In this study, we report the comparative genomics and phylogenetic analysis of Corynebacterium diphtheriae strain B-D-16-78 that was isolated from a clinical specimen in 2016. The complete genome of C. diphtheriae strain B-D-16-78 was sequenced using PacBio Single Molecule, Real-Time sequencing technology and consists of a 2,474,151-bp circular chromosome with an average GC content of 53.56%. The core genome of C. diphtheriae was also deduced from a total of 74 strains with complete or draft genome sequences and the core genome-based phylogenetic analysis revealed close genetic relationship among strains that shared the same MLST allelic profile. In the context of CRISPR-Cas system, which confers adaptive immunity against re-invading DNA, 73 out of 86 spacer sequences were found to be unique to Malaysian strains which harboured only type-II-C and/or type-I-E-a systems. A total of 48 tox genes which code for the diphtheria toxin were retrieved from the 74 genomes and with the exception of one truncated gene, only nucleotide substitutions were detected when compared to the tox gene sequence of PW8. More than half were synonymous substitution and only two were nonsynonymous substitutions whereby H24Y was predicted to have a damaging effect on the protein function whilst T262V was predicted to be tolerated. Both toxigenic and non-toxigenic toxin-gene bearing strains have been isolated in Malaysia but the repeated isolation of toxigenic strains with the same MLST profile suggests the possibility of some of these strains may be circulating in the population. Hence, efforts to increase herd immunity should be continued and supported by an effective monitoring and surveillance system to track, manage and control outbreak of cases.
Little is known about the sero-prevalence of diphtheria anti-toxoid antibody levels among medical students in Malaysia. They too, just like other health care workers (HCWs) are at risk of contracting and transmitting diphtheria. Fortunately, this can be prevented by giving a specific vaccine: the diphtheria, tetanus and pertussis (DTP) vaccine. Nonetheless, data from local or regional surveys are needed before any decision is made by the respective authorities. General objective: We studied the epidemiology of diphtheria anti-toxoid antibody levels and vaccination history amongst medical students and staff in Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. Specific objectives: We determined the level of diphtheria anti-toxoid antibodies amongst pre-clinical students and staff. Methodology: A total of 152 sera were collected from subjects aged 19 to 63, and diphtheria anti-toxoid levels were measured by an enzyme-linked immunosorbent assay. Results: One hundred and fifty-two (94.4%) blood samples out of 161 participants were successfully withdrawn, which comprised 105 (69.1%) and 47 (30.9%) medical students and staff, respectively. A total of 77.6% and the other 22.4% of the subjects had full and basic protection, respectively. Higher levels were predominant amongst males and they were 1.3 times more protected than females in 20-29 year-old group (85.1% vs 66.2%; odd ratios 1.25 [95% CI 1.03-1.50]; P=0.03). No significant difference in the levels of immunity among subjects for ethnicity and academic position (P>0.05). Recommendations: Level of full protection against diphtheria toxin should be clearly defined by broad population based studies using several comparable detection methods. Medical students and staff with basic protection should be closely monitored or should be given a booster dose for those who are at high risk of acquiring the disease. Thus, a standard degree of coverage should be clearly determined for health workers to prevent a potential outbreak. Conclusion: Students and staff possess immunity towards diptheria toxin however the level of full protective antibody is yet to be determined in future.