Accepted Manuscript The diversity and impact of hookworm infections in wildlife Mauricio Seguel, Nicole Gottdenker PII: S2213-2244(17)30008-1 DOI: 10.1016/j.ijppaw.2017.03.007 Reference: IJPPAW 192 To appear in: International Journal for Parasitology: Parasites and Wildlife Received Date: 17 January 2017 Revised Date: 23 March 2017 Accepted Date: 31 March 2017 Please cite this article as: Seguel, M., Gottdenker, N., The diversity and impact of hookworm infections in wildlife, International Journal for Parasitology: Parasites and Wildlife (2017), doi: 10.1016/ j.ijppaw.2017.03.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DIVERSITYACCEPTED MANUSCRIPT Black Bear Ancylostoma pluridentatum Red Fox Ancylostoma tubaeforme Bobcat Uncinaria stenocephala Host species Hookworm diversity Host diversity Hookworm species x x IMPACT Anemia Retarded Growth MANUSCRIPT Mortality Felids Canids Canids Felids Ursids Otariids Otariids Elephantids Otariids ACCEPTED Hookworm biomass (Prevalence + burden + hookworm size) Temperature Humidity Host density 1 The diversity and impact of hookworm infections in wildlife 2 3 Mauricio Seguel a,* , Nicole Gottdenker a 4 aDepartment of Pathology, College of Veterinary Medicine, University of Georgia, 501 DW Brooks 5 Dr, Athens, Georgia 30602, USA. 6 7 * Corresponding Author. ACCEPTED MANUSCRIPT 8 Email address: [email protected] 9 10 Highlights 11 - At least 68 hookworm species have been described in 111 species of wild mammals. 12 - Wildlife are permanent hosts of important hookworms of humans and domestic animals. 13 -Hookworms cause anemia, retarded growth and mortality in canids, felids and otariids. 14 - Hookworm biomass is a key driver of pathogenic effects in a host population. MANUSCRIPT 15 16 Abstract 17 Hookworms are blood-feeding nematodes that parasitize the alimentary system of mammals. 18 Despite their high pathogenic potential, little is known about their diversity and impact in wildlife 19 populations. We conducted aACCEPTED systematic review of the literature on hookworm infections of wildlife 20 and analyzed 218 studies qualitative and quantitatively. At least 68 hookworm species have been 1 described in 9 orders, 24 families, and 111 species of wild mammals. Black bears, red foxes, and 2 bobcats harbored the highest diversity of hookworm species and Ancylostoma pluridentatum , A. 3 tubaeforme , Uncinaria stenocephala and Necator americanus were the hookworm species with the 4 highest host diversity index. Hookworm infections cause anemia, retarded growth, tissue damage, 5 inflammation and significant mortality in several wildlife species. Anemia has been documented 6 more commonly in canids, felids and otariids, and retarded growth only in otariids. Population- 7 level mortality has been documented through controlled studies only in canines and eared seals 8 although sporadic mortality has been noticed in felines, bears and elephants. The main driver of 9 hookworm pathogenic effects was the hookworm biomass in a population, measured as prevalence, 10 mean burden and hookworm size (length). Many studies recorded significant differences in ACCEPTED MANUSCRIPT 11 prevalence and mean intensity among regions related to contrasts in local humidity, temperature, 12 and host population density. These findings, plus the ability of hookworms to perpetuate in 13 different host species, create a dynamic scenario where changes in climate and the domestic animal- 14 human-wildlife interface will potentially affect the dynamics and consequences of hookworm 15 infections in wildlife. 16 17 Keywords: Ancylostoma, hookworm, Uncinaria, pathology, epidemiology, wildlife 18 MANUSCRIPT 19 Contents 20 1. Introduction 21 2. Materials and Methods 22 3. Characterization of studies describing hookworm infections in wild animals 23 4. Mammalian orders andACCEPTED families infected with hookworms 24 4.1Carnivora 1 4.1.1 Canidae 2 4.1.2 Felidae 3 4.1.3 Otariidae 4 4.1.4 Procyonidae 5 4.1.5 Mustelidae 6 4.1.6 Ursidae 7 4.1.7 Mephtididae, Herpestidae, Phocidae, Hyenidae and Viverridae. 8 4.2 Arctiodactyla 9 4.2.1 Bovidae 10 4.2.2 Suidae and Tayassuidae ACCEPTED MANUSCRIPT 11 4.2.3 Cervidae and Giraffidae 12 4.3 Primate 13 4.4 Rodentia 14 4.5 Perissodactyla 15 4.6 Proboscidea 16 4.7 Pholidota 17 4.8 Afrosoricida and Scandentia 18 5. The impact of hookworm infections on wildlife hosts and populations. 19 5.1 Pathologic effects MANUSCRIPT 20 5.1.1 Anemia 21 5.1.2 Retarded growth 22 5.1.3 Tissue damage and inflammation 23 5.1.4 MortalityACCEPTED 24 5.2 Drivers of hookworm pathologic effects 1 1. Discussion and Conclusions 2 References 3 4 5 1. Introduction 6 Hookworms (Nematoda: Strongylida: Ancylostomatoidae) are blood-feeding nematodes that 7 parasitize the mammalian alimentary system (Popova, 1964). Regardless of the large diversity 8 within this parasitic group, all Ancylostomatoidae species share basic morphologic, physiologic and 9 life history traits that translate into similar consequences for their host. In humans and domestic 10 animals, the deleterious effects of hookworms are well documented at the individual and population ACCEPTED MANUSCRIPT 11 level, being one of the most significant neglected tropical diseases of humans (Bartsch et al., 2016), 12 and an important cause or contributory factor of anemia and neonatal mortality in domestic dogs 13 and cats (Traversa, 2012). Despite the potential deleterious impact in their hosts, there is no 14 currently available summary on the number of hookworm species described and the significance of 15 hookworm infection in free-ranging wild mammals. 16 The modification of landscapes and climate change create additional challenges for wildlife disease 17 study, and it is predicted that these phenomena will modify the dynamics of nematode infections 18 (Weaver et al., 2010; Weinstein and Lafferty, 2015). Therefore, improved description, analysis, and 19 understanding of hookworm infections in wildlife arMANUSCRIPTe necessary to direct future research efforts and 20 understand host-parasite relationships in a regional and global scale. 21 In this context, the objectives of this review are to i) provide a systematic summary of the literature 22 available on hookworm infections of wildlife, ii) evaluate the reported hookworm diversity in 23 wildlife corrected for sampling effort, iii) identify significant pathologic features of these infections 24 and the potential drivers of theACCEPTED deleterious effects of hookworms on wildlife hosts. 25 1 2. Materials and Methods 2 2.1 Searching methods and inclusion criteria 3 A systematic literature review of Ancylostomatoidae nematodes of wildlife was performed using 4 Google scholar, Web of Science and Biosis search engines on April 27th 2016; following 5 recommended practices for systematic reviews in the field of parasitology (Haddaway and Watson, 6 2016). The initial term searched was “hookworm(s)” AND “wildlife”. The abstracts of the papers 7 retrieved were reviewed and included in the study if they met the following criteria: i) The parasitic 8 nematode found belonged to a genus within the Ancylostomatoidae family. (Studies describing the 9 presence of eggs or nematodes as “hookworms” or “strongyles” without genus identification were 10 excluded). ii) The host species was anyA CCEPTEDfree-rangin MANUSCRIPTg non-domesticated (wild) animal. Captive wild 11 animals were only included if they were taken from the wild soon before the study, and therefore, 12 transmission of parasites was assumed to occur in the wild. In the case of domestic animal-wildlife 13 hybrids, these were included if they were free-ranging. Additional searches were performed using 14 the preliminary list of genera identified in the initial search plus the word “wildlife” (e.g. 15 “Ancylostoma wildlife”). The studies selected based on abstract screening (N=216) were fully 16 reviewed and the most significant findings summarized into a master spreadsheet (supplementary 17 material). 18 2.2 Data analyses MANUSCRIPT 19 To identify host species with high hookworm diversity, an index penalized for sampling effort was 20 calculated based on previously published methods (Nunn et al., 2003; Ezenwa et al., 2006). Briefly; 21 the citations for each host species were extracted from the databases and after factor analyses 22 condensed into one variable, citation-principal component (citation-PC). Additional sampling effort 23 measures included the number of animals sampled in the reviewed studies and the number of ACCEPTED 24 studies in our review for each host species. Negative binomial regression models were fitted for 25 each measure of sampling effort and the residuals were used as a penalized index of hookworm 1 diversity. To assess which hookworm species parasitized higher number of wildlife species a 2 similar approach was used with the difference that citation-PC was not used because of “too high” 3 penalization for highly studied hookworm species infecting humans or domestic animals (e.g. 4 Necator americanus ). We used instead, the total number of mammalian species screened in the 5 studies where that hookworm species was found, since in many