The Zika Virus

An Introduction

The Zika virus (ZIKV) outbreak recently in Latin America highlights a tremendous need for a reliable detection and effective prevention approach to control the transmission of ZIKV globally. ZIKV infection is a mosquito-borne disease. The virus is transmitted to people primarily through the bites of a daytime active infected female Aedes species mosquito (Aedes aegypti and Aedes albopictus) (Figure 1). Due to the nature of its infection, ZIKV infection has become a significant public health threat in many devel­oping tropical countries. ZIKV is a member of the Flavivirus genus of the Flaviviridae family. Other viruses found in the same family include dengue viruses (DENV), yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and tick-borne encephalitis virus (TBEV).

ZIKV was initially identified in a rhesus monkey in Uganda in 1947. The name was given after the Zika Forest in Uganda. The first transmission in humans was reported in 1952. Since then, ZIKV outbreaks have been reported in tropical Africa, Southeast Asia and the Pacific Islands. From 2007 to 2016, the virus has spread across the Pacific Ocean to the tropical Latin America where ZIKV epidemic reached pandemic levels in the last two years. There are several ways for ZIKV transmission. It includes ZIKV-infected mosquito bite (majority), mother to child transmission through placenta tissues and via sexual contact (spread by an infected man to his sex partners as the virus remains longer in semen than in the blood).

Symptoms

People infected with ZIKV usually show mild clinical illness. The majority of individuals have minimal symptoms and they rarely die of ZIKV infection. The first symptom of Zika could develop within three to 12 days which is also known as incubation period. The most common symptoms are fever, rash, joint pains and red eyes. Symptoms may also include muscle pain and headache. The diagnosis for ZIKV infection is complicated because the symptoms are not specific and they are hard to be distinguished from other flavivirus infections such as dengue.

ZIKV infection and pregnancy

ZIKV infection has gained immense attention from public health authorities since there is a probable link between ZIKV infection during pregnancy and microcephaly. Microcephaly is a severe birth defect which causes incomplete brain development (Figure 2). Newborn babies diagnosed with microcephaly usually possess abnormal heads. In November 2015, Brazil’s Ministry of Health has reported that there was an unusual 20-fold increase in the number of babies born with microcephaly, with an extensive ZIKV outbreak in the Northeast region. The remarkable spike in the number was associated with the ZIKV outbreak reported in previous months. Evidence has shown that ZIKV remains in the blood stream of an infected individual for about a week. If it occurs in a pregnant woman, the virus can be transmitted to the fetus through placenta tissues. This could potentially lead to neurological defects and induce fetal microcephaly. However, there are no reports showing the transmission of ZIKV through breastfeeding. Therefore, mothers in the ZIKV high risk area are still highly encouraged to breastfeed their babies.

Diagnosis

An ideal diagnostic method for ZIKV infection is based on the nucleotide amplification of ZIKV-specific DNA using polymerase chain reaction (PCR) technique. The presence of ZIKV in human blood can be distinguished by the detection of specific gene sequence (e.g. NS1) found uniquely in ZIKV. This rapid PCR-based diagnostic method can potentially reduce the probability of false positive results arising from cross-reactivity with other flaviviruses.

The serology method used for detection of IgM antibodies elicited by a ZIKV infection is another good option. Serology method such as ELISA or Dipstick have been widely used for diagnostics of diseases because they are easily accessible, relatively cheap and sensitive. Current serology assay is based on the detection of antibodies against flaviviral structural proteins. This is relatively important to discriminate the false positive detection arising from cross-reactivity with others potential flaviviruses infection. As precaution, women who have previously resided or visited a ZIKV affected area during their pregnancy are recommended an ultrasound examination between the 32nd and 35th weeks of gestation. If microcephaly is suspected, the pregnant woman should be referred to a healthcare professional for an appropriate fetal medicine service.

Vaccine Development

Since decades, vaccines have been developed for many other flaviviruses but there is still a lack of safe and effective vaccine for ZIKV. A further acceleration of research in the field of vaccine development for ZIKV is essential especially for pregnant women. Currently, there is an extensive ongoing research on preclinical vaccine trial level. The first phase of clinical trials in humans are expected to be completed before the end of 2016. Both inactivated and live attenuated virus vaccines are conceived to be effective for the protection against ZIKV infection. Additionally, other types of vaccine include subunit vaccine, plasmid DNA vaccine and recombinant vaccine, all of which designed to express ZIKV structural proteins, have been tested for their potency and efficacy in animal models. The immense effort in development of ZIKV vaccine for human use will contribute to effectively control the spread of this potentially devastating ZIKV.

Precautions advice from CDC

People who have travelled to or reside in endemic areas of ZIKV infection are under possible exposure to ZIKV. Center for Disease Control and Prevention (CDC) of the United States has advised travelers to take extra precautions when travelling to the areas with active ZIKV transmission. The precautions suggested include:

• Avoid mosquito bites by wearing long sleeved shirts and trousers

• Use EPA-registered insect repellents (insect repellents containing active ingredients such as DEET, picaridin and IR3535 are safe in pregnancy)

• Sleep in screened (with mosquito nets) and air-conditioned rooms to keep mosquitoes outside

• Pregnant women are advised to avoid traveling to countries with documented or suspected ZIKV epidemics

• Do not use insect repellents on newborn babies

• Dress children in clothing that covers arms and legs

• Men who have traveled to ZIKV suspected area are advised to use effective contraception such condoms for at least 28 days when having sex with his partners

• Pregnant women who have travelled to ZIKV endemic areas for two weeks are recommended to seek healthcare professional for ZIKV assessment.

Due to the non-availability of suitable drugs, those suspected with ZIKV are to take the following steps to relief symptoms: -

• Get plenty of rest

• Drink plenty of water to avoid dehydration

• Take medicine such as acetaminophen or paracetamol to reduce fever and pain

• Pregnant women are advised to refer to healthcare professionals (medical doctors).

References

1. Center for Disease Control and Prevention (CDC). Available from: https://www.cdc.gov/zika/

2. Stagg, D. and H.M. Hurst, Zika Virus and Pregnancy. Nurs Womens Health, 2016. 20(3): p. 299-304.

3. Vogel, G., INFECTIOUS DISEASE. Evidence grows for Zika virus as pregnancy danger. Science, 2016. 351(6278): p. 1123-4.

4. De Carvalho, N.S., et al., Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data. Braz J Infect Dis, 2016. 20(3): p. 282-9.

5. Tripp, R.A. and T.M. Ross, Development of a Zika vaccine. Expert Rev Vaccines, 2016: p. 1-3.

6. Basarab, M., et al., Zika virus. BMJ, 2016. 352: p. i1049.

Dr. Leow Chiuan Yee is currently a senior lecturer at Institute for Research in Molecular Medicine (INFORMM) at Universiti Sains Malaysia. He completed his doctoral study at University of Queensland in Australia. His doctorate research finding brought him an opportunity to receive an Edward Jenner Award conferred by Australian Centre for Vaccine Development. Prior to returning to Malaysia, he worked as a postdoctoral scientist at QIMR Berghofer Medical Research Institute to study the roles of T cells in initiating immunity against severe malaria. Yee’s primary research interest is on the understanding of the molecular basis of immunity associated with infectious diseases. A key focus of his research is to identity potential antigenic targets, and hence to develop the optimal formulations delivery mechanisms for the potential therapeutic vaccines.