Vampire Bat Rabies: Ecology,Epidemiology and Control

Extensive surveillance in bat populations in response to recent emerging diseases has revealed that this group of mammals acts as a reservoir for a large range of viruses. However, the oldest known association between a zoonotic virus and a bat is that between rabies virus and the vampire bat. Vampire bats are only found in Latin America and their unique method of obtaining nutrition, blood-feeding or haematophagy, has only evolved in the New World. The adaptations that enable blood-feeding also make the vampire bat highly effective at transmitting rabies virus. Whether the virus was present in pre-Columbian America or was introduced is much disputed, however, the introduction of Old World livestock and associated landscape modification, which continues to the present day, has enabled vampire bat populations to increase. This in turn has provided the conditions for rabies re-emergence to threaten both livestock and human populations as vampire bats target large mammals. This review considers the ecology of the vampire bat that make it such an efficient vector for rabies, the current status of vampire-transmitted rabies and the future prospects for spread by this virus and its control.     

Towards Development of an Anti-Vampire Bat Vaccine for Rabies Management: Inoculation of Vampire Bat Saliva Induces Immune-Mediated Resistance

The common vampire bat (Desmodus rotundus) is a hematophagous species responsible for paralytic rabies and bite damage that affects livestock, humans and wildlife from Mexico to Argentina. Current measures to control vampires, based upon coumarin-derived poisons, are not used extensively due in part to the high cost of application, risks for bats that share roosts with vampires and residual environmental contamination. Observations that vampire bat bites may induce resistance in livestock against vampire bat salivary anticoagulants encourage research into novel vaccine-based alternatives particularly focused upon increasing livestock resistance to vampire salivary components. We evaluated the action of vampire bat saliva-Freund’s incomplete adjuvant administered to sheep with anticoagulant responses induced by repeated vampire bites in a control group and examined characteristics of vampire bat salivary secretion. We observed that injections induced a response against vampire bat salivary anticoagulants stronger than by repeated vampire bat bites. Based upon these preliminary findings, we hypothesize the utility of developing a control technique based on induction of an immunologically mediated resistance against vampire bat anticoagulants and rabies virus via dual delivery of appropriate host and pathogen antigens. Fundamental characteristics of host biology favor alternative strategies than simple culling by poisons for practical, economical, and ecologically relevant management of vampire populations within a One Health context.     

Evidence of Rabies Virus Exposure among Humans in the Peruvian Amazon

Abstract. In May of 2010, two communities (Truenococha and Santa Marta) reported to be at risk of vampire bat depredation were surveyed in the Province Datem del Mara?ón in the Loreto Department of Perú. Risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. Rabies virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG) antibodies were detected in the sera of three individuals, two of whom were also seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent with positive rVNA results reported prior vaccination and 86% (six of seven) of rVNA-positive respondents reported being bitten by bats, these data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.     

Rabies in a nine-year-old child: The myth of the bite.

A nine-year-old boy died from rabies encephalitis caused by a rabies virus variant associated with insectivorous bats. The patient was most likely infected in the Laurentian Mountains of western Quebec, but neither the patient nor his parents remembered any direct contact with an animal. The diagnosis was made seven days after the start of symptoms. After examining the most recent cases of rabies in North America, it is obvious that rabies following bat exposure can occur without history of a documented bite. The present case report emphasizes that the general public and medical care providers need better information about the risks associated with exposure to bats.     

Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

Australian bat lyssavirus (ABLV) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats (genus Pteropus) and the other in insectivorous microbats (genus Saccolaimus). Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incubation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G). Recent studies have revealed that proposed rabies virus (RABV) receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen.     

Antigenic and genetic characterization of the first rabies virus isolated from the bat Eumops perotis in Brazil

Although the main transmitters of rabies in Brazil are dogs and vampire bats, the role of other species such as insectivorous and frugivorous bats deserves special attention, as the rabies virus has been isolated from 36 bat species. This study describes the first isolation of the rabies virus from the insectivorous bat Eumops perotis. The infected animal was found in the city of Ribeir?o Preto, S?o Paulo. The virus was identified by immunofluorescence antibody test (FAT) in central nervous system (CNS) samples, and the isolation was carried out in N2A cell culture and adult mice. The sample was submitted to antigenic typing using a panel of monoclonal antibodies (CDC/Atlanta/USA). The DNA sequence of the nucleoprotein gene located between nucleotides 102 and 1385 was aligned with homologous sequences from GenBank using the CLUSTAL/W method, and the alignment was used to build a neighbor-joining distance-based phylogenetic tree with the K-2-P model. CNS was negative by FAT, and only one mouse died after inoculation with a suspension from the bat's CNS. Antigenic typing gave a result that was not compatible with the patterns defined by the panel. Phylogenetic analysis showed that the virus isolated segregated into the same cluster related to other viruses isolated from insectivorous bats belonging to genus Nyctinomops ssp. (98.8% nucleotide identity with each other).     

Gene Expression Profile Induced by Two Different Variants of Street Rabies Virus in Mice

Pathogenicity and pathology of rabies virus (RABV) varies according to the variant, but the mechanisms are not completely known. In this study, gene expression profile in brains of mice experimentally infected with RABV isolated from a human case of dog rabies (V2) or vampire bat-acquired rabies (V3) were analyzed. In total, 138 array probes associated with 120 genes were expressed differentially between mice inoculated with V2 and sham-inoculated control mice at day 10 post-inoculation. A single probe corresponding to an unannotated gene was identified in V3 versus control mice. Gene ontology (GO) analysis revealed that all of the genes upregulated in mice inoculated with V2 RABV were involved in the biological process of immune defense against pathogens. Although both variants are considered pathogenic, inoculation by the same conditions generated different gene expression results, which is likely due to differences in pathogenesis between the dog and bat RABV variants. This study demonstrated the global gene expression in experimental infection due to V3 wild-type RABV, from the vampire bat Desmodus rotundus, an important source of infection for humans, domestic animals and wildlife in Latin America.     

Rabies in a nine-year-old child: The myth of the bite

A nine-year-old boy died from rabies encephalitis caused by a rabies virus variant associated with insectivorous bats. The patient was most likely infected in the Laurentian Mountains of western Quebec, but neither the patient nor his parents remembered any direct contact with an animal. The diagnosis was made seven days after the start of symptoms. After examining the most recent cases of rabies in North America, it is obvious that rabies following bat exposure can occur without history of a documented bite. The present case report emphasizes that the general public and medical care providers need better information about the risks associated with exposure to bats.Key Words: Bat, Children, Encephalitis, Prophylaxis, RabiesRabies is a zoonosis responsible for more than 50,000 human deaths every year worldwide, as reported by the World Health Organization. In North America and Europe, human rabies has become a very rare disease, because of the systematic vaccination of domestic animals, massive vaccination campaigns of wild animals, efficacy of rabies postexposure prophylaxis (RPEP) and education programs (1,2). While knowledge about the risk of rabies associated with a bite from a terrestrial animal seems relatively adequate among the general public and medical care providers, a lack of information may exist regarding the risk of human rabies following contact with a bat. Between 1980 and 1996, 32 cases of human rabies were diagnosed in the United States, 17 of which occurred after a contact with an indigenous bat (of which only two patients had a definite bite), 14 cases after a dog bite and one after a skunk bite (3). In Canada, three of the four cases of human rabies that have occurred since 1970 followed exposure to bats, the last case dating to 1985 (4). Since September 2000, five cases of human rabies have been reported in the United States (5). One was consecutive to a dog bite contracted in Africa and four have been attributed to bats; in the latter cases, a definite history of a bite was noted in only one case. In 1996, the National Association of State Public Health Veterinarians of the United States stated that "since rabies is endemic in bats, bats should be excluded from houses and surrounding structures to prevent direct association with humans" (6). Possible measures to reduce the bat population to a critical threshold below which the virus might be unable to propagate or to induce immunity in the vector via vaccination seem physically, economically and ecologically impractical (7). The case that we report emphasizes that the bite or the scratch of a rabid bat can go unnoticed and may lead to the development of human rabies.     

Genetic divergence of rabies viruses from bat species of Colorado, USA

Molecular epidemiological studies have linked many cryptic human rabies cases in the United States with exposure to rabies virus (RV) variants associated with insectivorous bats. In Colorado, bats accounted for 98% of all reported animal rabies cases between 1977 and 1996. The genetic divergence of RV was investigated in bat and terrestrial animal specimens that were submitted for rabies diagnosis to the Colorado Department of Public Health and Environment (CDPHE), Colorado, USA. RV isolates from animal specimens across the United States were also included in the analysis. Phylogenetic analyses were performed on partial nucleoprotein (N) gene sequences, which revealed seven principal clades. RV associated with the colonial big brown bat, Eptesicus fuscus, an bats of the genus Myotis were found to segregate into two distinct clades (I and IV). Clade I was harbored by E. fuscus and Myotis species, but was also identified in terrestrial animals such as domestic cats and striped skunks (Mephitis mephitis). Clade IV was divided into subclades IVA, IVB, and IVC; IVA was identified in E. fuscus, and Myotis species bats, and also in a fox; subclades IVB and IVC circulated predominantly in E. fuscus. Clade II was formed by big free-tailed bat (Nyctinomops macrotis) and striped skunk (Mephitis mephitis) samples. Clade III included RVs that are maintained by generally solitary, migratory bats such as the silver-haired bat (Lasionycteris noctivagans) and bats of the genus Lasiurus. Big brown bats were found to harbor this RV variant. None of the Colorado specimens segregated with clades V and VII that harbor RVs associated with terrestrial animals. Different species of bats had the same RV variant, indicating active inter-species rabies transmission. In Colorado, animal rabies occurs principally in bats, and the identification of bat RVs in cat, gray fox Urocyon cinereoargenteus), and striped skunks demonstrated the importance of rabies spillover from bats to domestic and terrestrial wildlife species.     

Antigenic typing of Brazilian rabies virus samples isolated from animals and humans, 1989-2000

Animal and human rabies samples isolated between 1989 and 2000 were typified by means of a monoclonal antibody panel against the viral nucleoprotein. The panel had been previously established to study the molecular epidemiology of rabies virus in the Americas. Samples were isolated in the Diagnostic Laboratory of the Pasteur Institute and in other rabies diagnostic centers in Brazil. In addition to the fixed virus samples CVS-31/96-IP, preserved in mouse brain, and PV-BHK/97, preserved in cell culture, a total of 330 rabies virus samples were isolated from dogs, cats, cattle, horses, bats, sheep, goat, swine, foxes, marmosets, coati and humans. Six antigenic variants that were compatible with the pre-established monoclonal antibodies panel were defined: numbers 2 (dog), 3 (Desmodus rotundus), 4 (Tadarida brasiliensis), 5 (vampire bat from Venezuela), 6 (Lasiurus cinereus) and Lab (reacted to all used antibodies). Six unknown profiles, not compatible with the panel, were also found. Samples isolated from insectivore bats showed the greatest variability and the most commonly isolated variant was variant-3 (Desmodus rotundus). These findings may be related to the existence of multiple independent transmission cycles, involving different bat species.     

A new case of bat rabies in France

INTRODUCTION: Bat rabies represents an emerging zoonosis in Europe and the only endemic cause of rabies in France. CASE RECORD: A 29 year-old woman was bitten at the hand by a bat. The diagnosis of bat rabies was positive and the viral strain was an European Bat Lyssavirus 1a. A combination of rabies vaccine and human rabies immune globulin was provided to the patient. DISCUSSION: Any direct contact with a bat must be avoided. In case of exposure to bats, the postexposure treatment must associate the rabies vaccine and human rabies immune globulin because of antigenic diversity of Lyssavirus circulating in bat species.     

Cryptogenic rabies, bats, and the question of aerosol transmission

Human rabies is rare in the United States; however, an estimated 40,000 patients receive rabies postexposure prophylaxis each year. Misconceptions about the transmission of rabies are plentiful, particularly regarding bats. Most cases of human rabies caused by bat variants have no definitive history of animal bite. Three hypotheses are proposed and reviewed for the transmission of rabies from bats to human beings. They include nonbite transmission (including aerosol transmission), the alternate host hypothesis (an intermediate animal host that acquires rabies from a bat and then transmits rabies to human beings), and minimized or unrecognized bat bites. Nonbite transmission of rabies is very rare, and aerosol transmission has never been well documented in the natural environment. The known pathogenesis of rabies and available data suggest that all or nearly all cases of human rabies attributable to bats were transmitted by bat bites that were minimized or unrecognized by the patients.     

Molecular characterization of rabies virus isolates from Mexico: implications for transmission dynamics and human risk.

Twenty-eight samples from humans and domestic and wild animals collected in Mexico between 1990 and 1995 were characterized by using anti-nucleoprotein monoclonal antibodies and limited sequence analysis of the nucleoprotein gene. The variants of rabies viruses identified in these samples were compared with other isolates from Mexico and the rest of the Americas to establish epidemiologic links between cases and outbreaks and to increase the understanding of rabies epidemiology in the Western Hemisphere. Antigenic and genetic diversity was found in all samples from dogs and dog-related cases, suggesting a long-term endemic situation with multiple, independent cycles of virus transmission. Two isolates from bobcats were antigenically and genetically homologous to the rabies variant circulating in the Arizona gray fox population, indicating a wider distribution of this variant than previously reported. Rabies isolates from skunks were unrelated to any variant analyzed in this study and represent a previously unrecognized cycle of rabies transmission in skunks in Baja California Sur. Two antigenic and genetic variants co-circulating in southern and eastern Mexico were found in viruses obtained from cases epidemiologically related to vampire bats. These results serve as a baseline for the better understanding of the molecular epidemiology of rabies in Mexico.     

Human rabies in the United States, 1960 to 1979: epidemiology, diagnosis, and prevention

Thirty-eight cases of human rabies occurred in the United States and its territories from 1960 to 1979. The major source of exposure to rabies has changed from indigenous dogs and cats in the 1940s and 1950s to wild carnivores and bats (11 of the 27 cases with known exposures); unusual exposures (3 cases) and exposures in a foreign country (7 cases) have also become more important. No exposure could be identified for 6 of the 38 cases. Two patients received optimal prophylaxis, 14 suboptimal, and 22 no prophylaxis after exposure. Some cases might have been prevented by an increased awareness of the risks and treatment for exposure to rabies, and use of the new rabies vaccines. The diagnosis was often made late in the clinical course including after death in 8 cases. This delay, in part, resulted from the diversity in the clinical presentation. Rabies should be considered in any case of encephalitis or myelitis. Laboratory confirmation of the diagnosis was often delayed. Testing for serum antibodies was the most reliable test in unvaccinated patients, and isolation of virus was the test most likely to be positive early in the illness.     

Resolving the roles of immunity,pathogenesis, and immigration for rabies persistence in vampire bats

Bats are important reservoirs for emerging infectious diseases, yet the mechanisms that allow highly virulent pathogens to persist within bat populations remain obscure. In Latin America, vampire-bat–transmitted rabies virus represents a key example of how such uncertainty can impede efforts to prevent cross-species transmission. Despite decades of agricultural and human health losses, control efforts have had limited success. To establish persistence mechanisms of vampire-bat–transmitted rabies virus in Latin America, we use data from a spatially replicated, longitudinal field study of vampire bats in Peru to parameterize a series of mechanistic transmission models. We find that single-colony persistence cannot occur. Instead, dispersal of bats between colonies, combined with a high frequency of immunizing nonlethal infections, is necessary to maintain rabies virus at levels consistent with field observations. Simulations show that the strong spatial component to transmission dynamics could explain the failure of bat culls to eliminate rabies and suggests that geographic coordination of control efforts might reduce transmission to humans and domestic animals. These findings offer spatial dynamics as a mechanism for rabies persistence in bats that might be important for the understanding and control of other bat-borne pathogens.Bats (Chiroptera) host some of the most significant newly emerging viruses affecting humans and domestic animals, and have been suggested as the evolutionary origin of several endemic human infections (1, 2). Predicting the spatiotemporal distribution of pathogen transmission from bats to other species requires understanding both the ecological factors that encourage cross-species exposures and the transmission dynamics within bat populations (3). Understanding viral persistence in bat populations is challenging because seemingly ideal ecological traits for explosive pathogen transmission such as high mobility and colonial aggregation contrast with the limited supply of new susceptible individuals generated by characteristically long-lived and slow-reproducing host species. Consequently, epizootiological models of bat viruses have required complex immunological or behavioral mechanisms to achieve long-term persistence, such as waning maternal immunity or an extended incubation period through hibernation (4–6). These studies also demonstrated the power of a combined field, experimental, and modeling approach for identifying persistence mechanisms in bats, but such holistic investigations are still absent for most systems (3).In Latin America, vampire bat (Desmodus rotundus) transmitted rabies virus (VBRV) is among the most significant wildlife zoonoses for agricultural development and human health (7). Growth in the livestock industry likely exacerbates VBRV outbreaks by providing an almost unlimited food source for these blood-feeding bats, fueling population growth and range expansions (8–10). The combination of large vampire bat populations and frequent contacts with livestock as bats bite to drink blood contributes to losses of ca. $30 million (US dollars) per year in livestock mortality alone (7). Simultaneously, lethal human rabies outbreaks are increasingly recognized in remote areas of the Amazon rainforest; these may be linked to a combination of human encroachment into forested areas, natural prey depletion, and improved detection (11). Attempts to control vampire bat populations and VBRV transmission have been in place since the 1960s, and include indiscriminate killing of bats and a topical anticoagulant poison, “vampiricide,” that kills conspecifics that groom treated bats (12). A similar vehicle has been proposed—but not attempted in natural populations—for oral vaccination of vampire bats (13). To date, no control method has eliminated viral circulation as evidenced by recurrent cases in livestock and humans, even in areas where culling is performed regularly.Developing effective control strategies for VBRV relies on understanding the transmission dynamics within the reservoir host (14), an issue that has been largely neglected despite recognition of VBRV and its health risks since the early 1900s (15). Spatiotemporal patterns of VBRV mortality in livestock at the edge of the vampire bats’ range in northern Argentina suggested traveling waves of infection in vampire bats that were speculated to recur upon recovery of an unknown threshold density of susceptible bats (16, 17). However, in many regions of Peru, Brazil, and Mexico, VBRV continuously affects livestock, suggesting enzootic persistence rather than invasion. Several possible but untested mechanisms of persistence have been suggested, including sufficiently large bat population sizes (i.e., above the critical community size, ref. 18), a healthy carrier state, and a variety of immunological scenarios (19–21). Distinguishing these competing scenarios is fundamental to understanding persistence and improving control.We evaluated the determinants of viral persistence in vampire bat colonies by developing a maximum likelihood framework to parameterize and evaluate stochastic epizootiological models. This was achieved using data from infection studies in captive vampire bats and a unique longitudinal field study in wild vampire bats, where rabies exposures were monitored in individually marked bats from 17 colonies across four departments of Peru between 2007 and 2010 (Fig. 1). Because culling is the most common practice currently used to control VBRV in vampire bat populations, we simulated potential culling practices to examine their impact on both the seroprevalence and its expected exposure rate to livestock.Open in a separate windowFig. 1.(Right) Map of South America with Peru indicated by gray shading. Antibody prevalence field data on VBRV were sampled across 17 sites in four departments of Peru [Apurimac (red), Cajamarca (orange), Lima (blue), and Madre de Dios (green)] and are provided for 2007, 2009, and 2010 (19). Sites were sampled approximately yearly. For each site in a given year, the proportion of seropositive bats is denoted by off-white with the proportion seronegative denoted by the color associated with the department where the colony is located. The radius of each observation is proportional to sample size. See SI Appendix for the complete dataset.     

Retrospective Enhanced Bat Lyssavirus Surveillance in Germany between 2018–2020

Lyssaviruses are the causative agents for rabies, a zoonotic and fatal disease. Bats are the ancestral reservoir host for lyssaviruses, and at least three different lyssaviruses have been found in bats from Germany. Across Europe, novel lyssaviruses were identified in bats recently and occasional spillover infections in other mammals and human cases highlight their public health relevance. Here, we report the results from an enhanced passive bat rabies surveillance that encompasses samples without human contact that would not be tested under routine conditions. To this end, 1236 bat brain samples obtained between 2018 and 2020 were screened for lyssaviruses via several RT-qPCR assays. European bat lyssavirus type 1 (EBLV-1) was dominant, with 15 positives exclusively found in serotine bats (Eptesicus serotinus) from northern Germany. Additionally, when an archived set of bat samples that had tested negative for rabies by the FAT were screened in the process of assay validation, four samples tested EBLV-1 positive, including two detected in Pipistrellus pipistrellus. Subsequent phylogenetic analysis of 17 full genomes assigned all except one of these viruses to the A1 cluster of the EBLV-1a sub-lineage. Furthermore, we report here another Bokeloh bat lyssavirus (BBLV) infection in a Natterer’s bat (Myotis nattereri) found in Lower Saxony, the tenth reported case of this novel bat lyssavirus.     

Profile of Cytokines and Chemokines Triggered by Wild-Type Strains of Rabies Virus in Mice

Rabies is a lethal infectious disease that causes 55,000 human deaths per year and is transmitted by various mammalian species, such as dogs and bats. The host immune response is essential for avoiding viral progression and promoting viral clearance. Cytokines and chemokines are crucial in the development of an immediate antiviral response; the rabies virus (RABV) attempts to evade this immune response. The virus''s capacity for evasion is correlated with its pathogenicity and the host''s inflammatory response, with highly pathogenic strains being the most efficient at hijacking the host''s defense mechanisms and thereby decreasing inflammation. The purpose of this study was to evaluate the expression of a set of cytokine and chemokine genes that are related to the immune response in the brains of mice inoculated intramuscularly or intracerebrally with two wild-type strains of RABV, one from dog and the other from vampire bat. The results demonstrated that the gene expression profile is intrinsic to the specific rabies variant. The prompt production of cytokines and chemokines seems to be more important than their levels of expression for surviving a rabies infection.     

Encephalitis caused by human herpesvirus‐6B in pancreas‐after‐kidney transplantation

Human herpesvirus‐6 (HHV‐6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV‐6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV‐6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV‐6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV‐6 encephalitis may be important for affected patients. We report the case of a 53‐year‐old pancreas‐after‐kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV‐6B encephalitis in solid organ transplant recipients.     

Imported African Tick Bite Fever in Japan: A Literature Review and Report of Three Cases

African tick bite fever (ATBF) is an acute febrile illness caused by Rickettsia africae. ATBF is an important differential diagnosis of acute febrile illness among returned travelers. However, little information is available on ATBF cases imported to Japan, as only seven have been reported to date. To characterize the epidemiological and clinical profiles of patients diagnosed with ATBF in Japan, we reported three new ATBF cases at our hospital between May 2015 and April 2018 and conducted a literature review.