Zika Virus: An Emerging Global Pandemic

Abstract

Zika virus is a virus that has been known to cause human illness for more than half a century, but it has only recently emerged as a global pandemic. WHO has declared this pandemic as a public health emergency of international concern in February 2016. The Zika virus disease is caused by a virus transmitted by Aedes mosquitoes, which are found in heavy populations in most tropical countries, including India. The real threat that the virus poses is not due to the acute febrile illness but due to the possible effects on the growing fetus and the postulated association with neurological illnesses like Guillian-Barre Syndrome. Though no cases of Zika virus disease have been reported in India as yet, India remains very much susceptible to the disease due to its nonimmune population, heavy Aedes density in most areas, and a growing international traveler community. Hence, all health care providers in India need to be aware of the illness and appropriate preventive measures. Pregnant women and infants are groups that need specific protection and care. The Ministry of Health and family welfare has recently released the guidelines on the Zika virus disease.

Introduction

Zika virus is an emerging mosquito-borne virus. It was first identified in Uganda in 1947 in rhesus monkeys through a monitoring network of sylvatic yellow fever. Its name comes from the Zika Forest of Uganda, where it first isolated.¹

It was subsequently identified in humans in 1952 in Uganda and the United Republic of Tanzania. Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia, and the Pacific.²

The virus belongs to the Genus Flaviviridae and it is closely related to the Dengue virus. Its principal vector is the Aedes mosquito, which usually bites during the morning and late afternoon/evening hours. Its reservoir is not known, though serological evidence has been found in West African monkeys and rodents.^2,3

Epidemiology

Zika virus is a member of the virus family Flaviviridae and the genus Flavivirus. It is transmitted to people through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions, which also transmits dengue, chikungunya and yellow fever.⁴ It has also been isolated from A. africanus, A. coargenteus, A. luteocephala, A. vitattus and A. furcifer.⁵

There are reported cases of possible sexual transmission as well as vertical perinatal transmission.⁶ Like other flaviviruses, it could potentially be transmitted by blood transfusion and several affected countries have developed strategies to try and screen blood donors.⁷

Zika virus disease outbreaks were reported for the first time from the Pacific in 2007 and 2013 (Yap and French Polynesia, respectively), and in 2015 from the Americas (Brazil and Colombia) and Africa (Cape Verde). In addition, more than 13 countries in the Americas have reported sporadic Zika virus infections indicating rapid geographic expansion of the Zika virus.⁸

So far, the following countries have reported the Zika virus: Brazil, Barbados, Bolivia, Columbia, Dominican Republic, Ecuador, El Salvador, French Guyana. Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, St Martin, Suriname, Virgin Island, and Venezuela.⁹ Due to the ongoing spread of the virus, more countries are likely to be affected.

The first human cases of Zika virus infection were reported in Nigeria in 1954. A few outbreaks have been reported in tropical Africa and in some areas in Southeast Asia.¹⁰ There have been no documented cases of Zika virus in the Indian subcontinent, though antibodies to Zika have been found in healthy people in India which could indicate past exposure, or more likely, cross-reaction with other flaviviruses.¹¹

Zika virus had spread to Southeast Asia by 1945. In 1977-1978, it was described as a cause of fever in Indonesia.¹²

In 2007, the first major outbreak, with 185 confirmed cases occurred in the Yap Islands of the Federated States of Micronesia.¹³ This was also the first time Zika fever had been reported outside Africa and Asia. Before the Yap Island outbreak, only 14 human cases had ever been reported.¹⁴

Zika virus has now rapidly spread throughout South and Central America, reaching Mexico in November 2015.¹⁵ It has appeared sporadically in travelers to the United States and Europe but has not established person to person spread in those areas.¹⁶

In May 2015, Brazil officially reported its first 16 cases of the illness¹⁷, following which thousands were infected. Possibly, the most disastrous consequence of this rapid spread has been 2,400 cases of microcephaly and 29 infant deaths in Brazil in 2015.¹⁸

Due to the outbreak which started in Brazil in 2015, the World Health Organization declared it a Public Health Emergency of International Concern in February 2016.¹⁹

Effects On The Fetus

In November 2015, the Brazilian Health Ministry described a connection between the Zika virus and newborn microcephaly. Two cases of severely affected babies in Northwestern Brazil were described, in whom amniocentesis had confirmed the presence of the Zika virus in the amniotic fluid.²² Antenatal ultrasound imaging showed both fetuses to have microcephaly. One of the fetuses was also found to have calcifications in their eye and microphthalmia. Since then the evidence for the connection between Zika infection in pregnant women and newborn microcephaly has grown stronger, with at least 2,400 suspected cases of microcephaly in the country in 2015 as of 12 December, and 29 fatalities.^24,25 Brain abnormalities reported in infants with microcephaly and laboratory-confirmed congenital Zika infection include microcephaly and disrupted brain growth. A report of 35 infants with microcephaly who was born during an outbreak of Zikus virus infection in Brazil in 2015 described the following brain abnormalities: intracranial calcifications, ventriculomegaly, and neuronal migration disorders (lissencephaly and pachygyria). Other anomalies included congenital contractures and clubfoot. An important distinction is that neither these infants nor their mothers had laboratory-confirmed Zika virus; however, most of the mothers (~75%) reported symptoms consistent with the Zika virus.²⁰

For infants diagnosed with microcephaly, head size correlates with underlying brain size. However, these measurements do not consistently predict long term sequelae. Neurologic sequelae may include seizures, vision or hearing problems, and developmental disabilities. Symptoms vary with the extent of brain disruption.²⁰

No treatment is currently available for the Zika virus infection. Care for these infants is focused on diagnosing and managing conditions that are present, monitoring the child’s development over time, and addressing problems as they arise.

Clinical Features

The incubation period of the Zika virus disease is approximately three to 12 days after the bite of an infected mosquito. Most of the infections remain asymptomatic (between 60 to 80%).

When symptomatic, the infection is usually mild and characterized by a short-lasting self-limiting febrile illness of 4-7 days duration without severe complications and a low hospitalization rate. Deaths have not been reported.²⁰

The main symptoms are macular or papular rash, fever, arthralgia, non-purulent conjunctivitis/conjunctival hyperemia, myalgia, and headache. The maculopapular rash often starts on the face and then spreads throughout the body. Less frequently, retro-orbital pain and gastro-intestinal signs are present.²¹

These are typical of most arboviral illnesses, like dengue, and don’t help in differentiating cases of Zika from other arboviral illnesses.

During the recent outbreaks in French Polynesia and Brazil in 2013 and 2015 respectively, potential neurological and auto-immune complications of Zika virus disease were reported. Also in Brazil, a simultaneous increase in the incidence of Zika virus infections in the general public as well as an increase in babies born with microcephaly has been observed. This has led to the postulation that Zika virus infection during pregnancy can cause microcephaly in the baby, though further research is needed and is underway to fully elucidate the nature of this causation.^22,23

Differential Diagnosis

The differential diagnosis for Zika virus infection, based on its clinical features, is broad. In addition to dengue, other considerations include leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, and parvovirus, enterovirus, adenovirus, and alphavirus infections (e.g., Chikungunya, Mayaro, Ross River, Barmah Forest, O'nyong-nyong, and Sindbis viruses)."²⁶

Diagnosis

The diagnostic tests for the Zika virus are not as yet available in India. In the Americas and other endemic countries, the Zika virus is diagnosed through PCR (polymerase chain reaction) and virus isolation from blood samples. However, the period of viremia can be short and it is recommended that RT-PCR testing be done on serum collected within 1 to 3 days of symptom onset or on saliva or urine samples collected during the first 3 to 5 days.²⁷

Diagnosis by serology is unreliable due to cross-reacting antibodies with other flaviviruses such as dengue, West Nile, and yellow fever.

WHO Recommendations

On 17 January 2016, the Pan American Health Organization (PAHO), the regional office of the United Nations' World Health Organization, considering the increased number of cases of congenital anomalies, Guillain-Barré syndrome, and other neurological or autoimmune syndromes in Zika-affected areas, recommended that its member states "establish and maintain the capacity to detect and confirm Zika virus cases, prepare healthcare facilities to respond to possible increase demand of specialized care for neurological syndromes, as well to strengthen antenatal care".³⁰ After WHO declared the Zika virus as a global health emergency in February 2016, all countries including India are advised to take measures to contain the spread of the virus.⁹

Infection Control, Personal Protection And Prevention³¹

Prevention is solely based on protection against mosquito bites. Aedes mosquitoes have diurnal biting activities in both indoor and outdoor environments. Therefore personal protection measures should be applied all day long and especially during the hours of highest mosquito activity (mid-morning, late afternoon to twilight).

Personal protection measures to avoid mosquito bites should be applied when staying in risk areas by:

• using repellents containing DEET, picaridin, oil of lemon eucalyptus (OLE), or IR3535 and wearing long-sleeved shirts and long pants especially during the hours of highest mosquito activity. Repellent use must be strictly done in accordance with the instructions indicated on the product label. For newborn children under three months of age, repellents are not recommended.

• using long-lasting insecticidal treated mosquito bed nets

• keeping accommodations are adequately screened or air-conditioned

• removing mosquito breeding sites in close outdoor/indoor premises by eliminating standing water, repairing septic tanks and using screens on doors and windows

• Travellers, especially children, pregnant women, and people with immune disorders or severe chronic illnesses, should consult their doctor or seek advice from a travel clinic to receive personalized recommendations on the use of repellents and protection before traveling;

• Similar protective measures apply to the asymptomatic patients in order to prevent transmitting the disease to non-infected mosquitoes.

Ministry Of Health And Family Welfare, Government Of India Guidelines On Zika Virus Disease⁹

• The Ministry of Health and Family Welfare has advised enhanced surveillance through the Integrated Disease Surveillance Programme (IDSP) which would involve tracking clustering of acute febrile illness if any, among those who traveled to areas with ongoing transmission in the 2 weeks preceding the onset of illness. Clustering of cases of microcephaly among newborns and reporting of Guillain Barre Syndrome would also be undertaken.

• All the International Airports will display information to travelers on Zika virus disease and would have a quarantine/isolation facility for returning travelers with febrile illness.

• National Centre for Disease Control (NCDC), Delhi, and National Institute of Virology (NIV), Pune, have been designated as the nodal agencies providing laboratory diagnosis of the Zika virus disease. Ten additional laboratories would be strengthened to expand the scope of laboratory diagnosis.

• RT- PCR test would remain the standard test. As of now, there is no commercially available test for the Zika virus disease. Serological tests are not recommended.

• The state health departments will promote increased awareness among clinicians including obstetricians, pediatricians and neurologists about Zika virus disease and its possible link with adverse pregnancy outcome (foetal loss, microcephaly)

• Augmented measures for vector control would be taken

• Travel Advisory for public

• Non-essential travel to the affected countries to be deferred/canceled

• Pregnant women or women who are trying to become pregnant should defer/cancel their travel to the affected areas.

• All travelers to the affected countries/areas should strictly follow individual protective measures, especially during day time, to prevent mosquito bites (use of mosquito repellant cream, electronic mosquito repellants, use of bed nets, and clothing that appropriately covers most of the body parts).

• Persons with co-morbid conditions (diabetes, hypertension, chronic respiratory illness, Immune disorders, etc) should seek advice from the nearest health facility, prior to travel to an affected country.

• Travelers having febrile illness within two weeks of return from an affected country should report to the nearest health facility.

• Pregnant women who have traveled to areas with Zika virus transmission should mention their travel during ante-natal visits in order to be assessed and monitored appropriately.

Treatment

Zika virus disease is usually relatively mild and requires no specific treatment. People sick with the Zika virus should get plenty of rest, drink enough fluids, and treat pain and fever with paracetamol. If symptoms worsen, they should seek medical care and advice. There is currently no vaccine available.

Some authorities have recommended against using aspirin and other NSAIDs as these have been associated with hemorrhagic syndrome when used for other flaviviruses. Additionally, aspirin use is generally avoided in children when possible due to the risk of Reye syndrome.²⁹

Zika virus had been relatively little studied until the major outbreak in 2015, and no specific antiviral treatments are available as yet. Advice to pregnant women is to avoid any risk of infection so far as possible, as once infected there is little that can be done beyond supportive treatment.