Zika Virus Disease Symptoms and Diagnosis

Zika Virus Disease
DR RAMDHAN KUMAR KAMAT
SR IGIMS PATNA

Introduction
• Zika virus is an emerging mosquito-borne virus that was
first identified in Uganda in 1947 in rhesus monkeys
through a monitoring network of sylvatic yellow fever.
• 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.
http://www.who.int/mediacentre/factsheets/zika/en/ accessed on 13/02/2016

• Genre: Flavivirus
• Vector: Aedes mosquitoes (which usually bite during the
morning and late afternoon/evening hours)
• Reservoir: Unknown

History
• Virus isolation in monkeys and mosquitoes, 1947
• The virus was first isolated in April 1947 from a rhesus
macaque monkey that had been placed in a cage in the Zika
Forest of Uganda, near Lake Victoria, by the scientists of the
Yellow Fever Research Institute.
• A second isolation from the mosquito A. africanus followed
at the same site in January 1948.
• When the monkey developed a fever, researchers isolated
from its serum a "filterable transmissible agent" that was
named Zika virus in 1948 with the first published
description in 1952 in the Transactions of the Royal Society
of Tropical Medicine and Hygiene.
https://en.wikipedia.org/wiki/Zika_fever on 13/02/2016

History
• First evidence of human infection, 1952
• Zika virus had been known to infect humans from the results of serological surveys in
Uganda and Nigeria.
• A serosurvey of 84 people of all ages showed 50 had antibodies, with all above 40 years
of age being immune.
• It was not until 1954 that the successful isolation of Zika virus from a human was
published.
• This came as part of a 1952 outbreak investigation of jaundice suspected to be yellow
fever.
• It was found in the blood of a 10 year old Nigerian female with low grade fever,
headache, and evidence of malaria, but no jaundice, who recovered within three days.
• Blood was injected into the brain of laboratory mice, followed by up to 15 mice
passages.
• The virus from mouse brains was then tested in neutralization tests using
rhesusmonkey sera specifically immune to Zika virus.
• In contrast, no virus was isolated from the blood of two infected adults with fever,
jaundice, cough, diffuse joint pains in one and fever, headache, pain behind the eyes
and in the joints.
• Infection was proven by a rise in Zika virus specific serum antibodies.
• A 1952 research study conducted in India had shown a "significant number" of
Indians tested for Zika had exhibited an immune response to the virus, suggesting it
had long been widespread within human populations.

History
• Spread in equatorial Africa and to Asia, 1951-1981
• From 1951 through 1981, evidence of human infection with Zika virus
was reported from other African countries, such as the Central African
Republic, Egypt, Gabon, Sierra Leone, Tanzania, and Uganda, as well
as in parts of Asia including India, Indonesia, Malaysia, the
Philippines, Thailand, and Vietnam.
• From its discovery until 2007, confirmed cases of Zika virus infection
from Africa and Southeast Asia were rare.
• Micronesia, 2007
• In April 2007, the first outbreak outside of Africa and Asia occurred on
the island of Yap in the Federated States of Micronesia, characterized
by rash, conjunctivitis, and arthralgia, which was initially thought to
be dengue, chikungunya, or Ross River disease.
• Serum samples from patients in the acute phase of illness contained
RNA of Zika virus.
• There were 49 confirmed cases, 59 unconfirmed cases, no
hospitalizations, and no deaths.
• More recently, epidemics have occurred in Polynesia, Easter Island, the
Cook Islands, and New Caledonia.

ZIKA OUTBREAK IN THE
AMERICAS AND THE PACIFIC
• An evolving outbreak of Zika virus infections is currently
spreading in the Americas and the Pacific region, coinciding
with an increase in cases of microcephaly and other adverse
outcomes during pregnancy and of Guillain–Barré syndrome
(GBS) in adults.
• On January 22, 2016, CDC activated its Emergency Operations
Center (EOC) to respond to outbreaks of Zika occurring in the
Americas and increased reports of birth defects and Guillain-
Barré syndrome in areas affected by Zika.
• On 1 February 2016 WHO declared a Public Health Emergency
of International Concern (PHEIC) regarding clusters of
microcephaly cases and neurological disorders in some areas
affected by Zika virus.
http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/Pages/index.aspx accessed on 13/02/2016

Areas with active mosquito-
borne transmission of Zika virus
• Prior to 2015, Zika virus outbreaks occurred in areas of
Africa, Southeast Asia, and the Pacific Islands.
• In May 2015, the Pan American Health Organization
(PAHO) issued an alert regarding the first confirmed
Zika virus infections in Brazil.
• Currently, outbreaks are occurring in many countries.
• Zika virus will continue to spread and it will be difficult
to determine how and where the virus will spread over
time.
http://www.cdc.gov/zika/geo/index.html accessed on 13/02/2016

Zika virus disease & India
• Zika virus disease has the potential for further
international spread given the
• Wide geographical distribution of the mosquito vector,
• Lack of immunity among population in newly affected
areas and
• High volume of international travel.
• As of now, the disease has not been reported in India.
• However, the mosquito that transmits Zika virus, namely
Aedes aegypti , that also transmits dengue virus, is
widely prevalent in India.
http://pib.nic.in/newsite/PrintRelease.aspx?relid=136006 accessed on 13/02/2016

Transmission
• Through mosquito bites
• Zika virus is transmitted to people primarily through the bite
of an infected Aedes species mosquito (A. aegypti and A.
albopictus). These are the same mosquitoes that spread dengue
and chikungunya viruses.
• These mosquitoes typically lay eggs in and near standing water
in things like buckets, bowls, animal dishes, flower pots and
vases.
• They prefer to bite people, and live indoors and outdoors near
people.
• Mosquitoes that spread chikungunya, dengue, and Zika are
aggressive daytime biters.
• They can also bite at night.
• Mosquitoes become infected when they feed on a person
already infected with the virus. Infected mosquitoes can then
spread the virus to other people through bites.
http://www.cdc.gov/zika/transmission/index.html accessed on 13/02/2016

Transmission
• Rarely, from mother to child
• A mother already infected with Zika virus near the time of
delivery can pass on the virus to her newborn around the
time of birth, but this is rare.
• It is possible that Zika virus could be passed from a mother
to her baby during pregnancy.
• To date, there are no reports of infants getting Zika virus
through breastfeeding.
• Because of the benefits of breastfeeding, mothers are
encouraged to breastfeed even in areas where Zika virus is
found.
• Through infected blood or sexual contact
• Spread of the virus through blood transfusion and sexual
contact have been reported.
http://www.cdc.gov/zika/transmission/index.html accessed on 13/02/2016

Symptoms
• About 1 in 5 people infected with Zika virus become ill (i.e.,
develop Zika).
• The most common symptoms of Zika are fever, rash, joint pain, or
conjunctivitis (red eyes).
• Other common symptoms include muscle pain and headache.
• The incubation period (the time from exposure to symptoms) for Zika
virus disease is not known, but is likely to be a few days to a week.
• The illness is usually mild with symptoms lasting for several days
to a week.
• People usually don’t get sick enough to go to the hospital, and
they very rarely die of Zika.
• Zika virus usually remains in the blood of an infected person for
about a week but it can be found longer in some people.
http://www.cdc.gov/zika/symptoms/index.html on 13/02/2016

Diagnosis
• It is difficult to diagnose Zika virus infection based on
clinical signs and symptoms alone due to overlaps with
other arboviruses that are endemic to similar areas.
• The US Centers for Disease Control and Prevention (CDC)
advises that "based on the typical clinical features, the
differential diagnosis for Zika virus infection 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)."

Diagnosis
• Zika virus can be identified by RT-PCR in acutely ill patients.
• However, the period of viremia can be short and the World
Health Organization recommends 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.
• The longest period of detectable virus has been 11 days and
Zika virus does not appear to establish latency.
• Later on, serology for the detection of specific IgM and IgG
antibodies to Zika virus can be used.
• IgM antibodies can be detectable within 3 days of the onset of
illness.
• Serological cross-reactions with closely related flaviviruses
such as dengue and west nile fever as well as vaccines to
flaviviruses are possible.
• Commercial assays for Zika antibodies are now available but
have not yet been FDA approved

Diagnosis
• Screening in pregnancy
• The CDC recommends screening some pregnant women even if they do not have
symptoms of infection.
• Pregnant women who have travelled to affected areas should be tested between two
and twelve weeks after their return from travel.
• Due to the difficulties with ordering and interpreting tests for Zika virus, the CDC
also recommends that healthcare providers contact their local health department for
assistance.
• For women living in affected areas, the CDC has recommended testing at the first
prenatal visit with a doctor as well as in the mid-second trimester, though this may be
adjusted based on local resources and the local burden of Zika virus.
• Additional testing should be done if there are any signs of Zika virus disease.
• Women with positive test results for Zika virus infection should have their fetus
monitored by ultrasound every three to four weeks to monitor their anatomy and
growth

Diagnosis
• Infant testing
• For infants with suspected congenital Zika virus disease, the CDC
recommends testing with both serologic and molecular assays such as
RT-PCR, IgM ELISA and plaque reduction neutralization test (PRNT).
• Newborns with a mother who was potentially exposed and who have
positive blood tests, microcephaly or intracranial calcifications should
have further testing including a thorough physical investigation for
neurologic abnormalities, dysmorphic features, splenomegaly,
hepatomegaly, and rash or other skin lesions.
• Other recommended tests are cranial ultrasound, hearing evaluation,
and eye examination.
• Testing should be done for any abnormalities encountered as well as
for other congenital infections such as syphilis, toxoplasmosis, rubella,
cytomegalovirus infection, lymphocytic choriomeningitis virus
infection, and herpes simplex virus.

Prevention
• The virus is spread by mosquitoes, making mosquito avoidance an
important element to disease control.
• The US Centers for Disease Control (CDC) recommends that individuals:
• Cover exposed skin by wearing long-sleeved shirts and long pants.
• Use an insect repellent containing DEET, picaridin, oil of lemon eucalyptus
(OLE), or IR3535
• Always follow product directions and reapply as directed
• If you are also using sunscreen, apply sunscreen first, let it dry, then apply
insect repellent.
• Follow package directions when applying repellent on children. Avoid
applying repellent to their hands, eyes, or mouth.
• Stay and sleep in screened-in or air-conditioned rooms.
• Use a bed net if the area where you are sleeping is exposed to the outdoors.

Prevention
• The CDC recommends strategies for controlling
mosquitoes such as eliminating standing water, repairing
septic tanks and using screens on doors and windows.
• Spraying insecticide is used to kill flying mosquitoes and
larvicide can be used in water containers.
• As Zika virus may be sexually transmitted men who
have gone to an area where Zika fever is occurring are
recommended to either not have sex or use condoms if
their partner is pregnant and should consider condom
use if they are not

Prevention
• Based on the available information of previous
outbreaks, severe forms of disease requiring
hospitalization is uncommon and fatalities are rare.
• There is no vaccine or drug available to prevent/ treat
Zika virus disease at present

Treatment
• There is currently no specific treatment for Zika virus infection.
• Care is supportive with treatment of pain, fever, and itching.
• 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.
• 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.
• One in vitro study found that Zika virus may be sensitive to interferon
treatment, which is commonly used against other viral infections;
however, these results have not been tested in animals or humans

WHO response
• WHO is supporting countries to control Zika virus disease through:
• Define and prioritize research into Zika virus disease by convening experts and
partners.
• Enhance surveillance of Zika virus and potential complications.
• Strengthen capacity in risk communication to help countries meet their commitments
under the International Health Regulations.
• Provide training on clinical management, diagnosis and vector control including
through a number of WHO Collaborating Centres.
• Strengthen the capacity of laboratories to detect the virus.
• Support health authorities to implement vector control strategies aimed at reducing
Aedes mosquito populations such as providing larvicide to treat standing water sites
that cannot be treated in other ways, such as cleaning, emptying, and covering them.
• Prepare recommendations for clinical care and follow-up of people with Zika virus, in
collaboration with experts and other health agencies.

Directorate General of Health Services, Ministry of
Health and Family Welfare,
Govt. of IndiaAdvisory
1. Enhanced Surveillance
a) Community based Surveillance
• Integrated Disease Surveillance Programme (IDSP) through its
community and hospital based data gathering mechanism would
track clustering of acute febrile illness and seek primary case, if
any, among those who travelled to areas with ongoing
transmission in the 2 weeks preceding the onset of illness.
• IDSP would also advise its State and District level units to look for
clustering of cases of microcephaly among newborns and reporting
of Gullian Barre Syndrome.
• The Maternal and Child Health Division (under NHM) would also
advise its field units to look for clustering of cases of microcephaly
among new borns.

b) International Airports/ Ports
• All the International Airports / Ports will display billboards/ signage
providing information to travelers on Zika virus disease and to report
to Custom authorities if they are returning from affected countries and
suffering from febrile illness.
• The Airport / Port Health Organization (APHO / PHO) would have
quarantine / isolation facility in identified Airports.
• Directorate General of Civil Aviation, Ministry of Civil Aviation will
be asked to instruct all international airlines to follow the
recommended aircraft disinsection guidelines
• The APHOs shall circulate guidelines for aircraft disinsection (as per
International Health Regulations) to all the international airlines and
monitor appropriate vector control measures with the assistance from
NVBDCP in airport premises and in the defined perimeter.

c) Rapid Response Teams
• Rapid Response Teams (RRTs) shall be activated at Central and State surveillance
units. Each team would comprise an epidemiologist / public health specialist,
microbiologist and a medical / paediatric specialist and other experts
(entomologist etc) to travel at short notice to investigate suspected outbreak.
• National Centre for Disease Control (NCDC), Delhi would be the nodal agency for
investigation of outbreak in any part of the country.
d) Laboratory Diagnosis
• NCDC, Delhi and National Institute of Virology (NIV), Pune, have the capacity to
provide laboratory diagnosis of Zika virus disease in acute febrile stage.
• These two institutions would be the apex laboratories to support the outbreak investigation
and for confirmation of laboratory diagnosis.
• Ten additional laboratories would be strengthened by ICMR 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 Zika virus disease. Serological tests are not recommended.

2. Risk Communication
• The States/ UT Administrations would create increased awareness among clinicians
including obstetricians, paediatricians and neurologists about Zika virus disease and
its possible link with adverse pregnancy outcome (foetal loss, microcephaly etc).
• There should be enhanced vigilance to take note of travel history to the affected
countries in the preceding two weeks.
• The public needs to be reassured that there is no cause for undue concern.
• The Central/ State Government shall take all necessary steps to address the challenge of this
infection working closely with technical institutions, professionals and global health partners.
3. Vector Control
• There would be enhanced integrated vector management.
• The measures undertaken for control of dengue/ dengue hemorrhagic fever will be further
augmented. The guidelines for the integrated vector control will stress on vector surveillance
(both for adult and larvae), vector management through environmental modification/
manipulation; personal protection, biological and chemical control at household, community
and institutional levels. Details are at Annexure-I.
• States where dengue transmission is going on currently due to conducive weather
conditions (Kerala, Tamil Nadu etc) should ensure extra vigil.

4. Travel Advisory
• Non-essential travel to the affected countries to be deferred/ cancelled.
• 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 dress
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 travelled to areas with Zika virus transmission should
mention about their travel during ante-natal visits in order to be assessed and
monitored appropriately.

5. Non-Governmental Organizations
• Ministry of Health &FW / State Health Departments would work closely
with Non-Governmental organizations such as Indian / State Medical
Associations, Professional bodies etc to sensitize clinicians both in
Government and private sector about Zika virus disease.
6. Co-ordination with International Agencies
• National Centre for Disease Control, Delhi, the Focal Point for International
Health Regulations (IHR), would seek/ share information with the IHR
focal points of the affected countries and be in constant touch with World
Health Organization for updates on the evolving epidemic.
7. Research
• Indian Council of Medical Research would identify the research priorities
and take appropriate action.
8. Monitoring
• The situation would be monitored by the Joint Monitoring group under
Director General of Health Services on regular basis.
• The guidelines will be updated from time to time as the emerging situation
demands.

To Summarize
• Zika virus disease is caused by a virus transmitted by Aedes
mosquitoes.
• People with Zika virus disease usually have symptoms that
can include mild fever, skin rashes, conjunctivitis, muscle and
joint pain, malaise or headache. These symptoms normally last
for 2-7 days.
• There is no specific treatment or vaccine currently available.
• The best form of prevention is protection against mosquito
bites.
• The virus is known to circulate in Africa, the Americas, Asia
and the Pacific.

Zika Virus Disease Symptoms and Diagnosis

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