ZIKA VIRUS

ByDr. Sayan Chakraborty

2nd Year JR- MD Tropical MedicineSchool of Tropical Medicine, Kolkata

E-mail: dr.sayan@gmail.com

Background

• Zika fever: a febrile or sub-febrile illness caused by ZIKV• Flaviviridae ( DENV, WNV, YF,JE)• Aedes mosquitoes• First isolated from the blood of a sentinel

rhesus monkey from the Zika Forest in Uganda in 1947• Genome sequenced in 2006

Zika Fever• Infection symptomatic in 18% of cases• Illness is usually mild lasting from several days to

a week• Dengue like illness• Severe disease requiring hospitalisation

uncommon• Deaths rare• During 1st wk Zika virus can be found in blood of

infected person and can be transmitted to others.

Transmission

1. Infected mosquito bite.(Aedes africanus, Aedes luteocephalus, Aedes aegypti)

2. From infected mother to fetus.3. Possibility of a secondary sexual transmission

has been reported recently. (Colorado,USA)4. One report of possible spread of virus through

blood transfusion.5. No reports of spread through breastfeeding.

Epidemiology

• Outbreaks in Africa, SE Asia, Pacific Islands, and the Americas.• Sequential entry in western hemisphere

over 20 years Dengue in 1990s, West nile virus in 1999, Chikungunya in 2013, and now Zika virus.• Previously confined to a narrow equatorial

belt running across Africa and Asia.

Epidemiology

• The virus circulated predominantly in wild primates and arboreal mosquitoes such as Aedes africanus, Aedes aegypti, etc and rarely caused recognized “spillover” infections in humans.• First human cases of ZIKA infection were

described in the 1960s, first in Africa, then in southeast Asia.

• First large documented outbreak occurred in 2007 in Yap Island, Micronesia, in the North Pacific, characterised by rash, conjunctivitis and arthralgia. (N Engl J Med 2009;360:2536-43.)

• This outbreak documented transmission of Zika virus outside Africa and Asia.

• Blood specimens were obtained during the acute phase (i.e., within 10 days after the onset of symptoms) and during the convalescent phase (i.e., 14 days later).

Laboratory Analysis and Case Classification• Serum samples were tested by ELISA for IgM Abs against Zika

virus and dengue virus.• Titres of neutralizing Ab to Zika virus and dengue virus were

determined by plaque reduction neutralization tests with a cutoff value of 90% (PRNT90).

• Patients in the acute phase were tested by RT-PCR for Zika virus and dengue virus RNA.

Confirmed Zika virus disease• Zika virus RNA was detected in the serum OR• All of the following present

a. IgM antibody against Zika virus (detected by ELISA)b. Zika virus PRNT90 titer ≥ 20.c. Ratio of Zika virus PRNT90 titer to dengue virus PRNT90 titer ≥

4.

Probable Zika virus disease• Zika virus IgM detected by ELISA.• Zika virus PRNT90 titre ≥ 20. • Ratio of Zika virus PRNT90 titer to dengue virus PRNT90 titer < 4.• No Zika virus RNA was detected by RT-PCR or the serum sample

was inadequate for the performance of RT-PCR.

• 185 cases of suspected Zika virus disease were identified. Of these, 49 (26%) were confirmed and 59 (32%) were probable cases.

• Median age of patients with confirmed or probable disease was 36 yrs (range, 1 to 76); 66 of these patients (61%) were female.

• Signs and symptoms no(%)Macular or papular rash 28 (90)Fever 20 (65)Arthritis or arthralgia 20 (65)Nonpurulent conjunctivitis 17 (55)Myalgia 15 (48)Headache 14 (45)Retro-orbital pain 12 (39)Edema 6 (19)Vomiting 3 (10)

• The median duration of rash was 6 days (range, 2 to 14), and that of arthralgia was 3.5 days (range, 1 to 14).

• No deaths, hospitalizations, or hemorrhagic complications.• No h/o travel outside of Yap within 2 weeks before the onset of

symptoms.• Household surveys were completed in 173 of 200 randomly

selected households.

• Population estimates showed 5005 of the 6892 Yap residents who were 3 years of age or older were infected with Zika virus during the outbreak, an infection rate of 73%.

• Among the survey participants who were positive for IgM antibody against Zika virus, a total of 19% reported a clinical illness that was probably attributable to Zika virus infection.

• Aedes hensilli was thought to be the responsible vector in this outbreak.

• Attack rates: Females > Males & Older persons > younger persons.• In contrast, prevalence of IgM Ab against Zika detected

by the survey was higher in male participants (perhaps because of the possibility of their greater exposure to mosquitoes)• These discrepancies may be because of differences in

health care–seeking behaviour for this relatively mild illness.

• Precise estimates of the persistence of IgM antibody against Zika virus are not available.

• Yap island was followed by a large epidemic in French Polynesia in 2013–14.

• Subsequently, ZIKV spread to several countries in Oceania.• First case of laboratory-confirmed Zika virus infection

imported into Europe was reported in November 2013, diagnosed in a German traveller returning from Thailand.

• ZIKV was believed to cause only mild diseases prior to the French Polynesian epidemic, during which severe neurological complications (Guillain-Barre syndrome) were confirmed.

• Data from French Polynesia documented a concomitant epidemic of 73 cases of GBS and other neurologic conditions in a population of approximately 270,000, which may represent complications of Zika.

• Underlying physiopathological mechanisms of Zika related GBS is unknown, could be of immunological origin.

• First case report : (Zika virus infection complicated by Guillain-Barré syndrome – case report, French Polynesia,December 2013) E Oehler et al.

• Tetraparesis predominantly in the lower limbs, paresthesia of the extremities, diffuse myalgia, a b/l but asymmetric facial palsy, with abolition of DTR.

• No respiratory or deglutition disorders. C/o chest pain related to a sustained VT, and orthostatic hypotension, both s/o dysautonomia.

• Electromyogram a diffuse demyelinating disorder.• Treated with intravenous Ig.• Discharged on Day 13, but paraparesis persisted after the end of

hospitalisation.• On day 40, she was able to walk without help.

• Between April and November,2015, 18 of the 27 Brazilian states reported indigenous ZIKV cases.

• After ZIKV emerged in Brazil, a 20-fold annual increase of microcephaly cases was observed.

• In 2015─ 1248 new suspected cases, a prevalence of 99·7 per 100 000 livebirths.

• The Brazilian Ministry of Health confirmed the relation between ZIKV and microcephaly.

• Virus was detected in the amniotic fluid of 2 pregnant women whose fetuses presented a reduction in the circumference of the head.

• Perinatal transmission was reported previously in 2 women from French Polynesia.

• Zika virus RNA was also detected in the breast milk of those 2 women.

• The possible routes of perinatal transmission are transplacental, during delivery, during breastfeeding and by close contact between the mother and her newborn.

• Ophthalmic findings in three children with microcephaly. ( the lancet, Vol 387 January 16, 2016).

• These infants had cerebral calcifications detected by CT scans and presumable intrauterine ZIKV infection.

• One of the mothers reported rash and arthralgia in the first trimester.

• The three infants had unilateral ocular findings involving solely the macular region.

• Gross macular pigment mottling and foveal reflex loss.

Severe macular neuroretinal atrophy in an infant with microcephaly ( the Lancet, Vol 387 January 16, 2016 )

• This study investigated the diagnostic utility of urine as a source for detection of ZIKV RNA by real-time RT-PCR. • Results suggest that urine might be useful for

confirmation of ZIKV infection because virus was detected at higher titres and for a longer period in urine samples than in serum samples.

AdvisoryDiagnosis: • During 1st week of illness: RT-PCR on serum for ZIKV RNA• Virus-specific IgM and neutralizing Ab develop after 1st week

of illness; cross-reaction with related flaviviruses common• Plaque reduction neutralization testing (PRNT) can be

performed to measure virus-specific neutralizing Ab & discriminate between cross-reacting Ab in primary flavivirus infections

Travel advisory:• All pregnant women consider postponing travel to areas

where Zika virus transmission is ongoing

Management & Prevention

• Bed rest and supportive care• Protection from mosquito bites.• Among the best preventive measures against Zika

virus are: house screens, air-conditioning,removal of yard and household debris and

containers that provide mosquito-breeding sites.

ISSUES

• No vaccines.• Better public health strategies to control arboviral

spread, including vaccine platforms for flaviviruses, alphaviruses, and other arbovirus groups.• Dengue and chikungunya, which result in similar

clinical pictures, confounds clinical diagnoses.• Zika being closely related to dengue, serologic

samples may cross-react in tests for either virus.

ISSUES

• Zika-specific tests are not yet widely available.• Broad-spectrum antiviral drugs effective

against whole classes of viruses are urgently needed.