OBJECTIVES:Artemisinin-resistant Plasmodium falciparum has emerged in several East African countries neighbouring Madagascar. Despite the island's substantial malaria burden, recent data on artemisinin partial resistance are limited, raising concerns about the potential emergence of resistant parasites. This study provides an updated overview of the prevalence and diversity of P. falciparum Kelch13 (pfkelch13) polymorphisms in Madagascar. METHODS:During a nationally representative, cross-sectional survey conducted between January and May 2024, dried blood samples were collected from 4850 febrile patients at 65 health facilities. Pfkelch13 genotyping was performed using a targeted amplicon deep sequencing approach. RESULTS:Of the 1944 P. falciparum-positive samples, 963 (49.5%) pfkelch13 sequences were successfully obtained, and 885 (91.9%) corresponded to the 3D7 wild-type. Non-synonymous and synonymous mutations were detected in 1.8% (17/963) and 6.2% (60/963) of isolates, respectively, whereas one isolate (0.1%) carried double mutations. Of the 18 mutations identified, 5 had not been previously reported. The two most frequent polymorphisms in Madagascar were the synonymous mutations C469C (3.0%, 29/963) and P417P (2.8%, 27/963). None of the WHO-validated artemisinin partial resistance markers were detected. CONCLUSION:This study provides an updated baseline of pfkelch13 polymorphisms in Madagascar, with no evidence of artemisinin partial resistance emergence. Importantly, no parasites harbouring a validated artemisinin resistance marker were detected across the regions sampled, suggesting that resistant parasites have not yet become established. These findings provide a valuable baseline for future genomic surveillance efforts aimed at the early detection of mutations associated with artemisinin partial resistance.
Bats are reservoir hosts for numerous well-known zoonotic viruses, but their broader virus-hosting capacities remain understudied. Picornavirales are an order of enteric viruses that cause disease across a wide range of mammalian hosts, including Hepatitis A in humans and foot-and-mouth disease in ungulates. Host-switching and recombination drive the diversification of Picornavirales worldwide. Picornaviridae and Caliciviridae (families within Picornavirales) have been described in bats across mainland Africa, but surveillance for these viruses has been rare in the Southwest Indian Ocean Islands. Prior work in Madagascar has described numerous bat viruses, some with zoonotic potential, that demonstrate both high identity to and extreme divergence from viruses found in sister bat species in Africa. Using metagenomic Next Generation Sequencing of urine and fecal samples obtained from three species of endemic Malagasy fruit bats (Eidolon dupreanum, Pteropus rufus, and Rousettus madagascariensis), we identify and describe 13 full-length and 38 partial-length genomic sequences within the Picornaviridae and Caliciviridae families (36 picornavirus and 15 Sapovirus sequences). We find evidence that host-switching between Madagascar and mainland African bat picornaviruses and sapoviruses, followed by host-parasite co-speciation, likely shaped the diversification pattens of these novel sequences, with little evidence for cross-species transmission among Malagasy bat species in close contact.
This research aimed to investigate the prevalence and diversity of Bartonella in small mammals and their ectoparasites from the Central Highlands of Madagascar and to refine existing information on potential associated zoonotic diseases. A retrospective analysis was performed on mammals and their ectoparasites collected in the Fandriana and Ankazobe districts, including 253 spleen samples from seven small mammal species and 183 individual ectoparasites (132 fleas and 51 ticks). Genomic DNA was extracted and amplified by polymerase chain reaction (PCR) targeting the nuoG gene (346 bp). Sanger sequencing of the PCR products was performed to assess Bartonella diversity using phylogenetic analysis. In total, 60.1
The Mandoto District in the central highlands of Madagascar experiences year-round transmission of Plasmodium vivax (P. vivax) and Plasmodium falciparum (P. falciparum). Monthly malaria case data from 27 health centers across Mandoto between 2019 and 2024 were analyzed alongside meteorological data to understand transmission dynamics and forecast potential influences of climate change using descriptive, cross-correlation, and seasonal autoregressive integrated moving average forecast models. Over a period of 6 years, 276,318 rapid diagnostic tests (RDTs) were performed, yielding a 39.6% positivity rate, totaling 109,428 malaria cases. After 2021, when multispecies RDTs became available, 71.5% of cases were attributed to P. falciparum, and 28.5% were attributed to P. vivax. Both species were co-endemic across all health centers, with the western region experiencing a higher transmission risk. Malaria cases peaked in January, with a second peak from April to June after the rainy season, and declined between July and September. Precipitation and temperature effectively revealed the seasonality of malaria dynamics, thereby improving model accuracy. Plasmodium falciparum exhibited stronger associations with precipitation and temperature variability. The present study highlights that combining time-series modeling with precipitation and temperature data can help predict malaria cases and support timely planning and resource allocation.
Background Reproductive tract infections (RTIs) and bacterial vaginosis (BV) cause significant reproductive morbidity but often remain undetected. We evaluated cervicovaginal cytokine signatures associated with RTIs and vaginal dysbiosis in women from South Africa, Madagascar, and Zimbabwe. Methods Vaginal swabs from 676 sexually-active women (18–35 years) were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), Candida spp., and BV. IL-1α, IL-1β, and IP-10 were measured by ELISA; associations were assessed using multivariable regression and population attributable fractions. Results BV prevalence was 50.4% (337/668), followed by CT (15.0%), TV (11.8%), NG (5.7%), MG (4.5%), and Candida spp. (6.8%). BV dominated elevated IL-1α/IL-1β, accounting for >60% of high cytokine responses. Intermediate microbiota (Nugent 4–6) showed similar inflammatory profiles and, with BV, reduced IP-10. Independently, NG was associated with elevated IL-1α/IL-1β; CT with elevated IL-1β/IP-10; TV with elevated IP-10; Candida spp. with all cytokines; MG showed no association. Most infections were asymptomatic, eliciting similar inflammatory profiles to symptomatic cases. Pathogen-specific inflammatory signatures were consistent across countries. Conclusions RTIs and dysbiosis elicited consistent inflammatory signatures across countries. Their high prevalence in asymptomatic women highlights the potential of host-response biomarkers to identify undetected genital inflammation (ClinicalTrials.gov: NCT05723484 ). Lay summary Reproductive tract infections and bacterial vaginosis (BV; a common condition in which the normal protective bacteria in the vagina are replaced by a mix of other bacteria) are major causes of poor reproductive health, but many women have no symptoms and remain undiagnosed. In this study, we measured inflammatory proteins in vaginal samples from 676 women in South Africa, Madagascar, and Zimbabwe and examined how these markers were associated with infections and changes in the vaginal microbiota. We found that BV was the strongest driver of genital inflammation and that women with intermediate vaginal microbiota, often considered a transitional microbial state, showed similar inflammatory profiles. Different infections were associated with distinct inflammatory patterns, but many women with substantial inflammation had no symptoms. Importantly, these inflammatory responses were broadly similar across all three countries. Together, these findings highlight important limitations of symptom-based diagnosis and support the development of host-response diagnostics that can identify by reproductive tract infections and vaginal dysbiosis, including in women who would otherwise remain undiagnosed.
