Hand, Foot and Mouth Disease in Vietnam: Epidemiology, Heart Rate Variability and Economic Burden

Le Nguyen Thanh Nhan (2020). Hand, Foot and Mouth Disease in Vietnam: Epidemiology, Heart Rate Variability and Economic Burden. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0001137c


Over the last two decades, hand, foot and mouth disease (HFMD) has become a major clinical problem in Vietnam and the Asia-Pacific region. HFMD affects children, especially those under 5 years old, and has pandemic potential. Since 1997, there have been several outbreaks with severe clinical phenotypes, including brain stem encephalitis, attacking millions of children and causing thousands of deaths. Synthesizing data on epidemiology, etiology, disease pathophysiology and economic burden of this emerging infection remains essential to inform clinical management and health policy makers in prioritizing the development of intervention strategies.

Using data from >56,000 hospitalized cases over an 11 year period, I described the spatial and temporal distribution of HFMD in Ho Chi Minh City, the main hotspot of HFMD in Vietnam. I found that the disease started in the west and then moved to the south-east and finally came back the west of the city.

Results from a prospective multi-hospital based study conducted during 2015–2018 showed that of ~1200 enrolled patients, enterovirus A71 (EV-A71) was the most common HFMD pathogen detected, while coxsackievirus A6 (CV-A6) has emerged and replaced CV-A16 to become the second most common virus causing HFMD in Vietnam during the study period. Despite the emergence of other pathogens and the diversity of enterovirus serotypes (~20 serotypes) detected in HFMD patients, EV-A71 was the main cause of severe HFMD. Using long-term data synthesized as part of the research program, I also demonstrated for the first time that compared to EV-A71 subgenogroup B5, subgenogroup C4 was associated with more severe clinical phenotypes. Moreover, the predominance of subgenogroup C4 coincided with large, severe HFMD outbreaks in Vietnam (e.g. in 2011-12 and 2018). Collectively, the data suggest that an EV-A71 vaccine would be likely to substantially reduce the burden of HFMD, but a multivalent vaccine should be developed to control the ongoing HFMD epidemic because CV-A6, CV-A10 and CV-A16 were responsible for approximately 12% of severe HFMD cases and cross-reaction between these CV-As and EV-A71 is poor.

In order to improve our knowledge of HFMD pathophysiology, I used ECG signal recorded by a wearable device (e-Patch) to depict the distribution of heart rate variability (HRV) indices by severity and by detected pathogens and found that compared to mild disease HRV parameters reflecting parasympathetic nervous system activation in the severe group decreased whereas those mirroring sympathetic activity and autonomic nervous system imbalance increased. In a similar trend, compared to HFMD associated with non-EV-A71, HRV indices reflecting the imbalance between sympathetic and parasympathetic activation in HFMD associated with EV-A71 were significantly higher. This suggests that children with EV-A71 infection were more likely to have ANS imbalance. Alongside with these findings, the feasibility of this wearable device in children has brought promising applications in HFMD case management by early detection of severe disease in future.

To inform health policy makers in Vietnam about the burden of HFMD, I also estimated its economic burden. I showed that the total cost per case for mild and severe disease was $245.8 and $1326.7, respectively. Additionally, I also found that compared to CV-A infections, EV-A71 infection resulted in higher illness costs. At nationwide level, the total economic burden in Vietnam was estimated at >US$90 million for two-year period of 2016 – 2017. [math mode missing closing $]

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