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Revista Peruana de Ginecología y Obstetricia

On-line version ISSN 2304-5132

Rev. peru. ginecol. obstet. vol.62 no.2 Lima Apr./Jun. 2016



Zika virus - A new challenge for obstetricians and gynecologists

Virus zika - Un nuevo reto para los ginecólogos y obstetras


José Pacheco-Romero, MD, PhD, MSc, FACOG1,2

1 Professor of Gynecology and Obstetrics, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru

2 Editor-in-Chief, Revista Peruana de Ginecología y Obstetricia


The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. The Zika virus is transmitted by Aedes mosquitoes and by sexual relations. It has been found in humans’ blood, saliva, urine, semen, amniotic fluid. Zika infection lasts only a few days, and signs and symptoms present in only about 20% of people are typically mild. The Zika virus has been considered a teratogen that causes microcephaly and other serious brain anomalies as it may invade fetal nerve cells and disrupt brain development. It has also been related to Guillian-Barré syndrome and to an autoimmune syndrome called acute disseminated encephalomyelitis, or ADEM. A review is done on the Zika virus transmission, perinatal problems and prevention in women of reproductive age, during pregnancy and labor, and fertility treatments, as well as strategic preventive considerations implemented in Peru.

Keywords: Zika Virus; Aedes aegypti; Fetal Microcephaly; Fetal Anomalies.


El virus zika se ha extendido rápidamente en las Américas desde su identificación en Brasil a principios de 2015. El virus es transmitido por los mosquitos Aedes y por relaciones sexuales. Se le encuentra en el ser humano en sangre, saliva, orina, semen y líquido amniótico. La infección por zika dura solo unos días, y los signos y síntomas presentes en solo 20% de personas son por lo general leves. El virus zika ha sido considerado como un teratógeno que causa microcefalia y otras anomalías graves del cerebro, porque parece invadir las células nerviosas fetales y perturbar el desarrollo del cerebro. También se le ha relacionado al síndrome de Guillian-Barré y a un síndrome autoinmune llamado encefalomielitis diseminada aguda o ADEM. Se presenta una revisión sobre el virus zika, la transmisión del virus, los problemas perinatales y su prevención tanto en mujeres en edad reproductiva, en el embarazo y parto, así como en tratamientos de infertilidad, y las estrategias preventivas implementadas en el Perú.

Palabras clave: Virus Zika; Aedes aegypti; Microcefalia fetal; Anomalías fetales.

A short history of Zika virus infection

The International Journal of Clinical Practice has recently published Zika: where it has been, where it is going, and how to stop it(1). We read that over the past few decades, emerging and re-emerging infectious diseases have provided insights into the dynamic complexity of the host-pathogen interface. By late 2012, at least 219 human viral species were recognized, and three to four new human viruses are discovered annually(2).

The Zika virus was first identified in pyrexial rhesus monkeys in 1947, in Zika forest, a Uganda, East Africa forest; then it was found in Aedes africanus mosquitoes in 1948 and in humans in 1952 in Uganda and the United Republic of Tanzania(3). Initially the virus was confined to Africa and Asia but subsequently it spread to French Polynesia in 2013-2014, and other Pacific Islands. Then, this viral disease has spread to other regions in Africa, the Americas, Asia and the Pacific. There are separate African and Asian lineages of the vi-rus(4), and the latter strains have caused the outbreaks in the Pacific and the Americas(5).

In March 2015, several patients developed mild fever, rash, conjunctivitis and arthralgia in Rio Grande do Norte from Northeastern Brazil, and as November 2015 three deaths were attributed to Zika in Brazil, including a newborn with microcephaly(6). The Brazilian outbreak would have occurred during a sporting event in Rio de Janeiro where teams from French Polynesia, New Caledonia, Cook Islands and Eastern Island participated(7).

The virus has been spreading throughout the Western Hemisphere at a rapid rate. In the American College of Obstetricians and Gynecologists (ACOG) practice advisory, pregnant women are asked to consider postponing travel to areas where Zika virus transmission is ongoing: Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, Venezuela, and the Commonwealth of Puerto Rico(8).

As of April 13, 2016, American places with active Zika virus transmission are Mexico, The Caribbean and the north of South America. Peru, Chile, Argentina and Uruguay are not included(9). And in continental USA the mosquito Aedes aegypty is present in a broader range extending from the southern states to central and eastern states, having enlarged its presence from 12 to 30 states. Recommendation is the states to be ready for maybe hundreds of thousands of cases of ZIka, with main concern on Puerto Rico. The mosquito Aedes aegypty was eradicated from Chile in 1963, but it has recently been found (18 April 2016) in Arica, Chile, and preventive measures have been implemented(10).

Virus transmission

The Zika virus is transmitted by Aedes mosquitoes(3) (Aedes aegypti and Aedes albopictus in Brazil)(11), the same mosquitoes that spread dengue, chikungunya and yellow fever. Other Aedes ge-nus mentioned include Ae. africanus, Ae. hensilli, Ae. polynesiensi, Ae. luteocephalus(1).

The virus has been found in saliva and urine, but is also transmitted by semen(12) and amniotic fluid(13). Due to the singularity of Zika virus transmission in recent years the idea of sexual transmission is currently considered as important or more important that the mosquito transmission(14).

Other ways of transmission are of concern. Asymptomatic blood donors have been found positive by PCR. Transplacental infection(15), i.e. perinatal or vertical transmission, has been considered because in Brazil the thousands of infected cases in 2015 correlated with an exponential increase in newborns with microcephaly characterized by abnormally small head and impaired brain development(15,16). The virus has been detected by amniocentesis(1).

Sexual transmission was reported in Texas in February 2016(17,18). The Centers for Disease Control and Prevention (CDC) on April 14 reportedthe first known case of sexual transmission of the Zika virus from male to male(19).

Adaptive changes during the evolution of the virus have been encountered, including recombination events and modifications in protein glycosylation patterns(20). The virus has had de ability to adapt to Ae. albopictus, a vector that has spread to 36 States in the USA and to many countries in Europe, Central and South America(1).

Air transportation is of concern as, for exam ple, millions of departing travelers flew to the USA, Argentina, Chile, Italy, Portugal and France, where some of populations in these countries reside in areas conducive to seasonal Zika virus transmission(21). In Peru, persons were infected by the Zika virus in neighboring countries, and one case of local infection has been reported.

Between October, 2013 and April, 2014 French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome(22). Forty-two patients were diagnosed with Guillain-Barré syndrome during the study period, 41 had anti-Zika virus IgM or IgG, and all had neutralizing antibodies against Zika virus compared with the control group (p<0·0001). Most had Zika virus IgM and experienced a transient illness in a median of 6 days before the onset of neurological symptoms. They had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type; evolution of the disease was rapid (about 10 days), and almost one third required respiratory assistance. No patients died.

In Pernambuco, Brazil, six patients were seen last year in the emergency department and the neurology outpatient department, two with acute disseminated encephalomyelitis (ADEM) and four with Guillain-Barré syndrome. All six patients had experienced fever and rash and some had pruritus, myalgia, arthralgia, and conjunctival hyperemia. Neurologic complications appeared 0 to 15 days later. Blood and cerebrospinal fluid molecular tests for arboviruses were positive only for Zika virus. MRI showed white matter lesions in two cases and elevated protein concentration with normal cell count in the four cases of Guillain-Barré syndrome. After hospital discharge, five patients had sustained motor dysfunction, one patient had low visual acuity, and another suffered cognitive decline(23). This was the first report of ADEM associated with the virus. These reports of ADEM and Guillain-Barré syndrome suggest a different mechanism; the virus is triggering an immunological response that is causing these neurological conditions.

Finally, a paper on Zika virus and birth defects published in New England Journal of Medicine by officials from the Centers for Disease Control and Prevention (CDC) assessed Zika virus as a potential teratogen. The review concluded that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this causal relationship included Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants(24).

Symptoms and complications

The incubation period of Zika infection is only a few days, and signs and symptoms present in only about 20% of people are typically mild, with the most common being acute onset of fever, macular or papular rash, arthralgia, and conjunctivitis that last 2-7 days; severe disease requiring hospitalization is uncommon(8).

A relation of Zika virus infection and Guillain-Barré’s syndrome –a disorder in which the body’s immune system attacks part of the peripheral nervous system(22,25)-has been found. Cases of Guillain Barré syndrome-related deaths supposedly caused by Zika virus infection have been found in Colombia(26).

And scientists in Brazil have uncovered a new brain disorder associated with Zika infections in adults: an autoimmune syndrome called acute disseminated encephalomyelitis, or ADEM, that attacks the brain and spinal cord. The findings add to the growing list of neurological damage associated with Zika. Six from 151 patients infected with arboviruses developed symptoms consistent with autoimmune disorders. Of these six, four had Guillain-Barré and two had ADEM. In both ADEM cases, brain scans showed damage to white matter. ADEM symptoms typically last about six months(27).

Zika virus and perinatal problems

Increasing epidemiologic, clinical, laboratory, and pathologic evidence supports a link between Zika virus infection during pregnancy and adverse pregnancy and birth outcomes, including pregnancy loss, microcephaly, and brain and eye abnormalities(28-30). A retrospective analysis of the 2013–2014 Zika virus outbreak in French Polynesia identified eight fetuses and infants with microcephaly; using mathematical model ing, it was estimated that microcephaly affected approximately 1% of fetuses or infants born to women infected with Zika virus during the first trimester of pregnancy(31). Among 42 Brazilian women with laboratory-confirmed Zika virus infection at any time during pregnancy who underwent prenatal ultrasonographic studies, 12 (29%) had abnormal findings, including microcephaly, intracranial calcifications, other brain abnormalities, abnormal cerebral artery flow, intrauterine growth restriction, and fetal death(32).

Brazil, which has registered an estimated 1.5 million Zika infections in the current outbreak, has seen 641 cases of microcephaly since October. Brazil typically reports 150 cases of microcephaly per year(33). By January 2016, a total of 3 530 suspected microcephaly cases had been reported, many of which occurred in infants born to women who lived in or had visited areas where Zika virus transmission was occurring(34).

And brain scans of 23 Brazilian Pernambuco state infants with microcephaly showed widespread and severe abnormalities suggesting that Zika may invade fetal nerve cells and disrupt brain development. Samples of cerebrospinal fluid were available for serologic testing in 7 of the 23 infants, and results on enzyme-linked immunosorbent assay for ZIKV IgM antibody were positive in all 7 samples(35). Zika virus may also be linked to eye abnormalities in the infant(15).

Early reports suggest there might be adverse outcomes associated with Zika virus infection in early pregnancy: two women with Zika virus disease at <7 weeks’ gestation both had pregnancy losses, with Zika virus RNA detected in products of conception, and another woman with clinical illness consistent with Zika virus disease at 7–8 weeks’ gestation delivered a full-term infant with severe microcephaly(36).

Zika investigators now believe that the birth defect microcephaly and the paralyzing Guillain-Barré syndrome may be just the most obvious maladies caused by the mosquito-borne virus. Fueling that suspicion are recent discoveries of serious brain and spinal cord infections - including encephalitis, meningitis and myelitis - in people exposed to Zika. The suspicion that Zika acts directly on nerve cells began with autopsies on aborted and stillborn fetuses showing the virus replicating in brain tissues. Doctors also are worried that Zika exposure in utero may have hidden effects, such as behavioral problems or learning disabilities that are not apparent at birth(37).

The latency period between fetal Zika virus (ZIKV) infection and the development of changes visible with ultrasound (US) may be prolonged, and a fetal brain magnetic resonance imaging (MRI) scan might be needed to detect those changes. In addition, ZIKV RNA testing in pregnant women might be advisable for longer than currently recommended. Persistent ZIKV viremia in a pregnant woman might signal ongoing placental or fetal infection(38). In the postmortem examination for fetal neurologic examination, microscopic analysis revealed abundant apoptosis primarily affecting the intermediately differentiated postmigratory neurons in the neocortex. Early mineralization was seen in association with apoptotic neurons focally. In contrast, the well-differentiated neurons of the basal ganglia and limbic regions as well as primitive cells in the germinal matrix appeared to be unaffected. The subventricular zone and white matter showed severe volume loss with extensive axonal rarefaction and macrophage infiltrates. The highest ZIKV viral loads were found in fetal brain, with substantial viral loads in the placenta, fetal membranes, and umbilical cord.

And severe cerebral damage has been found on imaging (computed tomography and magnetic resonance imaging) in most of 23 children with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical de velopment, often with a simplified gyral pattern and predominance of pachygyria or polymicro gyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem(39).

CDC has developed updated interim guidance to provide preconception counseling following possible Zika virus exposure. This guidance is based on expert opinion, the limited available data on Zika virus, and knowledge about risks for other viral infections in the periconceptional period(40).


Zika virus disease can often be diagnosed by re-verse transcriptase-polymerase chain reaction (RT-PCR) with viral RNA genoma detection in serum, urine, semen. Because viremia decreases over time, a negative RT-PCR collected 5-7 days after symptom onset does not exclude flavivirus infection and serologic testing should be performed. Commercial kits for Zika virus detection are still unpredictable.

Laboratory diagnosis is challenging because of low viremia and cross-reactivity of Zika virus antibod ies with other flavivirus (including dengue) which require confirmation by neutralization assays and make rapid serologic confirmation difficult(41).

AntiZika virus IgM antibody capture enzyme-linked immunosorbent assay (Zika MAC-ELISA) is intended for use in detecting antibodies that the body makes to fight a Zika virus infection(42). It is used on blood in acute phase specimens, >4 days after onset of illness(43). Due to serological cross-reactivity between flaviviruses, an IgM positive result in a dengue or Zika IgM ELISA test should be con sidered indicative of a recent flavivirus infection.

Plaque-reduction neutralization tests (PRNT) can be performed to measure virus-specific neutralizing antibodies and may be able to determine the cause of primary flavivirus infection(43).

The structure of Zika virus is similar to other known flavivirus structures except for the ~10 amino acids that surround the Asn154 glycosylation site found in each of the 180 envelope glycoproteins that make up the icosahedral shell. The carbohydrate moiety associated with this residue, recognizable in the cryo-EM electron density, may function as an attachment site of the virus to host cells. This region varies not only among Zika virus strains but also in other flaviviruses and suggests that changes in this region influence virus transmission and disease(44).


The risk for acquiring mosquito-borne Zika virus in areas with active transmission depends on the duration and extent of exposure to infected mosquitoes and the steps taken to prevent mosquito bites.

There is no vaccine or treatment available for the virus.

The World Health Organization has issued preventive measures in compromised regions consisting in wearing clothes (preferably light-colored) that cover as much of the body as possible; using physical barriers such as screens, closed doors and windows, and sleeping under mosquito nets. Spraying of insecticides should be carried out and use of larvicides to treat large water containers.

As a safety measure, the U.S. Food and Drug Administration recommends the deferral of individuals from donating blood if they have been to areas with active Zika virus transmission(45).

People infected with Zika, chikungunya, or dengue virus should be protected from further mosquito exposure during the first few days of illness to prevent other mosquitoes from becoming infected and reduce the risk of local transmission.

Prevention measures for women of reproductive age are read further down.

And men who were in Zika areas should use condoms to prevent sexual transmission of the virus, especially with pregnant women(46).

Although there are no reports of transmission of Zika virus from infected patients to health care personnel or other patients, minimizing exposures to body fluids is important to reduce the possibility of such transmission. CDC recommends Standard Precautions in all health care settings to protect both health care personnel and patients from infection with Zika virus as well as from blood-borne pathogens (e.g., human immunodeficiency virus [HIV] and hepatitis C virus [HCV])(47). Because of the potential for exposure to large volumes of body fluids during the labor and delivery process and the sometimes unpredictable and fast-paced nature of obstetrical care, the use of Standard Precautions in these settings is essential to prevent possible transmission of Zika virus from patients to health care personnel(13). The goals of Standard Precautions include: 1) Preventing contact between a patient’s body fluids and health care personnel’s mucous membranes (including conjunctivae), skin, and clothing; 2) Preventing health care personnel from carrying potentially infectious material from one patient to another; and, 3) Avoiding unnecessary exposure to contaminated sharp implements.

Anesthesia providers in the labor and delivery setting should adhere to Standard Precautions and wear sterile gloves and a surgical mask when placing a catheter or administering intrathecal injections; additional personal protective equipment (PPE) should be worn based on anticipated exposure to body fluids. Patient body fluids also should not come into direct contact with health care personnel clothing or footwear. When performing procedures including vaginal deliveries, manual placenta removal, bimanual uterine massage, and repair of vaginal lacerations, PPE should include impermeable gowns and kneehigh impermeable shoe covers. Clothing, skin, and mucous membrane protections should be maintained for procedures performed in operat ing room settings. Health care providers should use soap and water or alcohol-based products (gels, rinses, foams), at a minimum, before and after a patient contact and after removing PPE, including gloves(13).

As transmission of Zika to the fetus has been documented in all stages of pregnancy, the World Health Organization recently declared Zika virus a public health emergency of international con-cern(48). Similarly, the United Nations (UN) High Commissioner for Human Rights recently called for countries with the Zika virus to make sexual and reproductive health counseling available to women and to uphold their right to terminate pregnancies(49). Additionally, the UN Human Rights Committee has previously declared that access to safe, medically indicated abortion is a human right(50). Therapeutic abortion for Zika virus infection in early pregnancy has been considered in many countries, but it has not been accepted by the Ministry of Health in Peru.

What has been acknowledged a virtually unprecedented in the annals of public health, the government of El Salvador – a country with one of the most stringent antiabortion laws in the worldadvised women to avoid having babies for at least the next two years(12). The secretary of the Puerto Rico Department of Health has also advised women to consider delaying their pregnancies. But infertility experts know that may not be a realistic option for couples who have already struggled for years to conceive, and for women 35 years or older and currently in infertility treatments(51).

Prevention of sexual transmission of Zika virus

Zika virus is primarily transmitted through the bite of infected Aedes species mosquitoes. However, Zika virus can be sexually transmitted from a man to his sex partners, both by vaginal and rectal intercourse; and now attention to the idea that sexual transmission would be more important than mosquito transmission is considered.

Transmission of Zika virus is of particular concern during pregnancy(52). The first documented case of sexual transmission of Zika virus in USA was in 2008. As of March 18, 2016, there are a total of six confirmed cases of sexual transmission in the United States associated with this out-break. Other cases of sexual transmission have occurred in other countries and there have been two reports of replication-competent Zika virus isolated from semen at least 2 weeks after onset of illness; blood plasma specimens tested negative for Zika virus by reverse transcription-–polymerase chain reaction (RT-PCR)(53). There is one case of confirmed sexual transmission in Peru.

The duration of persistence of infectious Zika virus in semen remains unknown. Sexual transmission of Zika virus from infected women to their sex partners has not been reported.

CDC issued interim guidance for the prevention of sexual transmission of Zika virus include recommendations to men who have traveled to or reside in areas with active Zika virus transmission to use a condom with their female or male sex partners (vaginal intercourse, anal intercourse, or fellatio)(53). These recommendations of consistently and correctly use condoms during sex also apply to their pregnant sex partners or abstain from sex for the duration of the pregnancy. This course would be the best way to avoid adverse fetal effects when Zika virus is contracted during pregnancy. Couples who do not desire pregnancy should use available strategies to prevent unintended pregnancy, including use of the most effective contraceptive methods. Condom use should be encouraged aside to contraception.

At present, Zika virus testing for the assessment of risk for sexual transmission is of uncertain value. Zika virus testing is recommended for persons who have had possible sexual exposure to Zika virus and develop signs or symptoms consistent with Zika virus disease. A pregnant woman with possible sexual exposure to Zika virus should be tested if either she or her male partner developed symptoms consistent with Zika virus disease(41).

CDC urges health care providers to report cases of suspected sexual transmission of Zika virus to local and state health departments.

Prevention in women of reproductive age

The following is an updated guidance of the Society for Maternal-Fetal Medicine and The American College of Obstetricians and Gynecologists for care of women of reproductive age(54).

Society for Maternal – Fetal Medicine and The American College of Obstetricians and Gynecologists Summary of Updated Guidance:

  • Women diagnosed with ZIKV disease should wait at least 8 weeks after symptom onset to attempt pregnancy. Men diagnosed with ZIKV disease should wait at least 6 months after symptom onset to attempt pregnancy. Asymptomatic women and men with possible exposure to ZIKV should wait at least 8 weeks after exposure before attempting pregnancy.

  • Consideration of amniocentesis has been removed from the CDC recommended testing algorithm. A decision regarding amniocentesis should be individualized for each clinical scenario on a case by case basis as with other con-genital infections.

  • Prevention of unintended pregnancies in the context of a ZIKV outbreak is especially important as an approach to reducing the likelihood of congenital infections.

  • Adherence to Standard Precautions is necessary to protect health care providers and patients in labor and delivery settings from transmission of ZIKV. The appropriate use of personal protective equipment is important for all health care providers to minimize the risk of transmission of infectious pathogens

  • through exposure to blood and body fluids. There is no evidence that contact precautions or respiratory isolation of ZIKV infected patients is warranted.
  • CDC established the U.S. Zika Pregnancy Registry and is collaborating with state, tribal, local, and territorial health departments to collect information about ZIKV infection during pregnancy and congenital ZIKV infection. Obstetrician– gynecologists and other health care providers are asked to report laboratory-confirmed cases of ZIKV to their state, tribal, local, or territorial health department and should notify state, tribal, local, or territorial health department staff or CDC registry staff of adverse events.

  • CDC maintains a 24/7 clinical consultation service for health care providers evaluating and caring for pregnant women and infants with possible ZIKV infection. Call CDC’s Zika Pregnancy Hotline for Healthcare Providers at 770488-7100 or e-mail for any concerns related to clinical management.

  • ZIKV testing is performed at the CDC Arbovirus Diagnostic Laboratory and a few state health departments. Contact your state health department (ACOG members only) to facilitate testing using this list provided by CDC.

The International Federation of Gynecology and Obstetrics - FIGO Working Group for the Prevention of Unsafe Abortion (2016) has outlined an initiative to contribute to the reduction of unplanned pregnancies and newborns with malformations in 10 Latin America countries at risk for infection by the Zika virus. The intervention will consist of further information on the effectiveness to prevent pregnancy and the side effects of different contraceptive methods, including methods of long duration; it will motivate and train providers in the practice of insertion and removal of intrauterine devices (IUDS) and subdermal implants; and will place these methods accessible to the population of women in selected public health services. It aims to reduce the risk of unsafe abortion among pregnant women who acquire the infection through counseling on the risks and access to legal interruption of pregnancy in countries where it is permitted by law.

In our region, the Committee on Sexual and Reproductive Rights of the Latin American Federation of Societies of Obstetricians and Gynecologists -FLASOG supports the Declaration of a Zika virus public health emergency by the World Health Organization, but expresses great concern to declarations of several Governments in the region that advise women to avoid getting pregnant until better understanding and control of the virus is achieved (eg. Colombia: to delay pregnancy for 6-8 months; El Salvador: to delay pregnancy until the year 2018; Jamaica: to delay for 6-12 months). Taking into account that in our region more than half of pregnancies are not desired/sought after and there is a high rate of sexual violence/abuse, the recommendations of Governments to postpone pregnancies without expanding access to contraception and safe abortion are not reasonable. The poorest and most vulnerable women of our region have more possibility of being infected by the conditions of inequality in which they live and are less likely to have access to sex education, contraception and safe abortion services. In this statement, FLASOG calls upon the Governments of the region so that this global crisis be the opportunity for reducing inequality within and between countries (Objective 10 of Sustainable Development), because without the elimination of inequalities the agenda of sustainable development will not move forward(55).

Special considerations for women undergoing fertility treatment

No instances of Zika virus transmission during fertility treatment have been documented, but transmission through donated gametes or embryos is theoretically possible, given that Zika virus can be present in semen, and sexual transmission has occurred(30). The Food and Drug Administration (FDA) has developed guidance for donated tissues in the context of a Zika virus outbreak, including donated sperm, oocytes, and embryos(56). Professional organizations recommend recipients be informed and counseled about potential risks before use of the donated tissue(57).


Symptoms of Zika infection last for 4-7 days and are self-limiting. Neurological and autoimmune complications are rare. So far, there is no specific antiviral treatment or effective vaccine, so it´s giving priority symptomatic and supportive treatment for the acute phase and make an early diagnosis of atypical and severe forms(58).

Recommendations include getting plenty of rest, drinking enough fluids to prevent dehydration, treat pain and fever with acetaminophen or paracetamol, do not take aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) until dengue can be ruled out to reduce the risk of bleeding(59).

Zika in Peru

Until April 15, 2016 only five cases of confirmed imported cases were reported in Peru. On April 16, the first case of Zika virus sexual transmission was reported in La Molina, Lima (there is no Aedes aegypti in this area) by the Ministry of Health(60). The virus was detected in semen of a man returning from Venezuela who infected his wife; his parents who had traveled with him also gave positive for Zika virus. And there is a pregnant woman who acquired Zika virus disease in the jungle frontier between Peru and Colombia and is now in Lima for perinatal surveillance. More cases would have been encountered in the past few weeks.

Aedes aegypti is currently being surveyed by ovitraps (oviposition traps) in 392 districts in 20 Regions. The vector is found mainly in the mountain area, the jungle, and both the northern and central Peruvian coast. Zika virus ARN genoma detection in serum, urine, semen by RT-PCR is currently done at the Peruvian Instituto Nacional de Salud and diagnosis by ELISA assay is performed in several regions.

Infection with Zika virus is known to be asymptomatic in three fourth of patients. Women with 12-weeks pregnancies who develop fever and exanthema are considered of high risk for microcephaly.

Surveillance of cases of both Guillain Barré and pregnant women has been implemented as well as a fluxogram for cases of microcephaly.

There is a recommendation to people returning from infected areas to abstain from going to Peruvian areas where the vector exists in order to decrease the probability of propagation of the disease. Condoms are provided in Peruvian airports to persons returning from Zika infected areas to be used for at least eight weeks, estimated life-time of the virus in our body.

Most probably Peru will not be most affected by Zika virus disease, but preventive measures have been opportunely taken by the Ministry of Health. Surveillance should continue because even though the disease now seems to slow down in Brazil, and problems will start just in the summer season in the southern USA, we still do not know if ZIKV outbreak will have seasonal reappearance and to what extent.

Latest news on Zika

When this review paper was going to press, the following were the latest news on Zika.

The most important infectious diseases (ID) sto ry for early 2016 is the exploding epidemic of Zika, with widespread penetration in Central and South America, Mexico, and the Caribbean. The epidemic has had substantial consequences in Brazil, where more than 1.5 million cases of Zika infection have occurred(61). By April 11, 2016, the National Library of Medicine had indexed more than 500 Zika-related articles, the CDC had published more than 10 guidance documents, and New York City had a 6-point Zika plan.

According to the Ministry of Health, the number of confirmed and suspected cases of microcephaly in Brazil associated with the Zika virus was down to 4 759 in the week through May 7, hundreds less than more than 5 200 suspected in late March. As doctors and Brazilian health officials find that some suspected cases of microcephaly are not the disorder, the total number of confirmed cases in Brazil stands at 1 326. A further 3 433 cases are still being investigated. Most of the cases in Brazil remain focused in the country’s northeast, where 1 190 cases have been confirmed(62).

According to the CDC statement, a total of 279 pregnant women have tested positive for Zika in either the U.S. or its territories. Within the U.S., 49 percent of the 157 infected pregnant women reported feeling symptomatic. Of the 122 infected pregnant women in the U.S. territories, 66 percent reported clinical symptoms. In addition to the CDC’s report, the World Health Organization announced that the same strain of virus that is currently being spread across the Americas has also infected 7 500 people in Cape Verde, a small island off the coast of West Africa(63).

Although the Zika epidemic is on the decline in certain countries, such as Brazil, Colombia, and Cape Verde, the number of cases imported into Europe from the American continent is clearly on the increase. However, at this stage of the research, the risk for an epidemic seems small. It is highly likely that there will be a few autochthonous cases, like there were last year with the chikungunya virus(64).

Following reporting mucocutaneous findings and course in an adult with ZIka virus infection, the researchers suggest that a detailed aware ness of mucocutaneous findings associated with Zika virus infection will support its early recognition and will facilitate elimination of Zika infection from consideration for concerned patients who present with other, more common erythematous eruptions(65).

Resistance of mosquitoes to insecticides and the logistics of identifying and eliminating mosquito breeding sites in large urban centers present challenges to mosquito control. Novel approaches such as the release of genetically modified mosquitoes to reduce local populations of A. aegypti are being explored and could decrease the transmission of ZIKV and perhaps some other arboviruses. However, the possibility that additional mosquito species, such as Aedes albopictus, could act as vectors for ZIKV warrants additional consideration for the design of vector control strategies(66).

Diagnostic testing for Zika virus infection can be accomplished using molecular and serologic methods. Real-time reverse transcription–polymerase chain reaction (rRT-PCR) is the preferred test for Zika virus infection because it can be performed rapidly and is highly specific. However, in most patients, Zika virus RNA is unlikely to be detected in serum after the first week of illness. Recent reports using adaptations of previously published methods suggest that Zika virus RNA can be detected in urine for at least 2 weeks after onset of symptoms(67). The CDC interim guidance recommends ZIka virus rRT-PCR testing of urine collected less than 14 days after symptom onset, along with testing of patient-matched serum samples, for the diagnosis of suspected Zika infection. If the PCR result is negative, serologic (IgM) testing should be performed. CDC recommendations for Zika virus testing of serum and other clinical specimens remain unchanged at this time.

In a French report of two cases of Zika infection, a complete ZIKV genome was sequenced from saliva samples obtained from Patient 1 and semen samples obtained from Patient 2. Only four mutations, all of them synonymous, differentiated the sequences of the two patients. The complete nucleotide coding sequences of ZIKV identified in these semen and saliva samples cluster together within the phylogenetic tree. These data support the hypothesis of sexual transmission (either oral or vaginal) of ZIKV from Patient 2 to Patient 1. The investigators could not rule out the possibility that transmission occurred not through semen but through other biologic fluids, such as pre-ejaculate secretions or saliva exchanged through deep kissing(68).

The length of time that Zika virus remains in semen is unknown(69). In a man with symptomatic Zika virus infection and who recovered in a few days, blood, urine, and semen samples were collected 2 weeks after diagnosis. Zika virus RNA loads were quantified. The RNA virus loads were 2·8 log10 copies per mL in plasma, 3·1 in urine, and 8·6 in semen. The viral load in the semen was roughly 100 000 times that of his blood or urine more than 2 weeks after symptom onset. The reason for this difference is unknown and needs investigation(70). Zika virus RNA has been identified in breast milk, but attempts to culture the virus were unsuccessful(69).

Microcephaly, brain atrophy, ventricular enlargement, and intracranial calcifications have been reported in neonates who have tested positive for Zika virus infection. Ocular defects, scalp rugae, and joint contractures also have been reported in cases of suspected congenital Zika virus infection (ie, neonates with microcephaly for whom Zika virus testing had not been performed). In addition to transmission during pregnancy, peripartum transmission of Zika virus has been reported in two mother–newborn pairs during the 2013–2014 French Polynesian outbreak.

There is no standard definition for fetal microcephaly; it may be suspected if the head circumference is more than 2 or 3 standard deviations below the mean for gestational age. In a recent study of microcephaly from causes other than Zika virus infection, prenatal ultrasound diagnosis of microcephaly at gestational ages ranging from 22 weeks to 38 weeks had a positive predictive value for neonatal microcephaly of about 57%. Other abnormalities that have been detected ultrasonographically in association with congenital Zika virus infections include corpus callosal and vermian dysgenesis, enlarged cisterna magna, severe unilateral ventriculomegaly, agenesis of the thalami, cataracts, and intraocular calcifications(69).

Considering different infection-rate scenarios (from 10 to 80%), possible overreporting (0% or 100%), and an uncertain baseline microcephaly rate (2 to 12 cases per 10 000 births), a strong association between the risk of microcephaly and infection risk in the first trimester and a negligible association in the second and third trimesters has been encountered, in keeping with the associations found in population-level estimates for French Polynesia. The baseline risk of microceph aly was low, approximately 2 per 10 000 births, but the estimated risk due to infection in the first trimester ranged from 0.88% (95% credible interval, 0.80 to 0.97), when an 80% overall ZIKV infection rate and 100% overreporting of microcephaly cases was assumed, to 13.2% (95% credible interval, 12.0 to 14.4), when a 10% ZIKV infection rate and no overreporting was considered(71).

On 9 June 2016, the Ministry of Health of Peru reported there are 70 native and 14 imported cases of Zika virus in our country. The National Health Emergency Operative Committee for Prevention and Control of Zika has been activated in order to prevent the spread of the virus in places that show active transmission as Jaén, Yurimaguas, Zarumilla, Tocache and Pucallpa(72).

And for June 15, 2016, 75 cases of Zika, 38 of them in pregnant women, were reported in Jaen, Caja-marca, in the North Andes of Peru. The rapid spread of the Zika virus in Peru has led the Revista Peruana de Ginecología y Obstetricia Editorial Committee to publish a symposium on the infection by Zika virus in Peru in the next issue of the journal.


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Conflict of interest disclosure: No conflict of interest to report.


Artículo recibido el 23 de abril de 2016 y aceptado para publicación el 3 de mayo de 2016.