A large outbreak of HFMD occurred in Vietnam in 2011. The death of 170 children from HFMD allowed the opportunity to describe and better understand how so many young children died.
The median age of children who died from HFMD in this study was higher than those found in Taiwan and Malaysia (25 months vs. 17 months and 18 months, respectively) [12, 13], but it was the same in Singapore in 2000 [6]. However, the proportion of cases aged 3 years or younger were the same in Taiwan (79% vs. 78%) [12]. The ratio of male and female was 2.2:1, higher than in outbreaks in other countries such as 1.4:1 in Taiwan [12], 1.3:1 in Singapore [6] and 1.9:1 in Malaysia [13]. We found no plausible explanation for this skewed ratio.
The exposure history of the cases, i.e. those who attended daycare or had known contact with other HFMD cases, was poorly recorded and did not indicate any particular source of transmission. HFMD is known to spread through direct contact with mucus, saliva, or feces of an infected person. Data from this study showed that only 18% of the fatal cases attended daycare which suggested that most of the HFMD transmission occurred at home and could be from contact with other family members having asymptomatic or mild infection such as parents, older siblings, nannies and other caregivers [14]. Therefore, health education efforts including behavior change communication to prevent HFMD transmission should be conducted not only in school but widely in the community, targeting households and families with young children. Further studies on virus circulation and virulence in different populations and settings are needed to provide a rational basis for targeting prevention and control measures.
Most of HFMD cases and deaths were reported in Southern provinces, from May to October. The occurrence of HFMD during the rainy season (May to October) was higher than the dry season (November to April): 90% vs. 10%. The mean air temperature of Southern provinces was always higher than other provinces (mean air 27.5°C in southern provinces (Ca Mau) compared with range 18.1-26.9°C in other provinces). The monthly air temperature from March to November was higher than December, January and February (range 27.2-28.7 vs. 26.3-26.4°C) [15].
There were two peaks of HFMD deaths. In October, at the peak of the rainy season, HFMD deaths reached the highest number as the epidemic spread to the North where health workers had limited experience in case management of HFMD. A study in Hong Kong on the relationship between meteorological parameters and HFMD activity showed that meteorological parameters helped in predicting HFMD activity and could assist in explaining the winter peak detected in recent years and in issuing early warning [16]. Other studies on the association between meteorological parameters and occurrence of HFMD are warranted. In Vietnam, HFMD surveillance data need to be compiled for some more years to demonstrate the seasonality as HFMD is a newly emerging disease.
Fever was reported in most cases, followed by myoclonus which was markedly higher than other symptoms. In reality, the myoclonus symptoms could be observed more frequently than in this study [17]. In a survey at Children Hospital Number 2 in Ho Chi Minh City, myoclonus was observed in almost all (98%) severe cases [18]. The explanation for the low rate of myoclonus could be due to missing data in medical records. Proportions of the cases having fever and oral ulcer were slightly lower than in a study in Sarawak, Malaysia (fever 100%, oral ulcer 66%) [13] and another study in Peninsular Malaysia in 1997 (fever 100%, oral ulcer 72%) [19]. Taken together, warning signs of severe HFMD could be considered as high fever, myoclonus and persistent vomiting with or without oral ulcers and vesicular erythema.
The classification of HFMD in Vietnam [9] is different from the WHO guide [5], however the Vietnamese clinical grading is generally consistent with that of WHO. Almost all HFMD fatalities were from grade 2a or above at admission. Given the rapid clinical progression of HFMD, clinicians should be able to recognize early the uncomplicated forms of the disease (grades 1 and 2a) as their proportions were found higher in the present study than those found in a previous study in Vietnam [20]. It is also important to note that 34% of HFMD were misdiagnosed even upon referral to provincial or regional hospitals. Although clinicians working at the provincial and district hospitals have received training on case management of HFMD according to the Ministry of Health guidelines [11], it was uncertain whether they could apply the guidelines at their respective level of care.
Laboratory abnormalities of the cases included elevated levels of white blood cell count, blood sugar, severe metabolic acidosis, Troponin I, and platelet which may help to predict a poor outcome [19, 21]. A study to determine the risk factors predictive of death from HFMD in Singapore showed that elevated white blood cell count was a risk factor and should alert the physician of a fatal course of illness [6, 22].
There are no specific treatments for HFMD. In this study, dobutamine was used in almost all (96%) cases as recommended by WHO [5] and the Ministry of Health [9]. On the contrary, dopamine which increases sympathomimetics, production of cytokines, inflammation and severity of disease was administered to 18% of cases. Dopamine has been considered as one of potential risk factors contributing to fatal outcome of HFMD [5]. Respiratory failure, prolonged shock and coma were recorded as main causes of deaths. Similar results were found in studies conducted in Taiwan [12] and Malaysia [19]. The rapid onset and progression of pulmonary and cardiac failure in previously healthy children stand out as a unique feature of this disease [13, 17]. As the median time from referral hospital admission to death was only 1 day, only few patients had access to hemofiltration which is considered to have some therapeutic effects on HFMD. In view of this, more timely referral or initiating hemofiltration treatment prior to referral at the provincial hospitals may potentially be lifesaving.
This is the first national study describing a large number of deaths caused by HFMD during an outbreak in Vietnam in 2011. In this respect it has the requisites to provide an overall epidemiological picture and reveal some factors potentially associated with the deaths. However, some limitations of this study merit noting. Firstly, the retrospective study could not obtain key epidemiological and clinical data of HFMD patients during the time of disease. Secondly, patient records may have been incompletely filled. Despite these limitations, the results provided some hypothesis for further studies. An analytical study may help to identify risk factors of acquiring severe HFMD that can potentially be prevented. Understanding these factors will provide a rational basis for developing successful preventive interventions and treatments of severe HFMD.