Update on Zika virus infection for primary care providers

Pui-yi Siu 蕭珮儀，David VK Chao 周偉強

HK Pract 2016;38:70-73

Summary

Zika virus infection is usually asymptomatic. However, there is scientific consensus that Zika virus is a cause of microcephaly and Guillain-Barre syndrome. This article aims to review the epidemiology, transmission, clinical features and differential diagnosis of Zika virus infection, and explore the role of primary care providers in the management of suspected cases and prevention of transmission.

摘要

大部分寨卡病毒感染並沒有病徵。科學共識認為寨卡病毒是 小頭症和吉巴氏綜合症的成因。本文回顧寨卡病毒感染的流 行病學、傳播途徑、臨床病徵和鑒別診斷，並探討家庭醫生 在治療懷疑個案和預防感染傳播方面的角色。

lntroduction

Although most cases of Zika virus infection are asymptomatic or have mild symptoms, the recently identified associations with congenital microcephaly and Guillain-Barre Syndrome have raised global concerns. In February 2016, the World Health Organisation declared a Public Health Emergency of International Concern in view of clusters of microcephaly and other neurological complications in some areas affected by Zika.¹ Forty-two countries and territories have reported ongoing mosquito transmission from 1 January 2015 to 27 April 2016, and nine countries have reported evidence of person-to-person transmission probably via a sexual route.² Outbreaks have been identified in the Americas, Pacific islands, Asia and Africa^1,3, while sixteen imported cases have been diagnosed in the Mainland China as of 10 April 2016.⁴ Since international travel is common nowadays and the potential vector Aedes albopictus is present in Hong Kong, the risk of introduction and transmission of Zika virus in Hong Kong cannot be ignored. At present, there is no effective antiviral treatment or vaccine against Zika virus, and so prevention is of utmost importance.

Transmission

Zika virus is a flavivirus that is primarily transmitted through bites from infected Aedes mosquitoes. Aedes aegypti, which is found in tropical regions, is the main vector. This mosquito also transmits dengue, Chikungunya and yellow fever.³ Although Aedes aegypti is not found in Hong Kong, other locally present Aedes mosquito species such as Aedes albopictus are considered potential vectors.

Zika virus can be transmitted from pregnant woman to foetus during pregnancy and around the time of delivery. Sexual transmission is also a known route of spread since Zika virus can be isolated in semen. Transmission of virus between men who have sexual contact with men has been identified. Blood transfusion is also considered as a potential route of transmission. There have been multiple reports of blood transmission cases in Brazil, which are currently under investigations.^5,6

Clinical features

The incubation period of Zika virus is not clear. Though most (80%) infected cases are asymptomatic, symptoms typically begin from 2 to 7 days after a bite of an infected mosquito in those who are symptomatic. Clinical features are similar to other arbovirus infections like dengue, including fever, maculopapular rash, conjunctivitis, myalgia, arthralgia, malaise and headache. A few patients may present with retro-orbital pain, anorexia, vomiting, diarrhoea and abdominal pain. These symptoms are usually mild and last for 2 to 7 days. Severe disease requiring hospitalisation is rare and mortality is low. However, neurological complications such as Guillain-Barre syndrome^3,6,7, and acute disseminated encephalomyelitis may also occur.⁶

Pregnant women infected with Zika virus have similar clinical presentations comparing with those who are non-pregnant. It was observed that the number of babies born with microcephaly increased during the outbreaks of Zika virus infections. Substantial new research has strengthened the association between Zika infection and foetal malformations.³ Therefore, foetuses and infants of pregnant women with Zika virus infection should be evaluated for possible infection and neurological abnormalities.^8,9

Differential diagnosis

Many diseases share similar clinical presentation with Zika virus and the differential diagnosis is broad, including dengue, leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, Chikungunya, parvovirus, enterovirus and adenovirus. Clinical suspicion of Zika virus infection is based on clinical features and travel history. Date, place and activity of travelling should be enquired.^9,10 The Centre for Health Protection (CHP) has regular updates on the list of Zika virus affected areas (http://www.chp.gov. hk/en/view_content/43209.html).

Investigations

Since clinical features alone are not diagnostic, laboratory tests should be arranged for clinically compatible cases within two weeks of returning from an affected area.¹⁰ A case is confirmed if either one of the following laboratory criteria is fulfilled⁷:

• detection of Zika virus by nucleic acid testing or virus isolation.
• demonstration of seroconversion or a four-fold or greater rise in antibody titres against Zika virus in acute and convalescent serum samples.

RNA of Zika virus can be identified by reverse transcriptase-PCR (RT-PCR) in blood or urine. RT-PCR can give a negative result if test is done more than 7 days after the onset of disease when the viraemia stage has passed. Zika virus may be detectable for a longer period of time in urine than in blood. To test for Zika virus, prior arrangement with Public Health Laboratory Services Branch of the Department of Health is required. Primary care providers should seek advice from microbiologists in the Hospital Authority or relevant laboratories in order to determine which test is more appropriate. Doctors in private sector may consider referring suspected patients to public hospitals if there is difficulty in arranging the necessary test. At the time of writing, serology for Zika virus is not available in Hong Kong.¹¹

Management

In addition to testing for Zika virus, evaluation for dengue and Chikungunya should also be performed in view of their potential overlap in geographical distribution and clinical features. Notification of suspected or confirmed cases of Zika virus infection to the CHP is required by law.⁷

No specific antiviral agent is available for Zika virus infection. Treatment aims at symptomatic relief, which includes rest, fluid replacement, and medications like analgesics and antipyretic. Aspirin and non-steroidal anti-inflammatory drugs (NSAID) should be avoided until dengue is ruled out to decrease the risk of haemorrhage.⁹

Based on a growing body of preliminary research, there is scientific consensus that Zika virus is a cause of microcephaly and Guillain-Barre syndrome.^2,9 Patients are recommended to seek medical attention if neurological symptoms occur. Pregnant women with a travel history to affected area should be referred to obstetricians to monitor for foetal abnormality.^9,10,11

Patient should be reminded to adopt measures to prevent mosquito bites for 14 days to avoid local spread of infection.

Prevention

Prevention plays an important role in the control of transmission and avoidance of potential complications. There is currently no effective vaccine against Zika virus infection. Preventive measures aim at reducing mosquito bites and spread of virus through sexual contact or blood transfusion. Table 1 illustrates the preventive measures for the general public, travellers to affected areas, pregnant women and women preparing for pregnancy.

DEET containing insect repellent is protective against mosquito bites. However, using such chemicals in infants under 6 months of age is to be avoided. Table 2 shows the precautions of using DEET containing insect repellents.¹²

Zika virus can be found in breast milk, but in very small amount and is unlikely to cause harm to neonates. There are no reports of infants getting Zika virus through breastfeeding up to the time of writing. The current recommendation is to continue breastfeeding since the benefits would likely outweigh the potential risks.^5,11

Conclusion

Zika virus has become widespread since 2015 and poses a significant health threat due to the associations with microcephaly and Guillain Barre syndrome. Primary care providers have an important role in early identification and notification of suspected cases, arrangement of investigations and appropriate referral, provision of symptomatic relief and reinforcement of measures to prevent transmission of the infection.