Zika Virus

Zika virus is a mosquito-borne flavivirus that was first identified in Uganda in 1947 in monkeys through a network that monitored yellow fever. It was later identified in humans in 1952 in Uganda and the United Republic of Tanzania. Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia and the Pacific. From the 1960s to 1980s, human infections were found across Africa and Asia, typically accompanied by mild illness. The first large outbreak of disease caused by Zika infection was reported from the Island of Yap (Federated States of Micronesia) in 2007. In July 2015 Brazil reported an association between Zika virus infection and Guillain-Barré syndrome. In October 2015 Brazil reported an association between Zika virus infection and microcephaly.

An evolving outbreak of Zika virus infections is currently spreading in the Americas and the Pacific region, coinciding with an increase in cases of microcephaly and other adverse outcomes during pregnancy and of Guillain–Barré syndrome (GBS) in adults.On 1 February 2016 WHO declared a Public Health Emergency of International Concern (PHEIC) regarding clusters of microcephaly cases and neurological disorders in some areas affected by Zika virus.

 

Transmission

Zika virus is primarily transmitted to people through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions. Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. This is the same mosquito that transmits dengue, chikungunya and yellow fever. Sexual transmission of Zika virus is also possible. Other modes of transmission such as blood transfusion are being investigated.

The true extent of the vectors is still unknown. Zika has been detected in many more species of Aedes, along with Anopheles coustani, Mansonia uniformis, and Culex perfuscus, although this alone does not incriminate them as a vector.Transmission by A. albopictus, the tiger mosquito, was reported from a 2007 urban outbreak in Gabon where it had newly invaded the country and become the primary vector for the concomitant chikungunya and dengue virus outbreaks. There is concern for autochthonous infections in urban areas of European countries infested by A. albopictus because the first two cases of laboratory-confirmed Zika infections imported into Italy were reported from viremic travelers returning from French Polynesia. The potential societal risk of Zika can be delimited by the distribution of the mosquito species that transmit it. The global distribution of the most cited carrier of Zika, A. aegypti, is expanding due to global trade and travel.  A. aegypti distribution is now the most extensive ever recorded – across all continents including North America and even the European periphery (Madeira, the Netherlands, and the northeastern Black Sea coast). A mosquito population capable of carrying Zika has been found in a Capitol Hill neighborhood of Washington, D. C., and genetic evidence suggests they survived at least four consecutive winters in the region. The study authors conclude that mosquitos are adapting for persistence in a northern climate.  Since 2015, news reports have drawn attention to the spread of Zika in Latin America and the Caribbean. The countries and territories that have been identified by the Pan American Health Organisation as having experienced “local Zika virus transmission” are Barbados, Bolivia, Brazil, Colombia, the Dominican Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Saint Martin, Suriname, and Venezuela.

Sexual

On 7 June 2016, WHO updated its Interim guidance on prevention of sexual transmission of Zika virus, and in particular the advice to returning travellers.

Although the primary transmission route of Zika virus is via the Aedes mosquito, sexual transmission of Zika virus is possible and more common than previously assumed. As the current evidence base on Zika virus remains limited, WHO regularly reviews its guidance and updates the recommendations as new evidence emerges.

The latest version of the guidance updates the advice on preventive measures for travellers returning from Zika-affected areas summarised as follow:
  • “Couples or women planning a pregnancy who are returning from areas where transmission of Zika virus is known to occur, are strongly recommended to wait at least 8 weeks before trying to conceive to ensure that any possible Zika virus infection has cleared; and 6 months if the male partner was symptomatic.”
  • “Men and women returning from areas where transmission of Zika virus is known to occur should adopt safer sex practices or consider abstinence for at least 8 weeks upon return. If before or during that period Zika virus symptoms (rash, fever, arthralgia, myalgia or conjunctivitis) occur, men should adopt safer sex practices or consider abstinence for at least 6 months”.

Zika can be transmitted from a man to his sex partners. As of April 2016 sexual transmission of Zika has been documented in six countries – Argentina, Chile, France, Italy, New Zealand and the United States – during the 2015 outbreak.

In 2014, Zika capable of growth in lab culture was found in the semen of a man at least two weeks (and possibly up to 10 weeks) after he fell ill with Zika fever. In 2011 a study found that a United States biologist who had been bitten many times while studying mosquitoes in Senegal developed symptoms six days after returning home in August 2008, but not before having unprotected intercourse with his wife, who had not been outside the US since 2008. Both husband and wife were confirmed to have Zika antibodies, raising awareness of the possibility of sexual transmission. In early February 2016, the Dallas County Health and Human Services department reported that a man from Texas who had not travelled abroad had been infected after his male monogamous sexual partner had anal penetrative sex with him one day before and one day after onset of symptoms. As of February 2016, fourteen additional cases of possible sexual transmission have been under investigation, but it remained unknown whether women can transmit Zika to their sexual partners. At that time, the understanding of the “incidence and duration of shedding in the male genitourinary tract [was] limited to one case report.” Therefore, the CDC interim guideline recommended against testing men for purposes of assessing the risk of sexual tranmission. As of March 2016, the CDC updated its recommendations about length of precautions for couples, and advised that heterosexual couples with men who have confirmed Zika fever or symptoms of Zika should consider using condoms or not having penetrative sex (i.e., vaginal intercourse, anal intercourse, or fellatio) for at least 6 months after symptoms begin. This includes men who live in—and men who traveled to—areas with Zika. Couples with men who traveled to an area with Zika, but did not develop symptoms of Zika, should consider using condoms or not having sex for at least 8 weeks after their return in order to minimize risk. Couples with men who live in an area with Zika, but have not developed symptoms, might consider using condoms or not having sex while there is active Zika transmission in the area.

Pregnancy

The Zika virus can spread from an infected mother to her fetus during pregnancy or at delivery.

Blood transfusion

As of April 2016, two cases of Zika transmission through blood transfusions have been reported globally, both from Brazil, after which the US Food and Drug Administration recommended screening blood donors and deferring high-risk donors for 4 weeks.  A potential risk had been suspected based on a blood-donor screening study during the French Polynesian Zika outbreak, in which 2.8% (42) of donors from November 2013 and February 2014 tested positive for Zika RNA and were all asymptomatic at the time of blood donation. Eleven of the positive donors reported symptoms of Zika fever after their donation, but only three of 34 samples grew in culture.

Clinical features and sequelae

The incubation period likely ranges between three and 12 days after the bite by an infected mosquito. Most of the infections remain asymptomatic (approximately 80%). Disease symptoms are usually mild, and the disease is commonly short-lasting and self-limiting. Its duration is between 2–7 days without severe complications, with no associated fatalities and a low hospitalisation rate.
The main symptoms are maculopapular rash (+/-itchy), with or without mild fever, arthralgia, fatigue, non-purulent conjunctivitis/conjunctival hyperaemia, myalgia and headache. The maculopapular rash often starts on the face and then spreads throughout the body. Less frequently, retro-orbital pain and gastro-intestinal signs might be present.
Differential diagnostic with dengue and chikungunya fever based on clinical symptoms remains challenging, and co-infection can occur. The other usual differential diagnoses are measles, rubella, parvovirus and enterovirus infections, and malaria.Among women infected during pregnancy, congenital central nervous system malformations of the foetus (such as microcephaly) and foetal losses were notified during several recent Zika disease outbreaks. Unusual increases of Guillain–Barré syndrome incidence, coinciding with the Zika virus outbreaks, were reported in several countries in the Americas and French Polynesia.

Diagnostics

Zika virus disease diagnostics is primarily based on the detection of viral RNA from clinical specimens (blood, saliva, urine, cerebrospinal fluid, amniotic fluid, semen, and breast milk). The viraemic period appears to be short, allowing for direct virus detection from blood and saliva, usually during the first 3–5 days after the onset of symptoms (sometimes up to 7–8 days). In several cases, Zika virus RNA has been detected in urine up to 2–3 weeks after onset of symptoms. Virus presence in semen has been documented up to 62 days after symptom onset. Serological investigations can be conducted from day 5 after the onset of disease, by detection of Zika-specific IgM antibodies and confirmation by neutralisation, seroconversion or fourfold antibody titre increase of Zika-specific antibodies in paired serum samples. Eight to 14 days after the onset of symptoms, diagnostic testing of urine with RT-PCR can be considered in addition to Zika virus serology. Serological results should be interpreted according to the vaccination status and previous exposure to other flaviviral infections (e.g. dengue, West Nile, Japanese encephalitis).

Infection control, personal protection and prevention

Primary prevention is based on protection against mosquito bites. Aedes mosquitoes have diurnal biting activities in both indoor and outdoor environments. Therefore personal protection measures should be applied all day, especially during the hours of the highest mosquito activity (mid-morning, late afternoon to twilight).
Personal protection measures to avoid mosquito bites should be applied when in risk areas:
  • applying appropriate mosquito repellents and wearing long-sleeved shirts and long trousers to cover as much of the body as possible, especially during the hours of highest Aedes mosquito activity
  • sleeping or resting in screened or air-conditioned rooms, otherwise use of insecticide-treated mosquito nets, even during the day
  • removing mosquito breeding sites in nearby outdoor/indoor premises.

Use of mosquito repellents should be in accordance with the instructions indicated on the product label. Pregnant women and women who are planning to become pregnant and planning to travel to areas with widespread transmission should postpone non-essential travel. Those who are planning to travel to areas with sporadic transmission should consult their physician or a travel clinic and consider postponing non-essential travel. Pregnant women residing in countries with active transmission (sporadic and widespread) should consult their healthcare providers for advice and follow strict measures to prevent mosquito bites. Travellers with immune disorders or severe chronic illnesses should consult their doctors or seek advice from a travel clinic before travelling, particularly with regard to effective prevention measures. Similar protective measures apply to a symptomatic patients in order to prevent human-to-mosquito-to-human transmission. Sexual transmission of Zika virus through semen has been documented, therefore practicing safer sex (including the use of condoms) is recommended throughout pregnancy to protect the foetus.

Concerns about Zika
The mosquito-borne Zika virus (ZIKV) is prompting worldwide concern due to its connection to a neurological birth disorder and its rapid spread across the globe. The virus was first found in a monkey in 1947 in Uganda and has historically occurred in parts of Africa, South East Asia and the Pacific Islands. ZIKV appeared in Brazil for the first time in May 2015 and has since spread to 21 countries and territories. Brazil has reported a dramatic (over 20-fold) increase in the incidence of microcephaly cases, which is a developmental disorder of the head and brain in newborns. In February 2016, the WHO declared a global emergency putting ZIKV in the same category of concern as Ebola.
ZIKV is closely related to other mosquito-borne flaviviruses such as the dengue, Japanese encephalitis, yellow fever, and West Nile viruses. It is primarily transmitted by infected Aedes species mosquitos (A. aegypti and A. albopictus). It has been reported that ZIKV can be spread through blood transfusion and sexual contact. Although Zika fever is generally a mild disease only causing a rash, fever, joint pain, and malaise, it has been linked to cases of several neurological complications including microcephaly, Guillain-Barré syndrome and hearing difficulties.