Monkeypox is a viral zoonotic disease on the rise across endemic habitats. Despite the growing importance of monkeypox virus, our knowledge on its host spectrum and sylvatic maintenance is limited. Here, we describe the recent repeated emergence of monkeypox virus in a wild, human-habituated western chimpanzee (Pan troglodytes verus, hereafter chimpanzee) population from Taï National Park, Ivory Coast. Through daily monitoring, we show that further to causing its typical exanthematous syndrome, monkeypox can present itself as a severe respiratory disease without a diffuse rash. By analysing 949 non-invasively collected samples, we identify the circulation of at least two distinct monkeypox virus lineages and document the shedding of infectious particles in faeces and flies, suggesting that they could mediate indirect transmission. We also show that the carnivorous component of the Taï chimpanzees’ diet, mainly consisting of the sympatric monkeys they regularly hunt, did not change nor shift towards rodent consumption (the presumed reservoir) before the outbreaks, suggesting that the sudden emergence of monkeypox virus in this population is probably due to changes in the ecology of the virus itself. Using long-term mortality surveillance data from Taï National Park, we provide evidence of little to no prior viral activity over at least two decades. We conclude that great ape sentinel systems devoted to the longitudinal collection of behavioural and health data can help clarify the epidemiology and clinical presentation of zoonotic pathogens.
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Raw reads of 16S amplicons are available in the European Nucleotide Archive (ENA) under project accession number PRJEB34040 and sample accession numbers ERS3658904–ERS3659288. Raw reads resulting from MPXV target enrichment in non-invasive samples are available in the ENA under project accession number PRJEB34056, sample accession numbers ERS3659494–ERS3659510. Consensus sequences are available in GenBank, accession numbers MN346690–MN3466703. Annotated MPXV genomes, as well as sequences derived from the fly species identification, are available in Zenodo (https://zenodo.org record number 3373886 and 3606577, respectively). Source Data for Fig. 6 and Extended Data Figs. 7–9 are provided with the paper.
Durski, K. N. et al. Emergence of monkeypox — West and Central Africa, 1970–2017. Morb. Mortal. Wkly Rep. 67, 306–310 (2018).
Vaughan, A. et al. Two cases of monkeypox imported to the United Kingdom, September 2018. Eurosurveillance 23, 1800509 (2018).
Erez, N. et al. Diagnosis of imported monkeypox, Israel, 2018. Emerg. Infect. Dis. 25, 980–983 (2019).
Ng, O. et al. A case of imported monkeypox in Singapore. Lancet Infect. Dis. 19, 1166 (2019).
Nakazawa, Y. et al. A phylogeographic investigation of African monkeypox. Viruses 7, 2168–2184 (2015).
Chen, N. et al. Virulence differences between monkeypox virus isolates from West Africa and the Congo basin. Virology 340, 46–63 (2005).
Parker, S., Nuara, A., Buller, R. & Schultz, D. Human monkeypox: an emerging zoonotic disease. Future Microbiol. 2, 17–34 (2007).
Sklenovská, N. & Van Ranst, M. Emergence of monkeypox as the most important orthopoxvirus infection in humans. Front. Public Health 6, 241 (2018).
Yinka-Ogunleye, A. et al. Reemergence of human monkeypox in Nigeria, 2017. Emerg. Infect. Dis. 24, 1149–1151 (2018).
von Magnus, P., Andersen, E., Petersen, K. & Birch-Andersen, A. A pox-like disease in cynomolgus monkeys. Acta Pathol. Microbiol. Scand. 46, 156–176 (1959).
Petersen, E. et al. Monkeypox — enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era. Int. J. Infect. Dis. 78, 78–84 (2019).
Khodakevich, L., Jezek, Z. & Kinzanzka, K. Isolation of monkeypox virus from wild squirrel infected in nature. Lancet 327, 98–99 (1986).
Radonić, A. et al. Fatal monkeypox in wild-living sooty mangabey, Cote d’Ivoire, 2012. Emerg. Infect. Dis. 20, 1009–1011 (2014).
Tiee, M. S., Harrigan, R. J., Thomassen, H. A. & Smith, T. B. Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time. R. Soc. Open Sci. 5, 171089 (2018).
Leendertz, F. H. et al. Pathogens as drivers of population declines: the importance of systematic monitoring in great apes and other threatened mammals. Biol. Conserv. 131, 325–337 (2006).
Wittig, R. M. in Encyclopedia of Animal Cognition and Behavior (eds Vonk, J. & Shackelford, T.) 1–7 (Springer, 2018).
Gillespie, T. R., Nunn, C. L. & Leendertz, F. H. Integrative approaches to the study of primate infectious disease: implications for biodiversity conservation and global health. Am. J. Phys. Anthropol. 137, 53–69 (2008).
Hoffmann, C. et al. Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest. Nature 548, 82–85 (2017).
Köndgen, S. et al. Pandemic human viruses cause decline of endangered great apes. Curr. Biol. 18, 260–264 (2008).
Reynolds, M. G. et al. Clinical manifestations of human monkeypox influenced by route of infection. J. Infect. Dis. 194, 773–780 (2006).
Saijo, M. et al. Virulence and pathophysiology of the Congo Basin and West African strains of monkeypox virus in non-human primates. J. Gen. Virol. 90, 2266–2271 (2009).
Monkeypox Fact Sheet (World Health Organization, 2019); https://www.who.int/news-room/fact-sheets/detail/monkeypox
Huhn, G. D. et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin. Infect. Dis. 41, 1742–1751 (2005).
Rambaut, A., Lam, T. T., Max Carvalho, L. & Pybus, O. G. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evol. 2, vew007 (2016).
Drummond, A. J., Suchard, M. A., Xie, D. & Rambaut, A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969–1973 (2012).
Duchene, S. et al. Bayesian evaluation of temporal signal in measurably evolving populations. Preprint at bioRxiv https://doi.org/10.1101/810697 (2019).
Duffy, S., Shackelton, L. A. & Holmes, E. C. Rates of evolutionary change in viruses: patterns and determinants. Nat. Rev. Genet. 9, 267–276 (2008).
Babkin, I. V. & Babkina, I. N. A retrospective study of the orthopoxvirus molecular evolution. Infect. Genet. Evol. 12, 1597–1604 (2012).
Kerr, P. J. et al. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia. PLoS Pathog. 13, e1006252 (2017).
Duggan, A. T. et al. 17th century variola virus reveals the recent history of smallpox. Curr. Biol. 26, 3407–3412 (2016).
Porter, A. F., Duggan, A. T., Poinar, H. N. & Holmes, E. C. Characterization of two historic smallpox specimens from a Czech museum. Viruses 9, 2–5 (2017).
Andersen, K. G. et al. Clinical sequencing uncovers origins and evolution of Lassa virus. Cell 162, 738–750 (2015).
Boesch, C. & Boesch-Achermann, H. The Chimpanzees of the Taï Forest (Oxford Univ. Press, 2000).
Smithson, C., Purdy, A., Verster, A. J. & Upton, C. Prediction of steps in the evolution of variola virus host range. PLoS ONE 9, e91520 (2014).
Schweneker, M. et al. The vaccinia virus O1 protein is required for sustained activation of extracellular signal-regulated kinase 1/2 and promotes viral virulence. J. Virol. 86, 2323–2336 (2012).
Hendrickson, R. C., Wang, C., Hatcher, E. L. & Lefkowitz, E. J. Orthopoxvirus genome evolution: the role of gene loss. Viruses 2, 1933–1967 (2010).
Reynolds, M. G., Guagliardo, S. A. J., Nakazawa, Y. J., Doty, J. B. & Mauldin, M. R. Understanding orthopoxvirus host range and evolution: from the enigmatic to the usual suspects. Curr. Opin. Virol. 28, 108–115 (2018).
Hoffmann, C., Stockhausen, M., Merkel, K., Calvignac-Spencer, S. & Leendertz, F. H. Assessing the feasibility of fly based surveillance of wildlife infectious diseases. Sci. Rep. 6, 37952 (2016).
Calvignac-Spencer, S. et al. Carrion fly-derived DNA as a tool for comprehensive and cost-effective assessment of mammalian biodiversity. Mol. Ecol. 22, 915–924 (2013).
Gogarten, J. F. et al. Fly‐derived DNA and camera traps are complementary tools for assessing mammalian biodiversity. Environ. DNA 2, 63–76 (2020).
Samuni, L., Preis, A., Deschner, T., Crockford, C. & Wittig, R. M. Reward of labor coordination and hunting success in wild chimpanzees. Commun. Biol. 1, 138 (2018).
Stagegaard, J. et al. Seasonal recurrence of cowpox virus outbreaks in captive cheetahs (Acinonyx jubatus). PLoS ONE 12, e0187089 (2017).
ProMED. Monkeypox - Africa (07): Liberia; archive no. 20180411.5740756. ProMED http://www.promedmail.org/post/5740756 (2018).
Reil, D. et al. Puumala hantavirus infections in bank vole populations: host and virus dynamics in Central Europe. BMC Ecol. 17, 9 (2017).
Aleman, J., Jarzyna, M. & Staver, A. Forest extent and deforestation in tropical Africa since 1900. Nat. Ecol. Evol. 2, 26–33 (2018).
Luis, A. D., Kuenzi, A. J. & Mills, J. N. Species diversity concurrently dilutes and amplifies transmission in a zoonotic host–pathogen system through competing mechanisms. Proc. Natl Acad. Sci. USA 115, 7979–7984 (2018).
Schroeder, K. & Nitsche, A. Multicolour, multiplex real-time PCR assay for the detection of human-pathogenic poxviruses. Mol. Cell. Probes 24, 110–113 (2010).
Kurth, A. et al. Rat-to-elephant-to-human transmission of cowpox virus. Emerg. Infect. Dis. 14, 670–671 (2008).
Folmer, O., Black, M., Hoeh, W., Lutz, R. & Vrijenhoek, R. DNA primers for amplification of mitochondrial cytochrome c oxidase subunit I from diverse metazoan invertebrates. Mol. Mar. Biol. Biotechnol. 3, 294–299 (1994).
Kearse, M. et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647–1649 (2012).
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
Nurk, S., Meleshko, D., Korobeynikov, A. & Pevzner, P. A. metaSPAdes: a new versatile metagenomic assembler. Genome Res. 27, 824–834 (2017).
Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772–780 (2013).
Zhao, K., Wohlhueter, R. M. & Li, Y. Finishing monkeypox genomes from short reads: assembly analysis and a neural network method. BMC Genomics 17, 497 (2016).
Gouy, M., Guindon, S. & Gascuel, O. Sea view version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol. Biol. Evol. 27, 221–224 (2010).
Villesen, P. FaBox: an online toolbox for FASTA sequences. Mol. Ecol. Notes 7, 965–968 (2007).
Darriba, D., Taboada, G. L., Doallo, R. & Posada, D. jModelTest 2: more models, new heuristics and high-performance computing. Nat. Methods 9, 772 (2015).
Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 29, 307–321 (2010).
Letunic, I. & Bork, P. Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res. 47, W256–W259 (2019).
Baele, G. et al. Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty. Mol. Biol. Evol. 29, 2157–2167 (2012).
Boyer, F. et al. obitools: a unix-inspired software package for DNA metabarcoding. Mol. Ecol. Resour. 16, 176–182 (2016).
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal 17, 10–12 (2011).
Ficetola, G. F. et al. An in silico approach for the evaluation of DNA barcodes. BMC Genomics 11, 434 (2010).
Csárdi, G. & Nepusz, T. The igraph software package for complex network research. InterJournal Complex Systems http://igraph.org (2006).
We thank the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique, the Ministère de Eaux et Fôrets in Ivory Coast and the Office Ivoirien des Parcs et Réserves for permitting the study. We are grateful to the Centre Suisse de Recherches Scientifiques en Côte d’Ivoire and the staff members of the Taï Chimpanzee Project for their support. The Max Planck Society has provided core funding for the Taï Chimpanzee Project since 1997. We thank all primatologists, research assistants and veterinarians who collected samples for the Taï Chimpanzee project over the years. We are grateful to the Sequencing Unit of the Robert Koch Institute for their support. We thank S. Lemoine for providing the map illustrating the territories of the Taï chimpanzees. This work was supported by the Robert Koch Institute, the Alexander von Humboldt Foundation postdoctoral fellowship programme, the German Research Council projects LE1813/10-2, LE1813/14-1, WI2637/4-2 and WI2637/3-1 within the research group FOR2136 (Sociality and Health in Primates) and LE1813/11-1 (Great Ape Health in Tropical Africa), and the ARCUS Foundation grant G-PGM-1606-1874. Work was partly carried out under the Global Health Protection Programme supported by the Federal Ministry of Health on the basis of a decision by the German Bundestag.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Pictures a-h show the evolution of the skin lesions over a 19-day period. Day 1 corresponds to the first day of symptoms’ observation by researchers. a Papular lesions covering the entire body. b Lesions in vesiculopustular stage, also evident on eyelids. c Ulceration and umbilication of facial lesions, some crusts already visible. d Most facial lesions have ulcerated and crusted, lesions on limbs are still at a vesicular stage. e Most facial lesions have crusted and scabbed, lesions on the abdomen and extremities are still in previous stages. f Facial lesions mostly scabbed and crusts fallen off, on the abdomen and extremities crusting and scabbing are underway. g, h Lesions on the entire body have resolved.
Extended Data Fig. 2 Clinical signs associated with MPXV infection during the 3 outbreaks in wild chimpanzees.
The number following the group name is the total number of chimpanzees in the group. Dates below each group indicate the timeframe when clinical signs were observed. Numbers in brackets after each age group correspond to the number of chimpanzees belonging to that age group. Numbers under disease manifestation categories indicate the number and age class of chimpanzees who manifested those clinical signs. The number of asymptomatic chimpanzees in which MPXV DNA was detected in faeces is also reported in the last column.
Extended Data Fig. 3 Summary of samples types and MPXV DNA detection in all non-invasive samples collected before, during and after the appearance of clinical signs associated with MPXV infection in the three chimpanzee communities.
Collection periods are reported for each group.
a, Detection of MPXV DNA and non-chimpanzee mammalian DNA b, in chimpanzee faecal samples from the South community over time. Each line represents a chimpanzee. Bold names correspond to chimpanzees in which mild to severe signs compatible with MPXV infection were observed. Boxes represent age groups (infant, juvenile, adolescent and adult). Vertical light grey shadowing indicates the period in which clinical signs were observed in the group. Horizontal dark grey shadowing indicates the period in which clinical signs were observed in severely ill chimpanzees.
a, Detection of MPXV DNA and non-chimpanzee mammalian DNA b, in chimpanzee faecal samples from the North community over time. Each line represents a chimpanzee. Bold names correspond to chimpanzees in which mild to severe signs compatible with MPXV infection were observed. Boxes represent age groups (infant, juvenile, adolescent and adult). Vertical light grey shadowing indicates the period in which clinical signs were observed in the group. Horizontal dark grey shadowing indicates the period in which clinical signs were observed in severely ill chimpanzees.
a, Detection of MPXV DNA and non-chimpanzee mammalian DNA b, in chimpanzee faecal samples from the East community over time. Each line represents a chimpanzee. Bold names correspond to chimpanzees in which mild to severe signs compatible with MPXV infection were observed. Boxes represent age groups (infant, juvenile, adolescent and adult). Vertical light grey shadowing indicates the period in which clinical signs were observed in the group. Horizontal dark grey shadowing indicates the period in which clinical signs were observed in severely ill chimpanzees.
Individual social network metrics in-strength a, out-strength b, in-degree c, and out-degree d, in the North community. Individuals (n=9) are classified as MPXV negative and positive according to PCR results from faecal samples. Timeframes before, during and after the outbreak are based on first and last positive PCR result. The network metrics are also shown for the year 2015 as control. The horizontal line in the whisker plots represents the mean. The lower and upper bounds of the boxes indicate the first and third quartile, respectively. Vertical lines are the upper and lower whisker representing a maximum of the largest/smallest value, but not over 1.5 times the interquartile distance. P values were calculated with a two-sided Mann-Whitney test. (female male). Source data
Extended Data Fig. 8 Ratio of non-chimpanzee mammalian DNA detection in chimpanzee faecal samples from the three communities.
Individuals (n=46) are divided into MPXV positive and negative based on PCR results from faecal samples. The horizontal line in the whisker plots represents the mean. The lower and upper bounds of the boxes indicate the first and third quartile, respectively. Vertical lines are the upper and lower whisker representing a maximum of the largest/smallest value but not over 1.5 times the inter quartile distance. P values were calculated with a two-sided Mann-Whitney test. (female male). Source data
Extended Data Fig. 9 Ratio of non-chimpanzee mammalian DNA detection in faecal samples of female chimpanzees with offspring from the three communities.
Individuals (n=23) are divided into MPXV positive and negative based on the status of their offspring during the outbreaks. The horizontal line in the whisker plots represents the mean. The lower and upper bounds of the boxes indicate the first and third quartile, respectively. Vertical lines are the upper and lower whisker representing a maximum of the largest/smallest value but not over 1.5 times the inter quartile distance. P values were calculated with a two-sided Mann-Whitney test. Source data
Supplementary information guide, discussion, tables 1–6 and Fig. 1.
Monkeypox respiratory symptoms in a wild chimpanzee. This video shows the severe respiratory symptoms, such as breathing with an open mouth, and limited rash observed in a chimpanzee (Pushkin) from the south group infected with MPXV in 2017.
Monkeypox-limited exanthema and grooming in a wild chimpanzee. This video shows the limited rash observed in a chimpanzee (Ravel) from the south group infected with MPXV in 2017 and grooming, including ingestion of nasal discharge, by group members.
Monkeypox diffuse rash and grooming in wild chimpanzees. This video shows the diffuse exanthema and lethargy observed in the chimpanzees from the east community infected with MPXV in 2018. Grooming activity, including ingestion of lesion material, by the mother is also shown.
Monkeypox diffuse rash and grooming in wild chimpanzees. This video shows the diffuse exanthema and lethargy observed in the chimpanzees from the east community infected with MPXV in 2018. Grooming activity, including ingestion of lesion material, by the sister is also shown.
Monkeypox diffuse rash and grooming in wild chimpanzees. This video shows the diffuse exanthema and lethargy observed in the chimpanzees from the east community infected with MPXV in 2018. Grooming activity, including ingestion of lesion material, by the mother and sister is also shown.
This excel file contains several sheets showing the results that were derived from the non-invasive samples collected during the three MPXV outbreaks (Supplementary Table 3). Results shown include PCR, whole-genome sequencing and virus isolation. The excel file also contains the information on the necropsy samples collected in TNP and included in this study (Supplementary Table 6), providing details on the species that necropsies were performed on as well as types of tissue tested.
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Patrono, L.V., Pléh, K., Samuni, L. et al. Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity. Nat Microbiol (2020). https://doi.org/10.1038/s41564-020-0706-0