Accuracy of yellow fever case definition of epidemiologic surveillance, São Paulo, 2018

ABSTRACT OBJECTIVE To evaluate the accuracy of yellow fever (YF) suspected case definitions from the Brazilian Ministry of Health (BMH) and World Health Organization (WHO), as well as propose and evaluate new definitions of suspected cases, considering confirmed and discarded cases. METHODS The retrospective study was conducted at the Instituto de Infectologia Emílio Ribas (IIER), using the Epidemiologic Surveillance Form of YF cases. From the confirmed and discarded cases of YF, a logistic regression model was developed. The independent variables were used in a proposed definition of a suspected case of YF and its accuracy was evaluated. RESULTS In total, 113 YF suspect cases were reported, with 78 confirmed (69.0%). The definitions by BMH and WHO presented low sensitivity, 59% and 53.8%, and reduced accuracy, 53.1% and 47.8%, respectively. Predictive factors for YF were thrombocytopenia, leukopenia, and elevation of transaminases greater than twice normal. The definition including individual with acute onset of fever, followed by elevation of ALT or AST greater than twice the reference value AND leukopenia OR thrombocytopenia presented high sensitivity (88.3%), specificity (62.9%), and the best accuracy (80.4%), as proposed in the model. CONCLUSION The YF suspected case definitions of the BMH and the WHO have low sensitivity. The inclusion of nonspecific laboratory tests increases the accuracy of YF definition.

Predictors of mortality in patients with yellow fever: an observational cohort study.

BACKGROUND: Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of São Paulo city, Brazil. METHODS: In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in São Paolo-the Hospital das Clínicas, University of São Paulo and the Infectious Diseases Institute "Emilio Ribas". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). FINDINGS: Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clínicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute "Emilio Ribas". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5·1 log10 copies/mL or greater died (95% CI 72-100), compared with only three (11%) of 27 (95% CI 2-29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5·1 log10 copies/mL. INTERPRETATION: We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever. FUNDING: São Paulo Research Foundation (FAPESP).

Debating Diseases in Nineteenth-Century Colombia: Causes, Interests, and the Pasteurian Therapeutics.

This article explores the medical conceptualization of the causes of diseases in nineteenth-century Colombia. It traces the history of some of the pathologies that were of major concern among nineteenth-century doctors: periodic fevers (yellow fever and malaria), continuous fevers (typhoid fever), and leprosy (Greek elephantiasis). By comparing the transforming conceptualizations of these diseases, this article shows that their changing pattern, the idea of climatic determinism of diseases (neo-Hippocratism and medical geography), the weak standing of the medical community in Colombian society, as well as Pasteurian germ practices were all crucial in the uneven and varied reshaping of their understanding.

[City-laboratory: Campinas and yellow fever at the dawn of the Republican era]. / Cidade-laboratório: Campinas e a febre amarela na aurora republicana.

In the late nineteenth century, there were yellow fever epidemics in Campinas. Considered a seaside disease, the fever startled lay people and physicians. The scientific debate about the etiology of the disease left the domain of magazines and medical correspondence to orient political and sanitary actions. In order to combat the disease, the city began to resemble a laboratory and experienced its "era of sanitation and demolition," with victories over the ailment and inconvenience to the public. The State Sanitary Commission led by Emilio Ribas, aware of Finlay's Culicidae theory, rehearsed in Campinas what would happen with Oswaldo Cruz and Pereira Passos in Rio de Janeiro. The novelty of combating mosquitoes coexisted with age-old practices dear to miasmatic theory, such as disinfection.

Cidade-laboratório: Campinas e a febre amarela na aurora republicana / City-laboratory: Campinas and yellow fever at the dawn of the Republican era

No final do século XIX ocorreram epidemias de febre amarela em Campinas. Considerada doença litorânea, a febre assustou leigos e médicos. O debate científico sobre a etiologia da doença deixou revistas e correspondências médicas para orientar ações políticas e sanitárias. Visando combater a enfermidade, a cidade ganhou contornos de laboratório e vivenciou sua "era do saneamento e das demolições", com vitórias sobre o achaque e transtornos à população. A Comissão Sanitária Estadual comandada por Emílio Ribas, ciente da teoria culicidiana de Finlay, ensaiou em Campinas o que ocorreria no Rio de Janeiro de Oswaldo Cruz e Pereira Passos. A novidade do combate aos mosquitos conviveu com antigas práticas caras à teoria miasmática, como as desinfecções.

In the late nineteenth century, there were yellow fever epidemics in Campinas. Considered a seaside disease, the fever startled lay people and physicians. The scientific debate about the etiology of the disease left the domain of magazines and medical correspondence to orient political and sanitary actions. In order to combat the disease, the city began to resemble a laboratory and experienced its "era of sanitation and demolition," with victories over the ailment and inconvenience to the public. The State Sanitary Commission led by Emilio Ribas, aware of Finlay's Culicidae theory, rehearsed in Campinas what would happen with Oswaldo Cruz and Pereira Passos in Rio de Janeiro. The novelty of combating mosquitoes coexisted with age-old practices dear to miasmatic theory, such as disinfection.

Cidade-laboratório: Campinas e a febre amarela na aurora republicana / City-laboratory: Campinas and yellow fever at the dawn of the Republican era

No final do século XIX ocorreram epidemias de febre amarela em Campinas. Considerada doença litorânea, a febre assustou leigos e médicos. O debate científico sobre a etiologia da doença deixou revistas e correspondências médicas para orientar ações políticas e sanitárias. Visando combater a enfermidade, a cidade ganhou contornos de laboratório e vivenciou sua “era do saneamento e das demolições”, com vitórias sobre o achaque e transtornos à população. A Comissão Sanitária Estadual comandada por Emílio Ribas, ciente da teoria culicidiana de Finlay, ensaiou em Campinas o que ocorreria no Rio de Janeiro de Oswaldo Cruz e Pereira Passos. A novidade do combate aos mosquitos conviveu com antigas práticas caras à teoria miasmática, como as desinfecções. (AU)

Short biography of Louis Daniel Beauperthuy (1807-71): pioneer of microbiology and medical science in Venezuela.

Louis Daniel Beauperthuy was a pioneer of microbiology in Venezuela where he developed microscopic and clinical research together with academic and scientific observation related to leprosy and the role of insects in the transmission of febrile illnesses.

Cerejeiras e cafezais: relações médico-científicas entre Brasil e Japão e a saga de Hideyo Noguchi / Cherry trees and coffee fields: medical and scientific relations between Brazil and Japan and the saga of Hideyo Noguchi

História dos sanitaristas da FSP/USP destaque nas páginas, 220-229, 297-299, 397, entre outras....

Adolpho Lutz and the origins of medical entomology in Brazil.

Adolpho Lutz (1855-1940) formed a bridge between the Bahian Tropicalist School and post-Mansonian medicine. Before taking over as head of the São Paulo Bacteriological Institute (1893), Lutz traveled through a variety of regions and delved into various disciplines. In the 1880s, he was already arguing that leprosy was transmitted by mosquitoes. Carbuncles, cholera, and typhoid fever were then the accepted models for investigating the etiology of infectious diseases. Following the discovery of how malaria was transmitted, attention turned to hematophagous diptera. Physicians, bacteriologists, zoologists, and veterinarians reshaped the network of actors involved in the 'hunt' for the agents and transmitters of diseases, as they began relying on analogies with malaria and yellow fever. Edwin Ray Lankester, director of the British Museum (Natural History), launched then a worldwide investigation into species that might be linked to human disease. The species described by Lutz and his proposed classification system were vital to Frederick Theobald's fundamental work in medical entomology, published in the early twentieth century. In 1908, Lutz brought with him to the Oswaldo Cruz Institute a remarkable quantity of research and experiments in all branches of the newly created "tropical medicine," devoted especially to entomology.

Febre amarela, malária e protozoologia

Após introdução sobre a formação de Adolpho Lutz e sua capacitação como cientista, analisa alguns trechos de relatórios do Instituto Bacteriológico de 1893 a 1908; o parecer de Adolpho Lutz sobre um soro proposto para o tratamento da febre amarela; o relatório sobre sua missão em Montevidéu para verificar a provável 'descoberta' do Dr. Sanarelli relativa ao micróbio da febre amarela; os trabalhos sobre a febre amarela em São Paulo e sobre o mosquito como seu agente de propagação; a descoberta da malária silvestre; as instruções para profilaxia do impaludismo; e, finalmente, as suas 'Reminiscências da febre amarela no Estado de São Paulo', publicadas em 1930, quando Adolpho Lutz já era pesquisador do Instituto Oswaldo Cruz havia mais de 20 anos.

Adolpho Lutz: obra completa / Adolpho Lutz: complete works

Após introduçäo sobre a formaçäo de Adolpho Lutz e sua capacitaçäo como cientista, analisa alguns trechos de relatórios do Instituto Bacteriológico de 1893 a 1908; o parecer de Adolpho Lutz sobre um soro proposto para o tratamento da febre amarela; o relatório sobre sua missäo em Montevidéu para verificar a provável "descoberta" do Dr. Sanarelli relativa ao micróbio da febre amarela; os trabalhos sobre a febre amarela em Säo Paulo e sobre o mosquito como seu agente de propagaçäo; a descoberta da malária silvestre; as instruções para profilaxia do impaludismo; e, finalmente, as suas "Reminiscências da febre amarela no Estado de Säo Paulo", publicadas em 1930, quando Adolpho Lutz já era pesquisador do Instituto Oswaldo Cruz havia mais de 20 anos. (AU)