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Observational Study
. 2018 Apr;146(6):788-798.
doi: 10.1017/S0950268818000468. Epub 2018 Mar 12.

Factors associated with fatal outcome of children with enterovirus A71 infection: a case series

S D Yang  1 , P Q Li  2 , Y G Huang  3 , W Li  4 , L Z Ma  5 , L Wu  6 , N Wang  7 , J M Lu  2 , W Q Chen  2 , Guang-Ming Liu  2 , Y M Xiong  2 , Y L Chen  3 , Ying Zhang  2
Affiliations
Observational Study

Factors associated with fatal outcome of children with enterovirus A71 infection: a case series

S D Yang et al. Epidemiol Infect. 2018 Apr.

Abstract

Enterovirus A-71 (EV-A71) may be fatal, but the natural history, symptoms, and signs are poorly understood. This study aimed to examine the natural history of fatal EV-A71 infection and to identify the symptoms and signs of early warning of deterioration. This was a clinical observational study of fatal cases of EV-A71 infection treated at five Chinese hospitals between 1 January 2010 and 31 December 2012. We recorded and analysed 91 manifestations of EV-A71 infection in order to identify early prognosis indicators. There were 54 fatal cases. Median age was 21.5 months (Q1-Q3: 12-36). The median duration from onset to death was 78.5 h (range, 6 to 432). The multilayer perceptron analysis showed that ataxia respiratory, ultrahyperpyrexia, excessive tachycardia, refractory shock, absent pharyngeal reflex, irregular respiratory rhythm, hyperventilation, deep coma, pulmonary oedema and/or haemorrhage, excessive hypertension, tachycardia, somnolence, CRT extension, fatigue or sleepiness and age were associated with death. Autopsy findings (n = 2) showed neuronal necrosis, softening, perivascular cuffing, colloid and neuronophagia phenomenon in the brainstem. The fatal cases of enterovirus A71 had neurologic involvement, even at the early stage. Direct virus invasion through the neural pathway and subsequent brainstem damage might explain the rapid progression to death.

Keywords: Brainstem damage; Enterovirus A71; Southern China; clinical manifestations; death.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Fig. 1.
Fig. 1.
Median duration of symptoms/signs occurring before death in patients with enterovirus A7 infection.
Fig. 2.
Fig. 2.
Macroscopic examination of the brainstem (a), lung (b) and heart (c). Gliacyte proliferation and accumulation of tuberculum in the brainstem; vacuolar degeneration of neurons formed reticular necrosis lesion (d). Brainstem neurons showed neuronophagia in fatal cases of enterovirus A71. The pathological studies of brainstem showed neuronophagia, HE × 400 (e). Lymphocytes and small glial cell infiltration around vessels in the brainstem, showing ‘sleeve like’ change (f).
Fig. 3.
Fig. 3.
Invasion entrance of enterovirus A71 (mucosa of the oropharynx, throat, nose and eyes).
Fig. 4.
Fig. 4.
Neurological invasion pathway of enterovirus A71.
See this image and copyright information in PMC

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