A multi‐year, prospective cohort study of healthcare personnel (HCP) in Lima, Peru, is underway, named Estudio Vacuna de Influenza Peru (VIP). Here, we summarize the objectives and design, results of recruitment during the first 3 years of the study, and rates of participation in active surveillance during the first 2 years of the study.

A meta‐analysis of studies of seasonal influenza estimated that 1/5 HCP are infected with influenza virus annually, based on serologic and clinical testing. ¹ Estimates of influenza virus infection among HCP vary widely depending on the extent of active surveillance and whether studies relied on serologic ² or molecular diagnostics. ³ , ⁴ Healthcare personnel are believed to be at increased risk because of frequent patient contact. They may also transmit influenza to their patients, though the extent of these risks is unclear. ⁵ Because HCP often work while ill, ³ , ⁶ , ⁷ more information is needed on the number and types of contacts HCP may have with patients while HCP are symptomatic with influenza and other viral infections. ³ , ⁶ , ⁷ , ⁸ Recent research suggests that certain subgroups of HCP, such as those that perform aerosol‐generating procedures, may be at heightened risk of infection with respiratory pathogens including influenza. ⁹ Our cohort study was designed to address gaps in our knowledge of influenza burden and impact among HCP. The first objective of the VIP Cohort is to describe the frequency of influenza virus infections among HCP, including acute illnesses and asymptomatic infections.

Vaccination of HCP against influenza virus infection is an important component of infection control in healthcare settings, ¹⁰ but relatively low uptake among HCP outside the United States remains a topic of international concern and debate. ¹¹ , ¹² , ¹³ Although numerous studies of the knowledge, attitudes, and practices (KAP) associated with influenza vaccine acceptance have been conducted among HCP in high‐income countries, ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ less is known about barriers to vaccine acceptance among HCP in low‐ and middle‐income countries. ¹³ , ¹⁵ , ¹⁸ The second objective is to identify predictors of vaccine acceptance and hesitancy in HCP.

Studies of influenza vaccine immunogenicity among HCP have demonstrated that repeated vaccination can blunt the antibody response to hemagglutinin ¹⁹ , ²⁰ and neuraminidase. ²¹ Further research is needed to examine how influenza vaccination across multiple seasons may affect immunogenicity ²² and how these effects are mediated by specific humoral ²⁰ and cell‐mediated immune responses. ²² The third objective is to examine how repeated influenza vaccination may modify immunogenicity.

Although recent reviews confirm that seasonal influenza vaccine is moderately effective in reducing the risk of illness among adults, ²³ there are limited data regarding the value of vaccine for HCP. To date, the only randomized controlled trial of influenza vaccine efficacy among HCPs relied on serologic outcomes, ²⁴ which are biased among vaccinees and may inflate influenza vaccine effectiveness (IVE) estimates. ²⁵ , ²⁶ Reports of reduced IVE among frequent vaccinees in some studies ²⁰ , ²² , ²⁷ and seasons ²⁸ make it important to examine IVE among HCP, a population that receives frequent annual influenza vaccinations in the United States. Few data are available about the value of influenza vaccine in reducing missed work due to infection or reducing frequency of time worked while ill. ⁵ , ⁸ Given that influenza vaccine may only reduce the risk of influenza illness by 40%‐60% during years with a good match between circulating and vaccine viruses, further research is needed on whether factors like age, patient‐care responsibilities, and the use of personal protective equipment (PPE) modify the risk of vaccine failure. Limited research suggests that vaccination may also modify illness duration and severity among those who develop influenza illness despite vaccination. ⁸ , ²⁹ , ³⁰ , ³¹ The fourth objective of the VIP Cohort is to evaluate IVE in preventing influenza illness and associated missed work and working while ill. See Appendix S1 for more detail on study objectives.

The VIP Cohort is poised to address knowledge gaps regarding the burden of laboratory‐confirmed influenza illness and the preventive value of influenza vaccines among HCP. This study is unique in its ability to assess the risk of rRT‐PCR‐confirmed influenza illness and immune response to infection and influenza vaccination among HCP who received Southern‐hemisphere influenza vaccines for several seasons. The study includes serology on all participants which affords the opportunity to quantify sub‐clinical or asymptomatic infections that may not be captured by PCR‐based testing. Insights provided by such results may be particularly timely given recent efforts by the World Health Organization to enhance influenza vaccine coverage among HCP, especially in middle‐income countries, to protect HCP and their patients during seasonal influenza epidemics and increase pandemic preparedness. ³⁵

A strength of this study is the ability to describe all stages of recruitment starting with a known source population denominator. Because we can quantify the source population, we can assess potential selection bias, which is an important source of potential bias in observational IVE studies. ³⁶ , ³⁷ The VIP Cohort study successfully reached 92% of potential participants, enrolled 76% of eligible HCP, and has retained ≥90% of participants between years. This represents very high overall participation rates compared to earlier studies of HCP ¹⁷ , ³⁸ and other cohort studies of adults. ³⁹ , ⁴⁰ Statistically significant differences in enrollment between hospitals and by sex, age, and occupation are consistent with differences noted in a previous HCP cohort in the United States ¹⁷ and highlight the importance of the study's stratified recruitment strategy to insure participants with combinations of these characteristics are represented. The target enrollment of ≥50 HCP per 18 recruitment strata was met for all strata except for the least common combination, male nurses aged ≥50. The stratified recruitment strategy generated variability in participant characteristics that can aid in adjusted IVE models, assessment of possible IVE effect modification, and estimating the weighted incidence of influenza virus infection in the source population of HCP across hospitals.

During the first 2 years, over half of the participants completed ≥70% of surveillance weeks. This is higher than surveillance participation reported in similar studies of acute respiratory illness, ⁴⁰ but reports of participation at this level of detail are rarely published. Despite use of SMS text messaging and other modes of communication for surveillance, illness status was uncertain in about 30% of participants per week, on average. In years 1 and 2, 10% and 7% of participants, respectively, reported that they failed to report an acute illness during the season. Gaps in surveillance data create potential for information bias; in a multivariable model, we found male sex, age ≥50, occupation as a nurse/technician or medical assistant, self‐rated overall health as “fair” or “poor,” and having not received the vaccination in the current season were associated with missing more weeks of surveillance. Nonetheless, the ability to quantify this missing information and address it in statistical models for IVE and influenza virus infection incidence represent a strength of the study.

This study has several other limitations. Like all studies of IVE and influenza incidence, the ability to broadly generalize results is limited by the unpredictability of circulating virus types and potential for mismatch between vaccine components and circulating strains in any year. Although conducting the study in Peru allows us to examine IVE in a middle‐income and Southern‐hemisphere country, where data on IVE are limited, the generalizability of findings to the United States and other countries is unknown. Additionally, the overall intensity and impact of influenza seasons are variable, and low influenza activity in a study season could negatively affect our ability to precisely estimate IVE and incidence. There is potential for bias in recall of information collected by self‐report, including vaccination history and details about illness severity and duration.

This study provides a unique opportunity to characterize and understand influenza illness among HCP and the impact of influenza illness on work in healthcare settings. In this context, we can better understand the role influenza vaccines play in protecting HCP from becoming infected, missing work, or working while sick, and the serologic response produced by influenza vaccines in a repeatedly vaccinated population.

Meredith Wesley: Data curation (equal); Formal analysis (lead); Writing – original draft (lead); Writing – review & editing (equal). Giselle Soto: Conceptualization (equal); Data curation (equal); Investigation (lead); Methodology (equal); Writing – review & editing (equal). Carmen Arriola: Conceptualization (equal); Investigation (equal); Methodology (equal); Writing – review & editing (equal). Miriam Gonzales: Data curation (equal); Investigation (equal); Project administration (equal); Writing – review & editing (equal). Gabriella Newes‐Adeyi: Conceptualization (equal); Investigation (equal); Methodology (equal); Project administration (equal); Supervision (equal); Writing – review & editing (equal). Candice Romero: Data curation (equal); Investigation (equal); Project administration (equal); Writing – review & editing (equal). Vic Veguilla: Investigation (equal); Methodology (equal); Writing – review & editing (equal). Min Levine: Investigation (equal); Methodology (equal); Writing – review & editing (equal). Maria Silva: Investigation (equal); Methodology (equal); Writing – review & editing (supporting). Jill Ferdinands: Conceptualization (equal); Investigation (equal); Methodology (equal); Writing – review & editing (equal). Fatimah Dawood: Conceptualization (equal); Investigation (equal); Methodology (equal); Writing – review & editing (equal). Sue Reynolds: Formal analysis (equal); Methodology (equal); Writing – review & editing (equal). Avital Hirsch: Methodology (equal); Writing – review & editing (equal). Mark Katz: Methodology (equal); Writing – review & editing (equal). Eduardo Matos: Investigation (equal); Project administration (equal); Writing – review & editing (equal). Eduardo Ticona: Investigation (equal); Project administration (equal); Writing – review & editing (equal). Juan Castro: Investigation (equal); Project administration (equal); Writing – review & editing (equal). Maria Castillo: Investigation (equal); Project administration (equal); Writing – review & editing (equal). Eduar Bravo: Investigation (equal); Project administration (equal); Writing – review & editing (equal). Angela Cheung: Data curation (equal); Writing – review & editing (equal). Rachael Phadnis: Data curation (equal); Writing – review & editing (equal). Emily Martin: Investigation (equal); Methodology (equal); Writing – review & editing (equal). Yeny Tinoco: Investigation (equal); Methodology (equal); Project administration (equal); Writing – review & editing (equal). Joan Manuel Neyra Quijandria: Data curation (equal); Methodology (equal); Project administration (equal); Writing – review & editing (equal). Eduardo Azziz‐Baumgartner: Conceptualization (equal); Investigation (equal); Methodology (equal); Writing – review & editing (equal). Mark Thompson: Conceptualization (lead); Investigation (lead); Methodology (lead); Supervision (lead); Writing – original draft (equal); Writing‐review & editing (lead).

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