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Pneumococcal and Influenza vaccine Dr. Amukoye KEMRI Epidemiology- morbidity/mortality lKenya has a young population with 43% under the age 15 years lUnder 5ve mortality had reached 12% though this has improved to 7.4% l 2-3% of under 5ves suffer from severe pneumonia yearly Under Five Mortality Rates by Provinces of Kenya, KDHS 2008. Pneumoccocal l10.6 million children under five years of age die each year; l90% of these deaths occur in developing countries. lStreptococcus pneumoniae, is a leading cause of pneumonia, meningitis and septicemia, l1.6 million people die each year including 700,000 to 1 million children under five. lPPV23 is estimated to be effectiveness to between 50 and 60% of IPD in children aged 24 to 59 months lPneumococcal bacteremia of 597/100,000 children less than 5 years of age per year (Kenya). lCase fatality ratios range from 5-20% for bacteremia to 40- 50% for meningitis. lpneumococcal pneumonia in a pandemic influenza setting is anticipated to range from 5 to 13%. Serotype lNasopharynx is the reservoir for pneumoccocal l90+ serotypes based on capsular polysaccharide lApproximately 20 serotypes account for over 70% of invasive disease; lJust about 10 serotypes are commonly associated with pediatric infections -1,4,6,3,7f,9v,14,18c, 19f, 23f lBased on molecular typing of multiple housekeeping genes, pneumococcal strains can be characterized into clones. there is a strong association between lserotype and clones. lspecific clones, serotypes and antimicrobial resistance pattern. lThe majority of these are associated with antibiotic resistance. Strains that are penicillin-resistant are much more likely also to contain genes conferring resistance to other drug classes Serotype l The global distribution of serotypes varies. lPCV 7- 4,6B, 9V, 14, 18C, 19F and 23F conjugated to an immunogenic mutant diphtheria toxin, CRM197 lPCV 10- 1,5,7F, 4,6B, 9V, 14, 18C,19F,23F lPCV 13- 3, 19A, 6A,1,5,7F, 4,6B, 9V, 14, 18C,19F,23F lSome serotypes 1 and 5 are common in developing countries. lSerotypes associated with invasive infections among HIV infected children are similar to the serotypes that infect healthy children. Polysaccharide vs conjugate lPneumococcal capsular polysaccharides, serves as the primary pneumococcal antigens eliciting a host immune response, induce a T-cell independent immune response which is not develop in children until around two years of age lConjugate vaccine- polysaccharides are covalently coupled to immunogenic proteins such as the mutant diphtheria toxin CRM197 used in PCV7 and PCV9, a T cell-dependent response is elicited. lconjugate vaccines can confer both systemic and mucosal immunity. Serum IgG and secretory IgA can be detected in the saliva of toddlers and infants after parenteral vaccination with PCV formulations. Immunogenecity lWHO expert panel determined that an antibody concentration of 0.35 mcg/ML for all vaccine- included serotypes corresponded to clinical efficacy against invasive disease due to vaccine-included serotypes lPCV was as immunogenic in low birth weight and preterm infants as in normal birth weight and full term infants lReplacement disease (19A) Preventing pneumonia by immunization lMeasles -Immunization coverage is 80% in Kenya lHIB meningitis more or less eradicated in Kiliffi lPneumoccal-There are 814,000 pneumococcal deaths in children aged 6 months with certain risk factors (including but not limited to asthma, cardiac disease, sickle cell disease, human immunodeficiency virus HIV and diabetes) lIt is recommended that measures to prevent pneumonia infections be discussed with families, including: lhandwashing, especially when exposed to individuals with respiratory infections (Morton Roberts et al., 2000 A) lbreastfeeding (Levine et al., 1999 C) llimiting exposure to other children PRIORITY GROUP FOR VACCINE lAsplenia or splenic dysfunction (including sickle cell disease and coeliac disease). lChronic renal disease, nephrotic syndrome or renal transplant. l Chronic heart, lung, or liver disease, including cirrhosis. l Diabetes mellitus. lComplement deficiency (particularly early component deficiencies C1, C2, C3, C4). lImmunosuppressive conditions (e.g. some B- and T-cell disorders, lHIV infection, leukaemia, lymphoma, Hodgkins disease) and those limmunosuppressive therapies. l CSF leaks either congenital or complicating skull fracture or lneurosurgery. lIntracranial shunt. lChildren under 5 years of age following invasive pneumococcal disease, irrespective of vaccine history lSmokers and alcoholics Way forward lMalnutrition lMacronutrient lMicronutrient (zinc, Vit. A,D.,) lPollution control-indoor (biomass fuel, cigarette) lAccess to health care lNo and distribution, case management lVaccine lPneumococal, HIB, measles, pertusis Influenza References l Williams BG, Gouws E, Boschi-Pinto C, et al. Estimates of world -wide distribution of child deaths from acute respiratory infections. Lancet Infect Dis 2002;2(1):25-32 lMulholland K. Childhood pneumonia mortality- a permanent global emergency.Lancet. 2007 ;370(9583) :285-9. lZar HJ. Pneumonia in HIV-infected and uninfected children in developing countries epidemiology, clinical features and management. Curr Opin Pulm Med. 2004;10(3):176-182 VIRAL PNEUMONIA lViruses -occur in 30-40% of acute respiratory infections in hospitalised children lRSV- lInfluenza virus- lAdenovirus lParamyxovirus lMetapneumovirus lMeasles (ribeola virus) l- lSeasonal influenza causes an estimated annual average of l226 000 hospitalizations and 36 000 deaths in the United lStates. The highest rates of influenza-associated hospitalizations land death occur among the elderly, young children, land persons with certain high-risk medical conditions. Influenza: the virus. Classification RNA virus Type AType B Influenza virus Type C Influenza C virus ORTHOMYXOVIRIDAE Family: Genus: Types: Specificity: Man Animal ManMan Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87 Internal antigens Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87 Structure of the virus Nucleocapsid: Nucleoprotein (NP) -RNA (7 or 8 segments) Matrix protein (M) Lipid bilayer Haemaglutinin (HA) Neuraminidase (NA) 80 to 120 nm Surface antigens lFrequent with Influenza A, less for type B, never for type C lTo escape population immunity lInvolves the external antigens : HA and NA lTwo types of mutations depending on whether the RNA segment variation is small or great : l Antigenic drift l Antigenic shift Each year, evolution can induce a different virus Betts FR, Douglas RG, Mandell G.L., Douglas R. G., Bennett J.E., Principles and practice of infectious diseases, 3rd ed., 1990;39:1306-25 Antigenic variation : intelligence of influenza viruses “ “FluFlu spreadsspreads acrossacross thethe worldworld andand ages“ ages“ Murphy B.R., Webster R.G., Virology, IInd edition, New York, 1990, 1091-2 Ghendon Y. Introduction to pandemic influenza through history Eur Jour of Epid, 1994;10: 451-453 “Spanish influenza“ killed 20-40 million people 412 B.C412 B.C Middle agesMiddle ages 1781 45:306-11 FactorsFactors whichwhich favorfavor contagion : contagion : HumidHumid or cold or cold weatherweather Indoor Indoor lifelife CrowdedCrowded public transport public transport Speed Speed ofof modernmodern intercountryintercountry traveltravel Every year, about 10% of the worlds population catch influenza : some 600 million people. Attack rates of 40% in pre-school and 30% in school age children. Influenza impact : a yearly infection that occurs worldwide Impact of influenza in children: The burden of influenza in young healthy children is as high as that in the elderly and high risk groups. 30-40% of all acute Otitis Media cases in children are related to influenza. Economical benefits: absenteeims both at school and the work place. More severe in at risk children: 4-fold increased hospitalisation rate. Betts FR et al principles and of infectious disease 3rd edtion 1990.39: 1302-5. A call to action, improving influenza and pneumococcal infectins among high risk adults ./ncai/publications/roundtable/. The american lung association asthma lung clincial research centers. Annual attack rate of 15-40%: the spread of flu vaccination in the family starts with school going children. Children shed the virus for a longer time and shed higher titres. 13.8 16 million illness years in the USA in individuals under 20 years. Excess number for out patient visits. 10-30% increased antibiotic use. Incre