Hema Madhuri Mekala, M.D., Priyanga Jayakumar, M.D., Rajashekar Reddy Yeruva, M.D., Steven Lippmann, M.D.
Zika is an alarming viral infection that is spreading around our planet. The World Health Organization recently declared Zika to be an international public health crisis (1). The first known article about Zika virus was published in 1952, and its first major outbreak occurred in 2007 (2). Until then it was not considered to be a serious illness, with only a few cases reported, all thought to be of no major health consequence (2,3). The recent outbreak in Brazil evidenced that manifestations of Zika virus infection can range from only a minor symptomatic ailment to one inducing dangerous gestational and neurological sequelae. This dramatic epidemic forced awareness to this emerging disease that is primarily, but-not-only mosquito-transmitted.
Zika virus is named after the Zika Forest in Uganda from where it was first described in 1947 by Yellow Fever Research Institute scientists (2). It was isolated from a sentinel monkey; the following year, the viral presence was noted in the Aedes africanus mosquitoes (2). In 1952, for the first time, human Zika cases were identified in Uganda and United Republic of Tanzania. Two more strains of the virus were discovered from the Aedes africanus in 1958. Over the next several decades, other cases of Zika infection were recorded sporadically in Africa.
The first proof of Zika virus causing human disease was identified in 1964; a researcher contracted it while investigating this virus (4). Zika virus in Asia was first documented during 1966, by its isolation from Malaysian Aedes aegypti mosquitoes (4). Micronesia experienced an epidemic during 2007; this remarkable outbreak affected about 5,000 people out of a population of 6,700 (5). In 2013-2014, French Polynesia experienced over 32,000 human infections, which involved about two thirds of its inhabitants (6). By then, the virus had become broadly distributed throughout Asia and Africa (3).
The first outbreak of Zika in the Western Hemisphere was on Chile’s Easter Island during 2014 (7). In Brazil, that following year, there was a devastating outbreak affecting up to 1,300,000 people (3). As of June 2016, Zika virus presence is now detected also throughout the Americas, including in people of the United States and its territories.
During 1957, Zika infections in humans were described as a mild, self-limiting illness with only modest fever and a maculopapular cutaneous eruption (8). However, the 2007 outbreak in Micronesia included patients presenting also with conjunctivitis, pharyngitis, cephalgia, and arthralgia (9). The 2013-2014 epidemic in French Polynesia revealed a Zika association with Gullian Barre syndrome and meningoencephalitis (10). The Brazilian 2015 outbreak evidenced Zika as a direct cause of gestational microcephaly with mental retardation and significant neurologic or other congenital anomalies (3). This disease has evolved from a mild, localized condition to a dangerous public health crisis, involving huge numbers of people in the world.
Alteration in the pattern and effects of this infection may be related to replication and transcription changes in the virus’s genetic profile (11). The pre-membrane precursor (prM) protein of the Zika virus is documented with greater variability when comparing the virus in Asian humans to those in African mosquitoes. This suggests that variability contributes to significant structural change in the virus, and may partially explain why it spread to American human populations;sequence variations could mediate specific changes in the prM protein and play a role in its virulence (11). Amino acid or nucleotide changes might be responsible for increased neurotropism, heightened viral transmissibility, and greater mosquito vector infectivity to human hosts (11).
As of July 20, 2016, a report indicates that there are 1,404 cases of Zika virus infection in the United States and 3,827 cases in its territories (12). On July 14, 2016, data from a Zika pregnancy registry revealed 400 pregnant women with laboratory evidence of Zika virus infection in the United States. Among these cases, there were six miscarriages with birth defects and 12 live-born infants with congenital anomalies (12,13). Findings include microcephaly, intracranial calcifications, abnormal cerebral artery flow, other brain abnormalities, intrauterine growth restriction, and fetal death. This data helps us with understanding, treating and planning services for pregnant women affected by Zika virus (12).
Since Zika infection was initially considered a mild self-limiting illness, intervention was limited to rest, hydration, and symptomatic therapies (14). Aspirin is not recommended for use by Centers for Disease Control and Prevention until after dengue fever is ruled out, because of a risk of bleeding. A variety of homeopathic and ayurvedic medicines have efficacy against Japanese encephalitis virus, which is in the same genus as Zika (14).
To date, there is no vaccine for Zika virus despite its similarity with dengue, in the same genus, Flavivirus. Therapeutic option research currently lacks investment and support, but efforts to develop a vaccine are on-going.
Medical science is becoming aware of Zika as a serious viral infection with potentially dangerous consequences. Especially relevant are virus-induced congenital anomalies with permanent neurological sequelae. Originally considered to be a mild viral infection, it is now recognized contrarily as a dangerous disease affecting millions of people. Since its discovery seven decades ago, the virus has altered its structure and its consequences have become a major public health crisis. Sexual transmission of this disease has added to its virulence. Current research about Zika is focused on vaccine development.
- World Health Organization. Date last accessed July 25, 2016. (http://www.who.int/mediacentre/news/statements/2016/emergency-committee-Zika-microcephaly/en/).
- Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 1952; 46(5): 509–520.
- Bogoch II, Brady OJ, Kraemer MU, et al. Anticipating the international spread of Zika virus from Brazil. Lancet 2016; 387(10016): 335–336.
- Marchette NJ, Garcia R, Rudnick A. Isolation of Zika virus from Aedesaegypti mosquitoes in Malaysia. Am J Trop Med Hyg 1969; 18(3): 411–415.
- Lanciotti RS, Kosoy OL, Laven JJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008; 14(8): 1232-1239.
- Dyer O. Zika virus spreads across Americas as concerns mount over birth defects. BMJ 2015; 351: h6983. doi: 10.1136/bmj.h6983.
- Gatherer D, Kohl A. Zika virus: a previously slow pandemic spreads rapidly through the Americas. J Gen Virol 2016; 97:269.
- Simpson DI. Zika virus in man. Trans R Soc Trop Med Hyg 1964; 58: 335-338.
- Duffy MR, Chen TH, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl. J Med 2009; 360(24): 2536-2543.
- Cao-Lormeau VM, Blake A, Mons S, et al. Gullain-Barre syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016; 387(10027): 1531-1539.
- Wang L, Valderramos SG, Wu A, et al. From Mosquitos to Humans: Genetic Evolution of Zika Virus. Cell Press 2016; 561-565.
- Centers for Disease Control and Prevention (CDC). Last seen July 25, 2016. http://www.cdc.gov/Zika/geo/united-states.html.
- Brasil P, Pereira JP , Gabaglia CR, et al. Zika virus infection in pregnant women in Rio de Janeiro—preliminary report. N Engl J Med 2016. Doi: 10.1056/NEJMoa1602412
- Saxena SK, Elahi A, Gadugu S, et al. Zika virus outbreak: an overview of the experimental therapeutics and treatment. Virus Disease 2016; 27(2): 111-115.