Influenza vaccination in older adults during the COVID-19 pandemic: a population-based study in 133 Brazilian cities. / Vacinação para influenza em idosos na pandemia COVID-19: estudo de base populacional em 133 cidades brasileiras.

Routine immunization during pandemics can be harmed. This study estimated the influenza vaccination coverage in older adults during the COVID-19 through the EPICOVID-19, a population-based study conducted in 133 cities from the 26 Brazilian states and Federal District. We selected 25 census tracts per city, with probability proportional to the tract's size, ten households by census tract, and one random individual interviewed. A total of 8,265 older adults (≥60 years old) were interviewed and asked whether they had been vaccinated against flu in 2020. Vaccination coverage was 82.3% (95% CI: 80.1-84.2) with no difference by gender, age, and region; higher vaccination coverage was observed among the wealthiest (84.7% versus 80.1% in the poorest) and among the more educated (87.3% versus 83.2% less educated); lower coverage among indigenous (56.9% versus > 80% among other ethnic groups). A positive association was identified with the number of comorbidities among men but not among women. Most of the population was vaccinated (97.5%) in the public health system. The private network was chosen mainly in the South by the wealthiest and more educated. Vaccination coverage was seven percentage points lower than the government target (90%), and inequalities should be reversed in future campaigns.

Imunizações de rotina durante pandemias podem ser prejudicadas. Este estudo estimou a cobertura vacinal para influenza em idosos durante a COVID-19 através do EPICOVID-19, inquérito populacional realizado em 133 cidades sentinelas dos 26 estados brasileiros e Distrito Federal. Selecionou-se 25 setores censitários por cidade, amostragem proporcional ao tamanho, dez domicílios por setor e uma pessoa por domicílio, aleatoriamente. O quantitativo de 8.265 idosos (≥ 60 anos) foram entrevistados e responderam se haviam sido vacinados contra gripe em 2020. A cobertura foi 82,3% (IC95% 80,1; 84,2), sem diferenças por sexo, idade ou região. Maiores coberturas ocorreram nos mais ricos (84,7% versus 80,1% nos mais pobres) e nos mais escolarizados (87,3% versus 83,2% nos menos escolarizados). Menor cobertura nos indígenas (56,9% versus coberturas superiores a 80% nos demais grupos étnicos). Houve associação positiva com número de comorbidades entre homens, mas não entre mulheres. A maioria vacinou-se na rede pública (97,5%), sendo a rede privada mais utilizada na região Sul, pelos mais escolarizados e mais ricos. Conclui-se que a cobertura vacinal ficou sete pontos percentuais abaixo da meta governamental (90%), e que desigualdades devem ser revertidas em futuras campanhas.

Vaccination in pregnancy.

The evidence indicates that pregnancy is associated with increased severity of some infectious diseases. Given the high maternal morbidity associated with influenza in pregnancy and the high neonatal morbidity and mortality associated with pertussis, the traditionally two recommended vaccines during pregnancy were those against influenza and Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccines. The recent COVID-19 pandemic introduced a third vaccine that after much debate is now recommended for all pregnant women. Other vaccines can be offered based for high-risk pregnant women, and only when the benefits of receiving them outweigh the risks. The soon expected vaccines against group B streptococcus infection and respiratory syncytial virus infection will be a breakthrough in reducing perinatal mortality. In this paper, the recommendations for administration of each vaccine during pregnancy are discussed.

Influenza and pertussis vaccine coverage in pregnancy in Australia, 2016-2021.

Vaccination in pregnancy is the best strategy to reduce complications from influenza or pertussis infection in infants who are too young to be protected directly from vaccination. Pregnant women are also at risk of influenza complications preventable through antenatal vaccination. Both vaccines are funded under the National Immunisation Program for pregnant women in Australia, but coverage is not routinely reported nationally. We reviewed all reported Australian maternal influenza and pertussis vaccine coverage data for the period 2016-2021, to identify gaps and information needs. Maternal influenza vaccine coverage was suboptimal at < 58% for 2016-2018, with higher coverage of 62-75% reported in two states (Victoria and Western Australia) for 2019-2021. Maternal pertussis vaccine coverage from 2016 was generally higher than for influenza at > 70%, with the highest jurisdictional coverage of 89% reported in Western Australia in 2020. Vaccination rates were often suboptimal among First Nations pregnant women and up to 20% lower than among non-First Nations Australian women; while data were limited, coverage was low among culturally and linguistically diverse women and among women of lower socio-economic status. Jurisdictional perinatal data collections were the best source of information on antenatal vaccine coverage but were only available for a minority of the population; a nationally consistent systematic approach is lacking. Timely and comprehensive data are needed to provide feedback to improve maternal vaccination coverage, particularly among groups with higher risk and/or low uptake, and as new vaccines are recommended, including COVID-19 vaccination.

Acceptance of recommended vaccinations during pregnancy: a cross-sectional study in Southern Italy.

Background: Vaccine administration is a recommended, safe, and effective measure to protect pregnant women against vaccine-preventable diseases (VPDs). Despite available guidance, maternal immunization rates for vaccination against influenza and with the reduced antigen content tetanus-diphtheria-acellular pertussis vaccine (Tdap) in Italy remain incredibly low. The primary goal of the study was to explore what Italian pregnant women knew about VPDs and immunization during pregnancy and what factors affected their decision to be vaccinated. Methods: This cross-sectional study took place between October 2021 and April 2022 in the Southern part of Italy. All consecutive pregnant women, from those attending the selected facilities on randomly selected days, were approached to request participation. The inclusion criteria for participation were age ≥18 years, the ability to understand, speak, and read Italian, and being pregnant at any gestational age. The questionnaire, using a combination of checkboxes and free text answers, consisted of 32 items divided into five parts and lasted ~10 min. Results: The results showed that 61% knew that the influenza vaccine is recommended and 48.7% knew that influenza could be risky during pregnancy; 74.1% wrongly reported that the Measles-Mumps-Rubella (MMR) vaccine is recommended during pregnancy. Seven out of 10 pregnant women believed that strong evidence supported the safety of vaccinations during pregnancy, and more than half (55.6%) thought they were at increased risk of severe illness with COVID-19. Women in the sample believed that vaccines received during pregnancy pose a risk of adverse events to the unborn child with a median value of 6 (IQR 3-9), on a scale ranging from 1 to 10. Similarly, the fear of contracting pertussis and influenza during pregnancy showed a median value of 6 (IQR 3-9) and 5 (IQR 3-8), respectively. Only 21.1% and 36.5% of women received influenza and Tdap vaccines during pregnancy. Conclusion: Unrealistic risk perception with a negative attitude toward vaccines in pregnancy and a low percentage of vaccinated pregnant women confirm the urgency of training women to make informed choices to increase overall vaccine uptake.

Risk factors for infection with influenza A(H3N2) virus on a US university campus, October-November 2021.

BACKGROUND: Knowledge of the specific dynamics of influenza introduction and spread in university settings is limited. METHODS: Persons with acute respiratory illness symptoms received influenza testing by molecular assay during October 6-November 23, 2022. Viral sequencing and phylogenetic analysis were conducted on nasal swab samples from case-patients. Case-control analysis of a voluntary survey of persons tested was used to identify factors associated with influenza; logistic regression was conducted to calculate odds ratios and 95% CIs. A subset of case-patients tested during the first month of the outbreak was interviewed to identify sources of introduction and early spread. RESULTS: Among 3268 persons tested, 788 (24.1%) tested positive for influenza; 744 (22.8%) were included in the survey analysis. All 380 sequenced specimens were influenza A (H3N2) virus clade 3C.2a1b.2a.2, suggesting rapid transmission. Influenza (OR [95% CI]) was associated with indoor congregate dining (1.43 [1.002-2.03]), attending large gatherings indoors (1.83 [1.26-2.66]) or outdoors (2.33 [1.64-3.31]), and varied by residence type (apartment with ≥1 roommate: 2.93 [1.21-7.11], residence hall room alone: 4.18 [1.31-13.31], or with roommate: 6.09 [2.46-15.06], or fraternity/sorority house: 15.13 [4.30-53.21], all compared with single-dwelling apartment). Odds of influenza were lower among persons who left campus for ≥1 day during the week before their influenza test (0.49 [0.32-0.75]). Almost all early cases reported attending large events. CONCLUSIONS: Congregate living and activity settings on university campuses can lead to rapid spread of influenza following introduction. Isolating following a positive influenza test or administering antiviral medications to exposed persons may help mitigate outbreaks.

External validation of the parental attitude about childhood vaccination scale.

Introduction: Internal validation techniques alone do not guarantee the value of a model. This study aims to investigate the external validity of the Parental Attitude toward Childhood Vaccination (PACV) scale for assessing parents' attitude toward seasonal influenza vaccination. Methods: Using a snowball sampling approach, an anonymous online questionnaire was distributed in two languages (English and Arabic) across seven countries. To assess the internal validity of the model, the machine learning technique of "resampling methods" was used to repeatedly select various samples collected from Egypt and refit the model for each sample. The binary logistic regression model was used to identify the main determinants of parental intention to vaccinate their children against seasonal influenza. We adopted the original model developed and used its predictors to determine parents' intention to vaccinate their children in Libya, Lebanon, Syria, Iraq, Palestine, and Sudan. The area under the curve (AUC) indicated the model's ability to distinguish events from non-events. We visually compared the observed and predicted probabilities of parents' intention to vaccinate their children using a calibration plot. Results: A total of 430 parents were recruited from Egypt to internally validate the model, and responses from 2095 parents in the other six countries were used to externally validate the model. Multivariate regression analysis showed that the PACV score, child age (adolescence), and Coronavirus disease 2019 (COVID-19) vaccination in children were significantly associated with the intention to receive the vaccination. The AUC of the developed model was 0.845. Most of the predicted points were close to the diagonal line, demonstrating better calibration (the prediction error was 16.82%). The sensitivity and specificity of the externally validated model were 89.64 and 37.89%, respectively (AUC = 0.769). Conclusion: The PACV showed similar calibration and discrimination across the six countries. It is transportable and can be used to assess attitudes towards influenza vaccination among parents in different countries using either the Arabic or English version of the scale.

Facilitators and barriers for vaccination in patients with inflammatory rheumatic musculoskeletal diseases: a prospective cohort study.

INTRODUCTION: To identify facilitators and barriers towards vaccination in general and specifically against pneumococci, influenza and SARS-CoV-2 in patients with rheumatic musculoskeletal diseases (RMD). METHODS: Between February and April 2021, consecutive patients with RMD were asked to complete a structured questionnaire on general knowledge about vaccination, personal attitudes and perceived facilitators and barriers towards vaccination. General facilitators (n=12) and barriers (n=15) and more specific ones for vaccination against pneumococci, influenza and SARS-CoV-2 were assessed. Likert scales had four response options: from 1 (completely disagree) to 4 (completely agree). Patient and disease characteristics, their vaccination records and attitudes towards vaccination against SARS-CoV-2 were assessed. RESULTS: 441 patients responded to the questionnaire. Knowledge about vaccination was decent in ≥70% of patients, but <10% of patients doubted its effectiveness. Statements on facilitators were generally more favourable than on barriers. Facilitators for SARS-CoV-2 vaccination were not different from vaccination in general. Societal and organisational facilitators were more often named than interpersonal or intrapersonal facilitators. Most patients indicated that recommendations of their healthcare professional would encourage them to be vaccinated-without preference for general practitioner or rheumatologists. There were more barriers towards SARS-CoV-2 vaccination than to vaccination in general. Intrapersonal issues were most frequently reported as a barrier. Statistically significant differences in response patterns to nearly all barriers between patients classified as definitely willing, probably willing and unwilling to receive SARS-CoV-2 vaccines were noted. DISCUSSION: Facilitators towards vaccination were more important than barriers. Most barriers against vaccination were intrapersonal issues. Societal facilitators identified support strategies in that direction.

History through the eyes of a pandemic.

PURPOSE OF REVIEW: This review provides a historic perspective of the impact that major pandemics have had on human and their relationship with ophthalmology. The novel coronavirus epidemic is also analyzed, highlighting the relevance of the eye as a possible source of transmission, infection, and prognosis for the disease. RESULTS: Smallpox is suspected to be present for more than 12 000 years. However, trachoma seems to be the first recorded ophthalmological infectious disease. The deadliest pandemics include the bubonic plague, smallpox, and Spanish flu. The CoVID-19 epidemic is still developing and measures need to be implemented to prevent further escalation of the crisis. SUMMARY: Understanding the current facts in light of earlier historical evidence may help us prepare better to minimize the spread of infections in the future.

Addressing influenza's underestimated burden - Iberian experts call to action.

Having a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza's impact.

Estimated US Pediatric Hospitalizations and School Absenteeism Associated With Accelerated COVID-19 Bivalent Booster Vaccination.

Importance: Adverse outcomes of COVID-19 in the pediatric population include disease and hospitalization, leading to school absenteeism. Booster vaccination for eligible individuals across all ages may promote health and school attendance. Objective: To assess whether accelerating COVID-19 bivalent booster vaccination uptake across the general population would be associated with reduced pediatric hospitalizations and school absenteeism. Design, Setting, and Participants: In this decision analytical model, a simulation model of COVID-19 transmission was fitted to reported incidence data from October 1, 2020, to September 30, 2022, with outcomes simulated from October 1, 2022, to March 31, 2023. The transmission model included the entire age-stratified US population, and the outcome model included children younger than 18 years. Interventions: Simulated scenarios of accelerated bivalent COVID-19 booster campaigns to achieve uptake that was either one-half of or similar to the age-specific uptake observed for 2020 to 2021 seasonal influenza vaccination in the eligible population across all age groups. Main Outcomes and Measures: The main outcomes were estimated hospitalizations, intensive care unit admissions, and isolation days of symptomatic infection averted among children aged 0 to 17 years and estimated days of school absenteeism averted among children aged 5 to 17 years under the accelerated bivalent booster campaign simulated scenarios. Results: Among children aged 5 to 17 years, a COVID-19 bivalent booster campaign achieving age-specific coverage similar to influenza vaccination could have averted an estimated 5 448 694 (95% credible interval [CrI], 4 936 933-5 957 507) days of school absenteeism due to COVID-19 illness. In addition, the booster campaign could have prevented an estimated 10 019 (95% CrI, 8756-11 278) hospitalizations among the pediatric population aged 0 to 17 years, of which 2645 (95% CrI, 2152-3147) were estimated to require intensive care. A less ambitious booster campaign with only 50% of the age-specific uptake of influenza vaccination among eligible individuals could have averted an estimated 2 875 926 (95% CrI, 2 524 351-3 332 783) days of school absenteeism among children aged 5 to 17 years and an estimated 5791 (95% CrI, 4391-6932) hospitalizations among children aged 0 to 17 years, of which 1397 (95% CrI, 846-1948) were estimated to require intensive care. Conclusions and Relevance: In this decision analytical model, increased uptake of bivalent booster vaccination among eligible age groups was associated with decreased hospitalizations and school absenteeism in the pediatric population. These findings suggest that although COVID-19 prevention strategies often focus on older populations, the benefits of booster campaigns for children may be substantial.

Healthcare professionals' beliefs regarding influenza vaccination: What has COVID-19 changed?

Background: Influenza poses a potential public health threat among healthcare professionals since an infected healthcare professional can spread the virus to patients at higher risk as well as his/her own family members and colleagues. Annual influenza vaccination is the most effective way to protect HCPs. Aim: This study was conducted to determine whether demand for and beliefs about influenza vaccination have changed among healthcare professionals in the COVID-19 era and the factors that might have influenced them in the early phase of the pandemic when COVID-19 vaccines were eagerly awaited. Patients and Methods: This observational descriptive study was conducted between November 16, and December 15, 2020. A total of 317 healthcare professionals completed an online survey. Bivariate analysis and binary logistic regression analysis were performed. Results: Nineteen (6.0%) healthcare professionals were regularly vaccinated against influenza every year, and 199 (62.8%) had never been vaccinated. During the 2019-2020 season, 30 (9.5%) participants had been vaccinated and the proportion desiring to be vaccinated against influenza during the 2020-2021 season was 49.8% (n = 158). The results revealed that those with chronic diseases, those who believed they had adequate information about influenza vaccination and those who believed healthcare professionals should be vaccinated against influenza regularly every year, respectively, had 3.5 times, 4.7 times, and 11 times higher vaccination rates. Conclusion: Although the proportion of healthcare professionals with the intention to be vaccinated for influenza increased with the COVID-19 pandemic, it is still not high enough. Influenza vaccination rates should be promoted by in-service training programs.

Comparing the Use of a Mobile App and a Web-Based Notification Platform for Surveillance of Adverse Events Following Influenza Immunization: Randomized Controlled Trial.

BACKGROUND: Vaccine safety surveillance is a core component of vaccine pharmacovigilance. In Canada, active, participant-centered vaccine surveillance is available for influenza vaccines and has been used for COVID-19 vaccines. OBJECTIVE: The objective of this study is to evaluate the effectiveness and feasibility of using a mobile app for reporting participant-centered seasonal influenza adverse events following immunization (AEFIs) compared to a web-based notification system. METHODS: Participants were randomized to influenza vaccine safety reporting via a mobile app or a web-based notification platform. All participants were invited to complete a user experience survey. RESULTS: Among the 2408 randomized participants, 1319 (54%) completed their safety survey 1 week after vaccination, with a higher completion rate among the web-based notification platform users (767/1196, 64%) than among mobile app users (552/1212, 45%; P<.001). Ease-of-use ratings were high for the web-based notification platform users (99% strongly agree or agree) and 88.8% of them strongly agreed or agreed that the system made reporting AEFIs easier. Web-based notification platform users supported the statement that a web-based notification-only approach would make it easier for public health professionals to detect vaccine safety signals (91.4%, agreed or strongly agreed). CONCLUSIONS: Participants in this study were significantly more likely to respond to a web-based safety survey rather than within a mobile app. These results suggest that mobile apps present an additional barrier for use compared to the web-based notification-only approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT05794113; https://clinicaltrials.gov/show/NCT05794113.

Epidemiological characteristics of seasonal influenza under implementation of zero-COVID-19 strategy in China.

OBJECTIVE: Respiratory viral diseases have posed a persistent threat to public health due to their high transmissibility. Influenza virus and SARS-Cov-2 are both respiratory viruses that have caused global pandemics. A zero-COVID-19 strategy is a public health policy imposed to stop community transmission of COVID-19 as soon as it is detected. In this study, we aim to examine the epidemiological characteristics of seasonal influenza in the past five years before and after the emergence of COVID-19 in China and observe the possible impact of the strategy on influenza. METHODS: Data from two data sources were retrospectively analyzed. A comparison on influenza incidence rate between Hubei and Zhejiang provinces was conducted based on data from the Chinese Center for Disease Control and Prevention (CDC). Then a descriptive and comparative analysis on seasonal influenza based on data from Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital before and after the outbreak of SARS-CoV-2 was conducted. RESULTS: From 2010-2017, both provinces experienced relatively low influenza activity until the 1st week of 2018, when they reached peak incidence rates of 78.16/100000PY, 34.05/100000PY respectively. Since then, influenza showed an obvious seasonality in Hubei and Zhejiang until the onset of COVID-19. During 2020 and 2021, there was a dramatic decline in influenza activity compared to 2018 and 2019. However, influenza activity seemed to rebound at the beginning of 2022 and surged in summer, with positive rates of 20.52% and 31.53% in Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital respectively as of the time writing this article. CONCLUSIONS: Our results reinforce the hypothesis that zero-COVID-19 strategy may impact the epidemiological pattern of influenza. Under the complex pandemic situation, implementation of NPIs could be a beneficial strategy containing not only COVID-19 but also influenza.

Immune interference in effectiveness of influenza and COVID-19 vaccination.

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic.

Evaluation of missed influenza vaccination opportunities in the emergency department.

BACKGROUND: Seasonal influenza is associated with significant healthcare resource utilization. An estimated 490,000 hospitalizations and 34,000 deaths were attributed to influenza during the 2018-2019 season. Despite robust influenza vaccination programs in both the inpatient and outpatient setting, the emergency department (ED) represents a missed opportunity to vaccinate patients at high risk for influenza who do not have access to routine preventive care. Feasibility and implementation of ED-based influenza vaccination programs have been previously described but have stopped short of describing the predicted health resource impact. The goal of our study was to describe the potential impact of an influenza vaccination program in an urban adult emergency department population using historic patient data. METHODS: This was a retrospective study of all encounters within a tertiary care hospital-based ED and three freestanding EDs during influenza season (defined as October 1 - April 30) over a two-years, 2018-2020. Data was obtained from the electronic medical record (EPIC®). All ED encounters during the study period were screened for inclusion using ICD 10 codes. Patients with a confirmed positive influenza test and no documented influenza vaccine for the current season were reviewed for any ED encounter at least 14 days prior to the influenza-positive encounter and during the concurrent influenza season. These ED visits were deemed a missed opportunity to provide vaccination and potentially prevent the influenza-positive encounter. Healthcare resource utilization, including subsequent ED encounters and inpatient admissions, were evaluated for patients with a missed vaccination opportunity. RESULTS: A total of 116,140 ED encounters occurred during the study and were screened for inclusion. Of these, 2115 were influenza-positive encounters, which represented 1963 unique patients. There were 418 patients (21.3%) that had a missed opportunity to be vaccinated during an ED encounter at least 14 days prior to the influenza-positive encounter. Of those with a missed vaccination opportunity, 60 patients (14.4%) had subsequent influenza-related encounters, including 69 ED visits and 7 inpatient admissions. CONCLUSION: Patients presenting to the ED with influenza frequently had opportunities to be vaccinated during prior ED encounters. An ED-based influenza vaccination program could potentially reduce influenza-related burden on healthcare resources by preventing future influenza-related ED encounters and hospitalizations.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.