Severe yellow fever in Brazil: clinical characteristics and management

Abstract

Background Little is known about clinical characteristics and management of severe yellow fever as previous yellow fever epidemics often occurred in times or areas with little access to intensive care units (ICU). We aim to describe the clinical characteristics of severe yellow fever cases requiring admission to the ICU during the 2018 yellow fever outbreak in São Paulo, Brazil. Furthermore, we report on preliminary lessons learnt regarding clinical management of severe yellow fever. Methods Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated. Results From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to the ICU in a tertiary hospital in Sao Paolo because of rapid clinical deterioration. On admission, the median AST was 7,000 IU/L, ALT 3,936 IU/L, total bilirubin 5.3 ml/dL, platelet 74 × 103/mm3, INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. The in-hospital fatality rate was 67%. Patients with diabetes mellitus had a higher case fatality rate (CFR) of 80%, while patients without diabetes had a CFR of 65%. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multi-organ failure. Conclusions Severe yellow fever is associated with a high CFR. The following management lessons were learnt: Anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels >70 μmol/L was commenced which reduced the frequency of seizures from 28% to 17%. Other new therapy strategies included early institution of plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors should be administered.

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

“…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]. These studies highlighted the importance of pancreatitis in the evolution of YF and the need for further studies addressing this issue [25,28].…”

Disease Resurgence, Production Capability Issues and Safety Concerns in the Context of an Aging Population: Is There a Need for a New Yellow Fever Vaccine?

“…Supportive care may include nutritional support, administration of intravenous fluids, and acetaminophen for pain and fever. Patients with severe disease require intensive care management to prevent and treat shock, metabolic acidosis, hypoglycemia, stress-induced gastritis, bleeding, hepatic dysfunction, renal failure, and secondary bacterial infections [53]. Patients should be protected from mosquito bites for five days after fever onset to avoid infecting mosquitoes.…”

Improving clinical management of patients with severe yellow fever

“…Some laboratory findings were highly prevalent at ICU admission: high levels of transaminases, low platelets, greater prothrombin time, decreased factor V and fibrinogen, elevated ammonia, amylase and lipase, lower venous bicarbonate, elevated lactate, creatinine, creatinine phosphokinase, and C-reactive protein. 5 Ho et al noted a high incidence of severe pancreatitis in severe yellow fever which has not been described before to that extent. 5 In Ho`s cohort of patients with laboratory confirmed YF admitted to the intensive, three patients had received YF vaccination within the past 10 days.…”

“…5 Ho et al noted a high incidence of severe pancreatitis in severe yellow fever which has not been described before to that extent. 5 In Ho`s cohort of patients with laboratory confirmed YF admitted to the intensive, three patients had received YF vaccination within the past 10 days. Viscerotropic disease was excluded as no vaccine derived virus could be isolated.…”

“…Ho's paper in this issue of the Journal of Travel Medicine presents one of the biggest cohorts of severe yellow fever cases, thus offering many lessons for clinical management. 5 YF can be a treacherous disease as its initial clinical presentation may be quite benign and non-specific, but can then take a fulminant course within a matter of a few days.…”