On Feb. 1, 2016, the World Health Organization (WHO) Director-General, Dr Margaret Chan, based on the advice of Emergency Committee (EC), declared the current Zika virus outbreak a Public Health Emergency of International Concern (PHEIC).

Map of Uganda/Alvaro1984 18
Map of Uganda/Alvaro1984 18

How did we get to this point–a obscure, formerly believed to be a mild, essentially benign disease–is now a public health crisis?

Let’s look at some key points in the timeline history of Zika virus for a better understanding. (Source: WHO)

1947: Scientists conducting routine surveillance for yellow fever in the Zika forest of Uganda isolate the Zika virus in samples taken from a captive, sentinel rhesus monkey.

1948: The virus is recovered from the mosquito Aedes (Stegomyia) africanus, caught on a tree platform in the Zika forest.

1952: The first human cases are detected in Uganda and the United Republic of Tanzania in a study demonstrating the presence of neutralizing antibodies to Zika virus in sera.

1954: The virus is isolated from a young girl in Eastern Nigeria.

1958: Two further Zika virus strains are isolated from Aedes africanus mosquitos caught in the Zika forest area.

1964: A researcher in Uganda who fell ill while working with Zika strains isolated from mosquitoes provides the first proof, by virus isolation and re-isolation, that Zika virus causes human disease. Though a pink non-itchy rash lasting 5 days eventually covers most of his body, including the palms of his hands and soles of his feet, he reports his illness as “mild”, as he did not experience the “crippling bone pain” associated with dengue and chikungunya infections. Given the mild nature of the illness, the author concludes that “it is not surprising under normal circumstances the virus is not isolated frequently from man.”

1969–1983: The known geographical distribution of Zika expands to equatorial Asia, including India, Indonesia, Malaysia and Pakistan, where the virus is detected in mosquitos. As in Africa, sporadic human cases occur but no outbreaks are detected and the disease in humans continues to be regarded as rare, with mild symptoms.

Image/CDC
Image/CDC

2007: Zika spreads from Africa and Asia to cause the first large outbreak in humans on the Pacific island of Yap, in the Federated States of Micronesia. Prior to this event, no outbreaks and only 14 cases of human Zika virus disease had been documented worldwide.

2008: A US scientist conducting field work in Senegal falls ill with Zika infection upon his return home to Colorado and infects his wife in what is probably the first documented case of sexual transmission of an infection usually transmitted by insects.

2012: Researchers publish findings on the characterization of Zika virus strains collected in Cambodia, Malaysia, Nigeria, Senegal, Thailand and Uganda, and construct phylogenetic trees to assess the relationships. Two geographically distinct lineages of the virus, African and Asian, are identified.

2013–2014: The virus causes outbreaks in four other groups of Pacific islands: French Polynesia, Easter Island, the Cook Islands, and New Caledonia. The outbreak in French Polynesia, generating thousands of suspected infections, is intensively investigated. The results of retrospective investigations are reported to WHO on 24 November 2015 and 27 January 2016. These reports indicate a possible association between Zika virus infection and congenital malformations and severe neurological and autoimmune complications. In particular, an increase in the incidence of Zika infection towards the end of 2013 was followed by a rise in the incidence of Guillain-Barré syndrome.

20 March 2014: During the 2013–14 outbreak of Zika virus in French Polynesia, two mothers and their newborns are found to have Zika virus infection, confirmed by PCR performed on serum collected within four days of birth. The infants’ infections appear to have been acquired by transplacental transmission or during delivery.

2 March 2015: Brazil notifies WHO of reports of an illness characterized by skin rash in northeastern states. From February 2015 to 29 April 2015, nearly 7000 cases of illness with skin rash are reported in these states. All cases are mild, with no reported deaths.

7 May 2015: Brazil’s National Reference Laboratory confirms, by PCR, Zika virus circulation in the country. This is the first report of locally acquired Zika disease in the Americas.

16 October 2015: Colombia reports PCR confirmed cases of locally acquired Zika infection.

Image/Brazil Health Ministry
Image/Brazil Health Ministry

30 October 2015: Brazil reports an unusual increase in the number of cases of microcephaly among newborns since August, numbering 54 by 30 October.

24 November 2015: French Polynesia reports the results of a retrospective investigation documenting an unusual increase in the number of central nervous system malformations in fetuses and infants from March 2014 to May 2015. At the date of reporting, at least 17 cases are identified with different severe cerebral malformations, including microcephaly, and neonatal brainstem dysfunction.

28 November 2015: Brazil detects Zika virus genome in the blood and tissue samples of a baby with microcephaly and other congenital anomalies who died within 5 minutes of birth.

5 January 2016: Researchers report the first diagnoses of intrauterine transmission of the Zika virus in two pregnant women in Brazil whose fetuses were diagnosed with microcephaly, including severe brain abnormalities, by ultrasound. Although tests of blood samples from both women are negative, Zika virus is detected in amniotic fluid.

7 January 2016: Ophthalmologists in Brazil report severe ocular malformations in three infants born with microcephaly.

12 January 2016: In collaboration with health officials in Brazil, the United States Centers for Disease Control and Prevention release laboratory findings (notified to WHO under IHR protocol) of four microcephaly cases in Brazil (two newborns who died in the first 24 hours of life and two miscarriages) which indicate the presence of Zika virus RNA by PCR and by immunohistochemistry of brain tissue samples of the two newborns. In addition, placenta of the two fetuses miscarried during the first 12 weeks of pregnancy test positive by PCR. Clinical and epidemiological investigations in Brazil confirm that all four women presented fever and rash during their pregnancy. The findings are considered the strongest evidence to date of an association between Zika infection and microcephaly.

27 January 2016: French Polynesia reports retrospective data on its Zika outbreak, which coincided with a dengue outbreak. From 7 October 2013 to 6 April 2015, 8750 suspected cases of Zika were reported, with 383 PCR confirmed cases and an estimated 32 000 clinical consultations (11.5% of the total population). The outbreak ended in April 2014. During the outbreak, 42 cases of Guillain-Barré syndrome were diagnosed, representing a 20-fold increase in incidence over previous years. Though 10 of these patients required admission to an intensive care unit, none died. All 42 cases tested positive for Zika and dengue. Tests excluded other known causes of Guillain-Barré syndrome, including Campylobacter jejuni, cytomegalovirus, HIV, Epstein–Barr and herpes simplex viruses. The investigation concluded that successive dengue and Zika virus infections might be a predisposing factor for developing Guillain-Barré syndrome.

24 March 2016: Scientists from the University of Oxford (UK) and the Evandro Chagas Institute (Brazil) published a study that shows that Zika virus in the Americas arose from a single introduction, estimated to have occurred between May and December 2013, more than 12 months prior to the first detection of ZIKV in Brazil. This estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, and also with reported outbreaks in the Pacific Islands. One hypothesis discussed by the researchers involves virus introduction during the Confederations Cup soccer tournament, which involved French Polynesian participation from Tahiti.

31 March 2016: A team led by Purdue University researchers is the first to determine the structure of the Zika virus, which reveals insights critical to the development of effective antiviral treatments and vaccines.

13 April 2016: Scientists at the Centers for Disease Control and Prevention (CDC) concluded, after careful review of existing evidence, that Zika virus is a cause of microcephaly and other severe fetal brain defects.

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