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Outbreak of Zika virus infection in Singapore: an epidemiological, entomological, virological, and clinical analysis

https://doi.org/10.1016/S1473-3099(17)30249-9Get rights and content

Summary

Background

An outbreak of Zika virus infection was detected in Singapore in August, 2016. We report the first comprehensive analysis of a national response to an outbreak of Zika virus infection in Asia.

Methods

In the first phase of the outbreak, patients with suspected Zika virus infection were isolated in two national referral hospitals until their serum tested negative for the virus. Enhanced vector control and community engagement measures were deployed in disease clusters, including stepped-up mosquito larvicide and adulticide use, community participation in source reduction (destruction of mosquito breeding sites), and work with the local media to promote awareness of the outbreak. Clinical and epidemiological data were collected from patients with confirmed Zika virus infection during the first phase. In the second phase, admission into hospitals for isolation was stopped but vector control efforts continued. Mosquitoes were captured from areas with Zika disease clusters to assess which species were present, their breeding numbers, and to test for Zika virus. Mosquito virus strains were compared with human strains through phylogenetic analysis after full genome sequencing. Reproductive numbers and inferred dates of strain diversification were estimated through Bayesian analyses.

Findings

From Aug 27 to Nov 30, 2016, 455 cases of Zika virus infection were confirmed in Singapore. Of 163 patients with confirmed Zika virus infection who presented to national referral hospitals during the first phase of the outbreak, Zika virus was detected in the blood samples of 97 (60%) patients and the urine samples of 157 (96%) patients. There were 15 disease clusters, 12 of which had high Aedes aegypti breeding percentages. Captured mosquitoes were pooled into 517 pools for Zika virus screening; nine abdomen pools (2%) were positive for Zika virus, of which seven head and thorax pools were Zika-virus positive. In the phylogenetic analysis, all mosquito sequences clustered within the outbreak lineage. The lineage showed little diversity and was distinct from other Asian lineages. The estimated most recent common ancestor of the outbreak lineage was from May, 2016. With the deployment of vector control and community engagement measures, the estimated reproductive number fell from 3·62 (95% CI 3·48–3·77) for July 31 to Sept 1, 2016, to 1·22 (95% CI 1·19–1·24) 4 weeks later (Sept 1 to Nov 24, 2016).

Interpretation

The outbreak shows the ease with which Zika virus can be introduced and spread despite good baseline vector control. Disease surveillance, enhanced vector control, and community awareness and engagement helped to quickly curb further spread of the virus. These intensive measures might be useful for other countries facing the same threat.

Funding

National Medical Research Council Singapore, Centre for Infectious Disease Epidemiology and Research, and A*STAR Biomedical Research Council.

Introduction

Zika virus was first reported in Asia in 1966.1 Although endemic regionally,2, 3 no comprehensive reports of systematic surveillance or outbreaks of Zika virus have been made. Despite ongoing flavivirus surveillance in Singapore to monitor hyperendemic dengue, sporadic imported chikungunya, and other regional threats such as Japanese encephalitis,4 autochthonous Zika virus infections had not been previously detected.5 The number of local Zika virus infections has also been increasing in continental Asia.2

On May 13, 2016, the first confirmed case of Zika virus infection in Singapore (population density 7797 people per km2), was identified in a traveller returning from São Paulo, Brazil. The traveller was isolated in hospital to prevent transmission to mosquitoes because the two principal vectors of Zika virus, Aedes aegypti and Aedes albopictus, are widely prevalent in Singapore.6 Active case finding, enhanced vector control, and community education were implemented around his residence. No further cases were identified for 3 months. In August, 2016, primary health-care doctors in the Kallang-Aljunied neighbourhood reported an increased number of individuals with fever, rash, and joint pains. Further investigations confirmed the presence of a cluster of Zika virus infections.

In this study, we report epidemiological, entomological, virological, and clinical findings related to the Singapore Zika virus outbreak from detection on Aug 22 to Nov 30, 2016. We describe interventions implemented, which made use of existing vector control programmes and intersectorial coordination to curb the spread of the virus.

Research in context

Evidence before this study

As of May 1, 2017, no comprehensive reports have described a national response to an outbreak of Zika virus infection in Asia. We searched PubMed up to Feb 25, 2017, for reports published in English with no date limitations using the terms “Zika” and “Asia”, as well as “Zika” and “Singapore”. We identified 51 relevant articles with the first search and 13 with the second. However, these studies were case reports, commentaries, and reviews of what is known about Zika virus in the region. One published report included preliminary phylogenetic analysis of two of the Singaporean outbreak strains, with results suggesting a relation to the Asian Zika virus lineage.

Added value of this study

To our knowledge, this study represents the first comprehensive and multi-faceted analysis of the first Zika virus outbreak in Singapore. The outbreak shows the ease with which the virus can be introduced and spread despite an ongoing national vector control programme. Our results also show evidence of other imported Zika virus strains that did not establish themselves and how the use of measures such as enhanced vector control and community engagement helped to curb incidence within 4 weeks of implementation. We did a phylogenetic analysis of 117 complete and near-complete genomes from the outbreak, which represents a nearly 50% increase in the number of full Zika virus genomes available worldwide.

Implications of the available evidence

The ease of introduction and spread show that outbreaks of Zika virus infection can occur even with baseline vector control. Prompt national action, including targeted vector control, community outreach, and engagement with the media can help to curb the spread of large outbreaks. The implementation of these intensive control measures might be useful for other countries facing the same threat.

Section snippets

Case definitions and surveillance

From Jan 27, 2016, doctors were obliged by law to notify health authorities of any cases of Zika virus infection. National testing capability was increased and Zika virus RT-PCR assays were made available at the National Public Health Laboratory and four major public hospitals. RT-PCR was used because dengue virus serologically cross-reacts with Zika virus. Doctors were also required to report clusters of infectious disease syndromes, even if they had unknown aetiologies.

Since 2007, ad-hoc Zika

Results

On Aug 22, 2016, a primary health-care doctor in Singapore notified the Ministry of Health of an increased number of patients with fever, rash, and joint pains in the Kallang-Aljunied neighbourhood. The first case of Zika virus infection was confirmed on Aug 27. This patient had not travelled abroad recently and was considered to represent the first autochthonous case of Zika virus infection.

Retrospective identification of people with Zika-like symptoms in the preceding month was initiated in

Discussion

The high volume of travel and trade, high population density, presence of Aedes spp vectors, and the perennially warm and humid climate make Singapore (like other countries with similar conditions) particularly susceptible to mosquito-borne diseases. The regularity of dengue virus lineage replacement events16 and the outbreaks of chikungunya virus in 2008 and 2013 show the potential for regular exchange of viruses within the region.

The first case of Zika virus infection being introduced into

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