John S Tam

Wellcome Trust, Londinium, England, United Kingdom

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Publications (57)325.78 Total impact

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    ABSTRACT: Influenza vaccines have been recommended for populations at risk for severe infection in low and middle income countries (LMICs) although knowledge of the evidence-base for their effectiveness and efficacy is limited in these countries. The aim of this systematic review is to provide an overview of the evidence-base for the effectiveness and efficacy of influenza vaccines in LMICs and to explore critical knowledge gaps. PubMed, EMBASE, and Cochrane were searched for seasonal and pandemic A (H1N1) 2009 influenza vaccine effectiveness and efficacy studies performed in LMICs. Eligible studies included RCTs and observational studies, published in English, French, Spanish or Portuguese between 1960 and 2011, which assessed laboratory-confirmed influenza and/or influenza-related outcomes in any population. Risk of bias was assessed by two reviewers independently. Random effects pooled estimates were obtained when sufficient data were available. A total of 6465 articles were screened. Forty-one studies were included on seasonal influenza vaccine effectiveness and efficacy and one study on pandemic vaccine effectiveness. In middle income countries (MICs), efficacy of seasonal influenza vaccines was shown against laboratory-confirmed influenza in children (pooled efficacy 72% (95%CI: 65-77) and 81% (95%CI: 69-89), for one and two years follow-up respectively) and in the elderly (pooled efficacy 43% (95%CI: 25-56) and 58% (95%CI: 23-78), for live attenuated and inactivated vaccine respectively). Inactivated influenza vaccines were also found to be effective against cardiovascular outcomes in patients with coronary syndromes. Seasonal influenza vaccines can provide protection in children, the elderly and patients with coronary syndromes in MICs, and seem to be equally effective as compared to high income countries. Data for other high risk groups and from low income countries were limited or prone to bias, and are needed to further facilitate evidence-based decision making regarding influenza vaccination in LMICs.
    Vaccine 09/2013; · 3.77 Impact Factor
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    ABSTRACT: On January 24-26, 2013, the World Health Organization convened the first integrated meeting on "The development and clinical trials of vaccines that induce broadly protective and long-lasting immune responses" to review the current status of development and clinical evaluation of novel influenza vaccines as well as strategies to produce and deliver vaccines in novel ways. Special attention was given to the development of possible universal influenza vaccines. Other topics that were addressed included an update on clinical trials of pandemic and seasonal influenza vaccines in high-risk groups and vaccine safety, as well as regulatory issues.
    Vaccine 06/2013; · 3.77 Impact Factor
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    ABSTRACT: Objectives: Economic evaluations on influenza vaccination from low resource settings are scarce and have not been evaluated using a systematic approach. Our objective was to conduct a systematic review on the value for money of influenza vaccination in low- and middle-income countries. Methods: PubMed and EMBASE were searched for economic evaluations published in any language between 1960 and 2011. Main outcome measures were costs per influenza outcome averted, costs per quality-adjusted life years gained or disability-adjusted life years averted, costs per benefit in monetary units or cost-benefit ratios. Results: Nine economic evaluations on seasonal influenza vaccine met the inclusion criteria. These were model- or randomized-controlled-trial (RCT)-based economic evaluations from middle-income countries. Influenza vaccination provided value for money for elderly, infants, adults and children with high-risk conditions. Vaccination was cost-effective and cost-saving for chronic obstructive pulmonary disease patients and in elderly above 65 y from model-based evaluations, but conclusions from RCTs on elderly varied. Conclusion: Economic evaluations from middle income regions differed in population studied, outcomes and definitions used. Most findings are in line with evidence from high-income countries highlighting that influenza vaccine is likely to provide value for money. However, serious methodological limitations do not allow drawing conclusions on cost-effectiveness of influenza vaccination in middle income countries. Evidence on cost-effectiveness from low-income countries is lacking altogether, and more information is needed from full economic evaluations that are conducted in a standardized manner.
    Human vaccines & immunotherapeutics. 05/2013; 9(7).
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    ABSTRACT: There is an increasing focus on influenza in low-resourced areas as a vaccine-preventable cause of severe lower respiratory disease in young children, especially among those under two years of age. The extent of the disease burden is currently unclear: current etiologic studies may underestimate the impact of influenza if recognized or unrecognized infection occurs some time before severe disease manifestations prompt specimen collection for diagnosis. Because of various methodological challenges, a vaccine probe approach was used to estimate vaccine preventable disease incidence (VPDI) for Streptococcus pneumoniae and Haemophilus influenzae type b, particularly for pneumonia outcomes among young children. A similar approach could be used to determine VPDI for influenza. A highly effective vaccine would facilitate this approach; however, with appropriate design, a less than ideal vaccine also could be used to estimate VPDI. Because influenza vaccine efficacy against severe disease may be greater than against all symptomatic influenza disease, a vaccine probe approach could provide a better measure than etiologic studies of the public health utility of influenza vaccine. The first 6 months of life is a time of particularly increased influenza risk among young children, and an age group for which current vaccines are not approved. Previous studies have found that maternal influenza immunization can reduce acute respiratory infection in the infant during this vulnerable period. Additional randomized, controlled trials are currently underway using a vaccine probe approach to estimate VPDI among mothers and their infants following maternal influenza immunization. The World Health Organization now identifies pregnant women as the highest priority target group for influenza vaccination. Should countries implement this strategy, infants age 6-23 months likely would remain at increased risk; vaccine probe approaches could quantify the public health benefit of immunizing this group.
    Vaccine 05/2013; · 3.77 Impact Factor
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    ABSTRACT: On 16-17 November 2011, the Initiative for Vaccine Research of the World Health Organization convened jointly with the Wellcome Trust the fifth meeting on 'Influenza vaccines that induce broad spectrum and long-lasting immune responses'. The goals of the meeting were to examine new influenza vaccine research developments related to increased duration and breadth of protection, including immune responses against novel strains that may present zoonotic and pandemic threats; improved delivery and administration; and safety issues related to novel vaccine approaches. A number of investigational vaccines based on unique antigens, adjuvants, and/or modes of delivery were presented. The challenges for feasible regulatory pathways to approval of such vaccines were discussed.
    Vaccine 09/2012; 30(47):6612-22. · 3.77 Impact Factor
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    ABSTRACT: Please cite this paper as: Laurie et al. (2012) Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.0370a.x. Background  Serological studies can detect infection with a novel influenza virus in the absence of symptoms or positive virology, providing useful information on infection that goes beyond the estimates from epidemiological, clinical and virological data. During the 2009 A(H1N1) pandemic, an impressive number of detailed serological studies were performed, yet the majority of serological data were available only after the first wave of infection. This limited the ability to estimate the transmissibility and severity of this novel infection, and the variability in methodology and reporting limited the ability to compare and combine the serological data. Objectives  To identify best practices for conduct and standardisation of serological studies on outbreak and pandemic influenza to inform public policy. Methods/Setting  An international meeting was held in February 2011 in Ottawa, Canada, to foster the consensus for greater standardisation of influenza serological studies. Results  Best practices for serological investigations of influenza epidemiology include the following: classification of studies as pre-pandemic, outbreak, pandemic or inter-pandemic with a clearly identified objective; use of international serum standards for laboratory assays; cohort and cross-sectional study designs with common standards for data collection; use of serum banks to improve sampling capacity; and potential for linkage of serological, clinical and epidemiological data. Advance planning for outbreak studies would enable a rapid and coordinated response; inclusion of serological studies in pandemic plans should be considered. Conclusions  Optimising the quality, comparability and combinability of influenza serological studies will provide important data upon emergence of a novel or variant influenza virus to inform public health action.
    Influenza and Other Respiratory Viruses 04/2012; · 1.47 Impact Factor
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    ABSTRACT: To explore mutations around the interferon sensitivity-determining region (ISDR) which are associated with the resistance of hepatitis C virus 1b (HCV-1b) to interferon-α treatment. Thirty-seven HCV-1b samples were obtained from Hong Kong patients who had completed the combined interferon-α/ribavirin treatment for more than one year with available response data. Nineteen of them were sustained virological responders, while 18 were non-responders. The amino acid sequences of the extended ISDR (eISDR) covering 64 amino acids upstream and 67 amino acids downstream from the previously reported ISDR were analyzed. One amino acid variation (I2268V, P = 0.023) was significantly correlated with treatment outcome in this pilot study with a limited number of patients, while two amino acid variations (R2260H, P = 0.05 and S2278T, P = 0.05) were weakly associated with treatment outcome. The extent of amino acid variations within the ISDR or eISDR was not correlated with treatment outcome as previously reported. Three amino acid mutations near but outside of ISDR may associate with interferon treatment resistance of HCV-1b patients in Hong Kong.
    World Journal of Gastroenterology 12/2011; 17(48):5317-23. · 2.55 Impact Factor
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    ABSTRACT: On February 17-18, 2011, the World Health Organization convened the 7th meeting on "The Evaluation of Pandemic Influenza Vaccines in Clinical Trials" to review the progress made on pandemic A (H1N1) 2009 vaccines and the evaluation of their effectiveness in the field, especially in children less than 3 years of age and in pregnant women. Other topics to be addressed included a comparison of egg- and cell culture-based influenza vaccines, technical issues related to vaccine strain development and vaccine potency, and the status of development of prototype influenza vaccines using new technologies. Pandemic A (H1N1) vaccines were safe in young children, pregnant women and immunocompromized individuals. Overall effectiveness of inactivated A (H1N1) vaccines for all ages was found to vary between 72% and 100% in different countries and with different vaccine preparations. Effectiveness of pandemic A (H1N1) 2009 live attenuated vaccine was estimated to be approximately 80% in pediatric populations in the USA. A single dose of inactivated vaccine adjuvanted with AS03, MF59 or AF03 induced protective immunity in young children and pregnant women. However, unadjuvanted vaccines as well as low dose adjuvanted vaccines (1.9 μg HA) required two doses to elicit protective antibody levels in these populations. Clinical trials of influenza vaccines developed using new technologies showed they were well tolerated and induced antibody and/or T cell immune responses to viral proteins. Further studies are warranted to validate novel immunological criteria for evaluation and licensing of such new influenza vaccine concepts. On the regulatory side, work should be undertaken to harmonize the results of serological tests used to evaluate the immunogenicity of traditional influenza vaccines.
    Vaccine 08/2011; 29(44):7579-86. · 3.77 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) 6a accounts for 23.6% of all HCV infections of the general population and 58.5% of intravenous drug users in Hong Kong. However, the geographical origin of this highly predominant HCV subgenotype is largely unknown. This study explores a hypothesis for one possible transmission route of HCV 6a to Hong Kong. NS5A sequences derived from 26 HCV 6a samples were chosen from a five year period (1999-2004) from epidemiologically unrelated patients from Hong Kong. Partial-NS5A sequences (513-bp from nt 6728 to 7240) were adopted for Bayesian coalescent analysis to reconstruct the evolutionary history of HCV infections in Hong Kong using the BEAST v1.3 program. A rooted phylogenetic tree was drawn for these sequences by alignment with reference Vietnamese sequences. Demographic data were accessed from "The Statistic Yearbooks of Hong Kong". Bayesian coalescent analysis showed that the rapid increase in 6a infections, which had increased more than 90-fold in Hong Kong from 1986 to 1994 correlated to two peaks of Vietnamese immigration to Hong Kong from 1978 to 1997. The second peak, which occurred from 1987 through 1997, overlapped with the rapid increase of HCV 6a occurrence in Hong Kong. Phylogenetic analyses have further revealed that HCV 6a strains from Vietnam may be ancestral to Hong Kong counterparts. The high predominance of HCV 6a infections in Hong Kong was possibly associated with Vietnamese immigration during 1987-1997.
    PLoS ONE 01/2011; 6(9):e24889. · 3.73 Impact Factor
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    ABSTRACT: Studies on the association between sequence variability of the interferon sensitivity-determining region (ISDR) of hepatitis C virus and the outcome of treatment have reached conflicting results. In this study, 25 patients infected with HCV 6a who had received interferon-alpha/ribavirin combination treatment were analyzed for the sequence variations. 14 of them had the full genome sequences obtained from a previous study, whereas the other 11 samples were sequenced for the extended ISDR (eISDR). This eISDR fragment covers 192 bp (64 amino acids) upstream and 201 bp (67 amino acids) downstream from the ISDR previously defined for HCV 1b. The comparison between interferon-alpha resistance and response groups for the amino acid mutations located in the full genome (6 and 8 patients respectively) as well as the mutations located in the eISDR (10 and 15 patients respectively) showed that the mutations I2160V, I2256V, V2292I (P<0.05) within eISDR were significantly associated with resistance to treatment. However, the extent of amino acid variations within previously defined ISDR was not associated with resistance to treatment as previously reported. Four amino acid variations I248V (P=0.03-0.06) within E1, R445K (P=0.02-0.05) and S747T (P=0.03) within E2, I861V (P=0.01) within NS2 which located outside the eISDR may also associate with treatment outcome as identified by a prescreening of variations within 14 HCV 6a full genomes.
    Virus Research 10/2010; 153(1):44-9. · 2.75 Impact Factor
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    ABSTRACT: In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined.
    Vaccine 07/2010; 28(31):4895-902. · 3.77 Impact Factor
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    ABSTRACT: Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).
    Vaccine 12/2009; 28(6):1566-74. · 3.77 Impact Factor
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    ABSTRACT: This study assessed the clinical management and impact of diarrhoea aetiology (rotavirus positive/negative) and rotavirus genotype on diarrhoeal disease severity. Of 7391 diarrhoea admissions less than 5 years of age over a 2-year period, 80% of patients were tested for rotavirus, 87% were cultured for bacterial pathogens and 78% were assessed for both. Diarrhoeal severity scores were greatest in those children with mixed rotavirus and bacterial infections. Between 1.3 and 8.4% of infants were considered dehydrated yet intravenous fluids were used for 48% of infants (69% rotavirus positive, 72% mixed infection). These findings support the promotion of oral rehydration therapy over intravenous fluids.
    Vaccine 11/2009; 27 Suppl 5:F55-60. · 3.77 Impact Factor
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    ABSTRACT: The highly sensitive gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-gamma ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months, an intranasal dose of 10(7) fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination. The role of CMI in actual protection against community-acquired, culture-confirmed clinical influenza by CAIV-T was investigated in a large randomized, double-blind, placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to <36 months in the Philippines and Thailand. The estimated protection curve indicated that the majority of infants and young children with >or=100 spot-forming cells/10(6) peripheral blood mononuclear cells were protected against clinical influenza, establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN-gamma is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza, especially those used for children.
    Clinical and vaccine Immunology: CVI 07/2008; 15(7):1042-53. · 2.60 Impact Factor
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    ABSTRACT: This study was designed to evaluate the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) against culture-confirmed influenza in children 12 to <36 months of age during 2 consecutive influenza seasons at multiple sites in Asia. In year 1, 3174 children 12 to <36 months of age were randomized to receive 2 doses of CAIV-T (n = 1900) or placebo (n = 1274) intranasally > or =28 days apart. In year 2, 2947 subjects were rerandomized to receive 1 dose of CAIV-T or placebo. Mean age at enrollment was 23.5 +/- 7.4 months. In year 1, efficacy of CAIV-T compared with placebo was 72.9% [95% confidence interval (CI): 62.8-80.5%] against antigenically similar influenza subtypes, and 70.1% (95% CI: 60.9-77.3%) against any strain. In year 2, revaccination with CAIV-T demonstrated significant efficacy against antigenically similar (84.3%; 95% CI: 70.1-92.4%) and any (64.2%; 95% CI: 44.2-77.3%) influenza strains. In year 1, fever, runny nose/nasal congestion, decreased activity and appetite, and use of fever medication were more frequent with CAIV-T after dose 1. Runny nose/nasal congestion after dose 2 (year 1) and dose 3 (year 2) and use of fever medication after dose 3 (year 2) were the only other events reported significantly more frequently in CAIV-T recipients. CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia.
    The Pediatric Infectious Disease Journal 07/2007; 26(7):619-28. · 3.57 Impact Factor
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    ABSTRACT: A multiplex reverse transcription-polymerase chain reaction (mRT-PCR) method was developed for simultaneous detection and typing/subtyping of influenza viruses A/H1, A/H3 or B, and respiratory syncytial viruses A or B, followed by DNA semiquantitation using the Agilent 2100 Bioanalyzer. Such method provides a rapid, specific and sensitive diagnostic tool for detection and semiquantification of respiratory illness specimens.
    Journal of Virological Methods 02/2007; 139(1):90-2. · 1.90 Impact Factor
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    ABSTRACT: This study describes the distribution of hepatitis C genotypes among 106 intravenous drug users and 949 non-drug users in Hong Kong. Genotypes were identified by multiplex RT-PCR targeting the core region of viral genome. The accuracy of this typing system in identifying genotypes 1b and 6a was assessed by phylogenetic analysis. The distribution of hepatitis C virus (HCV) genotypes amongst non-drug users was 63.6% for genotype 1b, 23.6% for 6a, 4.5% for 1a, 3.9% for 3a, and 3.1% for 2a; whereas amongst the intravenous drug users, it was 58.5% for genotype 6a, 33.0% for 1b, 5.7% for 3a, 0.9% for 1a, and 0.9% for 2a. The proportion of genotype 6a was significantly higher (P < 0.001), whereas that for genotype 1b was significantly lower (P = 0.001) for the intravenous drug user group. Multivariate analysis revealed significant independent associations for the distribution of HCV genotypes 1b and 6a with age, sex, and intravenous drug user status. The co-circulation of a common (1b) and a rare (6a) HCV genotype in Hong Kong provides a unique opportunity for future studies to compare their transmission efficiency, clinical course, and response to treatment.
    Journal of Medical Virology 05/2006; 78(5):574-81. · 2.37 Impact Factor
  • Nancy Leung, Carol Chu, John S Tam
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    ABSTRACT: Hepatitis C virus (HCV) infection can lead to serious liver disease. Its medico-socio-economic burden on society can be immense. This study investigates the epidemiology of HCV infection in Hong Kong. Data from the Department of Health, relevant publications from Medline search and data from two acute hospitals were reviewed. The prevalence of anti-HCV among voluntary blood donors is stable, remaining at approximately 0.035-0.099% over the past 10 years, and is higher in the older age group. Among the high-risk groups, the anti-HCV prevalence is as follows: (1) hospital patients 0.8%, (2) intravenous drug users 46.0%, (3) patients infected with HIV 7.9%, (4) children with transfusion-dependent hematologic disease 16.3%, (5) patients on continuous ambulatory peritoneal dialysis 1.8%, patients on hemodialysis 16.4%, recipients of kidney transplants 6.2% and (6) patients with hepatocellular carcinoma 7.3%. Among blood donors, 58.8% were infected with HCV genotype 1b and 27.0% with genotype 6a. Genotype 6a is particularly common among intravenous drug users. Hong Kong has a low prevalence of HCV infection. Patients are mostly infected through transfusion with blood or products prior to the introduction of anti-HCV screening to the blood transfusion service. Illicit drug use constitutes another significant risk. Since 1997, there has been a great increase in population movement between China and Hong Kong which might affect the epidemiology of HCV infection.
    Intervirology 02/2006; 49(1-2):23-7. · 1.89 Impact Factor
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    ABSTRACT: Hemagglutinin sequences of 146 human influenza A/H3N2 strains identified in respiratory specimens from Asia and Europe during the 2001-2003 influenza seasons were analyzed by DNA sequencing. Our results suggest that four amino acid substitutions, L25I, H75Q, H155T, and Q156H, led to the antigenic conversion of the previously predominant A/Panama/2007/99-like strains to the more recent A/Fujian/411/2002-like strains.
    Journal of Clinical Microbiology 01/2006; 43(12):6130-2. · 4.07 Impact Factor
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    ABSTRACT: A TaqMan-based real-time RT-PCR assay was developed to detect and quantify human parainfluenza virus 3 (PIV3). Two sets of primer-probe pairs were designed based on the nucleotide (nt) sequence of the nucleocapsid (N) gene. The primer-probe pairs were derived from the 3' end of the N gene (set 1) and the 5' region of the gene (set 2), respectively. Using real-time RT-PCR, the sensitivity of set 1 was determined to be about 9 copies of PIV3 genome, while the sensitivity of set 2 was about 93 copies of PIV3 genome. Set 1 was chosen for subsequent experiments. This primer-probe pair detected PIV3, but not any of several other respiratory viruses, indicating that the assay is PIV3 specific. For clinical evaluation, the assay was employed to test 80 nasopharyngeal aspirates from children with respiratory symptoms. The results confirmed the presence of PIV3 in 12 specimens previously identified as positive by culture confirmation, and showed all of which contained more than 100 copies of PIV3 genome. In addition, the method also detected PIV3 genomes in specimens found negative by culture confirmation, indicating the value of this RT-PCR assay. These data thus demonstrate the application of the real-time RT-PCR assay for the detection and quantification of PIV3 in clinical specimens.
    Journal of Virological Methods 01/2006; 130(1-2):145-8. · 1.90 Impact Factor

Publication Stats

2k Citations
325.78 Total Impact Points


  • 2012
    • Wellcome Trust
      Londinium, England, United Kingdom
  • 2011
    • World Health Organization WHO
      Genève, Geneva, Switzerland
  • 2010
    • Fudan University
      Shanghai, Shanghai Shi, China
  • 2003–2010
    • The Chinese University of Hong Kong
      • • Department of Microbiology
      • • Prince of Wales Hospital
      Hong Kong, Hong Kong
  • 2006
    • Alice Ho Miu Ling Nethersole Hospital
      Ch’üan-wan, Tsuen Wan, Hong Kong