Jin Phang Loh

Publications of Jin Phang Loh

• Differing clinical characteristics between influenza strains among young healthy adults in the tropics.

  Authors: Jonathan Yap, Chi Hsien Tan, Alex R Cook, Jin Phang Loh, Paul A Tambyah, Boon Huan Tan, Vernon J Lee

  BMC infectious diseases. 01/2012; 12(1):12.

  ABSTRACT: Influenza infections may result in different clinical presentations. This study aims to determine the clinical differences between circulating influenza strains in a young healthy adultABSTRACT: Influenza infections may result in different clinical presentations. This study aims to determine the clinical differences between circulating influenza strains in a young healthy adult population in the tropics. A febrile respiratory illness (FRI) (fever ≥ 37.5°C with cough and/or sore throat) surveillance program was started in 4 large military camps in Singapore on May 2009. Personnel with FRI who visited the camp clinics from 11 May 2009 to 25 June 2010 were recruited. Nasal washes and interviewer-administered questionnaires on demographic information and clinical features were obtained from consenting participants. All personnel who tested positive for influenza were included in the study. Overall symptom load was quantified by counting the symptoms or signs, and differences between strains evaluated using linear models. There were 434 (52.9%) pandemic H1N1-2009, 58 (7.1%) seasonal H3N2, 269 (32.8%) influenza B, and 10 (1.2%) seasonal H1N1 cases. Few seasonal influenza A (H1N1) infections were detected and were therefore excluded from analyses, together with undetermined influenza subtypes (44 (1.5%)), or more than 1 co-infecting subtype (6 (0.2%)). Pandemic H1N1-2009 cases had significantly fewer symptoms or signs (mean 7.2, 95%CI 6.9-7.4, difference 1.6, 95%CI 1.2-2.0, p < 0.001) than the other two subtypes (mean 8.7, 95%CI 8.5-9.0). There were no statistical differences between H3N2 and influenza B (p = 0.58). Those with nasal congestion, rash, eye symptoms, injected pharynx or fever were more likely to have H3N2; and those with sore throat, fever, injected pharynx or rhinorrhoea were more likely to have influenza B than H1N1-2009. Influenza cases have different clinical presentations in the young adult population. Pandemic H1N1 influenza cases had fewer and milder clinical symptoms than seasonal influenza. As we only included febrile cases and had no information on the proportion of afebrile infections, further research is needed to confirm whether the relatively milder presentation of pandemic versus seasonal influenza infections applies to all infections or only febrile illnesses.

• Investigation of causes of oseltamivir chemoprophylaxis failures during influenza A (H1N1-2009) outbreaks.

  Authors: Vernon J Lee, Jonathan Yap, Sebastian Maurer-Stroh, Raphael T C Lee, Frank Eisenhaber, Joshua K Tay, Pei Jun Ting, Jin Phang Loh, Christopher W Wong, Boon Huan Tan, Evelyn S C Koay, Paul M Kelly, Martin L Hibberd

  Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 02/2011; 50(2):104-8.

  Antiviral post-exposure prophylaxis with oseltamivir has been used as a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been few reports of well-documented prophylaxisAntiviral post-exposure prophylaxis with oseltamivir has been used as a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been few reports of well-documented prophylaxis failures and the reasons for failure. We report herein a series of 10 cases of prophylaxis failures and explore the reasons behind their prophylaxis failure. In the early pandemic phase, the military employed oseltamivir post-exposure ring-prophylaxis of affected units. From June 22 to July 30, 2009, cases of laboratory-confirmed prophylaxis failures were identified. Nasopharyngeal swabs were collected and tested by PCR. Samples with sufficient RNA material were sent for whole genome sequencing, and screened for mutations that confer oseltamivir resistance, especially the H275Y mutation. Ten cases of laboratory-confirmed prophylaxis failure were identified, with a mean age of 22.3 years. One case was asymptomatic; the remaining 9 had fever or cough but without severe complications. The mean duration of exposure before starting oseltamivir was 1.9 days (SD 0.9), while the mean duration of oseltamivir consumption before symptom onset was 1.9 days (SD 1.4). None of the samples had the H275Y mutation or other known mutations that confer resistance. From the whole genome sequencing, several mutations at the HA (T220S, E275V, T333A, D239G); PB2 (K660R, L607V, V292I); NS1 (F103S), and NP (W104G) gene segments were detected, but none of them were likely to result in anti-viral resistance. Primary prophylaxis failures exhibited mild symptoms without complications; all did not have the H275Y mutation and were unlikely to result from other mutations.

• Effectiveness of pandemic H1N1-2009 vaccination in reducing laboratory confirmed influenza infections among military recruits in tropical Singapore.

  Authors: Vernon J Lee, Chi Hsien Tan, Jonathan Yap, Alex R Cook, Pei-Jun Ting, Jin-Phang Loh, Qiuhan Gao, Mark I Chen, Wee Lee Kang, Boon Huan Tan, Paul A Tambyah

  PloS one. 01/2011; 6(10):e26572.

  Limited information is available about pandemic H1N1-2009 influenza vaccine effectiveness in tropical communities. We studied the effectiveness of a pandemic H1N1 vaccination program in reducingLimited information is available about pandemic H1N1-2009 influenza vaccine effectiveness in tropical communities. We studied the effectiveness of a pandemic H1N1 vaccination program in reducing influenza cases in Singapore. A surveillance study was conducted among military personnel presenting with febrile respiratory illness from mid-2009 to mid-2010. Consenting individuals underwent nasal washes, which were tested with RT-PCR and subtyped. A vaccination program (inactivated monovalent Panvax H1N1-2009 vaccine) was carried out among recruits. A Bayesian hierarchical model was used to quantify relative risks in the pre- and post-vaccination periods. An autoregressive generalised linear model (GLM) was developed to minimise confounding. Of 2858 participants, 437 (15.3%), 60 (2.1%), and 273 (9.6%) had pandemic H1N1, H3N2, and influenza B. The ratio of relative risks for pandemic H1N1 infection before and after vaccination for the recruit camp relative to other camps was 0.14 (0.016,0.49); for H3N2, 0.44 (0.035,1.8); and for influenza B, 18 (0.77,89). Using the GLM for the recruit camp, post-vaccination weekly cases decreased by 54% (37%,67%, p<0.001) from that expected without vaccination; influenza B increased by 66 times (9-479 times, p<0.001); with no statistical difference for H3N2 (p = 0.54). Pandemic vaccination reduced H1N1-2009 disease burden among military recruits. Routine seasonal influenza vaccination should be considered.

• A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore.

  Authors: Vernon J Lee, Jonathan Yap, Alex R Cook, Chi Hsien Tan, Jin-Phang Loh, Wee-Hong Koh, Elizabeth A S Lim, Jasper C W Liaw, Janet S W Chew, Iqbal Hossain, Ka Wei Chan, Pei-Jun Ting, Sock-Hoon Ng, Qiuhan Gao, Paul M Kelly, Mark I Chen, Paul A Tambyah, Boon Huan Tan

  PloS one. 01/2011; 6(3):e17468.

  Influenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratoryInfluenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection. Personnel with FRI (defined as fever ≥ 37.5 °C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model. 821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria. Use of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI.

• Effectiveness of public health measures in mitigating pandemic influenza spread: a prospective sero-epidemiological cohort study.

  Authors: Vernon J Lee, Jonathan Yap, Alex R Cook, Mark I Chen, Joshua K Tay, Ian Barr, Anne Kelso, Boon Huan Tan, Jin Phang Loh, Raymond Lin, Lin Cui, Paul M Kelly, Yee Sin Leo, Kee Seng Chia, Wee Lee Kang, Paul A Tambyah, Benjamin Seet

  The Journal of infectious diseases. 11/2010; 202(9):1319-26.

  Few studies have validated the effectiveness of public health interventions in reducing influenza spread in real‐life settings. We aim to validate these measures used during the 2009 pandemic. FromFew studies have validated the effectiveness of public health interventions in reducing influenza spread in real‐life settings. We aim to validate these measures used during the 2009 pandemic. From 22 June to 9 October 2009, we performed a prospective observational cohort study using paired serum samples and symptom review among 3 groups of Singapore military personnel. "Normal" units were subjected to prevailing pandemic response policies. "Essential" units and health care workers had additional public health interventions (eg, enhanced surveillance with isolation, segregation, personal protective equipment). Samples were tested by hemagglutination inhibition; the principal outcome was seroconversion to 2009 influenza A(H1N1). In total, 1015 individuals in 14 units completed the study, with 29% overall seroconversion. Seroconversion among essential units (17%) and health care workers (11%) was significantly lower than that in normal units (44%) (P = .001). Symptomatic illness attributable to influenza was also lower in essential units (5%) and health care workers (2%) than in normal units (12%) (P = .06). Adjusted for confounders, unit type was the only significant variable influencing overall seroconversion ( P < .05). From multivariate analysis within each unit, age (P < .001) and baseline antibody titer (P = .012 ) were inversely related to seroconversion risk. Public health measures are effective in limiting influenza transmission in closed environments.

• Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks.

  Authors: Vernon J Lee, Jonathan Yap, Alex R Cook, Mark I Chen, Joshua K Tay, Boon Huan Tan, Jin Phang Loh, Seok Wei Chew, Wee Hong Koh, Raymond Lin, Lin Cui, Charlie W H Lee, Wing-Kin Sung, Christopher W Wong, Martin L Hibberd, Wee Lee Kang, Benjamin Seet, Paul A Tambyah

  The New England journal of medicine. 06/2010; 362(23):2166-74.

  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 chemoprophylaxisFrom 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. 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. 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. 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.

• Rapid identification of chloroquine and atovaquone drug resistance in Plasmodium falciparum using high-resolution melt polymerase chain reaction.

  Authors: Linda Seo Hwee Gan, Jin Phang Loh

  Malaria journal. 01/2010; 9:134.

  Drug resistance determination for Plasmodium falciparum infections are important to determining the type of treatment to be given. Besides in vivo experiments, molecular methods, such as sequencingDrug resistance determination for Plasmodium falciparum infections are important to determining the type of treatment to be given. Besides in vivo experiments, molecular methods, such as sequencing and PCR, are now increasingly being used. Here a cheaper alternative to sequencing or the use of multiplex 5'nuclease PCR assay for detection and differentiation of drug resistance haplotypes for chloroquine and atovaquone using polymerase chain reaction-high resolution melt (PCR-HRM) is reported. Separate PCR-HRM assays were designed for the detection and differentiation of chloroquine and atovaquone drug resistance haplotypes in P. falciparum. PCR was conducted on a thermal cycler and melt curves generated using a LightScanner. These were tested against reference strains of P. falciparum from MR4 as well as 53 local isolates. The PCR-HRM assays are able to detect and differentiate between the various haplotypes consistently. These assays can also be used to detect new variants. PCR-HRM is an inexpensive option for the determination of drug resistance profile in P. falciparum and will see increasing use as an alternative to sequencing and 5'nuclease PCR assays in reference laboratories or once PCR systems that are able to conduct HRM become commonplace.

• Serological response in RT-PCR confirmed H1N1-2009 influenza a by hemagglutination inhibition and virus neutralization assays: an observational study.

  Authors: Mark I Chen, Ian G Barr, Gerald C H Koh, Vernon J Lee, Caroline P S Lee, Robert Shaw, Cui Lin, Jonathan Yap, Alex R Cook, Boon Huan Tan, Jin Phang Loh, Timothy Barkham, Vincent T K Chow, Raymond T P Lin, Yee-Sin Leo

  PloS one. 01/2010; 5(8):e12474.

  We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The study included patients admitted toWe describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively. Appropriately timed paired serology detects 80-90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses.

• Naturally acquired human Plasmodium knowlesi infection, Singapore.

  Authors: Oon Tek Ng, Eng Eong Ooi, Cheng Chuan Lee, Piao Jarrod Lee, Lee-Ching Ng, Sze Wong Pei, Tian Ming Tu, Jin Phang Loh, Yee Sin Leo

  Emerging infectious diseases. 06/2008; 14(5):814-6.

  We report a case of naturally acquired Plasmodium knowlesi in Singapore, a malaria-free country. Diagnosis was confirmed by PCR with validated species-specific primers. In industrialized countries,We report a case of naturally acquired Plasmodium knowlesi in Singapore, a malaria-free country. Diagnosis was confirmed by PCR with validated species-specific primers. In industrialized countries, free-ranging primates are a potential source of P. knowlesi human infection. P. knowlesi infection is a differential diagnosis of febrile illness acquired in Singapore.

• Rapid molecular typing of Burkholderia pseudomallei, isolated in an outbreak of melioidosis in Singapore in 2004, based on variable-number tandem repeats.

  Authors: Yichun Liu, Jin Phang Loh, Lay Tin Aw, Eric Ph Yap, May-Ann Lee, Eng Eong Ooi

  Transactions of the Royal Society of Tropical Medicine and Hygiene. 08/2006; 100(7):687-92.

  An increase in the number of reported melioidosis cases was observed in the first 4 months of 2004. These cases were associated with a significant increase in case-fatality rate compared with theAn increase in the number of reported melioidosis cases was observed in the first 4 months of 2004. These cases were associated with a significant increase in case-fatality rate compared with the past 5 years. In order to exclude the possibility of a single source, including the possibility of intentional release of Burkholderia pseudomallei, we applied a multiplex PCR-based multilocus variable-number tandem repeat (VNTR) assay to determine the clonality of the clinical isolates. Our investigation indicated that a total of 30 different VNTR types could be distinguished in the 32 clinical isolates of B. pseudomallei obtained during this period, thus indicating that infection was unlikely to have occurred from a single source. Our experience underscores the usefulness of a rapid strain typing method in augmenting an epidemiological investigation into an infectious disease outbreak, particularly at a time where the intentional use of biological agents is a potential threat to public health.

• In vitro inhibition of human influenza A virus replication by chloroquine.

  Authors: Eng Eong Ooi, Janet Seok Wei Chew, Jin Phang Loh, Robert C S Chua

  Virology journal. 02/2006; 3:39.

  Chloroquine is a 9-aminoquinolone with well-known anti-malarial effects. It has biochemical properties that could be applied to inhibit viral replication. We report here that chloroquine is able toChloroquine is a 9-aminoquinolone with well-known anti-malarial effects. It has biochemical properties that could be applied to inhibit viral replication. We report here that chloroquine is able to inhibit influenza A virus replication, in vitro, and the IC50s of chloroquine against influenza A viruses H1N1 and H3N2 are lower than the plasma concentrations reached during treatment of acute malaria. The potential of chloroquine to be added to the limited range of anti-influenza drugs should be explored further, particularly since antiviral drugs play a vital role in influenza pandemic preparedness.

• Rapid molecular typing of Burkholderia pseudomallei, isolated in an outbreak of melioidosis in Singapore in 2004, based on variable-number tandem repeats

  Authors: Yichun Liu, Jin-Phang Loh, Lay Tin Aw, Eric PH Yap, May Ann Lee, Eng Eong Ooi

  Transactions of the Royal Society of Tropical Medicine and Hygiene.

  An increase in the number of reported melioidosis cases was observed in the first 4 months of 2004. These cases were associated with a significant increase in case-fatality rate compared with theAn increase in the number of reported melioidosis cases was observed in the first 4 months of 2004. These cases were associated with a significant increase in case-fatality rate compared with the past 5 years. In order to exclude the possibility of a single source, including the possibility of intentional release of Burkholderia pseudomallei, we applied a multiplex PCR-based multilocus variable-number tandem repeat (VNTR) assay to determine the clonality of the clinical isolates. Our investigation indicated that a total of 30 different VNTR types could be distinguished in the 32 clinical isolates of B. pseudomallei obtained during this period, thus indicating that infection was unlikely to have occurred from a single source. Our experience underscores the usefulness of a rapid strain typing method in augmenting an epidemiological investigation into an infectious disease outbreak, particularly at a time where the intentional use of biological agents is a potential threat to public health.