Every morning of the working week, early childhood educators around Singapore begin their day by inspecting the mouths, hands and feet of their toddler students. With a quick spray of hand sanitiser, the children can enter the classroom.
So familiar is the routine, that most parents give little thought to the consequences of a teacher missing that lone ulcer beneath the child’s tongue, or the single blister forming between the toes.
That is, until an outbreak of Hand, Foot, and Mouth Disease (HFMD) occurs.
An economic burden in Singapore
HFMD is a highly contagious viral infection that most commonly causes fever and sore throat, as well as ulcers in the mouth, and blisters on the hands and feet. The disease is predominantly caused by two strains of coxsackievirus type A (CA16 and CA6), as well as enterovirus 71 (EV71). It is spread via saliva, respiratory droplets, as well as unwashed hands that have come in contact with any contaminated bodily fluids. As such, the disease spreads rapidly amongst infants and children below the age of five.
HFMD is prevalent throughout the Western Pacific region. More than 86 per cent of the total cases reported to the World Health Organization between 2010 and 2014 occurred in China. However, the disease is also commonplace in Thailand, Vietnam, Malaysia, Japan, Taiwan and Australia. In Singapore, the last major outbreak occurred in 2018, when at its peak, 1,249 cases were reported in a single week.
Although the majority of children with HFMD experience only mild symptoms and fully recover within seven to 10 days, the economic burden placed on both families and society is substantial and often underestimated. On top of the medical costs incurred, additional productivity is lost as parents take leave to care of their sick child. In 2016, it was estimated that the cost to Singapore from HFMD topped $4.8 million.
Familiar routines underlie potential severity
Currently, the primary defence against HFMD is the very routine employed by childcare centres and schools around Singapore. Frontline inspections are supported by regular sterilisation and cleaning of the childcare facilities, together with early education on the importance of hygiene practices. Such procedures aim to minimise the chance of the disease being spread between classmates. In the event of an outbreak, schools may be closed and parents asked to avoid social gatherings. As infected individuals remain contagious for up to six weeks, long after apparent symptom recovery, this does not necessarily stop the transmission chain.
The employment of such routines likely has a significant impact on containing outbreaks. However, the fact remains that HFMD epidemics remain a prominent feature of Singapore’s social landscape. Until effective treatments, or preventative vaccines are developed, this will continue to be the case.
Underestimating the severity of EV71 infection
The idea of vaccinating against, or treating a disease that usually causes only mild symptoms, may seem unnecessary to many parents. However, what is often overlooked is the fact that when the disease is caused by EV71, the chances of developing life-threatening complications increases significantly. Meningitis, brainstem encephalitis, and cardiopulmonary dysfunction have all been tied to severe HFMD. In some cases, EV71 infection could be fatal, as was the case during a HFMD outbreak in Malaysia in 2018, where two children died.
Alarmingly, it is estimated that up to 20 per cent of the cases reported in Singapore, stem from EV71 infection.
Recent research has shown that the complications of severe HFMD arise when EV71 infects the central nervous system. This is believed to occur when the virus enters the neural network present in between the muscle layers of the gut, after which the virus infects the spinal cord and brain. Even when not fatal, the involvement of the nervous system in EV71 infection means that there is a significantly higher chance the child will suffer long-term cognitive and motor disorders.
With a significant prevalence of EV71 infection in Singapore, researchers at NUS believe that current control measures, such as social distancing, are insufficient as long-term solutions to protect children against complicated HFMD.
"Currently there are no drugs or vaccines available to treat or prevent this serious form of HFMD. This is particularly worrying given the severity of complications that we know can arise from EV71 infection," said Associate Professor Sylvie Alonso from NUS Microbiology and Immunology.
"Finding drugs that target the virus itself is challenging, as viruses constantly mutate, and become resistant very rapidly", Assoc Prof Alonso explained. "However, if we better understand the factors in our own cells that the virus exploits to thrive in the central nervous system, we should be able to identify ways to control EV71 infection."
With the knowledge that it is only a matter of time before another outbreak occurs, Assoc Prof Alonso and colleagues, are looking to secure funding that will enable them to continue working towards their goal of identifying new targets and effective drugs to ultimately reduce the severity of EV71 infection.