By Barbara Boughton

 

A new vaccine against enterovirus 71 (EV71) can effectively prevent hand, foot, and mouth disease (HFMD) as well as hospitalizations for severe HFMD and EV71-associated disease, according to a phase 3 trial.

 

Feng-Cai Zhu, MSc, from Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, and the Department of Clinical Microbiology and Immunology, College of Pharmacy, Third Military Medical University & National Engineering Research Center for Immunological Products, Chongqing, China, and colleagues, published the results of their study online May 28 in the Lancet.

 

In the randomized, double-blind, placebo-controlled study of more than 10,000 children in China, the vaccine's efficacy in preventing EV71-associated HFMD was 90.0% (95% confidence interval, 67.1% - 96.9%; P = .0001), relative to placebo. The results of the study also indicated that the new vaccine had 100% efficacy in preventing hospitalizations for severe HFMD and EV71-associated disease.

 

EV71 is the primary cause of HFMD in China and other Asian countries and is a major public health threat in Asia. More than 6 million cases of HFMD and 2000 associated deaths have been reported worldwide during the last 10 years, the authors note.

 

Although EV71-associated disease has been seen in the United States, the virus is not the major cause of HFMD there. However, EV71 can also cause central nervous system disease and illnesses such as aseptic meningitis.

 

"The trial will likely have tremendous impact in China on outbreaks of" HFMD, said Paul Krogstad, MD, professor of pediatrics and a specialist in pediatric infectious disease at the University of California, Los Angeles. The efficacy of the EV71 vaccine also indicates that vaccines against other enteroviruses more common in the United States could successfully prevent life-threatening disease such as aseptic meningitis, Dr. Krogstad added.

 

In the trial, the researchers randomly assigned 10,245 children aged from 6 months to 3 years to receive either the EV71 vaccine or a placebo at baseline and at day 28. Patients were visited at home or came to a medical clinic at 5, 8, 11, and 14 months, and researchers recorded any medically significant events or illness.

 

During the follow-up period, 8 children in the vaccine group developed EV71-associated disease, as did 41 children in the placebo group. Similarly, 3 children in the vaccine group and 30 in the placebo group developed EV71-associated HFMD. Eight patients in the placebo group required hospitalization for severe EV71-associated HFMD; 1 case was accompanied by encephalitis and oral herpes. None of the patients in the vaccine group required hospitalization.

 

The inactivated alum-adjuvanted EV71 vaccine used in the trial was produced in China; the placebo vaccine contained alum adjuvant but no EV71 antigen.

 

The vaccine had few serious adverse events, and adverse events were similar in the placebo and experimental groups (3644 events [71.2%] vs 3603 events [70.3%]; P = .33). The most common systemic adverse events after vaccination were fever, diarrhea, and decreased feeding, but the incidence of these reactions was similar in both the experimental and placebo groups.

 

"The study was extremely well done, and both the experimental and placebo groups were well matched. The patients were also followed with careful surveillance," Dr. Krogstad commented.

 

A major limitation of the study is that it is only clearly applicable to populations in China, according to Dr. Krogstad.

 

In an accompanying editorial, Nigel W. Crawford, BMBS, MPH, and Steve M. Graham, PhD, from the Department of Paediatrics, University of Melbourne, and Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Australia, note that the vaccine will only affect HFMD disease caused by EV71. In addition, because morbidity and mortality form EV71 infection is low, the major effect of the vaccine will be to reduce hospitalization, they said.

 

Whether or not the new EV71 vaccine will be offered in China's national immunization program will most likely depend on a cost-effectiveness analysis, they noted.

 

"Although EV71 is not a major problem in the United States, there is no reason to think that it could not emerge there," Dr. Krogstad said. "The work of the researchers in this trial might help us prepare for any possible public health emergency caused by EV71 in the future," he added.

 

Four authors are employees of the National Engineering Research Center of Innovative Vaccine of Beijing Vigoo Biological. Dr. Crawford has acted as chief investigator for studies sponsored by CSL and Merck. The other authors, Dr. Graham, and Dr. Krogstad have disclosed no relevant financial relationships.

 

Lancet. Published online May 28, 2013.