Isolation and molecular detection of dengue and chikungunya virus from field-collected adult mosquitoes in Kelantan, Malaysia.

BACKGROUND OBJECTIVES: Dengue and chikungunya infections are one of the major health problems that have plagued the human population globally. All dengue virus (DENV) serotypes circulate within Malaysia with particular serotypes dominating in different years/outbreaks. In the state of Kelantan, an increasing number of DENV and chikungunya virus (CHIKV) new cases have been reported, including several deaths. This study aimed to isolate and detect these arboviruses from adult mosquitoes in Kelantan. METHODS: Adult mo squito samples were collected from January to August 2019 and were identified according to gender, species and locality. The isolation of the virus was done in C6/36 cells. Dengue NS1 antigen was carried out using direct mosquito lysate and mosquito culture supernatant. Detection and serotyping of the DENV was performed using multiplex RT-PCR and CHIKV detection using a one-step RT-PCR assay. RESULTS: Of 91 mosquito pools, four were positive for NS1 antigen comprising two pools (2.2%) of male Ae. albopictus (Pulau Melaka and Kubang Siput) and two pools (2.2%) of Ae. aegypti (Kampung Demit Sungai). DENV 1 was detected in one pool (0.9%) of female Ae. albopictus among 114 tested Aedes pools. Two pools of 114 pools (1.7%) from both male Aedes species were positive with double serotypes, DENV 1 and DENV 2 (Pulau Melaka). However, no pool was positive for CHIKV. INTERPRETATION CONCLUSION: The presence of DENV and the main vectors of arboviruses in Kelantan are pertinent indicators of the need to improve vector controls to reduce arbovirus infections among people in the localities.

Serum and urine galactose deficient-IgA1 as alternative biomarkers in the management of IgA nephropathy.

INTRODUCTION: Immunoglobulin A (IgA) nephropathy (IgAN) results from abnormal accumulation of immune complexes containing galactose deficient IgA1 (Gd-IgA1) in the kidneys. About 40% of patients develop end-stage kidney disease within 20 years of renal biopsy. At present, the diagnosis and risk stratification of patients (using the international IgAN risk prediction tool) rely on renal biopsy, which is an invasive procedure. Also, treatment decisions are still dependent on proteinuria, which is not specific for IgA nephropathy. We discussed the role of serum and urine Gd- IgA1 in the diagnosis of IgAN, its association with disease progression and changes with treatment in patients with IgA nephropathy. MATERIALS AND METHODS: A systematic search of PubMed and Scopus databases was done to identify the articles that are relevant to the topic including systematic reviews and original articles. RESULTS: Several studies showed that both serum and urine Gd-IgA1 differentiate IgA nephropathy patients from healthy people and other glomerulonephropathies. Thus, it is useful as a less invasive diagnostic biomarker, although detection methods varied between studies with different sensitivities. There are various reports of its use as a prognostic parameter. Evidence is emerging for its use as a monitoring parameter for treatment. CONCLUSION: Galactose deficient IgA1 is a promising biomarker in the management of IgA nephropathy, although a more robust and standardised means of estimation is required.

Prevalence of Vancomycin-Resistant Enterococcus (VRE) in Poultry in Malaysia: The First Meta-Analysis and Systematic Review.

Databases such as PubMed, Scopus and Google Scholar were searched. Data extraction and assessment of study protocol was done by two independent reviewers and the results were reviewed by a third. OpenMeta analyst and comprehensive meta-analysis (CMA) were used for the meta-analysis. The random effect model was used, publication bias and between-study heterogeneity was assessed. Seventeen studies were added to the final meta-analysis. Studies were sampled from 2000-2018 and of the 8684 isolates tested, 2824 were VRE. The pooled prevalence of VRE among poultry in Malaysia was estimated at 24.0% (95% CI; 16.7-33.1%; I2 = 98.14%; p < 0.001). Between-study variability was high (t2 = 0.788; heterogeneity I2 = 98.14% with heterogeneity chi-square (Q) = 858.379, degrees of freedom (df) = 16, and p < 0.001). The funnel plot showed bias which was confirmed by Egger's test and estimates from the leave-one-out forest plot did not affect the pooled prevalence. Pooled prevalence of VRE in chickens and ducks were 29.2% (CI = 18.8-42.5%) and 11.2%, CI = 9.0-14.0%) respectively. Enterococcus faecalis was reported most with more studies being reported in Peninsular Malaysia Central region and used antibiotic disc diffusion as detection method. Increased surveillance of VRE in poultry in Malaysia is required.

The blood pressure variability, arterial elasticity and humoral factors in subjects with family history of hypertension.

Normotensive subjects with family history of hypertension (FHT) have been reported to have increased left ventricular mass index and reduced ventricular compliance. Of interest is whether blood pressure variability (BPV), which has been associated with target organ damage, is then part of this complex inherited syndrome? The objectives of this study are to determine whether there are any significant differences in BPV, arterial compliance and humoral factors in subjects with FHT as compared to controls. Thirty-five subjects with self reported FHT and 35 matched controls underwent 24 hour BP monitoring (BR-102, Schiller Inc. Germany). Arterial compliance was measured using systolic pulse wave tonometry (HDI/Pulsewave Cardiovascular Profiling Instrument, Hypertension Diagnostic Inc. USA). None of the subjects were hypertensive or diabetic. Out of these numbers, 25 subjects with FHT and 26 controls had measurements of plasma catecholamines, plasma renin and serum aldosterone. Catecholamines were assayed with high performance liquid chromatography, while both renin and aldosterone measurements were by radioimmunoassay. Subjects with FHT have higher night time BPV. There was no significant difference in arterial compliances between both groups. There were increased level of norepinephrine (NE) in subjects with FHT but epinephrine (E), renin and aldosterone levels were similar in both groups. There were no correlations between NE and BPV but E was negatively associated with daytime and mean arterial systolic BPV. In conclusion subjects with FHT demonstrated a higher night time BPV and NE level as compared to controls.

Blood pressure variability and arterial elasticity in hypertensive subjects.

Apart from the mean 24 hour ambulatory blood pressure (ABP), the blood pressure variability (BPV) also bears an independent relationship with target-organ damage in hypertension. A reduction in arterial compliance has been demonstrated in hypertension but its relation to BPV is still unknown. The aim of the study is to compare BPV and arterial compliance between hypertensive and normotensive subjects. Eighteen hypertensives and 18 controls were enrolled. Noninvasive 24-hour ABP monitoring was performed with BR-102 monitor (Schiller Inc. Germany). Arterial compliance was determined by the HDI/Pulsewave Research Cardiovascular Profiling Instrument (Hypertension Diagnostic Inc. USA). There were significantly higher systolic, diastolic and mean arterial BPV in hypertensives as compared to normotensive group. Only systolic BPV remained significantly high in hypertensives during night time. There were lower arterial compliances in hypertensive as compared to normotensive group. No significant relationship however was found between BPV and arterial compliance in hypertensive subjects. In conclusion, there were higher BPV and lower arterial compliances in hypertensive subjects as compared to normotensive subjects.

An evaluation of the World Health Organization's 1997 and 2009 dengue classifications in hospitalized dengue patients in Malaysia.

INTRODUCTION: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012. METHODOLOGY: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed. RESULTS: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively. CONCLUSIONS: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care.

Fatal persistence of West Nile virus subtype Kunjin in the brains of flavivirus resistant mice.

Flaviviruses cause febrile illnesses in humans that may progress to encephalitis and death. Both viral and host factors determine the level of virus replication and outcome of infection. In mice, genetically determined resistance conferred by the flavivirus resistance locus (Flv) is responsible for the restricted flavivirus replication and prevention of disease development. Majority of flaviviruses express significant virulence, replicate to high titers and cause high mortality in susceptible mice, while congenic resistant mice endure the infection, show significantly reduced levels of virus replication and remain healthy. In contrast, infection with West Nile virus subtype Kunjin (KUNV) causes morbidity and fatal outcomes even in mice that are naturally resistant to flaviviruses. There are two possible mechanisms that could account for such an unforeseen virulence of KUNV in resistant mice: (a) an abrogation of Flv-controlled natural resistance leading to high virus replication, or (b) massive virus-induced immunopathology in the brain. To identify the cause(s) of fatality of KUNV infection, disease progression, virus replication and brain histopathology were studied in parallel in resistant and congenic susceptible mice. While KUNV replicated to high titers causing early fatalities in susceptible mice, it showed only reduced replication associated with the delayed morbidity in resistant mice indicating no abrogation of the Flv resistance. No evidence of excessive immune cell infiltration and tissue damage following KUNV infection were found. However, incomplete KUNV clearance not previously described was perceived as an important source of pathogenesis in resistant mice.

Blood pressure variability and arterial elasticity in hyperlipidaemic subjects.

INTRODUCTION: It is debatable whether the assessment of low density lipoprotein or total cholesterol (TC) alone is sufficient to identify an individual's risk of having myocardial infarction. In the Framingham study, the risk of coronary artery disease was better indicated by an increase in the TC to high density lipoprotein cholesterol (TC: HDL) ratio. The aim of this study is to determine the relationship between blood pressure variability (BPV) and arterial compliances in hyperlipidaemics, which was defined as TC:HDL of more than 5.0 as compared to normolipidaemics. METHODS: 22 subjects with hyperlipidaemia were age-, gender- and weight-matched with normolipidaemic controls. 24-hour ambulatory blood pressure monitoring was recorded and arterial compliances were measured. RESULTS: There were significantly higher 24-hour systolic (SBP) (19.9 +/- 6.1 mmHg vs. 16.1 +/- 4.4 mmHg, p-value is less than 0.01), diastolic (16.6 +/- 4.7 mmHg vs. 13.9 +/- 4.8 mmHg, p-value is less than 0.05) and mean arterial (16.3 +/- 4.9 mmHg vs. 13.3 +/- 4.7 mmHg, p-value is less than 0.05) BPVs in the hyperlipidaemic group as compared to the normolipidaemic group. There were no significant differences in large and small arterial compliances between groups. There was a significant inverse relationship between SBP and large arterial compliance (r-value equals to -0.46, p-value is less than 0.05). There was no correlation between BPV and arterial compliances. CONCLUSION: The BPV was higher in hyperlipidaemic subjects as compared to normolipidaemic subjects. Large arterial compliance was negatively correlated with SBP in hyperlipidaemic subjects.