Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

Background

Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.

Methods

An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18–59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed.

Results

A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008–09 or 2009–10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000–01 to 2006–07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever.

Conclusions

A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.     

Inactivated trivalent seasonal influenza vaccine induces limited cross-reactive neutralizing antibody responses against 2009 pandemic and 1934 PR8 H1N1 strains

Background

In June 2009, we conducted a prospective study in Singapore on 51 individuals to determine their serologic responses before and following receipt of the 2009 Southern Hemisphere seasonal influenza vaccine.

Materials and methods

Paired serum samples were obtained before and 3–4 weeks after vaccination. Virus microneutralization assays were performed to quantify antibodies against A/Brisbane/59/2007 vaccine, pandemic H1N1-2009 and A/Puerto Rico/08/34 H1N1 strains.

Results

Post-vaccination, 43%, 12% and 24% of subjects displayed a 4-fold or greater rise in neutralizing antibody titers against the three strains, respectively. There was a positive correlation among individuals who showed increased titers to both pandemic H1N1-2009 and A/Puerto Rico/08/34 (p < 0.001). However, this correlation was not observed for A/Brisbane/59/2007 with either strain. The relative conservation and accessibility of predicted B-cell epitopes may explain the limited cross-reactivity of the antibodies directed against common H1N1 epitopes.

Conclusions

These results suggest that seasonal influenza vaccination confers a certain degree of cross-protection to other H1N1 strains. The correlation in cross-reactive antibody titers to A/Puerto Rico/08/34 and pandemic H1N1-2009 implies that previous exposure to pre-1957 H1N1 strains may confer some protection against the 2009 pandemic strain.     

Responses after one dose of a monovalent influenza A (H1N1) 2009 inactivated vaccine in Chinese population—A practical observation

Background

The globally large-scale immunization was the most important method of controlling the 2009 pandemic influenza.

Methods

We conducted an observational clinical trial, including 148 adults aged 18-60 years to evaluate the safety and immunogenicity of a licensed 2009 H1N1 influenza vaccine. All subjects received a single 15-μg dose of a monovalent, unadjuvanted inactivated vaccine. Antibody titers were measured by means of hemagglutinin-inhibition assays and neutralization assays based on Real-Time Cell Analyzer (RTCA) instruments at baseline, 7 days and 21 days after vaccination.

Results

Local and systemic reactions were respectively reported by 19.1% and 22.1% of subjects. All adverse events were mild to moderate in intensity, without any deaths or serious events. By day 21 after vaccination, hemagglutinin-inhibition antibody titers of 1:40 or more were achieved in 101 of 123 (82.1%) subjects and the geometric mean titers (GMTs) increased to 1:95.27. For neutralization assays, all subjects could provide the protection against wide influenza virus, with the GMT of 1:525.44. Moreover, the rates of seroconversion, as measured using hemagglutinin-inhibition assays and neutralization assays, were 73.98% and 91.87% of subjects, respectively.

Conclusions

A single 15-μg dose of a monovalent, unadjuvanted inactivated 2009 H1N1 influenza vaccine was well tolerated, and induced a protective immune response in the majority of subjects aged 18-60 years (clinical trials gov number, NCT01055990).     

Safety and immunogenicity of a trivalent single dose seasonal influenza vaccine containing pandemic A(H1N1) antigen in younger and elderly subjects: a phase III open-label single-arm study

Background

During the pandemic of the 2009 A(H1N1) influenza virus strain, 20-40% of the population in some areas were infected. Infection with A(H1N1) may be mild, with an average case fatality rate below 0.25%, but severe disease is not limited to patients with underlying medical conditions. Since A(H1N1) is expected to continue to circulate it is included in the seasonal influenza vaccines for the 2010-2011 winter season. We investigated the immunogenicity and safety of a preservative-free non-adjuvanted seasonal trivalent influenza vaccine.

Methods

We conducted a single center single-arm study involving 142 subjects (77 adults of 18-60 years and 65 subjects 61 years and above) to test the immunogenicity, safety, and tolerability of a trivalent split influenza vaccine. The vaccine contained 15 μg of hemagglutinin of each of the virus strains recommended for the 2010-2011 northern hemisphere winter season (A/California/7/2009 (H1N1)-like strain; A/Perth/16/2009 (H3N2)-like strain; B/Brisbane/60/2008-like strain) in a non-adjuvanted preservative-free formulation. Antibody response to each antigen was measured by hemagglutination inhibition (HI) 21 days after immunization. Subject diary cards and additional telephone interviews were used to assess the safety profile.

Results

By day 21 after the vaccination, seroconversion, or a 4-fold antibody increase in HI antibody titers, was detectable against A(H1N1) in 84% and 75% of younger and older adults, against A(H3N2) in 80% and 57%, and against the B influenza strain in 61% and 33%. HI antibody titers of 40 or more were observed against A(H1N1) in 99% and 90% of younger and older adults, against A(H3N2) in 100% and 90%, and against the B influenza strain in 91% and 78%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2), and B in 26%, 44% and 33%, respectively of the adults below 61 years and in 27%, 54% and 44% of the subjects of 61 years and above. Local and systemic reactions were more common in younger than in older subjects and the most frequently reported reactions were pain at the injection site (36%), myalgia (24%), and fatigue (15%). Five percent elderly subjects and 1% of younger subjects had mild or moderate unsolicited adverse events such as prolonged ecchymosis or night sweats that resolved within 7 days after vaccination.

Conclusions

This single dose trivalent seasonal influenza vaccine generated protective antibodies to all three viral strains and had an acceptable safety profile in both younger and older adults (ClinicalTrials.gov identifier: NCT01147081).     

Serologic survey of pandemic influenza A (H1N1 2009) in Beijing, China

Objective

To examine the frequency and distribution of antibodies against pandemic influenza A (H1N1 2009) [H1N1] in populations in Beijing and elucidate influencing factors.

Methods

In January 2010, a randomized serologic survey of pandemic influenza A (H1N1 2009) was carried out. Six districts that were randomly selected with a total of 4601 participants involved in the survey have their antibody level tested by hemagglutination inhibition assay.

Results

Among the 4601 participants, the overall seropositive rate for pandemic influenza A (H1N1 2009) antibodies was 31.7%. The seropositivity prevalence in participants who received the pandemic H1N1 vaccination was 60.9%. Only 53.1% of the pandemic influenza A (H1N1 2009) seropositive individuals who had not received the vaccination experienced respiratory tract infection symptoms. Multivariate logistic regression revealed that factors such as age, occupation, dwelling type, whether the participant's family included students in school, and the vaccination history with pandemic influenza A (H1N1 2009) were associated with antibody titers (p < 0.05).

Conclusions

Our data indicated that almost 30.0% of the residents had appropriate antibody titers against pandemic influenza A (H1N1 2009) in Beijing, and these titers may provide an immune barrier.     

H5N8 Highly Pathogenic Avian Influenza in the Republic of Korea: Epidemiology During the First Wave,from January Through July 2014

Objectives

This study describes the outbreaks of H5N8 highly pathogenic avian influenza (HPAI) in Korea during the first wave, from January 16, 2014 through July 25, 2014. Its purpose is to provide a better understanding of the epidemiology of H5N8 HPAI.

Methods

Information on the outbreak farms and HPAI positive wild birds was provided by the Animal and Plant Quarantine Agency. The epidemiological investigation sheets for the outbreak farms were examined.

Results

During the 7-month outbreak period (January–July 2014), H5N8 HPAI was confirmed in 212 poultry farms, 38 specimens from wild birds (stools, birds found dead or captured). Ducks were the most frequently infected poultry species (159 outbreak farms, 75.0%), and poultry in 67 (31.6%) outbreak farms was asymptomatic.

Conclusion

As in the previous four H5N1 epidemics of HPAI that occurred in Korea, this epidemic of H5N8 proved to be associated with migratory birds. Poultry farms in Korea can hardly be free from the risk of HPAI introduced via migratory birds. The best way to overcome this geographical factor is to reinforce biosecurity to prevent exposure of farms, related people, and poultry to the pathogen.     

Enhanced cross-lineage protection induced by recombinant H9N2 avian influenza virus inactivated vaccine

Background

Antigenic drift of H9N2 low pathogenic avian influenza viruses (AIV) may result in vaccination failure in the poultry industry and thus a cross-protective vaccine against H9N2 AIV is highly desirable.

Host immune response to A(H1N1)pdm09 vaccination and infection: a one-year prospective study on six cohorts of subjects

Background

The long-term immunogenicity after novel vaccine against A(H1N1)pdm09 administration or natural infection has not been well investigated.

Methods

Six cohorts of subjects were followed up for over one year: one-dose A(H1N1)pdm09 vaccine recipient, A(H1N1)pdm09-seasonal trivalent vaccine recipients in different orders, confirmed A(H1N1)pdm09 patients without vaccination, with previous A(H1N1)pdm09 or seasonal influenza vaccination. Peripheral blood mononuclear cells and sera samples were collected at baseline and month 1, 2, 3, 7 and 14 after vaccination (infection). The immunogenicity was determined by hemagglutination-inhibition (HI) and B cell enzyme-linked immunospot (ELISPOT) assays.

Results

Single dose of A(H1N1)pdm09 vaccine elicited antibody titer of greater than 1:40 in 40% adults for 1 year and mean live of this adequate antibody was determined as 8.35 months. In contrast, responses after natural infections had lower peaking level and a relatively longer antibody duration, with estimated mean lives of 11.8 months. Pre-vaccination with the seasonal flu vaccine led to a significant reduction in HI titer to A(H1N1)pdm09 one month after vaccination, while pre-vaccination with A(H1N1)pdm09 had no effect on seasonal influenza vaccination. Seasonal flu vaccination followed by A(H1N1)pdm09 infection elicited boosting effect on antibody response against A(H1N1)pdm09. A similar memory B cell response was elicited from both vaccination and infection by ELISPOT assay.

Conclusions

The long-term decay of immunity for A(H1N1)pdm09 vaccine and natural infection indicates the need of revaccination after the host lose protection acquired from either vaccination or infection. Prior infection, rather than the pre-vaccination with seasonal influenza could act on the host immunity to elicit boosting effect on the A(H1N1)pdm09.     

A live attenuated H5N2 prime- inactivated H5N1 boost vaccination induces influenza virus hemagglutinin stalk specific antibody responses

BackgroundThe emergence and spread of highly pathogenic avian influenza (H5N1) viruses have raised global concerns of a possible human pandemic, spurring efforts towards H5N1 influenza vaccine development and improvements in vaccine administration methods. We previously showed that a prime-boost vaccination strategy induces robust and broadly cross-reactive antibody responses against the hemagglutinin globular head domain. Here, we specifically measure antibodies against the conserved hemagglutinin stem region in serum samples obtained from the prior study to determine whether stalk-reactive antibodies can also be induced by the prime-boost regimen.MethodSerum samples collected from 60 participants before vaccination and on days 7, 28 and 90 following boosting vaccination were used in this study. 40 participants received two doses of live attenuated H5N2 vaccine (LAIV H5N2) followed by one dose of inactivated H5N1 vaccine a year later, while 20 participants received only the inactivated H5N1 vaccine. We tested these serum samples for stalk-reactive antibodies via enzyme-linked immunosorbent (ELISA) and microneutralization assays.ResultsStalk-specific antibody levels measured by both assays were found to be significantly higher in primed individuals than the unprimed group. ELISA results showed that 22.5, 70.5 and 57.5% of primed participants had a four-fold or more increase in stalk antibody titers on days 7, 28 and 90 following boosting vaccination, respectively; whereas the unprimed group had no increase. Peak geometric mean titers (GMT) for stalk antibodies in the LAIV H5N2 experienced group (24,675 [95% CI; 19,531–31,174]) were significantly higher than those who received only the inactivated H5N1 vaccine (8877 [7140–11,035]; p < 0·0001). Moreover, stalk antibodies displaying neutralizing activity also increased in primed participants, but not in the unprimed group.ConclusionOur finding emphasizes the importance of prime-boost vaccination for effectively inducing stalk antibodies, which is an attractive target for developing vaccines that induce stalk reactive antibodies.     

Ambient Influenza and Avian Influenza Virus during Dust Storm Days and Background Days

Background

The spread of influenza and highly pathogenic avian influenza (H5N1) presents a significant threat to human health. Avian influenza outbreaks in downwind areas of Asian dust storms (ADS) suggest that viruses might be transported by dust storms.

Objectives

We developed a technique to measure ambient influenza and avian influenza viruses. We then used this technique to measure concentrations of these viruses on ADS days and background days, and to assess the relationships between ambient influenza and avian influenza viruses, and air pollutants.

Methods

A high-volume air sampler was used in parallel with a filter cassette to evaluate spiked samples and unspiked samples. Then, air samples were monitored during ADS seasons using a filter cassette coupled with a real-time quantitative polymerase chain reaction (qPCR) assay. Air samples were monitored during ADS season (1 January to 31 May 2006).

Results

We successfully quantified ambient influenza virus using the filtration/real-time qPCR method during ADS days and background days. To our knowledge, this is the first report describing the concentration of influenza virus in ambient air. In both the spiked and unspiked samples, the concentration of influenza virus sampled using the filter cassette was higher than that using the high-volume sampler. The concentration of ambient influenza A virus was significantly higher during the ADS days than during the background days.

Conclusions

Our data imply the possibility of long-range transport of influenza virus.     

Clinico-Epidemiological Profile,Pandemic Influenza A H1N1/2009 and Seasonal Influenza,August 2009-March 2013, Himachal Pradesh,India

Background:

Novel influenza A (H1N1) virus emerged in April, 2009, spread rapidly to become pandemic by June, 2009. Objective: To study the clinco-epidemiological profile of pH1N1and seasonal influenza (SI) from 2009 to 2013.

Materials and Methods

Retrospective, hospital-based study was done by reviewing medical records for collecting demographic and clinical profile of the study samples.

Result:

Out of 969 samples, positivity and case fatality for pH1N1 and SI was 9.39 and 20.87% vs 11.76 and 7.89%, respectively. Among pH1N1and SI, sex distribution, mean age, and age group involved were 54.95% females, 37.10 years, and 20-29 years (23.08%) vs 43.86% females, 40.32 years, and 20-29 years (22.81%), respectively. Mortality shift was observed from younger to older and healthier, 75% to comorbid, 100% from 2009-2010 to 2012-13 for pH1N1.

Conclusion:

We observed seasonal variation, cocirculation, similar clinical features, decreased virulence, and community spread with respect to pH1N1 and SI from 2009-2013.     

Response to 2009 pandemic and seasonal influenza vaccines co-administered to HIV-infected and HIV-uninfected former drug users living in a rehabilitation community in Italy

Background

2009 A(H1N1) pandemic influenza vaccination was recommended as a priority to essential workers and high-risk individuals, including HIV-infected patients and people living in communities.

Methods

HIV-infected and HIV-uninfected former drug-users (18-60 years old) living in a rehabilitation community (San Patrignano, Italy) received one dose of a MF59-adjuvanted 2009 pandemic influenza vaccine and one dose of a 2009-2010 seasonal trivalent inactivated influenza vaccine (containing A/Brisbane/59/2007(H1N1), A/Brisbane/10/2007(H3N2), B/Brisbane/60/2008) simultaneously. Antibodies against each vaccine antigen were determined at the time of vaccination and one and six months post-vaccination by hemagglutination-inhibition test.

Results

49 HIV-infected and 60 HIV-uninfected subjects completed the study. Most (98%) HIV-infected participants were on antiretroviral treatment, the median CD4+ cell count was 350 (IQR 300) cells/μl and viremia was suppressed in 91.8% of cases. One month post-vaccination, no significant changes in immune-virological parameters were observed. One month post-vaccination, the immune responses to both pandemic and seasonal vaccine met the EMA-CPMP criteria for immunogenicity of influenza vaccines in both HIV-infected and HIV-uninfected subjects. No difference in vaccine responses was observed between the two groups. Six months after vaccination, the percentages of vaccinees with antibody titres ≥1:40 and antibody geometric mean titres significantly decreased in both groups. However, they were significantly lower in HIV-infected than in HIV-uninfected vaccinees. In subjects who had been primed to seasonal influenza the year before (through either vaccination or natural infection), levels of antibodies against 2009 A(H1N1) were higher than those measured in unprimed subjects, both one month and six months post-vaccination.

Conclusions

The co-administration of a single dose of 2009 pandemic MF59-adjuvanted influenza vaccine with a seasonal vaccine provided a protective immune response in both HIV-infected and HIV-uninfected individuals. Subjects who had been primed to seasonal influenza in the year preceding the pandemic had a more vigorous and long-lasting antibody response to 2009 pandemic vaccine.     

Neutralizing antibody but not hemagglutination antibody provides accurate evaluation for protective immune response to H5N1 avian influenza virus in vaccinated rabbits

In order to develop an animal model and an assay method to evaluate protective immune response to H5N1 avian influenza vaccination, H5N1 avian influenza vaccine was prepared. New Zealand rabbits were assigned to receive two doses of vaccine with different hemagglutinin (HA) dosage. The sera from vaccinated rabbits was evaluated to determine antibody titer and specificity using different tested methods including hemagglutination inhibition assay (HI), neutralizing assay (NT), cross-HI assay, cross-single immunodiffusion assay and cross-neutralization assay. The titer of HI antibody from rabbits immunized with different doses of HA were no less than 1:40 among groups 14 days after the first immunization. Whereas the NT antibody titer was less than 1:10 among groups 14 days after the first immunization. NT antibodies can be detected 14 days after the second immunization in rabbits immunized at HA doses higher than 6 μg, and the NT antibody titers were equal to or higher than 1:40. A good concentration-dependent NT antibody response can be detected in the vaccinated rabbits 14 days after the second immunization, and in contrast, no concentration-dependent relationship can be seen for HA antibody. The cross-HI test showed sera from vaccinated rabbits could cross react with influenza A H5N1 virus with the titers higher than 1:40. No cross reaction among different types (influenza A/H1N1 virus, influenza A/H3N2 virus, influenza B virus and influenza A/H5N1 virus) can be detected in the sera using the single immunodiffusion assay and using NT antibody test. This showed NT antibody test was demonstrated as a more accurate assay method for evaluating vaccination and quality of the vaccine than HI antibody test.     

Contact and communication with healthcare providers regarding influenza vaccination during the 2009-2010 H1N1 pandemic

Objective

The existence of two vaccines—seasonal and pandemic—created the potential for confusion and misinformation among consumers during the 2009-2010 vaccination season. We measured the frequency and nature of influenza vaccination communication between healthcare providers and adults for both seasonal and 2009 influenza A(H1N1) vaccination and quantified its association with uptake of the two vaccines.

Methods

We analyzed data from 4040 U.S. adult members of a nationally representative online panel surveyed between March 4th and March 24th, 2010. We estimated prevalence rates and adjusted associations between vaccine uptake and vaccination-related communication between patients and healthcare providers using bivariate probit models.

Results

64.1% (95%-CI: 61.5%-66.6%) of adults did not receive any provider-issued influenza vaccination recommendation. Adults who received a provider-issued vaccination recommendation were 14.1 (95%-CI: − 2.4 to 30.6) to 32.1 (95%-CI: 24.3-39.8) percentage points more likely to be vaccinated for influenza than adults without a provider recommendation, after adjusting for other characteristics associated with vaccination.

Conclusions

Influenza vaccination communication between healthcare providers and adults was relatively uncommon during the 2009-2010 pandemic. Increased communication could significantly enhance influenza vaccination rates.     

A prospective,double-blind,randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis

Objective

To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).

Predictors of acceptance of H1N1 influenza vaccination by FDNY firefighters and EMS workers

Background

There is a widely recognized need for vaccination of health care workers (HCWs). We undertook this study to assess the 2009-2010 H1N1 vaccination rates in ∼14,000 firefighters and emergency medical service (EMS) workers at the Fire Department of New York (FDNY) and to determine predictors of H1N1 vaccine acceptance.

Methods

After 9/11/01, FDNY developed a bio-preparedness drill where units are dispatched to FDNY-BIOPOD (biologic points of distributions) for rapid distribution of medications/vaccines in the event of a biological disaster. Since 2005, FDNY offers free, voluntary seasonal influenza vaccination during routine medical monitoring/treatment examinations and at FDNY-BIOPOD. In 2009, FDNY-BIOPOD instead offered the H1N1 vaccine. We report on FDNY H1N1 vaccination rates and on predictors of acceptance using bivariate and multivariable techniques.

Results

Overall, 10,612 (77%) FDNY workers were offered H1N1 vaccination, of whom 5831 (55%) accepted. Acceptance was 57.2% during FDNY-BIOPOD compared with 34.4% during medical monitoring/treatment exams (p = 0.0001). Workers who accepted prior seasonal influenza vaccinations were 4 times more likely to accept H1N1 vaccination (AOR = 4.4, CI₉₅ = 4.0-4.8).

Conclusion

FDNY offered H1N1 vaccination to 77% of its workforce during the 2009-2010 season. Prior seasonal vaccine acceptance and vaccination in a group setting such as FDNY-BIOPOD dramatically increased acceptance of the H1N1 vaccine. However, within a voluntary program, additional strategies are needed to further increase vaccine acceptance in first responders and other HCWs.     

Using Surveillance Data to Identify Risk Factors for Severe H1N1 in First Nations

Objective

We sought to measure from surveillance data the effect of proximity to an urban centre (rurality) and other risk factors, (e.g., age, residency on a FN reservation, and pandemic wave) on hospitalization and intensive care unit admission for severe influenza.

Introduction

Research has shown that Canadian First Nation (FN) populations were disproportionately affected by the 2009 H1N1 influenza pandemic. However, the mechanisms for the disproportionate outcomes are not well understood. Possibilities such as healthcare access, infrastructure and housing issues, and pre-existing comorbidities have been suggested. We estimated the odds of hospitalization and intensive care unit admission for cases of H1N1 influenza among FN living in Manitoba, Canada, to determine the effect of location of residency and other factors on disease outcomes during the 2009 H1N1 pandemic.

Methods

We obtained surveillance data on laboratory confirmed cases of pandemic H1N1 influenza from the province of Manitoba. These data described demographic characteristics, residence location, and dates of hospital and ICU admission. We measured the rurality of each case using a pre-exiting scale (Rambeau & Todd, 2000). We tabulated the number of hospitalizations (and ICU admissions) stratified first by reservation residency and second by rurality and calculated unadjusted odds ratios. We then used logistic regression to calculate the odds of hospitalization given infection (and the odds of ICU admission given hospitalization), adjusting for age, reservation residency, rurality, and pandemic wave. We also investigated the effect of rurality and reserve residency on time to hospitalization from infection.

Results

FN individuals diagnosed with influenza and living on-reserve were more likely to be hospitalized than those living off-reserve, even after controlling for the effects of rurality (OR: 2.16, 95% CI: 1.15, 4.05). FN living in rural areas were hospitalized more frequently and experienced longer delays between infection and hospitalization than FN residing in more urban areas. Rurality and reserve residency had less effect on ICU admissions once an individual was hospitalized.

Conclusions

While it is established that FN individuals had disproportionately high rates of severe outcomes from H1N1, the causal mechanisms at work are not well understood. Reasonable possibilities include barriers to healthcare access, lack of proper housing and infrastructure, and pre-existing comorbidities. This research using surveillance data suggests that geographic location has an effect on healthcare access, including both on vs. off reserve residency as well as rurality.