Zika Virus: Symptoms, Diagnosis, Prevention And Indian Scenario

Microcephaly

Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes. Clinical signs of Zika virus infection can be acute onset low-grade fever with rash, notably small joints of hands and feet, or conjunctivitis (non-purulent). Congenital Zika virus infection is associated with anomalies such as congenital microcephaly (along with other developmental problems among infants born to women infected during pregnancy), Guillain-Barré syndrome, myelitis, and meningoencephalitis (Besnard M et al. 2016).

Since its detection in Brazil in 2015, Zika virus has emerged as a growing concern, it is endemic in parts of Africa, has been reported in South East Asia and there is an ongoing Zika virus outbreak in the Americas, the Caribbean, and the Pacific.

Microcephaly

The World Health Organization (WHO), the United States Centers for Disease Control and Prevention, and other scientific groups have concluded that the Zika virus can cause microcephaly. In some cases, congenitally infected offspring of women with first or second trimester Zika virus infection have a normal head circumference at birth but subsequently develop microcephaly in the first year of life. Definition of microcephaly given by WHO is: Occipitofrontal circumference (head circumference) greater than two standard deviations below the mean or less than the third percentile based on standard growth charts for sex, age, and gestational age at birth.

Adverse Pregnancy Outcomes

Adverse pregnancy outcomes include miscarriage, stillbirth and impaired fetal growth.

Pregnancy Management

There is no specific treatment known to cure ZIKV infection. Its management includes rest and fluids intake to prevent dehydration and medicines are administered to relieve pain and fever. The World Health Organization (WHO) has issued initial guidance for infected persons and their families. Ultrasound is the major screening method for congenital Zika virus infection. Magnetic resonance imaging is more sensitive for diagnosis of fetal brain abnormalities. In women infected early in pregnancy, ultrasound findings associated with fetal infection may be detected as early as 18 to 20 weeks of gestation but are usually detected in the late second and early third trimesters of pregnancy. The United States Centers for Disease Control and Prevention (CDC) suggest fetal ultrasound examination every three to four weeks to look for signs of congenital Zika virus infection and monitor fetal growth in pregnant women with laboratory evidence of recent Zika virus infection. If the ultrasound report shows something not normal, amniocentesis for diagnosis of fetal infection should be considered.

Delivery

Timing and route of delivery are determined according to routine obstetric policies and standards. The appropriate location for delivery should be decided by late third trimester

Adverse Pregnancy Outcomes

Breast Feeding

Transmission of Zika virus through breast milk has not

been reported [42], although the virus has been detected

Breast Feeding

Transmission of Zika virus through breast milk has not

been reported [42], although the virus has been detected

Breast Feeding

Transmission of Zika virus through breast milk has not

been reported [42], although the virus has been detected

Breast Feeding

Transmission of Zika virus through breast milk has not

been reported [42], although the virus has been detected

Breast Feeding

Transmission of Zika virus through breast milk has not

been reported [42], although the virus has been detected

Breast Feeding

There are no reported cases of transmission of Zika virus through breast milk, although the virus has been detected in breast milk in some studies (Blohm GM et al, 2018).

Diagnosis

The diagnosis of Zika virus infection should be suspected in individuals with typical clinical

manifestations and relevant exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria) The differential diagnosis of Zika virus infection includes: Dengue fever, Chikungunya, Parvovirus, Rubella, Measles, Leptospirosis, Malaria, Rickettsia infection, group A Streptococcus. Health care providers should screen pregnant woman for possible exposure to Zika virus. Mother has one or more of the symptoms or she is residing in or travelled to an area where mosquito-borne transmission of Zika virus infection has been reported. Serum and urine are the primary diagnostic specimens; whole blood is an approved specimen for some nucleic acid tests. For individuals presenting more than 14 days after persistent symptoms, blood and urine tests for detection of Zika virus RNA should be performed. Any positive result establishes a diagnosis of Zika virus infection and in such cases no further testing is done. Negative results do not exclude the chances of infection and Zika virus serologic test should be done. The diagnostic approach is different in pregnant and non-pregnant women because Zika virus RNA can persist longer in a pregnant woman’s serum and because of the potential for congenital infection. The risk of transmission to unborn child is there throughout the pregnancy in both symptomatic and asymptomatic mothers.

Prevention

It is suggested that pregnant women should not travel to areas where mosquito transmission of Zika virus is well acknowledged. Protective measures should be taken to avoid mosquito bite as well as sexual transmission of the virus, stick to specific directions regarding blood donation and standard infection precautions. No vaccine is there for prevention of Zika virus infection, but a vaccine is under development.

Pregnancy Management

Indian Scenario

Since 2013, with the first reported Zika virus (ZIKV) outbreak in the Marquesas Islands and its subsequent spread to Brazil in May 2015, health agencies in India have been on alert and kept a watch on the Zika situation in India. There is an anticipation that ZIKV outbreak in India is possible due to presence of the vector-Aedes aegypti mosquitoes and the susceptible host. On May 15, 2017, the Ministry of Health and Family Welfare, Government of India, reported three laboratory-confirmed cases of ZIKV disease from Bapunagar area, Ahmedabad, Gujarat, India. Before this declaration, India was in WHO category-4 (virus may be present, but no notified cases documented), but with these three confirmed cases, India has shifted to WHO category-2. With recent confirmation of more Zika cases from different parts of India, concerns over spreading awareness and prevention of spreading of disease is required.

As evident from the present cases, Zika may not be a recent introduction in India. In 1954, National Institute of Virology (NIV), Pune (then Virus Research Centre), had tested samples from Bharuch district, which showed ZIKV antibody detection in 16.8 per cent of the samples^. However, due to high cross-reactivity of ZIKV with dengue virus (DENV) and other flaviviruses, it was difficult to confirm Zika virus infection in India based on serology. Cases detected did not reveal any travel history to ZIKV endemic region, suggesting that the ZIKV is not a recent introduction into the country.

It is difficult to confirm Zika infection (out of acute phase of 4-5 days) by serology, due to a very high cross-reactivity with DENV. In such a situation, performing serology is not advised where high false positivity will create panic. At present, only a few commercial serology kits are available. It is difficult to ascertain whether there will be congenital disabilities in children born to ZIKV-infected women or with history of infection. It is so far not feasible to screen all asymptomatic pregnant women by molecular tests. Now, that the presence of ZIKV in the country is confirmed, microcephaly may be made a notifiable disease in the country to indirectly estimate the burden caused by ZIKV.

Need for Research

Research is required to understand the ZIKV natural cycle in India and several questions need to be addressed. The virus has lived a ubiquitous life for decades in tropical and equatorial zone and has also not shown any dramatic evolutionary mutations, but the vector biology and pathogenesis of the ZIKV need to be better understood. Zika and microcephaly screening should ideally be made mandatory for pregnant women in collaboration with hospitals and laboratories across the country, which will help us know the burden of ZIKV in India.

Delivery

These mosquitoes breed throughout the year especially in stagnant water sources, but the density is very high during monsoon because of availability of more breeding sites. High humidity and optimal temperature support them in laying eggs every 3-4 days. The most effective and long-term preventive and control measure for Ae. aegypti as recommended by the authorities is source reduction which requires community participation.

Thus, to estimate the extent of ZIKV impact in India, a long-term surveillance network, active participation of the concerned health authorities and communities is needed.

 

Figure 1. WHO Zika Virus Research Agenda Implementation Framework

Problem Statement

Based on previous studies, it is observed that ZIKV, when first discovered, was a relatively benign disease. Currently more studies are being conducted on this subject and link of ZIKV with microcephaly and Guillain-Barré syndrome has been established by many scientists. There is a great amount of medical research regarding ZIKV is available but caring science research on the topic is still lacking to some extent. As the treatment options are very limited, the focus lies mostly on prevention and control of the infection before it spreads more. Therefore, there is a need for qualitative studies to explore the needs, attitudes and practices of women, men and healthcare service providers related to pregnancy prevention, abortion care, pregnancy care, and care for children affected by ZIKV.

Aim of the research

To study the attitude and practices of people towards ZIKV disease.

Sampling Method

Before the study started, a contact in India was established, the contact person was informed regarding the purpose of study and a variety of men, women and health professionals above the age of 18 years were interviewed. The participants who were not able to provide written consent and who did not align with the aim of the study were tried to be excluded. Research was conducted at accessible houses, colleges and health centres. Most current available Census Data from the year 2011 was used to estimate the number of households in the sampling frame. Randomisation of sampling is used so that the bias can be reduced, this is a method based on positivist paradigm.

Research Design and Technique

For this study, a qualitative approach based on structured interviews was used. Qualitative interviews are a suggested method to conduct research based on people’s living experiences, attitudes and practices. Research questions (Appendix 1) were asked from the people participating in the study after taking their written consent. Analysis of the responses is done using qualitative approach and representation using tables is included. The responses collected in hard copy were entered in electronic form and with the help of Microsoft excel tool, data analysis was done. Based on the analysis, results are reported in percentage form and conclusion is drawn from it.

Breast Feeding

Ethical Considerations

The ethical consideration in qualitative research helps to ensure that the research is thorough and accurate (Thomas & Magilvy, 2011). E. Thomas & Magilvy,2011 lists four ethical principles that are of importance while conducting research on this level which includes freedom, integrity, confidentiality and anonymity of the participants. While conducting the research, the participants were informed with the aim of the study and that they are not under any obligation to answer. Written consent was taken from the participant before asking research questions. The information provided by the participants will be handled with care and the data will be used for the ongoing study only. It will not be used for anything else and will not be kept for future studies.

Many households, colleges and health centres were approached for the structured interviews. A total of 270 participants gave full response to the questions asked in the interview.

Demographics

Characteristics of the sample

Sample Size, N = 270

Table 1

Age	No. of Individuals
18-28 yrs.	40
28-38 yrs.	110
38-48 yrs.	80
48 yrs. and above	40
Total	270

Reported Number of Pregnant Women

Pregnant women are at a very high risk of getting infected by ZIKV and therefore protecting them should be at the top in the priority list.  Studies have shown that ZIKV infection during pregnancy is the cause of congenital malformations in unborn baby, including microcephaly and other severe brain defects, and other adverse outcomes. This question was included to have an idea on the number of pregnant women and their responses. 5.5 % of the respondents were pregnant (Table 2).

Table 2

Gender	No. of Individuals
Male	120
Female	149
Pregnant, if Female	15

Zikv Health Communication

The purpose of including questions based on health communication of ZIKV was to determine how people are acquiring information about the disease, which sources of are most relevant for people to spread ZIKV awareness, and what additional information needs to be circulated.

Question – Which sources gave you information about ZIKV?

Table 3

Information Source	No. of Individuals
Radio/Television	149
Internet	57
Newspaper	15
Social Media	12
Relatives	7
Others	13
No Answer	17
Total	270

Most people get information about the disease and its prevention from television and radio (around 55 % of the respondents). Internet is the other prominent source, newspaper, social media etc are also referred by few respondents. Around 6% respondents did not choose any source. Those who marked others as their response, mentioned government sources, magazines, journals etc to name a few as the source which gave information about ZIKV (Table 3).

Question-What additional information would you like to receive regarding the ZIKV disease?

Table 4

Additional Information Needed	No. of Individuals
Signs and Symptoms	123
Prevention	69
Treatment Options	31
Cause	24
Risks	19
No Answer	3
Any Other	1
Total	270

Most of the respondents wanted to receive additional information about ZIKV signs and symptoms (45.56%) and prevention (25.56%), some wanted to get information about the treatment options (11.48%), cause (8.9%), and risk category (7%) (Table 4). One person who marked other wanted to know the long-term effects of the disease.

Diagnosis

Knowledge Regarding Zikv

Prevention methods should be adopted by the population primarily to avoid the risk of getting ZIKV infection especially the pregnant women and small children need extra care. Therefore, the questions regarding knowledge of ZIKV infection and mosquito prevention methods used by people were included in the questionnaire.

Importance of ZIKV knowledge

Question – Do you think ZIKV is an important issue?

Table 5

Response	No. of Individuals
Yes	223
No	32
No Answer	6
Don’t Know	9
Total	270

82.59% respondents believe that ZIKV is an important concern whereas 11.85% stated “No”, 3% “don’t know” and 2% “no answer” as their opinion. (Table 5).

Mode of transmission, risks of disease and symptoms

Question- Which are the different modes of transmission of ZIKV?

For this question, respondents were asked to mark all possible options as per their knowledge.

Table 6

Mode of transmission	No. of Responses
Mosquito Bite	189
Sexual Transmission	45
Passed from mother to child	23
Others	0
Don’t know	40
No Answer	3

63% response was for mosquito bite, sexual transmission mode had 15% response whereas only 7.6% response was reported for it can pass from mother to child (Table 6).

Prevention Methods

Question-Is there a vaccine for ZIKV?

Table 7

Responses	No. of individuals
Yes	24
No	177
Don’t Know	64
No Answer	5
Total	270

65.9% of individuals were aware that no vaccine is available for ZIKV, 23.7% said they “don’t know” whether ZIKV vaccine is available or not (Table 7).

Question-What are the symptoms of ZIKV infection?

Table 8

Responses	No. of Individuals
Fever	109
Headache	26
Other	39
Don’t Know	96
Total	270

Regarding the symptoms of ZIKV disease, 40% respondents stated “fever”, 35.5% accepted that they “don’t know”.  (Table 8). In addition, 14.4% participants reported “other” symptoms, which were not correct, for example, AIDS. Very few people responded with other common ZIKV symptoms such as: pain in joints, rash and conjunctivitis. Rarely people reported that a person infected with ZIKV might not show any such symptoms.

Question- If a pregnant woman has ZIKV disease, what are the risks for her unborn baby?

Respondents were asked to give multiple options if they are aware of more than one risks.

Table 9

Response	No. of Individuals
Microcephaly	23
Abnormality in development	81
Other	38
Don’t know	163

Most people recorded abnormality in development of unborn baby whose mother is affected by ZIKV as a risk, only 7.5% responses were for microcephaly (Table 9). Other risks stated by the respondents include miscarriage, premature birth, brain damage, zika infection.

The Government of India has published an advisory with the prevention and control measures which includes:

• Guidelines on Zika Virus Disease from Ministry of Health and Family Welfare
• Guidelines on Integrated Vector Management for Control of Aedes Egypti mosquitoes
• Fact sheet on Zika Virus Disease
• Vector management for Mosquito

Prevention Measures mentioned in the guidelines are as follows:

• No vaccines exist to prevent Zika Virus Disease
• Prevent Zika by avoiding mosquito bites
• Wear full sleeves shirts and pants
• Sleep under mosquito net
• Sleep in places with window screens or mesh
• Once a person has been infected he/she is likely to be protected from future infection.

Question-What actions can you take to be protected from ZIKV?

Respondents were asked to give multiple measures which they are aware of.

Table 10

Prevention Measures	No. of Responses
Mosquito Repellent	160
Cover and clean items that hold water	190
Wear long sleeved shirts/pants	41
Spray or fumigate home	70

The most frequent actions taken by participants as protection measure from ZIKV were: to use mosquito repellent, cover and clean items that hold water, wear long sleeved shirts/pants and spray fumigate home (Table10).

Prevention

Access to treatment/prevention

Question-Have you accessed resources from your local health department regarding prevention from ZIKV infection?

Table 11

Response	No. of Individuals
Yes	24
No	246
Total	270

91% respondents stated that they have not accessed local health department resources regarding ZIKV prevention (Table 11).

Conclusions

Urban Indians are receiving ZIKV information from various sources, most popular being radio/television and internet, newspapers, social media, and family has also been informative for some of them. There are some additional sources which people have referred in the study like the local health department and family doctor. Many people accepted that they are not accessing local health department ZIKV resources.Most Indians stated ZIKV to be an important issue considering the risks known to them but have moderate knowledge of all the modes of disease transmission. Most of them appropriately understand mosquito bites as a mode of transmission but they are not aware of the fact that ZIKV can cause birth defects in the babies born to those mothers who were infected with ZIKV during pregnancy. However most of Indians are not aware of the term microcephaly. Some of the respondents reported sexual transmission as a mode of ZIKV infection. Furthermore, interview responses indicated that people are not fully aware of all the signs and symptoms of the disease in question. Individuals wanted to get additional information about the symptoms, prevention, and treatment of ZIKV infection.

Awareness regarding mode of transmissions of ZIKV should be the focus of programs, especially Indians are not aware that this disease can be transmitted from pregnant mother to her child. Also, they are not fully aware of the risks caused to the unborn baby if the mother is ZIKAV infected.

Government should telecast advertisements mentioning the details of the disease as most of the Indians are referring to television/radio for information.

People should be advised to go through the advisory published by Government of India for prevention and control of ZIKV.

People are advised to avail the facilities provided by Health Department for vector management.

Government should identify strategies to ensure that the citizens and other stakeholders get accessibility to accurate mosquito management information and can utilise the prevention methods available to them.

References

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Besnard M, Eyrolle-Guignot D, Guillemette-Artur P, Lastere S, Bost-Bezeaud F, Marcelis L….Mallet HP.Congenital Cerebral Malformations and Dysfunction in Fetuses and Newborns following the 2013 to 2014 Zika Virus Epidemic in French Polynesia. (Euro Surveillance 2016)

Centres for Disease Control and Prevention (CDC). Zika Virus: Transmission and Risks. [Online]. [Atlanta (GA)]: CDC; [revised 2017]. Available at: https://www.cdc.gov/zika/prevention/transmission-methods.html

Ministry of Health and Family Welfare, National Guidelines for Zika Virus disease. Available at: https://mohfw.gov.in/media/disease-alerts/national-guidelines-zika-virus-disease

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