High Levels of Cytokine‐Producing Cells in the Lung Tissues of Patients with Fatal Hantavirus Pulmonary Syndrome

Mori, Michiyasu; Rothman, Alan L.; Kurane, Ichiro; Montoya, James M.; Nolte, Kurt B.; Norman, Joyce E.; Waite, Douglas C.; Koster, Frederick; Ennis, Francis A.

doi:10.1086/314597

Cited by 188 publications

(186 citation statements)

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“…Excess cytokines IL-1-α, IL-1-β, IL-6 and TNF-α interferon-γ, IL-2, IL-4 and TNF-β produced by activated macrophages in hantaviruses, specific T cells in recognition antigen infected pulmonary endothelial cells, are thought to be critical due to the increased permeability in the pathogenesis of HPS 8 .…”

Section: Introductionmentioning

confidence: 99%

Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina

Souza

Machado

Figueiredo

et al. 2011

Rev. Soc. Bras. Med. Trop.

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Introduction: According to reports by the Ministry of Health, in the far western region of the State of Santa Catarina, there have been no reports of hantavirus pulmonary syndrome, a zoonotic disease transmitted by feces of infected rodents. A seroepidemiological study of residents of this region, was conducted, with the aim of determining the presence of hantavirus infections. A total of 340 volunteers of both genus, from the towns of Belmonte and Paraíso, were studied. Methods: The serum of these patients was collected and used to detect IgG antibodies against recombinant N protein of Araraquara hantavirus, by ELISA assay. The positive samples were then titrated and confirmed by immunofluorescence assay. Results: This study demonstrated the presence of IgG antibodies against hantavirus N protein in 3.5% of the population. The most frequent occupation was farm worker, 81% had direct and indirect contact with rodents, 91.7% of positive cases were farm workers, indicating that the probable cause of infection occurred during barn cleaning. These antibodies are noteworthy, given that the levels of antibodies were verified in individuals whose contact with hantavirus may have occurred many years ago. Conclusions: This study shows the circulation of hantavirus in the region, a fact that until now, had not reported. All the serum reagents had contact with the pathogen, but did not develop pulmonary and cardiovascular syndrome. It is important to remain alert, because hantavirus is a serious and emerging disease of some relevance. Keywords: Hantavirus. Seroprevalence in Santa Catarina. Morbidity. RESUMO Introdução:De acordo com relatórios do Ministério da Saúde, na região do extremo oeste do Estado de Santa Catarina, não há relatos de síndrome pulmonar por hantavírus, doença zoonótica transmitida por excretas de roedores contaminados. Com a finalidade de demosntrar a infecção por hantavírus, um estudo soroepidemiológico de moradores da região foi realizado. Assim, foi estudado um total de 340 voluntários de ambos os gêneros, dos municípios de Belmonte e Paraíso. Métodos: O soro destes pacientes foi coletado e usado para a detecção de anticorpos IgG contra a proteína N recombinante de hantavírus Araraquara, pelo teste de ELISA. As amostras positivas foram tituladas e confirmadas por imunofluorescência indireta. Resultados: Este estudo demonstrou a presença de anticorpos IgG contra a proteína N hantavírus em 3,5% da população. A ocupação de lavrador foi a mais frequente, e 81% tiveram contato direto e indireto com os roedores, 91,7% dos casos positivos foram os agricultores, a causa provável da infecção foi através da limpeza de celeiros. Estes anticorpos são notáveis, dado que os níveis de anticorpos são encontrados nos indivíduos cujo contato com o hantavírus pode ter ocorrido há muitos anos. Conclusões: Este estudo mostra a circulação de hantavírus na região, um fato que até então não havia relatado, todos os reagentes soro tiveram contato com o patógeno, mas não desenvolveram a síndrome pulmonar e cardiovascu...

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Section: Introductionmentioning

confidence: 99%

Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina

Souza

Machado

Figueiredo

et al. 2011

Rev. Soc. Bras. Med. Trop.

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“…Little is known about the relationship between SNV and its rodent host, in part because no animal model is available (6). One reason such models have not yet been developed may be the requirement for high biological containment of the infected host rodent.…”

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confidence: 99%

Experimental infection model for Sin Nombre hantavirus in the deer mouse ( Peromyscus maniculatus )

Botten

Mirowsky

Kusewitt

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The relationship between hantaviruses and their reservoir hosts is not well understood. We successfully passaged a mouse-adapted strain of Sin Nombre virus from deer mice (Peromyscus maniculatus) by i.m. inoculation of 4-to 6-wk-old deer mouse pups. After inoculation with 5 ID50, antibodies to the nucleocapsid (N) antigen first became detectable at 14 d whereas neutralizing antibodies were detectable by 7 d. Viral N antigen first began to appear in heart, lung, liver, spleen, and͞or kidney by 7 d, whereas viral RNA was present in those tissues as well as in thymus, salivary gland, intestine, white fat, and brown fat. By 14 d nearly all tissues examined displayed both viral RNA and N antigen. We noted no consistent histopathologic changes associated with infection, even when RNA load was high. Viral RNA titers peaked on 21 d in most tissues, then began to decline by 28 d. Infection persisted for at least 90 d. The RNA titers were highest in heart, lung, and brown fat. Deer mice can be experimentally infected with Sin Nombre virus, which now allows provocative examination of the virus-host relationship. The prominent involvement of heart, lung, and brown fat suggests that these sites may be important tissues for early virus replication or for maintenance of the virus in nature.

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“…High levels of IL-2, IL-6, interferon-gamma and soluble receptors for tumour necrosis factor-alpha are found in the serum of patients with HCPS. Large numbers of cytokine-producing mononuclear cells are present in the lungs of patients dying from HCPS, in contrast to those dying from other causes of ARDS or from non-ARDS diseases (6). Surprisingly, there is little overt pulmonary capillary endothelial damage seen on electron microscopy, alternatively suggesting inflammation-induced intercellular gap formation (7).…”

Section: Discussionmentioning

confidence: 99%

Drotrecogin Alpha (Activated) in Two Patients with the Hantavirus Cardiopulmonary Syndrome

McDermid

Gibney

Brisebois

et al. 2006

Canadian Respiratory Journal

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Hantavirus cardiopulmonary syndrome (HCPS) is associated with rapid cardiopulmonary collapse from endothelial injury, resulting in massive capillary leak, shock and severe hypoxemic respiratory failure. To date, treatment remains supportive and includes mechanical ventilation, vasopressors and extracorporeal membrane oxygenation, with mortality approaching 50%. Two HCPS survivors initially given drotrecogin alpha (activated) (DAA) for presumed bacterial septic shock are described. Vasoactive medications were required for a maximum of 52 h, whereas creatinine levels and platelet counts normalized within seven to nine days. Given the similar presentations of HCPS and bacterial septic shock, empirical DAA therapy will likely be initiated before a definitive diagnosis of HCPS is made. Further observations of DAA in HCPS seem warranted.Key Words: Drotrecogin; Hantavirus; Respiratory failure; Septic shock Le drotrecogin alpha activé chez deux patients atteints du syndrome pulmonaire à hantavirus Le syndrome pulmonaire à hantavirus (SPH) s'associe à un collapsus cardiopulmonaire rapide découlant d'une lésion endothéliale et entraînant une fuite capillaire importante, un choc et une grave insuffisance respiratoire hypoxémique. Jusqu'à présent, on administre un traitement de soutien, qui inclut la ventilation mécanique, les vasopresseurs et l'oxygénation extracorporelle. La mortalité avoisine les 50 %. Est décrit le cas de deux survivants du SPH qui ont d'abord reçu du drotrecogin alpha activé (DAA) pour soigner un choc septique bactérien présumé. Des médicaments vasoactifs ont dû être administrés pendant une période maximale de 52 heures, tandis que les taux de créatinine et la numération plaquettaire se sont normalisés en sept à neuf jours. Étant donné la présentation similaire du SPH et du choc septique bactérien, un traitement empirique au DAA sera probablement entrepris avant qu'on pose un diagnostic définitif de SPH. D'autres observations du DAA dans le SPH semblent justifiées.T he hantavirus cardiopulmonary syndrome (HCPS) is a mouse-borne illness that was first described in 1993 (1), but it is now recognized retrospectively back to 1959 (2). HCPS is highly prevalent in northern Alberta, with a reported intensive care unit mortality of 46% (3), and is characterized by acute hypoxemic respiratory failure, hypotension, thrombocytopenia, renal dysfunction, hemoconcentration and coagulopathy. Initially, HCPS may be indistinguishable from bacterial septic shock with adult respiratory distress syndrome (ARDS). Drotrecogin alpha (activated) (DAA) reduces mortality in patients with severe septic shock (4). We report two HCPS survivors given DAA before their HCPS diagnoses were confirmed as part of an open-label preapproval drug access study with proxy consent. CASE PRESENTATIONSPatient 1: Acute physiology and chronic health evaluation (APACHE) II score 29 (67.2% predicted mortality) In November 2001, a 46-year-old previously healthy woman presented with a seven-day history of malaise, headache and myalgia. She developed r...

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High Levels of Cytokine‐Producing Cells in the Lung Tissues of Patients with Fatal Hantavirus Pulmonary Syndrome

Cited by 188 publications

References 31 publications

Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina

Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina

Experimental infection model for Sin Nombre hantavirus in the deer mouse ( Peromyscus maniculatus )

Drotrecogin Alpha (Activated) in Two Patients with the Hantavirus Cardiopulmonary Syndrome

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