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Zika Virus: New Developments; Microcephaly and Late Term Abortions

2016-02-23

NBC news reported today that the CDC has stated there are now fourteen suspected cases of sexual transmission of Zika virus in the United States.  Since there are 30 to 40 million travellers who visit Central and South America each year and return to the US, the potential for this method of transmission is very great.  Zika is transmitted primarily by the Aedes mosquito, which also transmits dengue fever and chikungunya, two much more severe diseases that are endemic to South America.  Only a fifth of people infected with Zika show symptoms, and it is not known whether an asymptomatic infected pregnant woman can transmit serious disease to her fetus.

Each of the cases of suspected sexual transmission occurred in a couple, the male partner travelling to South America, returning with symptoms of virus infection and having contact with the female partner within two weeks of returning.  Several of the suspected cases have occurred in pregnant women.  The Zika virus is known to be present during infection in semen, saliva, blood, and urine, although the only known cases of interpersonal infection have occurred through sexual intercourse.  The virus has been spreading through South America and the Caribbean after jumping across the Pacific in the last four years, with stops in Yap and Easter Island.  Before this spread, the virus had only been known in Asia and Africa after being discovered in a monkey in 1947.

The main reason for concern and for the CDC’s declaration of a public health emergency is the appearance of microcephaly and other fetal anomalies in the offspring of women who were pregnant when they became ill with acute Zika virus infection.  In addition to microcephaly, there are suspicions that prenatal Zika exposure is associated with schizophrenia, autism, and other mental disorders later in life.  The association with microcephaly has not actually been proven according to Koch’s postulates, but it is unlikely that these criteria will ever be fulfilled in the case of Zika.

This leads to an editorial in the New England Journal of Medicine (NEJM) which appeared on February 10, 2016.  The editorial enlarges on a case description which appeared in NEJM contemporaneously: a European woman who had been working in northeast Brazil returned to Europe with a history of Zika virus infection contracted when she was thirteen weeks pregnant.  An ultrasound performed late in the pregnancy showed microcephaly and intracranial calcifications similar to those that had been seen in other Zika cases.  She consulted with national and hospital ethics boards and chose to have a late-term “termination” (abortion.)

The fetus had a very small brain with complete absence of the cerebral gyri (forebrain.)  The ventricles (fluid-filled spaces in the brain) were grossly enlarged, there were calcifications in what little cerebral tissue was present, and the brain stem and spinal cord were hypoplastic (shrunken.)  Electron microscopy showed particles consistent with Zika virus, and large amounts of viral RNA (genetic molecules that carry instructions for assembling the virus) were found in the brain but nowhere else.

The editorial opined that these findings do not satisfy “Koch’s postulates”, the rules laid down by Robert Koch in the nineteenth century for determining if a disease is caused by a specific organism, whether a bacterium or a virus.  However, it is unlikely that these rules will ever be satisfied in this case.  The rules are: a specific organism must be isolated from a patient with the disease.  The organism must be transmitted by inoculation into a healthy patient.  The new patient must then show similar symptoms of disease.  Finally, the organism must be isolated again from the second patient.

These postulates were critical during the early days of the development of the science of infectious disease.  They were usually satisfied by using laboratory animals rather than humans.  In this case, however, performing the experiment in monkeys would take a long time and be very expensive.  Waiting for confirmation of Zika as the cause of this devastating birth defect would be unreasonable because the virus is spreading “explosively” through South and Central America right now, and many millions of young women are at risk in these areas.

The editorial in NEJM asks for the rapid development of specific tests that will confirm the presence of Zika and immunity to the disease.  The only test available at present that is sufficiently specific is RNA polymerase chain reaction, which detects the presence of the virus itself in blood or tissue.  Tests that confirm antibodies to Zika are not specific enough because they cross-react strongly with antibodies to dengue fever and other related flaviviruses endemic to South America.  We need a serologic (serum) test that will confirm past infection with Zika specifically enough to distinguish it from dengue.

The editorial also describes the need for really effective measures to control the Aedes mosquito, the vector of not only Zika but dengue, malaria, and yellow fever.  To date, there has not been deployed an effective control measure, although new developments show considerable promise.  The use of genetic “engineering” devices to create sterile mosquitoes and other advanced techniques offer hope for eventual destruction of Aedes.

The other measure that is desperately needed is effective birth control, prenatal care, and abortion for affected women.  These matters are especially difficult considering the deep penetration of Catholic control in many of the countries affected.  There is even controversy in countries where abortion is readily available during the first trimester because infection and fetal damage is likely to occur during the second trimester and not be detected until the third trimester.  Late-term abortion is controversial even in societies that condone the practice in the first trimester.  The damage of microcephaly and multiple fatal fetal anomalies frequently will not be apparent until after the fetus is theoretically viable.

To prevent the tragedy of late-term abortion or the delivery of a dead or severely retarded microcephalic child, a vaccine against Zika virus may be the best answer.  We will hope for a really effective vaccine before the Zika virus spreads to southern Europe.

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