Emerging Zika virus infection
Maria Jose Wiseman Pinto
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.
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. The virus has since crossed into the Western Hemisphere, reaching epidemic proportions in Brazil in 2015. 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. 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.
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. This was followed by a second large outbreak in French Polynesia in 2013-2014. Subsequently it spread to the Pacific and continued to circulate through 2015.
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.
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. 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.
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. It has been detected in the human blood as early as 3 days of illness onset up to 2 weeks thereafter. 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.
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. 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.
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.
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.
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.
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.
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.
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 with 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.
Nucleic acid amplification test and plaque reduction neutralization assay although designed are not practical.
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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