Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

Background

The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

Methods

During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member.

Results

In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03).

Conclusion

The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.     

Antiviral Treatment among Older Adults Hospitalized with Influenza, 2006-2012

Objective

To describe antiviral use among older, hospitalized adults during six influenza seasons (2006—2012) in Davidson County, Tennessee, USA.

Methods

Among adults ≥50 years old hospitalized with symptoms of respiratory illness or non-localizing fever, we collected information on provider-initiated influenza testing and nasal/throat swabs for influenza by RT-PCR in a research laboratory, and calculated the proportion treated with antivirals.

Results

We enrolled 1753 adults hospitalized with acute respiratory illness. Only 26% (457/1753) of enrolled patients had provider-initiated influenza testing. Thirty-eight patients had a positive clinical laboratory test, representing 2.2% of total patients and 8.3% of tested patients. Among the 38 subjects with clinical laboratory-confirmed influenza, 26.3% received antivirals compared to only 4.5% of those with negative clinical influenza tests and 0.7% of those not tested (p<0.001). There were 125 (7.1%) patients who tested positive for influenza in the research laboratory. Of those with research laboratory-confirmed influenza, 0.9%, 2.7%, and 2.8% received antivirals (p=.046) during pre-pandemic, pandemic, and post-pandemic influenza seasons, respectively. Both research laboratory-confirmed influenza (adjusted odds ratio [AOR] 3.04 95%CI 1.26-7.35) and clinical laboratory-confirmed influenza (AOR 3.05, 95%CI 1.07-8.71) were independently associated with antiviral treatment. Severity of disease, presence of a high-risk condition, and symptom duration were not associated with antiviral use.

Conclusions

In urban Tennessee, antiviral use was low in patients recognized to have influenza by the provider as well as those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza.     

School absenteeism as an adjunct surveillance indicator: experience during the second wave of the 2009 H1N1 pandemic in Quebec, Canada

Background

A school absenteeism surveillance system was implemented in the province of Quebec, Canada during the second wave of the 2009 H1N1pandemic. This paper compares this surveillance approach with other available indicators.

Method

All (3432) elementary and high schools from Quebec were included. Each school was required to report through a web-based system any day where the proportion of students absent for influenza-like illness (ILI) exceeded 10% of current school enrolment.

Results

Between October 18 and December 12 2009, 35.6% of all schools met the 10% absenteeism threshold. This proportion was greater in elementary compared to high schools (40% vs 19%) and in smaller compared to larger schools (44% vs 22%). The maximum absenteeism rate was reached the first day of reporting or within the next two days in 55% and 31% of schools respectively. The first reports and subsequent peak in school absenteeism provincially preceded the peak in paediatric hospitalization by two and one weeks, respectively. Trends in school surveillance otherwise mirrored other indicators.

Conclusion

During a pandemic, school outbreak surveillance based on a 10% threshold appears insufficient to trigger timely intervention within a given affected school. However, school surveillance appears well-correlated and slightly anticipatory compared to other population indicators. As such, school absenteeism warrants further evaluation as an adjunct surveillance indicator whose overall utility will depend upon specified objectives, and other existing capacity for monitoring and response.     

School-Located Influenza Vaccination Reduces Community Risk for Influenza and Influenza-Like Illness Emergency Care Visits

Background

School-located influenza vaccination (SLIV) programs can substantially enhance the sub-optimal coverage achieved under existing delivery strategies. Randomized SLIV trials have shown these programs reduce laboratory-confirmed influenza among both vaccinated and unvaccinated children. This work explores the effectiveness of a SLIV program in reducing the community risk of influenza and influenza-like illness (ILI) associated emergency care visits.

Methods

For the 2011/12 and 2012/13 influenza seasons, we estimated age-group specific attack rates (AR) for ILI from routine surveillance and census data. Age-group specific SLIV program effectiveness was estimated as one minus the AR ratio for Alachua County versus two comparison regions: the 12 county region surrounding Alachua County, and all non-Alachua counties in Florida.

Results

Vaccination of ∼50% of 5–17 year-olds in Alachua reduced their risk of ILI-associated visits, compared to the rest of Florida, by 79% (95% confidence interval: 70, 85) in 2011/12 and 71% (63, 77) in 2012/13. The greatest indirect effectiveness was observed among 0–4 year-olds, reducing AR by 89% (84, 93) in 2011/12 and 84% (79, 88) in 2012/13. Among all non-school age residents, the estimated indirect effectiveness was 60% (54, 65) and 36% (31, 41) for 2011/12 and 2012/13. The overall effectiveness among all age-groups was 65% (61, 70) and 46% (42, 50) for 2011/12 and 2012/13.

Conclusion

Wider implementation of SLIV programs can significantly reduce the influenza-associated public health burden in communities.     

Effectiveness of A(H1N1)pdm09 Influenza Vaccine in Adults Recommended for Annual Influenza Vaccination

Introduction

Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness.

Methods

VE against influenza and/or pneumonia was assessed in the cohort study (n>25000), and vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza was assessed in a matched case-control study (16 pairs). Odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated by using multivariate logistic regression; vaccine effectiveness was estimated as (1-odds ratio)*100%.

Results

Vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia was 98% (84–100%) and 33% (2–54%) respectively. The vaccine did not prevent influenza and/or pneumonia in 18–59 years old subjects, and was 49% (16–69%) effective in 60 years and older subjects.

Conclusions

Even though we cannot entirely rule out that selection bias, residual confounding and/or cross-protection has played a role, the present results indicate that the MF59-adjuvanted A(H1N1)pdm09 influenza vaccine has been effective in preventing laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia, the latter notably in 60 years and older subjects.     

Effects of Green Tea Gargling on the Prevention of Influenza Infection in High School Students: A Randomized Controlled Study

Background

The anti-influenza virus activity of green tea catechins has been demonstrated in experimental studies, but clinical evidence has been inconclusive. School-aged children play an important role in the infection and spread of influenza in the form of school-based outbreaks. Preventing influenza infection among students is essential for reducing the frequency of epidemics and pandemics. As a non-pharmaceutical intervention against infection, gargling is also commonly performed in Asian countries but has not yet been extensively studied.

Methods and Findings

A randomized, open label, 2-group parallel study of 757 high school students (15 to 17 years of age) was conducted for 90 days during the influenza epidemic season from December 1st, 2011 to February 28th, 2012, in 6 high schools in Shizuoka Prefecture, Japan. The green tea gargling group gargled 3 times a day with bottled green tea, and the water gargling group did the same with tap water. The water group was restricted from gargling with green tea. The primary outcome measure was the incidence of laboratory-confirmed influenza using immunochromatographic assay for antigen detection. 757 participants were enrolled and 747 participants completed the study (384 in the green tea group and 363 in the water group). Multivariate logistic regression indicated no significant difference in the incidence of laboratory-confirmed influenza between the green tea group (19 participants; 4.9%) and the water group (25 participants; 6.9%) (adjusted OR, 0.69; 95%CI, 0.37 to 1.28; P = 0.24). The main limitation of the study is the adherence rate among high school students was lower than expected.

Conclusions

Among high school students, gargling with green tea three times a day was not significantly more efficacious than gargling with water for the prevention of influenza infection. In order to adequately assess the effectiveness of such gargling, additional large-scale randomized studies are needed.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01225770","term_id":"NCT01225770"}}NCT01225770     

Modeling Seasonal Influenza Outbreak in a Closed College Campus: Impact of Pre-Season Vaccination,In-Season Vaccination and Holidays/Breaks

Background

College and university students experience substantial morbidity from influenza and influenza-like illness, and they can benefit substantially from vaccination. Public health authorities encourage vaccination not only before the influenza season but also into and even throughout the influenza season. We conducted the present study to assess the impact of various vaccination strategies including delayed (i.e., in-season) vaccination on influenza outbreaks on a college campus.

Methods/Findings

We used a Susceptible → Infected → Recovered (SIR) framework for our mathematical models to simulate influenza epidemics in a closed, college campus. We included both students and faculty/staff in the model and derived values for the model parameters from the published literature. The values for key model parameters were varied to assess the impact on the outbreak of various pre-season and delayed vaccination rates; one-way sensitivity analyses were conducted to test the sensitivity of the model outputs to changes in selected parameter values. In the base case, with a pre-season vaccination rate of 20%, no delayed vaccination, and 1 student index case, the total attack rate (total percent infected, TAR) was 45%. With higher pre-season vaccination rates TARs were lower. Even if vaccinations were given 30 days after outbreak onset, TARs were still lower than the TAR of 69% in the absence of vaccination. Varying the proportions of vaccinations given pre-season versus delayed until after the onset of the outbreak gave intermediate TAR values. Base case outputs were sensitive to changes in infectious contact rates and infectious periods and a holiday/break schedule.

Conclusion

Delayed vaccination and holidays/breaks can be important adjunctive measures to complement traditional pre-season influenza vaccination for controlling and preventing influenza in a closed college campus.     

Influenza surveillance among outpatients and inpatients in Morocco, 1996-2009

Background

There is limited information about the epidemiology of influenza in Africa. We describe the epidemiology and seasonality of influenza in Morocco from 1996 to 2009 with particular emphasis on the 2007–2008 and 2008–2009 influenza seasons. Successes and challenges of the enhanced surveillance system introduced in 2007 are also discussed.

Methods

Virologic sentinel surveillance for influenza virus was initiated in Morocco in 1996 using a network of private practitioners that collected oro-pharyngeal and naso-pharyngeal swabs from outpatients presenting with influenza-like-illness (ILI). The surveillance network expanded over the years to include inpatients presenting with severe acute respiratory illness (SARI) at hospitals and syndromic surveillance for ILI and acute respiratory infection (ARI). Respiratory samples and structured questionnaires were collected from eligible patients, and samples were tested by immunofluorescence assays and by viral isolation for influenza viruses.

Results

We obtained a total of 6465 respiratory specimens during 1996 to 2009, of which, 3102 were collected during 2007–2009. Of those, 2249 (72%) were from patients with ILI, and 853 (27%) were from patients with SARI. Among the 3,102 patients, 98 (3%) had laboratory-confirmed influenza, of whom, 85 (87%) had ILI and 13 (13%) had SARI. Among ILI patients, the highest proportion of laboratory-confirmed influenza occurred in children less than 5 years of age (3/169; 2% during 2007–2008 and 23/271; 9% during 2008–2009) and patients 25–59 years of age (8/440; 2% during 2007–2009 and 21/483; 4% during 2008–2009). All SARI patients with influenza were less than 14 years of age. During all surveillance years, influenza virus circulation was seasonal with peak circulation during the winter months of October through April.

Conclusion

Influenza results in both mild and severe respiratory infections in Morocco, and accounted for a large proportion of all hospitalizations for severe respiratory illness among children 5 years of age and younger.     

Predictive Validation of an Influenza Spread Model

Background

Modeling plays a critical role in mitigating impacts of seasonal influenza epidemics. Complex simulation models are currently at the forefront of evaluating optimal mitigation strategies at multiple scales and levels of organization. Given their evaluative role, these models remain limited in their ability to predict and forecast future epidemics leading some researchers and public-health practitioners to question their usefulness. The objective of this study is to evaluate the predictive ability of an existing complex simulation model of influenza spread.

Methods and Findings

We used extensive data on past epidemics to demonstrate the process of predictive validation. This involved generalizing an individual-based model for influenza spread and fitting it to laboratory-confirmed influenza infection data from a single observed epidemic (1998–1999). Next, we used the fitted model and modified two of its parameters based on data on real-world perturbations (vaccination coverage by age group and strain type). Simulating epidemics under these changes allowed us to estimate the deviation/error between the expected epidemic curve under perturbation and observed epidemics taking place from 1999 to 2006. Our model was able to forecast absolute intensity and epidemic peak week several weeks earlier with reasonable reliability and depended on the method of forecasting-static or dynamic.

Conclusions

Good predictive ability of influenza epidemics is critical for implementing mitigation strategies in an effective and timely manner. Through the process of predictive validation applied to a current complex simulation model of influenza spread, we provided users of the model (e.g. public-health officials and policy-makers) with quantitative metrics and practical recommendations on mitigating impacts of seasonal influenza epidemics. This methodology may be applied to other models of communicable infectious diseases to test and potentially improve their predictive ability.     

Adaptive Vaccination Strategies to Mitigate Pandemic Influenza: Mexico as a Case Study

Background

We explore vaccination strategies against pandemic influenza in Mexico using an age-structured transmission model calibrated against local epidemiological data from the Spring 2009 A(H1N1) pandemic.

Methods and Findings

In the context of limited vaccine supplies, we evaluate age-targeted allocation strategies that either prioritize youngest children and persons over 65 years of age, as for seasonal influenza, or adaptively prioritize age groups based on the age patterns of hospitalization and death monitored in real-time during the early stages of the pandemic. Overall the adaptive vaccination strategy outperformed the seasonal influenza vaccination allocation strategy for a wide range of disease and vaccine coverage parameters.

Conclusions

This modeling approach could inform policies for Mexico and other countries with similar demographic features and vaccine resources issues, with regard to the mitigation of the S-OIV pandemic. We also discuss logistical issues associated with the implementation of adaptive vaccination strategies in the context of past and future influenza pandemics.     

Profiling of Humoral Response to Influenza A(H1N1)pdm09 Infection and Vaccination Measured by a Protein Microarray in Persons with and without History of Seasonal Vaccination

Background

The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood.

Methods

We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent MF59-adjuvanted vaccine (Focetria®, Novartis), with and without a history of seasonal influenza vaccination. Antibodies were measured by hemagglutination inhibition (HI) assay for influenza A(H1N1)pdm09 and by protein microarray (PA) using the HA1 subunit for seven recent and historic H1, H2 and H3 influenza viruses, and three avian influenza viruses. Serum samples for the infection group were taken at the moment of collection of the diagnostic sample, 10 days and 30 days after onset of influenza symptoms. For the vaccination group, samples were drawn at baseline, 3 weeks after the first vaccination and 5 weeks after the second vaccination.

Results

We showed that subjects with a history of seasonal vaccination generally exhibited higher baseline titers for the various HA1 antigens than subjects without a seasonal vaccination history. Infection and pandemic influenza vaccination responses in persons with a history of seasonal vaccination were skewed towards historic antigens.

Conclusions

Seasonal vaccination is of significant influence on the antibody response to subsequent infection and vaccination, and further research is needed to understand the effect of annual vaccination on protective immunity.     

Implementation of Non-Pharmaceutical Interventions by New York City Public Schools to Prevent 2009 Influenza A

Introduction

Children are important transmitters of influenza in the community and a number of non-pharmaceutical interventions (NPIs), including hand washing and use of hand sanitizer, have been recommended to mitigate the transmission of influenza, but limited information is available regarding schools'' ability to implement these NPIs during an influenza outbreak. We evaluated implementation of NPIs during fall 2009 in response to H1N1 pandemic influenza (pH1N1) by New York City (NYC) public schools.

Methods

From January 25 through February 9, 2010, an online survey was sent to all the 1,632 NYC public schools and principals were asked to participate in the survey or to designate a school nurse or other school official with knowledge of school policies and characteristics to do so.

Results

Of 1,633 schools, 376(23%) accessed and completed the survey. Nearly all respondents (99%) implemented at least two NPIs. Schools that had a Flu Response Team (FRT) as a part of school emergency preparedness plan were more likely to implement the NPI guidelines recommended by NYC public health officials than schools that did not have a FRT. Designation of a room for isolating ill students, for example, was more common in schools with a FRT (72%) than those without (53%) (p<0.001).

Conclusions

Implementing an NPI program in a large school system to mitigate the effects of an influenza outbreak is feasible, but there is potential need for additional resources in some schools to increase capacity and adherence to all recommendations. Public health influenza-preparedness plans should include school preparedness planning and FRTs.     

Estimating the Effectiveness of Early Control Measures through School Absenteeism Surveillance in Observed Outbreaks at Rural Schools in Hubei,China

Background

School absenteeism is a common data source in syndromic surveillance, which allows for the detection of outbreaks at an early stage. Previous studies focused on its correlation with other data sources. In this study, we evaluated the effectiveness of control measures based on early warning signals from school absenteeism surveillance in rural Chinese schools.

Methods

A school absenteeism surveillance system was established in all 17 primary schools in 3 adjacent towns in the Chinese region of Hubei. Three outbreaks (varicella, mumps, and influenza-like illness) were detected and controlled successfully from April 1, 2012, to January 15, 2014. An impulse susceptible-exposed-infectious-recovered model was used to fit the epidemics of these three outbreaks. Moreover, it simulated the potential epidemics under interventions resulting from traditional surveillance signals. The effectiveness of the absenteeism-based control measures was evaluated by comparing the simulated datasets.

Results

The school absenteeism system generated 52 signals. Three outbreaks were verified through epidemiological investigation. Compared to traditional surveillance, the school absenteeism system generated simultaneous signals for the varicella outbreak, but 3 days in advance for the mumps outbreak and 2–4 days in advance for the influenza-like illness outbreak. The estimated excess protection rates of control measures based on early signals were 0.0%, 19.0–44.1%, and 29.0–37.0% for the three outbreaks, respectively.

Conclusions

Although not all outbreak control measures can benefit from early signals through school absenteeism surveillance, the effectiveness of early signal-based interventions is obvious. School absenteeism surveillance plays an important role in reducing outbreak spread.     

Stabilization of Influenza Vaccine Enhances Protection by Microneedle Delivery in the Mouse Skin

Background

Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.

Methodology/Principal Findings

Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.

Conclusions/Significance

The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.     

Influenza Pneumonia Surveillance among Hospitalized Adults May Underestimate the Burden of Severe Influenza Disease

Background

Studies seeking to estimate the burden of influenza among hospitalized adults often use case definitions that require presence of pneumonia. The goal of this study was to assess the extent to which restricting influenza testing to adults hospitalized with pneumonia could underestimate the total burden of hospitalized influenza disease.

Methods

We conducted a modelling study using the complete State Inpatient Databases from Arizona, California, and Washington and regional influenza surveillance data acquired from CDC from January 2003 through March 2009. The exposures of interest were positive laboratory tests for influenza A (H1N1), influenza A (H3N2), and influenza B from two contiguous US Federal Regions encompassing the study area. We identified the two outcomes of interest by ICD-9-CM code: respiratory and circulatory hospitalizations, as well as critical illness hospitalizations (acute respiratory failure, severe sepsis, and in-hospital death). We linked the hospitalization datasets with the virus surveillance datasets by geographic region and month of hospitalization. We used negative binomial regression models to estimate the number of influenza-associated events for the outcomes of interest. We sub-categorized these events to include all outcomes with or without pneumonia diagnosis codes.

Results

We estimated that there were 80,834 (95% CI 29,214–174,033) influenza-associated respiratory and circulatory hospitalizations and 26,760 (95% CI 14,541–47,464) influenza-associated critical illness hospitalizations. When a pneumonia diagnosis was excluded, the estimated number of influenza-associated respiratory and circulatory hospitalizations was 24,816 (95% CI 6,342–92,624). The estimated number of influenza-associated critical illness hospitalizations was 8,213 (95% CI 3,764–20,799). Around 30% of both influenza-associated respiratory and circulatory hospitalizations, as well as influenza-associated critical illness hospitalizations did not have pneumonia diagnosis codes.

Conclusions

Surveillance studies which only consider hospitalizations that include a diagnosis of pneumonia may underestimate the total burden of influenza hospitalizations.