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Introduction Accurate diagnosis of malaria, caused by Plasmodium falciparum , remains challenging in endemic resource-limited settings. Molecular diagnostics, like PCR, offer a higher sensitivity, but are often impractical at the point-of-care. A relatively simple molecular diagnostic test has been developed to overcome the technological challenges frequently encountered during the implementation of molecular tools. We present here the results of the field evaluation of this novel mini direct-on-blood PCR platform with lateral flow readout (dbPCR-NALFIA), in a rural setting of Burkina Faso. Methods A phase 3 diagnostic accuracy study was conducted over one year in a high P. falciparum transmission setting in Burkina Faso. Febrile patients of all ages (n = 438) were screened using Pf HRP2-based RDT, microscopy, and the investigational dbPCR-NALFIA test. Reference diagnostic test was qPCR targeting the P. falciparum varATS gene. Diagnostic accuracy metrics (sensitivity, specificity, predictive values) and agreement (Cohen’s kappa) were calculated for each method. Results Malaria prevalence by qPCR was 65.5% (287/438). A total of 99.2% (259/261) of P. falciparum microscopy-positive samples were detected by qPCR, 97.7% (253/259) detected with RDT and 99.6% (258/259) with the investigational dbPCR-NALFIA. Overall, 85.2% (149/177) of microscopy negative samples were also confirmed negative with qPCR. Among these qPCR negative samples, 80.5% (120/149) were concordantly negative by RDT, while 98.0% (146/149) were confirmed negative by dbPCR-NALFIA. Using qPCR as reference, the dbPCR-NALFIA demonstrated a sensitivity of 96.5% and specificity of 98.0%, comparable to RDT sensitivity (95.1%) and microscopy specificity (98.7%), but out-performed RDT specificity (80.8%) and microscopy sensitivity (90.2%). dbPCR-NALFIA detected 67.9% of sub microscopic qPCR-positive samples missed by the microscopy. Agreement with qPCR was the highest for dbPCR-NALFIA (kappa value = 0.90), compared to microscopy (kappa value = 0.80) and RDT (kappa value = 0.71). Conclusion The dbPCR-NALFIA shows excellent diagnostic performance to detect P. falciparum under field conditions. It addresses key limitations of other diagnostics and could play a vital role in case detection.

Objective To assess the impact of an intervention package on the prescription of antibiotic and subsequently the rate of clinical recovery for non-severe acute febrile illnesses at primary health centers. Methods Patients over 6 months of age presenting to primary health care centres with fever or history of fever within the past 7 days were randomized to receive either the intervention package constituted of point-of-care tests including COVID-19 antigen tests, a diagnostic algorithm and training and communication packages, or the standard practice. The primary outcomes were antibiotic prescriptions at Day 0 (D0) and the clinical recovery at Day 7 (D7). Secondary outcomes were non-adherence of participants and parents/caregivers to prescriptions, health workers’ non-adherence to the algorithm, and the safety of the intervention. Results A total of 1098 patients were enrolled. 551 (50.2%) were randomized to receive the intervention versus 547 (49.8%) received standard care. 1054 (96.0%) completed follow-up and all of them recovered at D7 in both arms. The proportion of patients with antibiotic prescriptions at D0 were 33.2% (183/551) in the intervention arm versus 58.1% (318/547) under standard care, risk difference (RD) -24.9 (95% CI -30.6 to -19.2, p  < 0.001), corresponding to one more antibiotic saved every four (95% CI: 3 to 5) consultations. This reduction was also statistically significant in children from 6 to 59 months (RD -34.5; 95% CI -41.7 to -27.3; p  < 0.001), patients over 18 years (RD -35.9; 95%CI -58.5 to -13.4; p  = 0.002), patients with negative malaria test (RD -46.9; 95% CI -53.9 to -39.8; p  < 0.001), those with a respiratory diagnosis (RD -48.9; 95% CI -56.9 to -41.0, p  < 0.001) and those not vaccinated against COVID-19 (-24.8% 95%CI -30.7 to -18.9, p -value: <0.001). A significant reduction in non-adherence to prescription by patients was reported (RD -7.1; 95% CI -10.9 to -3.3; p  < 0.001). Conclusion The intervention was associated with significant reductions of antibiotic prescriptions and non-adherence, chiefly among patients with non-malaria fever, those with respiratory symptoms and children below 5 years of age. The addition of COVID-19 testing did not have a major impact on antibiotic use at primary health centers. Trial registration Clinitrial.gov; NCT04081051 registered on 06/09/2019.

Rapid Diagnostic Tests (RDTs) have become the cornerstone for the management of malaria in many endemic settings, but their use is constrained for several reasons: (i) persistent malaria antigen (histidine-rich protein 2; HRP2) leading to false positive test results; (ii) hrp2 deletions leading to false negative PfHRP2 results; and (iii) limited sensitivity with a detection threshold of around 100 parasites/μl blood (pLDH- and HRP2-based) leading to false negative tests. Microscopy is still the gold standard for malaria diagnosis, and allows for species determination and quantitation, but requires trained microscopists, maintained microscopes and has detection limit issues. Consequently, there is a pressing need to develop and evaluate more sensitive and accurate diagnostic tests. To address this need we have developed a direct on blood mini PCR-NALFIA test that combines the benefits of molecular biology with low infrastructural requirements and extensive training. This is a Phase 3 diagnostic evaluation in 5 African countries. Study sites (Sudan, Ethiopia, Burkina, Kenya and Namibia) were selected to ensure wide geographical coverage of Africa and to address various malaria epidemiological contexts ranging from high transmission to near elimination settings with different clinical scenarios and diagnostic challenges. Study participants will be enrolled at the study health facilities after obtaining written informed consent. Diagnostic accuracy will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and reported according to STARD principles. Due to the lack of a 100% specific and sensitive standard diagnostic test for malaria, the sensitivity and specificity of the new test will be compared to the available diagnostic practices in place at the selected sites and to quantitative PCR as the reference test. This phase 3 study is designed to validate the clinical performance and feasibility of implementing a new diagnostic tool for the detection of malaria in real clinical settings. If successful, the proposed technology will improve the diagnosis of malaria. Enrolment started in November 2022 (Kenya) with assessment of long term outcome to be completed by 2023 at all recruitment sites. Pan African Clinical Trial Registry (www.pactr.org) PACTR202202766889963 on 01/02/2022 and ISCRTN (www.isrctn.com/) ISRCTN13334317 on 22/02/2022.

ObjectivesThis study aimed to understand the knowledge possessed by informal medicine vendors regarding antibiotics and antibiotic resistance, identify the perceptions held by informal medicine vendors about antibiotics and their uses and examine the practices employed by informal medicine vendors in the sale and distribution of antibiotics.DesignExploratory qualitative study using semi-structured interviews and direct observations.SettingMarkets and shops across 11 villages in the Nanoro health district, Burkina Faso.Participants23 informal medicine vendors, aged between 25 and 55 years and with 8–30 years of experience, were recruited through snowball sampling in the Nanoro health district of Burkina Faso.ResultsInformal medicine vendors exhibited a limited understanding of antibiotics, often confusing them with other treatments and referring to them using local terminologies based on perceived use and effectiveness. Antibiotics were perceived as universal remedies, supported by therapeutic belief, empirical reasoning and community solidarity, with empirical diagnosis, approximate dosing and informal preparation techniques passed on through imitation. These findings emerged across themes including perceptions, symbolic attributes and sales practices.ConclusionInformal medicine vendors in rural Burkina Faso demonstrated limited understanding of antibiotics and antimicrobial resistance, with practices shaped by local beliefs and empirical experience. These findings underscore the need for context-sensitive interventions that include tailored education and regulatory engagement to improve antibiotic stewardship and mitigate the spread of resistance.

BackgroundIn rural sub-Saharan Africa (sSA), the burden of antimicrobial resistance (AMR) remains high. As AMR continues to rise, there is a strong need for practical, implementable surveillance to monitor and mitigate risks, as well as inform timely, evidence-based clinical decision-making. Emerging evidence points to possible community-level drivers, such as transmission between human, animal and environmental reservoirs as contributing factors, yet microbiological surveillance or opportunities for wastewater-based surveillance are often limited and insufficient in these settings. Therefore, alternative sustainable and affordable approaches are needed. We intend to build on the demonstrated potential of metagenomic profiling of pooled faecal material, which accurately predicted population-level AMR prevalence in invasive Enterobacterales infections.Methods and analysisWe aim to validate this metagenomic pooled approach on additional populations, and to evaluate whether AMR patterns could be similarly predicted from surveillance of community One Health reservoirs. We will assemble existing data from hospital-based microbiology diagnostic laboratories in rural Burkina Faso and Kenya, and determine to what extent community-level metagenomic data, and/or faecal material of patients on hospital admission, can predict AMR in clinical isolates. We will perform community-level surveys in eight clusters per country, randomly selecting 15 households per cluster. We will systematically sample suspected environmental AMR exposure sites in and around households (soil, drinking water, latrines, chicken faeces) and collect data on community-level antibiotic use, hygiene practices, contact with domestic animals and sanitary facilities. Samples and data will be collected twice: during the dry and during the rainy season.In addition to evaluating the accuracy of predicting resistance in clinical isolates, we will quantify community-level exposure risks. We will conduct metagenomic profiling on pooled DNA extracts from human stool samples (hospital and community-level) and from household environments. Bayesian statistical models will quantify relationships between AMR gene abundance in the environment and in human stool, and invasive bacteria identified among clinical patients, accounting for geography and seasonality. A cost-utility analysis will determine under what circumstances the use of pooled metagenomic data to inform empirical antibiotic policies would represent an efficient use of resources.Ethics and disseminationThe proposed surveillance protocol is developed in partnership with local communities and local and international researchers and has received ethical approval in Kenya and Burkina Faso. It will assess whether intermittent, pooled-sample metagenomics provides a viable, low-cost and practical approach for population-level AMR surveillance in settings that—like many in rural sSA—lack systematic microbiological diagnostics and where sewage systems for wastewater-based surveillance are absent. By providing an alternative to routine microbiological-based surveillance where this proves challenging to implement, this approach may help improve treatment outcomes, contribute to equity and public health. Findings will be disseminated through peer-reviewed publications and academic conferences and will contribute to the recently proposed WHO AMR surveillance strategy, which combines survey-based approaches with routine AMR surveillance.

Low birthweight (LBW) is a worldwide problem that particularly affects developing countries. However, limited information is available on its magnitude in rural area of Burkina Faso. This study aimed to estimate the prevalence of low birthweight and to identify its associated factors in Nanoro health district. A secondary analysis of data collected during a cross-sectional survey was conducted to assess the prevalence of low birthweight in Nanoro health and demographic surveillance system area (HDSS). Maternal characteristics extracted from antenatal care books or by interview, completed by malaria diagnosis were examined through a multi-level logistic regression to estimate odd-ratios of association with low birthweight. Significance level was set at 5%. Of the 291 neonates examined, the prevalence of low birthweight was 12%. After adjustment for socio-demographic, obstetric and malaria prevention variables, being primigravid (OR = 8.84, [95% CI: 3.72–21.01]), or multigravid with history of stillbirth (OR = 5.03, [95% CI: 1.54–16.40]), as well as the lack of long-lasting insecticide treated bed net use by the mother the night preceding the admission for delivery (OR = 2.5, [95% CI: 1.1–5.9]) were significantly associated with neonate low birthweight. The number of antenatal visits however did not confer any direct benefit on birthweight status within this study area. The prevalence of low birthweight was high in the study area and represents an important public health problem in Burkina Faso. In light of these results, a redefinition of the content of the antenatal care package is needed.

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 p LDH 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 Pf HRP2/ p LDH 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 the RDT 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 the 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 4 March 2022 with long-term outcome being assessed completely by 2023.

Background In low- and middle-income countries, the prevalence of antimicrobial resistance (AMR) is increasing. To control AMR, WHO recommends monitoring antibiotic use, in particular Watch antibiotics. These are critically important antibiotics, with restricted use because at risk of becoming ineffective due to increasing AMR. We investigated pre-hospital antibiotic use in rural Burkina Faso. Methods During 2016–2017, we collected data from patients aged > 3 months presenting with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, including antibiotic use in the two weeks prior to consultation or hospitalization. We analysed reported antibiotic use by applying the WHO Access, Watch, Reserve classification. Results Of 920 febrile participants (63.0% ≤ 14 years), pre-hospital antibiotic use was reported by 363 (39.5%). Among these 363, microbiological diagnoses were available for 275 (75.8%) patients, of whom 162 (58.9%) were non-bacterial infections. Use of more than one antibiotic was reported by 58/363 (16.0%) participants. Of 491 self-referred patients who did not previously visit a primary health care center, 131 (26.7%) reported antibiotic use. Of 424 antibiotics reported, 265 (62.5%) were Access and 159 (37.5%) Watch antibiotics. Watch antibiotic use was more frequent among patients > 14 year olds (51.1%) compared to those 0–14 year old (30.7%, p  < 0.001) and among referrals from the primary health care centers (42.2%) compared to self-referred patients (28.1%, p  = 0.004). Most frequently reported Watch antibiotics were ceftriaxone (114, 71.7%) and ciprofloxacin (32, 20.1%). Conclusion The reported frequent use of Watch group antibiotics among febrile patients prior to presentation to the hospital in rural Burkina Faso highlights the need to develop targeted interventions to improve antibiotic use in community settings as part of strengthening antibiotic stewardship in low- and middle-income countries. This should include facilitating referral, access to qualified prescribers and diagnostic tools in rural primary health care centers. Trial registration ClinicalTrials.gov identifier: NCT02669823. Registration date was February 1, 2016.

Food-borne diseases affect nearly 10% of the global population annually, with Salmonella being a major cause, particularly impacting children, the elderly, and populations in low- and middle-income countries. This study aimed to assess the prevalence, serotype distribution, antibiotic resistance profiles, and genetic determinants of resistance and virulence of Salmonella enterica in humans and poultry in the Nanoro health district. A community-based cross-sectional study involving humans and poultry was conducted in the Nanoro health district. Fresh stool samples (human and poultry cloacal/cecal) were collected, transported under sterile conditions, and processed within two hours using standard bacteriological methods. Phenotypic antibiotic resistance was determined by the Kirby–Bauer disk diffusion method, and whole-genome sequencing (Illumina) identified serotypes, resistance genes, and virulence factors. Logistic regression analyzed associations between Salmonella carriage and host or environmental factors. Salmonella enterica carriage was detected in 8.7% of humans and 7.2% of poultry. Human isolates showed 24% resistance to cephalosporins, while poultry isolates showed 36.8% resistance. Resistance genes, including fosA7, qnrB19, and a cryptic aminoglycoside resistance gene, and virulence genes encoding T3SS-1 and T3SS-2, were detected in both hosts. Logistic regression indicated that residence in Sitaon and Zimidin was associated with ~70% lower odds of carriage (aOR = 0.3), while individuals aged 11–20 and 51–60 years had 2.8-fold higher odds. Carriage was also 60% higher during the rainy season. These findings suggest possible cross-transmission of Salmonella between humans and poultry and the circulation of resistant, potentially virulent strains in the community. Seasonal and age-related variations highlight environmental and behavioral influences on asymptomatic carriage. Integrated One Health surveillance and targeted hygiene interventions are essential to reduce Salmonella transmission and antimicrobial resistance in rural settings.

The malaria parasite 'Plasmodium falciparum' ('Pf') can sequester in the placenta resulting in low density of peripheral parasitemia and consequently in false negative malaria diagnosis (by microscopy) in pregnant women. Moreover, the use of rapid diagnostic tests (RDTs) in diagnostic strategies, including those for the detection of a malaria infection during pregnancy, is constrained by either persistent malaria antigen (histidine-rich protein 2; HRP2) after successful treatment, leading to false positive test results, or by false negative results as previously mentioned due to parasite sequestration (which is further exacerbated due to the low limited of detection [LoD] of conventional RDTs) or to HRP2 deletion. Recently, a direct blood polymerase chain reaction combined with a nucleic acid lateral flow immunoassay (dbPCR-NALFIA) has been developed, which circumvents these challenges and has demonstrated its diagnostic potential in phase 1 and 2 studies. The PREGDIAGMAL trial presented in this manuscript will assess the diagnostic performance of dbPCRNALFIA for the diagnostic of malaria in pregnant women and its potential to monitor treatment efficacy in these subjects. The work is ancillary embedded in an ongoing EDCTP funded trial, the PyraPreg project (PACTR202011812241529) in which the safety and efficacy of a newly registered Artemisinin-Based Combination (Pyronaridine-Artesunate) is being evaluated in pregnant women. This is a Phase 3 diagnostic evaluation conducted in 2 African countries: Democratic Republic of the Congo (DRC) and Burkina Faso. Pregnant women fulfilling the inclusion criteria of the PyraPreg study will be also invited to participate in the PREG-DIAGMAL study. Diagnostic accuracy will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and reported according to STARD principles. Due to the lack of a 100% specific and sensitive standard diagnostic test for malaria, the sensitivity and specificity of the new test will be compared to the available diagnostic practice in place at the selected settings (microscopy and/or RDT) and to quantitative PCR as the reference test. This phase 3 diagnostic study is designed towards the evaluation of the performance of a new diagnostic tool for the screening of malaria and the monitoring of treatment in pregnant women under real conditions life. If successful, the dbPCR-NALFIA could be a valuable tool to add to the diagnostic arsenal for malaria, in particular during pregnancy. Trial registration: Pan African Clinical Trial Registry database (PACTR202203780981413). Registered on 17 March 2022.