Syed Zulkifli Syed Zakaria

Dengue epidemic in Malaysia: Not a predominantly urban disease anymore

BackgroundDengue infection has been an important and serious public health concern in Malaysia ever since its first reported case here in 1902. Nevertheless, to our knowledge, no nationwide investigation has been carried out to determine the actual magnitude of dengue endemicity in the Malaysian population. In this study, we describe a cross sectional seroepidemiology study of dengue IgG seroprevalence in the Malaysian adult population.FindingsFrom 1000 subjects (35-74 years old), 91.6% subjects were found to be dengue seropositive. Age is found to be a significant risk factor associated with dengue seroposivity, where the seroprevalence increased with every 10 year increase in age. Nevertheless, gender and ethnicity did not have an effect. Interestingly, there were similar seroprevalence rates between urban and rural samples, showing that dengue is presently not confined to urban areas in Malaysia.ConclusionsHigh dengue IgG seropositivity found in the population is an indication that dengue might be endemic in Malaysia for a long time into the future. Public awareness, proper vector control and vigilant surveillance are critical to keep the infection rates low and to prevent outbreaks.

Neutrophil Gelatinase-Associated Lipocalin as an Early Marker of Contrast-Induced Nephropathy After Coronary Angiography

We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) was an early predictive biomarker of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (n = 100) undergoing coronary catheterization. Serum creatinine (SCr) levels were measured at baseline, 24 hours, and 48 hours post procedure. Serum NGAL was measured preprocedure, 4 hours, and 24 hours post procedure. The frequency of CIN was 11%. In patients with CIN, SCr achieved significance only at 48 hours (P = .006), whereas serum NGAL increased ≥25% from baseline at 24 hours in 7 of 11 patients with CIN (P = .04) but did not change in the other 4. However, serum NGAL also rose ≥25% in 12 of 89 non-CIN patients. This subgroup could have had “incipient CIN.” Serum NGAL delta value at baseline, 24 hours was superior to SCr for early diagnosis of CIN. In conclusion, serum NGAL is an early predictive biomarker for CIN.

Serum neutrophil gelatinase-associated lipocalin and cystatin C are early biomarkers of contrast-induced nephropathy after coronary angiography in patients with chronic kidney disease

We had previously reported on serum neutrophil gelatinase-associated lipocalin (NGAL) as an earlier biomarker of contrast-induced nephropathy (CIN) than serum creatinine (SCr) in 100 patients with chronic kidney disease undergoing coronary angiography.1 We then compared serum NGAL to serum cystatin C (CysC) in the same group of patients. The SCr, estimated glomerular filtration rate, serum NGAL, and serum CysC were measured at baseline and various time points as appropriate postprocedure. The frequency of CIN was 11% (n = 11). Serum NGAL increased ≥25% from baseline at 24 hours in 7 patients with CIN (P = .04). Serum CysC increased ≥25% from baseline at 24 hours in 4 patients with CIN (P = .008). Changes in serum NGAL and serum CysC from baseline at 24 hours (▵ values) could diagnose CIN 24 hours earlier than SCr with serum NGAL showing a superior performance.

Vincristine-induced vocal cord palsy: case report and review of the literature.

Vincristine-induced vocal cord paralysis is a rare but serious complication. We report 2 patients with acute lymphoblastic leukemia who developed progressive stridor during induction chemotherapy. There were no clinical features of peripheral or autonomic neuropathy. Flexible laryngoscopy confirmed the diagnosis of bilateral vocal cord palsy; interestingly, the nerve conduction test revealed axonal motor neuropathy involving the median and common peroneal nerves in both patients. The first patient required prolonged ventilatory support necessitating unilateral cordectomy before extubation, whereas the second only required supplemental oxygen therapy. There was resolution of stridor in the first patient after cordectomy and gradual clinical improvement in the second. These cases illustrate that a high index of suspicion of vincristine-induced vocal cord palsy with prompt otolaryngology consultation for laryngoscopy is required in the diagnostic evaluation of a patient who has received vincristine.

Cohort profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100 000 individuals aged 35–70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106 527participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my).

Emergence of chikungunya seropositivity in healthy Malaysian adults residing in outbreak-free locations: Chikungunya seroprevalence results from the Malaysian Cohort

BackgroundIn 1998, Malaysia experienced its first chikungunya virus (CHIKV) outbreak in the suburban areas followed by another two in 2006 (rural areas) and 2008 (urban areas), respectively. Nevertheless, there is still a lack of documented data regarding the magnitude of CHIKV exposure in the Malaysian population. The aim of this study was to determine the extent of chikungunya virus infection in healthy Malaysian adults residing in outbreak-free locations.MethodsA cross sectional study of chikungunya (CHIK) seroprevalence was carried out in 2009 amongst The Malaysian Cohort participants living in four states (Kuala Lumpur, Selangor, Pahang and Negeri Sembilan). A total of 945 participants were randomly identified for the study. Potential risk factors for CHIK infection were determined via questionnaires, and IgG antibodies against CHIK were detected by an enzyme-linked immunosorbent assay. Logistic regression identified risk factors associated with CHIK seropositivity, while geographical information system was used for visual and spatial analysis.ResultsFrom the 945 serum samples tested, 5.9% was positive for CHIK IgG. Being male, Malay, rural occupancy and Negeri Sembilan residency were identified as univariate predictors for CHIK seropositivity, while multivariate analysis identified being male and rural occupancy as risk factors.ConclusionsThis study provided evidence that CHIK is slowly emerging in Malaysia. Although the current baseline seroprevalence is low in this country, increasing number of CHIK cases reported to the Malaysia Ministry of Health imply the possibility of CHIK virus becoming endemic in Malaysia.

Evaluation of BV(®) Blue Test Kit for the diagnosis of bacterial vaginosis.

The aim of this study is to determine the sensitivity, specificity and the predictive value of the BV(®) Blue Test Kit in the diagnosis of bacterial vaginosis and to observe the risk factors associated with bacterial vaginosis (BV) in the study population. A prospective, cross-sectional study on 151 non-pregnant women who presented or referred to HUKM with presence of vaginal discharge, abnormal vaginal odour, pruritus vulvae of lower genital tract or incidental finding of abnormal PV discharge on pelvic examination. Samples of vaginal discharge were tested for bacterial vaginosis infection using Amsels criteria, BV(®) Blue test and Gram stain (Nugents score). Gram stain interpretation was made blinded without knowledge of other test result. Using Gram stains criteria as a gold standard, the sensitivity, specificity, positive and negative predictive value of BV(®) Blue test and each of Amsels criteria were estimated. The use of vaginal douches increased the risk of BV. The risk of BV with vaginal douching was 2.8 (95% CI 1.0-7.8) compared to never users. BV(®) Blue test showed a sensitivity of 100.0%, specificity of 98.3%, positive predictive value (PPV) of 94.4% and negative predictive value (NPV) of 100.0% compared to Gram stain (Nugents method). BV(®) Blue test had excellent agreement with Gram stain which was 98.7%. BV(®) Blue test is a simple, rapid and reliable test allowing immediate diagnosis and prompt treatment of BV in the absence of microscopy which would greatly benefit majority of women at the greatest risk of sequel of bacterial vaginosis.

GESTATIONAL DIABETES MELLITUS IN PRIMIGRAVIDAE: A MILD DISEASE

This prospective observational study was done to analyse the prevalence of gestational diabetes mellitus (GDM) among primigravidae and its outcome. All healthy primigravidae with singleton pregnancies were offered universal glucose tolerance testing between 16 and 28 weeks gestation. GDM and non GDM groups were managed according to hospital protocol. The antenatal features and pregnancy outcomes were analysed. Out of 616 primigravidae, 113 (18.34%) were GDM with slightly older (27.9 +/- 4.2 versus 26.32 +/- 3.3, p < 0.001) age. The mean fasting and two hours postprandial blood glucose in both groups were 4.99 +/- 1.08 mmol/l, 8.86 +/- 1.41 mmol/l(GDM) and 4.36 +/- 0.43 mmol/l, 5.71 +/- 1.11 mmol/l (Non GDM), respectively. Maternal family history of diabetes mellitus, weight exceeding 80 Kg, polyhydramnios (2.65% versus 0.2%, p = 0.028) and neonatal hyperbilirubinaemia (9.73% versus 2.98%, p = 0.01) occurred significantly more frequent in the GDM group compared to normal. There was no significant difference in other pregnancy outcomes and complications between the two groups. In conclusion GDM in primigravidae was detected at a relatively young age with more frequent maternal family history of DM, weight exceeding 80 Kg, polyhydromnions and neonatal hyperbilirubinaemia. The degree of disease was mild and treatment led to no significant complication.

Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy

Glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death. We screened 14 patients from 13 families with clinical and biochemical features suggestive of GCE for mutation in AMT, GLDC and GCSH genes by direct sequencing and genomic rearrangement of GLDC gene using a multiplex ligation-dependant probe amplification. We identified mutations in all 14 patients. Seven patients (50%) have biallelic mutations in GLDC gene, six patients (43%) have biallelic mutations in AMT gene and one patient (7%) has mutation identified in only one allele in GLDC gene. Majority of the mutations in GLDC and AMT were missense mutations and family specific. Interestingly, two mutations p.Arg265His in AMT gene and p.His651Arg in GLDC gene occurred in the Penan sub-population. No mutation was found in GCSH gene. We concluded that mutations in both GLDC and AMT genes are the main cause of GCE in Malaysian population.

Identification of Differentially Expressed Proteins in the Serum of Colorectal Cancer Patients Using 2D-DIGE Proteomics Analysis

Early detection of colorectal cancer (CRC) is vital for the improvement of disease prognosis. However to date there are no blood-based biomarkers sensitive and specific enough for early diagnosis. We analysed the differences in serum protein expression of early stage CRC (Dukes’ A and B) and late stage CRC (Dukes’ C and D) against normal controls using 2D Fluorescence Difference Gel Electrophoresis (2D-DIGE). Analysis of the 2D maps showed that 23 proteins were differentially expressed between groups (p ≤ 0.05) and these proteins were identified with LC-MS/MS. Eight proteins were up-regulated and 2 down-regulated in patients with early CRC, whereas 14 proteins were up-regulated and 4 down-regulated in those with late CRC compared to normal controls (p ≤ 0.05). Five proteins, namely apolipoprotein A1 (APOA1), apolipoprotein E (APOE), complement factor H (CFH), galectin-7 (GAL7) and synaptojanin-2 (SYNJ2) were validated using ELISA and only APOA1 and GAL-7 showed consistent findings. Further validation using immunohistochemistry showed negative immunoreactivity for GAL-7 in CRC tissues, suggesting that GAL-7 detected in the serum did not originate from the CRC tumour. APOA1 showed positive immunoreactivity but its expression did not correlate with Dukes’ staging (p = 0.314), tumour grading (p = 0.880) and lymph node involvement (p = 0.108). Differences in APOA1 isoforms and/or conformation between serum and tissue samples as well as tumour heterogeneity may explain for the discrepancies between DIGE and ELISA when compared to immunohistochemistry. Structural and functional studies of APOA1 in future would best describe the role of APOA1 in CRC.