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

Ma, Hongxia; He, Fan; Wan, Jianxin; Jin, Donghui; Zhu, Liye; Liu, Xuxiang; Liu, QiQuan; Zhang, Guohong; Ding, Zhen-Tao; Fontaine, Robert E.; Zhu, Bao-Ping; Jian, HaiHui; Zhang, Lijie; Xu, Wenbo; Zeng, Guang

doi:10.1097/inf.0b013e3181cdd178

Cited by 25 publications

(17 citation statements)

References 38 publications

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“…Our study results reinforce the previous findings that early use of glucocorticoids may increase the risk of subsequent severe or fatal HFMD2122. It has been reported that early use of glucocorticoids was associated with critical complications of HFMD within the first 48 hours of onset24. Glucocorticoids may impair innate immunity by inhibiting the activity of the innate immune system and suppressing the secretion of diverse immune mediators25.…”

Section: Discussionsupporting

confidence: 90%

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

Zhang

et al. 2017

Sci Rep

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The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD.

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Section: Discussionsupporting

confidence: 90%

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

Zhang

et al. 2017

Sci Rep

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“…In the present study, another risk factor of fatality was treatment with pyrazolone; this result is similar to studies reported previously [36, 37]. Pyrazolone derivatives (including aminopyrine, analginum, and phenylbutazone) have been banned and restricted in many developed countries for various adverse drug reactions [38].…”

Section: Discussionsupporting

confidence: 89%

“…However, early use of glucocorticoid in mild cases caused by human EV-A71 has been found to worsen the disease [35,36]. Also, using antibiotics in village clinics was identified as a risk factor of HFMD fatality.…”

Section: Discussionmentioning

confidence: 99%

Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors

Luo

Gao

et al. 2016

PLoS ONE

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Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1–3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0–1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1–3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0–1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5–2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions.

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“…In addition to rural–urban disparity in health care access and advanced life-sustaining technology, 41 widespread and inappropriate use of glucocorticoids and pyrazolones in mild HFMD stages 42,43 could have precipitated critical illness and death.…”

Section: Discussionmentioning

confidence: 99%

Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

Xing

Liao

Viboud

et al. 2014

The Lancet Infectious Diseases

800

935

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Summary Background Hand–foot–and–mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Increasingly it imposes a substantial disease burden throughout East and Southeast Asia. To better inform vaccine and other interventions, we characterized the epidemiology of HFMD in China based on enhanced surveillance. Methods We extracted epidemiological, clinical and laboratory data from reported HFMD cases during 2008–2012 and compiled climatic, geographic and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status and enterovirus subtype. Findings The surveillance registry captured 7,200,092 probable HFMD cases (annualized incidence, 1·2 per 1,000), of whom 3·7% were laboratory–confirmed and 0·03% died. Incidence and mortality were highest in children aged 12–23 months (in 2012: 38·2 cases per 1,000 and 1·5 death per 100,000). Median durations from onset to diagnosis and death were 1·5 days and 3·5 days respectively. The risk of cardiopulmonary or neurological complications was 1·1% and the severe-case fatality risk was 3·0%, with >90% of deaths associated with enterovirus 71. HFMD peaked annually in June in the North, whereas Southern China experienced semi-annual outbreaks in May and September/October. Geographic differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8-23% and 3–19%, respectively). Interpretation This is the largest population-based study to date of the epidemiology of HFMD. Future mitigation policies should take full account of the heterogeneities of disease burden identified. Additional epidemiologic and serologic studies are warranted to elucidate local HFMD dynamics and immunity patterns and optimize interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; World Health Organization; The Li Ka Shing Oxford Global Health Programme and Wellcome Trust; Harvard Center for Communicable Disease Dynamics; Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region.

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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

Abstract: Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.

Cited by 25 publications

References 38 publications

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors

Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

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