Background. Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no ...comparable quantitative data to our knowledge on naturally acquired infections. Methods. In a community-based study in Hong Kong in 2008, we followed up initially healthy individuals to quantify trends in viral shedding on the basis of cultures and reverse-transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. Results. Trends in symptom scores more closely matched changes in molecular viral loads measured with RT-PCR for influenza A than for influenza B. For influenza A virus infections, the replicating viral loads determined with cultures decreased to undetectable levels earlier after illness onset than did molecular viral loads. Most viral shedding occurred during the first 2–3 days after illness onset, and we estimated that 1%–8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding at RT-PCR were asymptomatic, and viral shedding was low in these cases. Conclusions. Our results suggest that “silent spreaders” (ie, individuals who are infectious while asymptomatic or presymptomatic) may be less important in the spread of influenza epidemics than previously thought.
Background. The relationship between seasonal influenza vaccine and susceptibility to 2009 pandemic A/H1N1 virus infection is not fully understood. Methods. One child 6–15 years of age from each of ...119 households was randomized to receive 1 dose of inactivated trivalent seasonal influenza vaccine (TIV) or saline placebo in November 2008. Serum samples were collected from study subjects and their household contacts before and 1 month after vaccination (December 2008), after winter (April 2009) and summer influenza (September–October 2009) seasons. Seasonal and pandemic influenza were confirmed by serum hemagglutinination inhibition, viral neutralization titers, and reverse-transcription polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes. Results. TIV recipients had lower rates of serologically confirmed seasonal A/H1N1 infection (TIV group, 8%; placebo group, 21%; P = .10) and A/H3N2 infection (7% vs 12%; P = .49), but higher rates of pandemic A/H1N1 infection (32% vs 17%; P = .09). In multivariable analysis, those infected with seasonal influenza A during the study had a lower risk of laboratory-confirmed pandemic A/H1N1 infection (adjusted odds ratio OR, 0.35; 95% confidence interval CI, 0.14–0.87), and receipt of seasonal TIV was unassociated with risk of pandemic A/H1N1 infection (adjusted OR, 1.11; 95% CI, 0.54–2.26). Conclusions. TIV protected against strain-matched infection in children. Seasonal influenza infection appeared to confer cross-protection against pandemic influenza. Whether prior seasonal influenza vaccination affects the risk of infection with the pandemic strain requires additional study. Clinical trials registration. ClinicalTrials.gov number NCT00792051.
Few data are available about the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission.
To investigate whether hand hygiene and use of facemasks prevents ...household transmission of influenza.
Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893)
Households in Hong Kong.
407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.
Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.
Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.
Sixty (8%) contacts in the 259 households had RT-PCR-confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR-confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 95% CI, 0.13 to 0.87). Adherence to interventions varied.
The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.
Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.
Centers for Disease Control and Prevention.
Background. Large clinical trials have demonstrated the therapeutic efficacy of oseltamivir against influenza. We assessed the indirect effectiveness of oseltamivir in reducing secondary household ...transmission in an incident cohort of influenza index patients and their household members. Methods. We recruited index outpatients whose rapid test results were positive for influenza from February through September 2007 and January through September 2008. Household contacts were followed up 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 or viral culture. Results. We followed up 384 index patients and their household contacts. Index patients who took oseltamivir within 24 h of symptom onset halved the time to symptom alleviation (adjusted acceleration factor, 0.56; 95% confidence interval CI, 0.42–0.76). Oseltamivir treatment was not associated with statistically significant reduction in the duration of viral shedding. Household contacts of index patients who had taken oseltamivir within 24 h of onset had a nonstatistically significant lower risk of developing laboratory-confirmed infection (adjusted odds ratio, 0.54; 95% CI, 0.11–2.57) and a marginally statistically significant lower risk of clinical illness (adjusted odds ratio, 0.52; 95% CI, 0.25–1.08) compared with contacts of index patients who did not take oseltamivir. Conclusions. Oseltamivir treatment is effective in reducing the duration of symptoms, but evidence of household reduction in transmission of influenza virus was inconclusive.
There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce ...influenza transmission among Hong Kong household members.
We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable.
The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008.
ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365.
Background. The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear. Methods. One child aged 6–17 years in each of 796 households was randomized to ...receive 2009–2010 seasonal trivalent inactivated influenza vaccine (TIV) or saline placebo between August 2009 and February 2010. Households were followed up with serology, symptom diaries, and collection of respiratory specimens during illnesses. The primary outcomes were influenza infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or a ≥4-fold rise in serum antibody titer measured by hemagglutination inhibition assay. Results. Receipt of TIV led to 8–13-fold mean geometric rises in antibody titers against seasonal A and B viruses, but only 1.5-fold mean geometric rises against the pandemic A(H1N1) virus that was not included in the vaccine. Children who received TIV had a reduced risk of seasonal influenza B confirmed by RT-PCR, with a vaccine efficacy estimate of 66% (95% confidence interval CI, 31%–83%). Children who received TIV also a had reduced risk of pandemic influenza A(H1N1) indicated by serology, with a vaccine efficacy estimate of 47% (95% CI, 15%–67%). Conclusions. Seasonal TIV prevented pandemic influenza A(H1N1) and influenza B infections in children. Pandemic A(H1N1) circulated at the time of vaccination and for a short time afterward with no substantial seasonal influenza activity during that period. The potential mechanism for seasonal TIV to provide protection, possibly short lived, for children against pandemic A(H1N1) infection despite poor cross-reactive serologic response deserves further investigation. Clinical Trials Registration. NCT00792051.
Since SARS epidemic in 2003, Hong Kong has experienced several major epidemic risks, but how general community might react to the repeated infectious diseases health risks have not been studied. In ...2013, imported human H7N9 influenza infected cases from China were reported. Our study aims to assess the knowledge, attitude and practice (KAP) concerning A/H7N9 among Hong Kong general population regarding pandemic preparedness in early 2014.
A cross-sectional, population-based telephone survey study was conducted among the Cantonese-speaking population aged over 15 years in Hong Kong in February 2014. The study survey was composed of 78 KAP questions. Factors associated with individual and household pandemic preparedness were analyzed.
Final study sample was 1,020 with a response rate of 45.9 %. Among the respondents, most of them believed personal hygiene and avoidance of avian contacts were effective in preventing H7N9 infections. The majority of respondents had satisfactory hand hygiene practices and avoided touching avian species but did not employ other preventive measures. Female, 25 years old or older, white collar workers, people with chronic diseases and people living in the city center tended to report better hygiene practices. The average State-Trait Anxiety Inventory score was 1.85, similar to that of the period during the first wave and at the start of the second wave of the H7N9 epidemic. Self-reported face masks wearing when having influenza-like illness in general population dropped from 92.4 % during H5N1 period in 2007 to 39.0 % in this study.
Hong Kong citizens show a low level of anxiety, misconceptions regarding the novel strains as well as gaps between perceived usefulness and practice of preventive measures towards influenza outbreaks. Educational campaigns and framing the issue to increase public and media awareness are crucial in preventing the current public fatigue towards outbreaks.
Disease surveillance allows prospective monitoring of patterns in disease incidence in the general community, specific institutions (e.g. hospitals, elderly care homes), and other important ...population subgroups. Surveillance activities are now routinely conducted in many developed countries and in certain easy-to-reach areas of the developing ones. However due to limited health resources, population in rural area that consisted of the most the vulnerable groups are not under surveillance. Cheaper alternative ways for disease surveillance were needed in resource-limited settings.
In this study, a syndromic surveillance system using disease specific absenteeism rates was established in 47 pre-schools with 1,417 students 3-6 y of age in a rural area of Kampot province, Cambodia. School absenteeism data were collected via short message service. Data collected between 1st January and 31st December 2012 was used for system evaluation for future potential use in larger scale. The system appeared to be feasible and acceptable in the rural study setting. Moderate correlation was found between rates of school absenteeism due to illness and the reference data on rates of attendance at health centers in persons <16 y (maximum cross-correlation coefficient = 0.231 at lag = -1 week).
School absenteeism data is pre-existing, easily accessible and requires minimum time and resources after initial development, and our results suggest that this system may be able to provide complementary data for disease surveillance, especially in resource limited settings where there is very little information on illnesses in the community and traditional surveillance systems are difficult to implement. An important next step is to validate the syndromic data with other forms of surveillance including laboratory data.
Multiple sources of influenza surveillance data are becoming more available; however integration of these data streams for situational awareness of influenza activity is less explored.
We applied ...multivariate time-series methods to sentinel outpatient and school absenteeism surveillance data in Hong Kong during 2004-2009. School absenteeism data and outpatient surveillance data experienced interruptions due to school holidays and changes in public health guidelines during the pandemic, including school closures and the establishment of special designated flu clinics, which in turn provided 'drop-in' fever counts surveillance data. A multivariate dynamic linear model was used to monitor influenza activity throughout epidemics based on all available data. The inferred level followed influenza activity closely at different times, while the inferred trend was less competent with low influenza activity. Correlations between inferred level and trend from the multivariate model and reference influenza activity, measured by the product of weekly laboratory influenza detection rates and weekly general practitioner influenza-like illness consultation rates, were calculated and compared with those from univariate models. Over the whole study period, there was a significantly higher correlation (ρ = 0.82, p≤0.02) for the inferred trend based on the multivariate model compared to other univariate models, while the inferred trend from the multivariate model performed as well as the best univariate model in the pre-pandemic and the pandemic period. The inferred trend and level from the multivariate model was able to match, if not outperform, the best univariate model albeit with missing data plus drop-in and drop-out of different surveillance data streams. An overall influenza index combining level and trend was constructed to demonstrate another potential use of the method.
Our results demonstrate the potential use of multiple streams of influenza surveillance data to promote situational awareness about the level and trend of seasonal and pandemic influenza activity.
In winter 2008, kindergartens and primary schools in Hong Kong were closed for 2 weeks after media coverage indicated that 3 children had died, apparently from influenza. We examined prospective ...influenza surveillance data before, during, and after the closure. We did not find a substantial effect on community transmission.
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