The test-negative design for estimating influenza vaccine effectiveness

Objective

The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed.

Methods

In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative.

Results

With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time.

Conclusions

The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata.     

Influenza vaccine effectiveness against medically-attended influenza illness during the 2012–2013 season in Beijing,China

Background

Influenza vaccine coverage remains low in China, and there is limited information on the preventive value of local vaccination programs.

Methods

As part of influenza virological surveillance in Beijing, China during the 2012–2013 influenza season, we assessed the vaccine effectiveness (VE) of one or more doses of trivalent inactivated influenza vaccine (IIV3) in preventing medically-attended influenza-like-illness (ILI) associated with laboratory-confirmed influenza virus infection using a test-negative case–control design. Influenza vaccination was determined based on self-report by adult patients or the parents of child patients.

Results

Of 1998 patients with ILI, 695 (35%) tested positive for influenza viruses, including 292 (42%) A(H3N2), 398 (57%) A(H1N1)pdm09, and 5 (1%) not (sub)typed influenza viruses. The rate of influenza vaccination among all patients was 4% (71/1998). Among influenza positive patients, 2% (57/1303) were vaccinated compared to 4% (14/695) among influenza negative patients, resulting in VE for one or more doses of vaccine (adjusted for age, sex, week, and days since illness onset) against all circulating influenza viruses of 52% (95% CI = 12–74%). A significant adjusted VE for one or more doses of vaccine for all ages against A(H1N1)pdm09 of 59% (95% CI, 8–82%) was observed; however, the VE against A(H3N2) was 43% (95% CI, −30% to 75%). The point estimate of VE was 59% (95% CI, 19–79%) for those aged <60 years, but a negative VE point estimate without statistical significance was observed among those aged ≥60 years.

Conclusions

IIV3 conferred moderate protection against medically-attended influenza in Beijing, China during the 2012–2013 season, especially against the A(H1N1)pdm09 strain and among those aged <60 years old.     

Estimates of influenza vaccine effectiveness in primary care in Scotland vary with clinical or laboratory endpoint and method—Experience across the 2010/11 season

Aim

This study examines estimation of seasonal influenza vaccine effectiveness (VE) for a cohort of patients attending general practice in Scotland in 2010/11. The study focuses on the variation in estimation of VE for both virological and clinical consultation outcomes and understanding the dependency on date of analysis during the season, methodological approach and the effect of use of a propensity score model.

Methods

For the clinical outcomes, three methodological approaches were considered; adjusted Poisson multi-level modelling splitting consultations in vaccinated individuals into those before and after vaccination, adjusted Cox proportional hazards modelling and finally the screening method. For the virological outcome, the test-negative case–control study design was employed.

Results

VE was highest for the most specific outcomes of ILI (Poisson end-of-season VE = 47% (95% CI: −69%, 83%); Cox VE = 34% (95% CI: −64%, 73.2%); Screening VE = 52.8% (95% CI: 3.8%, 76.8%)) and a virological diagnosis (VE = 54% (95% CI: −37%, 85%)). Using the Cox approach, adjusted for propensity score only gave VE = 46.5% (95% CI: −30.4%, 78.0%).

Conclusion

Our approach illustrated the ability to achieve relatively consistent estimates of seasonal influenza VE using both specific and less specific outcomes. Construction of a propensity score and use for bias adjustment increased the estimate of ILI VE estimated from the Cox model and made estimates more similar to the Poisson approach, which models differences in consultation behaviour of vaccinated individuals more inherently in its structure. VE estimation for the same data was found to vary by methodology which should be noted when comparing results from different studies and countries.     

The case test-negative design for studies of the effectiveness of influenza vaccine

Background

A modification to the case–control study design has become popular to assess vaccine effectiveness (VE) against viral infections. Subjects with symptomatic illness seeking medical care are tested by a highly specific polymerase chain reaction (PCR) assay for the detection of the infection of interest. Cases are subjects testing positive for the virus; those testing negative represent the comparison group. Influenza and rotavirus VE studies using this design are often termed “test-negative case-control” studies, but this design has not been formally described or evaluated. We explicitly state several assumptions of the design and examine the conditions under which VE estimates derived with it are valid and unbiased.

Methods

We derived mathematical expressions for VE estimators obtained using this design and examined their statistical properties. We used simulation methods to test the validity of the estimators and illustrate their performance using an influenza VE study as an example.

Results

Because the marginal ratio of cases to non-cases is unknown during enrollment, this design is not a traditional case-control study; we suggest the name “case test-negative” design. Under sets of increasingly general assumptions, we found that the case test-negative design can provide unbiased VE estimates. However, differences in health care-seeking behavior among cases and non-cases by vaccine status, strong viral interference, or modification of the probability of symptomatic illness by vaccine status can bias VE estimates.

Conclusions

Vaccine effectiveness estimates derived from case test-negative studies are valid and unbiased under a wide range of assumptions. However, if vaccinated cases are less severely ill and seek care less frequently than unvaccinated cases, then an appropriate adjustment for illness severity is required to avoid bias in effectiveness estimates. Viral interference will lead to a non-trivial bias in the vaccine effectiveness estimate from case test-negative studies only when incidence of influenza is extremely high and duration of transient non-specific immunity is long.     

Influenza vaccination and risk of hospitalization among adults with laboratory confirmed influenza illness

Background

Influenza vaccine is moderately effective for preventing influenza illness. It is not known if vaccination reduces the risk of subsequent hospital admission among patients with vaccine failure and laboratory confirmed influenza illness.

Methods

Patients in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza during 8 seasons to estimate seasonal vaccine effectiveness. Hospital admissions within 14 days after illness onset were identified for all participants aged ≥20 years with laboratory confirmed influenza. The association between vaccination and hospital admission was examined in a propensity score adjusted logistic regression model. The model was validated by examining the association between vaccination and hospital admission in participants without influenza.

Results

Influenza was identified in 1393 (28%) of 4996 participants. Sixty-two (6%) of 1020 with influenza A and 17 (5%) of 369 with influenza B were hospitalized. Vaccination was not associated with a reduced risk of hospital admission among all participants with influenza [adjusted odds ratio (aOR) = 1.08; 95% CI: 0.62, 1.88]; or among those with influenza A (aOR = 1.35; 95% CI: 0.71, 2.57) or influenza B (aOR = 0.67; 95% CI: 0.21, 2.15). Influenza vaccination was not associated with hospitalization after non-influenza respiratory illness (aOR = 1.14; 95% CI: 0.84, 1.54).

Conclusions

Influenza vaccination did not reduce the risk of subsequent hospital admission among patients with vaccine failure. These findings do not support the hypothesis that vaccination mitigates influenza illness severity.     

Effect of influenza vaccination on hospitalizations in persons aged 50 years and older

Objective

To estimate influenza vaccine effectiveness (VE) in preventing hospitalizations in persons over 50 years of age.

Design

We performed a retrospective, population based study, using a “difference-in-differences” approach to determine the association between hospitalization and prior vaccination. We examined this association when influenza was not circulating and compared it to the association found when influenza was circulating. VE was estimated from the difference in the association between hospitalization and prior vaccination, inside vs. outside influenza seasons.

Setting

Kaiser Permanente in Northern California.

Patients

Health plan members aged 50 years and older during the September 1997 to August 2008 study period, when there were about 68,000 pneumonia hospitalizations in 10 million person-years.

Results

Vaccination was associated with lower risk of hospitalization for pneumonia and influenza, even before flu season, presumably due to unmeasured confounders. When influenza arrived the hospitalization-vaccination association strengthened, yielding an adjusted VE estimate of 12.4% (95% CI: 1.6–22.0) in persons aged 50–64, and 8.5% (95% CI: 3.3–13.5) in those aged 65 years and older. There was no significant effect on hospitalizations for ischemic heart disease (IHD), congestive heart failure (CHF), cerebrovascular disease (CVD), or trauma.

Conclusions

Influenza vaccination has a modest but significant effect on prevention of hospitalization for pneumonia and influenza in persons 50 years of age and older.     

Health care professionals’ awareness of,knowledge about and attitude to influenza vaccination

Objectives

Influenza vaccination is recommended to all health care professionals (HCPs). However, vaccination rate among HCPs is low and may be due to uncertainty about the effectiveness of the vaccine and fear of its adverse effects. Therefore, this study aimed to investigate the awareness, knowledge, and attitude of HCPs towards influenza vaccination and we ascertain reasons for not getting vaccinated.

Method

A cross-sectional conducted in 6 major hospitals in Saudi Arabia. 245 anonymous questionnaires were distributed to a convenient sample of staff during the 2012–2013 influenza season. The validated questionnaire consists of five sections that collect information about: demographics, attitude towards influenza vaccination, knowledge about influenza virus and vaccination, current practice and awareness of published guidelines.

Results

242 completed questionnaires were received, a response rate of 98%. 38% of HCPs reported getting vaccinated. The most common reasons given by HCPs for not getting vaccinated were: fear of contracting illness (16%), belief that they are not at risk from influenza because they are young and healthy (13%) and being unaware of vaccine availability (13%). Non-availability of vaccine (43%) was the highest barrier for not providing vaccine for patients and HCPs followed by safety concerns for the patients (35%) and the respondents (33%). Almost 75% of HCPs were not aware of the influenza immunization guidelines published by the Advisory Committee on Immunization Practices and Centre for Disease Control.

Conclusion

Despite the recommendations, only low percentage of HCPs in Saudi Arabian hospitals is vaccinated against influenza. The attention of health policy makers is needed to improve compliance of HCPs with guidelines on influenza vaccination.     

Seasonal influenza vaccine effectiveness against influenza in 2012–2013: A hospital-based case-control study in Lithuania

Background

Due to scarce information on seasonal influenza vaccine effectiveness (SIVE) against severe clinical influenza outcomes in risk populations, we conducted a case-control study to assess its effects against laboratory-confirmed influenza in hospitalized patients during the 2012–2013 influenza season.

Methods

We conducted a test-negative case-control study among ≥18 years old patients with influenza-like illness (ILI) hospitalized in two Lithuanian hospitals. Cases were influenza A(H1N1), A(H3) or influenza B positive by RT-PCR, and controls were influenza negative. Additional demographic and clinical data to assess the role of confounding were collected. SIVE and its confidence intervals (95% CI) were estimated by using multivariate logistic regression as (1 − OR) × 100%.

Results

The sample consisted of 185 subjects. Seasonal influenza vaccine uptake was 5%. Among 111 (60%) influenza positive cases, 24.3% were A(H1N1), 10.8% were A(H3) and 24.3% were influenza B cases. Unadjusted SIVE was 79% (95% CI −6% to 96%) and after the adjustment it increased to 86% (95% CI 19% to 97%).

Conclusions

Seasonal influenza vaccination in 2012–2013 was associated with reduced occurrence of laboratory-confirmed influenza, but due to low sample size the estimate of SIVE is imprecise. Given high prevalence of influenza in hospitalized ILI cases and low influenza vaccination coverage, there is a need to increase influenza vaccination rates.     

Effectiveness of the 2011–12 Influenza Vaccine: Data from US Military Dependents and US-Mexico Border Civilians

Objective

To assess effectiveness of the influenza vaccine among US military dependents and US-Mexico Border populations during the 2011–12 influenza season.

Introduction

As a result of antigenic drift of the influenza viruses, the composition of the influenza vaccine is updated yearly to match circulating strains. Consequently, there is need to assess the effectiveness of the influenza vaccine (VE) on a yearly basis. Ongoing febrile respiratory illness (FRI) surveillance captures data and specimens that are leveraged to estimate influenza VE on an annual basis.

Methods

Data from ongoing FRI surveillance at US Military and US-Mexico border clinics were used to estimate VE. We conducted a case–control study between weeks 3 and 17 of the 2011–12 influenza season. Specimens were collected from individuals meeting FRI case definition (fever ≥ 100.0 F with either cough or sore throat). Cases were laboratory confirmed influenza infection and controls were negative for influenza. Interviewer-administered questionnaires collected information on patient demographics and clinical factors and vaccination status. Logistic regression was used to calculate the crude and adjusted odds ratios (OR) and VE was computed as (1-OR) × 100%. Vaccine protection was assumed to begin 14 days post-vaccination.

Results

A total of 155 influenza positive cases and 429 influenza negative controls were included in the analysis - 72 cases were influenza A(H3N2), 38 cases were influenza A(H1N1), and 45 cases were influenza B. Overall adjusted VE against laboratory-confirmed influenza was 46% (95% CI, 19–64%); unadjusted was 39% (95% CI, 11–58%). Influenza subtype analyses revealed moderate protection against A/H3 and A/H1 and lower protection against B. Lowest estimated VE was seen in older individuals, age 65 and older.

Conclusions

Influenza vaccination was moderately protective against laboratory confirmed influenza in this population. Continued surveillance is important in monitoring the effectiveness of the influenza vaccine.     

The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009–2013

Background

Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions.

Methods

We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment.

Results

Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: −25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B.

Conclusions

Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year.     

Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017–2018 influenza season

PurposeReceiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined.ResultsWe compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46–0.51).ConclusionsReceipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.     

Effectiveness of influenza vaccination in elderly diabetic patients: A retrospective cohort study

Purpose

Studies regarding the clinical benefits of influenza vaccination in diabetic patients are limited. This study evaluated if the elderly diabetic patients who have had influenza vaccination would have benefits such as reduced medical care and mortality.

Methods

We used the universal insurance claims data from 2001 to 2009 in Taiwan to identify annual elderly patients with diabetes cohorts with (N = 4454) and without (N = 4571) influenza vaccination. The risk of developing pneumonia or influenza, respiratory failure, intensive care, hospitalization, and mortality were measured and compared between cohorts within one year of follow-up.

Results

The vaccine cohort had lower incidences of pneumonia or influenza and respiratory failure compared with the non-vaccine cohort. More importantly, the vaccine cohort had a hospitalization rate that was 11% less than the non-vaccine cohort (29.6 vs. 33.1 per 100 person-years) with an adjusted hazard ratio (HR) of 0.88 (95% CI 0.81–0.96). The vaccine cohort was also less likely to be admitted to the intensive care unit (ICU) [0.58 vs. 2.05 per 100 person-year; adjusted HR 0.30 (95% CI 0.19–0.47)] and less likely to expire [3.13 vs. 7.96 per 100 person-year; adjusted HR 0.44 (95% CI 0.36–0.54)]. Influenza vaccination reduced the hospitalization cost by 1282.6 USD, compared with patients without influenza vaccination (95% CI −2210.3, −354.8).

Conclusion

Influenza vaccination is associated with a reduced risk of morbidity, hospitalization, ICU admissions, and mortality. In addition, the hospitalization cost is reduced.     

Seasonal influenza vaccine efficacy and its determinants in children and non-elderly adults: A systematic review with meta-analyses of controlled trials

Context

The true level of influenza vaccine efficacy is controversial and many factors may influence its estimation.

Objectives

To estimate the efficacy of vaccination of children and non-elderly adults for the prevention of influenza and to explore the impact of type of vaccine, age, degree of strain matching, influenza type and case ascertainment methods on vaccine efficacy estimates.

Data sources

Medline and EmBase databases until October 2011. References of relevant articles were also reviewed.

Study selection

Controlled trials evaluating seasonal influenza vaccines and presenting incidence of laboratory-confirmed influenza illness were eligible. Studies exploring efficacy after experimental challenge, presenting duplicate data, employing group randomization, or focusing on special populations were excluded.

Data extraction

The vaccine effect on influenza prevention was evaluated by calculating Mantel–Haenszel risk ratios (RR) and using random-effects models. Vaccine efficacies were calculated for each comparison as (1 − RR) × 100.

Results

Thirty studies were included in one or more of a total of 101 analyses, comprising 88.468 study participants. There was evidence of heterogeneity in 49% of the analyses. Summary vaccine efficacy was 65% against any strain, 78% against matched strains and 55% against not-matched strains. Both live-attenuated and inactivated vaccines showed similar levels of protection against not-matched strains (60% and 55%, respectively). Live-attenuated vaccines performed better than inactivated vaccines in children (80% versus 48%), whereas inactivated vaccines performed better than live-attenuated vaccines in adults (59% versus 39%). There was a large difference (20%) in efficacy against influenza A (69%) and influenza B (49%) types for not-matched strains. Summary estimates of vaccine efficacy were highest when ascertainment was based on culture confirmation.

Conclusion

Influenza vaccines are efficacious, but efficacy estimates depend on many variables including type of vaccine and age of vaccinees, degree of matching of the circulating strains to the vaccine, influenza type, and methods of case ascertainment.     

Is the adjuvanted influenza vaccine more effective than the trivalent inactivated vaccine in the elderly population? Results of a case–control study

Introduction

Influenza illness is an important public health problem and annual vaccination is globally recommended for high risk populations.

Objective

The aim was to evaluate and compare the effectiveness of influenza vaccines in reducing hospitalizations for influenza or pneumonia during two influenza seasons in the elderly.

Methods

A case–control study was performed, using administrative database of the Local Health Unit Roma-A (LHU RM-A). The included subjects were at least 65 years old and residing in one of the four districts of the LHU. The cases were hospitalized for influenza or pneumonia during influenza season in the years 2010–2011 and 2011–2012. The controls were hospitalized in the same period, but not for influenza or pneumonia. The subjects were immunized with the trivalent inactivated influenza vaccine (TIV) in the first influenza season (2010–2011) and with the adjuvanted influenza vaccine MF59 (ATIV) in the second season (2011–2012).

Results

A total of 269 cases and 1247 controls were included for the 2010–2011 influenza season, and 365 cases and 1227 controls were selected for the 2011–2012 season. Up to 63.6% cases and 53.5% controls in the 2010–2011 season and 78.6% of cases and 64.1% of controls in the 2011–2012 season have not been vaccinated. Female gender and high educational level were protective factors for hospitalization. Subjects over 75 years were at high risk of hospitalization compared to 65–74 years olds. Influenza vaccination reduced significantly hospitalization in both seasons. In subjects with 65–74 years TIV was more effective than ATIV; vice versa for those over 75 years old.

Discussion and conclusion

TIV and ATIV reduce hospitalization for influenza or pneumonia with a variable degree of protection in different age groups. In particular, ATIV is more effective in individuals over 75 years old.     

Respiratory viruses transmission from children to adults within a household

Background

The aim of this study was to examine the rate of transmission of influenza and other respiratory viruses from children attending an Emergency Department to their family members in the household using active surveillance.

Methods

A prospective hospital-based study was conducted over three consecutive winters (2006–2008) in children aged <1–15 years presenting with influenza-like illness (ILI). 168 children with ILI and their healthy families were recruited over three winter seasons.

Results

Respiratory viruses were detected in 101 (60.8%) children with ILI; in 91/166 (54.8%) a single pathogen was detected, and in the remaining 10 children more than one virus was detected concurrently. Influenza was the most common virus detected (34/101), followed by rhinoviruses (22/101) and adenoviruses (14/101). Of influenza viruses, 21/34 were influenza A and 13/34 influenza B. Meeting the clinical definition of ILI did not differentiate between influenza and other viruses. Clinical ILI developed within one week of follow up in 12% (26/205) of the family members who were swabbed. Viral pathogens were detected in 42.3% (11/26) of the symptomatic family members. In 6/11 cases the same virus was detected in the adult and child. The lower estimate of the household risk of transmission of respiratory viruses, based on concordant proven infection in both child and adult, from a single sick child to adult household contacts is therefore 3% per week.

Conclusion

This study provides quantitative, prospective data on rates of household transmission of infection from children to adults.     

Influenza vaccination uptake amongst pregnant women and maternal care providers is suboptimal

Objective

To assess the uptake of influenza vaccination by pregnant women and maternity care providers and explore their attitudes towards influenza vaccination.

Design, setting and participants

Cross-sectional survey administered in a Victorian tertiary level public hospital to 337 pregnant women and 96 maternity care providers.

Results

31.3% of patients planned to or had received influenza vaccination this year, but only a quarter had received education about influenza. Women were more likely to receive influenza vaccination if they had been vaccinated in the last two years (RR 4.5, 95% CI: 3.1–6.4, p < 0.001), received education about influenza (RR 2.3, 95% CI: 1.6–3.2, p < 0.001) or believed that they were at high risk of influenza-related complications while pregnant (RR 2.0, 95% CI: 1.4–2.7, p < 0.001). While only 56.8% of maternity care providers believed pregnant women were at high risk of influenza-related complications, 72.9% would recommend influenza vaccination to all pregnant women. Of the maternity care providers studied, 69% planned to or had been vaccinated in 2011, with this group more likely to recommend vaccination to their patients (RR 2.0, 95% CI: 1.3–3.0, p < 0.001). Significantly more maternity care providers indicated that they would routinely recommend influenza vaccination than the proportion of patients who reported receiving education.

Conclusions

Influenza vaccination rates in pregnant women are low, reflecting inadequate patient education despite most maternity care providers indicating that they would routinely recommend influenza vaccination. Increasing influenza vaccination uptake by women in pregnancy will require better education of both women and maternity care providers.     

The effect of seasonal influenza vaccine on medically-attended influenza and non-influenza respiratory viruses infections at primary care level,Hong Kong SAR, 2017/18 to 2019/20

Effectiveness of seasonal influenza vaccine (SIV) varies with the degree of matching with the vaccine and circulating viruses. We continued our SIV effectiveness against medically-attended influenza-like illness (ILI) under the Department of Health Hong Kong’s sentinel private medical practitioners (PMP) network, using the test-negative case-control design, for the 2018/19 and 2019/20 season. In addition, we studied the potential interference between SIV and ILI caused by non-influenza respiratory viruses (NIRV) based on data collated from 2017/18 to 2019/20 seasons. 3404 patients were analysed. Across the 2017/18 to 2019/20 seasons, the vaccine effectiveness (VE) of SIV was 44% (95% CI 30–56%) against pan-negative controls, 57% (95%CI. 42–68%) against NIRV controls and 50% (95%CI 38–59%) against both. SIV was moderately effective against medically-attended ILI caused by influenza A/B in both 2018/19 and 2019/20 winter seasons (53.2% (95%CI 36.7–65.5%) and 41.8% (95%CI 6.3–64.1%), respectively). The VE against the main circulating subtype, influenza A(H1), was higher for the 2018/19 season (57.2% (95%CI 39.8–69.9%), compared to 34.6% (95%CI −9.6–61.4%) in the 2019/20 season). When compared to pan negative controls, those with single NIRV infections were similarly likely to have received SIV (OR 1.05 (95%CI 0.72–1.54) within the influenza season; OR 0.97 (95%CI 0.73–1.29) when including non-influenza seasons). Analyses by type of virus showed no increased risk of SIV identified among those with single infections of EV/RV, HMPV and parainfluenza but a 2-fold increased risk was shown for those with single infections of adenovirus and parainfluenza virus (adenovirus: OR 2.54 (95%CI 1.24–5.14) within influenza season and OR 1.78 (95%CI 1.01–3.09) for the whole period; parainfluenza virus: OR 2.01 (95%CI 1.22–3.29) within influenza season and OR 1.89 (95%CI 1.29–2.76) for the whole period). SIV programme and surveillance of influenza and NIRV, including SARS-CoV-2, should continue during the COVID-19 pandemic.