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Chikungunya: From Zero to 1.24 Million

— Once-rare virus now causing thousands of cases a week in the Americas.

Last Updated March 4, 2015
MedpageToday
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In slightly more than a year, the Americas have seen more than 1.24 million cases of chikungunya virus, a mosquito-borne disease that causes high fever and debilitating joint pain.

The tropical virus was rare in North, Central, and South America until December 2013, when investigation of suspected dengue virus in the Caribbean island of St. Martin turned up 26 cases of chikungunya, without any sign they had been imported from elsewhere.

Action Points

  • The prevalence of infection with mosquito-borne chikungunya virus is increasing dramatically in nontropical areas including the U.S. and Europe.
  • An experimental live recombinant measles-based vaccine against chikungunya has shown excellent imunogenicity with an acceptable safety profile.

As of the end of February 2015, that handful of cases had exploded to 1,247,400 suspected and confirmed cases, affecting almost every country in the hemisphere, according to

Until the end of 2013, chikungunya in the Americas was almost entirely imported from countries in Africa or Asia where the tropical virus was endemic.

In the U.S., most cases are still imported -- a cumulative total of some 2,542 since 2013, according to the PAHO, with an additional 11 cases, all in Florida, blamed on local transmission. But most of that transmission now comes from the epidemics raging elsewhere in the region.

The U.S. numbers might be an underestimate. They're based on reports to the ArboNET, a national arboviral surveillance system managed by the CDC and state health departments.

But until this year, the virus was not a nationally notifiable disease, so some cases might have been missed.

The virus -- the name is pronounced chik-un-GUHN-ya -- is

The CDC notes that both species primarily bite in the daytime and urges that travelers take precautions against mosquito bites, including wearing long-sleeved shirts and long pants, if weather permits, and using insect repellents.

There is no specific treatment for the virus and no vaccine, but its dramatic spread has re-focused the attention of vaccine researchers.

this week, investigators are reporting that a recombinant candidate based on a measles vaccine had promising immunogenicity in a phase I dose-finding trial.

Regardless of dose, a single shot of the vaccine produced neutralizing antibodies to chikungunya, according to of the Medical University of Vienna in Austria, and colleagues.

A second dose, either 28 or 90 days after the first, led to seroconversion in all participants, Jilma and colleagues reported.

And last summer, investigators led by , of the National Institute of Allergy and Infectious Diseases, reported that a

Participants got three injections of the vaccine starting on day 0, and followed by one 4 weeks later and a final shot in week 20. The investigators are currently studying whether adding an adjuvant would allow them to use lower doses.

Both groups reported their vaccine candidates were safe.

Jilma and colleagues were testing a recombinant version of a standard live attenuated measles vaccine, engineered to present chikungunya antigens, after animal studies showed it could protect mice from a lethal challenge with the virus.

The 42 participants were randomly assigned to get one of three doses of the vaccine candidate or the active comparator, a commercial measles-mumps-rubella vaccine (Priorix).

They were also randomly assigned to get a booster at day 28 or day 90, with a placebo shot at the later time points to maintain masking.

The endpoint of the study was the presence of neutralizing anti-chikungunya antibodies on day 28 -- a mark that was reached by 44% in the low-dose group, 92% in the medium-dose group, and 90% in the high-dose group.

On the other hand, all participants had neutralizing antibodies after their second shot, Jilma and colleagues reported. Previous immunization to measles had no effect on outcomes, they found.

The researchers asked about a series of possible adverse events and solicited reports of headache in 24 participants, injection-site pain in 21 (50%), and influenza-like illness in 19.

The most frequent other adverse events were nasopharyngitis in 11 participants and oropharyngeal pain in five. Overall, transient musculoskeletal pain was reported by five participants.

The researchers said seven adverse events, in six participants, were regarded as severe, including five linked to the vaccinations. Two serious adverse events -- an attempted suicide and a meniscus tear -- were not related to the study drug, they reported.

Disclosures

The study was supported by Themis Bioscience GmBH. Jilma disclosed no relevant relationships. Several authors are employees of the study sponsor.

Primary Source

Lancet Infectious Diseases

Ramsauer K, et al "Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial" Lancet Infect Dis 2015; DOI: 10.1016/S1473-3099(15)70043-5.