Assessing the impact of COVID-19 on epidemiological changes of severe pediatric respiratory syncytial virus infections in Malaysia.

Introduction: Respiratory syncytial virus (RSV) is one of the leading causes of hospitalization and mortality among children with respiratory tract infections. The non-pharmaceutical preventive measures against severe acute respiratory syndrome coronavirus (COVID-19) may have reduced the transmission of RSV, altering its tropical epidemiological seasonality. Thus, this study represents the first attempt to evaluate changes in RSV epidemiology in the context of COVID-19 pandemic in Malaysia. Methods: Conducted at a tertiary hospital in Kuala Lumpur, Malaysia, this retrospective study analyzed collated data of children aged <12 years who were admitted for severe respiratory infections from 2017 to 2022. Time series models were used to predict the differences between actual and forecasted RSV cases, while logistic regression assessed the statistical association between RSV and COVID-19. Results: Among the 4,084 children analyzed, we reported a significant inverse relationship between RSV and COVID-19 infections during the pandemic (2020-2021) (p < 0.05). In 2020, the RSV positivity rate sharply declined to 8.3 and 5.9%, respectively, in the two prominent seasons. Time series analysis showed a tremendous decrease in cases compared to the expected values, with reductions of 98.3% in the first season and 95.7% in the second season. However, following the lifting of the restriction order in 2022, RSV infections rose sharply with a positivity rate of 36.3%, higher than pre-COVID-19 pandemic levels. Conclusion: This study provides evidence of increasing RSV cases post-COVID-19 pandemic, due to immunity debt. Hence, the healthcare system must be prepared to address future RSV outbreaks with the appropriate implementation of prophylaxis and public health measures.

Decoding the Clinical Significance of Immunoglobulin G4 in Rheumatoid Arthritis.

Immunoglobulin (Ig) G4 accounts for 4-6% of the total IgG in a healthy human. Several evidence-based studies have suggested that the level of IgG4 is significantly elevated in autoimmune diseases, including rheumatoid arthritis (RA). The clinical significance of IgG4 in RA with regard to disease activity, severity, and treatment response remains elusive. We consecutively recruited 174 patients with RA from our rheumatology clinic. All subjects were assessed for their disease activity based on DAS28, radiographic joint damage based on the Modified Sharp Score (MSS), the functional capacity based on the Health Assessment Questionnaire -Disability Index (HAQ-DI), and treatment responsiveness using the European League Against Rheumatism (EULAR) response criteria. The serum IgG4 of the recruited subjects was measured via the ELISA test. The mean serum IgG4 level was 60.23 ± 30.08 mg/dL. We found that serum IgG4 had significant positive correlations with disease activity (r = 0.406; p < 0.001), ESR (r = 0.155; p = 0.041), CRP (r = 0.269; p < 0.001), joint damage (r = 0.195; p = 0.012) and functional disability (r = 0.909; p < 0.001). Subjects with elevated IgG4 (IgG4 > 86 mg/dL) had significantly higher ESR, CRP, HAQ-DI, and DAS 28 and a poorer treatment response compared to the group with non-elevated IgG4. After multivariate analysis, only HAQ-DI (OR = 4.229, 95% CI 1.302, 15.751, p = 0.018) and DAS28 (OR = 3.743, 95% CI 1.062, 13.193, p = 0.040) remained significantly associated with elevated serum IgG4. The preliminary findings of this study could suggest serum IgG4 to be a potential biomarker of disease activity and functional disability in RA.

Determining the Relationship of Meteorological Factors and Severe Pediatric Respiratory Syncytial Virus (RSV) Infection in Central Peninsular Malaysia.

Respiratory syncytial virus (RSV) is the most common pathogen causing viral respiratory tract infections among younger children worldwide. The influence of meteorological factors on RSV seasonal activity is well-established for temperate countries; however, in subtropical countries such as Malaysia, relatively stable temperate climates do not clearly support this trend, and the available data are contradictory. Better understanding of meteorological factors and seasonality of RSV will allow effective strategic health management relating to RSV infection, particularly immunoprophylaxis of high-risk infants with palivizumab. Retrospectively, from 2017 to 2021, we examined the association between various meteorological factors (rainfall, rainy days, temperature, and relative humidity) and the incidence of RSV in children aged less than 12 years in Kuala Lumpur, Malaysia. RSV activity peaked in two periods (July to August and October to December), which was significantly correlated with the lowest rainfall (p < 0.007) and number of rainy days (p < 0.005). RSV prevalence was also positively associated with temperature (p < 0.006) and inversely associated with relative humidity (p < 0.006). Based on our findings, we recommend that immunoprophylaxis with palivizumab be administered in children aged less than 2 years where transmission of RSV is postulated to be the highest after the end of two monsoon seasons.

Isolation of an obscure fungus, Parengyodontium album, from the blood of a severely neutropenic patient: The first reported case from Malaysia.

Parengyodontium album is a very rarely encountered opportunistic fungal pathogen. A severely neutropenic 11-year-old boy with acute T-cell lymphoblastic leukemia/lymphoma was febrile and lethargic during his admission for elective chemotherapy. No cutaneous lesion or obvious source of infection was noted, and clinical examination was otherwise unremarkable. A blood specimen was sent for culture and fungal elements were visualized. Amphotericin B was administered empirically while awaiting fungal identification. Morphologically, a hyaline mould with thin septate hyphae plus smooth-walled conidiophores and conidiogenous cells arranged in whorls of up to four was cultured. Internal transcribed spacer region sequencing identified the fungus conclusively as P. album. Repeat blood culture was also positive for the same fungus. Following a two-week course of amphotericin B, fungemia clearance was attained.

Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review.

Immunoglobulin (Ig)G4 is a unique protein molecule and its role in autoimmune diseases remains elusive and controversial. Accumulating evidence suggests a pathogenic role of IgG4 in rheumatoid arthritis (RA). Rheumatoid factors (RF) in RA can recognize the Fc domains of IgG4 to form RF-IgG4 immune complexes that may activate the complement system leading to synovial injury. The aim of this article was to systematically review the literature from the past 2 decades to determine the frequency of elevated IgG4 and its clinical significance in RA. We comprehensively searched the Pubmed, Scopus, and Web of Science databases with the following terms: "IgG4", "rheumatoid arthritis", and "immunoglobulin G4", and scrutinized all of the relevant publications. Based on the selection criteria, 12 studies were incorporated, which involved a total of 1715 RA patients. Out of 328 subjects from three studies, the pooled frequency of elevated non-specific IgG4 was 35.98%. There was a significant positive correlation between the IgG4 levels and the RA disease activity based on DAS-28 measurements (r = 0.245-0.253) and inflammatory markers, i.e., erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels (r = 0.262-0.389). Longitudinal studies that measured the serial levels of IgG4 consistently showed a decline in the concentrations (up to 48% less than baseline) with disease modifying anti-rheumatic drug (DMARD) treatment. Current evidence suggests that serum IgG4 levels are significantly elevated in RA compared to the general population. This review indicates that IgG4 is a promising biomarker of disease activity and tends to decline in response to DMARD therapies. Biologic therapies have revolutionized the therapeutic armamentarium of RA in the recent decade, and IgG4 appears to be a potential treatment target.

Acute Infectious Gastroenteritis: The Causative Agents, Omics-Based Detection of Antigens and Novel Biomarkers.

Acute infectious gastroenteritis (AGE) is among the leading causes of mortality in children less than 5 years of age worldwide. There are many causative agents that lead to this infection, with rotavirus being the commonest pathogen in the past decade. However, this trend is now being progressively replaced by another agent, which is the norovirus. Apart from the viruses, bacteria such as Salmonella and Escherichia coli and parasites such as Entamoeba histolytica also contribute to AGE. These agents can be recognised by their respective biological markers, which are mainly the specific antigens or genes to determine the causative pathogen. In conjunction to that, omics technologies are currently providing crucial insights into the diagnosis of acute infectious gastroenteritis at the molecular level. Recent advancement in omics technologies could be an important tool to further elucidate the potential causative agents for AGE. This review will explore the current available biomarkers and antigens available for the diagnosis and management of the different causative agents of AGE. Despite the high-priced multi-omics approaches, the idea for utilization of these technologies is to allow more robust discovery of novel antigens and biomarkers related to management AGE, which eventually can be developed using easier and cheaper detection methods for future clinical setting. Thus, prediction of prognosis, virulence and drug susceptibility for active infections can be obtained. Case management, risk prediction for hospital-acquired infections, outbreak detection, and antimicrobial accountability are aimed for further improvement by integrating these capabilities into a new clinical workflow.

A Spuriously Negative Cryptococcal Antigen Assay Result in Disseminated Cryptococcosis: the Deception of the Postzone Phenomenon.

Cryptococcus is a basidiomycetous yeast responsible for considerable HIV-related morbidity and mortality. A cachectic 26-year-old HIV-positive man with a CD4 count of 103 cells/µl presented with fever, breathlessness, and bilateral lower limb weakness. A brain computed tomography scan could not elucidate the neurological deficit. His blood was sent for culture and serum cryptococcal antigen detection, with the latter testing as negative. By the fourth day of admission, the patient's condition had deteriorated drastically. A lumbar puncture was performed, and like his serum sample, the cerebrospinal fluid also tested negative for cryptococcal antigens. By this time, Cryptococcus neoformans was isolated from the admission blood culture. The laboratory diluted both the serum and cerebrospinal fluid specimens to retest for cryptococcal antigens, and finally, an antigen titer of ≥1:2560 was recorded.

Clinical and demographic pattern of chronic granulomatous disease (CGD) from a multicenter perspective: Malaysia's experience over 26 years.

BACKGROUND: A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia. METHODS: Data from the Malaysia Primary Immunodeficiency Network (MyPIN) with cases of CGD diagnosed from 1991 until 2016 were collated and analysed. RESULTS: Twenty patients were diagnosed as CGD. Males (N = 13, 65%) outnumber females (N = 7, 35%). CGD is commonest amongst the Malays (65%) followed by the Chinese (15.0%), Indians (10.0%) and natives of Borneo (10.0%), reflecting the ethnic composition of the country. The mean age of diagnosis was 3.7 years. There was a positive family history in 40% of the cases. Abscess was the main presenting feature in 16 patients (80%) with one involving the brain. Pneumonia occurred in 10 (50%) and one with complicated bronchiectasis. Catalase-positive bacteria were the most commonly isolated pathogen with Chromobacterium violaceum predominating (N = 5, 25%) with consequent high mortality (N = 4, 80%). All CGD patients with C. violaceum infection displayed CD4 + (T helper cells) lymphopenia. CONCLUSION: This study has shown CGD occurs in the major ethnic groups of Malaysia. To the best of our knowledge, this is the first and the largest series of chronic granulomatous disease in South East Asia which may be reflective of similar clinical pattern in the region. C. violaceum infection is associated with a higher mortality in CGD patients in Malaysia. All the CGD patients with C. violaceum infection in this patient series displayed CD4 + (T helper) lymphopenia. We recorded rare clinical manifestation of CGD viz. brain abscess and bronchiectasis.

Reduction in Urinary Chemokine (C-C Motif) Ligand 2 (CCL2) After Surgery-Induced Weight Loss.

Kidney dysfunction, a deleterious effect of obesity, is now recognized as a relevant health risk. Chemokine (C-C Motif) Ligand 2 (CCL2) is one of the critical chemokines that play a vital role in the development of obesity-related metabolic disease. We aim to measure the changes in urinary CCL2 in our patients before and after their bariatric procedure and examine the correlation between CCL2 and renal function. A prospective cohort study was conducted at our teaching university hospital. Ethics approval was obtained from our institutional review board. Patients with a BMI of ≥37.5 kg/m2 with no history of renal disease were included. They underwent single anastomosis gastric bypass (SAGB), Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), all performed via laparoscopic approach. Venous blood and urine samples were obtained preoperatively and six months after surgery. A total of 58 patients were recruited, with SG being performed in 74.1% of patients. At six-months follow-up, median (IQR) body weight reduced from 101.35 kgs (20.25) to 76.95 kg (24.62) p < 0.001. The mean (SD) estimated glomerular filtration rate (eGFR) improved from 96.26 ± 14.97 to 108.06 ± 15.00 mL/min/1.73 m2, p < 0.001. The median (IQR) urinary CCL2 levels reduced from 15.2 pg/ml (10.77) to 4.30 pg/ml (4.27) p < 0·001. There is a significant correlation between the reduction of BMI and the reduction of urinary CCL2 (r = -0.220, p = 0.048). We also found a significant correlation between the reduction of urinary CCL2 with the reduction of urine ACR (r = -0.240, p = 0.035). Urinary CCL2 is a promising biomarker that can be used to assess improvement in renal function in obese patients after bariatric surgery.

Syphilis in pregnancy.

Syphilis in pregnancy remains an important medical condition due to its consequences. We present two cases of young pregnant women who were diagnosed syphilis during their antenatal visit. The first case was a 29-year-old Malay lady diagnosed with syphilis during the first trimester of pregnancy, while the second case was a 21-year-old Chinese lady diagnosed with syphilis during the third trimester of pregnancy. The diagnosis and management of the syphilis in pregnancy are discussed.

Prevalence of albicans and non-albicans candiduria in a Malaysian medical centre.

OBJECTIVE: To determine the proportion of albicans and non-albicans candiduria in a hospital setting and to ascertain if fluconazole is still suitable as empirical antifungal therapy based on antifungal susceptibility patterns of Candida species. METHODS: The cross-sectional study was conducted between December 2010 and December 2011 at UKM Medical Centre, Kuala Lumpur, Malaysia and comprised 64 urine samples from patients who were either suspected or confirmed to have urinary tract infections. Yeasts were speciated using ID 32 C and subjected to antifungal susceptibility testing using Sensititre® YeastOne YO8. RESULTS: Candida albicans accounted for 38(59.4%) of the isolates, Candida tropicalis 18(28.1%), Candida glabrata 6(9.4%) and Candida parapsilosis 2(3.1%). Overall, the isolates were susceptible to both amphotericin B (MIC90 1 µg/ml) and to 5-flucytosine (MIC90 0.25 µg/ml), but susceptible-dose dependent towards fluconazole (MIC90 16 µg/ml). Individually, Candida albicans was susceptible to fluconazole (MIC90 2 µg/ml), amphotericin B (MIC90 0.5 µg/ml) and 5-flucytosine (MIC90 0.25 µg/ml). Candida tropicalis was also susceptible to fluconazole (MIC90 4 µg/ml), amphotericin B (MIC90 1 µg/ml) and 5-flucytosine (MIC90 0.125 µg/ml). Candida glabrata was resistant to fluconazole (MIC90 64 µg/ml), but susceptible to amphotericin B (MIC90 1 µg/ml) and 5-flucytosine (MIC90 0.125 µg/ml). Lastly, Candida parapsilosis was resistant to fluconazole (MIC90 256 µg/ml), but susceptible to amphotericin B (MIC90 0.5 µg/ml) and 5-flucytosine (MIC90 0.5 µg/ml). CONCLUSION: The commonest yeast associated with candiduria at the study site was Candida albicans, and fluconazole can still be used for empirical therapy of candiduria.

Pseudomonas aeruginosa bacteremia secondary to acute right leg cellulitis: case of community-acquired infection.

Pseudomonas aeruginosa is a gram-negative bacillus that causes wide spectrum clinical infections. However, it is most frequently associated with hospital-acquired infection. In this case a 58-year-old male with underlying hypertension and dyslipidaemia was admitted for acute right leg cellulitis. Pseudomonas aeruginosa was identified from the case, though it was not a usual suspected organism. It might be due to community-acquired infection.