Surveillance of hemorrhagic fever and/or neuroinvasive disease: challenges of diagnosis

ABSTRACT OBJECTIVE To evaluate the performance of post mortem laboratory analysis in identifying the causes of hemorrhagic fever and/or neuroinvasive disease in deaths by arbovirus infection. METHODS Retrospective cross-sectional study based on the differential analysis and final outcome obtained in patients whose samples underwent laboratory testing for arboviruses at the Pathology Center of the Adolfo Lutz Institute, in São Paulo, Brazil. RESULTS Of the 1355 adults clinically diagnosed with hemorrhagic fever and/or neuroinvasive disease, the most commonly attributed cause of death and the most common final outcome was dengue fever. Almost half of the samples tested negative on all laboratory tests conducted. CONCLUSION The failure to identify the causative agent in a great number of cases highlights a gap in the diagnosis of deaths of unknown etiology. Additional immunohistochemical and molecular assessments need to be added to the post-mortem protocol if all laboratory evaluations performed fail to identify a causative agent. While part of our findings may be due to technical issues related to sample fixation, better information availability when making the initial diagnosis is crucial. Including molecular approaches might lead to a significant advancement in diagnostic accuracy.

Surveillance of hemorrhagic fever and/or neuroinvasive disease: challenges of diagnosis

OBJECTIVE: To evaluate the performance of post mortem laboratory analysis in identifying the causes of hemorrhagic fever and/or neuroinvasive disease in deaths by arbovirus infection. METHODS: Retrospective cross-sectional study based on the differential analysis and final outcome obtained in patients whose samples underwent laboratory testing for arboviruses at the Pathology Center of the Adolfo Lutz Institute, in São Paulo, Brazil. RESULTS: Of the 1355 adults clinically diagnosed with hemorrhagic fever and/or neuroinvasive disease, the most commonly attributed cause of death and the most common final outcome was dengue fever. Almost half of the samples tested negative on all laboratory tests conducted. CONCLUSION: The failure to identify the causative agent in a great number of cases highlights a gap in the diagnosis of deaths of unknown etiology. Additional immunohistochemical and molecular assessments need to be added to the post-mortem protocol if all laboratory evaluations performed fail to identify a causative agent. While part of our findings may be due to technical issues related to sample fixation, better information availability when making the initial diagnosis is crucial. Including molecular approaches might lead to a significant advancement in diagnostic accuracy. DESCRIPTORS: Autopsy. Hemorrhagic Fevers, Viral, etiology. Arbovirus Infections, mortality

Patologia morfológica e molecular aplicadas à inovação diagnóstica e vigilância da leishmaniose visceral / Morphological and molecular pathology applied to diagnostic innovation and surveillance of visceral leishmaniasis

O conceito de Saúde Única surgiu para ressaltar a união indissociável entre a saúde animal, humana e ambiental. Nesse contexto, a leishmaniose visceral americana (LVA) é considerada uma importante doença de saúde pública no Brasil, devido a sua crescente expansão geográfica e aumento na incidência de casos humanos. A LVA é uma doença parasitária, zoonótica, causada pela Leishmania (Leishmania) infantum (syn. chagasi) e transmitida por flebotomíneos do gênero Lutzomyia. Os cães são considerados os principais reservatórios do parasito nas áreas urbanas. O diagnóstico da LVA é baseado em aspectos epidemiológicos, clínicos e laboratoriais. A demonstração da presença do parasito através de exames diretos em tecidos biológicos do hospedeiro é o diagnóstico de escolha, principalmente, em municípios em que a transmissão de LVA ainda não tenha sido confirmada. Diversas metodologias podem ser aplicadas com essa finalidade. O objetivo desse trabalho é apresentar as técnicas citológicas, anatomo-patológicas e moleculares em amostras fixadas em formalina e incluídas em parafina para o diagnóstico da leishmaniose visceral em humanos e cães. Esses dados são complementares à apresentação realizada no I Simpósio Internacional de Leishmaniose Visceral, realizado nos dia 23 e 24 de Abril de 2018, e organizado pelo Instituto Adolfo Lutz em São Paulo-SP, Brasil. (AU)

The One Health concept emerged to highlight the inseparable link between animal, human and environmental health. In this context, American Visceral Leishmaniasis (AVL) is considered an important public health disease in Brazil, due to its increasing geographic expansion and in the incidence of human cases. AVL is a parasitic and zoonotic disease caused by Leishmania (Leishmania) infantum (syn. chagasi) and transmitted by sandflies of the genus Lutzomyia. Dogs are considered the main reservoirs of the parasite in urban areas. The diagnosis of AVL is based on epidemiological, clinical and laboratory aspects. The demonstration of the presence of the parasite through direct examinations in biological tissues of the host is the diagnosis of choice, mainly in municipalities where the transmission of AVL has not yet been confirmed. Several methodologies can be applied for this purpose. The objective of this work is to present the cytological, anatomopathological and molecular techniques in formalin fixed and paraffin embedded samples for the diagnosis of visceral leishmaniasis in humans and dogs. These data are complementary to the present study at the First International Symposium on Visceral Leishmaniasis, held on April 23 and 24, 2018, and organized by Adolfo Lutz Institute in São Paulo, Brazil. (AU)

Patologia morfológica e molecular aplicadas à inovação diagnóstica e vigilância da leishmaniose visceral / Morphological and molecular pathology applied to diagnostic innovation and surveillance of visceral leishmaniasis

O conceito de Saúde Única surgiu para ressaltar a união indissociável entre a saúde animal, humana e ambiental. Nesse contexto, a leishmaniose visceral americana (LVA) é considerada uma importante doença de saúde pública no Brasil, devido a sua crescente expansão geográfica e aumento na incidência de casos humanos. A LVA é uma doença parasitária, zoonótica, causada pela Leishmania (Leishmania) infantum (syn. chagasi) e transmitida por flebotomíneos do gênero Lutzomyia. Os cães são considerados os principais reservatórios do parasito nas áreas urbanas. O diagnóstico da LVA é baseado em aspectos epidemiológicos, clínicos e laboratoriais. A demonstração da presença do parasito através de exames diretos em tecidos biológicos do hospedeiro é o diagnóstico de escolha, principalmente, em municípios em que a transmissão de LVA ainda não tenha sido confirmada. Diversas metodologias podem ser aplicadas com essa finalidade. O objetivo desse trabalho é apresentar as técnicas citológicas, anatomo-patológicas e moleculares em amostras fixadas em formalina e incluídas em parafina para o diagnóstico da leishmaniose visceral em humanos e cães. Esses dados são complementares à apresentação realizada no I Simpósio Internacional de Leishmaniose Visceral, realizado nos dia 23 e 24 de Abril de 2018, e organizado pelo Instituto Adolfo Lutz em São Paulo-SP, Brasil.

The One Health concept emerged to highlight the inseparable link between animal, human and environmental health. In this context, American Visceral Leishmaniasis (AVL) is considered an important public health disease in Brazil, due to its increasing geographic expansion and in the incidence of human cases. AVL is a parasitic and zoonotic disease caused by Leishmania (Leishmania) infantum (syn. chagasi) and transmitted by sandflies of the genus Lutzomyia. Dogs are considered the main reservoirs of the parasite in urban areas. The diagnosis of AVL is based on epidemiological, clinical and laboratory aspects. The demonstration of the presence of the parasite through direct examinations in biological tissues of the host is the diagnosis of choice, mainly in municipalities where the transmission of AVL has not yet been confirmed. Several methodologies can be applied for this purpose. The objective of this work is to present the cytological, anatomopathological and molecular techniques in formalin fixed and paraffin embedded samples for the diagnosis of visceral leishmaniasis in humans and dogs. These data are complementary to the present study at the First International Symposium on Visceral Leishmaniasis, held on April 23 and 24, 2018, and organized by Adolfo Lutz Institute in São Paulo, Brazil.