Table 3.

Studies related to the causes of HFMD

Study	Results	Conclusions
Zhu et al. Beijing, China 2009 [27]	51 cases with HFMD  25 CVA16 positive cases  4 C4aEV71 positive cases  7 Cases neither positive for EV71 nor CVA16	In 2007 in China there was a higher incidence of HFMD caused by CVA16
Osterback et al. Turku, Finland 2009 [31]	35 cases with HFMD  34 CVA6 positive cases	CVA6 is emerging as the primary cause of the disease
Zhang et al. Pekín, Beijing 2009 [5]	70 cases with HFMD  30 Positive for enterovirus initiation: 66.7 % positive for EV71  At 4 days: 66.7 % positive for EV71  At 5 days: 12.9 % positive for EV71	Samples must be collected within 4 days after the onset of the disease, because there is more likelihood of positive viral detection
Blomgvist et al. Helsinki, Finland 2010 [3]	317 cases with HFMD 212 positive cases of CVA6 and/or CVA10	Outbreak due to new genetic variants of the Coxsackie virus, CVA10 and CVA6
Rabenau et al. Frankfurt, Germany 2010 [52]	696 cases with HFMD  88–73 % of children under 4 years are susceptible to infection  30.6 % seropositive for both viruses  43.5 % neutralizing antibodies (Ntab)  25.9 % did not have antibodies	The seroprevalence study shows a common dissemination of CVA16 and EV71 in Germany, and a comparatively higher sensitivity in the younger population
Liu et al. Nanchang, China 2011 [14]	109 cases with HFMD  90 % children under 8 years  High prevalence of subgenotype C4	C4aEV71 genotype is now the more common infectious agent in China
Yang et al. Beijing, China 2011 [32]	301 cases with HFMD  Enterovirus (HEV) (88.4 %), EV71 (50.4 %), CVA16 (38.3 %), CVA4 (1.1 %), CVA6 (1.1 %), CVA10 (1.1 %), CVA12 (2.6 %), CVB (5.3 %)	HFMD epidemics can persist for a long time in China, due to the different genetic variations in the composition of the virus, enteroviral characteristics of recombination and co-infection, increased travel, migration and the lack of an effective vaccine
Yan et al. Shanghai, China 2011 [30]	3208 HFMD cases EV71—86.5 %, CVA16—6.9 %, CVA16 + EV71—17.6 % Children 1–4 years 76.9 % M:F—65.3 %: 34.7 % Subgenotype C4 of EV71 circulating	The subgenotype C4 of EV71 was the main causative agent of the epidemic in Shanghai. The group most affected were children under 4 years. There was a higher prevalence in boys than in girls. High incidence of mixed infections of EV71 and CVA16
Rabenau et al. Frankfurt, Germany 2010 [52]	696 cases with HFMD  88–73 % of children under 4 years are susceptible to infection  30.6 % seropositive for both viruses  43.5 % neutralizing antibodies (Ntab)  25.9 % did not have antibodies	The seroprevalence study shows a common dissemination of CVA16 and EV71 in Germany, and a comparatively higher sensitivity in the younger population

HFMD hand, foot and mouth disease