Questions

Zika virus — Questions

Study questions about Zika virus — exam-style, clinical-scenario and FAQ.

Mock Exam mode

Sit this set one question at a time. Multiple-choice questions mark themselves; written questions reveal a tickable mark scheme so you can score your own answer. You get a combined score at the end.

15 questions: 12 MCQ, 3 written.

High-priority (past-paper) questions only

A complete answer describes the clinical association, the biological mechanism and the determinants of risk.

The association

The 2015 to 2016 American epidemic was accompanied by a marked rise in infants born with microcephaly, first recognised in north-east Brazil, which drew the link between maternal Zika infection and congenital brain injury and prompted a WHO public health emergency in 2016.

Congenital Zika syndrome

Microcephaly is the hallmark of a broader congenital Zika syndrome that also includes intracranial calcification, ventriculomegaly, ocular lesions such as macular scarring, congenital contractures and sensorineural hearing loss, with later neurodevelopmental impairment; infection can also cause miscarriage and stillbirth.

Mechanism

Zika virus has a tropism for fetal neural progenitor cells, in which it impairs proliferation and causes cell death, interrupting cortical development; the placenta and fetal tissues sustain the infection that seeds the fetal brain.

Determinants of risk

The risk is greatest with infection in the first trimester, though injury can follow later infection. Because about 80% of maternal infections are asymptomatic, exposure is often unrecognised, which is why maternal serology and fetal ultrasound surveillance are central to management.

A complete answer marshals the epidemiological, virological and biological lines of evidence that together establish causation rather than mere association.

Epidemiological evidence

The temporal and geographic coincidence of the microcephaly surge with the wave of Zika transmission, the sharp rise above expected baseline rates, and the reproduction of the association across affected regions and in later outbreaks support a causal link. The greatest risk with first-trimester infection provides a biological gradient consistent with a teratogen.

Direct virological evidence

Zika viral RNA and antigen have been detected in the amniotic fluid, fetal brain tissue and placenta of affected pregnancies, and virus has been recovered from the brains of infants with microcephaly, placing the virus at the site of injury.

Biological plausibility

Zika virus infects and kills neural progenitor cells in cell and animal models, and infection of pregnant animals reproduces fetal brain injury, providing an experimental mechanism.

Judgement

Applying causal criteria of strength, consistency, temporality, biological gradient, plausibility and experimental support, the evidence is judged sufficient to conclude that Zika virus infection causes congenital microcephaly and the wider congenital Zika syndrome.

Zika IgM cross-reacts strongly with dengue and other flaviviruses, so a reactive result needs confirmation by plaque-reduction neutralisation, and interpretation is harder in people with prior flavivirus exposure or vaccination.

Neutralisation measures antibody rather than RNA, is more not less laborious, and the timing statements are incorrect.

About 80% of Zika infections cause no symptoms, so transmission is largely silent and outbreaks can be extensive before recognition; symptomatic disease is usually mild and lasts up to a week.

The lower figures understate the high asymptomatic fraction.

First-trimester infection carries the highest risk, and microcephaly is the hallmark, accompanied by intracranial calcification, ventriculomegaly, ocular lesions, contractures and hearing loss; infection can also cause miscarriage and stillbirth.

The other combinations misstate the timing or the pattern of injury.

Guillain-Barré syndrome, a post-infectious ascending flaccid paralysis, is the principal adult neurological complication and was the first severe outcome linked to Zika during the French Polynesian outbreak.

Anterior-horn paralysis is characteristic of West Nile virus, subacute sclerosing panencephalitis of measles, and parkinsonism of Japanese encephalitis.

Zika virus is transmitted mainly by Aedes aegypti, with a sylvatic Aedes-and-monkey cycle in Africa; the same vector transmits dengue and urban yellow fever.

Culex tritaeniorhynchus transmits Japanese encephalitis, Anopheles transmits malaria, Ixodes is a tick vector of tick-borne encephalitis, and Haemagogus drives sylvatic yellow fever.

Zika infection in pregnancy is teratogenic and causes congenital Zika syndrome, with microcephaly, brain and eye anomalies and fetal loss, even though maternal illness is usually mild.

Zika does not cause the maternal haemorrhage, high maternal mortality or arthritis suggested by the other options.

The urban cycle is a human-to-human loop transmitted by Aedes aegypti, distinct from the sylvatic (jungle) cycle that maintains these viruses among forest animals and forest mosquitoes. Anopheles transmits malaria, and Ixodes is a tick.

The Pacific and American epidemic strains descend from the Asian lineage; Zika virus sits in the Spondweni serocomplex and exists as a single serotype with African and Asian lineages.

There is no European or tick-borne Zika lineage, and Kunjin is a subtype of West Nile virus.

No Zika vaccine is licensed, although several candidates have advanced into clinical trials. Development is complicated by the need to protect pregnant women and by the theoretical concern that flavivirus antibody could enhance dengue infection.

The other statements describe vaccines that do not exist for Zika.

Zika viral RNA remains detectable in urine for longer than in serum, widening the diagnostic window for reverse-transcriptase PCR.

Blood PCR is validated, cross-reactivity is a serology problem rather than a PCR one, and urine does not carry more antibody.

Zika virus is sexually transmitted and persists in immune-privileged sites, notably the testis, for weeks to months, prolonging the window of sexual transmissibility; it is also transmitted vertically and by transfusion.

It is mosquito-borne rather than tick-borne, readily infects humans, does not cause a hepatic haemorrhagic fever, and has no licensed vaccine.

Zika virus was isolated in 1947 from a sentinel rhesus monkey in the Zika Forest of Uganda, and soon after from Aedes mosquitoes at the same site.

Yap Island (2007) and French Polynesia (2013 to 2014) were later outbreaks, and the Americas epidemic began in 2015; none was the site of first isolation.

a. Zika virus infection. The mild febrile illness with rash, arthralgia and non-purulent conjunctivitis after travel to an endemic region is characteristic (dengue and chikungunya are the main differentials).

b. Reverse-transcriptase PCR on blood and urine (urine has a longer detection window), with serology if presentation is later; the key pitfall is strong flavivirus cross-reactivity, so a positive IgM needs confirmation by plaque-reduction neutralisation and interpretation is harder with prior flavivirus exposure.

c. The concern is congenital Zika syndrome, particularly microcephaly, greatest after first-trimester infection; monitoring is by serial fetal ultrasound, with amniotic-fluid testing where indicated and paediatric assessment of the neonate.

d. Because Zika persists in semen and is sexually transmitted, the partner should use condoms or abstain for the recommended period to avoid re-exposing her during the pregnancy.

High priorityExam-styleComment on the relationship between Zika virus infection and microcephaly. [10]
Model answer
A complete answer describes the clinical association, the biological mechanism and the determinants of risk.

The association

The 2015 to 2016 American epidemic was accompanied by a marked rise in infants born with microcephaly, first recognised in north-east Brazil, which drew the link between maternal Zika infection and congenital brain injury and prompted a WHO public health emergency in 2016.

Congenital Zika syndrome

Microcephaly is the hallmark of a broader congenital Zika syndrome that also includes intracranial calcification, ventriculomegaly, ocular lesions such as macular scarring, congenital contractures and sensorineural hearing loss, with later neurodevelopmental impairment; infection can also cause miscarriage and stillbirth.

Mechanism

Zika virus has a tropism for fetal neural progenitor cells, in which it impairs proliferation and causes cell death, interrupting cortical development; the placenta and fetal tissues sustain the infection that seeds the fetal brain.

Determinants of risk

The risk is greatest with infection in the first trimester, though injury can follow later infection. Because about 80% of maternal infections are asymptomatic, exposure is often unrecognised, which is why maternal serology and fetal ultrasound surveillance are central to management.
High priorityExam-styleDiscuss the evidence supporting Zika virus infection as a cause of congenital microcephaly. [10]
Model answer
A complete answer marshals the epidemiological, virological and biological lines of evidence that together establish causation rather than mere association.

Epidemiological evidence

The temporal and geographic coincidence of the microcephaly surge with the wave of Zika transmission, the sharp rise above expected baseline rates, and the reproduction of the association across affected regions and in later outbreaks support a causal link. The greatest risk with first-trimester infection provides a biological gradient consistent with a teratogen.

Direct virological evidence

Zika viral RNA and antigen have been detected in the amniotic fluid, fetal brain tissue and placenta of affected pregnancies, and virus has been recovered from the brains of infants with microcephaly, placing the virus at the site of injury.

Biological plausibility

Zika virus infects and kills neural progenitor cells in cell and animal models, and infection of pregnant animals reproduces fetal brain injury, providing an experimental mechanism.

Judgement

Applying causal criteria of strength, consistency, temporality, biological gradient, plausibility and experimental support, the evidence is judged sufficient to conclude that Zika virus infection causes congenital microcephaly and the wider congenital Zika syndrome.
MCQ
A positive Zika IgM result in a returning traveller must be confirmed by plaque-reduction neutralisation mainly because:
- A. IgM is undetectable in true infection
- B. Plaque-reduction neutralisation is cheaper
- C. IgM cross-reacts strongly with dengue and other flaviviruses
- D. IgM appears only after one year
- E. Neutralisation detects viral RNA
Show answer
Correct answer: C
Zika IgM cross-reacts strongly with dengue and other flaviviruses, so a reactive result needs confirmation by plaque-reduction neutralisation, and interpretation is harder in people with prior flavivirus exposure or vaccination.

Neutralisation measures antibody rather than RNA, is more not less laborious, and the timing statements are incorrect.
MCQ
Approximately what proportion of Zika virus infections are asymptomatic?
- A. Around 1%
- B. Around 20%
- C. Around 50%
- D. Around 80%
- E. Essentially none
Show answer
Correct answer: D
About 80% of Zika infections cause no symptoms, so transmission is largely silent and outbreaks can be extensive before recognition; symptomatic disease is usually mild and lasts up to a week.

The lower figures understate the high asymptomatic fraction.
MCQ
Congenital Zika syndrome is most likely to follow maternal infection during which period, and its hallmark feature is:
- A. Third trimester; neonatal hepatitis
- B. Peri-conception; limb reduction defects only
- C. Second trimester; cardiac septal defects
- D. First trimester; microcephaly
- E. Any trimester; deafness alone
Show answer
Correct answer: D
First-trimester infection carries the highest risk, and microcephaly is the hallmark, accompanied by intracranial calcification, ventriculomegaly, ocular lesions, contractures and hearing loss; infection can also cause miscarriage and stillbirth.

The other combinations misstate the timing or the pattern of injury.
MCQ
The main adult neurological complication linked to Zika virus infection is:
- A. Poliomyelitis-like anterior horn cell paralysis
- B. Subacute sclerosing panencephalitis
- C. Parkinsonism
- D. Transverse myelitis alone
- E. Guillain-Barré syndrome
Show answer
Correct answer: E
Guillain-Barré syndrome, a post-infectious ascending flaccid paralysis, is the principal adult neurological complication and was the first severe outcome linked to Zika during the French Polynesian outbreak.

Anterior-horn paralysis is characteristic of West Nile virus, subacute sclerosing panencephalitis of measles, and parkinsonism of Japanese encephalitis.
MCQ
The principal mosquito vector of Zika virus is:
- A. Culex tritaeniorhynchus
- B. Aedes aegypti
- C. Anopheles gambiae
- D. Ixodes ricinus
- E. Haemagogus species
Show answer
Correct answer: B
Zika virus is transmitted mainly by Aedes aegypti, with a sylvatic Aedes-and-monkey cycle in Africa; the same vector transmits dengue and urban yellow fever.

Culex tritaeniorhynchus transmits Japanese encephalitis, Anopheles transmits malaria, Ixodes is a tick vector of tick-borne encephalitis, and Haemagogus drives sylvatic yellow fever.
MCQ
The principal reason a pregnant traveller should avoid areas with active Zika transmission is:
- A. Severe maternal haemorrhage during illness
- B. A high risk of maternal death
- C. Chronic disabling maternal arthritis afterwards
- D. The risk of congenital Zika syndrome
- E. Fetal hepatitis and liver failure
Show answer
Correct answer: D
Zika infection in pregnancy is teratogenic and causes congenital Zika syndrome, with microcephaly, brain and eye anomalies and fetal loss, even though maternal illness is usually mild.

Zika does not cause the maternal haemorrhage, high maternal mortality or arthritis suggested by the other options.
MCQ
The urban transmission cycle of yellow fever, dengue and Zika viruses is maintained mainly by which mosquito?
- A. Anopheles gambiae
- B. Culex pipiens
- C. Aedes aegypti
- D. Culicoides species
- E. Ixodes ricinus
Show answer
Correct answer: C
The urban cycle is a human-to-human loop transmitted by Aedes aegypti, distinct from the sylvatic (jungle) cycle that maintains these viruses among forest animals and forest mosquitoes. Anopheles transmits malaria, and Ixodes is a tick.
MCQ
The Zika virus strains responsible for the Pacific and American epidemics belong to which lineage?
- A. The Asian lineage
- B. The African lineage
- C. The European lineage
- D. The Kunjin sublineage
- E. A tick-borne lineage
Show answer
Correct answer: A
The Pacific and American epidemic strains descend from the Asian lineage; Zika virus sits in the Spondweni serocomplex and exists as a single serotype with African and Asian lineages.

There is no European or tick-borne Zika lineage, and Kunjin is a subtype of West Nile virus.
MCQ
What is the current status of Zika virus vaccines?
- A. A live-attenuated vaccine is on the routine schedule
- B. An inactivated vaccine is required for travel
- C. A single-dose vaccine gives lifelong protection
- D. A maternal vaccine is licensed for pregnancy
- E. No vaccine is licensed, though candidates are in clinical trials
Show answer
Correct answer: E
No Zika vaccine is licensed, although several candidates have advanced into clinical trials. Development is complicated by the need to protect pregnant women and by the theoretical concern that flavivirus antibody could enhance dengue infection.

The other statements describe vaccines that do not exist for Zika.
MCQ
When confirming acute Zika virus infection by reverse-transcriptase PCR, testing urine as well as blood is useful because:
- A. Urine is easier to store than blood
- B. Viral RNA persists longer in urine than in serum
- C. Blood PCR is not validated for Zika
- D. Urine contains more neutralising antibody
- E. Urine avoids all flavivirus cross-reactivity
Show answer
Correct answer: B
Zika viral RNA remains detectable in urine for longer than in serum, widening the diagnostic window for reverse-transcriptase PCR.

Blood PCR is validated, cross-reactivity is a serology problem rather than a PCR one, and urine does not carry more antibody.
MCQ
Which feature distinguishes Zika virus from most other medically important arboviruses?
- A. It is transmitted only by ticks
- B. It cannot infect humans
- C. It is sexually transmitted and persists in the testis
- D. It causes a haemorrhagic fever with hepatic necrosis
- E. It is prevented by a live-attenuated vaccine
Show answer
Correct answer: C
Zika virus is sexually transmitted and persists in immune-privileged sites, notably the testis, for weeks to months, prolonging the window of sexual transmissibility; it is also transmitted vertically and by transfusion.

It is mosquito-borne rather than tick-borne, readily infects humans, does not cause a hepatic haemorrhagic fever, and has no licensed vaccine.
MCQ
Zika virus was first isolated in 1947 from:
- A. A sentinel rhesus monkey in the Zika Forest of Uganda
- B. A febrile child in Brazil
- C. Aedes mosquitoes in Yap Island
- D. A pig in Malaysia
- E. A traveller returning from French Polynesia
Show answer
Correct answer: A
Zika virus was isolated in 1947 from a sentinel rhesus monkey in the Zika Forest of Uganda, and soon after from Aedes mosquitoes at the same site.

Yap Island (2007) and French Polynesia (2013 to 2014) were later outbreaks, and the Americas epidemic began in 2015; none was the site of first isolation.
Clinical scenarioA woman who is 10 weeks pregnant returns from a holiday in the Caribbean with a few days of low-grade fever, a maculopapular rash, joint pains and red eyes, now resolved. a) What is the most likely arboviral diagnosis? [1] b) Which laboratory tests would you use to confirm it and what interpretive pitfall must you keep in mind? [3] c) What is the principal fetal concern and how is the pregnancy monitored? [2] d) What advice would you give her partner? [1]
Model answer
a. Zika virus infection. The mild febrile illness with rash, arthralgia and non-purulent conjunctivitis after travel to an endemic region is characteristic (dengue and chikungunya are the main differentials).

b. Reverse-transcriptase PCR on blood and urine (urine has a longer detection window), with serology if presentation is later; the key pitfall is strong flavivirus cross-reactivity, so a positive IgM needs confirmation by plaque-reduction neutralisation and interpretation is harder with prior flavivirus exposure.

c. The concern is congenital Zika syndrome, particularly microcephaly, greatest after first-trimester infection; monitoring is by serial fetal ultrasound, with amniotic-fluid testing where indicated and paediatric assessment of the neonate.

d. Because Zika persists in semen and is sexually transmitted, the partner should use condoms or abstain for the recommended period to avoid re-exposing her during the pregnancy.