Yaws, a neglected tropical disease caused by Treponema pallidum subsp. pertenue, primarily affects children in impoverished rural areas. It is spread through direct skin contact. The disease progresses through clinical stages. In the primary stage, patients develop a papilloma or ulcer, usually painless, often on the lower extremities, that is highly contagious. If untreated, this lesion heals spontaneously but may progress to secondary yaws, characterized by disseminated skin lesions, scaly papules and painful hyperkeratotic plaques on the palms and soles. Tertiary cases occur in 10% of untreated individuals and can cause severe disfigurement, but with the wider availability of treatment, this is rare today. Although yaws can be treated with benzathine penicillin, oral azithromycin has become the preferred treatment owing to its ease of administration. Currently, it is known to be endemic in 16 countries, with the majority found in the Western Pacific, followed by West Africa and parts of South East Asia. The World Health Organization has renewed eradication efforts, targeting global eradication by 2030 through mass drug administration (MDA) campaigns and enhanced diagnostics. However, challenges such as emerging azithromycin resistance, difficulties in achieving high MDA coverage and potential zoonotic transmission from nonhuman primates threaten progress. Accurate diagnosis is critical, especially in distinguishing yaws from similar skin conditions and ensuring all communities where it is endemic are identified and offered treatment. Strengthening surveillance and enhancing laboratory capacity for molecular diagnostics is essential for the success of the eradication campaign. With sustained effort and innovation, the global eradication of yaws by 2030 remains achievable.
Monkeypox virus (MPXV) is a zoonotic pathogen known to be endemic to the Congo basin and West Africa, and which causes characteristic lesions disseminated on all skin surfaces of infected cases. Multiple MPXV outbreaks have been reported in the Central African Republic (CAR), a country in the Congo basin, at an increased frequency since 2020. The genomic history of these outbreaks in CAR is poorly characterized due to undersampling, with only a recent expansion in the number of sequences from CAR. Here, we report twenty-six new near-complete genomes from six prefectures of CAR, selected to represent outbreaks that occurred in the country between 2019 and 2024. Our analysis shows the sustained homogeneity of genomes in CAR, as all of them belonged to Clade Ia, but with an expansion of sub-lineages and therefore increased MPXV diversity within CAR. We highlight the introduction into CAR of a lineage previously known to occur only in Gabon and Cameroon, as well as the apparent regional clustering of MPXV genomes in CAR. Our analysis reveals limited APOBEC3-mediated activity, which is consistent with recent zoonotic origins and short human-to-human transmission chains observed in CAR. These analyses provide an in-depth view of the genomic diversity of MPXV in the Central African region.
BACKGROUND:Primary Epstein Barr Virus (EBV) infection occurs during late adolescence and is characterized by the symptomatic manifestation of infectious mononucleosis (IM). Primary EBV infection in malaria-endemic areas often occurs in young children by the age of 2 and is generally asymptomatic. Primary EBV infection in children of this age results in humoral immune suppression to unrelated antigenic challenges for approximately 4 weeks. Whether EBV in infants similarly suppresses the development of antibody responses against Plasmodium falciparum (Pf) predisposing infants to severe malaria is unknown. METHODS:We undertook a cross-sectional study of 195 infants aged 6-24 months in Cameroon. Infants were determined to be parasitaemic by microscopy or RDT, and their disease severity classified based on WHO criteria. The EBV infection status of each child was determined using a standard serological classification system, and the magnitude, breadth, and invasion blocking capacity of the anti-Pf antibody response were quantified. RESULTS:24% of children were serologically positive for active EBV infection, and the highest proportion of severe malaria cases was in children with active EBV. An elevated magnitude and breadth of the antibody response with increased in vitro invasion-blocking capacity was observed in children with active EBV but circulating parasitaemia in vivo was similar. CONCLUSION:Primary EBV infection may be a risk factor for developing severe malaria in children 6-24 months. Targeting EBV infection in young children may be beneficial in protecting against the development of severe falciparum malaria in children living in malaria-endemic areas.
BACKGROUND:We aimed to establish an external quality assessment (EQA) programme for the yaws eradication campaign that would meet the needs of reference and district-level laboratories in low- and middle-income countries. METHODOLOGY/PRINCIPAL FINDINGS:We designed proficiency testing items (PTIs) using a plasmid containing gene target sequences for Treponema pallidum (TP) and Haemophilus ducreyi (HD). The storage stability of the plasmids under different environmental conditions was then tested. A proficiency testing panel of seven swabs loaded with different concentrations of plasmids in different combinations, as well as human HEK293 cells to simulate the sample background, was prepared and sent to participating reference (RL) and district (DL) laboratories in Ghana, Côte d'Ivoire and Cameroon followed by three rounds of blinded proficiency testing. We tested quantitative real-time PCR (qPCR) performance of reference laboratories and loop-mediated isothermal amplification (LAMP) performance of district laboratories and retested 20% of human field samples at the London School of Hygiene & Tropical Medicine laboratories to further assess qPCR quality. FINDINGS:PTIs proved to be stable in dry conditions with no significant loss of copy number. Participating laboratories achieved qPCR results with a concordance of 95.0-100.0% (97.7% ± 5.2% (mean±standard deviation ((SD)) with the provider and a concordance of 76.0-100.0% (TP: 90.3 ± 13.7% and HD: 78.5 ± 7.5% (mean±SD)) for LAMP results, with inconsistencies, particularly in the detection of low HD plasmid DNA levels combined with high TP plasmid copies. Retesting of field samples resulted in 100% correct TP and HD sample identification by the African reference laboratories. CONCLUSIONS/SIGNIFICANCE:We have developed a functional plasmid-based EQA programme specifically designed to meet the needs of resource-poor settings in the tropics. The programme is suitable as a blueprint for other disease programmes.
Importance:Escherichia coli and Klebsiella pneumoniae are major causes of urinary tract infections. While antibiotic resistance in these critical pathogens is a global concern, data from Africa remain sparse, cover short time frames, and aggregate multiple specimen types. Objective:To model antimicrobial resistance trends in urinary E coli and K pneumoniae isolates from 6 African countries between 2010 and 2022 and to project future resistance patterns. Design, Setting, and Participants:Data for this retrospective cross-sectional study were obtained from Pasteur Network clinical laboratories located in the capital cities of 5 African countries (Cameroon, Central African Republic [CAR], Madagascar, Morocco, and Senegal) and from 1 university hospital in Benin. Urine samples yielding E coli or K pneumoniae collected during routine clinical care were included. Data collection spanned 2008 to 2023, with a shared observation period from October 2014 to December 2021. Data were analyzed from March through December 2025. Main Outcomes and Measures:The primary outcome was resistance in E coli and K pneumoniae urinary isolates, measured as nonsusceptibility to aminopenicillins (for E coli), fluoroquinolones, third- and fourth-generation cephalosporins, β-lactam and β-lactamase inhibitor combinations, aminoglycosides, and carbapenems. Resistance trends were analyzed using logistic regression with generalized estimating equations. Results:A total of 44 367 urinary isolates (mean [SD] age of patients, 35.8 [30.2] years; 26 935 isolates from women among 42 839 samples with sex data [62.9%]) were included. Mean (SD) age ranged from 29.1 (30.5) years among patients with K pneumoniae-positive samples in Cameroon to 54.3 (23.4) years among patients with E coli-positive samples in Morocco. E coli-positive samples were more common in women, with the highest proportions in Madagascar (11 948 women among 16 137 patients [74.0%]) and CAR (1329 women among 1893 patients [70.2%]), whereas K pneumoniae positive samples showed no clear sex pattern. At study end, amoxicillin resistance in E coli exceeded 85% across sites (eg, 96.0% [95% CI, 93.5%-97.6%] in Morocco), and amoxicillin-clavulanate resistance surpassed 50% for E coli (eg, 84.9% [95% CI, 77.7%-90.1%] in Morocco) and K pneumoniae (eg, 96.1% [95% CI, 89.4%-98.7%] in Morocco) in most countries. E coli resistance to third-generation cephalosporins (3GCs) and fluoroquinolones surpassed 35% at study end, with increasing trends in most countries (eg, 34.5% [95% CI, 27.3%-42.6%] to 59.8% [95% CI, 55.7%-63.8%] for cefotaxime in Benin and 32.4% [95% CI, 25.1%-40.7%] to 75.9% [95% CI, 72.4%-79.1%] for norfloxacin in Senegal). For K pneumoniae, resistance to 3GCs increased in Cameroon, Madagascar, CAR, and Senegal, exceeding 50% in most settings (eg, 50.7% [95% CI, 45.6%-55.9%] to 76.6% [95% CI, 71.7%-80.9%] for cefotaxime in Madagascar). Rates remained stable in Benin and Morocco. Fluoroquinolone resistance increased in Cameroon, Senegal, and CAR (eg, 38.5% [95% CI, 25.7%-53.0%] to 65.8% [95% CI, 58.8%-72.2%] for ciprofloxacin in Senegal); remained high in Benin and Morocco; and decreased in Madagascar but remained elevated (eg, 63.7% [95% CI, 58.7%-68.3%] to 59.9% [95% CI, 54.1%-65.4%] for norfloxacin). For both bacteria, carbapenem resistance remained less than 18% (eg, 17.2% [95% CI, 11.8%-24.3%] for K pneumoniae resistance to ertapenem in Senegal), but resistance to ertapenem reached 28.0% (95% CI, 25.7%-30.5%) for E coli and 27.8% (95% CI, 22.0%-34.5%] for K pneumoniae in Madagascar. Projections suggest that 3GC and carbapenem resistance could exceed 90% by 2050 in most countries (eg, 2037 [95% CI, 2032-2053] for E coli resistance to imipenem in Benin). Conclusions and Relevance:In this study, elevated and increasing resistance levels were observed, underlining the urgent need for improved measures against antimicrobial resistance in Africa.
