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From a Mosquito Bite to a Congenital Malformation; What Future Fathers Should know in the Era of Zika Virus?

Ali A. Dabaja, MD
Henry Ford Health System
Department of Urology
Detroit, Michigan


Zika virus was initially identified in 1947 in the Zika forest of Uganda, accidentally during a yellow fever research investigation (Dick, Kitchen et al. 1952). For the following decades, many cases human cases were identified in multiple African countries. Later, it was identified on the Asian continent and most recently, in April 2007 the first reported outbreak of Zika virus was reported in Micronesia. The next large outbreak was reported in French Polynesia in 2013, were over 70% of the population became infected. During this time it was noted an association with Guillain BarrĂ© syndrome (GBS) (Oehler, Watrin et al. 2014). The virus followed the path to the American continent, with description of cases in Eastern Island in 2014. It was not until 2015, when a major cohort of patients were identified in Zika virus infection in Brazil. It was noted a drastic increase in the number newborns with microcephaly. The was uncharted territory — a mosquito-borne infection leading to disabling birth defects (Slavov, Otaguiri et al. 2016). On February 1, 2016, the World Health Organization (WHO) declared that the Zika virus outbreak constituted an international public health emergency because of the possible link to microcephaly and other neurologic syndromes. The WHO declaration represents its highest level of alert and has only been invoked 3 other times so far: in 2009 during the H1N1 influenza epidemic, in May 2014 when poliomyelitis reemerged in Pakistan and Syria, and in August 2014 with Ebola virus.

Zika virus is primarily transmitted to humans through bites from Aedes mosquitoes, found in temperate regions including the tropical, and subtropical areas, mosquitoes that can transmit the virus are also present in several southern states in the United States. Although it was mainly thought that the virus is transmitted through a mosquito bite, the most recent outbreak has brought to light other modes of transmission.  For example, sexual transmission of Zika virus has been reported (Foy, Kobylinski et al. 2011), mostly transmission from men to women, and new evidence showing transmission from women to men and same sex partners. The virus has been detected in saliva, urine and breast milk, but not in vaginal swabs collected from women with active Zika virus infection. To date, there have been no reports of Zika being transmitted through kissing although transmission via tears or sweat has been postulated (Swaminathan, Schlaberg et al. 2016).

It is now recommended by the Centers for Disease Control and Prevention (CDC) and the WHO that men and women that inquired the infection or are at risk of contracting it and seeking to conceive, to wait to attempts to conceive until the risk of viremia or viral shedding in semen is believed to be minimal (For updated recommendations, please visit cdc.gov/zika). For men seeking to father children this raise concerns of passing this virus and the consequences of the birth defects, specifically microcephaly, to their offspring. The virus was first isolated from sperm during the Polynesian outbreak and It is not known how long the virus persists in sperm or whether asymptomatic persons infected with Zika virus can transmit infection to sexual partners (Musso, Roche et al. 2015). However, there are some evidence that the virus can be found in the semen for up to 6 months.

Approximately 80% of individuals infected with Zika virus have no symptoms. Most common reported symptoms of Zika infection are typically mild, including fevers, rash, myalgias and headache, and generally these symptoms are self limiting. Most notably, Zika virus has been in the press because of an association with microcephaly in newborns (head circumference less than 2 SD below the mean for gestational age at birth). Certain areas with high prevalence of suspected cases of Zika virus infection have reported a 20-fold increase in rate of newborn microcephaly. Although the causation has not been established, several investigations have suggested a link between maternal infection and microcephaly in infants. Affected fetuses are found to have widespread brain calcifications and ventricular enlargement secondary to cerebral atrophy.

There have been many recommendations and statements by the CDC about what women should do to prevent exposure of Zika and transmitting to their fetus. Woman who are pregnant should avoid travel to areas where Zika virus transmission is ongoing, and if they experience symptoms of Zika infection while traveling to these areas should be tested for virus. Asymptomatic women who report travel to such areas while pregnant should be offered testing. Both male and female travelers should undergo precautions for avoiding mosquitos and mosquito bites, like mosquito repellents, covering skin, and avoiding areas the attract mosquitos.

For men who live in or travel to active Zika virus transmission areas with a pregnant partner, the recommendation is to use condoms every time they engage sexual intercourse or not to have sexual relations for the duration of the pregnancy. To be effective, condoms must be used correctly during vaginal, anal, and oral sex from start to finish on all occasions. Most recently the CDC have updated these recommendations, based on available information about how long the virus remains in semen and on whether or not men had symptoms of infection. The CDC recommend couples with men who have confirmed Zika or symptoms of the infections to consider using condoms or to abstain from sexual relations for at least 6 months after symptoms begin. For men who travel to areas with Zika but did not develop symptoms of Zika, the couple should consider using condoms or to obtain for at least 6 months after their return in order to minimize risk. This will allow for late onset symptoms to develop during this period. Couple of live in an area with Zika outbreaks but have not developed symptoms, they should consider using condoms or not engage in intercourse while there is active Zika transmission in the area. These recommended waiting periods should also be considered for intrauterine insemination of a partner, or the use of donor eggs through IVF. Couples who do not want to get pregnant should use the most effective contraceptive methods that they can use consistently and correctly, and they should also use condoms to prevent the sexual transmission of Zika. Again, recommendations due evolve and SMRU members should visit the CDC website for the most current guidance.

If a man is planning to travel to an area of the world with active Zika and does not wish to risk having to wait 6 months before trying to have a child upon his return, he has the option of freezing his sperm prior to his departure. This sperm can be used for intrauterine insemination of the female partner or for insemination of the partner’s egg or a donor’s egg via IVF/ICSI. If the couple plan to transfer embryos to a gestational surrogate, In the case of a single male or a male/male couple, the sperm could be frozen and used for insemination at a future date. There is potential risk for transmission of Zika virus through donated tissues, including semen and oocytes. The FDA currently recommends living donors of eggs or sperm be considered ineligible because of Zika concerns if they have any of the following risk factors: medical diagnosis of Zika in the past 6 months, residence in or travel to an area with active Zika transmission within the past 6 months, or have been sexually active within the past 6 months with a partner who is known to have either of the risk factors above.


Reference:

Dick, G. W., et al. (1952). "Zika virus. I. Isolations and serological specificity." Trans R Soc Trop Med Hyg 46(5): 509-520.

Foy, B. D., et al. (2011). "Probable non-vector-borne transmission of Zika virus, Colorado, USA." Emerg Infect Dis 17(5): 880-882.

Musso, D., et al. (2015). "Potential sexual transmission of Zika virus." Emerg Infect Dis 21(2): 359-361.

Oehler, E., et al. (2014). "Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013." Euro Surveill 19(9).

Slavov, S. N., et al. (2016). "Overview of Zika virus (ZIKV) infection in regards to the Brazilian epidemic." Braz J Med Biol Res 49(5): e5420.

Swaminathan, S et al. (2016). "Fatal Zika Virus Infection with Secondary Nonsexual Transmission." N Engl J Med. 2016 Sep 28. epub ahead of press. cdc.gov/zika

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