By John C. Hobbins, MD
Professor, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora
SYNOPSIS: The Zika virus’s indolence in South American, Central American and Caribbean countries has not prevented concern from flourishing regarding its association with microcephaly and neurological impairment, especially as the 2016 Summer Olympics in Brazil loom large.
Zika was first described as transmitted in humans in its namesake, the Zika Valley in Uganda. A flavivirus transmitted by the same mosquito, Aedes aegypti, that carries the yellow fever, dengue fever and chikungunya viruses, Zika has gained renown as initial outbreaks in Pacific islands spread to the Caribbean as well as Central and South America. The few cases that have been diagnosed in North America have concerned individuals recently returning from countries where the outbreaks are occurring.
Zika infections typically do not manifest symptomatically, but one in five cases can be associated with headaches, fever, rash and conjunctivitis. Even in these cases, the symptoms still rarely last more than a week. In exceedingly rare occasions in adults, Zika has been associated with Guillain-Barre syndrome, causing neuromuscular weakness and, even more rarely, temporary paralysis. The most concerning aspect of Zika’s tangential effects has been its link with fetal and infant microcephaly in children of mothers infected with the virus. The virus has been found in maternal blood and amniotic fluid as well as in placental and brain tissue. It has also been found in the seminal fluid of infected men. The implications this has for fertile couples considering childbirth is not fully clear.
The initial study revealing the possible correlation between Zika and microcephaly was conducted in French Polynesia in 2014. During the past year, the rate at which microcephaly was discovered in newborns rose rapidly, particularly in the provinces of Bahia and Pernambuco. Though Brazil saw <150 cases of microcephaly in 2014, 2015 brought over 4,000 new cases. Investigation of 732 cases found that of the total 270 were both truly microcephalic and potentially linked to Zika. A lack of standardization in diagnostic methods has led to inaccuracy in diagnoses and therefore clouded research findings on the subject. Moreover, the Zika infection itself is not easily characterized, which further muddles analysis.
There has nonetheless been almost overwhelming evidence that in the areas most impacted by Zika microcephaly among infants has substantially increased. The virus has been identified not only in some mothers of microcephalic infants but in the fetal tissue of deceased infants.
DIAGNOSIS OF ZIKA INFECTION
Most commonly used in the identification of the Zika virus from human tissue are reverse transcriptase–polymerase chain reaction tests (RT-PCR), and the presence of Zika IgM in maternal serum indicates recent infection. RT-PCR tests can cross react with other arboviruses, so patients tested with such should undergo additional confirmatory tests. Analysis of maternal serum is also used and is occasionally favored as a testing method. Any result that returns a fourfold-or-higher count of Dengue/Zika neutralizing antibodies is considered a positive — lower antibody counts are presumed inconclusive. One problem with this method is that infections that occurred more than a week prior are less likely to be detected.
DIAGNOSIS OF MICROCEPHALY
One of Brazil’s primary problems with the diagnosis of microcephaly is the lack of consistency amongst utilized definitions for the disease. The variations in the head-circumference charts used in diagnosis as well as the non-uniform standards for the definition of microcephaly ensured that results would have serious discrepancies. Moreover, the fact that many babies with small heads are simply predisposed to having such, it becomes exceedingly difficult to accurately discern which cases are a result of outside factors like Zika.
Information pertaining to Zika’s effects on the brain are exceedingly recent discoveries. A report detailing two Zika cases portrayed Zika as equally apt to attack most or all parts of the brain in fetuses. Prenatal ultrasound results provide a variety of findings that attest to the widespread neurological damage Zika can cause.
More recent Brazilian Zika cases and studies have focused on infections in the second and third trimester, particularly monitoring changes to the frontal lobe and surrounding portions of the brain during infection. contrasting with earlier studies that suggested damage is predicated upon exposure to Zika during the first trimester. Other investigations of in vitro cases reveal a strong connection between Zika and attenuation of cortical progenitor cells — which would help account for the brain shrinkage common in microcephaly. The above findings are all potentially diagnosed by ultrasound, and pose the threat of progressing into serious neurological disorders and disabilities as well as loss of senses.
At present there is neither an available Zika vaccine nor an antiviral regimen designed to fight this infection. All measures should be taken to avoid or to kill the mosquitoes that transmit the disease in order to limit the spread of the virus. Cases appearing in Florida have prompted educational campaigns cautioning travelers against traveling unprepared to regions where the infections are common. The campaigns have also had middling success increasing preventative measures like use of mosquito spray and residential alerts. Precaution is particularly important for fertile women, in order to avoid infection. As of now, women who are currently pregnant or wish to conceive should avoid travel to certain countries (listed on the CDC website). Sexual partners returning from these listed countries should either always use a condom or abstain from intercourse completely for the duration of the pregnancy. Pregnant women returning from these areas are recommended to receive RT-PCR and antibody testing regardless of whether or not they display symptoms. In the event the woman displays flu-like symptoms they are strongly advised to undergo PCR and antibody tests with a week and within 3 months of the symptoms, respectively. Should a positive Zika diagnosis be made, a late second or third trimester trans-abdominal ultrasound can be used to diagnose microcephaly at a head circumference more than two standard deviations below mean. Transvaginal approaches can also be used to discern subtler brain deviations as long as the fetus is in vertex presentation. At the 15-week mark amniocentesis is a possible method for discovery of Zika RT-PCR, which can allow more informed decision making during pregnancy.
A more optimistic view is that in spite of the immediate threat Zika poses to women and their young children, there is precedent for this danger passing over time: French Polynesia has seen cases of infection drop drastically in recent times.