EV71-associated Hand, Foot, And Mouth Disease Research Articles

EV71 vaccine, an invaluable gift for children.

Enterovirus 71 (EV71) is a major pathogen for severe hand, foot and mouth disease (HFMD). Development of vaccines against EV71 would be the most effective approach to prevent the EV71 outbreak. Research and development (R&D) of EV71 vaccine was carried out in several Asian countries. Currently three companies in mainland China have completed Phase III clinical trials of inactivated EV71 whole-virus vaccines, whereas the other two companies have completed Phase I clinical trials separately in Taiwan and in Singapore. Results from those clinical trials have indicated high safety and immunogenicity of EV71 vaccine. Protective efficacies were over 90% on EV71-associated HFMD and over 80% on other EV71-associated diseases. In this paper, we summarize the results from three EV71 vaccine Phase III clinical trials and discuss the challenges of incorporating EV71 vaccine into Expanded Program on Immunization (EPI) in countries with EV71 epidemics.

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

EV71 vaccine: protection from a previously neglected disease

The eagerly awaited results of a phase 3 trial of an inactivated enterovirus 71 (EV71) vaccine are reported by Feng-Cai Zhu and colleagues in The Lancet.1 EV71 is an important cause of hand, foot, and mouth disease (HFMD), but is also associated with more severe diseases in young children (aged <5 years), including aseptic meningitis and encephalitis.2 This multicentre randomised controlled trial done in China is a notable advance in protection against EV71. It included more than 10 000 participants (aged 6–35 months), with a vaccine efficacy of 90·0% (95% CI 67·1–96·9) for EV71-associated HFMD and 80·4% (58·2–90·8) for EV71-associated disease (including herpangina, neurological complications, and non-specific illnesses caused by EV71).

Seroepidemiology of Enterovirus 71 infection prior to the 2011 season in children in Shanghai

BackgroundIn 2010, China experienced the largest outbreak on record of Enterovirus 71 (EV71)-associated Hand Foot and Mouth Disease (HFMD) with more than 1.7 million cases, 27,000 patients with severe neurological complications and 905 deaths. Understanding of the seroprevalence of neutralizing antibodies (NAb) against EV71 and their protective role against HFMD in children is crucial for the implementation of future therapeutic and prophylactic intervention. ObjectivesTo correlate the prevalence of NAb against EV71 genotype C4a in children prior to the 2011 epidemic season with severe EV71-associated HFMD disease during the subsequent 2011 epidemic season. Study design614 sera samples were collected from children without HFMD. EV71 NAb were tested by a quantitative PCR assay. Samples with NAb ≥1:8 were scored as positive. Results122 (19.9%) of 614 sera were EV71-seropositive. The NAb seroprevalence was highest in infants 0–5 months of age (28.6%) and lowest in children 1–1.9 years of age (13.4%). 64.1% of severe EV71-associated HFMD occurred in children 1–2.9 years. ConclusionsDespite the large 2010 outbreak, the overall seroprevalence of EV71 in children is relatively low. The seropositive rate of EV71 NAb prior to the 2011 season was inversely correlated with the number of EV71-infected severe cases in 2011. Loss of maternal antibodies in infants and lack of acquired anti-EV71 immunity are responsible for increased proportion of severe HFMD in the 1–2 years age group. Our data suggest that future vaccination campaigns should be initiated as early as 6 months.

Isolating Asian enterovirus 71 subgenogroup C4 in two Austrian clinical samples from 2004

Hamaguchi et al. recently reported on the on the occurrence of enterovirus type 71 (EV71) subgenogroup C4 in Japan [1]. According to the authors, this strain may have emerged in mainland China and in Taiwan. EV71 subgenogroup C4 has recently gained public health interest following reports of an ongoing outbreak in China and Vietnam in 2008: In June 2008, more than 176,000 cases of hand, foot and mouth disease (HFMD) were reported in China alone, and at least 24 deaths have been attributed to EV71 [2,3]. In the largest and most severe EV71-associated HFMD outbreak in Taiwan in 1998, 405 children had severe neurological complications and/or pulmonary oedema; 78 children died [4].