Abstract Purpose Antibiotic use (ABU) is a major driver of antimicrobial resistance (AMR), but ABU patterns are poorly understood in low-income countries where the burden of AMR is great and ABU is insufficiently regulated. Here, we report ABU from ten sites ranging from rural villages to small cities in Madagascar, a country with high AMR levels, and present results from modeling to identify factors that may be associated with ABU in this setting. Methods We conducted surveys of 290 individuals from ten sites in the SAVA Region of northeast Madagascar to gather data on sociodemographic characteristics, agricultural and animal husbandry practices, recent antibiotic use, the antibiotics that participants recalled using in their lifetimes, and the sources of their antibiotics. Using these data, we conducted statistical analyses with a mixed-effects logistic model to determine which characteristics were associated with recent antibiotic use. Results Nearly all respondents (N=283, 97.6%) reported ABU in their lifetimes, with amoxicillin being the most widely reported antibiotic (N=255, 90.1% of those reporting ABU). All recalled antibiotics were classified as frontline drugs except for ciprofloxacin. Most respondents who reported antibiotic use also reported obtaining antibiotics without prescriptions from local stores (N=273, 96.5%), while only 52.3% (N=148) reported obtaining antibiotics through a prescriptive route, such as from a health clinic or private doctor. Of the 127 individuals (44.9%) who reported recent ABU, men were found to be significantly less likely to have recently taken antibiotics than women. Conclusions Our findings provide new insights into ABU in agricultural settings in low-income countries, which have historically been understudied in AMR and pharmacoepidemiologic research. Knowledge of ABU patterns supports understanding of AMR dynamics and AMR control efforts in these contexts, such as interventions on inappropriate antibiotic dispensing. Key points Antibiotic use (ABU) in Madagascar is largely unstudied despite its role in antimicrobial resistance (AMR), which Madagascar faces a high burden of. ABU was widespread among livestock owners in northeast Madagascar, with the majority of study participants reporting ABU in their lifetimes and most people reporting ABU also having taken antibiotics in the previous three months. Most respondents reported obtaining their antibiotics from non-pharmaceutical stores, indicating high levels of unregulated ABU, though more than half also reported sourcing their antibiotics through prescriptive means (like doctors and health clinics). Men were less likely than women to have taken antibiotics in the previous three months. These findings support the development of interventions to mitigate the burden of AMR in Madagascar and similar contexts while underscoring the need for more comprehensive research on the drivers and patterns of ABU. Plain language summary In this study, we provide basic information on antibiotic use (ABU) patterns in Madagascar, a country that experiences high levels of resistance but has been particularly understudied in AMR and pharmacological research. We surveyed 290 farmers with livestock from ten sites across northeast Madagascar about their ABU and found that nearly all study participants (N=283, 97.6%) have used antibiotics in their lifetimes, while a little under half of those who reported ABU also reported using antibiotics in the previous three months (N=127, 44.9%). The most used antibiotic was amoxicillin (N=255, 90.1%). Most people obtained their antibiotics from sources that do not require prescriptions, like general stores, indicating that most ABU is unregulated. Through modeling, we also found that men were less likely than women to have taken antibiotics in the previous three months (OR=0.50, CI 0.30-0.82). These findings help us better understand the dynamics of ABU in low-income countries, which have historically been understudied in AMR and pharmacological research. They also support efforts to mitigate the burden of AMR by revealing ABU dynamics that may contribute to the emergence and spread of AMR, as well as identifying targets for intervention to curb inappropriate ABU.
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
Human-induced land-use change can affect the composition of small mammal communities and the ecology of their zoonotic pathogens - yet questions remain on the direction and generality of these changes, which can have opposite effects on disease prevalence depending on the ecological context and pathogen involved. These contrasting patterns highlight the need to investigate how specific host-pathogen assemblages respond to local anthropogenic land-use mosaics. To address this need, we studied terrestrial and bat species composition, Leptospira infection prevalence, and Leptospira species composition across a mosaic of land-use types in northeastern Madagascar. We found differences in host communities between forested, agricultural, and village land-use types for both bat (n = 400) and terrestrial (n = 2,053) small mammal communities. Leptospira infection prevalence was higher in bats (37.7%) than in terrestrial small mammals (13.8%), and bats were infected with Leptospira strains that were molecularly distinct from those shed by terrestrial small mammals. Non-native mice and rats were almost exclusively infected with cosmopolitan L. kirschneri and L. interrogans, respectively, while some native terrestrial small mammals sheltered L. mayottensis, and bats hosted a more diverse set of Leptospira species. Leptospira prevalence across land-use types varied in terrestrial small mammals, but not in bats. Altogether, the highest prevalence occurred in mice in flooded rice fields. Our data show that land use predominantly impacts Leptospira infecting terrestrial mammals, likely due to habitat disturbance favoring replacement of endemic hosts and pathogens with Muridae rodents and their associated pathogens, many of which are zoonotic. IMPORTANCE:Leptospirosis, a globally distributed, environmentally transmitted zoonosis, causes 2.9 million disability-adjusted life years annually, primarily among rural farmers in tropical regions. Infected animals' urine contaminates soils and water with Leptospira bacteria, where other individuals are then exposed. Understanding the impact of land use on the transmission of this disease is of considerable importance. In Madagascar, infection dynamics are impacted by the combined effects of converting forests to agricultural fields and colonization of these areas by non-native mammal species, which carry molecularly distinct lineages of Leptospira. We show that land use corresponds to the replacement of native species and endemic Leptospira lineages with non-native species and their cosmopolitan L. interrogans and L. kirschneri. Together, this contributes to higher infection prevalence in more disturbed habitats like flooded rice fields, where >50% of mice captured were infected, highlighting the important effects of land use on Leptospira prevalence and presence, which together impact zoonotic risk.
Heterogeneity in contact patterns can have marked effects on disease transmission, including through superspreading where few individuals drive most infections. Networks based on different types of human-human contacts quantify individuals' centrality, which can be used to identify individuals or sub-populations who are at increased risk of spreading disease. By understanding the predictors of centrality, high-risk individuals and sub-populations can be targeted to improve public health intervention strategies, even when detailed network data are unavailable. This study inferred transmission potential networks representing different pathogen transmission pathways among people living in rural villages of northeast Madagascar. We constructed four network types: social, close contact, household proximity, and environmental overlap using survey data and global positioning system (GPS) trackers. We then investigated how sociodemographic and anthropometric variables predicted different types of network centralities using multiple mixed effects linear models. Gender and wealth based on household material quality tended to be the most important sociodemographic predictors of centrality, but centrality outcomes varied by network type and had wide confidence intervals. Men tended to be more central to their environmental overlap network than women. Further, wealth based on household materials was an important, positive predictor of close contact network centrality. Gender and wealth were associated with centrality in transmission-potential networks but varied in their importance across different network types. Our study results suggest that targeted intervention efforts focused on diseases that are transmitted through shared environments (i.e., parasites shared through soil or water) or direct contact (i.e., respiratory infections) in similar agricultural settings should consider gender- and wealth-associated differences in contact patterns.
Abstract Among Madagascar primates, the sportive lemurs (family Lepilemuridae) have seen their species diversity increase from eight in 2005 to 26 in 2009 mostly by applying the phylogenetic species concept to DNA barcode data. Despite the genus being speciose, only one case of sympatry is known from northern Madagascar, where two sportive lemur species described based on low mtDNA divergence, Lepilemur ankaranensis and Lepilemur milanoii , were found to co-occur at the center of their joint distribution range. Here, to clarify the taxonomy of these two species and examine their sympatry, we apply an integrative taxonomic framework to genomic and morphological data from 84 individuals of L. ankaranensis and L. milanoii , encompassing their entire distribution range and the forest of Analafiana, beyond their southernmost limit. Using clustering, multivariate, and isolation by distance analyses, we find no evidence of a sympatric zone and show that despite clear genetic differentiation between regions, the genomic and morphological diversity of the L. ankaranensis - L. milanoii - Analafiana group is clinal and explained by geographic distance. These results clarify that L. milanoii is a junior synonym of L. ankaranensis and that the Analafiana forest population belongs to L. ankaranensis , extending its distribution. It further implies that the “sympatric” zone—the Andrafiamena forest—hosts conspecific individuals with slightly differentiated mtDNA backgrounds, rather than slightly differentiated sympatric species. Lastly, we re-evaluate the IUCN conservation metrics of L. ankaranensis , which continue to qualify as Endangered (EN) under the B1ab(i-v) criteria.
