By Marina Ramon, Hellen Bersacola and Joana Bessa
Marina Ramon is a PhD student at the University of Exeter, supervised by Dr Kimberley Hockings, Dr Camille Bonneaud and Prof Mike Bruford. Dr Hellen (Elena) Bersacola is a Darwin Research Fellow/ Postdoctoral Research Associate at the University of Exeter. Joana Bessa is a DPhil student at the University of Oxford, supervised by Dr Dora Biro and Dr Kimberley Hockings. All co-authors are members of the Cantanhez Chimpanzee Project.
Leprosy has been reported in wild chimpanzees for the first time by an international team of scientists and conservation practitioners of which we are part. Although the leprosy-causing bacteria, Mycobacterium leprae, was long considered to be an obligate human pathogen, we currently know that leprosy circulates in nine-banded armadillos in the Americas and in red squirrels in the UK. However, it had never been reported in wild animals in Africa until now. We confirmed cases of this chronic disease among two unconnected West African populations of chimpanzees, in Cantanhez National Park, Guinea-Bissau, and Taï National Park, Côte d’Ivoire. The monitoring of these populations revealed the progression of leprosy-like symptoms, and screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent. Phylogenetic analysis showed the presence of distinct strains of leprosy in each population, both uncommon in humans. Our findings suggest that M. leprae may be present in more wild animals than suspected.
How did this whole story start? How did we get here?
The journey towards the discovery of leprosy in wild chimpanzees started eight years ago, almost by chance, when Joana Bessa was doing her master’s in Cantanhez National Park, an agroforest mosaic located in the south-western part of Guinea-Bissau. There, chimpanzees and humans live in sympatry, meaning they share the space and resources. Because of this close overlap with humans, chimpanzees in Cantanhez are intentionally unhabituated to researchers to ensure they remain fearful to people, limiting negative interactions and potential disease transmission.
Map of the chimpanzee study sites: Cantahez National Park (CNP), in Guinea-Bissau, and Taï National Park (TNP), Côte d’Ivoire.
In May 2013, while searching for chimpanzee signs, Joana saw a group of chimpanzees in a recently burnt field in Caiquene-Cadique and noticed a young female at a distance showing patches of hair missing on her back and some open ulcerations. This was the first time she observed such a thing, but since the animal was in a burnt field, Joana thought that the most likely explanation was that the chimpanzee had suffered some burns.
A few months later, Joana photographed a juvenile female (later called Rita) during a road–crossing and later on feeding on a cashew orchard in Caiquene-Cadique. The chimpanzee had a folded ear and some discoloration in her face, but as this is a common characteristic of western chimpanzees, she didn’t associate it with a potential disease, but saved the photo in a “strange-looking chimpanzee” folder. Given that Joana’s work was based on indirect data collection and opportunistically observing the chimpanzees, she did not get the chance to re-encounter these two individuals again that year.
Rita, photographed by Joana Bessa in a cashew orchard in Caiquene-Cadique in 2013. Photo credit: Joana Bessa/ Cantanhez Chimpanzee Project.
A couple of years later, Joana and Hellen Bersacola went back to Cantanhez to set up camera traps for another project. The camera traps increased dramatically the amount of photographic and video data. Both females were captured on video, and their appearance had significantly worsened. The cameras also recorded a male (Jimi) in a second neighboring community, Lautchande, with similar clinical signs. The number of individuals found, with previously undescribed physical symptoms, made Joana and Hellen think that these were likely suffering from an unknown disease, and brought them to the attention of their supervisor Kimberley Hockings who immeditaley suspected leprosy.
Jimi, captured by a camera trap in Lautchande in 2015. Photo credit: Joana Bessa and Hellen Bersacola/ Cantanhez Chimpanzee Project.
Work with camera traps continued when Hellen and Joana went back to Cantanhez for their PhD projects in 2016 and 2017, respectively. More footage of the identified individuals was collected, showing the worsening of the physical symptoms. A fourth chimpanzee, an adult male from a third community (Baaba), Cambeque, showing similar symptoms, also started popping up in the camera traps. It became more and more clear that these chimps may be affected with a disease, something like leprosy… but the research team did not have any molecular evidence.
Hellen and Iaia checking the photos on one of the cameras used to monitor Caiquene-Cadique chimpanzees during Hellen’s PhD study. Joana and Mamadu Cassamá searching for signs of chimpanzee tool use, Joana’s PhD topic. Photo credits: Hellen Bersacola and Joana Bessa.
Baaba, captured by a camera trap in Cambeque 2017. Photo credit: Hellen Bersacola/ Cantanhez Chimpanzee Project
In early 2017 Kimberley Hockings contacted Prof Fabian Leendertz at the Robert Koch Institute (RKI) in Germany. Fabian suggested collecting faecal samples to check for traces of bacteria that may be causing the kind of symptoms found. Boxes filled with faecal sample kits were prepared and sent to Bissau, and with the help of an amazing local team of field assistants, Hellen and Joana, whilst doing their PhD fieldworks, began also collecting chimpanzee poos.
Djibi Abu Indjai collecting chimpanzee faecal samples and Iaia Tawél Camará checking camera traps, the two methods used to detect and monitor leprosy in chimpanzees. Photo Credit: Hellen Bersacola.
By the end of 2017, 121 samples had been collected by our team and sent to Germany, where they were analysed by Dr Benjamin Mubemba, by that time a PhD student at RKI. After years of wondering what was affecting the Cantanhez chimpanzees, and after months of sweaty fieldwork chasing after chimpanzee poos, in April 2018, we finally got the first positive results for M. leprae, which proved that leprosy was present in this wild chimpanzee population. Later on, the PhD student Josh Lynton-Jenkins, supervised by Dr Camille Bonneaud at the University of Exeter, carried out microsatellite analyses of the positive samples from Caiquene-Cadique, which confirmed that they originated from two distinct female individuals. That was exactly the same we had observed from footage!
The Cantanhez findings were significant. This was the first time wild chimpanzees were known to carry leprosy. But, was the Cantanhez population the only one affected? Could there be other western chimpanzees or even other animal species suffering from leprosy? Fabian and Dr Roman Wittig from the Max-Planck-Institute for Evolutionary Anthropology working at Taï National Park, in Côte d’Ivoire, began to wonder if any of the long-term habituated chimpanzees they studied for decades could be carrying the disease.
In June 2018, researchers at Taï first noticed leprosy-like lesions on an adult male called Woodstock. They also analysed his faeces and detected M. leprae from that month onwards, suggesting that this bacteria was causing the lesions. After this confirmation, they wanted to know if leprosy also affected other individuals. In order to do so, they checked necropsy samples, which have been collected from all dead individuals at Taï since 2000. Surprisingly, they found that a female chimpanzee called Zora who had lived in the same community as Woostock and had been killed by a leopard in 2009, tested positive for leprosy in samples from various organs and in faecal samples. When researchers looked at the photos taken from Zora in the years before her death, they could now identify leprosy-like symptoms. They also examined skin samples from Zora, which presented typical signs of leprosy. All in all, these combined evidences unambiguously pointed towards a M. leprae-induced leprosy.
Woodstock at Taï National Park, Côte d’Ivoire. Photo credit: Taï Chimpanzee Project.
In July 2018, Marina Ramon was sent as a research assistant to Cantanhez with the intent of continuing the camera trap monitoring and sample collection, now expanding to other chimpanzee communities to assess how widespread the disease was across the park and survey its progression in the sick individuals previously identified. While revising camera trap footage, Iaia T. Camará, one of our invaluable research assistants, named one of the females ‘Brinkos’, meaning ‘earrings’ in Guinea-Bissau creole, due to her appearance. By the end of 2018, our combined efforts enabled us to collect over 600 faecal samples from six different chimpanzee communities, which were sent to RKI to be analysed.
Brinkos, captured by a camera trap in Caiquene-Cadique in 2018. Photo credit: Marina Ramon/ Cantanhez Chimpanzee Project.
At the present, leprosy has only been molecularly confirmed in Caiquene-Cadique, but footage from camera traps points towards leprosy being present in at least three communities. These data form the starting point for the leprosy monitoring project, but data continues to be collected across the park to confirm the presence of the disease in other communities.
Marina Ramon and Mamadú Cassamá collecting faecal samples in Cantanhez National Park, Guinea-Bissau. Photo credit: Iaia T. Camará/Canthanez Chimpanzee Project.
How have the chimpanzees caught the disease?
M. leprae is considered a human-adapted pathogen and leprosy affecting other wildlife is assumed to have a human origin. Could then we just assume that chimpanzees caught leprosy from humans? It’s not that easy. Our knowledge of the study sites combined with the thorough work done by Charlotte Avanzi and her team characterising the M. leprae strains and performing phylogenomic comparisons shed some light.
The strains identified in Cantanhez and at Taï are different and belong to different and rare genotypes. While the strain from Guinea-Bissau (clustering within 4N/O genotype) has been identified in humans in West Africa and in captive primates from West Africa, the strain from Côte d’Ivoire (2F) has never been reported in the region.
Leprosy is endemic in Guinea-Bissau, with a current low number of human cases reported each year. This disease is transmitted through direct contact and inhalation of respiratory droplets and/or fomites, but it is thought to require prolonged and repeated exposure. Although chimpanzees in Cantanhez share access to wild and cultivated food with humans, at present time, direct contact between both species is uncommon, making current transmission unlikely. Nonetheless, we do not know what happened in the past and whether chimpanzees were hunted for meat or kept as pets, so the long-term coexistence between humans and chimpanzees makes humans a likely source of chimpanzee infection.
Another hypothesis can be that chimpanzees acquired leprosy from an environmental source such as water or soil, where mycobacteria can survive, or a nonhuman reservoir, like mammalian prey (analysis at RKI confirmed that chimpanzees in Cantanhez eat other mammals).
In any case, the fact that multiple individuals from several chimpanzee communities across Cantanhez show signs of symptomatic leprosy points towards the possibility that M. leprae is now transmitted between individuals within this population.
At Taï, chimpanzees are more distant from human settlements and in spite of being followed daily by researchers, there’s no direct contact between them and no cases of leprosy have been reported among researchers. Although a human source is impossible to rule out, low human contact combined with the rarity of the genotype among humans suggests that chimpanzees acquired the infection from another animal species or from an environmental source.
What does this mean for the conservation of western chimpanzees?
The western chimpanzee (Pan troglodytes verus) is classified as Critically Endangered by the IUCN. One of the major threats to this subspecies is infectious disease, especially for chimpanzee populations living in agricultural mosaics, where they coexist with humans.
Leprosy is very different to many of the fast-spreading respiratory viruses that have caused important population declines in great apes, but even the loss of a few individuals could be significant. We have observed how sick chimpanzees have worsened since the first symptoms of leprosy were observed, and suspect that their condition will continue to deteriorate allowing for secondary infections to take place and eventually leading to death, although this process might take years.
In humans, leprosy has a long incubation time, ranging from several months to 20 years, but only a low proportion of people exposed to the bacteria go on to develop the disease. Leprosy was reported in four captive chimpanzees, also going through a long incubation period, with disease manifesting 5 to 30 years after potentially contracting the disease in the wild. It’s possible that individuals that are under human and environmental stressors are more likely to develop leprosy. Moreover, the disease itself is not the only thing posing a threat to chimpanzee conservation, since people might perceive chimpanzees as a source of disease and might engage in hostile actions towards them.
What is being done?
To understand how leprosy is transmitted we need to adopt a holistic approach with an interdisciplinary human-chimpanzee-environment interaction framework.
A Darwin Initiative project started its implementation in 2019, with Kimberley Hockings as Principal Investigator and Hellen Bersacola as Research Fellow. The aim of this project is to improve public health by increasing resilience to infectious disease in local communities, as well as to increase conservation capacity by training park managers and guards to monitor biodiversity in Cantanhez. Kimberley and Hellen are working with the Institute for Biodiversity and Protected Areas (IBAP), who are responsible for the management of Protected Areas in Guinea-Bissau, and other project partners (CRIA, NADEL, RKI) to develop a One Health environmental management plan for Cantanhez NP.
Darwin team in a meeting at IBAP headquarters in Bissau, Guinea-Bissau.
Marina Ramon is currently doing a PhD supervised by Kimberley Hockings, whose main objective is to estimate leprosy occurrence, and study the spatiotemporal distribution and sociality of infected individuals to understand the transmission dynamics of leprosy in three central chimpanzee communities in Cantanhez. She is working closely with the masters by Research students Hattie Herridge and Ally Dell, supervised by Camille Bonneaud and Kimberley Hockings, respectively, to analyse faecal samples collected in Cantanhez. Marina is currently carrying out analysis at Cardiff University with Mike Brufford to obtain DNA profiles of the chimpanzees, while Hattie and Ally are conducting analysis at RKI to detect the presence of M. leprae and mammal prey in faeces.
All these projects are part of an integrated strategy to respond to leprosy in Cantanhez. While veterinary intervention in habituated great apes occurs in certain circumstances, it is not without risk to the veteranarian or the chimpanzee, and treatment requires multi-drug therapy for 6-12 months. Moreover, unhabituated chimpanzees are elusive and sick individuals cannot be targeted, which makes veterinary treatment not a viable option for chimpanzees in Cantanhez.
Instead of targeting chimpanzees, by combining landscape and fine scale data, we aim to map hotspots of disease transmission risk to enable the design of interventions targeting the environment (water holes, overlapping areas between chimpanzees, other animals and humans) or other components of the system (other wildlife or humans) to reduce opportunities for leprosy transmission.
We are only just scratching the surface of leprosy presence and transmission in wildlife and there are so many questions to be addressed!
Are other sympatric mammal species affected by leprosy? Could we find M. leprae in soil and water samples? Do chimpanzees suffering from leprosy have concomitant diseases? Are these chimpanzees more stressed? What’s the relatedness between infected individuals? Could we characterise candidate genes for leprosy susceptibility in chimpanzees?
If you want to read more about this research, please check out our article just published in Nature: https://www.nature.com/articles/s41586-021-03968-4