Demographic, clinical and laboratory features of leptospirosis and dengue co-infection in Malaysia.

Purpose. In this study, we aim to describe and compare the demographical, clinical and laboratory features of leptospirosis and dengue co-infections (LDCI) against single leptospirosis infections in Malaysia.Methodology. Data of patients admitted to various hospitals in Malaysia from 2011 to 2015 diagnosed with leptospirosis in our laboratory were obtained from their admission records. Co-infection with dengue was determined by collecting dengue serology results. Multivariate analysis and multiple logistic regression were used to differentiate features between single leptospirosis infection and confirmed LDCI.Results/Key findings. Only 602 (29.11 %) out of 2068 leptospira-positive patients were concurrently tested for dengue during their admission in which 44 (7.31 %) patients had positive non-structural protein 1 (confirmed LDCI) while 140 (23.26 %) were positive for dengue IgM (probable LDCI) with the highest number of cases recorded in high-density suburban districts. Myalgia and arthralgia were the only significant distinguishing clinical feature of LDCI while significant laboratory features were thrombocytopenia and high levels of alanine and aspartate transaminases. Only thrombocytopenia displayed a predictive value for LDCI from analysis of multiple logistic regression. Death occurred in 19 (3.16 %) patients in this dataset studied but only three (0.50 %) were attributed to LDCI.Conclusion. There is a considerable prevalence of LDCI in this country of which overlapping demographic, clinical and laboratory presentations pose diagnostic and therapeutic challenges. Efforts to raise awareness regarding LDCI, better access to diagnostic services and further prospective studies are warranted.

G1896A Precore Mutation and Association With HBeAg Status, Genotype and Clinical Status in Patients With Chronic Hepatitis B.

BACKGROUND: Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia. OBJECTIVES: We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate. PATIENTS AND METHODS: Serum samples from 93 patients confirmed as hepatitis B carriers were collected for molecular assay. The whole genome of HBV was amplified by polymerase chain reaction and directly sequenced. The precore and basal core promoter regions were analyzed for presence of mutations. RESULTS: The most commonly observed mutation in the precore region was C1858T with 64.5% prevalence. The precore mutation of interest (G1896A) was identified in 25.8% of isolates. The basal core promoter mutations detected were A1762T-G1764A (26.9%), C1653T (8.6%), A1752G (10.8%) and C1766T (2.2%). No significant association was observed between G1896A mutation and HBeAg-negativity. Nonetheless, G1896A was highly prevalent among HBV genotype B. Clinical association revealed that subjects with G1896A mutations were mainly detected in asymptomatic chronic hepatitis B (58.3%) and liver cirrhosis (41.7%). One subject was diagnosed with fulminant hepatitis (4.2%) and 8.3% had hepatocellular carcinoma (HCC). CONCLUSIONS: Our data suggested an intermediate prevalence of G1896A mutation among Malaysian hepatitis B carriers. The stop codon mutation has a significant association with genotype B and patients with chronic hepatitis B and liver cirrhosis.

Drug-resistance associated mutations in polymerase (p) gene of hepatitis B virus isolated from malaysian HBV carriers.

BACKGROUND: Mutations in the polymerase (P) gene of hepatitis B virus are often associated with drug resistance. The pattern of mutations varies geographically, thus giving rise to genotypes diversity. OBJECTIVES: This study was carried out to detect mutations in P gene of hepatitis B virus isolated from Malaysian HBV carriers. MATERIALS AND METHODS: A total of 58 sera samples were analyzed by PCR and sequencing, of which the P gene of isolated HBV was successfully amplified and sequenced from 40 samples. RESULTS: Genotyping of these samples revealed that the predominant genotype was genotype C (22/40, 55.0%), followed by genotype B (17/40, 42.5%), and only 1 sample showed genotype D (2.5%). A number of significant drug resistant mutations were found in five patients including S202I, N236T, M250L, L180M/V, M204I, A181T, T184G, M250V, and V173L. Of these, L180M/V and M204I were most frequently detected (80%) and associated with lamivudine in combination with emtricitabine and telbivudine drug resistance. Association with age, sex, and clinical symptoms revealed that these patients were all male, mid to elderly age and almost all hadcirrhotic liver disease. CONCLUSIONS: Detection and surveillance of the significant sites of mutations in HBV is crucial for clinicians to decide on the choice of antiviral treatment and further management of hepatitis B carriers.

S gene mutants occurrence among hepatitis B carriers in malaysia.

BACKGROUND: The S gene region of the hepatitis B virus (HBV) codes for surface antigen (HBs Ag) and is responsible for classification of HBV strains. OBJECTIVES: The current study aimed to identify important mutations in the S gene in Hepatitis B virus (HBV) isolated from Malaysian HBV carriers. MATERIALS AND METHODS: Isolated HBV DNAs were subjected for PCR amplification and sequencing of HBV full genome. RESULTS: A total of 76 HBV full genome and 17 partial genome sequences were obtained from the 93 sequenced sera samples Genotyping of the full genome sequences by HEPSEQ software revealed a distribution of 49.46%, 48.39% and 2.15% of genotypes C, B, and D, respectively; whereas phylogenetic and jumping profile Hidden Markov Model (jpHMM) analysis identified six (7.89%) recombinant B/C strains. The distribution of sub-genotypes were B2 (78.79%) and B3 (21.21%) for genotype B, sub genotype D2 (100%) for genotype D and sub genotype C1 (75.76%), C2 (15.15%), C3 (6.06%) and C5 (3.13%) for genotype C. Mutation analysis in the S gene demonstrated two significant mutations which were W182 stop codon and deletion at open reading frame (ORF) of pre-S1 with the frequency occurrence of 2.2% (2/93) and 5.4% (5/93), respectively. The two patients with W182 stop codon were both male, infected with HBV genotype C and one showed progression of liver disease to hepatocellular carcinoma (HCC). CONCLUSIONS: Association with sex, genotype and clinical symptoms revealed that the pre-S1 ORF deletion occurred in 40% , 40%,and 20% of genotypes B,C, and D respectively, and 80% of the female population, of which all but one were diagnosed with chronic hepatitis B. Additionally, several mutations were found in the BCP region with the following incidence rate; C1653 T (8.6%), A1752 G (10.8%),1762 AGG--TGA 1764 (26.9%), C1766T(2.2%),T1768 A (10.8%), C1858 T (64.5%), G1896 A (25.8%).

Current trend of pneumococcal serotypes distribution and antibiotic susceptibility pattern in Malaysian hospitals.

From January 2008 to December 2009, 433 Streptococcus pneumoniae strains were examined to determine the serotype distribution and susceptibility to selected antibiotics. About 50% of them were invasive isolates. The strains were isolated from patients of all age groups and 33.55% were isolated from children below 5 years. The majority was isolated from blood (48.53%) and other sterile specimens (6.30%). Community acquired pneumonia (41.70%) is the most common diagnosis followed by sepsis (9.54%). Serotyping was done using Pneumotest Plus-Kit and antibiotic susceptibility pattern was determined by modified Kirby-Bauer disk diffusion method and measurement of minimum inhibitory concentration (MIC) using E-test strip. Ten most common serotypes were 19F (15.02%), 6B (10.62%), 19A (6.93%), 14 (6.70%), 1 (5.08%), 6A (5.08%), 23F (4.85%), 18C (3.93%), 3 (2.08%) and 5 (1.85%). Penicillin MIC ranged between ≤ 0.012-4 µg/ml with MIC90 of 1 µg/ml. Penicillin resistant rate is 31.78%. The majority of penicillin less-susceptible strains belonged to serotype 19F followed by 19A and 6B. Based on the serotypes distribution 22 (44.00%), 28 (56.00%) and 39 (78.00%) of the invasive isolates from children ≤ 2 years were belonged to serotypes included in the PCV7, PCV10 and PCV13, respectively.

Characteristics of community- and hospital-acquired meticillin-resistant Staphylococcus aureus strains carrying SCCmec type IV isolated in Malaysia.

Community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) occurring among hospital isolates in Malaysia has not been reported previously. As CA-MRSA reported worldwide has been shown to carry SCCmec types IV and V, the aim of this study was to determine the SCCmec types of MRSA strains collected in Malaysia from November 2006 to June 2008. From a total of 628 MRSA isolates, 20 were SCCmec type IV, whilst the rest were type III. Further characterization of SCCmec type IV strains revealed 11 sequence types (STs), including ST22, with the majority being ST30/Panton-Valentine leukocidin positive. Eight out of nine CA-MRSA were ST30, one was ST80, and all were sensitive to co-trimoxazole and gentamicin. Five new STs designated ST1284, ST1285, ST1286, ST1287 and ST1288 were discovered, suggesting the emergence of novel clones of MRSA circulating in Malaysian hospitals. The discovery of the ST22 strain is a cause for concern because of its ability to replace existing predominant clones in certain geographical regions.