively hospitalized for stroke confirmed by CT and / or brain MRI, then reviewed every three months in outpatient Neurology, during at least 9 months after their stroke. The sociodemographic and clinical characteristics of the patients, the nature of the stroke, the existence of CPSP and, if applicable, its clinical characteristics, its treatment and its impact on the quality of life of the patients were recorded; a bivariate then multivariate analysis with logistic regression step by step, made it possible to search for the factors associated with the occurrence of CPSP. The significance threshold used was p < 0.05. Results: A total of 236 patients were collected, out of which 28 patients presented a CPSP (11.9%), after a mean duration of post-stroke follow-up of 12.9 months. Cerebral infarction, intracerebral hemorrhage and cerebral venous thrombosis accounted for 69.5%, 29.7% and 0.8% respectively. The mean age of patients with CPSP was 54.6 years, with a male predominance (53.6%). The mean time to onset for CPSP was 3.8 months after stroke. Pains such as burning (75%) and allodynia (67.8%) were the most common. The average CPSP intensity was 7.6 / 10 on the visual analog scale. Hypoaesthesia (96.4%) and paraesthesia (71.4%) were the signs or symptoms most commonly associated with CPSP. CPSP had a moderate to severe negative impact on usual work, general activity and mood of patients in 60.7%, 50% and 46.4% of patients, respectively. Amitriptyline (75%) and / or level II analgesics (60.7%,) were the most used molecules, and effective in 57% of cases. Only age ≤ 50 years was independently associated with the occurrence of CPSP (OR 2.86; p = 0.03). Conclusion: CPSP affects more than 1 in 10 stroke patients and moderately to severely affects the quality of life for most of these patients. Screening and adequate management of CPSP as part of multidisciplinary post-stroke follow-up will contribute to improve the quality of life of stroke patients and will facilitate their social and professional reintegration.

Prognosis for term breech presentations in Africa (Bobo Dioulasso, Burkina Faso).

to describe the mode of delivery and the fetal prognosis for breech presentations in Bobo Dioulasso, Burkina Faso. this prospective, descriptive, cross-sectional study covered the entire year 2013 and included patients from the city's three principal maternity units. The sample included 184 women who gave birth at term to fetuses in breech presentation and a control group of 368 women with infants in cephalic presentation. Data were collected with standardized case report forms. The analysis was conducted with Epi-Info 3.5.1 software. We used the Chi-square test to compare percentages and the Chi-square test for trend to study the variation in frequencies. Differences were considered significant when P ≤ 0.05. during the study period, the prevalence of breech presentation at term was 1.74%. In the breech group, 55.5% of the women had vaginal deliveries versus 92% in the cephalic group (P = 0.04). The comparative analysis of fetal and neonatal morbidity in the two groups found greater morbidity in the breech group, marked by complications including uterine rupture (P = 0.0045), cord prolapse (P = 0.02), dynamic dystocia (P = 0.001), fetal distress (P = 0.0001), postpartum hemorrhage (P = 0.003), and perinatal death (P = 0.006). vaginal delivery remains the most frequent mode of delivery for breech presentations in Bobo Dioulasso, and perinatal morbidity and mortality are relatively high. Improvement of hospital protocols and staff training for breech deliveries should help to improve this situation.

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso.

The WHO recommends that children living in areas of highly seasonal malaria transmission in the Sahel subregion should receive seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). We evaluated the use of dihydroartemisinin-piperaquine (DHAPQ) as an alternative drug that could be used if SPAQ starts to lose efficacy. A total of 1,499 children 3 to 59 months old were randomized to receive SMC with SPAQ or DHAPQ over 3 months. The primary outcome measure was the risk of clinical malaria (fever or a history of fever with a parasite density of at least 3,000/µl). A cohort of 250 children outside the trial was followed up as a control group. Molecular markers of drug resistance were assessed. The risk of a malaria attack was 0.19 in the DHAPQ group and 0.15 in the SPAQ group, an odds ratio of 1.33 (95% confidence interval [CI], 1.02 to 1.72). Efficacy of SMC compared to the control group was 77% (67% to 84%) for DHAPQ and 83% (74% to 89%) for SPAQ. pfdhfr and pfdhps mutations associated with antifolate resistance were more prevalent in parasites from children who received SPAQ than in children who received DHAPQ. Both regimens were highly efficacious and well tolerated. DHAPQ is a potential alternative drug for SMC. (This trial is registered at ClinicalTrials.gov under registration no. NCT00941785.).

[Risk factors in prematurity and intrauterine growth retardation in Burkina Faso]. / Facteurs de risque de prématurité et de retard de croissance intra-utérin au Burkina Faso.

A case-control study to investigate determinants of preterm delivery and intrauterine growth retardation (IUGR) in Bobo-Dioulasso, Burkina Faso, was conducted between December 1991 and November 1992. A total of 581 cases were recruited, 281 preterm infants with birthweight < 2500 g and 300 term infants with birthweight < 2500 g. 578 infants born at term with birthweights of 2500 g or more were recruited as controls. Logistic regression analyses identified three factors linked independently to both preterm delivery and IUGR: maternal illness during the pregnancy, nulliparity and failure to attend three antenatal consultations. In addition, primiparity and a maternal weight < 50 kg were associated with an increased risk of preterm delivery. Other factors associated with increased risk of IUGR were maternal height less than or equal to 155 cm, mid-upper arm circumference < 24 cm, and female sex of the infant. Improvements in the pre-pregnancy weight of women and in antenatal care focused on nulli- and primiparous women might in this population, reduce substantially the incidence of preterm delivery and IUGR.

[Protein and enzymatic criteria for the characterization of phytopathogenic Pseudomonas fluorescens]. / Critères protéiques et enzymatiques pour la caractérisation des Pseudomonas fluorescents phytopathogènes.

Polyacrylamide gel electrophoresis of proteins was carried out to characterize eight bacterial strains belonging to the genus Pseudomonas. The sampling included three species (P. cichorii, P. viridiflava and P. syringae), with three pathovars for this last species (pv. pisi, pv. syringae, pv. tomato). Several molecular markers were evaluated: native proteins, denatured proteins, esterases, superoxide dismutases (SOD) and polyphenoloxidases (PPO). Each species or pathovar of Pseudomonas was clearly differentiated by esterase patterns. SOD, PPO and native protein patterns allowed strains of P. cichorii, P. viridiflava and P.s. pv. tomato also to be distinguished. Strains of P.s. pv. pisi and P.s. pv. syringae were identical for these criteria. Denatured protein patterns of these two pathovars and P. viridiflava were similar.

The Beffa form of Simulium soubrense of the S. damnosum complex in Togo and Benin.

The Beffa form of Simulium soubrense Vajime & Dunbar, a member of the S. sanctipauli sub-complex of the S. damnosum complex, was found breeding throughout rivers in the Togo-Benin Gap, as far north as 9 degrees 30'N. Its distribution changed with the season. In southern Togo there were seasonal fluctuations in the relative abundancies of the Beffa form and of S. damnosum/S.sirbanum. There was considerable temporal and regional variation in the frequencies of different colour morphs of adult flies. The flies in Benin tended to be darker. Infections with Onchocerca volvulus (Leuckart) appeared to be independent of the host's colour morph category. Larger flies harboured significantly more first stage Onchocerca larvae but no significant relations with fly size were found for second and third stage larvae.