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.

Snakebites in Rural Areas of Brazil by Race: Indigenous the Most Exposed Group.

Animal stings are environmental hazards that threaten millions annually and cause a significant socioeconomic impact. Snakebite envenoming affects 2.7 million people globally every year, mostly the poorest and rural communities, with approximately 27,000 annual cases in Brazil. This study's objective is to identify the most exposed racial group for snakebites in rural areas of Brazil and analyze possible differences in the outcome of an accident. A retrospective epidemiological study was conducted using a database of rural snakebite cases from Brazil's Ministry of Health (2017). Descriptive analysis and a regression model were performed to examine the association of bad outcomes after a snakebite with several covariables. While mixed-race individuals presented the highest number of cases (61.79%), indigenous and white populations were the racial groups with the highest and lowest exposure rates (194.3 and 34.1 per 100,000 population, respectively). The fatality rate was 3.5 times higher in the indigenous population compared to the white population. In the multivariable model, the number of hours between the accident and health care received and the case classification suggested an association with a bad outcome. Snakebite is prominent in Brazil, particularly among indigenous groups. Antivenom is available in the Brazilian Health System; however, efforts need to be made for decentralization.

Overview of snakebite in Brazil: Possible drivers and a tool for risk mapping.

Snakebite envenoming affects close to 2.7 million people globally every year. In Brazil, snakebites are reported to the Ministry of Health surveillance system and cases receive antivenom free of charge. There is an urgent need to identify higher risk areas for antivenom distribution, and to develop prevention activities. The objective of this study is to provide an overview of the epidemiological situation of snakebite envenoming in Brazil and explore possible drivers; as well as to create a flowchart tool to support decision-makers identify higher risk areas. An ecological-type study was carried out using data by municipality (2013-2017). Study parts: 1) Create a geocoded database and perform a descriptive and cluster analysis; 2) Statistical analysis to measure the association of snakebite and possible environmental and socioeconomic drivers; 3) Develop a flowchart to support decision-makers and the application of this tool in one state (Rio Grande do Sul) as an example. An average of 27,120 snakebite cases per year were reported at the country level. Clusters of municipalities with high numbers of snakebites are mostly found in the Amazon Legal Region. The negative binomial regression model showed association with the snakebite case count: the type of major habitat, tropical or non-tropical; temperature; percentage of urbanization; precipitation; elevation; GDP per capita; a weaker relation with forest loss; and with venomous snake richness. The state where the instrument was applied reported 4,227 snakebites in the period. Most municipalities were considered as medium risk and 56/496 as high risk according to the tool created. Snakebite cases are distributed across the entire country with the highest concentration in the Legal Amazon Region. This creates a complex situation both for better understanding of the association of environmental and socioeconomic factors with snakebites and for the distribution and maintenance of antivenom to remote areas. Research into types of antivenom with a longer shelf life without the need for refrigeration is needed.

Towards the elimination of dog-mediated rabies: development and application of an evidence-based management tool.

BACKGROUND: International organizations advocate for the elimination of dog-mediated rabies, but there is only limited guidance on interpreting surveillance data for managing elimination programmes. With the regional programme in Latin America approaching elimination of dog-mediated rabies, we aimed to develop a tool to evaluate the programme's performance and generate locally-tailored rabies control programme management guidance to overcome remaining obstacles. METHODS: We developed and validated a robust algorithm to classify progress towards rabies elimination within sub-national administrative units, which we applied to surveillance data from Brazil and Mexico. The method combines criteria that are easy to understand, including logistic regression analysis of case detection time series, assessment of rabies virus variants, and of incursion risk. Subjecting the algorithm to robustness testing, we further employed simulated data sub-sampled at differing levels of case detection to assess the algorithm's performance and sensitivity to surveillance quality. RESULTS: Our tool demonstrated clear epidemiological transitions in Mexico and Brazil: most states progressed rapidly towards elimination, but a few regressed due to incursions and control lapses. In 2015, dog-mediated rabies continued to circulate in the poorest states, with foci remaining in only 1 of 32 states in Mexico, and 2 of 27 in Brazil, posing incursion risks to the wider region. The classification tool was robust in determining epidemiological status irrespective of most levels of surveillance quality. In endemic settings, surveillance would need to detect less than 2.5% of all circulating cases to result in misclassification, whereas in settings where incursions become the main source of cases the threshold detection level for correct classification should not be less than 5%. CONCLUSION: Our tool provides guidance on how to progress effectively towards elimination targets and tailor strategies to local epidemiological situations, while revealing insights into rabies dynamics. Post-campaign assessments of dog vaccination coverage in endemic states, and enhanced surveillance to verify and maintain freedom in states threatened by incursions were identified as priorities to catalyze progress towards elimination. Our finding suggests genomic surveillance should become increasingly valuable during the endgame for discriminating circulating variants and pinpointing sources of incursions.

Non-human primates as a reservoir for rabies virus in Brazil.

Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from non-human primates, Callithrix jacchus (the white-tufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in north-eastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from white-tufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection.

Non-human primates as a reservoir for rabies virus in Brazil

Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from non-human primates, Callithrix jacchus (the white-tufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in north-eastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from white-tufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection.

Non-human primates as a reservoir for rabies virus in Brazil

Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from non-human primates, Callithrix jacchus (the white-tufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in north-eastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from white-tufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection.

Non-human primates as a reservoir for rabies virus in Brazil

Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from non­human primates, Callithrix jacchus (the white­tufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in north­eastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from white­tufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection. (AU)

Visceral leishmaniasis epidemiologic evolution in timeframes, based on demographic changes and scientific achievements in Brazil.

Visceral leishmaniasis (VL) is a disease of chronic evolution which could be uniformly fatal, if left untreated. Human VL was first described in the Americas in 1913 and in 1936 in Brazil. The number of VL cases in Brazil is increasing steadily in the last three decades. Medical literature highlights this change in the disease epidemiology as a recent urbanization phenomenon, with most of the cases occurring in large cities since 1981, different to that observed previously, like a typical rural endemic. The aim of this study was to create a narrative review of the evolution of VL epidemiology since its first description in Brazil. To describe the process of urbanization of VL, timeframes were created historically consistent with the scientific and public health knowledge obtained about the VL and the demographics changes in Brazil, especially considering the extensive migratory movements in the country due to political or economic events. The first phase of VL was the decades of 30-50 when industrialization triggered internal migration process from countryside to the cities; during this period VL was studied for the first time and described as a rural endemic disease with no relevance to public health. Until the second phase, between the 50s and 80s of the 20th century, demography was characterized by expansion of immigration to the large cities and increase in population density in the suburbs with poor living standards. In this period, there was an advancement in the knowledge of the transmission of the disease being described as the first case acquired in the urban environment. The third phase was characterized by the explosion of cases in Brazilian cities and consolidation of urban endemic transmission. The possibility of urban transmission has been known since the 50s; however, the current phenomenon was due to the creation of ideal conditions for the establishment of transmission cycle in Brazilian cities.

Bat-transmitted human rabies outbreaks, Brazilian Amazon.

We describe 2 bat-transmitted outbreaks in remote, rural areas of Portel and Viseu Municipalities, Pará State, northern Brazil. Central nervous system specimens were taken after patients' deaths and underwent immunofluorescent assay and histopathologic examination for rabies antigens; also, specimens were injected intracerebrally into suckling mice in an attempt to isolate the virus. Strains obtained were antigenically and genetically characterized. Twenty-one persons died due to paralytic rabies in the 2 municipalities. Ten rabies virus strains were isolated from human specimens; 2 other cases were diagnosed by histopathologic examination. Isolates were antigenically characterized as Desmodus rotundus variant 3 (AgV3). DNA sequencing of 6 strains showed that they were genetically close to D. rotundus-related strains isolated in Brazil. The genetic results were similar to those obtained by using monoclonal antibodies and support the conclusion that the isolates studied belong to the same rabies cycle, the virus variants found in the vampire bat D. rotundus.

Bat-transmitted Human Rabies Outbreaks, Brazilian Amazon

We describe 2 bat-transmitted outbreaks in remote, rural areas of Portel and Viseu Municipalities, Pará State, northern Brazil. Central nervous system specimens were taken after patients' deaths and underwent immunofluorescent assay and histopathologic examination for rabies antigens; also, specimens were injected intracerebrally into suckling mice in an attempt to isolate the virus. Strains obtained were antigenically and genetically characterized. Twenty-one persons died due to paralytic rabies in the 2 municipalities. Ten rabies virus strains were isolated from human specimens; 2 other cases were diagnosed by histopathologic examination. Isolates were antigenically characterized as Desmodus rotundus variant 3 (AgV3). DNA sequencing of 6 strains showed that they were genetically close to D. rotundus–related strains isolated in Brazil. The genetic results were similar to those obtained by using monoclonal antibodies and support the conclusion that the isolates studied belong to the same rabies cycle, the virus variants found in the vampire bat D. rotundus.

Molecular epidemiology of rabies virus strains isolated from wild canids in Northeastern Brazil.

Rabies in wild canids in Northeastern Brazil is frequent and has been reported for some time, with episodes of rabies transmission from these animals to humans also reported. In this study, we analyzed the antigenic and genetic profiles of the rabies virus nucleoprotein gene, isolated from 20 samples taken from domestic animals and wild canids located in the Northeastern region of Brazil. All viruses isolated from domestic animals (dogs and cats) belonged to the antigenic variant 2 (AgV2). Among the wild animal samples, only four were AgV2, and nine showed a divergent antigenic profile. Phylogenetic analysis revealed two Brazilian clusters. Cluster 1 (Brazilian domestic carnivore-related strains) showed two subclusters, called 1A and 1B, and cluster 2 (Brazilian wild canid-related strains) also showed two subclusters, called 2A and 2B. The majority of the samples with divergent antigenic strains segregated into subcluster 2A. The intracluster identity of cluster 1 was 95.6% and that of cluster 2, 92.4%. When clusters 1 and 2 were compared, an identity of 88.6% was found. The genetic analysis of wild canid samples performed in this study indicates that there are two distinct rabies cycles among canids in Brazil, one represented by domestic canids and the other by wild canids. This study shows that the virus samples isolated in Northeastern Brazil are region and species-specific.