SINGAPORE: In a quiet neighbourhood in eastern Singapore, a 47-year-old woman was developing a rash, fever and conjunctivitis. Had the symptoms developed separately, her general practitioner would have barely batted an eyelid.
But together, the symptoms were indicative of the Zika virus, an illness that was spreading quickly around South America.
Patient A, as she became known, would be the first case of locally transmitted Zika in August 2016. As more people were diagnosed with the disease, which is spread by the aedes aegypti mosquito, authorities sought to control the mosquito population through regular fogging.
By the end of the year, about 450 people here were confirmed to have caught the virus.
“You have to have all of the stars lined up before you have that kind of transmission that you did last year,” said Emeritus Professor at Duke-NUS’ Emerging Infectious Diseases Programme Duane Gubler.
Prof Gubler told Channel NewsAsia that epidemic transmission is a “complicated interaction between the virus, the human host and the mosquito”, and all three “lined up” to propagate the virus quickly in a span of four months.
But just as quickly as new clusters appeared, Zika numbers dwindled globally as well as locally.
For scientists and infectious diseases experts, understanding the impact of the virus is a work in progress. With current research maturing over the next six months, Prof Gubler said the hope is to eventually be able to provide more answers than questions.
Until then, the focus for vulnerable countries needs to be on controlling the mosquito population.
FACTORS BEHIND LACK OF MICROCEPHALY IN SINGAPORE
Having circulated silently across Africa and Asia since the 1960s, Zika’s large outbreak was first reported on Yap Island, west of French Polynesia.
Prof Gubler said with about 5,000 reported cases, there were no signs of neurological diseases associated with Zika. They include microcephaly, which causes babies to be born with a smaller head due to abnormalities in the development of the brain. Another neurological disease linked to Zika is the Guillain-Barre syndrome, which causes temporary or permanent paralysis.
“When the virus got to French Polynesia with over 30,000 cases, then they started to see a few cases of microcephaly,” Prof Gubler said.
By the time it got to Brazil where it infected hundreds of thousands of people, Prof Gubler said the number of babies born with microcephaly rose even more.
Prof Arijit Biswas, a senior consultant at the National University Hospital's Women's Centre said there appears to be a link between Zika and microcephaly in a developing fetus.
In Singapore, the Health Ministry told Channel NewsAsia that of the 17 women who were diagnosed with Zika during their pregnancies in 2016, two had their pregnancies terminated while one had a miscarriage.
The reasons behind this were not linked to Zika.
It added the other 14 women gave birth to babies with no signs of microcephaly. Last year, the Health Ministry announced it would monitor the development of these babies until the age of three.
None of the babies evaluated under the surveillance programme have shown signs of abnormalities, the ministry said, adding that all are developing well so far.
Prof Biswas, who who is also the lead of the Health Ministry's Clinical Advisory Group on Zika and Pregnancy, said the small number of pregnant women affected in Singapore also lowers the probability of having a baby with microcephaly.
Prof Gubler agreed, saying this could explain why in places like Brazil where hundreds of thousands are thought to have been exposed, doctors started to see a rise in the number of microcephaly cases.
Both he and Prof Biswas added another reason for the lack of microcephaly cases in Singapore could be due to genetic variances in the Zika strains.
In September 2016, health authorities and researchers concluded that the Zika virus strains found in the first two locally transmitted cases in Singapore were not imported from the South American strain.
“To our surprise, the Zika strain causing the local outbreak was derived from a local version that has been circulating in Southeast Asia since the 1960s,” A*STAR’s Bioinformatics Institute’s (BII) Sebastian Maurer-Stroh was later quoted in a publication.
A*STAR said an analysis of the strains suggest Singapore’s strain diverged in early 2010, before the rapid spread through Brazil.
The agency's BII said Zika strains prior to 2013 have not been linked to severe neurological complications.
While there is research to suggest a mutation in the strain circulating in South America could have been the reason for the high rates of microcephaly, Prof Biswas cautioned there is insufficient data on the microcephaly rates among different strains.
DOES THE THREAT REMAIN?
For infectious diseases expert Dr Leong Ho Nam, the drastic decline of cases this year came as a surprise. He said he expected the number of cases to rise. Instead, Zika activity, like in the rest of the world, has been low.
The National Environment Agency (NEA) said this year’s Zika clusters were contained in “small localised areas” through intensive and targeted vector control operations and community awareness.
After the last Zika cluster in Serangoon North Avenue 1 closed in September, Zika cases have been sporadically appearing after weeks of inactivity. For example, after more than six weeks, a new case was highlighted in the Health Ministry’s weekly infectious diseases bulletin last week, bringing the total to 67 this year. This is a sharp decline from the 453 Zika cases this time last year.
Both Dr Leong and Prof Gubler expect the virus to continue to spread, though it is unclear how rapid its spread will be.
Prof Gubler said he expects Zika to go the way of dengue and chikungunya epidemics. All three are transmitted by the aedes mosquito.
“Chikungunya caused a major epidemic in Asia in the 1960s and 1970s and then disappeared and then reappeared in 2004 and spread again over several years,” Prof Gubler said.
“Dengue has done the same thing - it comes and goes. After several years of epidemics, the virus goes underground and it becomes “a silent transmission”, characterized by mildly asymptomatic cases that are not recognised as Zika or as dengue or as chikungunya.”
Prof Gubler said that’s because the viruses undergo genetic mutations that cause them to have a lower potential for epidemics and infectivity.
But Dr Leong offered a different explanation, saying that the likely reason for the lack of Zika cases in Singapore could be due to a better control of mosquito breeding. He pointed out there were about 2,500 cases of dengue this year, compared to more than 12,600 last year.
“But if you look beyond it and postulate and guess, is it because the Zika virus is not able to grow so well in Singapore?” he said.
“If Singapore is very good in controlling mosquito populations, my assumption would be that Indonesia and Thailand may not have set up the tremendous efforts Singapore has. Why aren’t they getting huge outbreaks of Zika?”
Compared to dengue, Dr Leong also pointed out that chikungunya also does not spread as quickly.
“It thus suggests that the mosquitoes here are not quite adapted to chikungunya and Zika transmission as compared to dengue,” he said.
“We must not assume that the mosquito will treat Zika, dengue and chikungunya equally. We will assume that like us, some would like to eat more fruits, some would like more meat and some would like more vegetables. So there will be a different propensity for the virus.”
Prof Gubler noted that a Zika vaccine could be about three years from being approved if all goes well.
Aside from the development of a vaccine, Prof Biswas said another interesting outcome of research on the virus is the unravelling of the "mechanism of nerve cell destruction, particularly nerve stem cells".
"One suggested mechanism is the destructive effects of the virus on neural stem cell which play a very active role in the development of fetal brain," Prof Biswas said.
This, he said, could explain how microcephaly characteristics of a small brain can develop in fetuses infected with Zika.
But this same understanding is being explored by researchers in treating other diseases.
"Researchers are also exploring the possibility of using Zika virus in the treatment of brain tumors, utilizing the same nerve cell destruction properties of this virus," Prof Biswas added.
CONTROL AND SURVEILLANCE IS CRITICAL
Until then, both experts agreed that mosquito controlling efforts need to be maintained on the island.
To that end, NEA told Channel NewsAsia it conducted more than 575,000 inspections between January and June this year. It said some 1,900 households were fined for mosquito breeding.
It said construction sites found to be breeding mosquitoes dropped from 11 per cent in 2013, to 6 per cent as of June this year, as a result of working with stakeholders.
Still, it said more than 20 stop-work orders were issued in the first half of the year.
“With more exposure, the viruses and mosquitoes will learn to adapt to each other. So if you are hungry and there is nothing to eat except vegetables, you end up adapting and liking vegetables,” Dr Leong said.
Another reason for eradicating the mosquito population is the worry that there are other viruses out there that could be transmitted through the aedes mosquito.
“I estimate there’s probably five or six viruses out there that can be transmitted by the aedes aegypti that will respond to the same type of pressures- urbanisation and global travel,” Prof Gubler said.
“That can move those viruses around the world. So the only way to prevent the epidemic of those viruses if they emerge is to have good mosquito control because we don’t have vaccines for them, we don’t have other antiviral drugs.”