Epidemics and aetiology of hand, foot and mouth disease in Xiamen, China, from 2008 to 2015.

Over the past 8 years, human enteroviruses (HEVs) have caused 27 227 cases of hand, foot and mouth disease (HFMD) in Xiamen, including 99 severe cases and six deaths. We aimed to explore the molecular epidemiology of HFMD in Xiamen to inform the development of diagnostic assays, vaccines and other interventions. From January 2009 to September 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription PCR that targeted the HEV 5' untranslated region and viral protein 1 region. Of these samples, 4290 were tested positive for HEV and the amplicons were sequenced and genotyped. Twenty-two genotypes were identified. Enterovirus 71 (EV71) and coxsackieviruses A16, A6 and A10 (CA16, CA6 and CA10) were the most common genotypes, and there were no changes in the predominant lineages of these genotypes. EV71 became the most predominant genotype every 2 years. From 2013, CA6 replaced CA16 as one of the two most common genotypes. The results demonstrate the vast diversity of HFMD pathogens, and that minor genotypes are able to replace major genotypes. We recommend carrying-out long-term monitoring of the full spectrum of HFMD pathogens, which could facilitate epidemic prediction and the development of diagnostic assays and vaccines.

Cytokine production by cells adherent to regenerative membranes.

Since cytokines play a critical role in tissue regeneration, we have assayed cytokine production by cells from tissue adherent to regenerative membranes. Cells were recovered from Gore-tex membranes in guided tissue regeneration (GTR) procedures to regenerate that attachment apparatus around teeth and from Gore-tex augmentation membranes (GTAM) used for guided gone regeneration (GBR) procedures in edentulous ridge augmentation with or without implant placement. Cells were screened for mineralized nodule formation in vitro to mRNA analysis to demonstrate that they could form mineralized tissue. Production in interleukin-1 alpha (IL-1 alpha) interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by reverse transcribed-polymerase chain reaction (RT-PCR) of mRNA from rescued regenerative cells, human gingival fibroblasts and periodontal ligament (PDL) cells. Both the gingival fibroblast and PDL cells isolates produced all 4 cytokines. However, the cell isolates from the regenerative membranes had various profiles of cytokine expression. Most GTR cell isolates were positive for all 4 cytokines. IL-1 beta was produced by all 6 GTR cell isolates but was not detected at the same number of cycles of RT-PCR amplification in any of the 6 GBR cell isolates. IL-1 beta transcripts were also not observed in cells derived from a direct biopsy of GBR tissue. Cells were recovered from unexposed GBR membranes did not produce detectable amounts of IFN-gamma, whereas cells recovered from exposed GBR and all GTR membranes produced IFN-gamma. These findings indicate that cells from regenerative tissues express different cytokines and that exposure to the tissue to the oral cavity during healing may modulate this expression.