Groll and Thomson's evaluation of the effectiveness of Ontario's Universal Influenza Immunization Campaign used per capita cases of laboratory-confirmed influenza. We argue that these data are susceptible to various biases and should not be used as an outcome measure. Laboratory data are traditionally used to identify the presence of influenza activity rather than to identify levels of influenza activity. A better measure of viral activity is the proportion of influenza tests positive; whereas the weekly proportion of tests positive was relatively consistent, a marked increase over time in the numbers of laboratory-confirmed cases paralleled an increase in the number of tests performed. Regardless, for evaluating universal influenza immunization program effectiveness, other established and available measures employed in previous studies describing the epidemiology of influenza should be used instead of laboratory data.
Comment On: Vaccine. 2006 Jun 12;24(24):5245-5016624458
Influenza causes a great disease burden on children especially in the outpatient setting. The signs and symptoms of influenza in unselected children treated as outpatients have not been previously published.
We assessed the clinical presentation of influenza in a prospective study of respiratory infections in preenrolled cohorts of children or =39.0 degrees C. Among children or =40.0 degrees C. Seventy-seven percent of the children had cough and 78% had rhinitis. In children 7 to 13 years of age, only 39% had headache and 13% had myalgia.
High fever is a prominent sign of influenza in children, and the clinical presentation of influenza is most severe in children
Few prospectively collected data are available to support the effectiveness of inactivated influenza vaccines in children younger than 2 years. We aimed to establish the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in a cohort of children younger than 3 years.
In a prospective cohort study during the influenza season of 2007-08 in Turku, Finland, between Jan 14 and April 9, 2008, we assessed the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in children aged 9 months to 3 years. Our study was part of a clinical trial on antiviral treatment of influenza in children (ClinicalTrials.gov, number NCT00593502). The vaccine was given as part of the Finnish vaccination programme as a 0?5 mL injection. Children enrolled into our study through mailed announcements and local advertisements were examined every time they had fever or signs of respiratory infection. No exclusion criteria were used for enrolment. Influenza was diagnosed with viral culture, antigen detection, and RT-PCR assays of nasal swab specimens. Vaccination status of children was determined by parental report. We calculated the primary effectiveness of influenza vaccination by comparing the proportions of infections in fully vaccinated and unvaccinated children in the follow-up cohort.
We enrolled 631 children into our study with a mean age of 2?13 years (range 9-40 months). Seven (5%) of 154 fully vaccinated children and 61 (13%) of 456 unvaccinated children contracted influenza during the study (effectiveness 66%, 95% CI 29-84; p=0?003). In the subgroup of children younger than 2 years, four (4%) of 96 fully vaccinated children and 21 (12%) of 172 unvaccinated children contracted influenza (66%, 9-88, p=0?03). We were unable to record any adverse events associated with the vaccination of the children in our study.
Trivalent inactivated influenza vaccine was effective in preventing influenza in young children, including those younger than 2 years. Our findings suggest that influenza vaccine recommendations should be reassessed in most countries.
We report a case-control design using a sentinel physician network to estimate vaccine effectiveness (VE) against laboratory-confirmed, medically attended influenza (LC-MAI) and provide results for the 2005-2006 season of dual A and B vaccine mismatch in Canada.
Participants were patients >or=5 years of age presenting with influenza-like illness (ILI) to a sentinel physician in British Columbia, Canada between November 1, 2005 and April 30, 2006. Cases were participants in whom influenza was identified; controls tested negative for influenza A and B by PCR, R-mix and culture. Isolates were characterized by gene-sequencing and hemagglutination-inhibition (HI) assays. Odds ratios (OR) for LC-MAI in vaccinated versus non-vaccinated persons were derived with adjustment for age and chronic conditions. VE was estimated as [1-OR (vaccinated/unvaccinated)].
The sample included 442 patient visits: median age was 26 years, 10% were >or=65 years, 15% had a chronic condition and 22% received the 2005-2006 trivalent inactivated influenza vaccine >or=2 weeks before ILI onset. Two hundred and six participants were positive for influenza; 107 (52%) had influenza A/H3N2 and 99 (48%) had influenza B/Victoria lineage. Gene sequencing identified mutations away from the vaccine strain at key antigenic binding sites of the hemagglutinin (HA) protein of H3N2 isolates; the neuraminidase (NA) protein was conserved. Based on HI assays, three-quarters of influenza A and all B isolates were mismatched to the 2005-2006 vaccine. Point estimates for VE against LC-MAI were in the range of 50 to 70% for both types of influenza.
2005-2006 was the third consecutive season of vaccine mismatch based on varying HA for the A/H3N2 component and the third also for the B component since 2001. Vaccine mismatch resulted in diminished VE but substantial cross-protection. More timely detection of drift variants through gene sequencing of isolates facilitates interpretation of VE results. Since it may be more antigenically conserved, the vaccine content and contribution of NA to overall VE should be further evaluated for both A and B components. Infrastructure for real-time epidemiologic assessment of vaccine performance is important annually and in preparation for a pandemic.
Oseltamivir prophylaxis was very effective in protecting nursing home residents from ILI and in halting this outbreak of influenza B. A portion of the total ILI cases may have been due to influenza A, as this strain was isolated in one resident. The 10% attack rate in this facility, controlled with oseltamivir, compares favourably with another influenza B outbreak in a similar facility in the same region, over the same time frame (ILI onset 27 December to 17 January). Oseltamivir prophylaxis was not used to manage this second outbreak of laboratory-confirmed influenza B. Of the 236 residents, 45 developed ILI for an overall attack rate of 19%, nearly double the rate in the oseltamivir-controlled setting (10%). While oseltamivir was effective in controlling influenza B in this outbreak, further experience and evaluation is required before it can be routinely recommended for prophylaxis of influenza in nursing home outbreaks. Although earlier attempts by others using oseltamivir in the control of influenza A outbreaks have also met with success, it is not yet licensed for this purpose. Compared to amantadine, oseltamivir has a relatively high cost for the control of influenza A outbreaks and this may continue to limit its wider acceptance. The cost-effectiveness of oseltamivir in the control of influenza B outbreaks needs to be specifically addressed given the typically milder nature of influenza B strains. However, such a distinction is not clinically reliable and elderly residents of long-term care facilities remain vulnerable to serious complications associated with influenza infection in general. An alternate agent for influenza chemoprophylaxis that is effective against both influenza A and B, is easily administered and has few side effects, could greatly enhance current prevention and control measures and warrants serious assessment. The spread of this outbreak from the geographically separate ward to other areas of the facility in which residents had not received prophylaxis, underscores the likely role of staff as a vehicle for transmission during facility outbreaks. While accurate staff ILI rates could not be determined, their immunization rates were low, and many staff were ill during the outbreak. Isolation of residents with ILI and prophylaxis of non-ill residents on the initial outbreak wards was insufficient to prevent the spread of the outbreak, although it was subsequently halted once prophylaxis was extended to all residents. In view of the uncertainty over this medication's widespread use, in the absence of licensure or previous studies demonstrating its effectiveness in the prophylaxis and control of influenza B outbreaks, initiation of oseltamivir prophylaxis was staggered by ward. In a declared influenza A outbreak, the protocol in a long term care facility is to initiate amantadine prophylaxis on all residents, rather than ward-by-ward. While anti-viral prophylaxis may be an effective secondary control measure in the management of influenza outbreaks, optimal primary prevention would be more effective. This would require increased vaccine coverage of residents and particularly of staff, who play an important role in the importation and transmission of influenza within these facilities.
Influenza activity varied across Europe during the 2002-2003 season both in terms of the intensity of clinical activity and the circulating virus types/subtypes. Influenza B was generally predominant in the 'western' parts of Europe (Portugal, Spain, the United Kingdom and Ireland) and influenza A (H3N2) in the 'central' and 'eastern' areas (Germany, Italy, Denmark, Switzerland, Poland, Slovenia, the Slovak Republic, the Netherlands). A number of countries experienced mixed seasons, first experiencing activity associated with influenza B and then with influenza A (Belgium, France and Spain). Generally, countries where influenza B was predominant had low (compared to historical data) levels of intensity (a mild season) and longer periods of influenza activity compared to countries where influenza A (H3N2) was predominant. A number of countries, all where influenza A (H3N2) was predominant, reported high levels of intensity compared to historical data: the Czech Republic, Denmark, Germany and Poland. In the six countries where age-specific incidence rates were available, the highest rates were observed among those aged 0-14 years. The influenza virus strains circulating in Europe had a good match with the virus strains in the influenza vaccine. A small number of isolates (A/Fujian/411/2002 (H3N2)-like) were reported at the end of the season that had a reduced reactivity to anti-sera of the vaccine strain. The composition of the 2003-2004 influenza vaccine is the same as during the 2002-2003 season.
Influenza is an important cause of respiratory illness in children, but data on virologically confirmed influenza infections in children treated as outpatients are limited.
We carried out a prospective cohort study of normal children younger than 13 years (n = 1338) in the winter of 2000 to 2001. During the study period of 32 weeks, the children were examined at the study clinic whenever they had fever or signs of respiratory infection. Nasal swabs were obtained during each episode of infection for determination of the viral etiology of the illness.
The overall attack rate of influenza in the cohort was 18.8%. Influenza viruses were isolated from the children from the beginning of November 2000 through May 2001. Virtually in each week between mid-November and the end of April (a period of 24 weeks), influenza viruses accounted for at least 5% of all respiratory infections in the children. During the peak of the epidemic, the percentage of influenza-positive children exceeded 20%.
This study confirms the important role of influenza as a cause of acute respiratory infections in children, even in winters of mild or moderate influenza activity. The study also shows that influenza viruses may circulate in the community at substantial levels much longer than previously thought.
Comment In: Pediatr Infect Dis J. 2004 May;23(5):48015131481