Guidance from CDC on Zika test results

June 15, 2016

The CDC has released new guidelines for interpreting Zika virus tests. Also, is the trend for triplet and higher-order birth rate going up or down? Plus: Do preemies benefit from maternal vaccines?

The Centers for Disease Control and Prevention (CDC) has issued new interim guidelines for interpretation of results of testing for Zika virus antibodies, which focus on a more conservative approach. The goal is to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

In the report, CDC cited recent evidence which suggests that a 4-fold higher titer by plaque reduction neutralization test (PRNT) may not discriminate between anti-Zika virus antibodies and cross-reacting antibodies in all individuals who have been previously infected with or vaccinated against a related flavivirus. (A PRNT using a 90% cutoff value with a titer ≥10 against Zika virus, together with negative PRNTs [i.e., <10] against other flaviviruses is confirmatory of recent infection with Zika.) PRNT may performed to confirm a diagnosis in cases in which immunoglobulin (Ig) M test results are positive, equivocal, or inconclusive. A positive real-time reverse transcription-polymerase chain reaction (rRT-PCR) result confirms Zika virus infection in individuals suspected to have Zika virus disease but a negative result does not exclude infection.

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An enzyme-linked immunosorbent assay (ELISA) can be used to detect anti-Zika virus IgM antibodies in serum or cerebrospinal fluid but the Zika virus IgM ELISA may produce false-positive results because of false-positive results because of cross-reacting IgM antibodies related flaviviruses or nonspecific reactivity. PRNT measures virus-specific neutralizing antibody titers and should be performed against various related flaviviruses to rule out false-positive ELISA results.

CDC recommends that all pregnant women with laboratory evidence of a recent Zika virus infection or flavivirus infection be evaluated and managed for possible adverse pregnancy outcomes and their cases reported to the appropriate Zika virus pregnancy registry. Patients whose serologic testing indicates recent flavivirus infection caused by either Zika or dengue virus should be clinically managed for both infections because they could be infected with either virus.  

NEXT: Looking at the trend of triplet and higher-order birth rate


Triplet and higher-order birth rate trending down

The prevalence of triple and higher-order births continues its decline from the highs of the 1980s and 1990s, according to a recent report from the National Center for Health Statistics. Overall the rate was down 41%, from 193.5 per 100,000 births in 1998 to 113.5 per 100,000 births, with a significant portion of that decrease happening only in the past decade. More than 90% of all triplet and higher-order births are triplets.

When looking at age, birth rates for triplets and higher-order were down by almost 50% in women aged 25 or older. During the studied period, the rate for women younger than 25 was unchanged. The largest decline was seen in mothers aged 45 and older, going from 2326 per 100,000 births in 1998 to 769.9 per 100,000 births. In both 1998 and 2014, the triplet and higher-order birth rate went up with increasing age. In 2014, women aged 45 and older were more than 35 times more likely than adolescent mothers to deliver triplets (769.9 vs 21.7).

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Non-Hispanic white women saw the most significant change in triplet and higher-order birth rates, with a continued decline of 46% from 262.8 per 100,000 births in 1998 to 140.9 per 100,000 births in 2014. In spite of the decrease, they were 57% more likely to have a triplet or higher-order birth than non-Hispanic black women and more than twice as likely as Hispanic women. Hispanic women had a fluctuating rate that eventually was down by 15% from 75.3 per 100,000 births in 1998 to 64.3 births in 2014. However, in non-Hispanic black women, the rate of triplet and higher-order births remained roughly the same from 1998 (87.3 per 100,000 births) to 2014 (89.7 per 100,000 births).

Over the course of the studied period, only 2 states saw an increase in triplet and higher-order multiple births: Oklahoma, 8%, and Louisiana, 4%. Maine, Montana, and the District of Columbia saw declines that were not statistically significant. Seven states—Minnesota, Illinois, New Jersey, Connecticut, Rhode Island, New Hampshire, and Massachusetts—saw decreases of at least 50%.

NEXT: Do maternal vaccines protect preterm infants?


Do maternal vaccines protect preterm infants?

Preterm infants can derive benefit from maternal vaccination with a combined tetanus, diphtheria, 5-component acellular pertussis, inactivated polio vaccine (Tdap/IPV), according to results of a substudy from a larger, multicenter, randomized control trial which were published in Pediatrics.

The researchers measured antibody concentrations at ages 2 months (before the primary vaccine), 5 months (1 month after primary vaccine), and 1 year in 160 premature infants whose mothers had been offered the Tdap/IPV at 28 weeks’ gestation during the course of routine antenatal care. Thirty-one of the mothers received the vaccination.

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Compared to the infants of unvaccinated mothers, those who were born to vaccinated mothers were found to have significantly higher antibody concentrations at age 2 months for all measured vaccine antigens (P < .001). The length of time between maternal vaccination and delivery and the concentration of immunoglobulin G at age 2 months was positively correlated for pertussis toxin (P = .011) and filamentous hemagglutinin (FHA; P = .001). After primary vaccination, children with vaccinated mothers had a significantly lower antibody concentrations of FHA (P = .003) when compared to infants whose mothers were unvaccinated. The differences between the groups resolved by age 1 year.

The researchers concluded that maternal vaccinations administered early in the third trimester can provide protection, even for infants who are delivered prematurely.