|Year : 2016 | Volume
| Issue : 2 | Page : 283-287
Zika virus infection: The resurgence of a neglected disease
Tushar Kambale1, Banyameen Iqbal1, Sonali Salve2, Iqra Mushtaq3
1 Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India
2 Department of Otorhinolaryngology (ENT), YCM Hospital, Pune, Maharashtra, India
3 Department of Ophthalmology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India
|Date of Web Publication||1-Mar-2016|
Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
"Zika virus" (ZIKV) is an enveloped, icosahedral virus and has a positive-sense, single-stranded RNA genome approximately 11 kb in length. Genetic studies have revealed three ZIKV lineages: East African, West African, and Asian. Serologic studies and virus isolations have demonstrated that the virus has a wide geographic distribution, spanning East and West Africa, the Americas, Indian subcontinent, and Southeast Asia. ZIKV can cause complications such as Guillain-Barré syndrome, meningitis, meningoencephalitis, and myelitis. During pregnancy ZIKV infection can lead to miscarriages and microcephaly, cerebral calcifications, macular neuroretinal atrophy, and loss of foveal reflex in the fetus. A clinically suspected case of infection with dengue negative result should be further tested for Flavivirus, including Zika. Immunofluorescence or enzyme-linked immunosorbent assay is used to detect specific IgM or IgG antibodies against ZIKV. In cases of positive ZIKV infection, symptomatic treatment should be given after excluding other condition such as dengue, malaria, and bacterial infections.
Keywords: Aedes aegypti, Flavivirus, Zika virus
|How to cite this article:|
Kambale T, Iqbal B, Salve S, Mushtaq I. Zika virus infection: The resurgence of a neglected disease. Med J DY Patil Univ 2016;9:283-7
| Introduction|| |
Zika virus (ZIKV) is a member of the Spondweni sero-complex of the genus Flavivirus and family Flaviviridae. Other mosquito-borne viruses of the same family are yellow fever, dengue, St. Louis encephalitis, West Nile, and Japanese encephalitis. In Northeast Brazil, an alert was issued on May 7, 2015, by the Pan American Health Organization about potential ZIKV transmission.  Between February 1, 2014, and January 17, 2016, around 18 countries and territories in the Americas have confirmed autochthonous circulation of ZIKV. Microcephaly of the newborn is one of the major complications of ZIKV infection during pregnancy. As of epidemiological week 1 of 2016, there were 3530 microcephaly cases recorded including 46 deaths in Brazil compared to an annual average of 163 microcephaly cases between 2010 and 2014. 
| History|| |
The literal meaning of Zika is "overgrown" in the Luganda language spoken by the natives of Uganda. It was first isolated from the overgrown lush forests of Uganda called "Zika forest" from a sentinel rhesus 766 macaque monkey in 1947. A year later in 1948, it was also isolated from Aedes africanus mosquitoes in the same forest during research on jungle yellow fever. , Serologic studies showed that humans could also be infected.  Transmission of ZIKV from Aedes aegypti mosquitoes to mice and monkey was demonstrated in the laboratory in 1956.  Later on ZIKV was also isolated from humans in Nigeria in 1968. , After that serologic studies and virus isolations have demonstrated that the virus has a wide geographic distribution, including Eastern and Western Africa, the Indian subcontinent, Southeast Asia, and most recently Micronesia. ,,, Subsequently, an outbreak broke out in French Polynesia with 10,000 cases in 2013 out of which approximately 70 cases showed neurological (Guillain-Barré syndrome, meningoencephalitis) or autoimmune (thrombocytopenic purpura, leukopenia) complications. These complications are due to primary or secondary co-infection with other flaviviruses, especially dengue virus. Vector A. aegypti and Aedes polynesiensis were responsible for this transmission. , Sporadic cases of ZIKV infection are also reported since last few years in other countries such as Thailand, Cambodia, Indonesia, and New Caledonia. In February 2014 in Chile, a case of ZIKV infection was detected which coincided with the presence of other foci of transmission in the Pacific Islands: French Polynesia, New Caledonia, and the Cook Islands.
| Virology|| |
ZIKV is an enveloped and icosahedral virus and has a positive-sense, single-stranded RNA genome approximately 11 kb in length. It is one of the two viruses enlisted in the Spondweni virus clade.  There are three structural proteins: The capsid, premembrane/membrane, and envelope, and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). In a genetic study three ZIKV lineages: East African, West African, and Asian are identified from NS5 gene nucleotide sequence. Phylogenetic studies indicate that the virus spreading in the Americas is most closely related to the Asian strain, the same which circulated in French Polynesia during the 2013 outbreak. ,
| Clinical Manifestations|| |
Transmission of ZIKV is due to the bite of an infected mosquito of the genus Aedes in urban areas (A. aegypti). Disease symptoms appear after an incubation period of 3-12 days. Infection may present as asymptomatic or with the moderate clinical picture. Symptomatic cases appear acutely with fever, nonpurulent conjunctivitis, headache, myalgia, arthralgia, asthenia, maculopapular rash, edema in the lower limbs and less frequently, retro-orbital pain, anorexia, vomiting, diarrhea, or abdominal pain. These symptoms are self-limiting and last for 4-7 days.  ZIKV can cause complications such as Guillain-Barré syndrome, meningitis, meningoencephalitis, and myelitis as described in French Polynesia outbreak.  In pregnant patient, ZIKV infection can lead to miscarriages and in newborn it may cause microcephaly, cerebral calcifications, macular neuroretinal atrophy, and loss of foveal reflex.  There is only one documented case of sexual transmission of ZIKV in which the virus is transmitted to female partner from male probably through infected semen or direct contact or exchange of body fluid like saliva. 
| Laboratory Detection|| |
During the acute phase (viremic period) detection of viral RNA can be performed on serum by using reverse transcription-polymerase chain reaction for dengue and a generic assay against Flavivirus. A clinically suspected case of infection with dengue negative should be further tested for Flavivirus, including Zika. The immunofluorescence or enzyme-linked immunosorbent assay is used to detect specific IgM or IgG antibodies against ZIKV. These tests are positive after 5-6 days of infection or increased antibody titer in paired samples within 2 weeks. As there is cross-reactivity with dengue, yellow fever, or other Flavivirus, confirmation of positive results with plaque reduction neutralization test showing at least a four-fold increase in the titer of neutralizing antibodies to ZIKV is recommended. Hence, considering the cross-reactivity between Flavivirus and previous dengue infection, serology results should be interpreted cautiously.
| Case Management|| |
In cases of ZIKV infection, symptomatic treatment should be given after excluding other severe condition such as dengue, malaria, and bacterial infection. No vaccine or specific antiviral treatment for ZIKV infection is available yet. Treatment includes symptomatic and supportive care, and the use of acetaminophen or paracetamol to relieve fever and antihistamines to control pruritus. Aspirin should be avoided due to the risk of bleeding and developing Reye's syndrome in children younger than 12 years of age. Patients should drink plenty of fluids to replenish fluid lost from sweating, vomiting, and other insensible losses  [Table 1].
|Table 1: Summarizing clinical aspects: Presentation, diagnosis and treatment|
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Recently, an Indian biotech firm from Hyderabad has claimed to produce two candidate vaccines for ZIKV. Both the candidate vaccines are awaiting animal and human trials before a decision on their suitability for use in public health can be taken. 
| Patient Isolation|| |
Patients should avoid being bitten by Aedes mosquitoes during the 1 st week of illness (viremic phase). Staying under a bed net or remaining in a place with intact window/door screens is highly recommended. Physicians or health care workers who attend to ZIKV infected patients should protect themselves against mosquito bites by using insect repellent (IR3535 or Icaridin) and wearing long sleeves and full pants. 
| Prevention and Control Measures|| |
An effective and operational integrated management strategy for the prevention and control of dengue provides the basis for adequate preparedness to ZIKV. Participation and collaboration at all levels of government and of health, education, environment, social development, and tourism agencies and nongovernmental organizations and private organizations are needed to control this virus. Mosquito control can interrupt the transmission of vector-borne viruses, such as dengue, Zika, and chikungunya. 
| Integrated Vector Management|| |
Integrated vector control measures should be instituted to prepare against ZIKV. Environmental management or source reduction to eliminate vector breeding sites in each household and in common areas of districts and cities (e.g., parks, schools, cemeteries, etc.) will prevent or minimize vector propagation and human contact with the vector mosquito. Mosquitoes should be eliminated within a radius of at least 400 m around from high-risk areas where people concentrate (e.g., schools, transport terminals, hospitals, health centers, etc.). Spraying by adequately trained personnel following internationally accepted technical guidelines should be adopted to remove infected adult mosquitoes. These measures will effectively interrupt transmission and buy time to consolidate the removal of larval breeding sites. Selecting appropriate insecticide, maintaining and using spraying equipment, and ensuring intensified monitoring are essential to achieve the greatest impact in the shortest time. 
| Personal Prevention Measures|| |
Potassium permanganate, ether, and temperatures >60°C are more effective against the ZIKV than 10% ethanol.  Patient infected with dengue, chikungunya, or ZIKV should minimize contact with the vector to prevent the spread of the virus and therefore the disease. The patient should rest under mosquito nets (bed nets), treated with or without insecticide, and cover the extremities. Application of repellents containing DEET, IR3535, or Icaridin to exposed skin or clothing in accordance with the instructions should be advised. Use of wire-mesh screens on doors and windows will keep infected mosquitoes away from dwellings. Health education for patients, family members, and the community to minimize disease transmission and vector control should be done. 
| Travelers|| |
Prior to departure, health guidelines advise travelers heading to any country with documented circulation of dengue, chikungunya, and/or ZIKV to take the necessary measures to protect themselves from mosquito bites. Travelers should be made aware of the symptoms of dengue, chikungunya, or ZIKV in order to assist them in identifying it promptly during their trip. This advice could be relayed through proper channels of communications. Travelers returning home should be briefed that if they suspect they have dengue, chikungunya, or ZIKV they should contact their health care provider for proper care.  These instructions should be thoroughly followed in order to prevent the spread of this virus.
In areas where active transmission is ongoing, humans are the primary amplifying hosts.  About 80% of people infected are asymptomatic. Severe disease requiring hospitalization is uncommon, and the infection is rarely fatal.
However, special travel precautions should be observed during pregnancy. This involves avoidance of travel to areas where local transmission of ZIKV virus is ongoing since during the current outbreak in Brazil the virus RNA has been identified in tissues from infants with microcephaly and from fetal losses in women.  In case of inadvertent exposure of pregnant women to regions of local transmission, evaluation for possible congenital infections should be undertaken. Countries and territories with documented local transmission reported to the Pan American Health Organization are shown in [Figure 1]. 
|Figure 1: Countries and territories with documented local transmission of Zika virus infection reported to the Pan American Health Organization — Region of the Americas, 2015-2016|
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| Implications for Asian Countries|| |
In the Asian region, the already known primary mosquito vectors are A. aegypti and/or Aedes albopictus, although several geographically distinct mosquito vectors may be responsible for the transmission of ZIKV.  Therefore, further studies are needed to ascertain other primary and secondary mosquito vectors which may be responsible for ZIKV transmission. Studies may provide further information about the spread of the Asian lineage virus and clues as to why certain geographical areas are more vulnerable. Robust surveillance systems are needed to understand the epidemiology of ZIKV infection to enable health authorities to cope with the threat of the present pandemic and set up an early warning system for future outbreaks.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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