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Pneumococcal and Influenza vaccine Dr. Amukoye KEMRI Epidemiologymorbidity/mortality Kenya has a young population with 43% under the age 15 years Under 5ve mortality had reached 12% though this has improved to 7.4% 2-3% of under 5ves suffer from severe pneumonia yearly Under Five Mortality Rates by Provinces of Kenya, KDHS 2008. Pneumoccocal 10.6 million children under five years of age die each year; 90% of these deaths occur in developing countries. Streptococcus pneumoniae, is a leading cause of pneumonia, meningitis and septicemia, 1.6 million people die each year including 700,000 to 1 million children under five. PPV23 is estimated to be effectiveness to between 50 and 60% of IPD in children aged 24 to 59 months Pneumococcal bacteremia of 597/100,000 children less than 5 years of age per year (Kenya). Case fatality ratios range from 5-20% for bacteremia to 4050% for meningitis. pneumococcal pneumonia in a pandemic influenza setting is anticipated to range from 5 to 13%. Serotype Nasopharynx is the reservoir for pneumoccocal 90+ serotypes based on capsular polysaccharide Approximately 20 serotypes account for over 70% of invasive disease; Just about 10 serotypes are commonly associated with pediatric infections -1,4,6,3,7f,9v,14,18c, 19f, 23f Based on molecular typing of multiple housekeeping genes, pneumococcal strains can be characterized into clones. there is a strong association between serotype and clones. specific clones, serotypes and antimicrobial resistance pattern. The 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 The global distribution of serotypes varies. PCV 7- 4,6B, 9V, 14, 18C, 19F and 23F conjugated to an immunogenic mutant diphtheria toxin, CRM197 PCV 10- 1,5,7F, 4,6B, 9V, 14, 18C,19F,23F PCV 13- 3, 19A, 6A,1,5,7F, 4,6B, 9V, 14, 18C,19F,23F Some serotypes 1 and 5 are common in developing countries. Serotypes associated with invasive infections among HIV infected children are similar to the serotypes that infect healthy children. Polysaccharide vs conjugate Pneumococcal 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 Conjugate 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. conjugate 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 WHO expert panel determined that an antibody concentration of 0.35 mcg/ML for all vaccineincluded serotypes corresponded to clinical efficacy against invasive disease due to vaccine-included serotypes PCV was as immunogenic in low birth weight and preterm infants as in normal birth weight and full term infants Replacement disease (19A) Preventing pneumonia by immunization Measles -Immunization coverage is 80% in Kenya HIB – meningitis more or less eradicated in Kiliffi Pneumoccal-There are 814,000 pneumococcal deaths in children aged <5 years in developing countries 1-4 million episodes of pneumococcal pneumonia yearly in Africa alone. Introduction of PCV will be effective where there is a demonstrable burden of IPD attributable to vaccine serotypes but herd protection and serotype replacement effects are unpredictable. Influenza Others-, Pertusis, RSV Prospect of vaccines The incidence of invasive pneumococcal disease (IPD) in young children decreased by over two-thirds following the programmatic introduction of pneumococcal conjugate vaccination in the United States In the developing world, the prospects for prevention by vaccination are uncertain. In South Africa, vaccination was shown to reduce IPD by 83% among human immunodeficiency virus-negative children. In The Gambia, vaccine efficacies were 77% against IPD and 37% against radiological proven pneumonia Prevention and Education It is recommended that immunizations which prevent CAP be kept upto-date, including: PCV10,13 heptavalent conjugated pneumococcal vaccine (PCV7, Prevnar®), annual influenza vaccine for It is recommended that measures to prevent pneumonia infections be discussed with families, including: all children 6 to 23 months of age, and 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) handwashing, especially when exposed to individuals with respiratory infections (Morton & Schultz, 2004 [A]; Roberts et al., 2000 [A]) breastfeeding (Levine et al., 1999 [C]) limiting exposure to other children PRIORITY GROUP FOR VACCINE Asplenia or splenic dysfunction (including sickle cell disease and coeliac disease). Chronic renal disease, nephrotic syndrome or renal transplant. Chronic heart, lung, or liver disease, including cirrhosis. Diabetes mellitus. Complement deficiency (particularly early component deficiencies C1, C2, C3, C4). Immunosuppressive conditions (e.g. some B- and T-cell disorders, HIV infection, leukaemia, lymphoma, Hodgkin’s disease) and those immunosuppressive therapies. CSF leaks either congenital or complicating skull fracture or neurosurgery. Intracranial shunt. Children under 5 years of age following invasive pneumococcal disease, irrespective of vaccine history Smokers and alcoholics Way forward Malnutrition Macronutrient Micronutrient (zinc, Vit. A,D.,) Pollution control-indoor (biomass fuel, cigarette) Access to health care No and distribution, case management Vaccine Pneumococal, HIB, measles, pertusis Influenza….. References 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 Mulholland K. Childhood pneumonia mortality- a permanent global emergency.Lancet. 2007 ;370(9583) :285-9. Zar 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 Viruses -occur in 30-40% of acute respiratory infections in hospitalised children RSV- Influenza virus- Adenovirus Paramyxovirus Metapneumovirus Measles (ribeola virus) ------------------------------------------------------------------------------------------Seasonal influenza causes an estimated annual average of 226 000 hospitalizations and 36 000 deaths in the United States. The highest rates of influenza-associated hospitalizations and death occur among the elderly, young children, and persons with certain high-risk medical conditions. Influenza: the virus . Classification Family: ORTHOMYXOVIRIDAE RNA virus Genus: Influenza virus Influenza C virus Types: Type A Type B Type C Specificity: Man Animal Man Man Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87 Structure of the virus Nucleocapsid: Nucleoprotein (NP) -RNA (7 or 8 segments) Internal antigens Matrix protein (M) Lipid bilayer Haemaglutinin (HA) Neuraminidase (NA) 80 to 120 nm Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87 Surface antigens Antigenic variation : intelligence of influenza viruses Frequent with Influenza A, less for type B, never for type C To escape population immunity Involves the external antigens : HA and NA Two types of mutations depending on whether the RNA segment variation is small or great : Antigenic drift 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 Influenza : true image of a serious and devastating disease "Flu spreads across the world and ages" 1977 "Russian" flu 1968 "Hong Kong" flu 1957 Epidemic recorded by Hippocrates 1933 "Asian flu" First human influenza virus isolated 1918 "Spanish influenza" killed 20-40 million people 412 B.C 1781 & 1830 Middle ages Epidemics spread across Russia from Asia Numerous episodes described 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 Seasonal Occurrence of Influenza, RSV and Parainfluenza Viruses, United States,1996-99 35 30 positive % respiratory specimens 40 25 20 15 10 5 0 7/96 1/97 7/97 Influenza 1/98 RSV 7/98 Para 1 1/99 Para 3 7/99 Results Seasonal Influenza Trends 2004 - 2007 140 120 100 80 Neg Pos 60 40 20 0 2004 | 2005 | 2006 | 2007 J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D Influenza impact : a yearly infection that occurs worldwide Every year, about 10% of the world's population catch influenza : some 600 million people. Attack rates of 40% in pre-school and 30% in school age children. Factors which favor contagion : Humid or cold weather Indoor life Crowded public transport Speed of modern intercountry travel Ghendon Y. Influenza - its impact and control Rapp. trimest. sanit. mond. 1992;45:306-11 Impact of influenza in children: 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. 30-40% of all acute Otitis Media cases in children are related to influenza. More severe in at risk children: 4-fold increased hospitalisation rate. Economical benefits: absenteeims both at school and the work place. Excess number for out patient visits. 10-30% increased antibiotic use. Increased hospitalizations. Death : Rare and mainly in under ones The burden of influenza in young healthy children is as high as that in the elderly and high risk groups. 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 http://www.nfid.org./ncai/publications/roundtable/. The american lung association asthma lung clincial research centers. Impact of Respiratory Viruses on Illness in Children Aged < 5 Years Percent 90 80 70 60 50 40 30 20 10 0 Paraflu RSV Flu LRI URI Fever >39 Reed G et al. J Infect Dis 1997; 175:807. AOM Clinical Courses of Croup in Finland Age (median) Influenza (n=29) 1.7 years Parainfluenza (n=88) 1.4 years Hospital stay 4 days (1-11) 2 days (1-27) Steroid rx 18 (62%) 28 (32%) Supp. O2 7 (24%) 3 (3%) ICU stay 8 (28%) 10 (11%) Pneumonia 19 (66%) 34 (40%) Peltola et al. Pediatr Infect Dis J 2002; 21: 76-78 INFLUENZA: Groups at increased risk for influenzarelated complications and mortality: Persons > 50 years of age, Residents of nursing homes, Adults and children with chronic disorders of the pulmonary or cardiovascular systems, Adults and children with chronic metabolic diseases, renal dysfunction, or hemoglobinopathies ( such as Sickle cell disease), Immunocompromised adults and children, including HIV infected persons and users of immunosuppressive medications Pregnant women belonging to the high-risk groups. Newly recognized: Healthy children aged 6-24 months(5 years) Each year one out of every three persons is infected by influenza ACIP, MMWR 1999; 48 [No RR-4]: 1-29. Palache A. M., Influenza subunit vaccine - ten years experience. European journal of clinical research 1992;3:117-138