Zika, more reasons for concern

When my collaborators and I investigated the epidemic of Chikungunya in Italy, i.e. the first example of an outbreak that had occurred in a temperate region,¹ one of the most striking, though somewhat expected, findings was the ability of the virus to rapidly spread in a new territory after the arrival of a single viremic subject, and within only a few hours. As for other viruses transmitted through Aedes mosquito bites, this explosive capacity appears to be shared by the most recent viral threat, the Zika virus. This new explosion of an old virus (first described in Uganda around seventy years ago) has quite rapidly affected South and Central America, as had happened a few years ago with Chikungunya, with imported cases following in the United States and Europe. Zika is usually transmitted by Aedes aegypti but data from several recent epidemics have disclosed Aedes albopictus, the tiger mosquito, as a permissive vector. This has important implications for virus surveillance in regions such as the Southern Mediterranean, where A. aegypti is now absent but its tiger mosquito companion is largely present. For instance, recent modeling that takes into account a number of travelers from Brazil, temperature profiles by country and niche data for A. albopictus suggests that in Italy more than 60% of the population reside in areas with potential Zika spread.²

Zika infection is reported to be mostly asymptomatic or causing mild symptoms and signs such as fever, rash and arthralgia, with a rather rapid healing course. Nonetheless, what has induced the WHO to declare a public health international emergency is a potential, severe sequela of Zika infection: its association with microchephaly, i.e. newborns’ low head and brain size. This suspicion was raised during clinical–epidemiological observations by Brazilian doctors and is somewhat supported by some virological and pathological findings including the recent reports on the Zika virus capacity of infecting and killing neural progenitor cells from human reprogrammed stem cells (see Nature, 531, 143, 2016).³ The evidence gathered so far for the above association is being given different weight by different investigators and health officers, yet it remains credible and of course threatening. In addition, some investigations make a sexual transmission of the virus quite likely, and hypothesize an inter-human transmission by the saliva, where infectious viral particles have been isolated from an imported case.^4–6

How to cope with this new threat, and more in general, how to defend against such an explosively transmissible virus?

While improving and implementing the best tools for a differential diagnosis is obviously a must, the present approach to the Zika patient cure is only medical support, as no specific antiviral therapeutics are available, and there are the usual, remarkable difficulties of arresting epidemics by vector control measures. In this scenario, as for other viral infections, a vaccine would be the ideal preventive measure in this case theoretically supported by some consensus that immune responses, particularly neutralizing antibodies, in flavivirus-infected subjects protect them from reinfection. However, the existence of different viral clades and, mostly, the current costs of producing and testing vaccines against a somewhat unpredictable and unmeasurable population target, in addition to the poorly known behavior of the virus’ spread in different populations, all make this strategy difficult, if not prohibitive.⁷ Nonetheless, if the current epidemiological and laboratory investigations will prove that Zika infection really causes microcephaly and can also be efficiently transmitted by nonvector routes, the health and social cost of the disease will undoubtedly drive the efforts to generate a Zika vaccine for women who are planning a pregnancy or are already pregnant. As for some Chikungunya vaccines,^8,9 an integration of public and private resources would be welcomed and probably necessary.

Being prepared to face new, emerging or re-emerging infectious threats has become a necessity since the early 80s, starting with the HIV-AIDS pandemic. When this was followed by new agents of viral respiratory infection and the eruption of ESKAPE bacteria, i.e. multi- or extremely drug-resistant bacterial pathogens, practically every few years, ‘what is next’ has become the most frequent subject of discussions and debates in microbiology laboratories and among public health authorities.¹⁰ Since then, the capacity of rapidly diagnosing these emerging infections by refined, rapid molecular and biophysical methods has made strong progress, unmatched, however, by an enhanced capacity to unravel the biology and pathogenicity of the infectious agent, and appropriately prevent its spread. All this is now the most impelling challenge.

Note from the Editor: Later this year, Pathogens and Global Health will be publishing a special focus on Zika virus, including articles on its relationship with microcephaly and its global threat.

Antonio Cassone, MD
Polo d’innovazione della genomica, genetica e biologia, University of Perugia, Perugia, Italy
[email protected]