BACKGROUND: Despite high childhood immunization coverage, sporadic cases of diphtheria have been reported in Malaysia in recent years. This study aims to evaluate the seroprevalence of diphtheria among the Malaysian population.
METHODS: A total of 3317 respondents age 2 years old to 60 years old were recruited in this study from August to November 2017. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of IgG antibody against the toxoid of C. diphtheriae in the blood samples of respondents. We classified respondent antibody levels based on WHO definition, as protective (≥0.1 IU/mL) and susceptible (diphtheriae infection.
RESULTS: Among the 3317 respondents, 57% were susceptible (38.1% of children and 65.4% of adults) and 43% (61.9% of children and 34.6% of adults) had protective antibody levels against diphtheria. The mean antibody level peaked among individuals aged 1-2 years old (0.59 IU/mL) and 6-7 years old (0.64 IU/mL) but generally decreased with age, falling below 0.1 IU/mL at around 4-6 years old and after age 20 years old. There was a significant association between age [Children: χ2 = 43.22(df = 2),p diphtheria toxoid IgG antibody level.
CONCLUSIONS: About 57% of the Malaysian population have inadequate immunity against diphtheria infection. This is apparently due to waning immunity following childhood vaccination without repeated booster vaccination in adults. Children at age 5-6 years old are particularly vulnerable to diphtheria infection. The booster vaccination dose normally given at 7 years should be given earlier, and an additional booster dose is recommended for high-risk adults.
A six-year-old Thoroughbred race horse was presented with left unilateral mucopurulent nasal discharge. Endoscopic examination revealed atypical mycotic lesion within the guttural pouch in which the fungal mass was not located on any neurovascular structures. This case was successfully treated by the combination of manual debulking of fungal diphtheritic plaques and medical treatment that included daily local irrigation and systemic medication. There were no complications and the horse returned to race three weeks later.
Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.
A throat swab from a 9 year old girl with pharyngitis yielded a non-toxigenic strain of Corynebacterium diphtheriae var mitis and Streptococcus group G. C pseudodiphtheriticum was isolated from the throats of two of her four brothers. In each case the isolate was sent to the reference laboratory before full identification. The growth was found to be mixed for one brother; the other isolate being a toxin producing C diphtheriae var gravis. The child was asymptomatic and the case proves that all colonial types on the Hoyles plate should be identified.
Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.
We present a case of a four-year-old boy who succumbed to diphtheria following incomplete course of immunisation, which included diphtheria vaccine. This case report focuses on the issues of parental refusal to vaccines and the development of "halal" vaccines for the prevention of infectious diseases.
Whole-cell Pertussis (wcPertussis) vaccines combined with diphtheria and tetanus toxoids are effective in preventing clinical pertussis. The study aimed at determining the cost of managing fever and convulsions and cost of adverse events associated with wcPertussis. Parents who brought their children to health clinics and parents of children who were admitted for febrile convulsions were interviewed using structured questionnaire and the information were used to determine the cost of managing adverse events. Mean cost of managing mild fever per case was RM249, mean cost of managing high fever per case was RM1,036 and mean cost of managing convulsions was RM1,225. Total cost of managing adverse events was RM261 million for mild fever, RM66.7 million for high fever and RM1.3 million for convulsions. Costs of managing mild and high fever were less than the cost of managing convulsions. Total cost of managing mild fever was highest at RM261 million compared with RM66.7 million for high fever and RM1.3 million for convulsions. Thus, lower risk of adverse events actually contributed to higher costs of managing the adverse event.
A 6-year-old boy presented to a university hospital in Malaysia with infective endocarditis complicating cyanotic congenital heart disease. Blood cultures showed a gram-positive, aerobic, coryneform-like bacillus identified by the hospital laboratory as Corynebacterium xerosis, but a reference laboratory identified the organism as a toxigenic strain of Corynebacterium diphtheriae. The two laboratories concurred on all biochemical test results except for sucrose fermentation.
The Municipal Maternal and Child Health Clinics at Kuala Lumpur were faced with a declining but continuing problem of diphtheria. The arrangements for immunization were such that a low coverage was obtained for triple vaccination, but a high one for smallpox, a disease they had not experienced for many years. By reversing the schedule, so that triple vaccine injections were administered first, and ensuring that fewer children were not immunized because of concurrent minor ailments, the diphtheria immunization coverage was greatly improved. There was some loss of smallpox cover.
The revision commenced in 1970 and the diphtheria incidence rate, which had been falling since 1965, continued to fall but at a lower rate. The author does not discuss possible explanations for this. The article illustrates a dramatic improvement in immunization cover by a simple re-arrangement better suited to the needs of the town
Matched MeSH terms: Diphtheria/prevention & control
Sporadic diphtheria cases in Malaysia have remained low in number since the 1990s. However, in 2016 a total of 31 cases were reported nationwide and to investigate this we performed molecular characterization of 30 Corynebacterium diphtheriae isolates collected from 1981 to 2016 using multilocus sequence typing (MLST). C. diphtheriae isolates were identified and biotyped using the API Coryne kit, while the toxigenicity was determined by PCR and the Elek test. All of the 2016 isolates belonged to biotype mitis, caused respiratory diphtheria and were toxigenic strains. MLST analysis identified 17 sequence types (STs), including 11 new ones. ST453 was the most common clone (7/30, 23.3 %), followed by ST141 (5/30, 16.7 %), ST451 (3/30, 10.0 %) and ST248 (2/30, 6.7 %). The clones identified in 2016 had not been detected in previous isolations and they were phylogenetically distinct. Our results suggest that the diphtheria cases in 2016 were caused by the emergence and spread of new clones in Malaysia.
In November 2016, a 28-year-old Malay man presented to the emergency department in respiratory distress, with a history of fever and sore throat. A clinical diagnosis of acute diphtheria was made and the patient was isolated and ventilated in the intensive care unit, and received diphtheria antitoxin and intravenous antibiotics. Initial laboratory findings failed to confirm diphtheria, leading to discontinuation of antibiotics and quarantine. Public health measures were reinstated after a reference laboratory cultured Corynebacterium diphtheriae. Although there was no contact with ill persons, investigation revealed incomplete immunisation history, and injection of high dose steroids prior to onset of symptoms.
Malaysia is a rapidly developing country with a very young population, about 36% of which are below the age of 15 years. The standard of child health has improved greatly. However, there are great changes in the morbidity and mortality patterns of childhood diseases relating mainly to an improved standard of living; availability of safe water supply and adequate sanitary latrines; a higher literacy rate; rapid industrialisation and urban migration. The infant mortality rate has droppedfrom 50.1 per 1,000 livebirths in 1986 to 10.4 in 1995, and similar trends apply also to neonatal, perinatal and toddler mortality rates. Nevertheless, current major child health problems are those relating to events in the perinatal period and to infections. Despite improvements in the standard of neonatal care with the use ofhigh technology, the commonest cause of certified deaths still occur in the neonatal period. A rapid and inexpensive screening test for G6PD deficiency, a disease present in 2-3% of the population, is now widely available and, together with the use of phototherapy is largely responsible for the declining incidence of kernicterus in the country. Infections remain an important cause of morbidity and mortality although their patterns have changed. The very high (>95%) WHO-EPI-vaccines coverage rate is linked to the great reduction in the incidence of diphtheria, pertussis, tetanus, poliomyelitis and measles. Childhood tuberculosis is less common now, with about 250 - 300 reported cases per year and TB meningitis is rare with about 30-40 reported cases/year. The hepatitis B carrier rate is high (5%) and the introduction of routine newborn hepatitis B vaccination in 1989 is expected to have a positive impact as is the immunisation of young girls against rubella introduced in 1985 in reducing the incidence of congenital rubella syndrome. The incidence of malaria has declined but remains prevalent in the interiors of PeninsularMalaysia and in Sabah and Sarawak. Filariasis is largely under control. Unfortunately, despite great efforts at mosquito control, dengue virus infection remains a major problem with thousands of cases reported every year. Children are most susceptible to dengue haemorrhagic fever with many dying from the shock syndrome. The incidence of acute gastroenteritis has also dropped with most cases being due to a viral aetiology. Acute respiratory infections, mostly viral in origin, account for most attendances at paediatric outpatient services. Although staphylococcal and streptococcal impetigo and pneumonia are common, the incidence of streptococcal related diseases like rheumatic fever and acute glomendonephritis is rapidly declining. The nutritional status of children has improved in tandem with the rise in the standard of living, but subclinical malnutrition is prevalent, particularly among urban squatters and the rural poor. There is a disturbing decline in breastfeeding among urban working mothers. Poor weaning practices and food habits are responsible for the common occurrence of nutritional anaemia (5%) among infants and young children. Greater prosperity, rapid industrialisation and urbanisation have resulted in changes in the childhood disease pattern where non-communicable diseases assume greater importance as the problems of malnutrition and infection are gradually overcome. Road traffic accidents are a major killer and home accidents, largely preventable, are an important cause of morbidity and mortality. Childhood cancer, with about 550 new cases a year, is an important cause of death beyond infancy. Major congenital malformations, with a 1% prevalence rate, cause much ill-health. Thalassaemia is a particularly common genetic disease with fl thalassaemia gene frequency of about 5%. The prevalence of asthma is increasing, with a rate of 13.9% in the Kiang Valley but the prevalence of asthma-related symptoms is much higher. Physical, sexual child abuse and neglect, abandoned babies, substance abuse are but signs of stress of modern city living and peoples inability to cope with it. Although the general standard of child health has greatly improved, there are several states where it is still not satisfactory. In Sabah where there is a large illegal immigrant population, the infant mortality and infection rates are relatively high. In Kelantan and Trengganu, it is common for parents to refuse permission for a lumbar puncture required to treat meningitis. Other still deeply entrenched, culturally-related adverse health practices include : a fatalistic attitude to illness; a preference for traditional practitioners of medicine resulting in late treatment; and 'doctor-hopping' with unrealistic expectations of 'instant cure'. Childhood illnesses that are uncommon in Malaysia include: cystic fibrosis, coeliac disease, ulcerative colitis, Crohns disease, Sudden Infant Death Syndrome, Encopresis, enuresis and epiglottitis due to Haemophilus Influen:ae.
Vaccines, used appropriately and efficiently, have changed the landscape of infectious diseases. Poliomyelitis is almost completely eliminated globally. In many industrialised countries, there has been over 99 percent reduction in incidence of diphtheria, tetanus, measles, mumps, rubella, Haemophilus in-fluenzae b meningitis and over 97 percent reduction in whooping cough.',2Unlike anti-biotics, most vaccines have remained equally effective despite years of continuous usage.
From August till November 1998, the Paediatric and Anaesthetic Units of Hospital Kuala Terengganu managed three patients from Kuala Terengganu District who were ventilated for respiratory diphtheria. Their ages were 5, 4 and 7 years old and their immunisation for diphtheria were not complete. All three patients presented with respiratory distress and were ventilated for upper airway obstruction. Their treatment included intravenous penicillin and diphtheria antitoxin. One patient died of cardiogenic shock with secondary pneumonia. Pharyngeal and tonsillar swabs of all three patients grew toxigenic Corynebacterium diphtheriae biotype mitis. There were 765 throat cultures taken from contacts. The confirmed positive cultures grew 2 toxigenic and 3 non-toxigenic Corynebacterium diphtheriae biotype mitis and surprisingly, 10 non-toxigenic biotype gravis. A prevalence study is needed to document the endemicity of diphtheria in Kuala Terengganu and to determine the carrier rate of both biotypes. Steps have been taken to increase the immunisation coverage in children. The giving of regular booster doses of diphtheria toxoid to the adult population should be considered.
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.