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Flu Vaccination Dr Sharda Jain

The document discusses influenza, its impact, symptoms, transmission, and the importance of vaccination, particularly the advancements towards quadrivalent vaccines. It highlights the risk factors for severe influenza outcomes, especially among pregnant women and healthcare workers, and provides data on influenza cases in India from 2010 to 2019. Additionally, it elaborates on the benefits of maternal vaccination and the role of immunization in protecting vulnerable populations.

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FLU Vaccination Dr Sharda Jain
CONTENT What is Influenza Influenza outbreaks and pandemics Impact of Influenza Influenza vaccine: Rationale Influenza vaccine safety & effectiveness When, whom & how to vaccinate? IND1134295
Influenza From Italian Influentia2 Respiratory disease Epidemics described by Hippocrates 5th century BC1 Source: 1. Martin. Emerg .Inf. 2006;12:976-980. 2. Online Etymology Dictionary 1933: Discovery of influenza virus4 1173-74 First description of influenza epidemic in Europe3 IND1134295
HA, hemagglutinin; NA, neuraminidase Influenza is a member of the Orthomyxoviridae family of viruses  Influenza A and B cause seasonal epidemics, C mainly causes mild respiratory illness  Influenza A is divided into subtypes based on the HA and NA proteins H1N1 H1N2 H2N1 H2N2 Orthomyxovirida e family A 18 HA proteins 11 NA proteins B C H1 H2 N1 N2 INFLUENZA VIRUS HAS SEVERAL SUBTYPES! IND1134295
INFLUENZA INFECTION HAS A VARIETY OF SYMPTOMS! Clinical symptoms Asymptomatic in 30–50% of cases • Common symptoms include abrupt onset of fever (38–40°C), sore throat, unproductive cough, runny or stuffy nose, headache, myalgia, chills, anorexia and extreme fatigue • Uncommon symptoms include photophobia, abdominal pain and diarrhea • Illness improves in under 7 days, cough and malaise may persist for weeks Virus shedding • Adults: from the day before symptoms appear until 5 days after illness onset • Young children: several days before illness onset until >10 days afterwards • Severely immunocompromised patients: weeks to months Symptoms associated with seasonal influenza are well defined and can vary between individuals IND1134295
CLINICAL DIFFERENTIATION: COMMON COLD & FLU High fever lasting 3 to 4 days Headache Myalgia Fatigue and weakness Extreme exhaustion Severe chest discomfort and cough • Stuffy nose is common • Sneezing is common • Cough is generally mild to moderate • Symptoms such as fever, headache, aches and pains and exhaustion are rare in those with colds More common in influenza than common cold More common in common cold than Influenza Sources:https://www.cdc.gov/flu/consumer/symptoms.htm IND1134295
INFLUENZA VIRUSES ARE SPREAD BY VIRUS-LADEN AEROSOLS! Spread: • Respiratory droplet transmission • droplets only travel <1m • By contact with surfaces contaminated with respiratory droplets • By airborne transmission of evaporated droplets that may remain in the air for long periods of time Virus transmission may be slowed by social distancingCDC IND1134295
RESERVOIRS OF INFLUENZA VIRUSES MIGRATING AQUATIC BIRDS Source: http://www.aht.org.uk/cms-display/science_eqflu.html as accessed on 12 June 2014, 11:06 am IND1134295
INFLUENZA VIRUS: DRIFT AND SHIFT Shift: Reassortant; pandemic flu Avian flu Source: Doherty and Turner Journal of Biology 2009 8:46 doi:10.1186/jbiol147. http://jbiol.com/content/8/5/46/figure/F1?highres=y as accessed on 12 June 2014, 11:10 am Drift: seasonal flu IND1134295
HUMAN INFLUENZA: APPEARANCES Seasonal Influenza (A: H3N2, H1N1; B)* Avian Influenza (A: H7N7, H5N1….) Pandemic Influenza (A: H1N1, H2N2, H3N2, …..?) Less Severity Higher Frequency Source: http://www.who.int/mediacentre/factsheets/fs211/en/ as accessed on 12 June 2014, 11:12 am Lower FrequencyGreater Severity *Type C seasonal disase is rarely reported IND1134295
INFLUENZA PANDEMICS & EMERGING NEW PANDEMIC THREATS EXIST SINCE 1900! The emergence of H1N1 has demonstrated the difficulty in predicting pandemics Source: Nicholson KG, Wood JM, Zambon M. Lancet 2003; 362:1733-1745; WHO, Cumulative number of confirmed human cases of avian influenza A/(H5N1), available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_09_10/en/index.html (accessed 5 November 2008); CDC, Avian Influenza, available at: http://www.cdc.gov/flu/avian/outbreak.htm as accessed 12 June 2014, 11:14 am. Pandemic outbreaks Recent outbreaks of influenza 1918 1957 1977 2000 2008 >50 million deaths H1N1 1918 Spanish 1957 Asian ~2 million deaths H2N 2 1968 Hong Kong ~1 million deaths H3N 2 <1 million deaths H1N1 1977 Russia n H9N 2 1999 Hong Kong 2 cases H5N1 1997 Hong Kong 18 cases Six deaths H7N7 82 cases One death H5N1 2003- 2008 Global 387 cases 245 deaths 2003 Dutch 1968 H1N1 2009 Global ~30,00 0 cases 145 deaths 2009 Pandemic IND1134295
Sources: 1. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2010 to 2017. Available from http://www.idsp.nic.in/showfile.php?lid=3933 ; accessed on 28th June 2018 . 2. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2012 to 2019. Available from https://ncdc.gov.in/showfile.php?lid=280 ; accessed on 20th Jan 2020 Year Cases (Lab confirmed) Deaths 2010 20604 1763 2011 603 75 2012 5044 405 2013 5253 699 2014 937 218 2015 42592 2990 2016 1786 265 2017 38811 2270 2018 15266 1113 2019 (As on 22nd Dec 2019) 28714 1216 INDIA - SEASONAL INFLUENZA CASES - 2 0 1 0 TO 2 0 1 9
Recent Lab-confirmed Indian Flu Data IND1134295
DESCRIPTIVE STATISTICS OF SAMPLE POPULATION Sample population 12,825 Mean age 35.9 Years Standard deviation 23.9 Range (Age) 8 months – 100 years Males 6,608 (51.5%) Time interval Apr 2014 – Dec 2017 State wise sample mix Maharashtra: 8,553 (66.7%) Delhi: 2,192 (17.1%) Tamilnadu: 1,169 (9.1%) Uttar Pradesh / Uttarakhand: 558 (4.4%) Haryana: 313 (2.4%) Rajasthan: 40 (0.3%) Source: Jain D, Singh M, Budhiraja S, Arora S, Tarai B and Singhal B. Influenza in India. Lab-based real world evidence insights. Data on file. IND1134295
Maharashtra: 8,553 (66.7%) Delhi: 2,192 (17.1%) Tamilnadu: 1,169 (9.1%) Uttar Pradesh / Uttarakhand: 558 (4.4%)Haryana: 313 (2.4%) Rajasthan: 40 (0.3%) IND1134295
0-3 years 9% 3-5 years 6% 5-18 years 10% 18-30 years 14% 30-50 years 32% 50-60 years 14% 60-70 years 9% >70 years 6% Percentage H1N1 burden across age 0-3 years 3-5 years 5-18 years 18-30 years 30-50 years 50-60 years 60-70 years >70 years P E R C E N T A G E D I S T R I B U T I O N O F T O T A L B U R D E N ( P O S I T I V E C A S E S ) B Y A G E C A T E G O R Y 30-50 years group (Adults) shows the highest (almost one third) contribution of total H1N1 burden Source: Jain D, Singh M, Budhiraja S, Arora S, Tarai B and Singhal B. Influenza in India. Lab-based real world evidence IND1134295
Influenza vaccines IND1134295
Whole virus vaccine (1945) Split virus vaccine (1964) 3rd generation 1st generation 2nd generation Subunit vaccine (1976) 1. Wood JM, Williams MJ. Textbook of Influenza 1998; pg no 317-323. 2. Shah R et al. Asian Journal of Paediatric Practice. 2018; 1(5): 19-28. HISTORICAL DEVELOPMENT IN INFLUENZA VACCINATION SUV presents better tolerability and lower reactogenicity as compared to other vaccine types IND1134295
Influenza: QIV – for Whom is it Must? IND1134295
WHY NOT TIV? Shasha D et al, where QIV was compared with TIV over 2 flu seasons: • protection offered by the TIV is unsatisfactory. • transition from the TIV to QIV should be considered, similar to the transition from a bivalent vaccine (A/H3N2 and B) to a trivalent vaccine (A/H1N1, A/H3N2 and B) in 1977 due to lack of cross protection and adequate coverage by the bivalent vaccine. • the inclusion of a fourth antigen in the vaccine is feasible and safe, and does not reduce immunogenicity to the other antigens in the TIV, or the overall manufacturing capacity of influenza vaccines. Source: Shasha D et al. Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons, historical cohort study. Clin Microbiol Infect. 2019 May 17. pii: S1198-743X(19)30216-2. IND1134295
RATIONALE FOR QUADRIVALENT INACTIVATED INFLUENZA VACCINE (QIV) Sources: 1) Beyer WEP et al. Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials. Vaccine. 2017 Jul 24;35(33):4167-4176. 2) Tisa V et al. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden. J Prev Med Hyg. 2016 Mar; 57(1): E28–E33. IND1134295
IMPACT OF QIV • QIV can prevent 11.2% of all influenza B infections which still occur with TIV, thus reducing the influenza burden on the community. • QIVs could reduce both direct costs in term of medical visits, hospitalizations and antibiotic prescriptions, and indirect costs related to working days lost by affected people and their caregivers. Source: Tisa V et al. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden. J Prev Med Hyg. 2016;57(1):E28-33. IND1134295
DIFFERENCES IN STRAIN COMPOSITIONS SH 2020:  an A/Brisbane/02/2018 (H1N1) pdm09-like virus  an A/South Australia/34/2019 (H3N2)-like virus  a B/Washington/02/2019-like (B/Victoria lineage) virus  a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) NH 2020-21:  an A/Guangdong-Maonan/ SWL1536/2019 (H1N1) pdm09-like virus  an A/Hong Kong/2671/2019 (H3N2)- like virus  a B/Washington/02/2019 (B/Victoria lineage)-like virus  a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus Source: 1) WHO Recommended composition of influenza virus vaccines for use in the 2020 southern hemisphere influenza season. Available from: https://www.who.int/influenza/vaccines/virus/recommendations/2020_south/en/ ; accessed on 11th August 2020 @ 11:30 AM. 2) WHO Recommended composition of influenza virus vaccines for use in the 2020 - 2021 northern hemisphere influenza season. Available from: https://www.who.int/influenza/vaccines/virus/recommendations/2020-21_north/en/ ; ; accessed on 11th August 2020 @ 11:30 AM.
High Risk Groups Pregnant women/women trying to conceive Children (6 mths - 5 yrs old) Elderly (≥65 yrs) Health-care workers Individuals with chronic medical conditions Source: http://www.cdc.gov/flu/about/disease/high_risk.htm as accessed on 02/07/2014 12:30 pm HIGH RISK GROUPS
26 INFLUENZA: PREGNANT WOMEN Burden • Pregnant women are at particular risk of severe complications and death from influenza • And the risk is exacerbated by co-morbidities such as asthma, diabetes mellitus, and obesity, and late trimester pregnancy. • May also lead to complications such as stillbirth, neonatal death, pre-term delivery, and decreased birth weight. SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. Mosby LG. et al. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol. 2011; 205:10–18. CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR 2010;59(RR-8):1-62. Omer SB. et al. Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study. PLoS Medicine 2011;8:e1000441. IND1134295
27 INFLUENZA: PREGNANT WOMEN Benefits • Maternal immunization against influenza not only protects the women but also prevents negative effects on fetal development due to maternal influenza infections and reduces rates of illness in infants for at least the first 6 months of life. • Inactivated vaccines have been shown to be safe and effective in pregnant women and their offspring when given at any trimester. SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. IND1134295
28 INFLUENZA: HEALTH CARE WORKERS Burden: • Health care workers are additional risk of being exposed to influenza compared to the general population. • They risk passing on influenza to patients who are at increased risk of severe disease and may respond less well to vaccine. • Transmission of influenza from HCW to patients was given as a principle source of infection for patients in a review of nosocomial influenza infection. • Last, staff absences due to influenza can impact and disrupt health services. • Vaccination rates of HCW remain low in many countries. • A review on health care workers attitudes to influenza vaccination found lack of knowledge and lack of convenient access to the vaccine as the main reasons for lack of vaccine uptake. SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. Kuster SP. et al. Incidence of influenza in healthy adults and healthcare workers: a systematic review and meta-analysis. PLoS One 2011 6:e26239. Hollmeyer HG. et al. Influenza vaccination in health care workers in hospitals – a review of studies on attitudes and predictors. Vaccine 2009 27:3935-44. IND1134295
29 INFLUENZA: HEALTH CARE WORKERS Benefits • Vaccination not only protects health care workers and it also protects vulnerable patients. • It also may reduce work absenteeism and consequent disruption to health services. IND1134295
BURDEN OF INFLUENZA IN PREGNANCY 31 Disease burden of influenza among pregnant women is significant, particularly in low- resource environments/developing countries1 4.3% of deaths due to the 2009 pandemic were of pregnant women (previously healthy prior to onset of the disease)2 Up to 18-fold increase in likelihood of hospitalization due to RI during flu season among pregnant women (vs year preceding pregnancy)3 Source: 1. Mulholland EK et al. Etiology of serious infections in young Gambian infants. The Pediatric Infectious Disease Journal 1999;18(October (10 Suppl.)):S35–41. 2. Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. Obstetrics and Gynecology 2010;115 (April (4)):717–26. 3. Mark H Yudin. Risk management of seasonal influenza during pregnancy: current perspectives. Int J Womens Health. 2014; 6: 681–689.
IMPACT OF INFLUENZA ON PREGNANCY OUTCOMES 34 Influenza during pregnancy Spontaneous abortion1 Still birth or premature birth1 4-fold increase in odds of Cesarean delivery2 Women who delivered preterm were more likely to be infected by flu virus during 3rd trimester, to have a secondary pneumonia and to have been admitted to an ICU2 Source: 1. Pierce M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M. Perinatal outcomes after maternal 2009/ H1N1 infection: national cohort study. BMJ 2011; 342:d3214; 2. Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Hospitalizations with respiratory illness among pregnant women during influenza season. Obstet Gynecol 2006; 107:1315-22;
RISK OF INFLUENZA INFECTION IN INFANTS Infants & young children (particularly < 6 mths of age) have the highest rate of influenza infection & hospitalization rates amongst the pediatric population Factors involved include Immaturity of the infant’s immune system Absence of prior immunity/exposur e to the virus Increased vulnerability to cardiorespiratory conditions Source: Blanchard-Rohner and Siegrist. Vaccination during pregnancy to protect infants against influenza: Why and why not? Vaccine 2011. 29: 7542–7550.
Source: 1. Poehling KA, Edwards KM, Weinberg GA, Szilagyi P, Staat MA, Iwane MK, et al. The underrecognized burden of influenza in young children. The New England Journal of Medicine 2006;355(July (1)):31–40.) 2. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, et al. Influenza-associated deaths among children in the United States, 2003–2004. The New England Journal of Medicine 2005;353(December (24)):2559–67. 3. Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342:225-31. IMPACT OF INFLUENZA IN YOUNG INFANTS 36 Population-based surveillance study found hospital admission rates for laboratory-confirmed influenza US National Assessment of pediatric mortality associated with lab-confirmed influenza in 4 flu season 0-5 mths of age = 4.5/1000 children 6-23 mth of age = 0.9/1000 children1 Highest in children <6 mths of age2
• Reduces number of influenza-related hospitalizations & deaths • Vaccination of pregnant women reduces the burden of influenza in children <6 mths old in 2 ways: • Reduce the risk of being infected after delivery, thus also reducing the risk of transmission to the child during the 1st mths of life • Transmission of influenza antibodies from the mother to the child RATIONALE FOR INFLUENZA VACCINATION Because both the use of antiviral therapy as well as influenza vaccine are not indicated for use in children < 6 mths, there is lack of alternatives to protect these children against influenza Source: http://ecdc.europa.eu/en/publications/Publications/Seasonal%20influenza%20vaccination%20of%20children%20and%20pregnant%20women.pdf as accessed on 12th December 2015, at 2:28pm
Source: Maltezou HC1 et al. Impact of postpartum influenza vaccination of mothers and household contacts in preventing febrile episodes,influenza-like illness, healthcare seeking, and administration of antibiotics in young infants during the 2012-2013 influenza season. Clin Infect Dis. 2013 Dec;57(11):1520-6. POST-PARTUM INFLUENZA VACCINATION OUTCOMES: IN INFANTS 38 Outcomes in Infants Acute Respiratory illness Febrile episode Influenza-like illness Healthcare seeking Administration of antibiotics 37.7% Reduction 50.3% Reduction 53.5% Reduction 41.8% Reduction 45.4% Reduction
SAFETY OF INFLUENZA VACCINE 39 Conclusions: Results do not indicate that maternal influenza vaccination is associated with an increased risk of fetal death, spontaneous abortion, or congenital malformations.2 Excellent and robust safety profile of multiple inactivated influenza vaccine preparations over many decades, and the potential complications of influenza disease during pregnancy, support WHO recommendations that pregnant women should be vaccinated.1 This systematic review did not indicate an increased risk for congenital anomalies after maternal influenza immunization consolidating the safety of influenza vaccination in pregnancy.3 Source: 1. http://www.who.int/vaccine_safety/publications/safety_pregnancy_nov2014.pdf. 2. McMillan M, Porritt K, Kralik D, Costi L, Marshall H. Influenza vaccination during pregnancy: a systematic review of fetal death, spontaneous abortion, andcongenital malformation safety outcomes. Vaccine. 2015 Apr 27;33(18):2108-17. 3. Polyzos KA1, Konstantelias AA, Pitsa CE, Falagas ME. Maternal Influenza Vaccination and Risk for Congenital Malformations: A Systematic Review and Meta-analysis. Obstet Gynecol. 2015 Nov;126(5):1075-84.
HOW TO VACCINATE ?
• All persons 6 mths & older should be vaccinated annually CDC Centers for Disease Control and Prevention • All women who are pregnant during influenza season receive inactivated influenza vaccine ACIP Advisory committee on immunization practices • Recommends seasonal influenza vaccination to pregnant women as the highest priority WHO World Health Organization • Recommends all women who are pregnant during influenza season receive inactivated influenza vaccine ACOG The American College of Obstetricians and Gynecologists • Recommended from 26 weeks onwardsFOGSI INFLUENZA VACCINE RECOMMENDATION: PREGNANCY Source: http://www.who.int/immunization/newsroom/newsstory_seasonal_influenza_vaccination_pregnancy/en/ as accessed on 06/07/2014, 4:30 pm. https://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Obstetric%20Practice/co468.pdf?dmc=1&ts=20140702T0616350498, as accessed 06/07/14. http://www.fogsi.org/images/stories/pdf/vaccination_women.pdf
Maternal immunity is the only effective strategy in newborns because the vaccine is not approved for use in infants younger than 6 months WHAT IS THE BEST VACCINATION STRATEGY TO PROTECT INFANTS <6 MONTHS? Source: http://www.ecdc.europa.eu/en/publications/publications/seasonal%20influenza%20vaccination%20of%20children%20and%20pregnant%20women.pdf as accessed on 02/07/2014, 3:30 pm Protecting the mother and her unborn child from serious illness by vaccinating pregnant women
Source: http://gamapserver.who.int/mapLibrary/Files/Maps/GISRS_20130425_1.png as accessed on 11 June 2014, 5:51 pm 106 Member countries 136 NIC 6 WHO CCS 4 ERLS 11 H5 Ref Labs GLOBAL SURVEILLANCE NETWORK: WHO IND1134295
SEASONALITY OF FLU • India has distinct seasonality • Rainfall correlates with influenza peaks in many of the cities • Recent surveillance data from tropical regions of Asia have revealed a seasonal pattern characterized by year round low- level influenza virus circulation with peaks occurring during the monsoon (rainy) season Source: 1) Chadha MS et al. Dynamics of influenza seasonality at sub-regional levels in India and implications for vaccination timing. PLoS One. 2015 May 4;10(5):e0124122. 2) Saha S et al. Divergent seasonal patterns of influenza types A and B across latitude gradient in Tropical Asia. Influenza Other Respir Viruses. 2016 May;10(3):176-84. IND1134295
LIMITED INFLUENZA ACTIVITY IS USUALLY SEEN THROUGHOUT THE YEAR • Limited influenza activity is usually seen throughout the year in India with a clear peaking during the rainy season. • The rainy season in the country lasts from June to August in all the regions except Tamil Nadu where it occurs from October to December. IND1134295
THANK YOU

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In this document
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Introduction to influenza, its impact, vaccination rationale, and guidelines for vaccination.

Historical context of influenza, virus types, and subtypes, including symptoms and clinical differences.

Details on influenza transmission, symptoms, and differentiating factors from common cold.

Reservoirs of the virus, antigenic drift and shift, and various influenza virus appearances and severities.

Overview of past influenza pandemics with significant mortality rates and recent Indian flu data.

Descriptive statistics of sampled population for influenza studies in India.

Distribution of H1N1 burden by age and the rationale for Quadrivalent Inactivated Influenza Vaccine.

Impact of quadrivalent vaccines, benefits over trivalent vaccines, and detailed strain compositions.

Identification of high-risk groups for influenza and the importance of vaccination for pregnant women.

Burden on healthcare workers from influenza and the benefits of their vaccination.

Challenges and impacts of influenza in pregnant women, including potential adverse outcomes.

Hospitalization rates and risks of influenza in young children, and importance of maternal vaccination.

Benefits of maternal vaccination on infant health and safety data regarding influenza vaccines.

Guidelines for annual vaccination and strategies to protect infants through maternal vaccination.

WHO surveillance mechanisms for influenza and the seasonal patterns observed in India.

Flu Vaccination Dr Sharda Jain

  • 1.
  • 2.
    CONTENT What is Influenza Influenzaoutbreaks and pandemics Impact of Influenza Influenza vaccine: Rationale Influenza vaccine safety & effectiveness When, whom & how to vaccinate? IND1134295
  • 3.
    Influenza From Italian Influentia2 Respiratory disease Epidemics describedby Hippocrates 5th century BC1 Source: 1. Martin. Emerg .Inf. 2006;12:976-980. 2. Online Etymology Dictionary 1933: Discovery of influenza virus4 1173-74 First description of influenza epidemic in Europe3 IND1134295
  • 4.
    HA, hemagglutinin; NA,neuraminidase Influenza is a member of the Orthomyxoviridae family of viruses  Influenza A and B cause seasonal epidemics, C mainly causes mild respiratory illness  Influenza A is divided into subtypes based on the HA and NA proteins H1N1 H1N2 H2N1 H2N2 Orthomyxovirida e family A 18 HA proteins 11 NA proteins B C H1 H2 N1 N2 INFLUENZA VIRUS HAS SEVERAL SUBTYPES! IND1134295
  • 5.
    INFLUENZA INFECTION HASA VARIETY OF SYMPTOMS! Clinical symptoms Asymptomatic in 30–50% of cases • Common symptoms include abrupt onset of fever (38–40°C), sore throat, unproductive cough, runny or stuffy nose, headache, myalgia, chills, anorexia and extreme fatigue • Uncommon symptoms include photophobia, abdominal pain and diarrhea • Illness improves in under 7 days, cough and malaise may persist for weeks Virus shedding • Adults: from the day before symptoms appear until 5 days after illness onset • Young children: several days before illness onset until >10 days afterwards • Severely immunocompromised patients: weeks to months Symptoms associated with seasonal influenza are well defined and can vary between individuals IND1134295
  • 6.
    CLINICAL DIFFERENTIATION: COMMON COLD& FLU High fever lasting 3 to 4 days Headache Myalgia Fatigue and weakness Extreme exhaustion Severe chest discomfort and cough • Stuffy nose is common • Sneezing is common • Cough is generally mild to moderate • Symptoms such as fever, headache, aches and pains and exhaustion are rare in those with colds More common in influenza than common cold More common in common cold than Influenza Sources:https://www.cdc.gov/flu/consumer/symptoms.htm IND1134295
  • 7.
    INFLUENZA VIRUSES ARESPREAD BY VIRUS-LADEN AEROSOLS! Spread: • Respiratory droplet transmission • droplets only travel <1m • By contact with surfaces contaminated with respiratory droplets • By airborne transmission of evaporated droplets that may remain in the air for long periods of time Virus transmission may be slowed by social distancingCDC IND1134295
  • 8.
    RESERVOIRS OF INFLUENZAVIRUSES MIGRATING AQUATIC BIRDS Source: http://www.aht.org.uk/cms-display/science_eqflu.html as accessed on 12 June 2014, 11:06 am IND1134295
  • 9.
    INFLUENZA VIRUS: DRIFT ANDSHIFT Shift: Reassortant; pandemic flu Avian flu Source: Doherty and Turner Journal of Biology 2009 8:46 doi:10.1186/jbiol147. http://jbiol.com/content/8/5/46/figure/F1?highres=y as accessed on 12 June 2014, 11:10 am Drift: seasonal flu IND1134295
  • 10.
    HUMAN INFLUENZA: APPEARANCES SeasonalInfluenza (A: H3N2, H1N1; B)* Avian Influenza (A: H7N7, H5N1….) Pandemic Influenza (A: H1N1, H2N2, H3N2, …..?) Less Severity Higher Frequency Source: http://www.who.int/mediacentre/factsheets/fs211/en/ as accessed on 12 June 2014, 11:12 am Lower FrequencyGreater Severity *Type C seasonal disase is rarely reported IND1134295
  • 11.
    INFLUENZA PANDEMICS &EMERGING NEW PANDEMIC THREATS EXIST SINCE 1900! The emergence of H1N1 has demonstrated the difficulty in predicting pandemics Source: Nicholson KG, Wood JM, Zambon M. Lancet 2003; 362:1733-1745; WHO, Cumulative number of confirmed human cases of avian influenza A/(H5N1), available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_09_10/en/index.html (accessed 5 November 2008); CDC, Avian Influenza, available at: http://www.cdc.gov/flu/avian/outbreak.htm as accessed 12 June 2014, 11:14 am. Pandemic outbreaks Recent outbreaks of influenza 1918 1957 1977 2000 2008 >50 million deaths H1N1 1918 Spanish 1957 Asian ~2 million deaths H2N 2 1968 Hong Kong ~1 million deaths H3N 2 <1 million deaths H1N1 1977 Russia n H9N 2 1999 Hong Kong 2 cases H5N1 1997 Hong Kong 18 cases Six deaths H7N7 82 cases One death H5N1 2003- 2008 Global 387 cases 245 deaths 2003 Dutch 1968 H1N1 2009 Global ~30,00 0 cases 145 deaths 2009 Pandemic IND1134295
  • 12.
    Sources: 1. IntegratedDisease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2010 to 2017. Available from http://www.idsp.nic.in/showfile.php?lid=3933 ; accessed on 28th June 2018 . 2. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2012 to 2019. Available from https://ncdc.gov.in/showfile.php?lid=280 ; accessed on 20th Jan 2020 Year Cases (Lab confirmed) Deaths 2010 20604 1763 2011 603 75 2012 5044 405 2013 5253 699 2014 937 218 2015 42592 2990 2016 1786 265 2017 38811 2270 2018 15266 1113 2019 (As on 22nd Dec 2019) 28714 1216 INDIA - SEASONAL INFLUENZA CASES - 2 0 1 0 TO 2 0 1 9
  • 13.
    Recent Lab-confirmed IndianFlu Data IND1134295
  • 14.
    DESCRIPTIVE STATISTICS OF SAMPLEPOPULATION Sample population 12,825 Mean age 35.9 Years Standard deviation 23.9 Range (Age) 8 months – 100 years Males 6,608 (51.5%) Time interval Apr 2014 – Dec 2017 State wise sample mix Maharashtra: 8,553 (66.7%) Delhi: 2,192 (17.1%) Tamilnadu: 1,169 (9.1%) Uttar Pradesh / Uttarakhand: 558 (4.4%) Haryana: 313 (2.4%) Rajasthan: 40 (0.3%) Source: Jain D, Singh M, Budhiraja S, Arora S, Tarai B and Singhal B. Influenza in India. Lab-based real world evidence insights. Data on file. IND1134295
  • 15.
    Maharashtra: 8,553 (66.7%) Delhi:2,192 (17.1%) Tamilnadu: 1,169 (9.1%) Uttar Pradesh / Uttarakhand: 558 (4.4%)Haryana: 313 (2.4%) Rajasthan: 40 (0.3%) IND1134295
  • 16.
    0-3 years 9% 3-5 years 6% 5-18years 10% 18-30 years 14% 30-50 years 32% 50-60 years 14% 60-70 years 9% >70 years 6% Percentage H1N1 burden across age 0-3 years 3-5 years 5-18 years 18-30 years 30-50 years 50-60 years 60-70 years >70 years P E R C E N T A G E D I S T R I B U T I O N O F T O T A L B U R D E N ( P O S I T I V E C A S E S ) B Y A G E C A T E G O R Y 30-50 years group (Adults) shows the highest (almost one third) contribution of total H1N1 burden Source: Jain D, Singh M, Budhiraja S, Arora S, Tarai B and Singhal B. Influenza in India. Lab-based real world evidence IND1134295
  • 17.
  • 18.
    Whole virus vaccine (1945) Splitvirus vaccine (1964) 3rd generation 1st generation 2nd generation Subunit vaccine (1976) 1. Wood JM, Williams MJ. Textbook of Influenza 1998; pg no 317-323. 2. Shah R et al. Asian Journal of Paediatric Practice. 2018; 1(5): 19-28. HISTORICAL DEVELOPMENT IN INFLUENZA VACCINATION SUV presents better tolerability and lower reactogenicity as compared to other vaccine types IND1134295
  • 19.
    Influenza: QIV – forWhom is it Must? IND1134295
  • 20.
    WHY NOT TIV? ShashaD et al, where QIV was compared with TIV over 2 flu seasons: • protection offered by the TIV is unsatisfactory. • transition from the TIV to QIV should be considered, similar to the transition from a bivalent vaccine (A/H3N2 and B) to a trivalent vaccine (A/H1N1, A/H3N2 and B) in 1977 due to lack of cross protection and adequate coverage by the bivalent vaccine. • the inclusion of a fourth antigen in the vaccine is feasible and safe, and does not reduce immunogenicity to the other antigens in the TIV, or the overall manufacturing capacity of influenza vaccines. Source: Shasha D et al. Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons, historical cohort study. Clin Microbiol Infect. 2019 May 17. pii: S1198-743X(19)30216-2. IND1134295
  • 21.
    RATIONALE FOR QUADRIVALENT INACTIVATED INFLUENZA VACCINE (QIV) Sources:1) Beyer WEP et al. Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials. Vaccine. 2017 Jul 24;35(33):4167-4176. 2) Tisa V et al. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden. J Prev Med Hyg. 2016 Mar; 57(1): E28–E33. IND1134295
  • 22.
    IMPACT OF QIV •QIV can prevent 11.2% of all influenza B infections which still occur with TIV, thus reducing the influenza burden on the community. • QIVs could reduce both direct costs in term of medical visits, hospitalizations and antibiotic prescriptions, and indirect costs related to working days lost by affected people and their caregivers. Source: Tisa V et al. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden. J Prev Med Hyg. 2016;57(1):E28-33. IND1134295
  • 23.
    DIFFERENCES IN STRAINCOMPOSITIONS SH 2020:  an A/Brisbane/02/2018 (H1N1) pdm09-like virus  an A/South Australia/34/2019 (H3N2)-like virus  a B/Washington/02/2019-like (B/Victoria lineage) virus  a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) NH 2020-21:  an A/Guangdong-Maonan/ SWL1536/2019 (H1N1) pdm09-like virus  an A/Hong Kong/2671/2019 (H3N2)- like virus  a B/Washington/02/2019 (B/Victoria lineage)-like virus  a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus Source: 1) WHO Recommended composition of influenza virus vaccines for use in the 2020 southern hemisphere influenza season. Available from: https://www.who.int/influenza/vaccines/virus/recommendations/2020_south/en/ ; accessed on 11th August 2020 @ 11:30 AM. 2) WHO Recommended composition of influenza virus vaccines for use in the 2020 - 2021 northern hemisphere influenza season. Available from: https://www.who.int/influenza/vaccines/virus/recommendations/2020-21_north/en/ ; ; accessed on 11th August 2020 @ 11:30 AM.
  • 24.
    High Risk Groups Pregnant women/women trying to conceive Children (6mths - 5 yrs old) Elderly (≥65 yrs) Health-care workers Individuals with chronic medical conditions Source: http://www.cdc.gov/flu/about/disease/high_risk.htm as accessed on 02/07/2014 12:30 pm HIGH RISK GROUPS
  • 25.
    26 INFLUENZA: PREGNANT WOMEN Burden •Pregnant women are at particular risk of severe complications and death from influenza • And the risk is exacerbated by co-morbidities such as asthma, diabetes mellitus, and obesity, and late trimester pregnancy. • May also lead to complications such as stillbirth, neonatal death, pre-term delivery, and decreased birth weight. SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. Mosby LG. et al. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol. 2011; 205:10–18. CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR 2010;59(RR-8):1-62. Omer SB. et al. Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study. PLoS Medicine 2011;8:e1000441. IND1134295
  • 26.
    27 INFLUENZA: PREGNANT WOMEN Benefits •Maternal immunization against influenza not only protects the women but also prevents negative effects on fetal development due to maternal influenza infections and reduces rates of illness in infants for at least the first 6 months of life. • Inactivated vaccines have been shown to be safe and effective in pregnant women and their offspring when given at any trimester. SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. IND1134295
  • 27.
    28 INFLUENZA: HEALTH CAREWORKERS Burden: • Health care workers are additional risk of being exposed to influenza compared to the general population. • They risk passing on influenza to patients who are at increased risk of severe disease and may respond less well to vaccine. • Transmission of influenza from HCW to patients was given as a principle source of infection for patients in a review of nosocomial influenza infection. • Last, staff absences due to influenza can impact and disrupt health services. • Vaccination rates of HCW remain low in many countries. • A review on health care workers attitudes to influenza vaccination found lack of knowledge and lack of convenient access to the vaccine as the main reasons for lack of vaccine uptake. SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. Kuster SP. et al. Incidence of influenza in healthy adults and healthcare workers: a systematic review and meta-analysis. PLoS One 2011 6:e26239. Hollmeyer HG. et al. Influenza vaccination in health care workers in hospitals – a review of studies on attitudes and predictors. Vaccine 2009 27:3935-44. IND1134295
  • 28.
    29 INFLUENZA: HEALTH CAREWORKERS Benefits • Vaccination not only protects health care workers and it also protects vulnerable patients. • It also may reduce work absenteeism and consequent disruption to health services. IND1134295
  • 29.
    BURDEN OF INFLUENZAIN PREGNANCY 31 Disease burden of influenza among pregnant women is significant, particularly in low- resource environments/developing countries1 4.3% of deaths due to the 2009 pandemic were of pregnant women (previously healthy prior to onset of the disease)2 Up to 18-fold increase in likelihood of hospitalization due to RI during flu season among pregnant women (vs year preceding pregnancy)3 Source: 1. Mulholland EK et al. Etiology of serious infections in young Gambian infants. The Pediatric Infectious Disease Journal 1999;18(October (10 Suppl.)):S35–41. 2. Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. Obstetrics and Gynecology 2010;115 (April (4)):717–26. 3. Mark H Yudin. Risk management of seasonal influenza during pregnancy: current perspectives. Int J Womens Health. 2014; 6: 681–689.
  • 30.
    IMPACT OF INFLUENZAON PREGNANCY OUTCOMES 34 Influenza during pregnancy Spontaneous abortion1 Still birth or premature birth1 4-fold increase in odds of Cesarean delivery2 Women who delivered preterm were more likely to be infected by flu virus during 3rd trimester, to have a secondary pneumonia and to have been admitted to an ICU2 Source: 1. Pierce M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M. Perinatal outcomes after maternal 2009/ H1N1 infection: national cohort study. BMJ 2011; 342:d3214; 2. Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Hospitalizations with respiratory illness among pregnant women during influenza season. Obstet Gynecol 2006; 107:1315-22;
  • 31.
    RISK OF INFLUENZAINFECTION IN INFANTS Infants & young children (particularly < 6 mths of age) have the highest rate of influenza infection & hospitalization rates amongst the pediatric population Factors involved include Immaturity of the infant’s immune system Absence of prior immunity/exposur e to the virus Increased vulnerability to cardiorespiratory conditions Source: Blanchard-Rohner and Siegrist. Vaccination during pregnancy to protect infants against influenza: Why and why not? Vaccine 2011. 29: 7542–7550.
  • 32.
    Source: 1. PoehlingKA, Edwards KM, Weinberg GA, Szilagyi P, Staat MA, Iwane MK, et al. The underrecognized burden of influenza in young children. The New England Journal of Medicine 2006;355(July (1)):31–40.) 2. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, et al. Influenza-associated deaths among children in the United States, 2003–2004. The New England Journal of Medicine 2005;353(December (24)):2559–67. 3. Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342:225-31. IMPACT OF INFLUENZA IN YOUNG INFANTS 36 Population-based surveillance study found hospital admission rates for laboratory-confirmed influenza US National Assessment of pediatric mortality associated with lab-confirmed influenza in 4 flu season 0-5 mths of age = 4.5/1000 children 6-23 mth of age = 0.9/1000 children1 Highest in children <6 mths of age2
  • 33.
    • Reduces numberof influenza-related hospitalizations & deaths • Vaccination of pregnant women reduces the burden of influenza in children <6 mths old in 2 ways: • Reduce the risk of being infected after delivery, thus also reducing the risk of transmission to the child during the 1st mths of life • Transmission of influenza antibodies from the mother to the child RATIONALE FOR INFLUENZA VACCINATION Because both the use of antiviral therapy as well as influenza vaccine are not indicated for use in children < 6 mths, there is lack of alternatives to protect these children against influenza Source: http://ecdc.europa.eu/en/publications/Publications/Seasonal%20influenza%20vaccination%20of%20children%20and%20pregnant%20women.pdf as accessed on 12th December 2015, at 2:28pm
  • 34.
    Source: Maltezou HC1et al. Impact of postpartum influenza vaccination of mothers and household contacts in preventing febrile episodes,influenza-like illness, healthcare seeking, and administration of antibiotics in young infants during the 2012-2013 influenza season. Clin Infect Dis. 2013 Dec;57(11):1520-6. POST-PARTUM INFLUENZA VACCINATION OUTCOMES: IN INFANTS 38 Outcomes in Infants Acute Respiratory illness Febrile episode Influenza-like illness Healthcare seeking Administration of antibiotics 37.7% Reduction 50.3% Reduction 53.5% Reduction 41.8% Reduction 45.4% Reduction
  • 35.
    SAFETY OF INFLUENZA VACCINE 39 Conclusions:Results do not indicate that maternal influenza vaccination is associated with an increased risk of fetal death, spontaneous abortion, or congenital malformations.2 Excellent and robust safety profile of multiple inactivated influenza vaccine preparations over many decades, and the potential complications of influenza disease during pregnancy, support WHO recommendations that pregnant women should be vaccinated.1 This systematic review did not indicate an increased risk for congenital anomalies after maternal influenza immunization consolidating the safety of influenza vaccination in pregnancy.3 Source: 1. http://www.who.int/vaccine_safety/publications/safety_pregnancy_nov2014.pdf. 2. McMillan M, Porritt K, Kralik D, Costi L, Marshall H. Influenza vaccination during pregnancy: a systematic review of fetal death, spontaneous abortion, andcongenital malformation safety outcomes. Vaccine. 2015 Apr 27;33(18):2108-17. 3. Polyzos KA1, Konstantelias AA, Pitsa CE, Falagas ME. Maternal Influenza Vaccination and Risk for Congenital Malformations: A Systematic Review and Meta-analysis. Obstet Gynecol. 2015 Nov;126(5):1075-84.
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  • 37.
    • All persons6 mths & older should be vaccinated annually CDC Centers for Disease Control and Prevention • All women who are pregnant during influenza season receive inactivated influenza vaccine ACIP Advisory committee on immunization practices • Recommends seasonal influenza vaccination to pregnant women as the highest priority WHO World Health Organization • Recommends all women who are pregnant during influenza season receive inactivated influenza vaccine ACOG The American College of Obstetricians and Gynecologists • Recommended from 26 weeks onwardsFOGSI INFLUENZA VACCINE RECOMMENDATION: PREGNANCY Source: http://www.who.int/immunization/newsroom/newsstory_seasonal_influenza_vaccination_pregnancy/en/ as accessed on 06/07/2014, 4:30 pm. https://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Obstetric%20Practice/co468.pdf?dmc=1&ts=20140702T0616350498, as accessed 06/07/14. http://www.fogsi.org/images/stories/pdf/vaccination_women.pdf
  • 38.
    Maternal immunity isthe only effective strategy in newborns because the vaccine is not approved for use in infants younger than 6 months WHAT IS THE BEST VACCINATION STRATEGY TO PROTECT INFANTS <6 MONTHS? Source: http://www.ecdc.europa.eu/en/publications/publications/seasonal%20influenza%20vaccination%20of%20children%20and%20pregnant%20women.pdf as accessed on 02/07/2014, 3:30 pm Protecting the mother and her unborn child from serious illness by vaccinating pregnant women
  • 39.
    Source: http://gamapserver.who.int/mapLibrary/Files/Maps/GISRS_20130425_1.png asaccessed on 11 June 2014, 5:51 pm 106 Member countries 136 NIC 6 WHO CCS 4 ERLS 11 H5 Ref Labs GLOBAL SURVEILLANCE NETWORK: WHO IND1134295
  • 40.
    SEASONALITY OF FLU •India has distinct seasonality • Rainfall correlates with influenza peaks in many of the cities • Recent surveillance data from tropical regions of Asia have revealed a seasonal pattern characterized by year round low- level influenza virus circulation with peaks occurring during the monsoon (rainy) season Source: 1) Chadha MS et al. Dynamics of influenza seasonality at sub-regional levels in India and implications for vaccination timing. PLoS One. 2015 May 4;10(5):e0124122. 2) Saha S et al. Divergent seasonal patterns of influenza types A and B across latitude gradient in Tropical Asia. Influenza Other Respir Viruses. 2016 May;10(3):176-84. IND1134295
  • 41.
    LIMITED INFLUENZA ACTIVITYIS USUALLY SEEN THROUGHOUT THE YEAR • Limited influenza activity is usually seen throughout the year in India with a clear peaking during the rainy season. • The rainy season in the country lasts from June to August in all the regions except Tamil Nadu where it occurs from October to December. IND1134295
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