History

Zika virus was discovered for the first time in April 1947 in Uganda at Zika forest near Victoria Lake, when a veterinarian and his monkey had the same symptoms (fever, malaise, conjunctivitis and drowsiness). In 1952 infection was proven by a rise in Zika virus-specific antibodies in a Nigerian female.¹

The first outbreak occurred in April 2007 in Africa and Asia. The second outbreak occurred in May 2015 in South America and Mexico.

In July 2015 some cases were reported in Malaysia, India, Thailand and upper Egypt. The third outbreak occurred at the end of 2016 at the Olympic Games in Brazil.

Virology, Pathogenesis

Zika virus is an arthropod-borne virus, a member of the virus family Flaviviridae, genus Flavivirus and transmitted by Aedes aegypti mosquito. The virus is transmitted through mosquito bites, blood transfusion, sexual contact (from male to female) and from mother to fetus.²

The incubation period is three to seven days.

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  It is a neurotropic virus which particularly targets neural progenitor cells.

  
  
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  Studies suggest the hypothesis that maternal infection leads to placental infection and injury, followed by transmission of the virus to the fetal brain, hence killing neuronal progenitor cells and disrupting neuronal proliferation, migration and differentiation, slowing brain growth and reducing viability of neural cells.^{3, 4}

  
  
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  In the placenta, the virus infects and then replicates in placental macrophages (Hofbauer cells), and to a lesser extent in cytotrophoblasts.⁵

  
  
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  In a series from Brazil and in other case series, there was immune-histochemical and molecular evidence of virus persistence in the brain of newborns with microcephaly and severe arthrogryposis who died shortly after birth.^{6, 7} [EL 2]

Clinical Manifestations

Clinical manifestations of Zika virus infection occur in 20 per cent of patients:

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   1 Acute onset low grade fever

   
   
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   2 Maculopapular pruritic rash

   
   
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   3 Arthralgia (mostly in small joints of hands and feet)

   
   
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   4 Non-purulent conjunctivitis⁸

Diagnosis

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   1. Clinical manifestation of infection, history of exposure in epidemiologic areas or those who travel to Zika virus infection prone area, or had unprotected sexual contact with a person who meets these criteria.

   
   
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   2. Antigen antibody testing: antibody response to all related flavivirus infections (dengue viruses, West Nile virus and/or in women vaccinated against yellow fever virus) has been known to be cross-reactive.

   
   

   In populations previously exposed to any of the above-mentioned conditions antibody detection of ZIKV is not specific.

   
   
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   3. Real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) for Zika virus RNA (in serum, urine or whole blood). PCR tests should be carried out within two weeks of first suspicion of infection.

   
   
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   4. Nucleic acid assays in the whole blood.

Differential Diagnosis

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  Dengue fever

  
  
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  Parvovirus

  
  
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  Rubella

  
  
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  Measles

  
  
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  Leptospirosis

  
  
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  Malaria

  
  
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  Rickettsial infection.

Congenital Infection

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  The risk for vertical transmission can occur throughout pregnancy and affect the fetus of both symptomatic and asymptomatic mothers.

  
  
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  If a woman is infected during pregnancy, the overall risk of birth defect or abnormality ranges from 6 to 42 per cent.⁹ [EL 2 & 3]

  
  
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  In endemic areas, or on clinical suspicion of Zika viral infection (maculopapular pruritic rash, arthralgia, conjunctivitis or fever), pregnant women should be offered screening to exclude or confirm Zika virus infection.

Fetal Implications and Features of Congenital Zika Virus Syndrome

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   1. Microcephaly (head circumference > 2 standard deviations below the mean of the standard growth charts for sex, age and gestational age).

In some cases, congenitally infected offspring of women during the first or second trimester have a normal head circumference at birth but may subsequently develop microcephaly in the first year of life.¹⁰

Estimates of the risk of microcephaly exposure range from 1 to 4 per cent.

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   2. Central nervous system abnormalities (ventriculomegaly, intracranial calcifications).¹¹

   
   
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   3. Positional abnormalities (club foot and arthrogryposis) may be of neurogenic origin.

   
   
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   4. Miscarriage.

   
   
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   5. Stillbirth.

   
   
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   6. IUGR.

   
   
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   7. Hydrops fetalis.

Placental insufficiency is the mechanism postulated for fetal loss later in pregnancy.