Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6: A Preliminary Report from Istanbul

Abstract

Hand, foot, and mouth disease (HFMD) is caused by various serotypes of Enterovirus genus. Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) were known to be the only responsible agents for these epidemics; however, this opinion was challenged after the detection that coxsackievirus A6 (CV-A6) was the responsible species for the outbreak in Finland in 2008. HFMD is frequently seen in Turkey, and no detailed study on its clinical and microbiological epidemiology has previously been reported. The present study addresses this question. Twenty-seven patient samples collected between 2015 and 2017 were included in the study. Typing was conducted by RT-PCR and the sequencing applied directly to patient’s samples and as well as to the viral cultures with pan-enterovirus and serotype-specific primers. The presence of Enterovirus in 12 of 27 HFMD samples was shown with RT-PCR. The causative agent for three of these 12 samples was CV-A16, one of the most frequent two serotypes around the world, and the remaining nine samples was CV-A6. The findings of the study are relevant since it pertains to the molecular epidemiology of HFMD in Turkey, a gateway country where different serotypes might be circulating and transmitted. The findings also support the notion that CV-A6 cases are rising in number, which has caused more severe clinical features and widespread rashes in recent outbreaks.

Evolutionary and Genetic Recombination Analyses of Coxsackievirus A6 Variants Associated with Hand, Foot, and Mouth Disease Outbreaks in Thailand between 2019 and 2022

“…Phylogenetic analysis revealed that the nt sequences from the 3Dpol region belonged to 23 bootstrap-supported clades (recombinant forms (RFs); A–X) in agreement with previous reports ( Figure 2 B) [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 43 , 44 , 45 , 46 , 47 ]. Most of the CV-A6/TH strains (84%, 147/174) in this study belonged to the previously described RF-A, while only ~6% (11/174) of the strains were assigned to RF-N (6%), and one strain was classified as RF-H (0.6%).…”

“…Since 2008, the coxsackievirus (CV)-A6 strain has become the predominant genotype associated with global outbreaks of atypical hand, foot, and mouth disease (HFMD) [ 1 , 2 , 3 , 4 , 5 , 6 ]. Recent surveillance data have shown the epidemic potential of CV-A6 worldwide, including in Brazil [ 7 ], China [ 8 ], France [ 9 ], Hong Kong [ 10 ], India [ 11 ], Japan [ 12 ], Turkey [ 13 ], Uruguay [ 14 ], and Vietnam [ 15 ]. Severe clinical manifestations, such as vasculitis-like rash and vesiculobullous exanthema, are caused by CV-A6 and have been described in children and adults in several countries, such as Argentina [ 16 ], Brazil [ 17 ], China [ 18 ], Israel [ 19 ], Italy [ 20 ], and Japan [ 21 ].…”

Emergence of Recombinant Subclade D3/Y in Coxsackievirus A6 Strains in Hand-Foot-and-Mouth Disease (HFMD) Outbreak in India, 2022

“…Since 2008, atypical HFMD outbreaks have been primarily associated with the CV-A6 variant [ 3 , 4 , 5 , 6 , 7 ]. Contemporary surveillance data have demonstrated the potential of the CV-A6 virus for epidemic spread around the world, particularly in Brazil [ 8 ], China [ 9 ], France [ 10 ], Hong Kong [ 11 ], India [ 12 ], Japan [ 13 ], and Turkey [ 14 ]. CV-A6 has been associated with severe clinical symptoms in both children and adults in several nations, including Argentina [ 15 ], Brazil [ 16 ], China [ 17 ], Israel [ 18 ], Italy [ 19 ], and Japan [ 20 ].…”