Connect with us

Health

Leprosy in wild chimpanzees | Nature

 


Leprosy is a neglected tropical disease caused by the bacterial pathogens M. leprae and the more recently discovered Mycobacteriumlepromatosis8,9. In humans, the disease presents as a continuum of clinical manifestations with skin and nerve lesions of increasing severity, from the mildest tuberculoid form (or paucibacillary) to the most severe lepromatous type (or multibacillary)10. Symptoms develop after a long incubation period ranging from several months to 30 years, averaging 5 years in humans. As a result of sensory loss, leprosy can lead to permanent damage and severe deformity11. Although leprosy prevalence has markedly decreased over recent decades, approximately 210,000 new human cases are still reported every year, of which 2.3% are located in West Africa12. Transmission is thought to occur primarily between individuals with prolonged and close contact via aerosolized nasal secretions and entry through nasal or respiratory mucosae, but the exact mechanism remains unclear13,14. The role of other routes, such as skin-to-skin contact, is unknown.

Leprosy-causing bacteria were once thought to be obligate human pathogens1. However, they can circulate in other animal hosts in the wild, such as nine-banded armadillos (Dasypusnovemcinctus) in the Americas and red squirrels (Sciurusvulgaris) in the UK2,3. Although initial infection was most probably incidental and of human origin, secondary animal hosts can subsequently represent a source of infection to humans15,16,17,18. In captivity, nonhuman primates, such as chimpanzees (Pantroglodytes)4, sooty mangabeys (Cercocebusatys)5,6 and cynomolgus macaques (Macacafascicularis)7, have been known to develop leprosy without any obvious infectious source. However, due to their captive status, it is unclear how they acquired M. leprae and whether these species can also contract leprosy in the wild.

Here, we report leprosy infections and their disease course in two wild populations of western chimpanzees (P. troglodytes verus) in Cantanhez National Park (CNP), Guinea-Bissau, and in Taï National Park (TNP), Côte d’Ivoire, using a combination of camera trap and veterinary monitoring (Extended Data Fig. 1a and Supplementary Notes 1 and 2). From analyses of faecal samples and postmortem tissues, we identified M. leprae as the causative agent of the lesions observed and determined the phylogenetic placement of the respective strains based on their complete genome sequences.

Chimpanzees at CNP are not habituated to human observers, precluding systematic behavioural observations. Longitudinal studies necessitate the use of camera traps, which we operated between 2015 and 2019. Of 624,194 data files (videos and photographs) obtained across 211 locations at CNP (Extended Data Fig. 1b, Extended Data Table 1 and Supplementary Table 1), 31,044 (5.0%) contained chimpanzees. The number of independent events (images separated by at least 60 min) totalled 4,336, and of these, 241 (5.6%) contained chimpanzees with severe leprosy-like lesions, including four clearly identifiable individuals (two adult females and two adult males) across three communities (Extended Data Fig. 2 and Supplementary Note 2). As with humans, paucibacillary cases in chimpanzees may be present but easily go undetected. Such minor manifestations of leprosy are not reported. All symptomatic chimpanzees showed hair loss and facial skin hypopigmentation, as well as plaques and nodules that covered different areas of their body (limbs, trunk and genitals), facial disfigurement and ulcerated and deformed hands (claw hand) and feet (Fig. 1a–c), consistent with a multibacillary form of the disease. Longitudinal observations showed progression of symptoms across time with certain manifestations similar to those described in humans (such as progressive deformation of the hands) (Extended Data Fig. 2 and Supplementary Videos 13). To confirm infection with M. leprae, we collected faecal samples and tested them with two nested polymerase chain reaction (PCR) assays targeting the M. leprae-specific repetitive element (RLEP) and 18 kDa antigen gene. One out of 208 DNA extracts from CNP was positive in both assays and a second was positive only in the more sensitive RLEP-PCR19 (Extended Data Table 2, Supplementary Table 2 and Supplementary Note 3). Microsatellite analyses of the two positive samples confirmed that they originated from two distinct female individuals (Supplementary Note 4 and Supplementary Tables 3 and 4). Our results suggest that M. leprae is the most likely cause of a leprosy-like syndrome in chimpanzees from CNP.

Fig. 1: Clinical manifestations of leprosy in three chimpanzees at CNP, Guinea-Bissau and TNP, Côte d’Ivoire.
figure1

a–c, Clinical signs of leprosy in two adult female chimpanzees in CNP (images extracted from camera traps). a, Rita has large hypopigmented nodules covering the entire body; disfigurement of the face, ears, hands and feet (ulcerated lesions and swelling). b, Rita has extensive plaques covering all limbs, with hair loss. c, Brinkos has large hypopigmented nodules covering the entire face, with extreme disfigurement of the face and ears, and ulcerated plaques on the arms and the nipples. dg, Clinical signs of leprosy in an adult male chimpanzee, Woodstock, at TNP. d, Multiple hypopigmented nodules on the ears, brow ridges, eyelid margins, nostrils, lips and the area between the upper lip and the nose. e, Hypopigmentation and swelling of the hands with ulcerations and hair loss on the dorsal side of the joints. f, Claw hand with nail loss and abnormal overgrowth of fingernails. g, Scrotal reddening and ulceration with fresh blood.

At TNP, chimpanzees are habituated to the presence of researchers and have been followed daily since 1979. In addition, necropsy samples have been collected from all dead individuals recovered since 2000. In June 2018, researchers first noticed leprosy-like lesions on Woodstock, an adult male chimpanzee from one of the three habituated communities (south) (Extended Data Fig. 1c). The initial small nodules on the ears, lips and under the eye became more prominent and were followed by nodules on the eyebrows, eyelids, nostrils, ears, lips and face. The skin on facial nodules, hands, feet and testicles became hypopigmented and the loss and abnormal growth of nails was observed (Fig 1d–g, Extended Data Fig. 3 and Supplementary Videos 4 and 5). Mycobacterium leprae DNA was detected in all samples from June 2018 (Extended Data Table 2, Supplementary Table 2 and Supplementary Note 2). Here, continuous noninvasive detection of M. leprae was associated with the onset and evolution of a leprosy-like disease.

Retrospective PCR screening of all chimpanzee spleen samples (n = 38 individuals) from the TNP necropsy collection led to the identification of M. leprae DNA in two further individuals. An adult female from the same community named Zora, who had been killed by a leopard in 2009, tested positive in both PCR assays. The presence of M. leprae DNA was confirmed by PCR in various other organs (Extended Data Table 2). Retrospective analyses of photographs taken in the years before her death showed progressive skin hypopigmentation and nodule development since 2007 (Extended Data Fig. 3). Formalin-fixed skin samples (hands and feet) were prepared for histopathological examination using haematoxylin and eosin as well as Fite-Faraco stains. The skin presented typical signs of lepromatous leprosy characterized by a diffuse cutaneous cell infiltration in the dermis and the subcutis clearly separated from the basal layer of the epidermis (Extended Data Fig. 4a). We detected moderate numbers of acid-fast bacilli (single or in clumps) within histiocytes, indicative of M. leprae (Extended Data Fig. 4b). As antibodies against the M. leprae-specific antigen phenolic glycolipid-I (PGL-I) are a hallmark of M. leprae infection in humans20, we also performed a PGL-I lateral flow rapid test21 on a blood sample from this individual, which showed strong seropositivity (Extended Data Fig. 4c). Faecal samples collected in the years before Zora’s death contained M. leprae DNA from 2002 onwards, implying at least 7 years of infection (Extended Data Table 2). In this case, disease manifestations, histopathological findings, serological and molecular data, as well as the overall course of the disease, all unambiguously point towards M. leprae-induced leprosy.

To ascertain whether other individuals in the south community of TNP were infected at the time of Zora’s death in 2009, cross-sectional screening of contact animals (n = 32) was performed by testing all available faecal samples (n = 176) collected in 2009 (Supplementary Table 2). Three other chimpanzees were PCR-positive in single samples, including Woodstock. Clinical symptoms of leprosy have not been observed in other individuals, despite daily monitoring of south community members for 20 years and of neighbouring communities for 40 years22,23. Considering that, over this period, 467 individuals have been observed, it seems that leprosy is a rare disease with low transmission levels in these chimpanzee communities.

To characterize the M. leprae strains causing leprosy in wild chimpanzees and to perform phylogenomic comparisons, we selected DNA extracts that were positive in both the RLEP and the less-sensitive 18-kDa PCR, which indicates relatively high levels of M. leprae DNA. For TNP, we selected individuals that were positive in multiple samples. Following targeted enrichment using hybridization capture, samples were subjected to Illumina sequencing. Sufficient M. leprae genome coverage was obtained for sample GB-CC064 (Guinea-Bissau) and for Zora (Côte d’Ivoire) with mean depth of 39.3× and 25.8×, respectively (Extended Data Table 2 and Supplementary Table 5). We generated 21 M. leprae genomes from human biopsies from five West African countries (Niger, Mali, Benin, Côte d’Ivoire and Senegal) and depth of coverage ranged from 4.7× to 170×. We assembled a dataset that included the genomes generated in this study and all previously available M. leprae genomes. Of the total 286 genomes, 64 originated from six West African countries (Extended Data Fig. 5 and Supplementary Note 5).

Bayesian and maximum-parsimony analyses (Extended Data Figs. 6 and 7) place the strain from Guinea-Bissau (GB-CC064) on branch 4, where it clusters outside the standard genotypes 4N, 4O and 4P, but within the so-called 4N/O genotype24,25 (Fig. 2a, c). This 4N/O genotype is rare and only comprises five M. leprae strains; one strain (Ng13-33) from a patient in Niger, two strains (2188-2007 and 2188-2014) obtained from a single patient in Brazil (of 34 strains in Brazil)26 and two strains from two captive nonhuman primates originating from West Africa (Ch4 and SM1)25. The branching order of these five strains and GB-CC064 was unresolved in our analyses, with a basal polytomy suggestive of star-like diversification within this genotype, and within the group comprising all genotype 4 strains (4N/O, 4N, 4P and 4O). Divergence from the most recent common ancestor for this group is estimated to have occurred in the sixth century ad (mean divergence time, 1,437 years ago, 95% highest posterior density (HPD) 1,132–1,736 years ago). The strain that infected Zora in Côte d’Ivoire, designated TNP-418, belongs to branch 2F, within which, the branching order was also mostly unresolved (Fig. 2a, b). The branch is currently composed of human strains from medieval Europe (n = 7) and modern Ethiopia (n = 2), and this genotype has thus far never been reported to our knowledge in West Africa. Bayesian analysis estimated a divergence time during the second century ad (mean of 1,873 years ago (95% HPD 1,564–2,204 years ago)), similar to previous predictions27.

Fig. 2: Phylogeny of M. leprae strains from human and animal hosts.
figure2

a, Bayesian dated phylogenetic tree of 278 M. leprae genomes including the two new chimpanzee strains (in bold red). Hypermutated samples with mutations in the nth gene were excluded from the analysis. The tree is drawn to scale, with branch lengths representing years of age. Median estimates of node ages are shown in black above branches; 95% HPD intervals are shown in grey. Some M. leprae branches are collapsed to increase readability. b, Maximum parsimony tree of branch 2F. c, Maximum parsimony tree of the branch 4. The tree was initially constructed using 286 genomes (Supplementary Table 6), including 2 new chimpanzee strains (in bold red) and 21 new genomes from West Africa (in bold), 500 bootstrap replicates and M. lepromatosis as outgroup. Sites with missing data were partially deleted (80% genome coverage cutoff), resulting in 4,470 variable sites used for the tree calculation. Subtrees corresponding to branches were retrieved in MEGA765. Corresponding genotypes are indicated on the side of each subtree. Samples are binned according to geographical origin as given in the legend. Scale bars (b, c), number of nucleotide substitutions. Animal silhouettes are available under Public Domain licence at PhyloPic (http://PhyloPic.org/).

Samples from Woodstock did not yield enough Illumina reads to reconstruct full genomes for phylogenomic analysis. However, single-nucleotide polymorphisms (SNPs) recovered from the few available Illumina reads and Sanger sequences derived from PCR products allowed us to assign this second M. leprae strain from Côte d’Ivoire to the same genotype as TNP-418 (Supplementary Note 5). Overall, phylogenomic analyses show that M. leprae strains in chimpanzee populations at CNP and TNP are not closely related.

The finding of M. leprae-induced leprosy in wild chimpanzee populations raises the question of the origin(s) of these infections. Mycobacterium leprae is considered a human-adapted pathogen and previous cases of leprosy affecting wildlife were compatible with anthroponosis. Therefore, the prime hypothesis would be human-to-chimpanzee transmission. Potential routes of transmission include direct (such as skin-to-skin) contact and inhalation of respiratory droplets and/or fomites, with the assumption that, in all cases, prolonged and/or repeated exposure is required for transmission11. Chimpanzees at CNP are not habituated to humans and are not approached at distances that would allow for transmission via respiratory droplets. Although these chimpanzees inhabit an agroforest landscape and share access to natural and cultivated resources with humans28, present-day human–chimpanzee direct contact is uncommon. The exact nature of historic human–chimpanzee interactions at CNP remains, however, unknown. For example, robust data on whether chimpanzees were kept as ‘pets’ or were hunted for meat are lacking. Long-term human–chimpanzee coexistence in this shared landscape makes humans the most probable source of chimpanzee infection. However, multiple individuals from several chimpanzee communities across CNP show symptomatic leprosy demonstrating that M. leprae is now probably transmitted between individuals within this population.

At TNP, the south chimpanzee community is distant from human settlements and agriculture. Human-to-animal transmission of pathogens has been shown at TNP29,30 but involved respiratory pathogens (pneumoviruses and human coronavirus OC43) that transmit easily and do not require prolonged exposure. In addition, M. leprae is thought to be transmitted from symptomatic humans31 and no cases of leprosy have been reported among researchers or local research assistants. Although a human source is impossible to rule out, low human contact coupled with the rarity of the M. leprae genotype detected in TNP chimpanzees among human populations in West Africa suggests that recent human-to-chimpanzee transmission is unlikely. This is supported by the absence of drug-resistant mutations (Supplementary Note 6). The relatively old age of the lineage leading to the chimpanzee strain at TNP nevertheless raises the possibility of an ancient human-to-chimpanzee transmission. However, the human population density 1,500–2,000 years ago was probably even lower than it is currently, making this unlikely. If such an ancient transmission had occurred and the bacterium had persisted for a long time in chimpanzees, it should have spread more broadly as observed in M. leprae-infected squirrels and armadillos3,16,17. Therefore, an ancient human-to-chimpanzee transmission is not the most plausible mechanism to explain the presence of M. leprae in chimpanzees at TNP.

These findings may be better explained by the presence of a nonhuman leprosy reservoir. As chimpanzees hunt frequently, transmission may originate from their mammalian prey32. Nonhuman primates are the most hunted prey at TNP33 and are hunted at CNP (Supplementary Note 3). Chimpanzees also consume other mammalian prey such as ungulates. Notably, this scenario assumes that the animal host range of M. leprae is even broader than is currently known. Perhaps more intriguingly, an environmental source may be at the origin of chimpanzee infections. Other mycobacteria can survive in water, including M. ulcerans and other non-tuberculous mycobacteria34,35, and molecular investigations have reported that M. leprae can survive in soil36. Experimental data also show that M. leprae multiplies in amoebae37, arthropods38 and ticks39, which could contribute to the persistence of the bacteria in the environment. Testing these hypotheses will require thorough investigation of the distribution of M. leprae in wildlife and the environment and so shed light on the overall transmission pathways of the pathogen.

Sources

1/ https://Google.com/

2/ https://www.nature.com/articles/s41586-021-03968-4

The mention sources can contact us to remove/changing this article

What Are The Main Benefits Of Comparing Car Insurance Quotes Online

LOS ANGELES, CA / ACCESSWIRE / June 24, 2020, / Compare-autoinsurance.Org has launched a new blog post that presents the main benefits of comparing multiple car insurance quotes. For more info and free online quotes, please visit https://compare-autoinsurance.Org/the-advantages-of-comparing-prices-with-car-insurance-quotes-online/ The modern society has numerous technological advantages. One important advantage is the speed at which information is sent and received. With the help of the internet, the shopping habits of many persons have drastically changed. The car insurance industry hasn't remained untouched by these changes. On the internet, drivers can compare insurance prices and find out which sellers have the best offers. View photos The advantages of comparing online car insurance quotes are the following: Online quotes can be obtained from anywhere and at any time. Unlike physical insurance agencies, websites don't have a specific schedule and they are available at any time. Drivers that have busy working schedules, can compare quotes from anywhere and at any time, even at midnight. Multiple choices. Almost all insurance providers, no matter if they are well-known brands or just local insurers, have an online presence. Online quotes will allow policyholders the chance to discover multiple insurance companies and check their prices. Drivers are no longer required to get quotes from just a few known insurance companies. Also, local and regional insurers can provide lower insurance rates for the same services. Accurate insurance estimates. Online quotes can only be accurate if the customers provide accurate and real info about their car models and driving history. Lying about past driving incidents can make the price estimates to be lower, but when dealing with an insurance company lying to them is useless. Usually, insurance companies will do research about a potential customer before granting him coverage. Online quotes can be sorted easily. Although drivers are recommended to not choose a policy just based on its price, drivers can easily sort quotes by insurance price. Using brokerage websites will allow drivers to get quotes from multiple insurers, thus making the comparison faster and easier. For additional info, money-saving tips, and free car insurance quotes, visit https://compare-autoinsurance.Org/ Compare-autoinsurance.Org is an online provider of life, home, health, and auto insurance quotes. This website is unique because it does not simply stick to one kind of insurance provider, but brings the clients the best deals from many different online insurance carriers. In this way, clients have access to offers from multiple carriers all in one place: this website. On this site, customers have access to quotes for insurance plans from various agencies, such as local or nationwide agencies, brand names insurance companies, etc. "Online quotes can easily help drivers obtain better car insurance deals. All they have to do is to complete an online form with accurate and real info, then compare prices", said Russell Rabichev, Marketing Director of Internet Marketing Company. CONTACT: Company Name: Internet Marketing CompanyPerson for contact Name: Gurgu CPhone Number: (818) 359-3898Email: [email protected]: https://compare-autoinsurance.Org/ SOURCE: Compare-autoinsurance.Org View source version on accesswire.Com:https://www.Accesswire.Com/595055/What-Are-The-Main-Benefits-Of-Comparing-Car-Insurance-Quotes-Online View photos

ExBUlletin

to request, modification Contact us at Here or [email protected]