key: cord-0721820-z8frc0mj authors: Colunga‐Salas, Pablo; Sánchez‐Montes, Sokani; Grostieta, Estefania; Verde‐Arregoitia, Luis D.; Cabrera‐Garrido, Martín Y.; Becker, Ingeborg; León‐Paniagua, Livia title: What do studies in wild mammals tell us about human emerging viral diseases in Mexico? date: 2019-10-07 journal: Transbound Emerg Dis DOI: 10.1111/tbed.13336 sha: 6d485bc2164e62ee702e5d2a2010739ba58c967e doc_id: 721820 cord_uid: z8frc0mj Multiple species of viruses circulate in wild mammals, some of them potentially causing zoonosis. Most of the suspected viral zoonotic diseases affecting human patients remain unidentified with regard to their aetiological agent. The aim of this study is to summarize the state of knowledge of the viral richness associated with wild mammals in Mexico throughout 1900–2018 and their relationship with human cases. We compiled two databases, one of them containing all available published studies on potentially zoonotic viruses in wild mammals and another with human cases related to zoonotic viruses. The database on wild mammals covers the period of 1900–2018; the human case database spans 2000–2013. We calculated the richness of viral potential zoonotic agents and evaluated their geographical distribution. We found 262 records of 42 potential zoonotic viral species associated with 92 wild mammal species in 28 states across Mexico. Records of human viral cases were only found in 29 states, which did not overlap with the reports in wild mammals. We detected 25.6% (42/164) of viral zoonotic agents reported worldwide. This analysis opens a relevant topic of discussion for public health attention. , hantavirus (Byers, 2018) and rabies (Begeman et al., 2018) . It is noteworthy that in Mexico the Ministry of Health has reported an important number of patients with suspected viral diseases without identification of the aetiological agent (CENAVECE, 2013) . For this reason, the aim of this study was to summarize the state of knowledge of the viral richness associated with wild mammals in Mexico and the possible relationship with human cases recorded in the country. We compiled a database of all the published studies we could identify through a literature search that focused on potential human zoonotic viral species associated with wild mammals in Mexico during the period of 1900-2018. We consider as potential zoonotic viral species those which belong to the viral families of viral species listed by Taylor et al. (2001) . For this step, an exhaustive literature research, using the following specialized databases: BioOne, Elsevier, HighWire, Iris, JSTOR, PubMed, Scopus, Records, was carried out. For this, a combination of several keywords: "virus", "wild", "mammals", "pathogens" and "Mexico" were used. Only those papers that met all of the following specifications were considered: (a) studies on wild mammals that occur and were sampled in Mexico, (b) viral species identification (at least at genus level) and (c) viral agent considered as zoonotic or potentially zoonotic. The following information was recorded from each study: • Family, genus and species of potential zoonotic viruses. The nomenclature used is in accordance with the 10th report of The International Committee on Taxonomy of Viruses' review (Lefkowitz et al., 2017) . • Order, family, genus and species of the mammalian host. Mammalian nomenclature was updated following the most recent taxonomical review for both terrestrial (Ramírez-Pulido, González-Ruíz, Gardner, & Arroyo-Cabrales, 2014 ) and marine mammals (Ceballos & Arroyo-Cabrales, 2012 ). • Disease caused by the viral species, and whether it has been reported as human disease based on ICD-10 (WHO, 2008). • Locality and collection date. We gathered spatial coordinate data for the reported localities or geo-referenced all localities from studies which did not provide spatial coordinates using the Fallingrain electronic catalogue for localities (http://www.falli ngrain.com/world/ index.html), and corroborated with Google Earth software, following the best practices for geo-referencing described in Chapman and Wieczorek (2006) . For wild mammals in Mexico, we evaluated the richness of potential zoonotic viral species obtained from passive or active surveillance in wild mammals through simple frequencies analyses. Graphics were done using GraphPad Prism v. 6 (GraphPad Software). A similar analysis was done for the human case database. To estimate how many species we expected to record in Mexico, we calculated a species accumulation curve with the R package vegan (Oksanen et al., 2016) with a rarefaction method. First, we performed a descriptive spatial analysis to summarize the overall spatial distribution of viral species recorded from wild mammals and across human populations using QGIS 2. With the geo-referenced coordinate data for the collecting localities of the mammalian hosts and the centroid coordinates of the geo-statistical locality polygons for the human records, we could investigate co-distribution as a point process. We followed Wheeler, Worden, and McLean (2016) and implemented a random relabelling permutation approach of the cross-K function. This method allows us to test whether there is a spatial patterning or association between wild mammal virus records and human viral cases. The cross-K function is the bivariate version of Ripley's K function and can be used to characterize point patterns and determine whether they are clustered, dispersed or randomly distributed (Dixon, 2002) . To test co-distribution under a realistic null hypothesis, we kept the point locations fixed, but randomly assigned each one to be either a wild mammal viral record or a human case under the same marginal frequencies. This test is appropriate for instances in which sampling is biased or uneven (Wheeler et al., 2016) . We called functions from the R packages spatstat (Baddeley, Turner, & Rubak, 2018) , sp and rgdal to run this test. We compared our data with known spatial and taxonomic patterns of research effort in mammalogy in Mexico, drawn from a review of 2,527 abstracts for work presented at 11 meetings of the Mexican We obtained 371 records, each one represents the mammalian host and its associated viral species per locality and study. From these records, 262 were identified at species level and the remaining 109 were identified at genus level (Colunga-Salas et al., 2019) . From the 262 species-identified records, 42 species of potentially zoonotic viruses were identified from 52 published scientific articles (Table S1) (Tables 1 and S1 ). The species accumulation curve is increasing without a clearly defined asymptote ( Figure 1 ). Moreover, studies on viruses associated with Mexican wild mammals were scattered and not systematic, and it was not until the early 1990s that more studies focusing on these taxa and the report of new species increased exponentially We recorded a total of 91 species of potential mammalian hosts (89 wild species and two peri-domestic wild mammals [Mus musculus, the house mouse and Rattus rattus, the black rat]) from 21 families of seven orders (Table 2) . Rodentia had the highest number of studies with 24, followed by Chiroptera (23) (Figures 5 and 6b; Table S4 ). We found that the distributions of human cases were not spatially related to the distribution of wild mammals harbouring the zoonotic virus. The observed K r distance function lies within the 99% simulation band and mirrors the mean of the simulation bands almost exactly, suggesting that the spatial records for human cases are spatially random conditional on where viruses were detected in wild mammals (Figure 7) . Note: New species were determined as those species not included in the last ICTV report, and with molecular information in their original publication. TA B L E 2 (Continued) (Calisher, Childs, Field, Holmes, & Schountz, 2006; Han et al., 2016; Luis et al., 2013; Mills & Childs, 1998; Plyusnin & Sironen, 2014; Taylor et al., 2001) . That reason could lead to even more studies on those mammalian orders, leaving many orders unattended. F I G U R E 3 Viral richness per virus family in each mammal order. Rodentia and Chiroptera orders are the most studied and show the highest record of viral species in the wildlife inventory. Cetacea is the only one with one species recorded [Colour figure can be viewed at wileyonlinelibrary.com] F I G U R E 4 Incidence rate of viral species associated with wild Mexican mammals. Colour intensity of states corresponds to incidence rate calculated (for data, see Table S2 ). * Rate per 100 mammalian species [Colour figure can be viewed at wileyonlinelibrary.com] Until the decade of 2000, Hantaviridae family was restricted to Rodentia, (Padula et al., 2004; Schmaljohn & Hjelle, 1997; Torres-Pérez et al., 2004) ; however, since the early 2000s, recent discoveries found some hantavirus species in Indian shrews [order: Soricomorpha] (Klempa et al., 2007; Zhang, 2014) and American and European bats (Sabino-Santos et al., 2018; Straková et al., 2017; Těšíková, Bryjová, Bryja, Lavrenchenko, & Goüy de Bellocq, 2017; Zhang, 2014) . This new information opens the possibility to assess the role of North American shrews and bats as host of hantavirus species. On this point, it is important to note that in Mexico Soricomorpha comprises 38 species (Ramírez-Pulido et al., 2014) , distributed along the entire national territory, and some of them distributed into isolated patches (Carraway, 2007) , all of these features, could lead to a high hantavirus richness. We clearly identified well-defined periods in which research on zoonotic viruses was focused on specific species, particularly, during the 1990s and 2000s when studies focused on rabies. Meanwhile, during the last decade the Hantaviridae family has been the most studied taxon. Since the 1980s, the knowledge of viruses associated with wild mammals has been increasing, perhaps due to the improvement of detection techniques, followed by the development of several serological and molecular tests, since they are straightforward, sensitive and specific (Schochetman, Ou, & Jones, 1988; Weigle, Murphy, & Brunell, 1984; Zambon, Hays, Webster, Newman, & Keene, 2001) . However, it is important to note that not all serological tests are specific, due to unspecific or cross-reaction with antibodies among other related viral species (Gónzalez-Barrio & Ruiz-Franco, 2019) . To avoid that, we consider necessary to use molecular techniques as confirmatory tests. It is also important to emphasize the high number of potential new species recorded in Mexico; in the case of the Cororonaviridae family, all species recorded until now in Mexico are likely new species, since phylogenetic analyses show that these species form separate clades . The same occurs with the genus Pegivirus, where at least three different lineages of that genus are clearly identified from Bayesian phylogenetic analysis (Quan et al., 2013) . Geographically, Veracruz and Chiapas were the states with the highest species richness of zoonotic virus associated with wild mammals and human cases. This can be related to the high wild mammal richness and the environmental conditions of both states, and in particular to their weather conditions, which can be an important driver for the proliferation of the invertebrate vectors of viral agents, given F I G U R E 5 Incidence rate of confirmed viral human cases from 2000 to 2013. Colour intensity of states corresponds to incidence rate calculated (for data, see Table S2 ). * Rate per 1,000,000 inhabitants [Colour figure can be viewed at wileyonlinelibrary.com] the vast areas of tropical forest and montane ecosystems where vectors are often found (Ceballos & Oliva, 2005; González-Christen, 2008; Krasnov, Shenbrot, Khokhlova, & Degen, 2004; Retana & Lorenzo, 2002) . We found that records of human cases seem to be spatially unrelated to viruses in wild mammals. This may be because most viral human cases were not fully confirmed and most of them were notified as unspecified viral fever or as unspecified arthropod-borne viral fever (Table S4) . Additionally, there are fundamental differences in how human cases and wildlife records are reported and sampled spatially. Despite known roadside bias in wild mammal sampling, wild mammal records are more likely to come from less urbanized landscapes than reports for human cases, which are tied more closely with health infrastructure in or close to human settlements. Our method for testing co-distribution accounts for distance and could potentially overcome these biases, but larger-scale simulation-based studies may be needed to accurately measure the sensitivity of this approach to sampling biases. (Table S1 ) (CENAVECE, 2013) . Therefore, it is critically important to enhance the surveillance of infecting zoonotic viruses in patients, since until now dengue fever is the only disease for which reporting is mandatory. It is essential to increase sampling efforts and enhance studies in more mammal species and states, in order to increase our knowledge about the biology, systematics, ecology and epidemiology of Furthermore, it is important to consider that areas with higher biodiversity rates are also considered a buffer to prevent the spillover of infectious diseases to human and domestic animals. Usually, the disruption of these ecosystems is the cause of the viral emergence; for this reason, the implementation of buffer zones and plans for sustainable exploitation should be the main axes for government decision-makers. This work was supported by grants PAPIIT IN216713, PAPIIT IN217515 and CONACyT 221405. The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, nonfinancial interest in the subject matter or materials discussed in this manuscript. Pablo Colunga-Salas, Sokani Sánchez-Montes and Estefania Grostieta contributed equally to database compilation and analysed the wildlife and human viral cases, wrote and reviewed the manuscript. Luis Darcy Verde-Arregoitia performed, analysed and discussed the statistical analyses. He also made substantial contributions to manuscript. Martín Yair Cabrera-Garrido reviewed and updated the mammalian species and made contributions to manuscript. Ingeborg Becker made substantial contributions to manuscript and reviewed early versions. Livia León-Paniagua contributed to identifying and updating the mammalian species, and contributed substantially with the manuscript. The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is a review article with no original research data. https://orcid.org/0000-0002-1355-0939 Sokani Sánchez-Montes https://orcid.org/0000-0001-6316-2187 Estefania Grostieta https://orcid.org/0000-0002-8573-1253 Luis D. Verde-Arregoitia https://orcid.org/0000-0001-9520-6543 Livia León-Paniagua https://orcid.org/0000-0002-1748-0915 Adams, A. P., Navarro-López, R., Ramírez-Aguilar, F. J., López-González, I., Leal, G., Flores-Mayorga, J. M., … Estrada-Franco, J. G. (2012) . F I G U R E 7 Cross-K statistics. Grey band represents simulated 99% confidence intervals based on 999 permutations where the point labels for human cases or wild mammal virus detection were randomly reallocated. The dark solid line shows the observed statistic. 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