Abrupt onset of systemic and respiratory signs and symptoms Influenza can also present as croup , bronchiolitis , pneumonia , febrile disease mimicking bacterial sepsis Influenza can predispose to bacterial infections (otitis media, pneumonia, bronchiolitis)
5 INFLUENZA: a devastating disease - The highly contagious, acute respiratory illness known as influenza occurs in epidemics and appears to have afflicted humans worldwide since ancient times. - One such influenza-like epidemic was recorded by Hippocrates in 412 B.C., and numerous episodes were described in the middle ages. Those of 1781 and 1830 appeared to have spread accross Russia from Asia. - While influenza has killed untold millions throughout centuries, the 1918-1919 pandemic was particularly severe. &quot;Spanish Influenza&quot;, as it was called, killed between 20 and 40 million people worldwide . - The first human influenza A virus was isolated in 1933. - Since 1933, there has been three pandemics which also killed millions of people. In between these pandemics which occur every 10 to 40 years epidemics occur every year. The global impact of those smaller epidemics is as high as a pandemic and makes prevention worthwhile. Influenza is one of the major infectious diseases !   Complementary information: The word influenza comes from the latin influentia or &quot;influence&quot;, as it was once widely believed that epidemics resulted from adverse astrological alignments or other occult influences. The first human influenza A virus was isolated in 1933 by Wilson Smith, Sir Christopher Andrew and P. O. Laidlow of the National Institute for Medical Research in London, England. Influenza B virus by Francis in 1939 and Influenza C virus in 1950 by Taylor. &quot;Spanish influenza&quot;: all the armies in Europe were hit hard by this outbreak; in fact, 80% of the U.S. Army's war deaths were due to influenza. A massive epidemic of worldwide distribution is called pandemic. Since 1933, there were in 1957 the &quot;Asian flu&quot; and in 1968 the &quot;Hong Kong flu&quot;. These two pandemics also killed a million people. In 1977 the &quot;Russian flu&quot; was less severe.
In the four financial years 2000-2004, there were a total of 3,629 admissions to hospitals in Australia where identified influenza virus infection was the principal diagnosis. Of these, 1,129 (31%) were aged under one year, and 1,376 (38%) were aged between one and five years. It should be noted that a recent analysis of hospital admission data in NSW Australia by Beard et al from the National Centre for Immunisation Research and Surveillance (NCIRS) has estimated that the real admission figures for influenza are probably up to eleven times higher than the officially recorded figures. (ref Arch Dis Child 2006;91:20-25)
Key Messages Children play an important role in the transmission of influenza 3 Disease burden may decline as a result of both reduced susceptibility to infection among vaccinees and reductions in disease transmission to others in the community 2 Improved vaccination rates in school-age children may help reduce the overall spread of influenza in the community References Glezen WP, Couch RB. Interpandemic influenza in the Houston area, 1974-76. N Engl J Med . 1978;298:587-592. Weycker D, Edelsberg J, Halloran ME, et al. Population-wide benefits of routine vaccination of children against influenza. Vaccine. 2005;23:1284-1293. Glezen WP, Taber LH, Frank AL, et al. Influenza virus infections in infants. Pediatr Infect Dis J. 1997;16:1065-1068. Reichert TA, Sugaya N, Fedson DS, et al. The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med . 2001;344:889-896.
India in 2010
The data represents consistent peaking of circulation from June to September which coincides with the rainy season across the country
The latest news was published by India Today on 29 th March 2012, discussing a study conducted by AIIMS indicating the presence of influenza throughout the year in Delhi, in addition to the seasonal increase in the virus activity . This further stresses on the necessity to immunize the population.
VAXI GRIP manufacturing time-table - Once the virus strains, to be included in the vaccine are defined by the WHO, work starts against the clock for vaccine manufacturers. - From the time they receive from the WHO reference centers, the reassortant strains to be used in the vaccine, manufacturers only have six to seven months to produce, test, fill, package and distribute the new vaccine. To face this tight production schedule, without any failure, a great deal of experience and know-how are required. - PMC has this expertise. - In this race against time, each year PMC takes up the challenge to release on time a sufficient amount of vaccine allowing a very broad segment of the population to be protected. - For the countries following the WHO recommendations, the choice of strains is carried out in end of February, thus VAXIGRIP is available at the beginning of October. - For the countries following the Melbourne recommendations (Australia, South Africa and New Zealand) the choice of strains is carried out in September, thus Vaxigrip is available as from February in those countries.  Complementary information: In case of a pandemic it would be possible to produce mass doses of monovalent influenza vaccine in two to three months. 
Influenza vaccination in childrenRationale and Opportunities Dr Gaurav Gupta, Pediatrician, Member AAP, IAP, Charak Clinics, Mohali April 2012
Conflict of Interest Received grants from various vaccine manufacturers including - Sanofi Pasteur - GSK - Abbott (Manufacturers of different Influenza vaccines)
Overview Influenza – what is it ? Is it really that big a problem – World/ India/ Children ? Influenza vaccine – rationale for use What data exists regarding Influenza vaccine safety & effectiveness, especially from India ? When, whom & how to vaccinate ?
CASEAlisha is a 7-year-old girl brought to your Clinic by her mother, who tells you her daughter “suddenly came down with a bad cold.” She reports that “Alisha was fine when she went to bed” but in the morning suddenly became ill with vomiting, a dry cough, sore throat, and high fever. W H A T D O YO U T H IN K IS T H IS ? ?
O f t e n m is u n d e r s t o o d a n d u n d e r e s t im a t e d ,In f lu e n z a is n o t ju s t “ a b a d c o ld ” ! Annual Influenza pandemics:influenza epidemics exceptional epidemiological events occurring every few decades (11–36 years)
C L IN IC A L F E A T U R E S & C A S E D E F IN IT IO NInfluenza can also present as croup, bronchiolitis, pneumonia, febrile diseasemimicking bacterial sepsisCan predispose to bacterial infections (otitis media, pneumonia, bronchiolitis) Laboratory Confirmation required for epidemiological purposes only JAMA 2000; 284 (13): 1740
IN F L U E N Z A P A N D E M IC S IN H IS T O R Y 1968 Hong Kong flu H3N2 1957 Asian flu H2N2 1933 Influenza virus isolated for the first time 1918 Spanish flu H1N1 Epidemic reported 1889 by & 1891 H3N8 pandemicHippocrates 412 BC 1173-1174 Influenza-like epidemics first reported Potter CW. A history of influenza. J Appl Microbiol 2001; 91(4):572-579. H1N1 pandemic- 2009 being the latest faced by the globe
D U R IN G E A C H A N N U A LE P ID E M IC : 5 to 10 % of the world’s population catches influenza i.e., 500 million people Including 3 to 5 million serious cases And 500 000 to 1 000 000 deaths each year Influenza does not discriminate: it affects men and women, boys and girls of all ages, in all sectors of the population, and in all countries
A F R E Q U E N T D IS E A S E I N C H I Lproportion in young Greatest D R E N children Hospital admissions for influenza, Australia, 2000-2004 40 Identified influenza virus (J10) 35 % total hospitalisations 30 25 20 2000-2004 15 10 5 0 30 29 45 44 15 14 20 19 25 24 35 34 40 39 50 49 55 54 60 59 65 64 70 69 75 74 80 79 4 4 10 9 + <1 -8 1- 5- 85 - - - - - - - - - - - - - - Age (years)AIHW National Hospital Morbidity Database
IN F L U E N Z A IN IN D IA N C H IL D R E N Hospital based survey at AIIMS, Delhi: Influenza virus isolated in 29 of 200 (14.5%) children suffering from acute LRI In bronchopneumonia cases (101) the most common viral pathogen was influenza virus (17%) Influenza virus infection in Delhi pediatric population peaked from September to DecemberJ Clin Virol. 2000; 16 (1): 41-7,
IN F L U E N Z A IN IN D IA N C H IL D R E N OPD based survey at KIPM, Chennai: Influenza virus isolated from 30 out of 240 (12.5%) children suffering from acute RTI Influenza activity commenced in February and continued till November, peaking in June coinciding with the onset of the Southwest MonsoonIndian J Med Res 2005; 121: 776-779
D IF F E R E N C E S B E T W E E N IN F L U E N Z A V A C C IN E S V a c c in e Im m u n o g e n i R e a c t o g e n C o m p o s it io n typ e c it y ic it y Whole-virus Whole virus +++ +++(no longer used) Surface, nucleocapsid & Split virion matrix proteins +++ + Subunit Surface proteins ++ ++ Surface proteins & Virosomal ++ + virosomes Surface proteins & Adjuvanted +++ ++ adjuvant Nasal Live attenuated +++ +++ + (Low) ++ (Medium) +++ (High) A ijJ Pham R 20 8 mor P. r es. 0 ;25(6):1256- . 1273
R A T IO N A L E F O R C H IL D H O O DV A C C IN A T IO N All children are at substantially increased risk for influenza-related hospitalisations As well as reducing the risk to their own health, it reduces influenza infection in their contacts May also reduce influenza infections in adults by interfering with the circulation of the virus in the community Annual influenza vaccine is widely recommended for children at high risk
C H IL D R E N A R E P R IM A R Y VE C TO R S Other Family members children and other close contacts Children Day care, preschool and school-age Community including high-risk populations1. Glezen WP, et al. N Engl J Med. 1978;298:587-592.2. Weycker D, et al. Vaccine. 2005;23:1284-1293.
V A C C IN A T IO N IN P R E -S C H O O L C Influenza D R E N Reduction in H I L related Morbidity URIs LRIs (Acute Bronchitis, Influenza A A.O.M (Pharyngitis,Croup) Wheezing, Pneumonia) 83% 36% 33% 22% Studies confirm effectiveness of Influenza vaccination in Pre-School Children 1. Neuzil KM et al Pediatr Infect Dis J, 2001: 20:733-40. 2. Heikkinen T et al.Influenza vaccination in the prevention of acute otitis media in children: Am J Dis Child 1991;45:445-8 3. Pediatric Infect Disease J 2006:25;5;401-404 4. New England J Med 2000; 342:225-31
V A C C IN A T IO N IN S C H O O L -G O I NDirect & Indirect L D Rof Influenza Vaccination G C H I Benefits E N Missed No. of antibiotic Maternal work Paternal work School Days Rxs absenteeism absenteeism 48% 32% 33% 43%Studies confirm Influenza vaccination in School-Going Children to be: • Not only effective in reducing the sufferings • But also a Cost Saving proposition 1. Principi N et al. socioeconomic impact of influenza on healthy children and their families Pediatr Infect Dis J 2003; 22:S2007-10.
IN F L U E N Z A V A C C IN A T IO N A M O N G C H IL D R E N – Respiratory-Related MorbidityC T IUnvaccinated 5- to 17-Year-Old P R O T E Among O N O F Household Contacts of Study Children C O N TA C TS Contacts of Control Children (N=31) Contacts of Vaccinated Children (N=28) 45Percent of Individuals 40 35 30 25 20 72% 15 91% 10 88% 88% 100% 5 0 Missed School Physician Visits Earache Antibiotic Use Adults Missed Work All comparisons significant (p <0,05) JAMA 2000;284:1677-84
Indian Scenario:Reality Limited data in public domain on annual Influenza cases and deaths in Indian scenario* Influenza vaccine is in Indian market since 2004 There is no published data on safety, tolerability and effectiveness of Influenza vaccine in Indian children***India to compile database for influenza. Available from: URL:http://www.livemint.com/2009/05/31215156/India-to-compile-database-on-s.html. Accessed on 22 May, 2010. 22**Joseph L Mathew. Influenza vaccination for children in India. Indian Pediatrics. 2009 ;46:304-307.
Private pediatric outpatient (clinical) settingAims of the study - Clinical Effectiveness of Seasonal Flu vaccine in preventing ILI 1, 2 Safety & Tolerability of the Seasonal Flu Vaccine 3 1. WSPID, Nov 2011, Melbourne, Poster Presentation. 2. ISPOR Asia Conference, September 2010, Thailand, Poster Presentation. 3. Singh H, Gupta G, Tiwari P. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).
Continued…..Methodology-Clinical Effectiveness Study 26
Clinical Effectiveness of Influenza vaccine-1 Fully vaccinated cohort (n=154) vs. Unvaccinated cohort (n=330)* Sr.N Parameters Odds Ratio CI VE % P-value o 1 Influenza like 0.58 0.24-0.92 42 0.009 illness 2 Visits to Physician 0.71 0.33-1.09 29 0.039 Conclusion: Influenza vaccine is effective in reducing the ILI and visits to physician for ARI in fully vaccinated Indian children as compared to unvaccinated children.*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine amonghealthy Indian children. WSPID-2011, Melbourne.
Clinical Effectiveness of Influenza vaccine-2 Age-wise efficacy for prevent of ILI* Sr.N Age group (no.) Odds CI P-value VE % o Ratio 1 6 m – 3 y (78) 0.57 0.46-1.31 0.55 2 3 y – 9 y (64) 0.48 0.17-0.72 0.002 52 % 3 9 y – 18 y (28) 0.69 0.39-1.03 0.06 Conclusion: Children aged 3-9 year had the best protection rates against ILI as compared to unvaccinated children.*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine amonghealthy Indian children. WSPID-2011, Melbourne.
Comparison of VE in 2 years in our center Fully vaccinated (154) vs Unvaccinated Cohort (330) (2010-11) # Parameter RR CI p value VE (%) 1 ILI 0.65 0.48-0.86 0.003 35 2 Unsch. Visit 0.74 0.51-0.99 0.007 26 Fully vaccinated (101) vs Unvaccinated Cohort (141) *(2009-10) # Parameter RR CI p value VE (%) 1 ILI 0.57 0.32-0.09 0.05 43 2 Unsch. Visit 0.43 0.22-0.09 0.007 57* Singh H, Gupta G, Tiwari P. Clinical effectiveness of the 2009-2010 seasonal influenza vaccineamong healthy Indian children. ISPOR 4th Asia Pacific Conference, Phuket, Thailand.
Safety and Tolerability of Influenza vaccine-1Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine inhealthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).
Conclusion Flu vaccine is effective in reducing ILI & unscheduled visits to doctor. No effect of partial vaccination It is safe & well tolerated by healthy Indian children.
IN F L U E N Z A V A C C IN ER E C O M M E N D A T IO N S : P E D IA T R IC A G E -G R O U P S • All healthy • In all high• All healthy • All healthy children 6-59 risk children children 6-23 children 6-59 months >6 months months months • All high risk• All high risk • All high risk children >6 children >6 children >6 months months months • All school• Children in • Children in going close contact close contact children with high risk with high risk adults adults
Recommendation on influenza vaccine. Available at:http://www.iapindia.org/component/content/article/315. Accessed on: 16 April 2012
Vaccination Schedules Age group Dosage (im/sc) No. of doses6-35 months 0.25 ml 1 or 2*3-8 years 0.5 ml 1 or 2*> 9 years 0.5 ml 1* 2 doses at least 1 month apart for children receiving vaccine for the first time
WH O R E C O M M E N D A T IO N S The World Health Organization (WHO) convenes technical consultations in February and September each year to recommend viruses for inclusion in influenza vaccines for the northern and southern hemispheres, respectively. For countries in equatorial regions, epidemiological considerations influences which recommendation (February or September) individual national and regional authorities consider more appropriate.WHO Influenza Vaccine Recommendations
Global surveillance network:106 Member countries136 NIC6 WHO CCS4 ERLS11 H5 Ref Labs
WHO National Influenza Center(as of April 2011) Pune (NIV), Kasauli (CRI) & Mumbai (Haffkine Institute)
IN F L U E N Z A C IR C U L A T IO N Influenza virus circulationD I A June-August I N I N peaks in
In d ia 2 0 0 9 (samples submitted nil to minimal from 1999-2008) Influenza virus circulation peaks in June-August Number of Samples positive for Influenza/week J F M A M J J A S O N DData source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN)
I n d i a 2 0 10 Influenza virus circulation peaks in June-August D J F M A M J J A S O N DData source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN)
India 2011 J J A S Influenza virus circulation peaks in June-August
IN F L U E N Z A V IR U S E S C IR C U L A T E IN D E L H I T H R O U G H O U T T H E YE A R Scientists from the All India Institute of Medical Sciences (AIIMS) have cautioned that different types of flu viruses widely circulate in the national Capital throughout the year causing Influenza Like Illness (ILI). The conclusion was drawn after a joint study was conducted by AIIMS, Center for Disease Control and Prevention, Atlanta and National Institute of Virology, Pune for three years. The study hashttp://indiatoday.intoday.in/story/influenza-viruses-circulate-in-delhi-throughout-the-year/1/179252.html
P r o c e s s o f In f lu e n z a R e c o m m e n d a t io n s a n d V a c cINTERNATIONAL SURVEILLANCE NETWORK in e A v a ila b ilit y VACCINE MANUFACTURER F M A M J J A S O N D J F M WHO PRODUCTION (Northern hemisphere) WHO PRODUCTION (Southern hemisphere) Choice of strains VACCINE on timeChalumeau HP. Vaccine manufacture at the time of a pandemic influenza. European journal of epidemiology 1994;10: 487-490
Q U A D R IV A L E N T L IV E IN F L U E N Z A V A C C IN EFDA NEWS RELEASEFor Immediate Release: Feb. 29, 2012FDA approves first quadrivalent vaccine to preventseasonal influenzaThe first quadrivalent live attenuatedvaccine to prevent seasonal influenza hasbeen approved by FDA. FluMist Quadrivalent(MedImmune), will be available for the2013-2014 flu season. This too will beadministered as a nasal spray. The vaccine isindicated for individuals ages 2 yearsthrough 49 years. FluMist Quadrivalent willcontain 2 strains of influenza A and 2 strains http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm294057.htm
The European vaccine study involved anantibody that neutralizes all the influenza-Asubtypes.
S UMMARY AND C O N C L U S IO N Influenza is a significant problem in most developing countries including India, causing mild serious disease, causing severe morbidity & mortality Influenza spreads from children to adults Influenza vaccine is safe & effective in Indian children. Yearly use of vaccines can decrease the impact of Influenza.