Doctor of Philosophy / Department of Geography / Douglas G. Goodin / Hantaviruses are zoonotic, RNA viruses that are harbored by muroid rodents of the families Muridae and Cricetidae. While the virus is endemic, and mostly non-symptomatic in its rodent reservoirs, when humans contact the virus it can result in serious disease. My purpose in this dissertation is to investigate the effect that landscape patterns and land cover condition can have on pathogen prevalence in a hantavirus reservoir species (Akodon montensis) within the Atlantic Forest region of Eastern Paraguay and to investigate ways to analyze those patterns using remotely sensed data. The first component to this research is to test potential improvements to image classifications on land use/land cover classifications useful for the study of small mammal communities. An object-based classification produced the best results with seven classes: Forest, Wet Cerrado, Dry Cerrado, Latifundia, Minifundia, Dry Pasture, and Wet Pasture. The classified imagery was then used to assess landscape effects on the presence of hantaviral antibodies (a 'marker' for exposure to the virus) in populations of A. montensis. In the overall landscape, proximity of similar habitat patches was related to seroprevalence in Akodon. When considering only the forest class, high amount of forest, high number of forest patches, and high diversity in forest patch sizes were all associated with seroprevalence. Next, was an analysis of ways to distinguish understory density variables through the use of satellite imagery. Horizontal and vertical density in the understory has been associated with the presence of hantavirus in A. montensis. Vertical and horizontal density measurements were correlated with NDVI and the Fourth band in the Tasseled Cap transformation. Finally, I consider the relationship between small mammal community diversity and seroprevalence, and their association with NDVI. Diverse small mammal communities are associated with low hantavirus seroprevalence. Low diversity metrics and high hantavirus seroprevalence were associated with high mean NDVI values. Many aspects of landscape patterns are important to hantavirus seroprevalence in small mammal communities in Eastern Paraguay. Several of the landscape patterns important to hantavirus seroprevalence can be studied using satellite-derived data.

Memoria para optar al Título Profesional de Médico Veterinario / El Síndrome Cardiopulmonar por Hanta (SCPH) es una enfermedad infecciosa aguda de rápida evolución a una insuficiencia respiratoria severa, presentando una alta letalidad. Los esfuerzos de las autoridades se han orientado principalmente a disminuir la letalidad mediante la prevención y detección temprana de la enfermedad. Los sobrevivientes tienen un alto riesgo de desarrollar secuelas cognitivas y/o físicas ya sea por efectos de la enfermedad o el tratamiento, tal como ha sido demostrado para otras enfermedades respiratorias. Se diseñó un estudio observacional descriptivo basado en una encuesta de opinión dirigida a los 8 pacientes sobrevivientes de SCPH los años 2005 a 2007 en la Región Metropolitana, Chile, con el fin de caracterizar la presentación de la enfermedad y la percepción del estado de salud actual de los pacientes. Se recopiló, además, la información epidemiológica de la infección de los pacientes existente. Mediante la recopilación de antecedentes epidemiológicos de los pacientes fue posible reafirmar que el factor de riesgo más comúnmente asociado a la enfermedad es el vínculo con las zonas rurales. Se confirmó, además, que la sintomatología más común era presencia de fiebre y, más manifiesto en esta serie de caso en particular, los síntomas gastrointestinales, además de la aparición de trombocitopenia (en el hemograma) y radiografía de tórax con infiltrado. Al momento de la entrevista, 7 pacientes indicaron percibir algún deterioro en sus condiciones mentales y/o físicas. Del total de los pacientes, 5 presentaban algún déficit cognitivo como daño en la memoria, la atención o la concentración y 6 pacientes señalaron tener una disminución de su capacidad física, ya sea por mialgias, fatigabilidad o debilidad. Durante la entrevista, se pudo observar la presencia de signos compatibles con algún estado de depresión o trastorno en la salud mental en 5 de los 8 pacientes. Con todos estos antecedentes y teniendo presente la edad de los pacientes y el corto período de tiempo transcurrido desde el momento de la infección hasta la realización del presente estudio, se estima que los sobrevivientes experimentan algún grado de deterioro en la calidad de vida debido a secuelas cognitiva y/o físicas que podrían asociarse a la hipoxemia, los efectos hemorrágicos del virus, el soporte agresivo en la Unidad de Tratamientos Intensivos (UTI), entre otros.

O risco transmissão de hantavírus para humanos na Mata Atlântica está diretamente relacionado à abundância de duas espécies de roedores, Oligoryzomys nigripes e Necromys lasiurus, reconhecidas como os principais reservatórios destes vírus naquele bioma. Ambas as espécies são beneficiadas por alterações antrópicas, porém, pouco se sabe sobre quais parâmetros da estrutura da paisagem e a escala espacial (em termos de extensão e resolução) em que a paisagem influencia a abundância destas espécies. Este trabalho procura preencher essa lacuna de conhecimento e investigar como uma definição adequada de parâmetros e escalas pode afetar modelos de extrapolação espacial das abundâncias destas espécies, o que pode ter amplas implicações para um melhor controle da propagação de hantavírus. O trabalho foi desenvolvido em seis paisagens da Mata Atlântica no Planalto Paulista, próximas ao local do primeiro registro de hantavirose no Brasil, sendo três de mata contínua e três paisagens fragmentadas, as quais diferiam com relação à porcentagem de cobertura florestal (11, 31 e 49%). Os pequenos mamíferos foram coletados em contextos de fragmentos florestais, mata contínua e matriz, totalizando 104 pontos de coleta. A análise, baseada em uma abordagem de seleção de modelos, considerou a estrutura da paisagem em diferentes extensões espaciais ao redor dos pontos de coleta (raios de 200, 500 e 800 m), em três mapeamentos que diferiam quanto a suas resoluções espaciais (10, 30 e 260 m). A partir do melhor modelo selecionado para cada espécie e para cada resolução, foi feita uma extrapolação das abundâncias, através da qual comparou-se os resultados obtidos em cada mapeamento. Foram capturados 1074 indivíduos de O. nigripes, a maioria nos fragmentos florestais. A maior abundância observada ocorreu nos fragmentos da paisagem de 11% de mata, diminuindo gradativamente nas paisagens com maiores porcentagens de cobertura florestal. N. lasiurus foi quase que exclusivamente coletado na matriz e, a maioria, na paisagem de 11% de mata. A abundância de O. nigripes foi diferentemente influenciada pela cobertura florestal da paisagem dependendo do contexto (fragmentos, mata contínua e matriz) em que a espécie se encontrava e também foi influenciada pela cobertura florestal e densidade de borda em escala local (200 m). A abundância de N. lasiurus foi negativamente influenciada pela cobertura florestal em escalas mais locais e variou de acordo com o tipo de cultura agrícola. A escala que mais influenciou ambas as espécies foi a de 200 m. Os mapeamentos com resolução de 10 e 30 m foram mais semelhantes entre si do que quando comparados com o mapeamento de 260 m, o que se refletiu nos melhores modelos de abundância selecionados, assim como nas extrapolações das abundâncias. Nossos resultados mostram que estas duas espécies respondem à degradação das paisagens e que paisagens mais biodiversas impedem um grande aumento da abundância de espécies que atuam como reservatórios dos hantavírus. Os resultados reforçam a necessidade de serem tomadas medidas que impeçam ou diminuam o desmatamento e a degradação da Mata Atlântica, ou que incentivem a regeneração e restauração florestal, para que possam ser evitados outros surtos de hantavirose. Além disso, evidenciam a importância de se escolher adequadamente a resolução do mapeamento em estudos ecológicos, baseando-se em atributos biológicos da espécie estudada, e ressaltam que extrapolações de abundância das espécies reservatório feitas em escalas muito grosseiras (e.g. acima da escala de resposta das espécies) podem levar a erros expressivos, potencialmente reduzindo a efetividade de ações voltadas para o controle da propagação de hantavírus. / Hantavirus transmission risk to humans in the Atlantic Forest is directly related to the abundance of two rodents species, Oligoryzomys nigripes and Necromys lasiurus, recognized as the main reservoir species of Hantavirus in this biome. Both species benefit by landscape anthropogenic changes, however, the structural parameters and the spatial scale (in terms of extension and resolution) in which the landscape influences the abundance of these two species remains to be examined. This study aims to fill this research gap and specifically test how a proper definition of parameters and scales may affect spatial extrapolation models of the abundance of these species, what may have broad implications for a better control of Hantavirus. This study was conducted in Plateau Paulista, Atlantic Forest, near to the first Hantavirus case in Brazil. Six landscapes were selected, being three control areas (continuous forest) and three fragmented landscapes, which differ in relation to the forest cover percentage (11, 31 e 49%). Small mammals were colected in forest patches, continuous forest and matrix contexts, totaling 104 collect stations. We performed a model selecting approach considering the landscape structure in different spatial extensions around each colect station (200, 500 and 800 m radius) in three different mapping that differ in their spatial resolution (10, 30 and 260 m). The best selected model to each specie in each map resolution was used to extrapolate the species abundance for the entire fragmented landscapes studied, whereby the obtained results for each mapping resolution were compared. A total of 1074 individuals of O. nigripes were captured, most of them in forest patches. The highest abundance ocurred in forest patches of the 11% forest cover landscape, decreasing gradually in landscapes with higher forest cover percentage. N. lasiurus was almost exclusively colected in the matrix with most of the individuals being colected in the 11% forest cover landscape. The abundance of O. nigripes was differently influenced by the landscape forest cover depending on the context (forest patches, continous forest and matrix) in which the species was colected and it was influenced by forest cover and edge density at the local scale (200 m). The abundance of N. lasiurus was negatively influenced by forest cover at more local scales and varied according with type of crop. The scale that most influenced both species was 200 m. The 10 and 30 m resolution mappings were more similar to each other than with the 260 m resolution mapping, what reflected on the best selected models of abundance, as well as on the abundance extrapolations. Our results show that these two species respond to the landscape degradation and that more biodiverse landscapes prevent the increase of the species abundance that act as Hantavirus reservoirs. Ours results reinforce the need of measures that prevent or reduce the Atlantic Forest deforestation and degradation, or encourage the regeneration and forest restoration, in order to avoid other Hantavirus outbreaks. Besides, our results evidence the importance of chosing accordingly the mapping resolution in ecological studies, which should consider the biological traits of the studied species. Additionally we highlight that abundance extrapolations of reservoir species done in a very coarse grain resolution (e.g. above the species response scale) may lead to significant errors, potentially reducing the effectiveness of actions aimed at controlling Hantavirus spread.

Realizou-se estudo analitico transversal relacionando caracteristicas individuais e familiares de 182 moradores pertencentes a 58 famílias de área de reserva ecológica à presença de infecções por arbovirus e hantavirus de interesse sanitário local. Pesquisou-se anticorpos para os antigenos dos virus Rocio, Ilhéus, da encefalite de st. Louis, das encefalites equinas do leste, oeste e venezuelana e Hantaan. Foram utilizados os testes de inibição de hemaglutinação, neutralização com redução de placas, imunofluorescência indireta e ensaio imunoenzimático com captura de anticorpos IgM (MAC-ELISA).· A associação estatistica foi pesquisada utilizando-se o teste de qui-quadrado e o grau de associação foi obtido calculando-se o odds ratio. Também foram pesquisadas a sensibilidade, a especificidade e os valores preditivos positivo e negativo das caracteristicas investigadas para avaliar seu poder de discriminar infectados de não infectados e de predizer infecções por arbovirus e hantavirus. A prevalência observada de anticorpos para arbovirus nos individuos foi de 26,9% e nas familias foi de 62,1%. Observou-se uma prevalência de 1,6% de anticorpos para hantavirus nos individuos e 5,2% nas familias. Não foram encontrados anticorpos para o virus da encefalite equina do oeste e nem anticorpos da classe IgM para os antigenos testados. Entre as caracteristicas estudadas, a idade, a ocupação, a naturalidade e o hábito de entrar na mata mostraram-se fatores de risco para infecções por arbovirus. Foram considerados fatores preditivos de infecção por arbovirus a presença de galinheiro anexo à casa, o hábito de criar galinhas e a presença de ratos no domicilio. Não foram observados fatores de risco ou de predição para infecção por hantavirus entre as caracteristicas estudadas. Os resultados obtidos sugerem que as caracteristicas, que mostraram ser fator de risco ou predição, poderiam ser usadas no diagnostico presuntivo preliminar de infecções por arbovirus e hantavirus, permitindo priorizar medidas de intervenção. O uso de um questionário ofereceria aos serviços de saúde ferramenta de simples aplicação e baixo custo, especialmente em condições de campo em áreas que, como a estudada, dispõe de escassos recursos humanos e laboratoriais. / In order to identify risk factors and predictive factors to arbovirus and hantavirus infections among individual and family characteristics, a cross-sectional study was carried out among 182 persons belonging to 58 families living at ecological reserve. The characteristics were associated with the presence of antibodies to the following virus of local interest: Hantaan, Rocio, Ilheus, Eastern, Western and Venezuelan equine encephalitis virus and st. Louis encephalitis virus using inhibition hemagglutination test, plaque reduction neutralization test, indirect immunofluorescence test and immunoglobulin M antibody capture enzyme immunoassay (MAC-ELISA). The associations were calculated using chi-square statistics and the odds ratio. Sensitivity, especificity, positive and negative predictive values of the individual and familiar characteristics were also analyzed to evaluate their capacity to discriminate between infected and non-infected people and to predict arbovirus and hantavirus infections. The prevalence of antibodies to arbovirus was 26.9% and 62.1% of the families had at least one member infected by these agents. Hantavirus antibodies were found in 1.6% of the sera analysed and 5.2% of the families had members infected by these agents. Antibodies to western equine encephalitis virus were not found. IgM antibodies were not observed sugesting no recent infection for those agents in that population. Age, ocupation, nativity and the habit to enter the forest were shown to be risk factors to arbovirus infections. The presence of annexes to the house, to breed chickens and the presence of rodents inside the house were considered predictive factors to arbovirus infections. Risk or predictive factors to hantavirus infections were not observed. The results suggest the use of some of the individual or family characteristics as a tool on the surveillance of arbovirus infections, to discriminate people with major probability of infections, specially in fie1d conditions, where human and laboratorial resources are scarce.

O gênero Hantavírus está incluído na família Bunyaviridae que são vírus emergentes associados a roedores que podem infectar o homem causando graves doenças. Nas Américas, os Hantavírus causam uma síndrome pulmonar e cardiovascular (SPCVH) com alta letalidade. Cerca de 1600 casos de SPCVH já foram notificados no Brasil causando mais de 600 óbitos. Sete espécies de Hantavírus são conhecidas no Brasil incluindo o vírus Araraquara que circula nas regiões de cerrado do país associado ao roedor Necromys lasiurus. Para o desenvolvimento de uma RT-PCR em tempo real para detecção e quantificação de Hantavírus, mostramos as etapas para o desenvolvimento de uma one-step RT-PCR em tempo real SYBR Green I para Hantavírus Araraquara que se mostrou específica para o gênero e capaz de detectar até 10 cópias por mL de RNA viral na amostra. Além disso, realizamos um estudo filogenético utilizando algoritmos bayesianos, com 190 sequências completas do gene da nucleoproteína, oriundas de 30 países durante um período de 25 anos (1985-2010) que encontravam-se disponíveis no GenBank (NCBI). Baseando-se em uma taxa média de 6.8 x 10-4 (2.5 x 10-4 - 1 x 10-3) substituições nucleotídicas por sítio/ano, foi possível inferir que os Hantavírus teriam aproximadamente 1917 anos. O processo de dispersão dos Hantavírus pelo mundo teria ocorrido há aproximadamente 500 anos, e a introdução destes vírus nas Américas teria ocorrido há 549 anos (95% HPD 1555-341 anos), via América Central ou México, originando os Hantavírus adaptados aos roedores da subfamília Neotominae, e pelo Brasil surgindo há 406 anos (95% HPD 1150-250 anos) os Hantavírus associados a roedores da subfamília Sigmodontinae, e posteriormente dispersaram para todo o continente sul-americano. O trabalho contribui de forma relevante para o diagnóstico das infecções por Hantavírus com a one-step RT-PCR em tempo real SYBR Green I e também, contribui para o entendimento da filogenia e história destes vírus, oferecendo subsídios ao entendimento sobre como teria ocorrido o espalhamento dos Hantavírus pelo mundo. / The genus Hantavirus is included in the family Bunyaviridae are viruses emerging carried by rodents, which can infect humans causing serious illness. In the Americas, the Hantavirus causing a pulmonary syndrome (HPS) with high lethality. About 1,600 cases of HPS have been reported in Brazil, cause over 1600 deaths. Seven species of Hantavirus are known in Brazil, including Araraquara virus circulating in Cerrado regions (or Savannah regions) of the related in rodents Necromys lasiurus. The development of a real-time RT-PCR for detection and quantitation of Araraquara virus, here we show the steps for developing a one-step SYBR Green real-time RT-PCR for virus Araraquara which proved to be specific for the genus and capable of detecting up to 10 copies of viral RNA per ml in the sample. Furthemore, we performed a phylogenetic analysis using Bayesian algorithms, with 190 complete sequences of the nucleoprotein gene, originating from 30 countries over a 25 year period (1985-2010) that were available in GenBank (NCBI). Based on an average rate of 6.8 x 10-4 (2.5 x 10-4 - 1 x 10-3) nucleotide substitutions per site/year, it was possible to infer that the Hantavirus would be about 1917 years old. The Hantavirus spreading in the world have occurred for nearly 500 years, and the introduction of these viruses have occurred in the Americas 549 years ago (95 years% HPD 1555-341) bye Central America or Mexico, causing the Hantavirus adapted to rodents subfamily Neotominae, and Brazil emerged 406 years ago (95% HPD 1150-250 years) the Hantavirus associated with rodents subfamily Sigmodontinae, and subsequently disseminated to South America. The work contributes significantly to the diagnosis of Hantavirus infections with one-step SYBR Green real-time RT-PCR and also contributes to an understanding of the phylogeny and evolutionary history of these viruses, offering subsidies have occurred understanding of how the Hantavirus spread of the worldwide.

Arenaviruses and hantaviruses are human pathogens that cause significant morbidity and mortality. The current lack of vaccines and treatment options for these viruses is a global concern. Despite producing only 4 proteins, these viruses are able to maintain a persistent and asymptomatic infection in wild rodents while being continuously shed into the environment. In humans, these viruses cause a spectrum of diseases ranging from aseptic meningitis to severe hemorrhagic fever syndromes. Little is known about how arenavirus and hantavirus proteins engage and interact with the human proteome during the complex process of viral biogenesis, or how the interactions with human proteins contribute to viral propagation as well as the onset and progression of disease. This dissertation provides a road map of the protein interactions formed between a prototypic envelope glycoprotein encoded by either an arenavirus or hantavirus, and the human proteome. The viral envelope glycoprotein (GP) decorates the surface of the virion. The primary function of the GP is to mediate attachment of the virus to specific cellular receptors, and after internalization of the virion, fuse the viral membrane with an internal endosomal membrane. In order to carry out these specific tasks, the viral GPs must first co-opt the extensive machinery found within the cellular secretory pathway to coordinate the proper glycosylation, folding, proteolytic maturation, and targeting of the GP during its biosynthesis. We identified a human protein with a conserved interaction amongst these two groups of viral GPs termed the Endoplasmic Reticulum (ER)-Golgi Intermediate Compartment Protein of 53 kiloDaltons (ERGIC-53). ERGIC-53 is an intracellular cargo receptor that normally cycles within the early secretory pathway of cells, where it is responsible for ferrying a small subset of cellular glycoproteins, most notably the coagulation factors FV and FVIII, from the ER to the Golgi apparatus. Herein we describe a novel role for ERGIC-53 in the propagation of not only arenaviruses, but also coronaviruses and filoviruses. Following infection with an arenavirus, ERGIC-53 leaves the early secretory pathway and becomes incorporated into the virus as it pinches off from the cell surface. Newly formed viruses lacking ERGIC-53 are no longer infectious due, in part, to a defect in their ability to attach to host cells. We suggest that ERGIC-53 represents a promising broad-spectrum antiviral target because of its association with the GPs from many families of pathogenic viruses, as well as its ability to exert control over their infectivity; and finally, because ERGIC-53 itself is not required for human health. The discovery of ERGIC-53 outside of its normal location inside of cells suggests that it may have additional unknown functions. Lastly, by revealing the importance of the cellular protein in controlling viral infectivity, we provide insight into the ongoing co-evolution of virus and host.

Hantaviruses can cause two severe human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Hantaviruses are spread to humans mainly through inhalation of infectious virions, secreted from infected rodents. The human diseases are characterized by an increased capillary leakage syndrome. Hantaviruses are known to infect endothelial cells, but they are non-cytopathogenic. The mechanism behind human disease is not well understood, but an overactive immune response is implicated in the pathogenesis. The aim of my thesis has been to investigate parts of innate and adaptive immune responses in Puumala virus-infected patients. In paper I we found a sex difference in the cytokine profile during acute infection. Females had significantly higher plasma levels of IL-9, FGF-2, GM-CSF and lower levels of IL-8 and IP-10 compared to males. These differences may affect the activation and function of the immune response. In paper II we studied the phenotype and kinetics of NK cells. We observed that CD56dim NK cells were elevated during acute infection and that these, predominantly NKG2C+ NK cells, remained elevated for at least two months after symptom debut. Our novel finding of a prolonged NK cell response, implicates that NK cells may possess adaptive immunity features.  In paper III we observed a vigorous cytotoxic T cell (CTL) response during acute infection, which contracted in parallel with decrease in viral load. The CTL response was not balanced by an increase in regulatory T cells. The T cells expressed inhibitory immunoregulatory receptors, known to dampen intrinsic T cell activity.  In paper IV, we found that a low IgG response in patients was significantly associated with more severe disease, while the viral load did not affect the outcome. Our findings support the use of passive immunization as a treatment alternative for hantavirus-infected patients. In conclusion, my thesis contributes to an increased knowledge about the immune response in hantavirus-infected patients. The findings, combined with future studies, will hopefully lead to a better understanding of the pathogenesis and possible treatment alternatives.

Diss. (sammanfattning). Umeå : Sveriges lantbruksuniv., 2003. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on July 16, 2010). Includes bibliographical references.

The genus Hantavirus, family Bunyaviridae, includes rodent-borne viruses that are transmitted to humans by inhalation of rodent secretions and excreta, or through direct contact with an infected rodent. They are associated with hemorrhagic fever and renal syndrome (HFRS) and with Hantavirus cardiopulmonary syndrome (HCPS). In Brazil, more than 1,500 HCPS cases have been recorded, since 1993. In this study, it was investigated the presence of hantavirus antibodies in the population of Alagoas. For this, it was carried out an active surveillance for acute cases of hantavirus infection in hospitals of Alagoas State and also it was analyzed sera samples sent by LACEN-AL, from patients suspected of having other diseases, such as dengue and leptospirosis. In addition, it was investigated the presence of memory antibodies IgG to hantavirus in rural workers from Coruripe-AL, by performing a pilot study of serological survey in Usina Coruripe. Sera samples were tested by an enzyme immunoassay (ELISA) in house for detection of hantavirus antibodies, using a recombinant N protein of Araraquara hantavirus as antigen. Of the 64 samples analyzed by serology from patients who were classified as suspected of HCPS or HFRS, none was positive for IgM anti-hantavirus, however, one (1,56%) was reagent for IgG anti-hantavirus. In the survey for antibodies in 124 patients with leptospirosis confirmed by LACEN-AL it was found three (2,42%) samples that were reagent for IgG to hantavirus and none of them was reagent for IgM. In the 170 patients with clinical suspicion of dengue but non-reagent for NS1 the survey for both IgM and IgG to hantavirus was negative. The pilot study of serological survey in Coruripe showed immunity against hantavirus in 10 (4%) of 250 studied workers, among which five attested that had never lived or travelled out of state of Alagoas. Taken together, our findings suggest the circulation of hantavirus in the state and its silent occurrence in the region, causing inapparent infections, or even symptomatic, but that remain undiagnosed. This study is pioneer in the surveillance for hantavirus in the state of Alagoas. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Hantavirus são vírus zoonóticos principalmente de roedores silvestres, pertencentes à família Bunyaviridae, os quais são transmitidos para seres humanos pela inalação de secreções ou excretas de roedores infectados ou pelo contato direto com os mesmos. Estes vírus podem causar graves doenças como a Febre Hemorrágica com Síndrome Renal (FHSR) e a Síndrome Pulmonar e Cardiovascular (SPCVH). No Brasil, já foram notificados mais de 1500 casos, desde 1993. Neste estudo, investigou-se a presença de anticorpos anti-hantavírus na população alagoana. Para isso, com finalidade diagnóstica, realizou-se uma busca ativa de casos agudos em hospitais de Alagoas e analisou-se amostras séricas encaminhadas pelo LACEN-AL, provenientes de pacientes suspeitos de outras enfermidades, como dengue e leptospirose. Também, foi investigada a presença de anticorpos de memória da classe IgG para hantavírus, em trabalhadores rurais de Coruripe/AL, em um estudo piloto para inquérito sorológico na Usina Coruripe. Para detecção dos anticorpos anti-hantavírus, amostras de soros foram submetidas a um teste imunoenzimático (ELISA) caseiro, utilizando-se como antígeno uma proteína N recombinante do hantavirus Araraquara. Foram estudadas 608 amostras séricas divididas nos seguintes grupos: 1- Pacientes internados, que se encaixavam nos critérios de suspeita clínica de hantavirose; 2- Pacientes com leptospirose; 3- Pacientes com suspeita clínica de dengue; 4- Estudo piloto para inquérito sorológico. Das 64 amostras séricas analisadas por sorologia procedentes de pacientes que se enquadravam como caso suspeito de SPCVH ou FHSR, nenhuma foi reagente para IgM anti-hantavirus, porém, uma (1,56%) foi reagente para IgG anti-hantavirus. Na pesquisa dos anticorpos em 124 pacientes com leptospirose confirmada pelo LACEN-AL foram encontrados três (2,42%) amostras reagentes para IgG anti-hantavirus e nenhuma reagente para IgM. Nos 170 pacientes com suspeita de dengue cuja pesquisa NS1 foi não reagente, não foram detectados nem IgG nem IgM anti-hantavírus. O estudo piloto do inquérito sorológico em Coruripe mostrou imunidade para hantavírus em 10 (4%) dos 250 trabalhadores estudados, dentre os quais, cinco alegaram nunca terem morado ou viajado para fora do Estado de Alagoas. Tomados em conjunto, nossos achados sugerem a circulação de hantavírus no estado e sua ocorrência silenciosa na região, causando infecções inaparentes, ou ainda, sintomáticas, mas que permanecem sem diagnóstico. Esse trabalho é pioneiro na busca por hantavirose no estado de Alagoas.