Hand, foot and mouth disease (HFMD) is a childhood illness, commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). In recent years, unusual HFMD outbreaks caused by coxsackievirus A6 (CV-A6) have been reported. From May 2012 to September 2013, enteroviruses were detected in 25 HFMD patients in University Malaya Medical Centre, Kuala Lumpur, Malaysia. The predominant serotypes were EV-A71 (48%) and CV-A6 (48%), followed by CV-A16 (4%). CV-A6 patients (mean age, 2.1) were significantly younger than EV-A71 patients (mean age, 3.3). There were no significant differences observed in clinical features between EV-A71 and CV-A6 patients. Since enteroviruses are difficult to differentiate clinically, the conserved 5’ untranslated region (5’ UTR) was used to identify enterovirus serotypes. Phylogenetic analysis of 5’ UTR showed distinct clustering of viruses as EV-A71, CV-A16 and CV-A6. Further genotyping with capsid genes showed that all the EVA71 sequences belonged to subgenotype B5, while the CV-A16 sequence belonged to subgenotype B2b. CV-A6 sequences were clustered into genotypes D1 and D2, with recent isolates from Seri Kembangan, Malaysia and China. In summary, 59.5% of HFMD cases in our centre in 2012-2013 were caused by EV-A71, CV-A16 and the newly emerging CV-A6. This study also demonstrated that 5’ UTR is suitable for preliminary identification of enteroviruses during HFMD outbreaks, but specific capsid genes such as VP1 and VP4/VP2 are required for further genotyping. Apart from measures to control the spread of the virus during an outbreak of HFMD, identification of EV-A71 as the etiological agent is important as EV-A71 is a major cause of severe neurological complications and potentially fatal.

Hand, foot and mouth disease (HFMD) is a common childhood infection caused by many enteroviruses, including enterovirus A71 (EV-A71). As EV-A71 is associated with severe neurological disease, early diagnosis is critical for clinical and public health management. In developing countries such as Malaysia, laboratory capacity to carry out EV-A71 IgM detection is greater than that of the gold standard methods of virus culture or molecular detection. This study evaluated two diagnostic kits, EV-A71 IgM-capture enzyme-linked immunosorbent (ELISA) and EV-A71 IgM-colloidal gold immunochromatographic assay (GICA), which had previously only been assessed in China. The assays were tested with 89 serum samples from patients with suspected HFMD. The sensitivity, specificity, positive predictive value, and negative predictive value rates were 78.4%, 80.8%, 74.4%, and 84.0%, respectively, for the IgM-capture ELISA, and 75.7%, 76.9%, 70.0%, and 81.6% for the IgM GICA. These performance measures were similar between the two assays. Concordance between the two assays was 91.1%. The sensitivity rates were lower than those previously reported, likely because the multiple circulating EV-A71 genotypes in Malaysia differ from the C4 subgenotype found in China and used in the assays. Both assays had low false positive rates (12.5% and 16.7% for ELISA and GICA, respectively) when tested on sera from patients confirmed to have enteroviruses. Both diagnostic kits are suitable for early diagnosis of HFMD caused by EV- A71 in Malaysia, but confirmation with culture or PCR is still important.

Three genomic regions, VP4 capsid, VP1 capsid and 3D RNA polymerase of human enterovirus 71 (EV-71) and coxsackievirus A16 (CV-A16) were sequenced to understand the evolution of these viruses in Malaysia. A total of 42 EV-71 and 36 CV-A16 isolates from 1997-2008 were sequenced. Despite the presence of many EV-71 subgenotypes worldwide, only subgenotypes B3, B4, B5, C1 and C2 were present in Malaysia. Importation of other subgenotypes such as C3, C4/D and C5 from other countries was infrequent. For CV-A16, the earlier subgenotype B1 was replaced by subgenotypes B2a and the recent B2c. Subgenotype B2a was present throughout the study while B2c only emerged in 2005. No genetic signatures could be attributed to viral virulence suggesting that host factors have a major role in determining the outcome of infection. Only three EV-71 B3 isolates showed non-consistent phylogeny in the 3D RNA polymerase region which indicated occurrence of recombination in EV-71. High genetic diversity was observed in the Malaysian EV-71 but Malaysian CV-A16 showed low genetic diversity in the three genomic regions sequenced. EV-71 showed strong purifying selection, but that occurred to a lesser extent in CV-A16.

Objective To assess the results of paediatric liver transplantation in our institution. Methods From September 1993 to November 1996, 10 living-related liver transplants (LRLT) and 3 reduced-size liver transplants (RSLT) were performed on 12 children at our hospital. The medical records of the patients were reviewed. All patients suffered from end-stage liver disease resulting from biliary atresia with failed Kasai's operations. Their ages at initial transplantation ranged from 8 months to 11 years. Excluding the 2 older children aged 7.5 and 11 years, the remaining patients were aged 10.5 months on the average and weighed 6 to 9.5 kg (mean: 6.8 kg) at the time of initial transplantation.Results All living donors were discharged on postoperative day 4 to 8 and resumed their previous normal activities. All recipients were alive with normal liver function and growing after a follow-up period of 3-40 months (mean: 21 months). The patient survival rate was 100%. One patient with RSLT had hepatitis of undetermined aetiology and underwent retransplant with a graft from her mother. The graft survival rate was 92%. Postoperative complications included: postoperative bleeding (n=3), hepatic vein stenosis (n=l), biliary-enteric anastomotic stenosis (n=3), intestinal perforation (n=l) and portal vein thrombosis (n=l). They were all treated promptly. In all patients, the hepatic artery (diameter ranged from 1.5 to 2.5 mm) anastomosis was achieved by microvascular technique. There was no hepatic artery thrombosis in our patients. Conclusion With technical refinements, early detection and prompt treatment of complications, and advances in immunotherapy, excellent results can be achieved in paediatric liver transplantation.