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1.  Estimation of the Association Between Antibody Titers and Protection Against Confirmed Influenza Virus Infection in Children 
The Journal of Infectious Diseases  2013;208(8):1320-1324.
Antibody titers measured by hemagglutination inhibition (HAI) correlate with protection against influenza virus infection and are used to specify criteria for vaccine licensure. In a randomized, controlled trial of seasonal influenza vaccination in 773 children aged 6–17 years, we estimated that HAI titers of 1:40 against A(H1N1)pdm09 and B(Victoria lineage) were associated with 48% (95% confidence interval [CI], 30%–62%) and 55% (95% CI, 32%–70%) protection against PCR-confirmed infection with each strain. Our analysis accounted for waning in antibody titers over time, and could be particularly useful in settings where influenza activity is delayed or prolonged relative to measurement of antibody titers.
PMCID: PMC3778972  PMID: 23908481
antibody; immunity; influenza; vaccine; children
2.  Mutation in xyloglucan 6-xylosytransferase results in abnormal root hair development in Oryza sativa  
Journal of Experimental Botany  2014;65(15):4149-4157.
OsXXT1 showed xyloglucan 6-xylosyltransferase activity and is involved in maintaining cell wall structure and tensile strength in rice. Mutation of OsXXT1 results in abnormal root hair development.
Root hairs are important for nutrient uptake, anchorage, and plant–microbe interactions. From a population of rice (Oryza sativa) mutagenized by ethyl methanesulfonate (EMS), a short root hair2 (srh2) mutant was identified. In hydroponic culture, srh2 seedlings were significantly reduced in root hair length. Bubble-like extrusions and irregular epidermal cells were observed at the tips of srh2 root hairs when grown under acidic conditions, suggesting the possible reduction of the tensile strength of the cell wall in this mutant. Map-based cloning identified a mutation in the gene encoding xyloglucan (XyG) 6-xylosyltransferase (OsXXT1). OsXXT1 displays more than 70% amino acid sequence identity with the previously characterized Arabidopsis thaliana XYG XYLOSYL TRANSFERASE 1 (AtXXT1) and XYG XYLOSYL TRANSFERASE 2 (AtXXT2), which catalyse the transfer of xylose onto β-1,4-glucan chains. Furthermore, expression of the full-length coding sequence of OsXXT1 could complement the root hair defect, and slow growth and XyG synthesis in the Arabidopsis xxt1 xxt2 double mutant. Transgenic plants expressing the β-glucuronidase (GUS) reporter under the control of the OsXXT1 promoter displayed GUS expression in multiple tissues, most prominently in root epidermal cells. These results demonstrate the importance of OsXXT1 in maintaining cell wall structure and tensile strength in rice, a typical grass species that contains relatively low XyG content in cell walls.
PMCID: PMC4112626  PMID: 24834920
Rice; root hair; type I cell wall; type II cell wall; xyloglucan; xylosyltransferase.
3.  Humoral Antibody Response after Receipt of Inactivated Seasonal Influenza Vaccinations one Year Apart in Children 
In a randomized controlled trial, we administered seasonal trivalent inactivated influenza vaccine (TIV) or placebo to subjects 6–15 years of age in two consecutive years. Receipt of TIV in year 2 induced seroprotection in most subjects. Among 39 children who received TIV in the second year, receipt of TIV in the first year was associated with lower antibody titer rises in the second year to seasonal influenza A(H1N1) and A(H3N2) strains for which the vaccine strains remained unchanged. Antibody response to a different influenza B strain in the second year was unaffected by receipt of TIV in the first year.
PMCID: PMC3422369  PMID: 22683675
vaccination; influenza; antibody response; children
4.  Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine 
We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.
PMCID: PMC3404712  PMID: 22423139
5.  The Effect of Age and Recent Influenza Vaccination History on the Immunogenicity and Efficacy of 2009–10 Seasonal Trivalent Inactivated Influenza Vaccination in Children 
PLoS ONE  2013;8(3):e59077.
There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6–8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.
Methods and Findings
We conducted a randomized controlled trial of 2009–10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9–17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6–8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6–8 y of age regardless of vaccination history.
Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.
PMCID: PMC3595209  PMID: 23554974
6.  Transmissibility of seasonal and pandemic influenza in a cohort of households in Hong Kong in 2009 
Epidemiology (Cambridge, Mass.)  2011;22(6):793-796.
The household secondary attack proportion is commonly used to measure the transmissibility of an infectious disease.
We analyzed the final outbreak distributions of pandemic A(H1N1), seasonal A(H1N1) and A(H3N2) infections identified in paired sera collected from members of 117 Hong Kong households in April and August-October 2009.
The estimated community probability of infection overall was higher for children than adults; the probability was similar for pandemic A(H1N1) and seasonal A(H3N2) influenza. The household secondary attack proportion for pandemic A(H1N1) was higher in children than adults, whereas for seasonal A(H3N2) it was similar in children and adults. The estimated secondary attack proportions were similar for seasonal A(H3N2) and pandemic A(H1N1) after excluding persons with higher baseline antibody titers from analysis.
Pandemic and seasonal influenza A viruses had similar age-specific transmissibility in a cohort of initially uninfected households after adjustment for baseline immunity.
PMCID: PMC3206962  PMID: 21878814
7.  Seroprevalence of Pandemic H1N1 Antibody among Health Care Workers in Hong Kong Following Receipt of Monovalent 2009 H1N1 Influenza Vaccine 
PLoS ONE  2011;6(11):e27169.
Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010.
We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February–March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays.
We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%–63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%–52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007–08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19–1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant.
Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.
PMCID: PMC3213124  PMID: 22102878
8.  An analysis of national target groups for monovalent 2009 pandemic influenza vaccine and trivalent seasonal influenza vaccines in 2009-10 and 2010-11 
BMC Infectious Diseases  2011;11:230.
Vaccination is generally considered to be the best primary prevention measure against influenza virus infection. Many countries encourage specific target groups of people to undertake vaccination, often with financial subsidies or a priority list. To understand differential patterns of national target groups for influenza vaccination before, during and after the 2009 influenza pandemic, we reviewed and analyzed the country-specific policies in the corresponding time periods.
Information on prioritized groups targeted to receive seasonal and pandemic influenza vaccines was derived from a multi-step internet search of official health department websites, press releases, media sources and academic journal articles. We assessed the frequency and consistency of targeting 20 different groups within populations which are associated with age, underlying medical conditions, role or occupations among different countries and vaccines. Information on subsidies provided to specific target groups was also extracted.
We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines), 72 (monovalent pandemic 2009-10 vaccine) and 34 (seasonal 2010 and 2010-11 vaccines) countries. In 2009-10, the elderly, those with chronic illness and health care workers were common targets for the seasonal vaccine. Comparatively, the elderly, care home residents and workers, animal contacts and close contacts were less frequently targeted to receive the pandemic vaccine. Pregnant women, obese persons, essential community workers and health care workers, however, were more commonly targeted. After the pandemic, pregnant women, obese persons, health care and care home workers, and close contacts were more commonly targeted to receive the seasonal vaccine compared to 2009-10, showing continued influence from the pandemic. Many of the countries provided free vaccines, partial subsidies, reimbursements or national health insurance coverage to specific target groups and over one-third of the countries offered universal subsidy regarding the pandemic vaccine. There was also some inconsistency between countries in target groups.
Differences in target groups between countries may reflect variable objectives as well as uncertainties regarding the transmission dynamics, severity and age-specific immunity against influenza viruses before and after vaccination. Clarification on these points is essential to elucidate optimal and object-oriented vaccination strategies.
PMCID: PMC3175216  PMID: 21871096
influenza; pandemic; seasonal; vaccine; target groups; subsidy
9.  Effects of oseltamivir treatment on duration of clinical illness and viral shedding, and household transmission of influenza virus 
Large clinical trials have demonstrated the therapeutic efficacy of oseltamivir against influenza. Here we assessed its indirect effectiveness in reducing household secondary transmission in an incident cohort of influenza index cases and their household members.
We recruited index outpatients whose rapid tests for influenza were positive in 2007 and 2008. Household contacts were followed for 7–10 days during 3–4 home visits to monitor symptoms. Nose and throat swabs were collected and tested for influenza by reverse transcription polymerase chain reaction (RT-PCR) or viral culture.
We followed 384 index cases and their household contacts. Index cases who took oseltamivir within 24 hours of symptom onset halved the time to symptom alleviation (adjusted acceleration factor (AF) 0.56; 95% CI: 0.42, 0.76). Oseltamivir treatment was not associated with statistically significant reduction in the duration of viral shedding. Household contacts of index cases who had taken oseltamivir within 24 hours of onset had a non-statistically significant lower risk of developing laboratory-confirmed infection (adjusted odds ratio (OR) 0.54; 95% CI: 0.11, 2.57) and a marginally statistically significant lower risk of clinical illness (adjusted OR 0.52; 95% CI: 0.25, 1.08) compared to contacts of index cases who did not take oseltamivir.
Oseltamivir treatment is effective in reducing the duration of symptoms but evidence for household reduction in transmission of influenza virus was inconclusive.
PMCID: PMC2840043  PMID: 20121573
Influenza; oseltamivir; antiviral; public health
10.  Defining reference genes in Oryza sativa using organ, development, biotic and abiotic transcriptome datasets 
BMC Plant Biology  2010;10:56.
Reference genes are widely used to normalise transcript abundance data determined by quantitative RT-PCR and microarrays. However, the approaches taken to define reference genes can be variable. Although Oryza sativa (rice) is a widely used model plant and important crop specie, there has been no comprehensive analysis carried out to define superior reference genes.
Analysis of 136 Affymetrix transcriptome datasets comprising of 373 genome microarrays from studies in rice that encompass tissue, developmental, abiotic, biotic and hormonal transcriptome datasets identified 151 genes whose expression was considered relatively stable under all conditions. A sub-set of 12 of these genes were validated by quantitative RT-PCR and were seen to be stable under a number of conditions. All except one gene that has been previously proposed as a stably expressed gene for rice, were observed to change significantly under some treatment.
A new set of reference genes that are stable across tissue, development, stress and hormonal treatments have been identified in rice. This provides a superior set of reference genes for future studies in rice. It confirms the approach of mining large scale datasets as a robust method to define reference genes, but cautions against using gene orthology or counterparts of reference genes in other plant species as a means of defining reference genes.
PMCID: PMC2923530  PMID: 20353606

Results 1-10 (10)