Clinical Trial: Neurodevelopment Outcomes Following Severe Hand Foot and Mouth Disease in Vietnam

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: A Prospective Cohort Study Evaluating Prognostic Indicators and Sequelae Following Severe Hand Foot and Mouth Disease

Brief Summary:

Hand Foot and Mouth Disease (HFMD) is a common infectious disease in childhood. Several enteroviruses are associated with the disease. However, since 1997, large outbreaks of HFMD in Taiwan, Malaysia and Vietnam have seen unusual neurological complications such as brainstem encephalitis with rare fatal outcomes. The pathogen associated with this severe disease is Enterovirus 71.

In 2011, Vietnam had a large outbreak of Hand Foot and mouth disease resulting in 110,000 cases and 164 deaths. HFMD affects children during their early years of child development, but there is limited information on what the potential long-term consequences are. Small studies have suggested language and cognitive difficulties in more severe disease but this has not been evaluated in a large cohort.

Internationally recognized and standardized assessment tools are not available for early childhood in Vietnam. This project will translate and adapt the Bayley Scales of Toddler and Infant Development 3rd edition (Bayley III) and Movement ABC, 2nd edition (MABC) into Vietnamese as outcome measures.

This study will evaluate whether there are neurodevelopment difficulties following severe HFMD. The study design is a prospective observational cohort study. Hospitalised children with a clinical diagnosis of HFMD will be eligible to enroll. Written parental consent will be required. Participants enrolled will be assessed 3 times over 18 months from discharge from hospital into the study. Since there is no standardization of Bayley III or MABC for Vietnam, a healthy cohort, age and sex matched to the least severe HFMD participants will be recruited. This healthy cohort will follow the same assessment program over 18 months. A total of 350 HFMD participants and 150 healthy children (matched to the least severe

Detailed Summary:

Background:

Hand foot and mouth disease outbreaks associated with enterovirus 71 (EV71) were unusual in their neurological manifestations. Since 1997, Taiwan, Malaysia and Vietnam have experienced large outbreaks of EV71-HFMD.

Neurological manifestations include meningitis, brainstem encephalitis, and rare cardiopulmonary failure, thought to be neurogenic in origin.

In Vietnam, children are admitted to hospital if they show signs of systemic disease. The Vietnam Ministry of Health has developed a grading system to stratify management and intervention. Grade 1 have solely the typical rash on palms of hands, soles on feet and buttock with ulcers in the mouth. Grade 2 have systemic features such has high fever, irritability and myoclonus. Grade 2 is split into 2a for parental report of symptoms or 2b if a health professional has observed neurological signs. Grade 2 onwards are admitted to hospital. Grade 3 develop irregular breathing, persistent tachycardia, hypertension, all features of autonomic disturbance due to brainstem encephalitis. Grade 4 develop often fatal cardiopulmonary failure, believed to be a consequence of excessive unopposed sympathetic activation from brainstem disease.

Different countries use different grading or staging systems for HFMD. A study in 142 EV71 suggested children affected at a younger age of onset of disease might have consequences for verbal comprehension. In 63 children with EV71 disease, 14% had cognitive or motor deficits.

Hypothesis and Aims:

The study aims to identify the neurological and neurodevelopmental outcomes following severe (hospitalised) HFMD in Vietnam.

Measured by: Children 36 months and under at enrollment will use the translated and adapted Bayley Scales of Toddler and Infant Development 3rd Edition (Bayley III) for Vietnam. Children 48 months and above at enrollment will use the Vietnamese translation of Movement ABC-2 tool for their assessments. The children aged between 37 and 47 months at enrolment will have both assessments done at both visits.