The Zika virus has quickly become one of the most pressing public health issues worldwide. Following its explosive spread throughout Latin America, Zika has the potential to significantly threaten the health and well-being of many across the globe.[1] The U.S. is not immune to these concerns, as local transmission of Zika has recently been confirmed in Florida and Texas. While it is unlikely that a large-scale outbreak will impact the continental U.S., the continued spread of Zika throughout affected regions is expected. By one estimate, Zika is projected to infect 93.4 million people in the Americas alone, including 1.65 million childbearing women.[2] Even more alarming than the scale of this epidemic are the neurological defects associated with Zika infection, which include the neurological conditions congenital microcephaly and Guillain-Barré syndrome.[3] Given the heightened public anxiety and concern about the effects of Zika, it is critical that not only a vigorous public health response is developed, but also an ethical one.
The Zika virus (ZIKV) garnered significant international attention in October of 2015 as Brazil’s Health Ministry reported a notable increase in the number of cases of microcephaly and central nervous system (CNS) malformations among newborns.[4] In July of 2015, the Brazilian Ministry of Health reported the detection of Guillain-Barré syndrome in patients recently infected with ZIKV. By February of 2016, the World Health Organization declared the association of Zika infection with microcephaly and other neurological disorders as a Public Health Emergency of International Concern due to the continued spread of the virus throughout Latin America and the Caribbean.[5] While the designation of Zika as a public health emergency was removed at the end of November, Zika continues to be an ongoing concern in areas affected by the virus and in regions where Aedes aegypti mosquitos are endemic.
Very little is known about the Zika virus itself. Scientists and epidemiologists are working to decipher the reasons behind the global increase and spread of the ZIKV. Known to be spread by the Aedes genus of mosquitos, in particular Aedes aegypti, the virus itself is a flavivirus similar to West Nile, yellow fever, and dengue. Zika infection causes a mild illness lasting 2–7 days, including symptoms of maculopapular rash, fever, conjunctivitis, muscle and joint pain, fatigue, and headache. Approximately 20% of those infected experience symptoms; the remainder are asymptomatic. It is unclear why ZIKV, specifically the Asian lineage, has recently emerged and led to epidemic spread. Several explanations for this emergence have been proposed, including whether viral mutations have caused an increase in transmission or virulence. It has also been suggested that climate changes associated with El Niño in South America in 2015 and global warming have facilitated an increase in the population and spread of Aedes mosquitos. Anthropological factors, such as globalization and urbanization, may also be a factor in the spread of mosquito vectors beyond their original geographic habitats.[6] It has also been recently discovered that Zika can be transmitted through non-vector modes, including through vertical transmission (mother to fetus), sexual activity, blood transfusion, and in one instance, through nonsexual transmission via contact with an infected patient’s sweat or tears.[7]
The virus was first identified in rhesus monkeys in 1947 in the Zika forest of Uganda. Prior to 2007, only 14 cases of human Zika virus infection were documented worldwide. The first major outbreak of the virus occurred on the island of Yap in Micronesia in 2007, where an estimated 73% of the population over the age of three was infected.[8] Subsequent outbreaks occurred in the Pacific Islands—French Polynesia, Easter Island, the Cook Islands, and New Caledonia—in 2013–2014.
A total of 75 countries and territories in the Americas, Southeast Asia, Pacific Islands, and Africa have reported evidence of mosquito-borne ZIKV transmission since 2007, with an estimated 3 to 4 million persons infected in the Americas alone.[9] An additional 12 countries have reported cases of person-to-person transmission of ZIKV through sexual transmission following travel in Zika-affected areas.[10] As of January 4, 2017, 210 cases of locally acquired mosquito-borne cases have been reported in the United States in Miami-Dade county in Florida and 6 cases in Brownsville, Texas. Of the total 4,835 cases (local and travel associated) reported in the U.S., 38 have been identified as being sexually transmitted. Zika has particularly devastated the U.S. territory of Puerto Rico, with a total of 34,045 cases reported so far.[11] In areas of local transmission it is unknown how many of these cases are sexually transmitted versus locally transmitted. It is likely that ZIKV infection is underreported given that the illness itself is relatively mild and the majority of cases are asymptomatic.
The primary means of preventing Zika spread is through vector control, including eliminating standing water, larviciding, and the application of insecticides via backpack, truck-mounted, and aerial spraying. A newer approach is the introduction of genetically modified mosquitos as a means of culling local populations of the Aedes aegypti mosquitos. A field trial testing this approach is set to begin in Key Haven, Florida, following recent voter approval.[12] Scientists are also currently working on developing a vaccine for ZIKV, with several vaccine candidates in different stages of development. Early investigations are promising, with one recent study demonstrating that three vaccine platforms were able to completely protect rhesus monkeys against ZIKV strains.[13] An additional three separate vaccine candidates have begun Phase 1 clinical trials to evaluate safety for human use.[14] It is unlikely, however, that a fully licensed Zika vaccine will be available for several years.
During the 2013–2014 outbreaks of Zika virus in French Polynesia, 38 cases of the rare syndrome Guillain-Barré and 25 cases with neurological complications (encephalitis, meningo-encephalitis, paraesthesia, facial paralysis, and myelitis) were reported, first indicating these neurological conditions may be linked to ZIKV infection.[15] This association was strengthened by a case-control study of patients diagnosed with Guillain-Barré syndrome providing serological evidence of recent ZIKV infection.[16] Similarly, from April 1, 2015 to March 31, 2016, a total of 164,237 confirmed and suspected cases of ZIKV infection and 1,474 cases of Guillain-Barré syndrome were reported in Brazil, Colombia, the Dominican Republic, El Salvador, Honduras, Suriname, and Venezuela, with a close association between ZIKV transmission and increased incidence of Guillain-Barré.[17]
Guillain-Barré syndrome is an acute, immune-mediated disease causing peripheral neuropathy, presenting 2–4 weeks following a viral or bacterial infection. Symptoms begin with tingling sensations and varying degrees of weakness in the legs. This weakness may progress over hours to days, involving the arms, truncal muscles, cranial nerves, and respiratory muscles to significantly impact motor function and the ability to walk independently. Approximately 25% of patients require mechanical ventilation following respiratory failure. With immunotherapy most patients recover; however, up to 20% of patients remain severely disabled and 5% die following medical complications, such as sepsis, pulmonary embolism, and cardiac arrest.[18]
It is unknown whether prior exposure to other endemic flaviviruses (e.g. chikungunya, dengue) results in more severe effects of ZIKV due to the immune response produced by the first infection leading to increased viremia. Recent research, presented at the 2016 Annual Meeting of the American Society of Tropical Medicine and Hygiene, suggests that Aedes aegypti mosquitos could be infected with ZIKV and chikungunya simultaneously; a separate study in Nicaragua found that one in five patients who tested positive for chikungunya, dengue, or ZIKV were co-infected with two or all three viruses.[19] Experimental models and expression studies of candidate viral entry receptors (e.g., AXL) have demonstrated that ZIKV infects human cortical neural progenitor cells and may target several other brain cell types, including radial glial cells, astrocytes, endothelial cells, and microglia.[20] In light of the epidemiological data and experimental models, it has become evident that ZIKV is an emerging neurotropic virus that targets neuronal cells in all stages of development.
Given the neurotropic effects of ZIKV on the developing brain, the Zika epidemic is hypothesized to potentially have a greater impact on a generation of children than the thalidomide and rubella crises of the 1960s.[21] The link between microcephaly and ZIKV was first identified six months into the epidemic in Brazil with an observed twenty-fold increase in congenital microcephaly.[22] Retrospective studies of the Zika epidemic on French Polynesia (2013–2014) and the current outbreak in Latin America (2014–present) have also noted an increase in cases of fetal abnormalities, including microcephaly, following ZIKV infection.[23] Microcephaly is defined by a smaller than normal head circumference, typically due to improper brain development leading to intracranial volume loss. This condition may cause impaired cognitive development, delayed motor functions and speech, seizures, difficulties with coordination and balance, reduced lifespan, and other brain or neurological abnormalities in affected persons.[24] The Centers for Disease Control (CDC) and World Health Organization (WHO) have concluded a causal relationship exists between prenatal Zika infection, microcephaly, and other serious brain anomalies. This link has been supported by a recent case-control study commissioned by the Brazilian Ministry of Health examining the association between microcephaly and in-utero Zika virus infection via molecular and serological data.[25]
The Zika virus can be vertically transmitted, across the placenta from an infected mother to the developing embryo or fetus during all stages of pregnancy. Recent evidence suggests a strong association between microcephaly and infection in the first trimester, with a risk estimated between 0.88–13.2%, with a potential peak risk during gestational weeks 14 to 17.[26] This indicates that the first trimester is the most critical period for infection.[27] The current understanding of the risks of intrauterine ZIKV infection is based on symptomatic patients. The effects of asymptomatic infection have yet to be elucidated. Several adverse outcomes have been observed following maternal ZIKV infection, including miscarriage, fetal death (including at 36 and 38 weeks gestation), placental insufficiency, fetal growth restriction with and without microcephaly, abnormal amniotic fluid volume, abnormal arterial flow in the cerebral or umbilical arteries, cerebral calcifications, and CNS injury.[28] Additionally, intrauterine ZIKV infection can also lead to intrauterine growth restriction and low birth weight. Hearing loss in infants with microcephaly and congenital retinal lesions have also been reported.[29] While there have been some reports of brain anomalies following third trimester ZIKV infection, no apparent defects were identified in a study of 1,850 pregnant women in Colombia, where more than 90% of women were infected in the third trimester.[30] Long-term study is needed to determine whether third-trimester infection gives rise to neurological abnormalities that may manifest later in childhood in infants with normal head circumference at birth.
From the clinical data, it is evident that ZIKV infection is associated with multiple abnormalities other than microcephaly. The CDC has now defined a distinct phenotype caused by intrauterine ZIKV infection, referred to as Congenital Zika Syndrome (CZS), the most notable clinical feature being severe microcephaly consistent with fetal brain disruption sequence. Specifically, there are five features identified as being unique to CZS: severe microcephaly with partially collapsed skull, thin cerebral cortices with subcortical calcifications (likely related to cell death), macular scarring and focal pigmentary retinal mottling, congenital contractures involving one or more joints (i.e., clubfoot or inflexible joints), and early hypertonia (i.e., increased muscle tone) and symptoms of extrapyramidal involvement.[31] These structural and functional anomalies cause significant cognitive, sensory, and motor disabilities. The full spectrum of phenotypes in affected infants has yet to be determined.
Initial research suggests that nearly a third of fetuses born to mothers infected with ZIKV will be affected by severe CNS damage.[32] Also worrisome are concerns that the neurotropic actions of ZIKV may lead to subtler CNS damage that is not detected at birth, ranging from auditory and visual problems to intellectual disabilities and seizure disorders, the impact of which may not be detected for years. In order to understand the long-term effects of ZIKV, the National Institutes of Health and Fiocruz (a scientific research organization linked to the Brazilian Ministry of Health) are launching a major prospective study entitled “Zika and Infants in Pregnancy (ZIP),” with the goal of enrolling 10,000 women at up to fifteen sites where the virus is endemic, including women who are both symptomatic and asymptomatic. This study also plans to follow children who are infected with ZIKV in early childhood.[33]
It may be that fears of widespread congenital Zika syndrome are misplaced. So far, more than 75% of the 2,175 infants with congenital Zika syndrome in the Americas have been born in northeastern Brazil, indicating that a factor additional to ZIKV is causing the high incidence of microcephaly in this region.[34] It is critical, however, that rigorous clinical, laboratory, and epidemiological data of pregnant women with exposure to ZIKV be collected during all stages of pregnancy and any infants with signs of congenital anomalies be closely monitored as they develop into childhood.
Recent evidence suggests that Zika is also sexually transmitted (male to female, male to male, female to male) via unprotected oral, anal, and vaginal intercourse.[35] Most reported cases of sexual transmission have been from symptomatic persons, although two cases (one likely, one more definitive) of sexual transmission from an asymptomatic partner have been reported.[36] It is not known how long Zika remains present in semen—the longest reported detection of ZIKV RNA in the semen of a symptomatic man is 188 days, although the virus has been cultured (to demonstrate the presence of replicative virus) in semen up to 69 days after the onset of illness.[37] It is also unknown how long ZIKV in infected semen may be sexually transmitted. To date, the longest duration between onset of symptoms and sexual transmission of infectious ZIKV to a female partner is 41 days.[38]
Zika RNA has been found to be present in vaginal fluids, blood, urine, saliva, and breast milk.[39] It has yet to be conclusively determined whether Zika can be transmitted though these bodily fluids as well. Identifying persons who contract ZIKV through sexual transmission is complicated by the fact that in areas with local transmission, many couples cohabitate and are thus exposed to the same vectors, making it difficult to determine whether mosquito-borne or sexual transmission is the culprit. Additionally, 80% of those infected with ZIKV are asymptomatic, adding to the challenge of tracking the spread of Zika and preventing its transmission through sexual contact. Considering the fetal congenital anomalies associated with ZIKV, the CDC recommends the use of condoms or sexual abstinence to reduce the risk of passing Zika between partners living in areas with active ZIKV transmission, especially if the female partner is pregnant. For couples who would like to conceive, the CDC recommends that symptomatic males and females be tested for ZIKV infection and if confirmed (or results indicate an unspecified flavivirus infection) suggests males should wait at least six months from symptom onset and women should wait at least eight weeks prior to attempting conception.[40]
The primary burden of the Zika epidemic is likely to disproportionately impact women, given the risks of intrauterine ZIKV infection and their traditional gender role as caretakers of children. In light of these risks, women in areas with active Zika transmission are being advised to consider delaying planned pregnancies for six to twelve months and to take steps to avoid unintended pregnancy. In El Salvador, the government is advising women to delay pregnancy until 2018.[41] In contrast to Colombia where the Zika epidemic appears to be waning and has been relatively short-lived, it is unknown how long the Zika epidemic will last in the rest of the Americas.
The most effective means of preventing sexual transmission of Zika to a partner is through the use of barrier contraceptive methods such as condoms. Pregnancy may also be avoided through oral or long-acting reversible contraceptives (i.e., intrauterine devices or implants). Contraceptives, however, may be difficult to access and afford in many affected countries. For example, a recent review of contraceptive prevalence rates (CPR)[42] in twenty-one countries with active Zika transmission in Latin America and the Caribbean reported that the use of modern contraceptive methods[43] ranged from 33.6% in Haiti to 75.7% in Costa Rica, with five countries with a CPR at 50% or below.[44] Contraceptive availability can also be an issue in many countries, with the Dominican Republic, El Salvador, Guatemala, Haiti, and Honduras reporting regular stock-outs of contraceptives.[45] Given the limited access to contraceptives in many Latin American countries and that 40% of pregnancies in Central America and 62% in South America are unplanned, these recommendations strike some as naïve, impractical, and unlikely to have a significant impact on the spread of ZIKV via sexual transmission.[46]
Even if contraception is available and affordable in Zika-affected countries, many women may decline contraceptive use as it may conflict with their deeply held moral and religious beliefs. Traditional teaching of the Roman Catholic Church considers the use of contraception, other than natural family planning, to be outside of God’s design for marital procreation.[47] Brazil has the largest population of Catholics in a single country, with approximately 65% of the population comprised of self-declared Catholics. While the CPR is high (75.2%) in Brazil, church leaders remain adamantly opposed to contraceptive use. The secretary general of the National Council of Bishops of Brazil recently stated, “Contraceptives are not a solution . . . . There is not a single change in the church’s position.”[48] Pope Francis indicated that it would be permissible for Catholic women to use contraception for the avoidance of pregnancy in Zika-affected areas, referring to the permission given by Paul VI for contraceptive use by nuns working in the Belgian Congo at risk of rape, stating, “On the other hand, avoiding pregnancy is not an absolute evil. In certain cases, as in this one, or in the one I mentioned of Blessed Paul VI, it was clear. I would also urge doctors to do their utmost to find vaccines against these two mosquitoes that carry this disease. This needs to be worked on.”[49] His comments were not without controversy, with many Catholic leaders reaffirming Roman Catholic teaching prohibiting contraception and abortion.[50] No formal pronouncement from the church has been issued to date in regards to contraceptive use in Zika endemic areas.
Pregnant women infected with ZIKV will be facing complicated clinical decisions regarding the health of their fetus, contending with the choice to continue their pregnancy in countries where abortion is legally permissible. The Zika epidemic has reignited the debate over abortion policy, particularly in Central and Southern America where only a few countries have broad abortion policies.[51] Like the previous thalidomide and rubella crises, it is thought that the increase in adverse fetal outcomes associated with Zika will promote sympathy for the plight of women carrying an affected fetus and will promote advocacy towards changing abortion policy and practices. In Brazil, abortion is illegal except in cases of rape, threat to the mother’s life, or fetal anencephaly.[52] Brazil’s attorney general is currently urging the Supreme Court to permit women infected with ZIKV the option of legal abortion, although public officials are divided over the expansion of abortion rights.[53] It has yet to be determined whether the Zika epidemic will substantially change existing abortion policies in countries that legally prohibit or highly restrict abortion.
Even if intrauterine infection is confirmed through serological testing and/or the presence of ZIKV RNA in amniotic fluid, a positive result is not necessarily predictive of subsequent fetal abnormality. Microcephaly and intracranial calcifications are typically detected in the late second or third trimester, although they may be diagnosed as early as 18 to 20 weeks gestation.[54] There are limits to what may be detected on ultrasound—the absence of brain anomalies on ultrasound does not exclude future microcephaly, nor does it conclusively determine the extent of neurological damage. One study, for example, found that prenatally diagnosed congenital microcephaly was confirmed postnatally in 21 out of 45 patients, with 12 out of the 15 patients having a normal scan between 15 and 20 weeks gestation.[55] Women and families may be faced with complex clinical decisions with uncertain outcomes for the life and health of their child, both in utero and in infancy.[56] It is likely that many women and their families will be impacted by miscarriage, stillbirth, and infants born with serious disability and uncertain prognoses given the adverse fetal outcomes associated with ZIKV infection. While it is imperative that the inherent dignity and value of human life, at all stages, is upheld in this crisis, women facing Zika-affected pregnancies need to be supported in making fully informed clinical decisions and provided with medical, psychological, and spiritual support in the face of a difficult diagnosis.
More broadly, Zika may have significant societal ramifications, both on a familial and systemic level. Infants born with congenital Zika syndrome or other medical challenges will need lifelong care requiring additional medical, educational, and developmental support. Costs of caregiving, medical treatment, and other therapies can be prohibitive for many families, especially the poor. It is estimated, for example, that the lifetime cost of care for an individual with the structural birth defect spina bifida is approximately $800,000 USD.[57] One estimate suggests that the direct cost of liveborn infants with Zika-associated microcephaly is $3.8 million USD.[58] In Brazil there have been multiple anecdotal reports of women giving up their infants with microcephaly to the state due to being abandoned by the child’s father, the high cost of care, and responsibilities that come with raising a disabled child.[59] Already fragile governmental infrastructures may be overwhelmed and poorly equipped to handle an increase in infants, children, and adults with serious disabilities and medical complications due to Zika infection.
In the global south, Zika has disproportionately affected the poor. In Brazil, the majority of Zika-related microcephaly cases have occurred in the northeast of the country, an area in which most of Brazil’s poverty is concentrated. Basic sanitation is lacking in north and northeast Brazil, with only 19.9% and 51% of households with piped water, connection to a sewage or septic system, or garbage collection, respectively.[60] Impoverished neighborhoods with poor-quality housing, uncollected debris, and standing water allow for the breeding of insects and subsequent transmission of vector-borne diseases. Those with lower incomes may be unable to afford mosquito repellent or window screens for their homes. Additionally, economically disadvantaged regions may lack the medical personnel, intensive-care facilities, and treatments needed to properly address complications from ZIKV, including Guillain-Barré syndrome and congenital Zika syndrome. These challenges are the result of existing inequalities of access to healthcare and communal resources. In the case of Zika, poverty is not simply an economic issue, but an ethical one.
Scientists are only beginning to understand the effects of ZIKV on human health and in utero development. There will be a tremendous challenge towards creating a comprehensive strategy to not only understand the transmission and clinical outcomes of Zika and develop effective vaccines and therapeutics, but to support the infants, children, and families impacted by this disease. In many ways this crisis is simply an old problem in a new context, highlighting disparities of access to medical care, the difficulty of making prenatal clinical decisions with uncertain outcomes, and the challenges of inclusiveness and care of the disabled. There is a tremendous opportunity to respond to the Zika crisis with great compassion and understanding towards the vulnerable lives this virus disproportionately affects. The health of a society is dependent upon how it treats the most marginalized of its citizens. It is essential that an ethic of life remains central to the response to this epidemic as the full impact of the Zika virus becomes more elucidated, in terms of how it affects both human health and the lives of the most vulnerable members of our collective humanity.
[1] World Health Organization, “Situation Report: Zika Virus, Microcephaly Guillain-Barré Syndrome,” November 10, 2016, http://apps.who.int/iris/bitstream/10665/251001/1/zikasitrep10Nov16-eng.pdf (accessed November 11, 2016).
[2] T. Alex Perkins et al, “Model-Based Projections of Zika Virus Infections in Childbearing Women in the Americas,” Nature Microbiology 1 (2016), doi:10.1038/nmicrobiol.2016.126.
[3] Lyle R. Petersen et al., “Zika Virus,” New England Journal of Medicine 374, no. 16 (2016): 1552–1563.
[4] Ministério da Saúde, “Ministério da Saúde Divulga Boletim Epidemiológico,” November 17, 2015, http://portalsaude.saude.gov.br/index.php/cidadao/principal/agencia-sau-de/20805-ministerio-da-saude-divulga-boletim-epidemiologico (accessed November 11, 2016).
[5] World Health Organization, “WHO Statement on the First Meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika Virus and Observed Increase in Neurological Disorders and Neonatal Malformations,” February 1, 2016, http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/ (accessed November 11, 2016).
[6] Similar patterns have been observed with dengue and chikungunya. Petersen et al., “Zika Virus,” 1560.
[7] Sankar Swaminathan et al., “Fatal Zika Virus Infection with Secondary Nonsexual Transmission,” New England Journal of Medicine 375, no. 20 (2016): 1907–1909. In this case Zika was spread from a patient to a family member after contact with the patient’s skin and wiping their eyes. This patient had a viral load 100,000 times higher than what is typically observed in persons infected with Zika
[8] Mark D. Duffy et al., “Zika Virus Outbreak on Yap Island, Federated States of Micronesia,” New England Journal of Medicine 360, no. 24 (2009): 2536–2543.
[9] World Health Organization, “Situation Report.” Local transmission of Zika has occurred in 65 countries since 2015; an additional 10 countries have reported local mosquito-borne Zika infections before 2015, with no cases observed in 2016.
[10] Ibid.
[11] Centers for Disease Control and Prevention, “Case Counts in the US,” U.S. Department of Health and Human Services, January 5, 2017, https://www.cdc.gov/zika/geo/united-states.html (accessed January 9, 2017).
[12] Marley Walker, “Florida Votes to Release Millions of Zika-Fighting Mosquitos,” Wired, November 10, 2016, https://www.wired.com/2016/11/florida-votes-release-millions-zika-fighting-mosquitos/ (accessed November 11, 2016).
[13] Peter Abbink et al., “Protective Efficacy of Multiple Vaccine Platforms against Zika Virus Challenge in Rhesus Monkeys,” Science (August 4, 2016): 1–4, doi:10.1126/science.aah6157.
[14] ClinicalTrials.gov identifiers: NCT02840487, NCT02887482, and NCT02937233.
[15] European Center for Disease Prevention and Control, “Rapid Risk Assessment: Zika Virus Infection Outbreak, French Polynesia,” Stockholm: ECDC, (February 14, 2014), http://ecdc.europa.eu/en/publications/Publications/Zika-virus-French-Polynesia-rapid-risk-assessment.pdf (accessed November 11, 2016). See also, Guillaume Carteaux et al., “Zika Virus Associated with Meningoencephalitis,” New England Journal of Medicine 374, no. 16 (2016): 1595–1596; Sylvie Mécharles et al., “Acute Myelitis Due to Zika Virus Infection,” The Lancet 387, no. 10026 (2016): 1481; Cristiane N. Sores et al., “Fatal Encephalitis Associated with Zika Virus Infection in an Adult,” Journal of Clinical Virology 83 (2016): 63–65.
[16] Van-Mai Cao-Lormeau et al.,“Guillain-Barré Syndrome Outbreak Associated with Infection in French Polynesia: A Case-Control Study,” Lancet 387, no. 10027 (2016): 1531–1539.
[17] Thais dos Santos et al., “Zika Virus and the Guillain- Barré Syndrome—Case Series from Seven Countries,” New England Journal of Medicine 375, no. 16 (2016): 1598–1601.
[18] Nobuhiro Yuki and Hans-Peter Hartung, “Guillain- Barré Syndrome,” New England Journal of Medicine 366, no. 24 (2012): 2294–2304.
[19] Burness, “New Evidence Finds Mosquitoes Could Infect Humans with Zika and Chikungunya Viruses at the Same Time,” EurekAlert, November 14, 2016, https://www.eurekalert.org/pub_releases/2016-11/b-nef110916.php (accessed November 14, 2016); Jesse J. Waggoner et al., “Viremia and Clinical Presentation in Nicaraguan Patients Infected with Zika Virus, Chikungunya Virus, and Dengue Virus,” Clinical Infectious Diseases 63, no. 12 (2016): 1584–1590, doi10.1093/cid/ciw589.
[20] Hengli Tang et al., “Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth,” Cell Stem Cell 18, no. 5 (2016): 587– 590; Patricia P. Garcez et al., “Zika Virus Impairs Growth in Human Neurospheres and Brain Organoids,” Science (2016): 1–6, doi:10.1126/ science.aaf6116; Tomasz J. Nowakowski et al., “Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells,” Cell Stem Cell 18, no. 5 (2016): 591–596.
[21] For example, in the 1959–1965 rubella epidemic there were 20,000 cases of congenital rubella syndrome; however, the majority of women of childbearing ages had antibodies against rubella, with only 17% lacking rubella antibodies. (Patricia Brasil et al., “Zika Virus Infection in Pregnant Women in Rio de Janeiro—Preliminary Report,” New England Journal of Medicine, March 4, 2016, doi:10.1056/NEJMoa1602412).
[22] Pan American Health Organization and World Health Organization, “Epidemiological Alert: Neurological Syndrome, Congenital Malformations, and Zika Virus Infection: Implications for Public Health in the Americas,” December 1, 2015, http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid-=270&gid=32405&lang=en (accessed November 11, 2016); Wanderson Kleber de Oliveira et al., “Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy—Brazil, 2015,” Morbidity and Mortality Weekly 65, no. 9 (2016): 242–247.
[23] Petersen, “Zika Virus,” 1553–1554.
[24] National Institute of Neurological Disorders and Stroke, “NINDS Microcephaly Information Page,” March 14, 2016, http://www.ninds.nih.gov/disorders/Microcephaly/microcephaly.htm (accessed June 1, 2016).
[25] Sonja A. Rasmussen et al., “Zika Virus and Birth Defects—Reviewing the Evidence for Causality,” New England Journal of Medicine 374, no. 20 (2016): 1981–1987; Thalia Velho Barreto de Araújo et al., “Association Between Zika Virus Infection and Microcephaly in Brazil, January to May, 2016: Preliminary Report of a Case-Control Study,” The Lancet Infectious Diseases 16, no. 1 (2016): 1356–1363.
[26] Michael A. Johansson et al., “Zika and the Risk of Microcephaly,” New England Journal of Medicine 375, no. 1 (2016): 1–4, doi:10.1056/NEJMp1605367.
[27] Oliveira, “Increase in Reported Prevalence of Microcephaly.”
[28] Brasil, “Zika Virus Infection”; Annemiek A. van der Eijk et al., “Miscarriage Associated with Zika Virus Infection,” New England Journal of Medicine 375, no. 10 (2016): 1002–1004.
[29] Bruno de Paula Freitas et al., “Ocular Findings in Infants with Microcephaly Associated with Presumed Zika Virus Congenital Infection in Salvador, Brazil,” JAMA Ophthalmology 134, no. 5 (2016): 529–535; Mariana C. Leal et al., “Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus Infection—Brazil, November 2015–May 2016,” Morbidity and Mortality Weekly Report 65, no. 34 (2016): 917–919.
[30] Antonio Soares de Souza et al., “Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases,” Clinical Infectious Diseases 63, no. 12 (2016): 1622–1625, doi:10.1093/cid/ciw613; Oscar Pacheco et al., “Zika Virus Disease in Colombia—Preliminary Report,” New England Journal of Medicine (June 15, 2016): doi:10.1056/NEJMoa1604037; Giovanny V.A. França et al., “Congenital Zika Virus Syndrome in Brazil: A Case Series of the First 1501 Live Births with Complete Investigation,” The Lancet 388, no. 10047 (2016): 891–897.
[31] Cynthia A Moore et al., “Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians,” JAMA Pediatrics (2016): E1–E8, doi:10.1001/jamapediatrics.2016.3982.
[32] Brasil, “Zika Virus Infection.”
[33] National Institutes of Health, “NIH Launches Large Study of Pregnant Women in Areas Affected by Zika Virus,” June 21, 2016, https://www.nih.gov/news-events/news-releases/nih-launches-large-study-pregnant-women-areas-affected-zika-virus, (accessed November 11, 2016).
[34] Pan American Health Organization and World Health Organization, “Zika Cases and Congenital Syndrome Associated with Zika Virus Reported by Countries and Territories in the Americas, 2015–2016 Cumulative Cases,” October 20, 2016, http://www.paho.org/hq/index.php?option-=com_docman&task=doc_view&Itemid-=270&gid=36621&lang=en (accessed November 11, 2016).
[35] Emily E. Petersen et al., “Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure—United States, September 2016,” Morbidity and Mortality Weekly Report 65, no 39, (2016): 1077–1081.
[36] Richard B. Brooks et al., “Likely Sexual Transmission of Zika Virus from a Man with No Symptoms of Infection—Maryland, 2016,” Morbidity and Mortality Weekly Report 65, no. 34 (2016): 915–916; T. Fréour et al. “Sexual Transmission of Zika Virus in an Entirely Asymptomatic Couple Returning from a Zika Epidemic Area, France, April 2016,” EuroSurveillance 21, no. 23 (2016): 30254.
[37] L. Barzon et al., “Infection Dynamics in a Traveller [sic] with Persistent Shedding of Zika Virus RNA in Semen for Six Months After Returning from Haiti to Italy, January 2016,” EuroSurveillance 21, no. 32 (2016): 30316; E. Nicastri et al., “Persistent Detection of Zika Virus RNA in Semen for Six Months After Symptom Onset in a Traveller [sic] Returning from Haiti to Italy, February 2016,” EuroSurveillance 21, no. 32 (2016): 30314.
[38] Jean Marie Turmel et al., “Late Sexual Transmission of Zika Virus Related to Persistence in the Semen,” The Lancet 387, no. 10037 (2016): 2501.
[39] Kristy O. Murray et al., “Prolonged Detection of Zika Virus in Vaginal Secretions and Whole Blood,” Emerging Infectious Diseases 23, no. 1 (2017), doi:10.3201/eid2301.161394; Ann-Claire Gourinat et al., “Detection of Zika Virus in Urine,” Emerging Infectious Diseases 21, no. 1 (2015), doi:10.3201/eid2101.140894; Didier Musso et al., “Detection of Zika Virus in Saliva,” Journal of Clinical Virology 68 (2015): 53–55; Myrielle Dupont-Rouzeyrol et al., “Infectious Zika Viral Particles in Breastmilk,” The Lancet 387, no. 10023 (2016): 1051.
[40] Petersen, “Update.”
[41] Azam Ahmed, “El Salvador Advises Against Pregnancy until 2018 in Answer to Zika Fears,” New York Times, January 23, 2016, http://www.nytimes.com/2016/01/24/world/americas/el-salvador-advises-against-pregnancy-until-2018-in-answer-to-zika-fears.html (accessed November 11, 2016).
[42] The percentage of women of reproductive age who are using (or whose partner is using) a contraceptive method at a particular point in time.
[43] For example, oral contraceptives, implants, injectables, intrauterine devices, condoms, sterilization, and basal body temperature method, as opposed to the traditional rhythm or withdrawal methods.
[44] Jennifer Kates, Josh Michaud, and Allison Valentine, “Zika Virus: The Challenge for Women,” Kaiser Family Foundation, April 15, 2016, http://kff.org/global-health-policy/perspective/zika-virus-the-challenge-for-women (accessed November 14, 2016). These percentages do not take into account economic disparities, and thus contraceptive access, within a country.
[45] Ibid.
[46] Gild Sedgh, Susheela Singh, and Rubina Hussain, “Intended and Unintended Pregnancies Worldwide in 2012 and Recent Trends,” Studies in Family Planning 45, no. 3 (2014): 301–314.
[47] Humanae Vitae—Encyclical Letter of His Holiness Paul VI on the Regulation of Birth, 25 July 1968, http://w2.vatican.va/content/paul-vi/en/encyclicals/documents/hf_p-vi_enc_25071968_humanae-vitae.html (accessed November 11, 2016).
[48] Laurie Goodstein, “Catholic Leaders Say Zika Doesn’t Change Ban on Contraception,” New York Times, February 13, 2016, http://www.nytimes.com/2016/02/14/world/americas/catholic-leaders-say-zika-doesnt-change-ban-on-contraception.html (accessed November 14, 2016).
[49] “Full Text of Pope Francis’ In-flight Interview from Mexico to Rome,” Catholic News Agency, February 18, 2016, https://www.catholicnewsagency.com/news/full-text-of-pope-francis-in-fli... (accessed November 14, 2016).
[50] See, for example: The National Catholic Bioethics Center, “Zika Does Not Justify Abortion or Contraception,” February 22, 2016, http://www.ncbcenter.org/resources/news/zika-does-notjustify-abortion-or-contraception/ (accessed June 1, 2016).
[51] United Nations, “World Abortion Policies 2013,” March 2013, http://www.un.org/en/development/desa/population/publications/pdf/policy/WorldAbortionPolicies2013/WorldAbortionPolicies2013_WallChart.pdf (accessed November 14, 2016).
[52] In practice these laws have not minimized abortion, with an approximately 1 million abortions performed each year. It is reported that 31% of all pregnancies end with an induced abortion (Lisa A Goldman et al., “Brazilian Obstetrician- Gynecologists and Abortion: A Survey of Knowledge, Opinions and Practices,” Reproductive Health 2 (2005): doi:10.1186/1742-4755-2-10).
[53] Rogerio Jelmayer and Reed Johnson, “Brazil’s Attorney General Asks High Court to Allow Abortions for Women with Zika,” Wall Street Journal, September 8, 2016, http://www.wsj.com/articles/brazils-attorney-general-askshigh-court-to-allow-abortions-for-women-with-zika-1473372289 (accessed November 14, 2016).
[54] Centers for Disease Control and Prevention, “Zika Virus: Pregnant Women,” U.S. Department of Health and Human Services, August 16, 2016, http://www.cdc.gov/zika/hc-providers/pregnant-women/prenatal-diagnosis-microcephaly.html (accessed November 11, 2016).
[55] Leanne Dahlgran and R. Douglas Wilson, “Prenatally Diagnosed Microcephaly: A Review of Etiologies,” Fetal Diagnosis and Therapy 16, no. 6 (2001): 323–326.
[56] For a sample of selected case studies, see: Dana Meaney-Delman et al., “Zika Virus Infection Among U.S. Pregnant Travelers—August 2015– February 2016,” Morbidity and Mortality Weekly Report 65, no. 8 (2016): 211–214.
[57] Scott D. Grosse et al., “Retrospective Assessment of Cost Savings from Prevention: Folic Acid Fortification and Spina Bifida in the U.S.,” American Journal of Preventive Medicine 50, no. 5 supplement 1 (2016): S74–S80.
[58] Ru Li et al., “Cost-effectiveness of Increasing Access to Contraception during the Zika Virus Outbreak, Puerto Rico, 2016,” Emerging Infectious Diseases 23 (2017): 74-82.
[59] Jill Langlois, “Zika-Linked Microcephaly Costs Are Stressing an Already Strapped Brazil,” Fortune, March 2, 2016, http://fortune.com/2016/03/02/zika-costs-microcephaly-brazil/ (accessed November 14, 2016); Stephen Eisenhammer, “Brazil’s Mothers Left to Raise Microcephaly Babies Alone,” Reuters, March 11, 2016, http://www.reuters.com/article/us-health-zika-women-idUSKCN0WD21D (accessed November 14, 2016).
[60] Instituto Brasileiro de Geografia e Estatística— IBGE, “Síntese de Indicadores Sociais Uma Análise das Condicões de Vida da Populacão Brasileira 2013,” Rio De Janiero, Brazil, 2013, http://biblioteca.ibge.gov.br/visualizacao/livros/liv66777.pdf (accessed November 11, 2016).
Kirsten Riggan, "Zika: An Emerging Virus with Critical Implications,” Dignitas 23, no. 4 (2016): 10–16.
