Influenza Illness In Adults Research Articles

Impact of HIV on the burden and severity of influenza illness in adults in Malawi: a cohort and case-control study

BackgroundAlthough annual vaccination of at-risk groups is the cornerstone of influenza prevention in many developed settings, it is unavailable in most sub-Saharan African countries. Since 70% of the estimated total population of HIV-infected persons reside in these countries, they might be an important group for whom policy makers could target influenza control strategies. This study aimed to determine the impact of HIV on the burden and severity of influenza illness in adults in a setting with high HIV prevalence. MethodsAt the Queen Elizabeth Central Hospital, Blantyre, Malawi, we conducted a prospective cohort study between April 1, 2013, and March 31, 2015, to compare influenza incidence between HIV-infected and HIV-uninfected adults. We also did a case-control study of adults with mild influenza (influenza-like illness) and severe influenza (admission to hospital with lower respiratory tract infection) to explore risk factors for severe influenza presentation. Poisson and unconditional logistic regression models, respectively, were performed. Findings608 adults were enrolled in the cohort study, of whom 360 (59%) were HIV-reactive (median CD4 count 390 cells per μL [IQR 244–547]). 24 (11%) of 229 episodes of influenza-like illness in HIV-infected and five (4%) of 119 in HIV-uninfected adults were influenza PCR positive (incidence rates 46 vs 15 per 1000 person-years, incidence rate ratio 2·75 [95% CI 1·02–7·44]). In the case-control study, 56 (11%) of 518 patients admitted with lower respiratory tract infection and 88 (14%) of 642 patients with influenza-like illness were influenza PCR positive. HIV prevalence in the influenza-positive cases and controls were 70% (39/56) and 30% (26/88), respectively. HIV was a significant risk factor for severe influenza presentation (odds ratio 4·98 [95% CI 2·09–11·88], population attributable fraction 57%). There was a tendency towards increased incidence and severity in individuals with CD4 count less than 200 cells per μL. InterpretationIn a setting with high HIV prevalence, HIV infection is an important risk factor for acquiring influenza infection and for severe presentation. Individuals with advanced immunosuppression can be particularly vulnerable. These results present a strong case to policy makers to consider targeted vaccination policy in HIV-infected adults in sub-Saharan Africa. However, the optimum mechanism for vaccine introduction and evaluation in overstretched health systems will need to be determined. FundingWellcome Trust.

Improved immunogenicity of high-dose influenza vaccine compared to standard-dose influenza vaccine in adult oncology patients younger than 65 years receiving chemotherapy: A pilot randomized clinical trial

PurposePatients undergoing chemotherapy often fail to develop robust responses to influenza vaccination. Compared to standard-dose influenza vaccine (SD), high-dose influenza vaccine (HD) has shown improved immunogenicity and protection against influenza illness in adults 65 years and older. This study compared the immunogenicity and tolerability of HD to SD in adults younger than 65 years of age receiving chemotherapy. MethodsThis double-blind study randomized patients receiving chemotherapy to vaccination with either SD or HD influenza vaccine. Hemagglutination inhibition assays (HAI) were performed prior to and 4 weeks after vaccination. HAI were summarized as geometric mean titers (GMT), seroconversion rates, and seroprotection rates. ResultsA total of 105 subjects were enrolled in the trial (51 received SD and 54 received HD). Subjects were well matched for demographic and medical conditions. Both vaccines were well tolerated with no SAEs. Of the 100 subjects with evaluable data, seroconversion rates for all 3 influenza antigens & post-vaccination GMTs for H3N2 & B strains were significantly improved with HD compared to SD. Seroprotection was excellent and equivalent in both groups. ConclusionsTrivalent high-dose influenza vaccine can be safely administered to patients receiving chemotherapy with improved immunogenicity and seroconversion compared to standard-dose vaccine. Post-vaccination seroprotection rates were similar in both groups. A larger study is needed to show clinical benefits with HD in this population.This study was registered at ClinicalTrials.gov as NCT01666782.

Efficacy and immunogenicity of high-dose influenza vaccine in older adults by age, comorbidities, and frailty

BackgroundA randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest. MethodsDouble-blind, randomized, active-controlled, multicenter trial. Adults ≥65 years were randomized 1:1 to receive IIV-HD or IIV-SD and followed for 6–8 months postvaccination for the occurrence of influenza. One third of participants were randomly selected to provide sera for measurement of hemagglutination inhibition antibody (HAI) titers. Efficacy (IIV-HD vs. IIV-SD) against laboratory-confirmed, protocol-defined influenza-like illness (PD-ILI) and HAI geometric mean titer (GMT) ratios (IIV-HD/IIV-SD) were evaluated by age, and number of high-risk comorbid and frailty conditions. ResultsEfficacy (95% confidence intervals) of IIV-HD relative to IIV-SD against laboratory-confirmed PD-ILI was 19.7% (0.4%; 35.4%) for participants 65–74 years, 32.4% (8.1%; 50.6%) for those ≥75 years, 22.1% (3.9%; 37.0%) for participants with ≥1 high-risk comorbidity, 23.6% (−3.2%; 43.6%) for those with ≥2 high-risk comorbidities, 27.5% (0.4%; 47.4%) for persons with 1 frailty condition, 23.9% (−9.0%; 47.2%) for those with 2 frailty conditions, and 16.0% (−16.3%; 39.4%) for those with ≥3 frailty conditions. There was no evidence of vaccine efficacy heterogeneity within age, comorbidity, and frailty strata (P-values 0.351, 0.875, and 0.838, respectively). HAI GMT ratios were significantly higher among IIV-HD recipients for all strains and across all subgroups. ConclusionsEstimates of relative efficacy consistently favored IIV-HD over IIV-SD. There was no significant evidence that baseline age, comorbidity, or frailty modified the efficacy of IIV-HD relative to IIV-SD. IIV-HD significantly improved HAI responses for all strains and in all subgroups. IIV-HD is likely to provide benefits beyond IIV-SD for adults ≥65 years, irrespective of age and presence of comorbid or frailty conditions.

Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses

Trivalent, live, cold-adapted influenza vaccine (CAIV-T) is highly effective in the prevention of influenza in children, and a variety of monovalent and bivalent cold-adapted influenza vaccines have been efficacious in adults. In order to determine the efficacy of CAIV-T in healthy adults, we administered CAIV-T, trivalent inactivated influenza vaccine (TIV) or placebo to 103 adults in randomized double-blind fashion, and then challenged those subjects who had pre-screening serum hemagglutination-inhibition antibody titers of 1:8 or less with wild-type influenza viruses corresponding to the strains contained in the vaccine. CAIV-T was well tolerated. Upon challenge with wild-type influenza virus, laboratory documented influenza illness (respiratory symptoms with either isolation of wild-type influenza virus from nasal secretions or 4-fold and/or greater HAI antibody response to challenge) occurred in 14/31 (45%) placebo recipients, 4/32 (13%) TIV recipients, and 2/29 (7%) CAIV-T recipients. The estimated protective efficacy of CAIV-T was therefore 85% and of TIV was 71%. These results are consistent with those of previous studies using monovalent preparations of cold-adapted influenza vaccine in this model, and indicate that CAIV-T will be an effective means to prevent influenza illness in adults.

New approaches to influenza chemotherapy. Neuraminidase inhibitors.

Epidemic influenza continues to be associated with significant morbidity in the general population, and mortality in the elderly and other high risk patients. Although the case fatality rate averages less than 0.01%, tens of thousands of deaths occur each year. Control through immunisation programmes has not been possible due to incomplete protective efficacy and antigenic variations that occur frequently. Currently available anti-influenza medications (amantadine and rimantadine) have had limited success due to underutilisation, lack of activity against influenza B, the rapid development of viral resistance to the drugs, and adverse effects. A new class of antiviral agents designed to inhibit influenza neuraminidase, an important surface glycoprotein, is currently under active development for use in the prophylaxis and treatment of influenza A and B infections. Two of these compounds, zanamivir (GG167) and GS4104 (the ethyl ester prodrug of GS4071) have reached clinical trials. Most studies of zanamivir have involved topical administration by inhalation of dry powder aerosols and/or intranasal doses of aqueous solutions. These routes rapidly provide high local concentrations at the sites of delivery. GS4104 is administered orally, which allows for greater ease of administration, and probably more uniform distribution of the parent compound GS4071 in the respiratory tract. Both have shown potent inhibitory activity against influenza in animal models and experimental human influenza with excellent tolerability profiles. Zanamivir treatment has been shown to reduce the severity and duration of naturally occurring, uncomplicated influenza illness in adults. Clinical resistance to these drugs has not been recognised as a significant problem to date, although strains resistant to each agent have been produced in the laboratory. This class of agents shows considerable promise as a novel approach to prophylaxis and treatment of influenza infections. Ongoing studies should provide the data needed to allow the addition of 1 or more of the neuraminidase inhibitors to the clinician's anti-influenza armamentarium.