Luciana Vilas Boas Casadio

Background: Severe yellow fever (YF) is classically defined by fever, jaundice, and hemorrhagic manifestations. However, whether these features accurately reflect early presentations in contemporary clinical settings remains uncertain. We aimed to characterize the clinical course of severe YF in a modern tertiary-care setting during a recent outbreak in Brazil. Methods: We conducted a retrospective descriptive cohort study of patients with confirmed YF admitted to a tertiary referral center in São Paulo, Brazil, between January 2018 and December 2019. All patients had YF confirmed by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and presented within 7 days of symptom onset. Clinical and laboratory data were collected from medical records, and patients were followed throughout hospitalization. Results: Among 126 patients, 45% died, 50% survived, and 5% underwent liver transplantation. Most deaths occurred within 11 days of symptom onset. Although fever was commonly reported prior to admission, only one-third of patients remained febrile during hospitalization, while hypothermia was observed in 93%. Jaundice, a hallmark feature of YF, was absent at admission in 35% of patients and typically developed later in the disease course. Neurological involvement occurred in nearly half of cases, and laboratory findings suggested frequent rhabdomyolysis and pancreatic injury. Markers of hepatic dysfunction and coagulopathy were more pronounced among patients with fatal outcomes. Conclusions: Severe YF frequently presents without classical features such as fever and jaundice in its early phase, challenging current clinical paradigms. Recognition of these atypical early presentations may be critical to improving timely diagnosis and clinical management in endemic settings.

Hepatitis A Virus (HAV) infects millions of individuals annually and is a major cause of acute viral hepatitis worldwide. This study aims to (1) assess HAV infection in suspected acute hepatitis patients at public healthcare institutions in Brazil; (2) evaluate the proportion of immunized individuals against HAV; (3) identify HAV genotypes; (4) examine the association between HAV infection and demographic data, as well as exposure to risk factors. This is a prospective, observational multicenter study conducted in primary health services in Brazil from October 2019 to May 2023, involving 1721 patients with suspected acute hepatitis. Acute HAV infection was identified in 108 (6.3%) patients, predominantly in young men (80%) and from South and Southeast regions of Brazil (97%). Anti‐HAV IgG, indicating previous exposure or vaccination, was detected in 78.6% of individuals (74% in the South to 91% in the North). Genotype I.A was found in all cases and approximately 450 mutations were identified, most of them in the structural proteins VP1‐3. Two viral groups were identified and related to two introductions of the virus: cosmopolitan sequences from North America, South America, and Europe, and a minor group of Brazilian sequences similar to Asian and South American ones. The high incidence of acute HAV infections highlights the need for targeted prevention and vaccination strategies. The characterization of HAV genetic diversity and molecular epidemiology contributes to monitoring and identifying emerging outbreaks.

: In 2016–2019, Brazil faced the most important yellow fever (YF) outbreak in recent decades. In 2019, cases were concentrated in Ribeira Valley, in the southeast region of Brazil, and largely affected rural Quilombola communities, which can trace their origins to escaped, freed, or abandoned slaves in the mid-1800s, and which traditionally practice subsistence agriculture. We aimed to explore aspects of the YF outbreak and vaccination from the perspective of the Quilombola communities. This was a cross-sectional descriptive study conducted in two Quilombola communities in Ribeira Valley (Sapatu and Nhunguara), using an interviewer-administered questionnaire that included both closed and open-ended questions. Thematic reflective analysis principles were applied for qualitative analysis. We adopted a theoretical domains framework to identify and categorize reported facilitators and barriers to YF vaccination. A total of 226 participants were enrolled: 46% male, median age 44 years. Eighty participants reported acute illness during the outbreak; fever, headache, myalgia, and nausea were the most common symptoms. Only eight participants reported laboratory-confirmed YF. Almost all participants (96.5%) reported YF vaccination. Less than two-thirds of the participants were vaccinated before the first case in the Ribeira Valley; over a third were vaccinated after the death of a community leader. The themes were: concerns about the vaccine, difficulty in accessing healthcare, perception of disease risk, knowledge about disease severity, cultural beliefs, and influence of leaders. The outbreak in the Ribeira Valley may have been averted with an understanding of the vaccination decision-making process, influenced by individual, sociocultural, and contextual factors.

The hepatitis E virus (HEV) is an important causative agent of acute hepatitis (AH). Despite reports of human infection in Brazil, the investigation is not routinely conducted, even in cases of elevated liver enzymes. This study evaluated two groups: group 1—patients with acute hepatitis A ( n = 44); group 2—patients with nonA‐C AH ( n = 47). They were tested by enzyme immunoassay for anti‐HEV IgM/IgG and real‐time PCR for HEV RNA detection. The positive sample for HEV RNA was submitted for sequencing. The seroprevalence of anti‐HEV IgM and IgG in group 1 was 4% (2/44) and 14.5% (7/44), respectively. Viral RNA was not detected in any sample. In group 2, the anti‐HEV IgM positivity was 4.3% (2/47), and IgG 14.9% (7/47). RNA was detectable in one case, which presented a viral load of 222.4 IU/μL and positive anti‐HEV IgM/IgG. In the phylogenetic analysis, the genotype identified was HEV‐3f. These results indicate that HEV infection should be considered a possible diagnosis in cases of non‐A–C AH. The patient identified with acute hepatitis E had recently traveled to the Northeast region of Brazil (Garanhuns city in Pernambuco state), where there are reports of high HEV seroprevalence among pigs. The close phylogenetic relationship observed between the sequence characterized in this study and strains isolated from pigs in nearby cities where the patient went suggested a possible zoonotic transmission in this region. This study highlights the importance of expanding studies and improving surveillance to understand better and manage HEV infections nationwide.

Outbreaks of hepatitis A may occur in countries of medium and high socioeconomic levels in which the population generally exhibits an increased susceptibility in young adults to this infection if they are not vaccinated against the hepatitis A virus (HAV). In Europe, an outbreak involved approximately 22 European countries with 4475 cases reported from 2016 to 2018; most of them were men who have sex with men (MSM). This outbreak expanded to North and South America, including Brazil, particularly in São Paulo city with 1547 reported cases from 2016 to 2019. In the present study, we characterized the HAV strains involved in the acute hepatitis A cases identified in the reference centers of São Paulo city during this outbreak. A total of 51 cases with positive anti-HAV IgM were included, 80.4% male, 68.6% of them between 20 and 40 years old and 41.7% MSM. HAV RNA was detected in 92% (47/51) of the cases. Subgenotype IA of HAV was identified and most of the strains were closely related to that isolated in outbreaks that occurred in different European countries in 2016. These results showed the epidemiological relation between these outbreaks and reinforce the need to implement vaccination against hepatitis A for the adult population, particularly for a population with a high-risk behavior.

In the most recent Brazilian yellow fever (YF) outbreak, a group of clinicians and researchers initiated in mid-January 2018 a considerable effort to develop a multicenter randomized controlled clinical trial to evaluate the effect of sofosbuvir on YF viremia and clinical outcomes (Brazilian Clinical Trials Registry: RBR-93dp9n). The approval of this protocol had urgency given the seasonal/short-lived pattern of YF transmission, large number of human cases, and epidemic transmission at the outskirts of a large urban center. However, many intricacies in the research regulatory and ethical submission systems in Brazil were indomitable even under such pressing conditions. By April 2018, we had enrolled 29 patients for a target sample size of 90 participants. Had enrollment been initiated 3 weeks earlier, an additional 31 patients could have been enrolled, reaching the prespecified sample size for the interim analysis. This recent experience highlights the urgent need to improve local preparedness for research in the setting of explosive outbreaks, as has been seen in the last few years in different countries.

Sabiá-like Mammarenavirus in Patient with Fatal Hemorrhagic Fever, Brazil, 2020

Brazil has had 2585 confirmed cases of yellow fever during the past 2 years. In this report, investigators from São Paulo describe cases of hepatitis occurring weeks to months after resolution of acute illness with yellow fever.