Influenza Vaccination

7-mark short note · 10 high-yield points

High-Yield Points

Latest Updates (2023–Present) — three points

Enhanced vaccines are now preferentially recommended. Since 2022 ACIP has preferentially recommended high-dose, adjuvanted or recombinant influenza vaccine over standard-dose vaccine for all adults aged 65 and above. A 2026 test-negative design study in Open Forum Infectious Diseases found comparable effectiveness between adjuvanted and high-dose quadrivalent vaccines, so either is acceptable — the recommendation is for an enhanced vaccine, not for one specific brand.

DANFLU-2 — the definitive trial, with a nuanced result. Published in NEJM (2025), this pragmatic registry-based randomised trial of 332,438 Danish adults aged 65 and above across three seasons is the largest individually randomised influenza vaccine trial ever conducted. High-dose vaccine did not significantly reduce the primary endpoint of hospitalisation for influenza or pneumonia. However, prespecified secondary analyses showed lower cardiorespiratory hospitalisation (2.25% vs 2.38%), driven by cardiovascular hospitalisation (1.30% vs 1.40%), and reduced myocarditis and pericarditis (relative effectiveness 45.7%). Benefit was consistent irrespective of diabetes status (JAMA Internal Medicine, 2026) and atrial fibrillation (JACC, 2025).

Pooled and meta-analytic data favour high-dose. Pooled with the methodologically harmonised GALFLU trial from Galicia, Spain — 466,320 individually randomised older adults in total — there were significant reductions in hospitalisation for influenza or pneumonia, cardiorespiratory illness, laboratory-confirmed influenza and all causes. A 2026 systematic review and meta-analysis in JAMA Network Open of 8 trials and 605,098 participants confirmed high-dose vaccine reduced hospitalisations for influenza, laboratory-confirmed influenza, pneumonia or influenza, cardiorespiratory disease and all causes compared with standard dose.

Current Practice Update

Aspect Textbook Position Current Evidence (2023–2026)

Which formulation Standard vaccine; adjuvanted particularly High-dose, adjuvanted or recombinant valuable in institutionalised and chronically preferentially recommended for all ill aged 65+ (ACIP since 2022); adjuvanted and high-dose comparable Strength of evidence for high-dose Not addressed DANFLU-2 neutral on primary endpoint, but pooled DANFLU-2 + GALFLU (466,320)

and 2026 meta-analysis (605,098) favour high-dose Cardiovascular benefit Not described Signal for reduced cardiovascular hospitalisation, myocarditis and pericarditis — exploratory, from a neutral primary trial Availability in India Not addressed Standard quadrivalent widely available; high-dose and adjuvanted formulations largely unavailable — standard-dose annual vaccination remains the practical recommendation Examiner's Tip

Rapid Revision Grid

Numbers, criteria and named evidence — the last-hour page Definitions and Diagnostic Criteria Entity Criterion Classical FUO (Petersdorf/Beeson 1961) >38.3°C on several occasions, >3 weeks, undiagnosed after 1 week inpatient work-up FUO (Durack/Street 1991) — current >38.3°C, >3 weeks, undiagnosed after 3 days inpatient or 3 outpatient visits IUO Prolonged raised acute-phase reactants without fever Fever in long-term care (elderly) Single oral >100°F, or repeated oral >99°F, or rise >2°F above baseline WHO influenza-like illness Acute respiratory infection, onset <10 days, measured fever ≥38°C, and cough Postherpetic neuralgia Pain persisting ≥90 days after rash onset Disseminated zoster >20 vesicles outside the primary dermatome Severe C. difficile infection WBC >15,000 cells/µl or serum creatinine ≥1.5 mg/dl Fulminant C. difficile Severe disease plus hypotension, shock, ileus or megacolon Diarrhoea ≥3 unformed stools in 24 hours Infection suspicion in LTC WBC >14,000 cells/mm³ or left shift >6% Key Numbers Fact Figure Fever absent in older adults with serious infection 30–50% (>50% in LTC residents) Fever and cough absent in elderly pneumonia 30–40% Zoster incidence, age >60 11.8 per 1000 per year (all ages 1.2–3.4)

Zoster incidence, India (ICMR) ~3.3 per 1000 per year; >90% VZV-seropositive by age 40 Lifetime zoster risk by age 85 Up to 50% PHN in those >60 with zoster >40% Shingrix vs Zostavax efficacy 90% vs 30% Antiviral window in zoster 72 hours from rash onset C. difficile recurrence after first episode 15–25% (40–60% thereafter)

Fidaxomicin NNT vs vancomycin (initial episode) 10 at 4 weeks; 7 at 30 days for recurrence Influenza deaths in those ≥65 during epidemics >90% of all pneumonia/influenza deaths Influenza vaccine benefit ~50% risk reduction; ~70% mortality reduction Influenza vaccine effectiveness in nursing homes ~40% against clinical illness; higher against death Nursing-home coverage preventing outbreaks >80% of residents PCV21 vs PCV20 IPD serotype coverage in adults ~84–86% vs ~58–59% Indian adult vaccination coverage <2–3% for most vaccines FDG PET-CT in over-75s with FUO/IUO Diagnosis in 30.8%; treatment changed 38.8%; false positive 15.2% Named Trials and Guidelines Name What it showed / what it changed DANFLU-2 (NEJM 2025) 332,438 adults ≥65; high-dose vs standard influenza vaccine. Neutral on primary endpoint (influenza/pneumonia hospitalisation); secondary reductions in cardiorespiratory and cardiovascular hospitalisation GALFLU (NEJM 2025) Galicia, Spain; harmonised with DANFLU-2. Pooled total 466,320 randomised — significant reductions in influenza/pneumonia, cardiorespiratory, lab-confirmed influenza and all-cause hospitalisation DANFLU-1 Pilot trial; post-hoc analyses by frailty score and atrial fibrillation (2025) CAPiTA PCV13 in community-dwelling adults >65 reduced pneumococcal pneumonia by 45% Shingles Prevention Study Original Zostavax trial; incidence of zoster in >60s 11.8/1000/year (Oxman, NEJM 2005)

Nature 2025 Welsh natural Herpes zoster vaccination reduced dementia incidence by ~20% over 7 years — strongest experiment (Eyting et al.) causal evidence JAMA 2025 (Pomirchy et al.) Australian natural experiment replicating the dementia finding Nature Medicine 2024 RZV vs live vaccine: 17% increase in dementia diagnosis-free time over 6 years (Taquet et al.)

DAN-ZOSTER Pragmatic RCT of RZV for MACE and dementia in adults ≥65; started 2026, completion 2029.

Results awaited

IDSA/SHEA 2021 focused Fidaxomicin first-line for initial and recurrent C. difficile; metronidazole not preferred update ACG 2021 / AGA 2024 ACG guideline on C. difficile; AGA restricts FMT to adjunct or last resort ACIP October 2024 Routine pneumococcal conjugate vaccination age lowered from 65 to 50 ACIP April 2025 RSV vaccination risk-based age lowered from 60 to 50 API Indian Consensus First unified Indian adult immunisation schedule; 13 collaborating societies Guidelines 2024 (updated 2026)

JIAG position statement Indian Academy of Geriatrics recommendations for vaccination in adults ≥60 2026 Drug Doses to Quote Indication Regimen Herpes zoster — valaciclovir 1 g three times daily × 7 days Herpes zoster — famciclovir 500 mg three times daily × 7 days Herpes zoster — aciclovir 800 mg five times daily × 7–10 days (reduce if CrCl <30 ml/min) Severe/disseminated zoster IV aciclovir 10 mg/kg 8-hourly Established PHN Topical lidocaine patch, gabapentin or pregabalin (FDA-approved); nortriptyline or opioids as alternatives C. difficile — initial episode Fidaxomicin 200 mg BD × 10 days, or oral vancomycin 125 mg QID × 10 days C. difficile — fulminant Oral vancomycin 500 mg QID (+ PR if ileus) plus IV metronidazole 500 mg 8-hourly Influenza outbreak in institution Oseltamivir within 24–48 h to cases and contacts throughout outbreak; reduce dose if CrCl <30 ml/min Tetanus primary series (adult) Td 0.5 ml IM, repeated at 2 and 6 months; booster every 10 years, at least one as Tdap Zoster vaccine (RZV) Two doses IM, 2–6 months apart, from age 50 Pneumococcal, PCV-naive adult ≥50 Single PCV20 or PCV21 alone; or PCV15 then PPSV23 ≥1 year later The five statements most likely to earn or lose you marks