Retrospective Study of the Incidence of HFMD and Seroepidemiology of Antibodies against EV71 and CoxA16 in Prenatal Women and Their Infants

Abstract

BackgroundHand, foot, and mouth disease (HFMD) has been emerging as an important public problem over the past few decades, especially in Asian and Pacific regions. A national program on EV71 vaccine development against HFMD was initiated in China, in 2008, which called for a need for seroepidemiological study for the target population.Methodology/Principal FindingsThis was a retrospective study conducted in Jiangsu Province, in October, 2010. We measured the neutralizing antibodies against EV71 and CoxA16 in a cohort of infants aged of 2, 7, 12, and 27–38 months and their mothers just before delivery. Series sera samples from 975 infants and 555 mothers were collected and analyzed. Questionnaires on the history of HFMD were completed in the survey. A total of 143 HFMD cases were collected, but only 11.2% were reported to the National Infectious Disease Information Management System. The level of maternal antibody titers decreased dramatically during the first 7 month and remained at a relatively low level thereafter. But it increased significantly from month 12 to months 27–38. The accumulate incidence density of HFMD demonstrated a significant increase after 14 months of age, resulting in a accumulate incidence density of 50.8/1000 person-years in survey period. Seropositivity of EV71 antibody in infants at the age of 2 months seems to demonstrate a protective effect against HFMD.Conclusions and SignificanceHigh seropositive rate of EV71 and CoxA16 antibody was found in prenatal women in mainland China, and there is a need to enhance the HFMD case management and the current surveillance system. We suggest that infants aged between 6 to 14 months should have the first priority to receive EV71 vaccine.

Coxsackievirus A16

“…Maternal antibodies against CA16 and EV71 were found to decline to the lowest level (CA16: 26.4%, 1:7.3; EV71: 41.3%, 1:11.3) in 7-mo-old infants from Jiangsu Province, and then gradually increase to high levels (CA16: 54.3% and 1:24.3; EV71: 56.2% and 1:35.3) at 27-30 mo of age. 49 In Ningbo, the positive rate of neutralizing antibodies against CA16 and EV71 was 43.2% and 13.5%, respectively, in 1-y-old infants, and increased to 67.6% and 67.6%, respectively, in the 5-y-old group. 48 The positive rate in the 5-y-old group was similar to the adult level.…”

“…30 A follow up study of 975 infants under 3 y old found that 143 infants presented with HFMD during the follow-up period. 49 The titers of neutralizing antibodies against CA16 and EV71 increased by 4-fold in 90 cases (62.9%) and 99 cases (69.2%), respectively. Fifty-four cases (37.8%) showed an increase in neutralizing antibodies against both CA16 and EV71.…”

“…The anti-CA16 neutralizing antibody-positive rate was found to be 83.0% for the 40-59-y-old group, 50 and the anti-EV71 neutralizing antibody-positive rate was about 75% in Germany 51 . The positive rates for CA16 and EV71 neutralizing antibodies were 89.1% and 85.3%, 49 respectively, for pregnant women group in Jiangsu province, and 78.4% and 83.8%, 48 respectively, for adults above 20 y old in Ningbo city of China.…”

“…52,53 It was reported that the genotype A strain isolated in 1951 and genotype B strains were used in different labs. 30,48,49 Another study reported that the titers of neutralizing antibodies against the genotype A strain were higher than those against B genotype. 48 Because of the genetic and antigenic differences existing between genotype A and genotype B stains, whether or not the genotype A strain could be used as the representative strain for neutralization assays evaluating vaccines requires further investigation.…”

How to understand the efficacy measurements for enterovirus type 71 vaccine?

“…In addition, EV71-associated disease are usually mild and self-limiting, so mild cases could be underreported significantly if patients did not seek for medical care. 23 If a case capture strategy detects moderate to severe cases easier than mild cases, or detects cases with typical symptoms easier than those with nonspecific symptoms, and if vaccinated cases are milder or more atypical than placebo cases, this will result in a too high efficacy estimate. 15 Therefore, in order to avoid missed EV71-associated cases, the active surveillance system we built in the efficacy trial covered all possible cases with suspected clinical symptoms without an obvious cause, by excluding only those with a definite other cause such as burning, traffic accident and so on.…”