UNDIAGNOSED ILLNESS, FATAL, CHILD - CAMBODIA (05): EV71 TREATMENT OPTIONS

Published Date: 2012-07-11 14:48:55
Subject: PRO/EDR> Undiagnosed illness, fatal, child - Cambodia (05): EV71 treatment options
Archive Number: 20120711.1197882
UNDIAGNOSED ILLNESS, FATAL, CHILD - CAMBODIA (05): EV71 TREATMENT OPTIONS

EV71 in the outbreak of fatal illness in Cambodian children ----------------------------------------------------------- In previous ProMED postings [listed below] the clinical illness in Cambodia was described as occurring mainly in children under 3, with a male/female ratio of 1.3 to 1. It was noted in 14 south and central provinces of the country. Around 60 children were admitted to Kantha Bopha hospital after having been treated in private clinics and most of these died within 24 hours of a syndrome with encephalitis and pulmonary edema, while platelets, liver function, and renal function appeared normal.
Epidemiology and clinical features ---------------------------------- EV71 has been associated with outbreaks of fatal encephalitis in infants in the 1970s in Hungary and Bulgaria (1, 2) and since 1998 with large outbreaks of hand-foot-mouth disease (HFMD) in Southeast Asia (3). A minority of patients in these outbreaks may develop rhombencephalitis and (neurogenic) autonomic dysregulation leading to pulmonary edema, which can be fatal within 24 hours, while laboratory markers of liver and kidney function usually stay within normal range.
The age distribution and male to female ratio of the children in Kantha Bopha is very similar to what was prospectively observed in Children's Hospital 1 in Ho Chi Minh City, Viet Nam among 4000 children hospitalized with HFMD with a median age of 20 months and a male to female ratio of 1.6 to 1. It was also noted that if children progressed to more severe disease this was within a median of 24 hours of admission.
 The case fatality rate was 0.2 percent of all hospitalizations and 6/19 patients with pulmonary edema (TH Khanh, unpublished data). Myoclonus, particularly of the fingers is often the 1st symptom of central nervous system involvement and is seen in a majority of patients with severe disease (4). Deterioration is hallmarked by autonomic dysregulation, which presents as hypertension and tachycardia in addition to uncontrollable fever and may lead to pulmonary edema and death (3). In Taiwan and Malaysia it was noted that a large fraction (one third to half) of the patients progressing to this severe form of disease do not have a rash (5, 6). On the paediatric ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam among the very severe cases 12/47 had no rash and 28/47 had myoclonic jerks. There is no mention of rash, myoclonus, and hypertension in the children in Cambodia, but this would be very interesting to know.
The laboratory findings from Institute Pasteur and the clinical and epidemiological features are compatible with the severe end of the spectrum of disease caused by EV71. The high case fatality rate is striking, but may be due to an underestimation of the total number of cases because less severe cases are not hospitalized and not reported. The absence of the typical rash of HFMD should not rule EV71 out as a causative agent.

Some notes on treatment ----------------------- Guidelines from the Vietnamese ministry of health advice to suppress myoclonus with oral or intravenous phenobarbital, and when suppression is incomplete to instill IVIg at 2g/kg in 2 dosages. Autonomic dysregulation, particularly hypertension, is treated with milrinone (7). Pleconaril, a drug with anti-enteroviral activity, has no activity against EV71 in vitro (11). Evidence for the use of IVIg comes from treatment of enteroviral meningitis in neonates and agammaglobulinaemic patients, but there is only observational and retrospective case data on its efficacy in HFMD and no evidence for who benefits (8-10). Large randomised controlled trials of all treatment options (IVIg, milrinone, magnesium, fluid regimens, etc) are urgently needed for EV71 HFMD. http://www.promedmail.org/