THE Zika virus emergency, which was, for a protracted period, the subject of intense media coverage, was declared at an end in November 2016. In its last situation report (March 2017), the World Health Organization noted that, although a decline in cases of Zika virus infection had been reported in some countries (or parts of countries), “vigilance needs to remain high”. The development of herd immunity through natural infection in populations in endemic areas might have contained local outbreaks. However, health authorities continue to recommend the use of risk assessment and preventative strategies.

Zika virus is a mosquito-borne flavivirus that was first identified in Uganda in 1947 in monkeys. Symptoms are generally mild and include fever, rash, conjunctivitis, muscle and joint pain, malaise and headache. Symptoms typically last for 2–7 days. Most people with Zika virus infection do not develop symptoms.

According to the WHO:

“The first recorded outbreak of Zika virus disease was reported from the Island of Yap (Federated States of Micronesia) in 2007. This was followed by a large outbreak of Zika virus infection in French Polynesia in 2013 and other countries and territories in the Pacific. In March 2015, Brazil reported a large outbreak of rash illness, soon identified as Zika virus infection, and in July 2015, found to be associated with Guillain-Barré syndrome. In October 2015, Brazil reported an association between Zika virus infection and microcephaly. Outbreaks and evidence of transmission soon appeared throughout the Americas, Africa, and other regions of the world. To date, a total of 86 countries and territories have reported evidence of mosquito-transmitted Zika infection.”

The Department of Health in Australia advises that it may take 3 to 12 days for symptoms to appear after infection. As at February 2018, all known cases of Zika virus infection in Australia were acquired overseas (parts of Queensland and the Torres Strait Islands do have the mosquito species that can carry the virus). The current advice for male travellers is to refrain from unprotected sexual activity for 6 months after the last day of travel to an endemic area. For women, the advice is to avoid unprotected sex and pregnancy for at least 8 weeks following their return from travel. Pregnant women are advised to refrain from travel to high or moderate risk countries. Individual risk assessment and testing for asymptomatic men, and women who are planning pregnancy despite recent travel to endemic areas is recommended.

Contribution of socio-economic factors

Several socio-economic factors contributed to the high rates of infection that were seen in many endemic areas. Problems associated with poverty and poor infrastructure (primarily pertaining to water and sanitation systems) aggravated the situation.

In Brazil, for example, two states that were hit hardest by the Zika virus had neglected and poorly run water supply and waste management systems. Lack of access to a steady supply of water forced people to collect water from communal sources and store it in containers at home. These storage containers became breeding grounds for the vector Aedes mosquito populations. Despite the urging of local authorities, households resisted efforts to empty out their containers and eliminate standing water. Poor infrastructure for wastewater management, and lack of access to proper sanitation and waste disposal facilities further exacerbated the situation.

In poorer neighbourhoods, girls and women did not have adequate knowledge about Zika transmission, or access to reproductive health information and services. Women reported that they did not know that Zika could be transmitted sexually, and that they received inconsistent and conflicting information from authorities. Political compulsions to demonstrate effective mitigation of endemic infection (particularly around the time of the FIFA World Cup in Brazil in June–July 2014) prompted some authorities to announce that Zika had been successfully contained. It is unclear to what extent subsequent efforts led to changes in public perception and the uptake of risk mitigation strategies in Brazil.

Current research

Several studies have investigated the impacts of Zika virus infection on maternal and child health, the links between Zika infection and other conditions, and potential preventive strategies and vaccines.

A 6-year prospective study, conducted by the US National Institutes of Health, will analyse how maternal Zika and HIV co-infections in pregnancy affect outcomes for both the mother and child.

Reports have pointed to the impacts of Zika–chikungunya co-infection, and links between Zika infection and Guillain–Barré syndrome.

In the public consciousness, Zika is widely associated with microcephaly and neurological disorders. Researchers’ understanding of the links between Zika and neurological disorders is continually evolving, with new research investigating different elements of these links.

The physiological processes involved in Zika infection are being delineated. A study in mBio described how the Zika virus infects human brain endothelial cells. Endothelial cells normally protect neurons from viruses. The endothelial cell lining of capillaries normally constrains transplacental transmission of pathogens. However, the Zika virus can persistently infect and replicate in primary human brain microvascular endothelial cells before it is released through the basolateral membrane. This occurs within the first 9 days of infection and could help explain the occurrence of microcephaly and other congenital disorders in fetuses.

Some studies have identified potential preventive strategies. A study found that in pregnant mice, the use of the malaria medicine hydroxychloroquine blocked maternal–fetal transmission of Zika virus. Researchers attributed this to hydroxychloroquine’s inhibitory effect on the autophagy response, a cellular waste-disposal process that the Zika virus manipulates in the placenta to infect the developing fetus. Another study focused on a synthetic peptide called Z2 (made from the stem region of the Zika virus envelope protein), and found that Z2 can penetrate the placental barrier, enter fetal tissues and block the vertical transmission of Zika virus.

Scientists and epidemiologists are learning more about Zika transmission. There are five known modes of transmission – mosquito–human transmission, maternal–fetal transmission, and transmission through sexual intercourse, blood transfusion and laboratory exposure.

A rare case of Zika transmission between two adults in Utah in the US, as described in a case report in Emerging Infectious Diseases, perplexed researchers because the infection ostensibly developed in a manner that precluded any of the above modes. A 38-year-old man became infected with Zika after caring for a 73-year-old male family member who had contracted the virus in an endemic area; the latter died from complications several weeks later in a hospital in Utah. Researchers noted at the time that the case points to the possibility of an unknown person-to-person transmission mechanism, and highlighted the need to further examine the risk of infection from exposure to different body fluids, the significance of viral load, host factors that may increase susceptibility to infection, and environmental factors.

Researchers have been developing candidates for a Zika vaccine. There are around 14 vaccine candidates in pre-clinical development (other projects, which were still in the pipeline this time last year, appear to have been curtailed, possibly due to the limited duration of the last outbreak and other factors). The broader goal of vaccine researchers and developers is to develop a vaccine that offers durable immunity, requires as few doses as possible (to rationalise vaccination campaigns) and has a good safety profile, for use among at-risk populations in endemic areas and unexposed populations in areas that have not experienced an outbreak. Many of the vaccine trials have been funded by the US government via the National Institutes of Health, while others have been funded by industry.

Some more experimental vaccine studies have been reported. One study, published in Cell, reported that two experimental vaccines – one a live-attenuated vaccine and the other a novel messenger RNA (mRNA) vaccine (at one dose and two doses respectively) – prompted strong antibody production in non-pregnant female mice, and, when the mice were subsequently mated, prevented the transmission of Zika to fetuses. The vaccinated mice had significantly lower levels of Zika RNA in maternal, placental and fetal tissues than those in control groups that received the placebo. Another vaccine study, which used tobacco leaves to develop a virus-like particle carrier based on the hepatitis B core antigen, also demonstrated the effectiveness of its candidate against multiple Zika strains. The researchers highlighted a potential advantage of their plant-based vaccine over other candidates – a reduced risk of antibody-dependent enhancement (a process that leads to greater infectivity, and that may occur if the recipient also becomes infected with dengue or another flavivirus).

Another interesting project has involved the identification of strains of bacteria that can block Zika transmission – these, when introduced to mosquito populations, can potentially prevent the vector from transmitting the virus. This research, which involves Australian scientists, has progressed to field tests in Australia, Indonesia and Vietnam.

Research on Zika is evolving continuously. It is important to understand the risk factors involved, particularly in relation to travel to endemic areas, and guide patients to undertake testing where appropriate in order to determine the need for risk mitigation.

Dr Arjun Rajkhowa is centre manager of the National Centre for Antimicrobial Stewardship at the Department of Medicine, University of Melbourne, the Doherty Institute and Royal Melbourne Hospital. You can find him on Twitter @ArjunRajkhowa

 

 

The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless that is so stated.

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