Detection of enteroviruses during a 2018 hand, foot and mouth disease outbreak in Malaysia

@#Hand, foot, and mouth disease (HFMD) is a common childhood disease caused by enteroviruses. In 2018, a HFMD outbreak in Malaysia affected over 76,000 children. In this study, we used RT-qPCR and CODEHOP PCR to detect the causative agents in 89 clinically diagnosed HFMD patients in Kuala Lumpur and Selangor. Most (62.9%) of the children were below 3 years old. PCR with either assay detected enteroviruses in 84.2% (75/89) and CODEHOP PCR successfully typed 66.7% (50/75) of the enteroviruses. Sequencing of CODEHOP amplicons showed co-circulation of multiple enteroviruses with coxsackievirus A6 (CV-A6) and A16 as the predominant serotypes, but not the neurovirulent enterovirus A71. CV-A6 infection was more common in children less than 12 months old (p=0.01) and was more likely to cause vesicles in the gluteal area (p=0.01) compared to other enteroviruses. Establishing a robust identification method during HFMD outbreaks is important for patient management and public health responses.

Monoclonal antibody-escape variant of dengue virus serotype 1: Genetic composition and envelope protein expression

Monoclonal antibody-escape variant of dengue virus type 1 (MabEV DEN-1) was discovered and isolated in an outbreak of dengue in Klang Valley, Malaysia from December 2004 to March 2005. This study was done to investigate whether DEN152 (an isolate of MabEV DEN-1) is a product of recombination event or not. In addition, the non-synonymous mutations that correlate with the monoclonal antibody-escape variant were determined in this study. The genomes of DEN152 and two new DEN-1 isolates, DENB04 and DENK154 were completely sequenced, aligned, and compared. Phylogenetic tree was plotted and the recombination event on DEN152 was investigated. DEN152 is sub-grouped under genotype I and is closely related genetically to a DEN-1 isolated in Japan in 2004. DEN152 is not a recombinant product of any parental strains. Four amino acid substitutions were unique only to DEN 152. These amino acid substitutions were Ser[326]Leu, Ser[340]Leu at the deduced E protein, Ile[250]Thr at NS1 protein, and Thr[41]Ser at NS5 protein. Thus, DEN152 is an isolate of the emerging monoclonal antibody-escape variant DEN-1 that escaped diagnostic laboratory detection.