Raymond T.P. Lin

2009 Influenza A(H1N1) Seroconversion Rates and Risk Factors Among Distinct Adult Cohorts in Singapore

CONTEXT Singapore experienced a single epidemic wave of 2009 influenza A(H1N1) with epidemic activity starting in late June 2009 and peaking in early August before subsiding within a month. OBJECTIVE To compare the risk and factors associated with H1N1 seroconversion in different adult cohorts. DESIGN, SETTING, AND PARTICIPANTS A study with serial serological samples from 4 distinct cohorts: general population (n = 838), military personnel (n = 1213), staff from an acute care hospital (n = 558), and staff as well as residents from long-term care facilities (n = 300) from June 22, 2009, to October 15, 2009. Hemagglutination inhibition results of serum samples taken before, during, and after the epidemic and data from symptom questionnaires are presented. MAIN OUTCOME MEASURES A 4-fold or greater increase in titer between any of the 3 serological samples was defined as evidence of H1N1 seroconversion. RESULTS Baseline titers of 40 or more were observed in 22 members (2.6%; 95% confidence interval [CI], 1.7%-3.9%) of the community, 114 military personnel (9.4%; 95% CI, 7.9%-11.2%), 37 hospital staff (6.6%; 95% CI, 4.8%-9.0%), and 20 participants from long-term care facilities (6.7%; 95% CI, 4.4%-10.1%). In participants with 1 or more follow-up serum samples, 312 military personnel (29.4%; 95% CI, 26.8%-32.2%) seroconverted compared with 98 community members (13.5%; 95% CI, 11.2%-16.2%), 35 hospital staff (6.5%; 95% CI, 4.7%-8.9%), and only 3 long-term care participants (1.2%; 95% CI, 0.4%-3.5%). Increased frequency of seroconversion was observed for community participants from households in which 1 other member seroconverted (adjusted odds ratio [OR], 3.32; 95% CI, 1.50-7.33), whereas older age was associated with reduced odds of seroconversion (adjusted OR, 0.77 per 10 years; 95% CI, 0.64-0.93). Higher baseline titers were associated with decreased frequency of seroconversion in community (adjusted OR for every doubling of baseline titer, 0.48; 95% CI, 0.27-0.85), military (adjusted OR, 0.71; 95% CI, 0.61-0.81), and hospital staff cohorts (adjusted OR, 0.50; 95% CI, 0.26-0.93). CONCLUSION Following the June-September 2009 wave of 2009 influenza A(H1N1), 13% of the community participants seroconverted, and most of the adult population likely remained susceptible.

Entomologic and Virologic Investigation of Chikungunya, Singapore

Data from longitudinal analyses can be useful in the design and implementation of control strategies.

Chikungunya: a bending reality.

Chikungunya fever is an acute illness caused by the arbovirus Chikungunya virus. The virus is transmitted primarily in a sylvatic cycle involving the Aedes mosquitoes. Since 2005, a Chikungunya fever outbreak of unprecedented magnitude occurred on several Indian Ocean islands. Since then, the disease has spread to many parts of the world due to imported cases among travellers returning from epidemic areas. Chikungunya virus causes a wide spectrum of illness including fever, a characteristic rash, disabling joint symptoms which can sometimes become severe that lasts months. This review summarises on this history of Chikungunya fever, host specificity, the characteristics of Chikungunya virus, clinical features of disease and current control measures. It focuses on how the re-emergence of an old changed the outlook of managing arboviral diseases in the present social and public health context.

Antimicrobial drug resistance in Singapore hospitals.

A new national antimicrobial resistance surveillance program in Singapore public hospitals that uses WHONET detected high levels of methicillin resistance among Staphylococcus aureus (35.3%), carbapenem resistance among Acinetobacter spp. (49.6%), and third-generation cephalosporin resistance among Klebsiella pneumoniae (35.9%) hospital isolates in 2006. Antimicrobial drug resistance is a major problem in Singapore.

Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks.

BACKGROUND From June 22 through June 25, 2009, four outbreaks of infection with the pandemic influenza A (H1N1) virus occurred in Singapore military camps. We report the efficacy of ring chemoprophylaxis (geographically targeted containment by means of prophylaxis) with oseltamivir to control outbreaks of 2009 H1N1 influenza in semiclosed environments. METHODS All personnel with suspected infection were tested and clinically isolated if infection was confirmed. In addition, we administered postexposure ring chemoprophylaxis with oseltamivir and segregated the affected military units to contain the spread of the virus. All personnel were screened three times weekly both for virologic infection, by means of nasopharyngeal swabs and reverse-transcriptase-polymerase-chain-reaction assay with sequencing, and for clinical symptoms, by means of questionnaires. RESULTS A total of 1175 personnel were at risk across the four sites, with 1100 receiving oseltamivir prophylaxis. A total of 75 personnel (6.4%) were infected before the intervention, and 7 (0.6%) after the intervention. There was a significant reduction in the overall reproductive number (the number of new cases attributable to the index case), from 1.91 (95% credible interval, 1.50 to 2.36) before the intervention to 0.11 (95% credible interval, 0.05 to 0.20) after the intervention. Three of the four outbreaks showed a significant reduction in the rate of infection after the intervention. Molecular analysis revealed that all four outbreaks were derived from the New York lineage of the 2009 H1N1 virus and that cases within each outbreak were due to transmission rather than unrelated episodes of infection. Of the 816 personnel treated with oseltamivir who were surveyed, 63 (7.7%) reported mild, nonrespiratory side effects of the drug, with no severe adverse events. CONCLUSIONS Oseltamivir ring chemoprophylaxis, together with prompt identification and isolation of infected personnel, was effective in reducing the impact of outbreaks of 2009 H1N1 influenza in semiclosed settings.

Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.

Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop “groove” as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.

Establishment of ST30 as the Predominant Clonal Type among Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates in Singapore

ABSTRACT The number of infections attributable to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Singapore is progressively increasing. Most cases in the past 2 years were caused by Panton-Valentine leukocidin-positive isolates belonging to sequence type 30, according to multilocus sequence typing. This has clearly become the predominant sequence type among CA-MRSA isolates in Singapore.

Chikungunya Virus Envelope-Specific Human Monoclonal Antibodies with Broad Neutralization Potency

Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics in Africa and Asia. Infection by CHIKV is often characterized by long-lasting, incapacitating arthritis, and some fatal cases have been described among elderly and newborns. Currently, there is no available vaccine or specific treatment against CHIKV. Blood B cells from a donor with history of CHIKV infection were activated, immortalized, amplified, and cloned. Two human mAbs against CHIKV, 5F10 and 8B10, were identified, sequenced, and expressed in recombinant form for characterization. In a plaque reduction neutralization test, 5F10 and 8B10 show mean IC50 of 72 and 46 ng/ml, respectively. Moreover, both mAbs lead to a strong decrease in extracellular spreading of infectious viral particles from infected to uninfected cells. Importantly, the mAbs neutralize different CHIKV isolates from Singapore, Africa, and Indonesia, as well as O’nyong-nyong virus, but do not recognize other alphaviruses tested. Both mAbs are specific for the CHIKV envelope: 5F10 binds to the E2 glycoprotein ectodomain and 8B10 to E1 and/or E2. In conclusion, these two unique human mAbs strongly, broadly, and specifically neutralize CHIKV infection in vitro and might become possible therapeutic tools against CHIKV infection, especially in individuals at risk for severe disease. Importantly, these mAbs will also represent precious tools for future studies on host–pathogen interactions and the rational design of vaccines against CHIKV.

Staphylococcus lugdunensis Carrying the mecA Gene Causes Catheter-Associated Bloodstream Infection in Premature Neonate

ABSTRACT A premature neonate had a catheter-associated bloodstream infection due to Staphylococcus lugdunensis. The MIC of oxacillin for the strain was >256 μg/ml, and the mecA gene of S. lugdunensis was detected by PCR. The infection was resolved after removal of the line and treatment with vancomycin for 2 weeks.

Molecular characterization of newly emerged blaKPC-2-producing Klebsiella pneumoniae in Singapore

ABSTRACT In Asia, bla KPC detection has been limited to East Asia and not yet seen in Southeast Asia. We report four bla KPC-2-containing Klebsiella pneumoniae isolates from two different hospitals in Singapore. All isolates belonged to strain type 11 (ST11) and were indistinguishable by pulsed-field gel electrophoresis (PFGE). bla KPC-2 was located on nonconjugative plasmids and flanked by mobile genetic structures composed of a partial Tn4401 transposon and a Tn3-based transposon which previously have been described only in Chinese isolates.