Glucocorticoid and Pyrazolone Treatment of Acute Fever is a Risk Factor for Critical and Life-Threatening Human Enterovirus 71 Infection During an Outbreak in China, 2008

Background: Human enterovirus 71 (HEV71) causes outbreaks of life-threatening diseases throughout the world. The genesis of these severe diseases is unknown. Methods: During an outbreak of HEV71 infection, we investigated risk factors for critical illness. We developed a modified pediatric index of mortality (mPIM) incorporating heart rate, temperature, white blood cell count, respiratory rate, chest infiltrates, skin color, reflexes, responsiveness, and mobility. We calculated the mPIM for 103 patients (22 deaths) using complete scoring criteria in the medical record. In a case-control study, we compared cases (mPIM >= 10 or death) with controls (mPIM = 0-9) by drugs received within 96 hours after onset of fever, initial temperature, age, and nutritional anthropometry. Results: About 66% (68/103) of the patients with an mPIM score (28 cases and 40 controls) had data on initial exposures. About 50% of the 28 cases and 18% of the 40 controls received an injection to treat fever during the first 96 hours after onset (Odds ratio [OR] = 7.0, 95% confidence interval [CI]: 1.8-28). Injections containing exclusively glucocorticoids (OR = 4.8, 95% CI: 1.2-21) or pyrazolones (OR = 4.1, 95% CI: 0.91-19, P = 0.047) were risk factors for severe HEV71 infection. About 25% of cases and 5% of controls received both drugs parenterally while 7% of cases and 30% of controls received neither (OR = 21, 95% CI: 1.8-305). Conversely, cases and controls had identical average initial temperature, and did not differ significantly by age, sex, nutritional measurements, use of other drugs, or timeliness of medical care received. Conclusion: Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.