Fifty Years of the National Rabies Control Program in Brazil under the One Health Perspective.

In 1973, the National Rabies Program was created in Brazil through an agreement between the Ministry of Health and Agriculture. Since its beginning, it developed integrated action through access to free post-exposure prophylaxis (PEP) for people at risk, dog vaccination campaigns, a joint surveillance system, and awareness. This study aims to describe human rabies in Brazil under the One Health perspective in recent decades, including achievements in the control of dog-mediated cases and challenges in human cases transmitted by wild animals. This paper also explores possible drivers of human rabies in the Northeast Region with half of the cases. The first part of this study was descriptive, presenting data and examples by periods. Statistical analysis was performed in the last period (2010-2022) to explore possible drivers. Dog-mediated human cases decreased from 147 to 0, and dog cases decreased from 4500 to 7. A major challenge is now human cases transmitted by wild animals (bats, non-human primates, and wild canids). Most current human cases occur in municipalities with a tropical and subtropical moist broadleaf forest biome and a Gini index higher than 0.5. In the multivariable analysis, an association with temperature was estimated (OR = 1.739; CI95% = 1.181-2.744), and primary healthcare coverage (OR = 0.947; CI95% = 0.915-0.987) was identified as a protector. It is possible to significantly reduce the number of dog-mediated human rabies cases through the efforts presented. However, Brazil has wildlife variants of the rabies virus circulating. The association of human cases with higher temperatures in the Northeast is a concern with climate change. To reduce human cases transmitted by wild animals, it is important to continue distributing free PEP, especially in remote at-risk areas in the Amazon Region, and to increase awareness.

Defining New Pathways to Manage the Ongoing Emergence of Bat Rabies in Latin America.

Rabies transmitted by common vampire bats (Desmodus rotundus) has been known since the early 1900s but continues to expand geographically and in the range of species and environments affected. In this review, we present current knowledge of the epidemiology and management of rabies in D. rotundus and argue that it can be reasonably considered an emerging public health threat. We identify knowledge gaps related to the landscape determinants of the bat reservoir, reduction in bites on humans and livestock, and social barriers to prevention. We discuss how new technologies including autonomously-spreading vaccines and reproductive suppressants targeting bats might manage both rabies and undesirable growth of D. rotundus populations. Finally, we highlight widespread under-reporting of human and animal mortality and the scarcity of studies that quantify the efficacy of control measures such as bat culling. Collaborations between researchers and managers will be crucial to implement the next generation of rabies management in Latin America.

Geographical Analysis for Detecting High-Risk Areas for Bovine/Human Rabies Transmitted by the Common Hematophagous Bat in the Amazon Region, Brazil.

BACKGROUND: The common hematophagous bat, Desmodus rotundus, is one of the main wild reservoirs of rabies virus in several regions in Latin America. New production practices and changed land use have provided environmental features that have been very favorable for D. rotundus bat populations, making this species the main transmitter of rabies in the cycle that involves humans and herbivores. In the Amazon region, these features include a mosaic of environmental, social, and economic components, which together creates areas with different levels of risk for human and bovine infections, as presented in this work in the eastern Brazilian Amazon. METHODOLOGY: We geo-referenced a total of 175 cases of rabies, of which 88% occurred in bovines and 12% in humans, respectively, and related these cases to a number of different geographical and biological variables. The spatial distribution was analyzed using the Kernel function, while the association with independent variables was assessed using a multi-criterion Analytical Hierarchy Process (AHP) technique. FINDINGS: The spatiotemporal analysis of the occurrence of rabies in bovines and humans found reduction in the number of cases in the eastern state of Pará, where no more cases were recorded in humans, whereas high infection rates were recorded in bovines in the northeastern part of the state, and low rates in the southeast. The areas of highest risk for bovine rabies are found in the proximity of rivers and highways. In the case of human rabies, the highest concentration of high-risk areas was found where the highway network coincides with high densities of rural and indigenous populations. CONCLUSION: The high-risk areas for human and bovine rabies are patchily distributed, and related to extensive deforested areas, large herds of cattle, and the presence of highways. These findings provide an important database for the generation of epidemiological models that could support the development of effective prevention measures and controls.

VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE BRAZILIAN AMAZON.

The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area.

The "Vampirome": Transcriptome and proteome analysis of the principal and accessory submaxillary glands of the vampire bat Desmodus rotundus, a vector of human rabies.

Vampire bats are notorious for being the sole mammals that strictly feed on fresh blood for their survival. While their saliva has been historically associated with anticoagulants, only one antihemostatic (plasminogen activator) has been molecularly and functionally characterized. Here, RNAs from both principal and accessory submaxillary (submandibular) salivary glands of Desmodus rotundus were extracted, and ~200 million reads were sequenced by Illumina. The principal gland was enriched with plasminogen activators with fibrinolytic properties, members of lipocalin and secretoglobin families, which bind prohemostatic prostaglandins, and endonucleases, which cleave neutrophil-derived procoagulant NETs. Anticoagulant (tissue factor pathway inhibitor, TFPI), vasodilators (PACAP and C-natriuretic peptide), and metalloproteases (ADAMTS-1) were also abundantly expressed. Members of the TSG-6 (anti-inflammatory), antigen 5/CRISP, and CCL28-like (antimicrobial) protein families were also sequenced. Apyrases (which remove platelet agonist ADP), phosphatases (which degrade procoagulant polyphosphates), and sphingomyelinase were found at lower transcriptional levels. Accessory glands were enriched with antimicrobials (lysozyme, defensin, lactotransferrin) and protease inhibitors (TIL-domain, cystatin, Kazal). Mucins, heme-oxygenase, and IgG chains were present in both glands. Proteome analysis by nano LC-MS/MS confirmed that several transcripts are expressed in the glands. The database presented herein is accessible online at http://exon.niaid.nih.gov/transcriptome/D_rotundus/Supplemental-web.xlsx. These results reveal that bat saliva emerges as a novel source of modulators of vascular biology. BIOLOGICAL SIGNIFICANCE: Vampire bat saliva emerges as a novel source of antihemostatics which modulate several aspects of vascular biology.

Serological investigation of rabies virus neutralizing antibodies in bats captured in the eastern Brazilian Amazon.

BACKGROUND: In 2004 and 2005 a total of 38 cases of human rabies transmitted by the hematophagous bat Desmodus rotundus were registered in the Brazilian state of Pará; 23 (60.5%) cases occurred in the northeastern region. Because of this, a serological investigation for the antibodies of rabies virus was performed in municipalities of the northeastern state of Pará, in order to assess whether the virus was circulating among different bat species. METHODS: Bats were collected in 2009 with mist-nets during the rainy and dry seasons and blood samples were collected for the serological survey. RESULTS: A total of 307 serum samples were obtained representing 28 bat species. The number of seropositives was high (50.8%, 156/307) and was significantly higher during the rainy season (67.4%, 95/141). No significant difference in rates was found between male and female or adult and juvenile. Seropositive individuals were recorded in 24 species sampled, the most prominent being Artibeus planirostris, with 52.2% (24/46) positive individuals. CONCLUSION: The serological proportion reported in this paper in a large numbers of individuals indicates that the rabies virus circulates quite actively in the study region, but, because of the production of antibodies, the expression of the disease in these individuals is low.

Exposure to rabies virus in a population of free-ranging capuchin monkeys (Cebus apella nigritus) in a fragmented, environmentally protected area in southeastern Brazil.

The aim of this study is to assess the frequency of rabies antibodies in free-ranging capuchin monkeys (Cebus apella nigritus) in a fragmented, environmentally protected, rural area of southeastern Brazil. Thirty-six free-ranging monkeys were tested by the rapid fluorescent focus inhibition test for detection of antibodies against rabies virus. Four individuals (11.11 %) had neutralizing antibody titers ≥ 0.25 IU/mL, demonstrating rabies virus exposure.

Preferential consumption of larger fruits of Piper arboreum (Piperaceae) by Carollia perspicillata (Phyllostomidae) in the brazilian tropical dry forest / Consumo preferencial de frutos maiores de Piper arboreum (Piperaceae) por Carollia Perspicillata (Phyllostomidae) em uma floresta tropical brasileira

Frugivorous animals may use morphological traits of food items such as size, hardness, shape, color and smell as cues that allow them to assess cost-benefit relationship of foraging activity. Fruit size is an important trait that influences feeding behavior of most frugivores, since there is a functional correlation between fruit size and frugivores' body size. Therefore, size-based preference is fundamental to understand plant-frugivore interactions and seed dispersal. In this sense, we tested the hypothesis of preferential consumption of larger fruits of Piper arboreum by the short-tailed fruit bat Carollia perspicillata in the Brazilian tropical dry forest. Results showed considerable variation in fruit size among and within plants. There was also significant difference in fruit ripening time among plants, which was not related to fruit size. Average size of remaining fruits reduced as they were removed from plants by the bats, which indicates preferential consumption of larger fruits. On the other hand, plant phenology constrained consumption of bigger fruits. Only a small fraction of plant crop was available for consumption each night, regardless of fruit size, which probably coerced bats to feed on smaller fruits as the availability of larger ones decreased. Results suggest that bat preference on fruit size is mediated by plant phenological strategies.

Os frugívoros utilizam as características morfológicas dos frutos tais como tamanho, dureza, forma, cor e cheiro, como pistas para avaliar o custo-benefício da atividade de forrageio. O tamanho dos frutos é uma característica importante que influencia o comportamento alimentar dos frugívoros, já que existe uma correlação funcional entre tamanho do fruto e o do tamanho do frugívoro. Por isso, a seleção do fruto a partir do seu tamanho é um elemento fundamental para a compreensão das interações frugívoro-planta e da dispersão de sementes. Neste sentido, nós testamos a hipótese de consumo preferencial de frutos maiores de Piper arboreum pelo morcego Carollia perspicillata em uma floresta tropical brasileira. Os resultados mostraram ampla variação no tamanho do fruto entre e dentro das plantas parentais. Também houve diferença significativa no tempo de maturação dos frutos entre as plantas, o qual não esteve relacionado com o tamanho do fruto. O tamanho médio dos frutos restantes na planta após a remoção pelos morcegos decresceu, o que indicou o consumo preferencial dos frutos maiores. Por outro lado, a fenologia da planta restringiu o consumo destes frutos. Um número pequeno de frutos maduros esteve disponível para o consumo por noite, independentemente de seu tamanho, o que provavelmente limitou a escolha dos morcegos, obrigando-os a se alimentarem dos frutos menores conforme a disponibilidade dos maiores reduziu-se. Os resultados sugerem que a preferência dos morcegos pelo tamanho dos frutos é mediada pelas estratégias fenológicas das plantas.

VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE BRAZILIAN AMAZON / Diagnóstico virológico e sorológico de raiva em morcegos de uma área urbana na Amazônia Brasileira

The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area.

Os surtos de raiva em humanos transmitida por Desmodus rotundus em 2004 e 2005 no nordeste do estado do Pará, Brasil, Amazônia Oriental, fizeram desta uma área prioritária para estudos sobre essa zoonose. Diante disso, o presente estudo fornece dados sobre esse fenômeno em contexto urbano, afim de avaliar uma possível circulação do vírus clássico da raiva (RABV) entre espécies de morcegos em Capanema, cidade localizada na bacia Amazônica. Os morcegos foram coletados em 2011, com auxílio de redes de espera durante as estações seca e chuvosa. Amostras de encéfalo e de sangue foram coletadas para o diagnóstico virológico e sorológico, respectivamente. Das 153 amostras de encéfalo analisadas, nenhuma encontrou-se positiva para infecção pelo RABV, porém, 50,34% (95% CI: 45,67-55,01) das amostras de soro analisadas estavam soropositivas. Artibeus planirostris foi a espécie mais comum, e seu percentual de indivíduos soropositivos foi bem elevado (52.46%, 95% CI: 52,31-52,60). Porções estatisticamente iguais de soropositivos foram registrados nas estações (c2 = 0,057, d.f. = 1, p = 0,88). Uma porção significativamente elevada de machos (55,96%, 95% CI: 48,96%-62,96%), e adultos (52,37%, 95% CI: 47,35%-57,39%) foram soropositivos. Apesar de nenhuma das amostras de encéfalo terem sido positivas para raiva, a alta proporção de espécimes soropositivos indica uma possível circulação do RABV nessa área urbana.

Rabies transmitted by vampire bats to humans: an emerging zoonotic disease in Latin America?

Human rabies transmitted by vampire bats reached new heights in Latin America in 2005. A total of 55 human cases were reported in several outbreaks, 41 of them in the Amazon region of Brazil. Peru and Brazil had the highest number of reported cases from 1975 to 2006. In Peru, outbreaks involving more than 20 cases of bat-transmitted human rabies were reported during the 1980s and 1990s. During this period, a smaller number of cases were reported from outbreaks in Brazil. A comparison of data from field studies conducted in Brazil in 2005 with those from the previous decade suggests similar bat-bite situations at the local level. The objective of this study was to review the epidemiological situation and, on the basis of this information, discuss possible factors associated with the outbreaks. Prevention and control measures already recommended for dealing with this problem are also reviewed, and some further suggestions are provided.

Rabies transmitted by vampire bats to humans: an emerging zoonotic disease in Latin America? / La rabia transmitida por murciélagos vampiros a humanos: ¿una zoonosis emergente en América Latina?

Human rabies transmitted by vampire bats reached new heights in Latin America in 2005. A total of 55 human cases were reported in several outbreaks, 41 of them in the Amazon region of Brazil. Peru and Brazil had the highest number of reported cases from 1975 to 2006. In Peru, outbreaks involving more than 20 cases of bat-transmitted human rabies were reported during the 1980s and 1990s. During this period, a smaller number of cases were reported from outbreaks in Brazil. A comparison of data from field studies conducted in Brazil in 2005 with those from the previous decade suggests similar bat-bite situations at the local level. The objective of this study was to review the epidemiological situation and, on the basis of this information, discuss possible factors associated with the outbreaks. Prevention and control measures already recommended for dealing with this problem are also reviewed, and some further suggestions are provided.

La rabia en humanos transmitida por murciélagos vampiros aumentó en América Latina en 2005. Se notificaron varios brotes con un total de 55 personas enfermas, 41 de ellas en la región amazónica de Brasil. Perú y Bolivia acumularon el mayor número de casos notificados entre 1975 y 2006. En Perú se informaron brotes de más de 20 personas con rabia transmitida por murciélagos en las décadas de 1980 y 1990. En ese período se informó un número menor de casos en los brotes de Brasil. Al comparar los datos de estudios de campo realizados en Brasil en 2005 con los obtenidos en décadas anteriores se observaron situaciones similares en cuanto a los casos de mordidas por murciélagos a nivel local. En este estudio se presenta una revisión de la situación epidemiológica y, a partir de esa información, se discuten los posibles factores asociados con los brotes. Se revisan también las medidas de prevención y control ya recomendadas para hacer frente a este problema y se ofrecen algunas recomendaciones adicionales.

Influência do sexo de indivíduos da mesma colônia no controle químico das populações do morcego hematófago Desmodus rotundus (Phyllostomidae) no estado de São Paulo / Influence of sex differences in the same colony for chemical control of vampire Desmodus rotundus (Phyllostomidae) populations in the state of São Paulo, Brazil

Os objetivos do presente trabalho foram estudar a fidelidade ao abrigo diurno por indivíduos de ambos os sexos da espécie Desmodus rotundus e verificar a eficácia da ação da pasta vampiricida 2 por cento na redução do tamanho de suas colônias no estado de São Paulo, por meio de estudo experimental de campo. Durante os anos de 1999 e 2000, 626 morcegos distribuídos em 12 abrigos foram capturados com redes-de-espera (armadas durante a noite) e marcados. Em seguida, 10 por cento da população previamente estimada recebeu a pasta vampiricida. No Experimento I foram tratados apenas machos, no Experimento II apenas fêmeas e no Experimento III, 5 por cento dos machos e 5 por cento das fêmeas foram tratados. Após 5 e 10 dias, foram feitas contagens dos morcegos que sobreviveram e morreram. As fêmeas mostraram-se mais fiéis aos abrigos (p<0,01) e melhores disseminadoras de pasta vampiricida (p<0,01).

Rabies in the insectivorous bat Tadarida brasiliensis in Southeastern Brazil

É registrado o primeiro caso de raiva no morcego insetívoro Tadarida brasiliensis no Estado de Säo Paulo. O animal raivoso foi encontrado vivo no período da tarde, enquanto pendurado na parede interna de um prédio urbano, o que reforça a noçäo que se deve ter cuidado com morcegos encontrados em situaçöes näo usuais

Raiva em morcegos insetívoros (Molossidae) do Sudeste do Brasil / Rabies in insectivorous bats (Molossidae) of southeastern Brazil

Quatro casos positivos para a raiva foram diagnosticados em morcegos de três espécies de molossídeos (um Molossus molossus, um Nyctinomops laticaudatus e dois N. macrotis) do Estado de Säo Paulo, Brasil. Três deles foram encontrados durante o dia em locais visíveis e näo habituais e o outro entrou pela janela, no início da noite. Quadro descritivo com 19 casos semelhantes, envolvendo oito espécies, é mostrado e indica que morcegos com comportamento atípico devem ser considerados fortemente suspeitos de estarem doentes, possivelmente com raiva

Common vampire bat attacks on humans in a village of the Amazon region of Brazil

Agressöes de morcegos a pessoas vêm sendo notificados em várias comunidades amazônicas nesta última década. Isto constitui um risco potencial para a raiva humana transmitida por morcegos. O objetivo foi de analisar fatores associados a estas agressöes em uma destas comunidades. Foi realizado um estudo transversal em um povoado de garimpeiros na Regiäo Amazônica brasileira (160 habitantes). Foi realizada a captura de morcegos junto às casas e foram enviadas amostras para o laboratório. Das 129 pessoas entrevistadas, 41 por cento foram agredidas por morcegos pelo menos uma vez, com 92 por cento das mordidas localizadas nos dedos dos pés. Por meio de regressäo logística, encontrou-se que adultos eram agredidos ao redor de quatro vezes mais do que crianças (OR = 3,75, IC: 1,46-9,62, p = 0,036). Honens foram agredidos com maior freqüência do que mulheres (OR = 2,08, IC:0,90-4,76, p = 0,067). Nove Desdomus rotundus e três morcegos frugívoros foram capturados e resultaram negativos para a raiva. Sugere que, em áreas de garimpo, adultos do sexo masculino têm maior probabilidade de serem agredidos por morcegos. As açöes de controle para a raiva humana a serem desenvolvidas nestes lugares devem dar ênfase especial a adultos homens. Recomendam-se mais investigaçöes sobre o modo como o garimpo na Regiäo Amazônica está colocando em risco as pessoas e o ambiente.