Mar Kyaw Win

Accuracy and User-Acceptability of HIV Self-Testing Using an Oral Fluid-Based HIV Rapid Test

Background The United States FDA approved an over-the-counter HIV self-test, to facilitate increased HIV testing and earlier linkage to care. We assessed the accuracy of self-testing by untrained participants compared to healthcare worker (HCW) testing, participants’ ability to interpret sample results and user-acceptability of self-tests in Singapore. Methodology/Principal Findings A cross-sectional study, involving 200 known HIV-positive patients and 794 unknown HIV status at-risk participants was conducted. Participants (all without prior self-test experience) performed self-testing guided solely by visual instructions, followed by HCW testing, both using the OraQuick ADVANCE Rapid HIV 1/2 Antibody Test, with both results interpreted by the HCW. To assess ability to interpret results, participants were provided 3 sample results (positive, negative, and invalid) to interpret. Of 192 participants who tested positive on HCW testing, self-testing was positive in 186 (96.9%), negative in 5 (2.6%), and invalid in 1 (0.5%). Of 794 participants who tested negative on HCW testing, self-testing was negative in 791 (99.6%), positive in 1 (0.1%), and invalid in 2 (0.3%). Excluding invalid tests, self-testing had sensitivity of 97.4% (95% CI 95.1% to 99.7%) and specificity of 99.9% (95% CI: 99.6% to 100%). When interpreting results, 96%, 93.1% and 95.2% correctly read the positive, negative and invalid respectively. There were no significant demographic predictors for false negative self-testing or wrongly interpreting positive or invalid sample results as negative. Eighty-seven percent would purchase the kit over-the-counter; 89% preferred to take HIV tests in private. 72.5% and 74.9% felt the need for pre- and post-test counseling respectively. Only 28% would pay at least USD15 for the test. Conclusions/Significance Self-testing was associated with high specificity, and a small but significant number of false negatives. Incorrectly identifying model results as invalid was a major reason for incorrect result interpretation. Survey responses were supportive of making self-testing available.

Epidemiology of travel-associated pandemic (H1N1) 2009 infection in 116 patients, Singapore.

During the containment phase, regions of exposure for imported infections changed rapidly.

Loss of TLR3 aggravates CHIKV replication and pathology due to an altered virus‐specific neutralizing antibody response

RNA‐sensing toll‐like receptors (TLRs) mediate innate immunity and regulate anti‐viral response. We show here that TLR3 regulates host immunity and the loss of TLR3 aggravates pathology in Chikungunya virus (CHIKV) infection. Susceptibility to CHIKV infection is markedly increased in human and mouse fibroblasts with defective TLR3 signaling. Up to 100‐fold increase in CHIKV load was observed in Tlr3−/− mice, alongside increased virus dissemination and pro‐inflammatory myeloid cells infiltration. Infection in bone marrow chimeric mice showed that TLR3‐expressing hematopoietic cells are required for effective CHIKV clearance. CHIKV‐specific antibodies from Tlr3−/− mice exhibited significantly lower in vitro neutralization capacity, due to altered virus‐neutralizing epitope specificity. Finally, SNP genotyping analysis of CHIKF patients on TLR3 identified SNP rs6552950 to be associated with disease severity and CHIKV‐specific neutralizing antibody response. These results demonstrate a key role for TLR3‐mediated antibody response to CHIKV infection, virus replication and pathology, providing a basis for future development of immunotherapeutics in vaccine development.

Surgical Masks for Protection of Health Care Personnel against Pandemic Novel Swine-Origin Influenza A (H1N1)-2009: Results from an Observational Study

There is ongoing debate about the efficacy of surgical masks versus N95 respirators for protection against pandemic novel swine-origin influenza A (H1N1)-2009. Our hospital, which is designated to manage outbreaks of emerging infection, has robust surveillance systems to detect infection in staff. The incidence of pandemic H1N1-2009 remained low in staff with use of surgical masks.

Surveillance for Clostridium difficile Infection: ICD-9 Coding Has Poor Sensitivity Compared to Laboratory Diagnosis in Hospital Patients, Singapore

Introduction Clostridium difficile infection (CDI) is an increasingly recognized nosocomial infection in Singapore. Surveillance methods include laboratory reporting of Clostridium difficile toxin assays (CDTA) or use of International Classification of Diseases, 9th Revision (ICD-9) discharge code 008.45. Previous US studies showed good correlation between CDTA and ICD-9 codes. However, the use of ICD-9 codes for CDI surveillance has not been validated in other healthcare settings. Methods We compared CDI rates based on CDTA to ICD-9 codes for all discharges in 2007 from our hospital to determine sensitivity and specificity of ICD-9 codes. Demographic and hospitalization data were analyzed to determine predictors for missing ICD-9 codes. Results During 2007, there were 56,352 discharges. Of these, 268 tested CDTA-positive but only 133 were assigned the CDI ICD-9 code. A total of 141 discharges had the ICD-9 code; 8 were CDTA-negative, the rest were CDTA-positive. Community-acquired CDI accounted for only 3.2% of cases. The sensitivity and specificity of ICD-9 codes compared to CDTA were 49.6% and 100% respectively. Concordance between CDTA and ICD-9 codes was 0.649 (p<.001). Comparing concordant patients (CDTA+/ICD9+) to discordant patients (CDTA+/ICD9−), concordant patients were more likely to be over 50 years of age (OR 3.49, 95% CI 1.66–7.34, p = .001) and have shorter time from admission to testing (OR 0.98, 95% CI 0.97–0.99, p = .009). Discussion Unlike previous studies in the US, ICD-9 codes substantially underestimate CDI in Singapore compared to microbiological data. Older patients with shorter time to testing were less likely to have missing ICD-9 codes.

Clinical and microbiological characteristics of cryptococcosis in Singapore: predominance of Cryptococcus neoformans compared with Cryptococcus gattii

OBJECTIVES To describe the clinical features, treatments, outcomes, and subtype prevalence of cryptococcosis in Singapore. METHODS All patients with laboratory confirmed cryptococcal infections admitted from 1999 to 2007 to a teaching hospital in Singapore were reviewed retrospectively. Identification and molecular types of Cryptococcus neoformans variants and Cryptococcus gattii were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serotypes were inferred with a multiplex PCR method. RESULTS Of 62 patients with cryptococcosis, C. neoformans var. grubii was the predominant subtype (in 95%), affecting mainly immunocompromised hosts (91%) with HIV infection (80%). Patients with HIV were younger (median age 36.5 vs. 49.5 years, p=0.006) and less likely to present with an altered mental status (14% vs. 50%, p=0.013). In contrast, delayed treatment (median 7 days vs. 2 days, p=0.03), pulmonary involvement (58% vs. 14%, p=0.03), and initial treatment with fluconazole (25% vs. 2%, p=0.02) were more common in HIV-negative patients. C. gattii was uncommon, affecting only three patients, all of whom were immunocompetent and had disseminated disease with pulmonary and neurological involvement. All C. gattii were RFLP type VG II, serotype B and all C. neoformans var. grubii were RFLP type VN I, serotype A, except for one that was RFLP type VN II. CONCLUSION C. neoformans var. grubii, subtype VN I, was the predominant subtype in Singapore, infecting younger, mainly immunocompromised hosts with HIV. C. gattii was uncommon, causing pulmonary manifestations in older, immunocompetent patients and were RFLP type VG II.

Influenza disease burden in adults by subtypes following the initial epidemic of pandemic H1N1 in Singapore

Please cite this paper as: Win et al. (2011) Influenza disease burden in adults by subtypes following the initial epidemic of pandemic H1N1 in Singapore. Influenza and Other Respiratory Viruses 5(6), e563–e567.

Length of stay an important mediator of hospital-acquired methicillin-resistant Staphylococcus aureus.

Hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is becoming increasingly established in Asian hospitals. The primary aim of this study was to decompose the risk factors for HA-MRSA based on conceptual clinical pathways. The secondary aim was to show the amount of effect attributable to antibiotic exposure and total length of stay before outcome (LBO) so that institutions can manage at-risk patients accordingly. A case-control study consisting of 1200 inpatients was conducted in a large tertiary hospital in Singapore between January and December 2006. Results from the generalized structural equation model (GSEM) show that LBO [adjusted odds ratio (aOR) 14·9, 95% confidence interval (CI) 8·7-25·5], prior hospitalization (aOR 6·2, 95% CI 3·3-11·5), and cumulative antibiotic exposure (aOR 3·5, 95% CI 2·3-5·3), directly affected HA-MRSA acquisition. LBO accounted for the majority of the effects due to age (100%), immunosuppression (67%), and surgery (96%), and to a lesser extent for male gender (22%). Our model enabled us to account and quantify effects of intermediaries. LBO was found to be an important mediator of age, immunosuppression and surgery on MRSA infection. Traditional regression approaches will not only give different conclusions but also underestimate the effects. Hospitals should minimize the hospital stay when possible to reduce the risk of MRSA.

Risk assessment and laboratory investigation of respiratory illness in travellers returning to Singapore 2012–2015: experience from the MERS-CoV Surveillance Programme

SUMMARY Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV), Singapore has enhanced its national surveillance system to detect the potential importation of this novel pathogen. Using the guidelines from the Singapore Ministry of Health, a suspect case was defined as a person with clinical signs and symptoms suggestive of pneumonia or severe respiratory infection with breathlessness, and with an epidemiological link to countries where MERS-CoV cases had been reported within the preceding 14 days. This report describes a retrospective review of 851 suspected MERS-CoV cases assessed at the adult tertiary-care hospital in Singapore between September 2012 and December 2015. In total, 262 patients (31%) were hospitalized. All had MERS-CoV infection ruled out by RT–PCR or clinical assessment. Two hundred and thirty (88%) of the hospitalized patients were also investigated for influenza virus by RT–PCR. Of these, 62 (27%) tested positive for seasonal influenza. None of the patients with positive influenza results had been vaccinated in the year prior to hospital admission. Ninety-three (36%) out of the 262 hospitalized patients had clinical and/or radiological evidence of pneumonia. This study demonstrates the potential benefits of pre-travel vaccination against influenza and pneumococcal disease.

Vancomycin-resistant enterococci with reduced daptomycin susceptibility in Singapore: prevalence and associated factors.

Prevalence of vancomycin-resistant enterococci (VRE) and use of daptomycin are increasing in Asia. To determine the prevalence of daptomycin non-susceptible enterococci (DNSE) and understand factors associated with reduced daptomycin susceptibility in VRE, we conducted a case-control study in a 1600-bed adult tertiary hospital in Singapore. All VRE isolates from inpatients in 2012 were tested for daptomycin susceptibility. Patients with VRE isolates of daptomycin minimum inhibitory concentration (MIC) ⩾3 µg/ml were classified as daptomycin-reduced susceptible VRE (DRS-VRE) and those with daptomycin MIC 4 µg/ml (DNSE). About half (135, 55%) had reduced susceptibility to daptomycin (MIC 3-4 µg/ml). None in the DS-VRE group had prior exposure to daptomycin. After adjusting for age, gender, comorbidity, hospitalization duration, surgical history, indwelling device use, and duration of antibiotic exposure in the prior 3 months, >1 movement between wards [odds ratio (OR) 0·35, 95% confidence interval (CI) 0·16-0·74, P = 0·006] and minocycline resistance (OR 0·45, 95% CI 0·25-0·84, P = 0·011) were independently associated with DRS-VRE. Our study suggests that daptomycin exposure, >1 movement between wards, and resistance to minocycline, were associated with reduced daptomycin susceptibility in VRE.