Friday, 2 September 2016

Zika in Singapore: Need for mosquito control and public health education

The Zika virus is likely to become endemic in Singapore. A strategy of minimising and testing for infection in pregnant women, outpatient management of patients, and controlling mosquito spread are key.
By Alex R. Cook and Hsu Li Yang, Published The Straits Times, 1 Sep 2016

The Zika virus is so named because it was discovered in a sentinel monkey in the Zika Forest near Entebbe, Uganda, by scientists working at the Yellow Fever Research Institute in 1947.

Closely related to dengue, Japanese encephalitis and yellow fever viruses, it is transmitted primarily by mosquitoes, including the Aedes aegypti, which is also the main vector of dengue in Singapore.

The Zika virus' original hosts are primates, including orang utans in the forests of Borneo. Prior to 2007, human infections were rarely reported and were believed to be mostly due to zoonotic (that is, from primate to human) transmission via a mosquito vector.

In 2007, the first known human epidemic of Zika occurred on the Micronesian island of Yap. The virus spread relentlessly eastwards to finally reach the Americas. Brazil was the first country in South America to report Zika cases in April last year, although researchers believe that the virus arrived during the Fifa Confederations Cup held in that country in June 2013, possibly around the Tahiti-Uruguay match held in Recife, Brazil.

Since then, Zika has spread explosively throughout the tropical countries of South America, Mexico and parts of Central America, with local transmission of the virus reported in Florida since July 19 this year.

The disease caused by the virus is generally mild. Four out of every five infected people are asymptomatic (that is, never develop any symptoms). Only 20 per cent of those infected develop Zika fever, which often presents as fever accompanied by other symptoms such as rash, joint pain, inflammation of the eyes, headaches and muscle aches, three to 12 days after infection sets in.

These symptoms are not unique to Zika. Due to similarities to the symptoms of dengue fever, Zika is oft referred to as "mild dengue". Most people with Zika fever recover within a few days, and many do not seek medical attention.

It is important to note that all infected people, symptomatic or not, can transmit the infection to others if they are bitten by Aedes mosquitoes during the first few days of infection as the virus circulates within the bloodstream; or, in rare cases, via unprotected sexual intercourse as the virus is able to persist in semen in excess of six weeks. People who are infected develop lifelong immunity to Zika after they recover.

There are, however, two devastating complications resulting from Zika infection - both of which are fortunately rare.

Approximately three out of every 10,000 infections lead to a rare neurological disease called Guillain-Barre syndrome, with paralysis of the limbs.

In women who are pregnant at the time of infection, the virus may also infect the unborn foetuses, causing miscarriages, congenital abnormalities including microcephaly (abnormally small heads), and brain damage. The risk appears highest during the first trimester of pregnancy, with an estimated 1 per cent to 10 per cent of infected pregnant women delivering babies with microcephaly. Children born to women infected during the third trimester of pregnancy are hardly affected.

A recently published study showed that a laboratory strain of Zika virus could damage the neural stem cells of immuno-compromised mice in a mouse model of Zika infection, with a postulated impact on memory and learning. This led to speculations that the impact of Zika infection in other adults could be more severe than previously thought. Whether evidence from animal models is truly predictive of human outcomes has long been a contentious issue, and it is therefore important to note that what happened to the mice in this single animal study on Zika may not necessarily reflect what will happen in humans.

The online Straits Times report ("41 cases of locally transmitted Zika confirmed in Aljunied Crescent cluster, 34 fully recovered", Aug 28) signals the first known outbreak of Zika in Singapore. There is currently no treatment for Zika. While a vaccine has already been developed, early-stage (Phase 1) clinical trials have just started. Should the vaccine prove to be effective, it will take several years before it becomes commercially available. Without a vaccine or cure, how should we respond to the Zika outbreak?


Hospitalising symptomatic people till they become non-infectious may not be a cost-effective option because asymptomatic Zika-infected people, who form the bulk of Zika infections, can also transmit the virus.

However, simple isolation of confirmed or suspected Zika-infected people from mosquitoes may help. In recovering male patients, the use of barrier protection (that is, condoms) during sexual intercourse for at least six months will minimise sexual transmission of Zika.

Having a strategy for pregnant women, including health advisories, Zika-negative blood products and means of testing foetuses for evidence of Zika infection (via amniotic fluid testing), is critical, and the Ministry of Health has this well in hand.

Ultimately, we must target the vectors, which are the very same mosquitoes responsible for the spread of dengue. The National Environment Agency (NEA) is already doubling its vector control efforts around Zika-affected areas in Singapore. Greater community participation in the Mozzie Wipeout campaign throughout the island will boost efforts in reducing Zika as well as dengue infections.

The current outbreak strengthens the case for pursuing innovative vector control methods over the long run. Scientists have recently used the gene-editing tool, CRISPR-cas9, on different mosquito species, including the Anopheles mosquitoes that transmit malaria, creating malaria-resistant mutants that passed the resistance genes to nearly all their offspring under laboratory conditions. Such a strategy could similarly be explored to "vaccinate" the Aedes population against dengue and Zika in the future.

Another approach that could prevent dengue and Zika infections is by releasing modified sterile mosquitoes, either genetically modified or naturally sterilised using the Wolbachia bacterium.

As only the female mosquitoes bite and feed on human blood, the mass release of male sterile mosquitoes will not pose a risk to people. Instead, these males compete with those in the wild for mates, reducing the density of mosquitoes, and thereby infections. This is a safe technology that has been used in agricultural pest control for decades, and has recently been tested in mosquitoes in countries like Australia and Brazil.

The NEA plans to test Wolbachia in small-scale releases this year, with a view to incorporating it in our national vector control programme. Such an initiative should be applauded. If proven successful, this programme could minimise the spread of dengue and Zika in this country, and serve as an effective strategy for other countries in the region to model.

Finally, we have to face the possibility that Zika may become endemic in Singapore, much like dengue and other infectious diseases. Repeated importation of the virus into Singapore is a near certainty even if this current outbreak (and there is a reasonable probability of this) is brought under control, because Singapore is a global transport and tourist hub, and the virus continues to spread unabated in many countries worldwide. Because the disease is mild for the vast majority of infected people, outpatient management by general practitioners and the polyclinics should be routine practice.

Risk mitigation strategies such as vector control as well as prevention and testing of Zika infection in pregnant women will be key, along with rapid adoption of an effective Zika vaccine should one be developed and commercialised.

Dr Alex R. Cook and Dr Hsu Li Yang are both associate professors at the Saw Swee Hock School of Public Health, National University of Singapore.

No comments:

Post a Comment