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We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post–symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post–symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment. [ABSTRACT FROM AUTHOR]

Background Infant mortality in Brazil has increased for the first time in 26 years. This study aimed to define the Zika Syndrome (ZS) perinatal case fatality rate (PCF) since the 2015 Zika outbreak in a Brazilian northeast state highly impacted by the virus. Methods Cross-sectional study conducted using data obtained through the State Health Department for cases of microcephaly (MCP) and congenital abnormalities (CA) in Rio Grande do Norte State (RN) from April 2015 to March 2, 2019. Perinatal period: commencing at 22 completed weeks (154 days) of gestation until 7 days after birth. PCF was defined as the number of deaths as a fraction of the number of sick persons with the specific disease (×100). Results There were 535 reported cases of MCP and others CA notified in RN during this period: 4 in 2014, 337 in 2015, 157 in 2016, 21 in 2017, 14 in 2018, and 2 in 2019. Of these, 151 were confirmed and 135 remain under investigation. The remaining 247 cases were ruled out by normal physical exams or due to noninfectious cause of MCP. Of the total confirmed cases, 35.8% (54/151) died after birth or during pregnancy. Zika virus infection during pregnancy was confirmed in 55.5% (30/54) of deaths and 1.8% (01/54) had a positive TORCH blood test. The odds ratio for the Zika PCF was found to be 1.57 (95% CI: 0.7940–3.1398; P = 0.1928). Deaths related to Zika were confirmed using a combination of clinical and epidemiological findings paired with either radiological information or molecular/serological data (RT–PCR and/or IgM/IgG antibodies against Zika). Twelve cases remain under investigation and 7 were ruled out as MCP. The highest number of confirmed MCP cases occurred between August 2015 and February 2016. The prevalence increased in September, with a peak in November 2015 (20.1 cases per 1,000 live births). Conclusion Before the recent Brazilian Zika outbreak, the incidence of MCP in RN between 2010 and 2014 was 1.8 cases/year. The real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). This study indicates that Zika virus accounted for a substantial proportion of MCP cases seen during the years studied, and suggests that ZS contributed to an increase in infant mortality in Brazil. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Congenital Zika Syndrome (CZS) has a broad spectrum of clinical presentations that are still being described. This cohort study aimed to describe the orthopedic complications in children with microcephaly (MCP) related to Zika virus (ZIKV). Methods We evaluated 36 children with CZS up to 17 months of age followed at a pediatric rehabilitation center in the northeast of Brazil. Cohort enrollment occurred with children born between January 2015 and May 2016. We assessed their social profiles and orthopedic findings. Results Of the 36 cases, 25 were male. All of them lived in rural area. 25 had at least one congenital orthopedic alteration. Hip subluxation was the most common problem detected (n = 15); other lower limb abnormalities included knee subluxation (n = 7), clubfoot (n = 7); congenital vertical talus (n = 4); plano-valgus foot (n = 5). In relation to the upper limbs, 11 children presented with some shoulder and/or elbow abnormality and 16 had some alteration in the hand and/or on the wrist. Conclusion Orthopedic problems appear to be common in children with CZS and should be a focus of larger clinical studies. An initial orthopedic assessment may provide a better quality of life by helping children avoid further complications/deformities. Our results emphasize the orthopedic problems associated with CZS and the need to better describe many complications in the natural history of this infection. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics. Methods We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded. Results Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk. Conclusions These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV. [ABSTRACT FROM AUTHOR]