Emerging Zika virus infection

 

Article By

 

Maria Jose Wiseman Pinto

 

 

Abstract

Zika Virus disease is caused by an  RNA virus, belonging to the Flaviviridae Family and  is transmitted  by hematophagous  insect vectors. Since its isolation in  1947, human  infections occurred in Africa and Asia. A large outbreak occurred in 2007 in Yap Island of Micronesia. The virus has now stepped into the Western Hemisphere. In May 2015, an outbreak was confirmed in northeast Brazil. The virus has since spread to various countries and territories of the Americas. Clinically, a large number of infections are asymptomatic or may show mild symptoms of fever, rash, conjunctivitis and arthralgia. Increasing evidence suggests a possible link of microcephaly in the newborn following infection in pregnancy and Guillain-Barre Syndrome in adults. Diagnosis is largely clinical and epidemiological. Serological tests are often fallacious due to cross reacting antibodies to other Flaviviruses, especially Dengue virus. There is no vaccine or drug available to prevent or treat Zika Virus disease. Prevention forms the mainstay in containing the disease by proper individual anti mosquito measures. Travel advisory will have to be followed when visiting affected countries.

Introduction

Various arthropod  borne  viruses have troubled mankind for decades, notorious among them being West Nile virus, Dengue virus and Chikun-gunya virus. Zika virus, also an arbovirus, was described in 1947 and caused occasional human infections, until its first outbreak in 2007, thus showcasing its potential as an emerging disease[1]. The  virus  has  since crossed  into  the  Western Hemisphere,  reaching epidemic proportions  in Brazil in 2015[2]. Although the clinical presentation is mild, its probable link to microcephaly in the newborn and Guillain-Barre Syndrome in adults in the recent times, has prompted  health authorities to assess the magnitude of the problem and to define ways to curtail its spread.

 

Historical perspective  and emergence

Zika Virus (ZIKV) was first recognized in 1947, in  Uganda,  when  fever developed in  a  rhesus monkey that had been placed in a cage on a tree platform in the Zika forest[3]. This monkey was a sentinel animal in the Rockefeller Foundation’s program for research on Yellow Fever. The serum of this monkey, when inoculated intracerebrally in mice, induced a cerebral infection. A filterable transmissible agent was isolated from the brain of the mouse, which was later named “Zika Virus.”

A year later, the virus was isolated from the Aedes africanus mosquitoes, trapped  in the same forest, thereby establishing a transmission cycle involving the mosquitoes and monkeys[4].

From  1951 through  1981, serological evidence of human ZIKV infection was reported in Africa and Asia, including Malaysia, Philippines, Thailand, Vietnam and Indonesia.

The first ZIKV outbreak occurred in Yap Island in Micronesia, in 2007, outside Africa and Asia[1]. This was followed by a second large outbreak in French Polynesia in 2013-2014[5]. Subsequently it spread to the Pacific and continued to circulate through 2015.

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ZIKV was rare in the Western Hemisphere, until May 2015, when the Public Health Authorities of Brazil confirmed an outbreak in Northeast Brazil. The virus has since spread to 22 countries and territories of the Americas; forcing the Pan American Health Organization to issue an alert, declaring Zika virus infection as a public health emergency of international concern[2].

This  virus has  the  potential  to  spread  further across international borders due to the wide prevalence of the mosquito  (Aedes) vector and lack of immunity  among the population.  As of now, the disease has not been reported in India. However, safety concerns have already been issued and the Indian  health authorities have already raised an alert to guard against the spread of this virus. The main concern for caution lies in the fact that the vector (Aedes mosquito) required for its transmission is prevalent in India and is also notorious for its role in transmission of Dengue to the population.

Virology and pathogenesis

ZIKV is classified in the Flavivirus Genus, of the Flaviviridae Family. It is a single stranded RNA virus, enclosed in a capsid and surrounded  by a host membrane  derived lipid bilayer, that  contains envelope proteins E and M. The surface proteins are arranged in an icosahedral symmetry[6]. The virus is killed by potassium permanganate, ether and temperature of more than 6000C, but not effectively neutralized by 10% ethanol.

The virus has two lineages, African and Asian. The African lineage has East and West African clusters. The Asian lineage appears to be spreading, emerging in the Pacific and South America[7].

Information regarding the pathogenesis of ZIKV is scarce but it is thought to replicate initially in the dendritic cells, near the site of inoculation, from where it spreads to the lymph nodes and blood  stream.  Although  Flaviviruses replicate in the cell cytoplasm, ZIKV antigens have been demonstrated in the nuclei[8]. It has been detected in the human blood as early as 3 days of illness onset up to 2 weeks thereafter[9].  It is also detected and remains in the semen for a long time and hence potential for a sexual transmission of the disease as well.

Transmission

ZIKV is transmitted by the bite of infected female Aedes mosquito, especially Aedes aegypti species. The virus has adapted from an enzootic cycle involving arboreal mosquitoes in Africa to a new urban cycle which includes humans as reservoirs and urban mosquitoes as vectors. Some evidence suggests that the virus can also be transmitted to humans  through  blood transfusions,  prenatally and sexually[10]. Although further investigations are required to determine this causality.

Risk Of Zika Virus Importation

The spread of Zika virus infections in the Americas and in the Caribbean constitutes a significant development in the epidemiology of this emerging vector borne disease. Travelers to countries with competent vectors and circulating Zika virus are at a risk of becoming infected through mosquito bites.

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Awareness of the risk of infection among travelers and  clinicians will increase the  number  of reported  travel related ZIKV infections. This is exemplified in the Netherlands, where six cases were reported after a return from Suriname[11].

Health guidelines in india:

At present there have been no cases identified in India however Indian health officials remain in high alert. There is cause for concern since the Aedes mosquito vector is widely prevalent in India. Another cause for concern is that the symptoms of Zika closely resemble that of Dengue, a disease widely prevalent in India, and hence differentiating the diagnosis may become a daunting task.

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Clinical presentation

A majority of individuals infected with Zika virus disease remain asymptomatic (up to 80%). It is a self-limiting disease, with symptoms such as mild fever, fatigue, cutaneous rash, arthralgia and conjunctivitis which last for about two to seven days. Other associated features include headache, malaise, edema  of extremities, retro  bulbar  pain, photophobia,  gastrointestinal disturbances, sore throat, cough and lymphadenopathy. None of these symptoms are specific and are often misdiagnosed as bacterial or other viral infections. Severe form of the disease is uncommon and fatalities are rare but have been reported in a few cases in which deaths have occurred from Zika related complications or sequelae.

ZIKV, microcephaly and Guillain-Barre syndrome: a possible link

A possible causal association between Zika virus infection in pregnancy and microcephaly in the newborn has been under investigation, since October  2015, when  the  Brazilian Ministry  of Health reported an unusual increase in cases of microcephaly after  the  outbreak.  French  Polynesia also reported an increase in cases of CNS malformations following Zika virus infection[11].

A similar association between the virus infection and Guillain-Barre Syndrome in adults has been observed in South and Central America. Cases of neurological manifestations with history of rash illness were evaluated in the Brazil epidemic and it  was observed that  62% of patients  reported symptoms  consistent  with Zika virus infection preceding the onset of neurological symptoms[11].

Laboratory diagnosis

There is no widely available test for Zika infection. In most cases, diagnosis is clinical and epidemiological. Diagnostic  tests  are  PCR based, which detect viral RNA on  acute phase serum samples in the first 3-5 days of illness onset[9].

 

Serological diagnosis can be attempted by detection of specific ZIKV antibodies in serum. However, serological evaluation is limited due to cross reactions within the Flavivirus Genus, especially TC- Apr 2016 - 009 - Zika 1with Dengue. IgM antibodies can be detected as early as 3 days after the onset of illness, while neutralizing  antibodies  develop after 5 days of illness.

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Nucleic acid amplification test and plaque reduction neutralization  assay although designed are not practical.

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Treatment Prevention and Control

No specific vaccines or medications are available to  prevent  or  treat  this  infection.  Fortunately, symptoms are mild and self-remitting, requiring rest, supportive care and fluids as in any other viral infection. Nonsteroidal  anti-inflammatory drugs (NSAID’s)  and Aspirin are to be avoided for the fever and acetaminophen be used instead.

A vaccine may be available in the future and the Indian  company  Bharat  Biotech Ltd. claims it may have the first Zika vaccine. However, this has to be further corroborated.

Prevention and control needs to be directed towards elimination and control of mosquitoes, prevention of mosquito bites and general public awareness.

It is imperative to track clustering of acute febrile illness among those with a history of a travel to affected areas, 2 weeks preceding the onset of illness, as also cases of microcephaly and Guillain- Barre Syndrome.

Travel advisory may be issued to defer visit to affected areas, especially in cases of pregnant women. Travelers visiting affected countries  should necessarily follow individual  protective  measures against mosquito bites. Individuals developing febrile illness on return  from affected areas should report to the health facility.

 

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