Hand, Foot and Mouth Disease (HFMD) plays a major role in childhood morbidity and mortality in Vietnam and the Asia-Pacific region. The spectrum of severe disease and predictors for poor outcome are not well understood, and the evidence-base for management of hypertension in severe cases is lacking.
In this thesis I describe the clinical features, their evolution over time, and the viral serotype/genotype findings, among 1272 HFMD cases admitted to PICU at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, during the the 2011-2012 Vietnam outbreak. Fever, skin rash, and myoclonic jerks happened in the early stage while the more severe features, including hypertension, tachypnea, irregular breathing, pulmonary edema and shock occurred after day 3. Most severe features were associated with EV-A71 infection rather than with Coxsackieviruses (CV). However having mouth ulcers without skin lesions was associated with CV infection. The C4 genogroup of EV-A71 was associated with more severe neurological involvement. Risk factors present within 24 hours of PICU admission that were associated with subsequent deterioration to severe outcome were skin lesions and tachypnea, while presence of mouth ulcers alone was protective.
I also describe the development and execution of a randomized controlled trial of a novel treatment, MgSO4, for severe HFMD with hypertension secondary to ANS dysregulation. However, only 26 of the planned 190 patients were enrolled before the outbreak was controlled, and with this small number we found no evidence of benefit in this trial. In another approach, I assessed the efficacy of MgOS4 on severe hypertension among 33 patients treated with open-label MgSO4 compared to 12 patients of similar clinical severity who did not receive this intervention, and found a significant reduction in mean arterial pressure among the MgSO4 recipients. However, It is clear that with the small sample size, these data are insufficient to address the important question originally posed. Using our pre-prepared protocol as a basis, a much larger trial could be developed at short notice in the event of another outbreak, to properly evaluate whether MgSO4 has a role in controlling the blood pressure in severe HFMD
