Sapronotic pathogens are constituents of complex trophic networks, such as those that structure aquatic and soil ecosystems. In such habitats, sapronotic pathogens live and reproduce among microbial consortia; they also may occasionally infect hosts and cause sapronotic disease (sapronosis). Sapronotic pathogens regroup almost all fungal microparasites and about a third of the bacterial pathogens infecting humans, including for instance nontuberculous mycobacteria. Even though sapronotic agents are naturally present in the environment, their population dynamics are unknown. Despite growing rates of sapronotic disease incidence among humans, wild, and domestic animals, very few studies have examined sapronotic transmission and dynamics in the context of spatially implicit trophic networks. Patterns of sapronotic pathogen transmission arise from complex interactions, including pathogen natural history, nonhost and host environments, and spatial and temporal scales of the system. In order to infer and ultimately predict how environmental disturbances affect trophic interactions and influence sapronotic ecology, we analysed host and nonhost species interacting as prey and as micro- and macropredators within a metacommunity context. Using a set of differential equation models, we assessed responses of environmental load dynamics of a sapronotic disease agent, i.e. a mycobacterial pathogen, within a general framework of environmental disturbance. We show that variation in top-down and horizontal interactions mediated sapronotic pathogen abundance and dynamics in the environment. Our findings indicate that habitat change and trophic interactions within these host-pathogen relationships may strongly affect sapronotic pathogen ecology through both synergistic and opposing mechanisms. This work provides for the first time an understanding of environmental disturbance consequences on trophic webs that include major sapronotic pathogens. In addition, the results provide a basis for interpreting the development of sapronotic epidemics and epizootics in the context of ecosystem modifications, particularly that of agriculture and land-use transformation. Further research of this type will provide a better understanding of the complex dynamics of sapronotic pathogens in animals and humans responding to global change.

BACKGROUND:Understanding the spatial distribution of skin neglected tropical diseases (NTDs) is paramount for surveillance and control strategies, although little is known regarding their natural origin, ecology, and distribution. This study aims to determine how natural and anthropogenic factors affect local to global spatial distribution patterns of a major skin NTD, Buruli ulcer (BU), and its pathogen, Mycobacterium ulcerans (MU). METHODS:Generalized linear modelling of 110 variables grouped into five categories (i.e., physical, edaphic/climatic, animal diversity, plant diversity, and socio-demographic/geographic) were used to estimate continental-scale patterns of both MU and BU cases in Africa. Spatial models allowed the production of BU and MU maps for tropical and subtropical zones worldwide. RESULTS:Natural factors and their interactions consistently influence MU and BU distributions in Africa, with these distributions also responding to anthropogenic factors such as invasive plant species, agriculture and other activities. BU case distribution was driven by sunlight radiation, especially UV-B seasonality. Our extrapolation maps provide a quantitative understanding of the potential distribution of this pathogen and associated BU disease burden. DISCUSSION:Our findings highlight the utility of a disease ecology perspective using large-scale spatial data for understanding drivers of skin NTDs. Complex interactions between natural and anthropogenic factors indicate that developing preventive and control measures is challenging. Particular attention is needed on the role of invasive plant species in the spread of these pathogens, and the complex influence of sun exposure on skin NTDs.

Despite recent interest in land-use and land-cover (LULC) change effects on emerging infectious diseases (EIDs), the debate on global potential health threats remains polarizing. These depend on diverse LULC changes, different types of infectious disease systems, and spatio-temporal scales of studies. Here, using both a bibliometric and scoping review method, we summarize the reliability and availability of published relevant studies on LULC effects on mycobacteria, an important group of infectious bacteria that affect humans and both wild and domestic animals. We make connections of LULC with environmental changes (e.g. soils) that likely lead to an increased risk of mycobacteria spillover to human and other animal populations. An important feature of our review is a focus on research from the richest countries of the world, though some studies have been done in Africa, Asia and South America. Geographically, regions experiencing important LULC transformations, such as many tropical regions of Meso- and South America and Southeast Asia, have been given little or no attention in this important topic. Research on Mycobacterium bovis, and to a larger extent on M. ulcerans, constitutes convincing illustrations of the importance of acknowledging shifts in spatio-temporal scales, from local to global and inter-annual to decadal ones, when evaluating responses of mycobacteria to LULC changes. However, studies on other pathogenic mycobacteria remain very much confined to local and dispersed scales. To date, the role of LULC change effects has not been adequately studied for many human and animal pathogens, and more research and attention to this issue is clearly needed. This review provides a comprehensive set of data on the updates of LULC change and their impact on animal and human mycobacterial infections. It also proposes several research recommendations, in particular to better understand the emergence of mycobacteria in context, by multiplying study sites in different regions of the world and in adopting an ecosystem-based perspective, in order to encourage interdisciplinary research better linking environmental microbiology, veterinary science and medical research.

SUMMARYDespite the clinical relevance of major tuberculous pathogens to domestic animals and humans, the understanding of mycobacterial transmission modes, pathways, and interactions in their natural habitats remains very limited. The reason for this is primarily because ecological and evolutionary concepts have not yet been widely applied to the understanding of these bacteria. Most existing research on mycobacterial transmission is not founded on hypothesis testing but rather tends to accept the most recent explanation and turn it into a canonical fact. In this comparative review, we discuss plausible alternative hypotheses against a null hypothesis of environmental origin to intensify research on mycobacterial pathogens and their capacity to spread in the context of global change. We highlight a major bias in perceptions of mycobacterial infection transmission, with most work concentrating only on the contagious stage of tuberculous clones. We suggest broadening the field to include research on environmental non-tuberculous mycobacteria and their life histories. A deeper understanding of mycobacterial ecology and evolution is more important now than ever, considering the vast diversity of known and unknown mycobacterial species in natural ecosystems. Infectious disease medicine, veterinary science, and public health surveillance should take a more integrative disease ecology approach to enhance the development of new approaches for control of these animal and human pathogens.

Buruli ulcer (BU) is a chronic and debilitating skin disease caused by the environmental pathogen, Mycobacterium ulcerans (MU). The primary virulence determinant is mycolactone, a cytotoxic lipid compound unique to MU and its other mycolactone producing mycobacteria (MPM) ecological variants. Although BU prevalence is highest in West Africa and Australia, little is known about MU and other MPM distribution in non-endemic regions such as the Southeastern United States (US). In this study, environmental samples (water filtrand, plant biofilm, soil, aquatic invertebrates) were collected from nine freshwater sites across Louisiana, Mississippi and Alabama over three sampling periods (August 2020, November 2020, March 2021). Samples were screened for MU and MPM presence and abundance by PCR and genotyped using variable number tandem repeat (VNTR) profiling. All nine sites were positive for MU or other MPM DNA in at least one substrate, except invertebrates. Overall, mean concentrations were 4.3 × 104 genome units (GU)/sample in August 2020, 1.26 GU/sample in November 2020, and 55.5 GU/sample in March 2021. Profiling by VNTR identified four MU (designated A-D) and one M. liflandii genotype(s), among environmental samples, with genotype frequencies varying by site and sampling time. Detection of MU and M. liflandii genotypes in Southeastern US aquatic environments, matching those from BU endemic regions, provides rationale for ongoing surveillance. Our findings broaden the known geographic range of MU and MPMs and offer baseline data to help predict and prevent and predict the possibility of zoonotic transmission in Southeastern US.

Seasonal patterns of mycobacterial infections affecting humans and animals remain a complex and understudied aspect of infectious disease dynamics. These intra-annual patterns are increasingly relevant in the context of global climate change, which may influence the timing and geographic spread of these diseases. A better understanding of such patterns could improve surveillance, prevention, and control strategies. We conducted a mixed-methods bibliometric review combining bibliographic searches and scoping analysis to synthesize decades of research on the seasonality of mycobacterial infections in humans and animals. We systematically searched three major scientific databases—Scopus, PubMed-MEDLINE, and Web of Science—for articles published between 1971 and April 2023. From an initial dataset of 1830 unique articles, we identified and analysed 122 studies that met predefined inclusion criteria. We extracted information on pathogen type, statistical methods, geographic location, and host species. In addition, we conducted a co-citation network analysis to identify key methodological influences and research clusters. The retained studies encompassed tuberculosis, Buruli ulcer, bovine tuberculosis, and other mycobacterial diseases such as leprosy and Johne’s disease. Most articles focused on tuberculosis in humans, followed by Buruli ulcer caused by Mycobacterium ulcerans. There was a marked increase in studies on seasonal trends in tuberculosis and Buruli ulcer over time, with notable variation in geographic and methodological coverage. Research was heavily concentrated in the northern hemisphere, especially in China, while southern regions remained underrepresented. Advanced statistical tools, including generalized linear models and time-series analyses, were instrumental in detecting seasonality, particularly for tuberculosis and Buruli ulcer. Seasonality appears to be a common yet understudied feature of many mycobacterial infections. Greater interdisciplinary collaboration and the use of appropriate analytical tools are essential to better understand these patterns, especially in underrepresented regions. Addressing methodological and geographic gaps will be crucial to improve responses to these diseases in a changing global environment.

Mycobacterium ulcerans pseudoshottsii is a mycolactone-producing bacterium previously isolated from Striped Bass (Morone saxatilis (Walbaum)) from Chesapeake Bay and adjacent waters of the Atlantic Coast of North America. We report the first molecular detection of this pathogen in the native Gulf strain of Morone saxatilis collected from the Pearl River, Mississippi (USA). Molecular identification was conducted using a novel PCR assay targeting the parA-625 intergenic spacer of the virulence-associated pMUM plasmid. The isolate was unambiguously assigned to M. u. pseudoshottsii based on diagnostic single nucleotide polymorphisms (SNPs) and phylogenetic analysis. This report expands the known range of M. u. pseudoshottsii to include Gulf Coast watersheds and highlights the need for enhanced surveillance in wild and aquacultured fish populations of the southern United States.

Understanding interactions between pathogens at the level of the individual host and the population in West Africa, may have noteworthy implications for predictions of diseases emergence and disease control programmes. Hence, the current study was aimed at investigating the interactions between Anaplasma marginale, Babesia bigemina and B. bovis in West African cattle. Twelve sentinel steers in each of the eight selected herds were randomly chosen to perform a one-year-long survey designed to monthly collect blood sample and to diagnose possible infections of the steers. This allowed identifying A. marginale as the most prevalent pathogen across the three surveyed regions (range: 0.60-1), followed by B. bigemina (0.24-0.85) and B. bovis (0.10-0.64); the same ranking order of the tick-borne pathogens was observed when considering the apparent duration of cattle infection. Regarding interaction patterns, mainly avoidance was revealed between A. marginale and B. bigemina and between B. bigemina and B. bovis. Such negative interaction seemed to be beneficial to the West African cattle surveyed, helping them to escape from babesiosis caused by B. bovis. Altogether, studied Boophilus tick-borne pathogens negatively interact within cattle in Benin and Burkina Faso. This pattern raises new questions regarding the underlying mechanisms and potential consequences.

Ehrlichia ruminantium is the tick-borne rickettsia causing heartwater to wild and domestic ruminants. Previously, Multilocus Sequence Typing of this pathogen (MLST) highlighted the co-circulation of two genotypic groups within nearby villages from Burkina Faso where vaccination assays had been previously recurrently performed. In the present study the laboratory strains that had been involved in vaccination assays, which evidenced their close relationships with strains that were later involved in local outbursts, were genotyped. Characterization of the bacterium genetic diversity was extended to four distant Beninese localities where no vaccination assays had ever been performed, through sampling of N=500 specimens of the local tick vector, Amblyomma variegatum. This led evidencing an even higher frequency of new multilocus MLST genotypes in Benin than in Burkina Faso, 93% of the Beninese genotypes included at least one new private allele (i.e., no detected elsewhere), while this was only the case of 80% bacteria genotypes sampled in Burkina Faso. Investigating the genetic structure of the bacterium across the Africa continent revealed a reduction of its diversity in the eastern and southern part of the continent relatively to West Africa. As the bacterial genetic diversity currently remains highest in West Africa than anywhere else in the continent, this area remains optimal for the development and/or testing of vaccines against heartwater.

Tick-borne bacteria of the genera Ehrlichia and Anaplasma cause several emerging human infectious diseases worldwide. In this study, we conduct an extensive survey for Ehrlichia and Anaplasma infections in the rainforests of the Amazon biome of French Guiana. Through molecular genetics and metagenomics reconstruction, we observe a high indigenous biodiversity of infections circulating among humans, wildlife, and ticks inhabiting these ecosystems. Molecular typing identifies these infections as highly endemic, with a majority of new strains and putative species specific to French Guiana. They are detected in unusual rainforest wild animals, suggesting they have distinctive sylvatic transmission cycles. They also present potential health hazards, as revealed by the detection of Candidatus Anaplasma sparouinense in human red blood cells and that of a new close relative of the human pathogen Ehrlichia ewingii, Candidatus Ehrlichia cajennense, in the tick species that most frequently bite humans in South America. The genome assembly of three new putative species obtained from human, sloth, and tick metagenomes further reveals the presence of major homologs of Ehrlichia and Anaplasma virulence factors. These observations converge to classify health hazards associated with Ehrlichia and Anaplasma infections in the Amazon biome as distinct from those in the Northern Hemisphere.

Rhipicephalus microplus, is an invasive tick species associated with the highest economic losses where it occurs. Invasion of West Africa, where breeding is in 95% of case with low input, started in 2000s and was followed by breeder’s complaints of acaricide resistance. Since understanding of population structure could help tick control, this study aimed to investigate processes which influence R. microplus invasion in Benin and Burkina Faso. Thus, seven microsatellites (SSRs) markers were applied to analyse 436 ticks from Benin and Burkina Faso. Subsequently, determination of population limits, population size, and investigation on isolation by distance pattern were achieved. Analyses revealed that herd is the relevant level of population limit in Benin and with the whole dataset. Significant differentiation was highlighted between herds and between R. microplus population from Benin and Burkina Faso. Migration occurred between herds, as indicated by assignment results and migration rates. Furthermore, any bottleneck was not evidenced within dataset. Results suggested that the origin of R. microplus population of Burkina Faso could be Côte d’Ivoire. The limit of population being the herd has obviously to be considered in tick control strategies. Thus, to be efficient, tick control programs should primarily focus on the cattle coming back north after transhumance.

Predicting the outbreak of infectious diseases and designing appropriate preventive health actions require interdisciplinary research into the processes that drive exposure to and transmission of disease agents. In the case of mycobacterial diseases, the epidemiological understanding of the scientific community hitherto was based on the clinical studies of infections in vertebrates. To evaluate the information gained by comprehensively accounting for the ecological and evolutionary constraints, we conducted literature searches assessing the role of mycobacteria interactions with non-vertebrate species in the origin of their pathogenicity and variations in disease risk. The reviewed literature challenges the current theory of person-to-person transmission for several mycobacterial infections. Furthermore, the findings suggest that diverse non-vertebrate organisms influence virulence, mediate transmission, and contribute to pathogen abundance in relation to vertebrate exposure. We advocate that an ecological and evolutionary framework provides novel insights to support a more comprehensive understanding of the prevention and management of diseases in vertebrates.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. We show that the persistence of bacilli in aquatic ecosystems is driven by a seasonal upstream supply, and that the attachment and development of cells to aquatic living forms is essential for such pathogen persistence and population dynamics. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

In light of current international public health challenges, calls for inter- and transdisciplinary research are increasing, particularly in response to complex and intersecting issues. Although widely used under the One Health flag, it is still unclear how inter- and transdisciplinary science should be applied to infectious disease research, public health, and the different stakeholders. Here, we present and discuss our common scientific and biomedical experience in French Guiana, South America to conduct and enrich research in vector-borne and zoonotic infectious diseases, with the aim to translate findings to public health and political stakeholders. We highlight the successful progressive dissolution of disciplinary boundaries that go beyond One Health positive-driven assumptions and argue that specific local conditions, as well as strong support from research and medical institutions, have facilitated an emulsion toward inter- and transdisciplinary science. This argument is intended to improve responses to public health concerns in French Guiana and other countries and regions of the world.

Heartwater, or cowdriosis, is a virulent tick-borne rickettsial disease of ruminants caused by Ehrlichia ruminantium, biologically transmitted by Amblyomma species (A. variegatum in West Africa). In West Africa, this bacterium was recently reported to naturally infect the invasive cattle tick, Rhipicephalus microplus (Rm) through trans-ovarian transmission from replete adult females to offspring. A 'sheep-tick-sheep' cycle was set up to determine whether feeding the progeny of these ticks on naïve sheep could lead to infection, and to compare clinical outcomes resulting from this transmission with those observed following infection by the natural A. variegatum (Av) vector. Using local strains of ticks (KIMINI-Rm and KIMINI-Av) and of E. ruminantium (BK242), we recorded, using the PCR technique, the presence of bacterial DNA in ticks (larvae for Av and females for Rm) engorged on sheep inoculated by BK242-infected blood. The bacterial DNA was also detected in the next stages of the lifecycle of R. microplus (eggs and larvae), and in sheep infested either by those R. microplus larvae or by A. variegatum nymphs moulted from larvae engorged on blood-inoculated sheep. Bacterial infection in these sheep was demonstrated by detecting antibodies to E. ruminantium using the MAP1-B ELISA and by isolation of the bacterium on cell culture from blood. The sequences of PCS20 gene detected in ticks and sheep were identical to that of the BK242 strain. Our results confirm that R. microplus can acquire and transmit E. ruminantium to the next stage. However, this transmission resulted in a mild subclinical disease whereas severe clinical disease was observed in sheep infested by A. variegatum infected nymphs, suggesting differences in the tick/bacteria relationship. Future studies will focus on replicating these findings with ticks of different isolates and life stages to determine if R. microplus is playing a role in the epidemiology of heartwater in West Africa. Additionally, studies will investigate whether sheep that are seropositive due to infestation by E. ruminantium-infected R. microplus are subsequently protected against heartwater. Such data will add to our understanding of the possible impact of R. microplus in areas where it has become recently established.

Understanding the interactions of ecosystems, humans and pathogens is important for disease risk estimation. This is particularly true for neglected and newly emerging diseases where modes and efficiencies of transmission leading to epidemics are not well understood. Using a model for other emerging diseases, the neglected tropical skin disease Buruli ulcer (BU), we systematically review the literature on transmission of the etiologic agent, Mycobacterium ulcerans (MU), within a One Health/EcoHealth framework and against Hill's nine criteria and Koch's postulates for making strong inference in disease systems. Using this strong inference approach, we advocate a null hypothesis for MU transmission and other understudied disease systems. The null should be tested against alternative vector or host roles in pathogen transmission to better inform disease management. We propose a re-evaluation of what is necessary to identify and confirm hosts, reservoirs and vectors associated with environmental pathogen replication, dispersal and transmission; critically review alternative environmental sources of MU that may be important for transmission, including invertebrate and vertebrate species, plants and biofilms on aquatic substrates; and conclude with placing BU within the context of other neglected and emerging infectious diseases with intricate ecological relationships that lead to disease in humans, wildlife and domestic animals.

Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen Mycobacterium ulcerans (MU). Neither the ecological niche nor the exact mode of transmission of MU are completely elucidated. However, some environmental factors, such as the concentration in chitin and pH values, were reported to promote MU growth in vitro. We pursued this research using next generation sequencing (NGS) and mRNA sequencing to investigate potential changes in MU genomic expression profiles across in vitro environmental conditions known to be suitable for MU growth. Supplementing the growth culture medium in either chitin alone, calcium alone, or in both chitin and calcium significantly impacted the MU transcriptome and thus several metabolic pathways, such as, for instance, those involved in DNA synthesis or cell wall production. By contrast, some genes carried by the virulence plasmid and necessary for the production of the mycolactone toxin were expressed neither in control nor in any modified environments. We hypothesized that these genes are only expressed in stressful conditions. Our results describe important environmental determinants playing a role in the pathogenicity of MU, helping the understanding of its complex natural life cycle and encouraging further research using genomic approaches.

Effective population sizes have rarely been estimated in ticks despite the importance of this parameter for evaluating the evolutionary and adaptive potential of tick populations. The present study was aimed at evaluating the effective population sizes of Amblyomma variegatum, the tropical bont tick, in three villages in Burkina Faso. For this purpose, microsatellites markers were developed. Eight out of 19 assessed markers provided good amplification results with 4 to 24 alleles recorded per marker on 216 genotyped ticks. The within-samples polymorphism was congruent with Hardy-Weinberg expectations at four markers while sex linkage and/or null alleles were observed at the others. As sampling involved two tick generations, effective population sizes were independently estimated by two methods insensitive to heterozygosity: the first one is based on linkage disequilibrium analysis within a single cohort while the second uses the changes in allele frequencies across generations. Both methods estimated the number of reproducing ticks ranging from two to a few tens reproductive adults per village and cohort. Such small estimates are congruent with the rarity of records of acaricide resistance in A. variegatum.