Zika virus is an arbovirus belonging to the Flavivirus genus (1). The virus was first identified from sentinel rhesus monkeys in the Zika forest of Uganda in 1948 and subsequently isolated from Aedes africanus mosquitoes from the same forest (2,3). Rare sporadic cases of Zika virus infection were recorded between the 1960s and 1980s in Africa and Asia until 2007, when the first outbreak of Zika virus disease was recorded in the Micronesian island of Yap (4). The next large outbreak was in French Polynesia and in other countries and territories in the Pacific in 2013 and then in Brazil in 2015 and in other countries in the Americas (5). Since the end of 2016, Zika virus transmission has markedly declined in the Americas. As of July 2019, 87 countries and territories in the subtropical and tropical areas have reported evidence of mosquito-transmitted Zika virus infection (6). In addition, in October 2019, the first case of locally acquired Zika virus was confirmed in France (7). The spatial heterogeneity in Zika virus infection rates created pockets of susceptible populations that can sustain transmission in the future (6).

The symptoms caused by Zika virus in the general population are mild, consisting of flu-like febrile illness for a few days (8). However, the most alarming feature of Zika virus infection is during pregnancy, with its ability to cause microcephaly, congenital malformations and fetal demise (8).

The diagnosis of Zika virus infection usually involves serological tests for Zika virus antibodies (immunoglobulin M (IgM) or IgG) or nucleic acid amplification test for Zika virus viral RNA. These approaches have limitations (6,9–12); both false-positive and false-negative results can occur with nucleic acid amplification testing, which is only useful during a short window when Zika virus viraemia is present (beginning 3–5 days after illness onset and persisting for about one week). Serological testing is limited because cross-reactivity to other flaviviruses can lead to false-positive results and, as the incidence of Zika virus declines, the rate of false-positives increases. Also, limited information is available on the persistence of IgM antibodies, which creates challenges for diagnosing acute infection. Because of these limitations, serological testing is used to classify “probable infection” and RNA testing for confirmed infection.

Zika virus is primarily transmitted to humans through the bite of infected Aedes mosquitoes, mainly Aedes aegypti. It can also be transmitted less virulently by sexual contact (13–15), blood transfusion (16–18), blood products (19) or organ transplantation (16,20). Zika virus has also been detected in urine, saliva, amniotic fluid, female genital tract secretions, semen, cerebrospinal fluid, aqueous humour, conjunctival fluid and nasopharyngeal swabs. It has been shown to be vertically transmitted through transplacental maternofetal passage or during birth (15–17,21). The incubation period for Zika virus is not clear. It is thought to be similar to that of other mosquito-borne flaviviruses: probably less than one week (22).

There are concerns for possible transmission of Zika virus during breastfeeding since it has been detected in breast-milk samples (21,23–28). WHO recommends exclusive breastfeeding the first six months of life and continued to two years and beyond. It is unclear whether breast-milk carries enough viral load or infectivity to lead to infection among infants (27–30) or whether breast-milk possesses antiviral activity. An in vitro study with 39 samples of human milk investigated the antiviral activity of human milk against two flaviviruses, Zika virus and Usutu virus. Human milk showed antiviral activity against Zika virus and Usutu virus at all stages of lactation, with no significant differences in the activity of colostrum, transitional or mature milk. The mechanism of action studies demonstrated that colostrum does not inactivate viral particles but hampers the binding of both flaviviruses to cells (31). In addition, during breastfeeding there could be exchange of other bodily fluids, such as sweat and blood, in addition to breast-milk.

WHO released an interim guideline on breastfeeding in the context of Zika virus in 2016 during the outbreak (32), with a rapid advice guideline following later that year (1). WHO published a toolkit for the care and support of people affected by complications associated with Zika virus in 2017 (33). In these documents, WHO recommended that mothers with possible or confirmed Zika virus infection or exposure continue to breastfeed, since the benefits of breastfeeding for the infant and mother outweigh any potential risk of Zika virus infection through breast-milk.

Transmission of Zika virus infection from mother to fetus during pregnancy may result in microcephaly (smaller than normal head size) and other major congenital anomalies among infants, collectively referred to as congenital Zika syndrome. Depending on its severity, microcephaly may lead to seizures, hearing and vision deficits, intellectual disability and impaired development and be life threatening. Zika virus infection may also lead to Guillain-Barré syndrome, including acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, ophthalmoplegia, ataxia and areflexia (6). Congenital Zika virus infection abnormalities in neurodevelopment, hearing and vision could appear postnatally, mainly during the first year of life. An in vitro study on the effects of Zika virus infection in the established mature myelinated central nervous system shows that Zika virus infection affects central nervous system cells even after myelination, a process critical for saltatory conduction and neuronal function, has taken place (34).

Proper nutritional status is a great concern for infants with congenital Zika syndrome. Poor nutritional status may occur due to decreased muscle tone leading to minimal activity, reduced feeding, dysphagia, difficulty feeding, gastroesophageal reflux, delayed gastric emptying and abnormal metabolic demands because of spasticity (35). Support for the caregivers of infants with congenital Zika syndrome may be a protective factor for optimizing long-term nutritional status, attaining developmental milestones and enhancing the quality of life.

In 2016, WHO published recommendations for screening, assessing and managing neonates and infants with complications associated with Zika virus exposure in utero (36). In this publication and in the 2017 toolkit for the care and support of people affected by complications associated with Zika virus (33), WHO recommended assessment for signs of neurodevelopmental abnormalities, including feeding difficulties, for infants born to mothers with suspected, probable or confirmed Zika virus infection during pregnancy, even without microcephaly. Follow-up visits should occur at three, nine and 24 months of age at a minimum. In addition, comprehensive neurodevelopmental assessment and supportive therapy should be in place for irritability, seizures and swallowing difficulties for infants with congenital Zika syndrome. Developmental and neurological assessment should be performed with the full engagement of caregivers to identify developmental delays and other nervous system abnormalities such as epilepsy and disorders of movement, posture and swallowing. Further, supplementation may be appropriate for children with poor weight gain through additional feeding and complementary foods. Fortification with micronutrients may also be needed if nutritional deficiencies are present (33).

Health issues among infants with congenital Zika syndrome may persist into adulthood, increasing the risk of poor health and additional requirements for health-care services (35). In Brazil, a case series ascertained 30 children with Zika-related microcephaly who were born during the 2015 epidemic in the state of Pernambuco. Children were referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months, and 53% were female. The most common endocrine dysfunctions were short stature, hypothyroidism and obesity (37).

Improving the knowledge, skills and behaviour of the caregivers of infants affected by complications of Zika virus infection may be imperative to preserving health, maximizing development and promoting quality of life. In turn, this may reduce the need for additional health-care services in the future (35). Although there is no longer an outbreak, Zika virus transmission continues in some areas of the world. It is important to have a standard guideline as part of efforts to manage infant feeding in areas with transmission. Other interim WHO guidance on Zika virus has been updated, including recommendations for preventing the sexual transmission of Zika virus (38). Since data about long-term outcomes associated with Zika virus infection among infants are becoming available, the WHO guideline on infant feeding in areas of Zika virus transmission will be updated into a standard WHO guideline, following the WHO processes for guideline development.