Genomics of infectious bacterial skin diseases in wild non-human primates: Yaws and Leprosy

Yaws-like disease in non-human primates (NHPs) caused by Treponema pallidum subsp. pertenue (TPE) has been largely reported in sub-Saharan Africa with diverse dermatological manifestations. However, it remained unclear how the genomic diversity of TPE lineages that do occur in NHPs is distributed across hosts and space. In Taï National Park (TNP), Côte d'Ivoire, symptomatic Cercocebus atys monkeys were observed to have yaws- and syphilislike lesions. The present study investigated the TPE diversity in wild NHPs in TNP and other sites where the disease occurs in sub-Saharan Africa.
Phylogenomic analyses from this study revealed that dermatological pathology observed among sooty mangabeys in TNP were caused by a large diversity of TPE lineages. All TPE genomes determined from these sooty mangabeys were different and exhibited divergence levels not observed in other field sites where the disease seems to be epizootic. The results presented in this dissertation, do not support the epizootic spread of a single TPE clone at TNP, but rather points towards frequent independent introductions of the bacterium, which can cause orofacial and genital-like lesions within a single social group of Cercocebus atys monkeys. Besides, simian TPE isolates determined in this study and those available in the public domain, did not form monophyletic clades based on host species or the type of symptoms caused by an isolate, but rather clustered based on geography. This phylogenetic pattern is compatible with cross-species transmission of TPE within ecosystems where this disease occurs, though it remains unclear how often and by what means this transmission occurs. This study now lays basis for future studies on the potential occurrence of TPE transmission among different NHP species and future studies should aim to reveal transmission pathways of TPE in NHP habitats.
This work also demonstrates that informative TPE genomic data can be obtained from old NHPs bones collected from endemic areas; helping to trace the disease back into the past as well as identify new sites that might be affected by the disease where no clinical cases are currently observed. Thus, using bone derived TPE short sequences coupled with phylogenetic read placement algorithm, this study showed that TPE infected NHPs in TNP for at least three decades ago, complementing clinical evidence which only started accumulating from 2014. Additionally, detection of TPE in field sites were no clinical cases are observed indicates that TPE infections in NHPs are underreported, warranting the intensive surveillance of the disease in wild NHPs.
In the second part, this study aimed to investigate the causative agent of leprosy-like symptoms observed in NHPs in both Cantanhez National Park and Täi National Park. The investigations involved adapting a suitable non-invasive screening tool to facilitate the determination and characterisation of the causative agent of the observed skin lesions.
Using faecal samples, this study determined that M. leprae was the cause of the leprosy- like lesions confirming the first ever observed sylvatic leprosy cases among NHPs in West Africa. This finding shows that faecal samples of NHP that are easily collected, can be used for surveillance of leprosy in wild NHPs and have the potential for scalability in terms of screening huge populations over large areas. Further, this study also presents sequence data highlighting that wild chimpanzees are infected with two genotypes of Mycobacterium leprae that are rare in human populations i.e. 4N/O and 2F and could potentially serve as reservoir hosts of these rare genotypes. For the first time, genotype 2F of M. leprae that circulated mostly in the medieval time in Europe was detected in West Africa. The detection of 2F in a region dominated by genotype 4 M. leprae strains questions the current understanding that the infection in NHPs was a result of a human strains spill overs. Finally, it is now evident that M. leprae is not only a human pathogen since red squirrels, armadillos and NHPs are also naturally infected. Therefore, investigations into the role these animal reservoir hosts play in the ecology of leprosy disease might be useful in informing strategies on the ongoing leprosy eradication campaign by WHO.