Yellow Fever: Factors Associated with Death in a Hospital of Reference in Infectious Diseases, São Paulo, Brazil, 2018

Ribeiro, Ana Freitas; Cavalin, Roberta Figueiredo; Suleiman, Jamal; Costa, J A; Vasconcelos, Marileide J.; Málaque, Ceila Maria Sant’Ana; Sztajnbok, Jaques

doi:10.4269/ajtmh.18-0882

Cited by 14 publications

(22 citation statements)

References 23 publications

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“…mosquito bites (9). YFV infection in humans shows a wide spectrum of disease severity, including asymptomatic infection; mild illness with dengue-like symptoms, including fever, nausea, vomiting, and fatigue; and disease, including fever with jaundice or hemorrhage and death (10).…”

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confidence: 99%

Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016–2019

Giovanetti

Mendonça

Fonseca

et al. 2019

J Virol

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The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics. IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.

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confidence: 99%

Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016–2019

Giovanetti

Mendonça

Fonseca

et al. 2019

J Virol

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“…During the recent epidemics in Brazil, the most common signs and symptoms observed in humans were fever, headache, vomiting, jaundice, chills, nausea, abdominal pain, myalgia, arthralgia, rash, diarrhea, bleeding or hemorrhagic signs [24][25][26][27]. Recently, in severe YF cases, a critical metabolic acidosis leading to the need for hemodialysis [25], increased levels of serum lipase [25,28] and a high prevalence of pancreatitis were observed [25].…”

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confidence: 99%

“…Studies have also been conducted to investigate the predictors of severity and death in different groups of YF patients. Age and elevated levels of AST, ALT, and creatinine have been independently associated with mortality in YF patients [26], while higher values of serum lipase and lower values of factor V were related to severe cases [28]. Kallas and colleagues (2019) analyzed data from 76 YF patients and observed that age, neutrophil count, AST, and viral load were independently related with death [27].…”

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confidence: 99%

Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease

Silva

Sacchetto

Rezende

et al. 2020

Virol J

141

166

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Yellow fever (YF) is an acute viral disease, affecting humans and non-human primates (NHP), caused by the yellow fever virus (YFV). Despite the existence of a safe vaccine, YF continues to cause morbidity and mortality in thousands of people in Africa and South America. Since 2016, massive YF outbreaks have taken place in Brazil, reaching YF-free zones, causing thousands of deaths of humans and NHP. Here we reviewed the main epidemiological aspects, new clinical findings in humans, and issues regarding YFV infection in vectors and NHP in Brazil. The 2016-2019 YF epidemics have been considered the most significant outbreaks of the last 70 years in the country, and the number of human cases was 2.8 times higher than total cases in the previous 36 years. A new YFV lineage was associated with the recent outbreaks, with persistent circulation in Southeast Brazil until 2019. Due to the high number of infected patients, it was possible to evaluate severity and death predictors and new clinical features of YF. Haemagogus janthinomys and Haemagogus leucocelaenus were considered the primary vectors during the outbreaks, and no human case suggested the occurrence of the urban transmission cycle. YFV was detected in a variety of NHP specimens presenting viscerotropic disease, similar to that described experimentally. Further studies regarding NHP sensitivity to YFV, YF pathogenesis, and the duration of the immune response in NHP could contribute to YF surveillance, control, and future strategies for NHP conservation.

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“…The current findings complement and extend other recent clinical observations of YF liver failure, including the presence of massive hepatocellular necrosis and microvesicular steatosis, plus the rapid progression of coagulopathy, encephalopathy, and acute kidney injury. ( 5‐7,37 ) Hepatocytes of infected patients also began to heavily express ITPR3, a calcium channel that is normally absent or minimally expressed in hepatocytes. ( 19,20,38 ) This change was observed in a mouse model of YFV infection as well.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection

Lemos¹,

França²,

Filho³

et al. 2020

Hepatol Commun

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Yellow fever (YF) is a viral hemorrhagic fever that typically involves the liver. Brazil recently experienced its largest recorded YF outbreak, and the disease was fatal in more than a third of affected individuals, mostly because of acute liver failure. Affected individuals are generally treated only supportively, but during the recent Brazilian outbreak, selected patients were treated with liver transplant. We took advantage of this clinical experience to better characterize the clinical and pathological features of YF‐induced liver failure and to examine the mechanism of hepatocellular injury in YF, to identify targets that would be amenable to therapeutic intervention in preventing progression to liver failure and death. Patients with YF liver failure rapidly developed massive transaminase elevations, with jaundice, coagulopathy, thrombocytopenia, and usually hepatic encephalopathy, along with pathological findings that included microvesicular steatosis and lytic necrosis. Hepatocytes began to express the type 3 isoform of the inositol trisphosphate receptor (ITPR3), an intracellular calcium (Ca2+) channel that is not normally expressed in hepatocytes. Experiments in an animal model, isolated hepatocytes, and liver‐derived cell lines showed that this new expression of ITPR3 was associated with increased nuclear Ca2+ signaling and hepatocyte proliferation, and reduced steatosis and cell death induced by the YF virus. Conclusion: Yellow fever often induces liver failure characterized by massive hepatocellular damage plus steatosis. New expression of ITPR3 also occurs in YF‐infected hepatocytes, which may represent an endogenous protective mechanism that could suggest approaches to treat affected individuals before they progress to liver failure, thereby decreasing the mortality of this disease in a way that does not rely on the costly and limited resource of liver transplantation.

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Yellow Fever: Factors Associated with Death in a Hospital of Reference in Infectious Diseases, São Paulo, Brazil, 2018

Cited by 14 publications

References 23 publications

Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016–2019

Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016–2019

Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease

Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection

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