Epidemiology of Recurrent Hand, Foot and Mouth Disease, China, 2008-2015

Abstract

Using China's national surveillance data on hand, foot and mouth disease (HFMD) for 2008-2015, we described the epidemiologic and virologic features of recurrent HFMD. A total of 398,010 patients had HFMD recurrence; 1,767 patients had 1,814 cases of recurrent laboratory-confirmed HFMD: 99 reinfections of enterovirus A71 (EV-A71) with EV-A71, 45 of coxsackievirus A16 (CV-A16) with CV-A16, 364 of other enteroviruses with other enteroviruses, 383 of EV-A71 with CV-A16 and CV-A16 with EV-A71, and 923 of EV-A71 or CV-A16 with other enteroviruses and other enteroviruses with EV-A71 or CV-A16. The probability of HFMD recurrence was 1.9% at 12 months, 3.3% at 24 months, 3.9% at 36 months, and 4.0% at 38.8 months after the primary episode. HFMD severity was not associated with recurrent episodes or time interval between episodes. Elucidation of the mechanism underlying HFMD recurrence with the same enterovirus serotype and confirmation that HFMD recurrence is not associated with disease severity is needed.

Keywords: CV-A16; China; EV-A71; coxsackievirus A16; enterovirus A71; enteroviruses; epidemiology; hand foot and mouth disease; recurrence; reinfection; viruses.

Figure 1

Flowchart showing screening for and analysis of patients with recurrent HFMD from the national HFMD surveillance database, 29 provinces of China, 2008–2015. Percentages do not equal 100% because of rounding. *The number of patients (427,953) with >2 HFMD episodes is higher than expected (528,513 – 102,540 = 425,973) because of improved patient matching. In some situations, the number of patients with >2 episodes did not change; for example, a patient initially identified with 3 episodes might have been determined to have only 2 episodes, with the third episode being attributed to a different patient. In other situations, the number of patients with >2 episodes decreased; for example, a patient initially identified as having 3 episodes might have been determined to be 3 different patients with 3 different episodes. Therefore, the reduced number of patients (528,513 – 427,953 = 100,560) with >2 HFMD episodes is smaller than the number of patients (102,540) excluded manually. †The number of patients (398,010) with recurrence of HFMD is higher than expected (427,953 – 31,029 = 396,924) because some patients needed to be excluded and included. In some situations, patients were completely included or excluded from the recurrent HFMD patient population sample; for example, all 3 episodes of a patient could have been determined to not be independent from each other. In other situations, patients were included and excluded from the recurrent HFMD patient population sample; for example, a patient with 3 episodes might have had 2 episodes that were not independent from each other. In these cases, the patient had 2 episodes included and 1 episode excluded; therefore, the number of included patients plus excluded patients (398,010 + 31,029 = 429,039) exceeded the starting population number (427,953). CV-A16, coxsackievirus A16; EV-A71, enterovirus A71; HFMD, hand, foot and mouth disease; other EVs, other non–EV-A71 and non–CV-A16 enteroviruses.

Figure 2

Hand, foot and mouth disease (HFMD) episodes in 29 provinces of China, 2008–2015. A) Patients with recurrent laboratory-confirmed HFMD. B) Patients with single episode of laboratory-confirmed HFMD. C) Patients with recurrent probable HFMD. D) Patients with single episode of probable HFMD.

Figure 3

Geographic distribution of patients with recurrent HFMD (A) and episodes of enterovirus infection (B) in 29 provinces of China, 2008–2015. A) Pie charts correspond to the number of recurrent laboratory-confirmed HFMD cases. B) Pie charts correspond to the number of laboratory-confirmed HFMD episodes. CV-A16, coxsackievirus A16; EV-A71, enterovirus A71; HFMD, hand, foot and mouth disease; other EVs, non–EV-A71 and non–CV-A16 enteroviruses.

Figure 4

Kaplan-Meier analysis of survival from HFMD recurrence after primary HFMD diagnosis, 29 provinces of China, 2008–2015. A) Probability of HFMD recurrence among all patients who had probable and laboratory-confirmed HFMD. B) Probability of HFMD recurrence among case-patients whose primary episode was an infection with EV-A71. C) Probability of HFMD recurrence among case-patients whose primary episode was an infection with CV-A16. CV-A16, coxsackievirus A16; EV-A71, enterovirus A71; other EVs, non–EV-A71 and non–CV-A16 enteroviruses; HFMD, hand, foot and mouth disease.