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Streptococcus pneumonia (pneumococcus)

Streptococcus pneumonia (pneumococcus)



Streptococcus pneumonia (pneumococcus)

Streptococcus pneumonia (pneumococcus)



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    Streptococcus pneumonia (pneumococcus) Streptococcus pneumonia (pneumococcus) Presentation Transcript

    • HISTORY OF PNEUMOCOCCAL DISEASE• S. pneumoniae first isolated by Pasteur in 1881• Confused with other causes of pneumonia until discovery of Gram stain in 1884• More than 80 serotypes described by 1940• First U.S. vaccine in 1977DR.T.V.RAO MD 2
    • STREPTOCOCCUS PNEUMONIAE• Streptococcus pneumoniae (pneumococcus)• Gram-positive, encapsulated diplococcus• Capsular swelling observed when reacted with type-specific antisera (Quelling reaction)DR.T.V.RAO MD 3
    • QUELLING REACTION • Capsular swelling observed when reacted with type-specific antisera (Quelling reaction)DR.T.V.RAO MD 4
    • IMPORTANT FOR MODELLING: PNEUMOCOCCAL SEROTYPES• Based on properties of capsular polysaccharides• Immunologically distinct and basis for classification • > 40 serogroups (e.g. group 19) • > 90 serotypes (e.g. types 19A, 19C, 19F)• No immunologic cross-reactivity between serogroups• Some cross-reactivity within some serogroups and some cross- protection• Geographical and temporal variation• Some more immunogenic than others DR.T.V.RAO MD 5
    • PNEUMOCOCCAL DISEASE: A MAJOR HEALTH THREAT•Pneumococcal disease: caused by Streptococcuspneumoniae•Pneumococcal disease: a major threat to health • Non-invasive diseases (e.g. otitis media, pneumonia) • Invasive diseases (e.g. bacteraemia, meningitis)•Invasive pneumococcal disease is serious and has a highrisk of mortality•Groups at high risk include elderly persons,persons with chronic diseases, asplenic patients,Immunocompromised patients
    • CLINICAL MANIFESTATIONSMeningitis Otits mediaPneumonia SinusitisPericarditis EndocarditisSepticemia PeritonitisOsteomyelitis ArthritisDR.T.V.RAO MD 7
    • DISEASES CAUSED BY STREPTOCOCCUS PNEUMONIAE PNEUMOCOCCAL INFECTION Non-invasive disease Invasive disease • Sinusitis (sinuses) • Bacteraemia (blood) • Otitis media (middle ear) • Pneumonia (lungs) • Meningitis (CNS) • Endocarditis (heart) • Peritonitis (body cavity) • Septic arthritis (bones and joints) • Others (appendicitis, salpingitis, soft-tissue infections) Musher, in Principles and Practice of Infectious Diseases, 1995
    • PNEUMOCOCCAL PNEUMONIA CLINICAL FEATURES• Abrupt onset• Fever• Shaking chills• Pleuritic chest pain• Productive cough• Dyspnea, tachypnea, hypoxiaDR.T.V.RAO MD 10
    • PNEUMOCOCCAL DISEASE IN CHILDREN• Bacteremia without known site of infection most common clinical presentation• S. pneumoniae leading cause of bacterial meningitis among children younger than 5 years of age• Highest rate of meningitis among children younger than 1 year of age• Common cause of acute otitis mediaDR.T.V.RAO MD 11
    • CONDITIONS THAT INCREASE RISK FOR INVASIVE PNEUMOCOCCAL DISEASE• Decreased immune function• Asplenia (functional or anatomic)• Chronic heart, pulmonary, liver or renal disease• Cigarette smoking• Cerebrospinal fluid (CSF) leakDR.T.V.RAO MD 12
    • LOWER RESPIRATORY TRACT INFECTIONS• S. pneumoniae is the most common cause of community- acquired bacterial pneumonia• >500,000 cases annually 25%-35% require hospitalization 10%-25% have concomitant bacteremiaDR.T.V.RAO MD 13
    • INVASIVE PNEUMOCOCCAL DISEASE• Bacteremia most common clinical presentation among children younger than 2 years• Most common cause of bacterial meningitis in the U.S.• Highest rate of meningitis among children younger than 2 yearsDR.T.V.RAO MD 14
    • CHILDREN AT INCREASED RISK OF INVASIVE PNEUMOCOCCAL DISEASE• Functional or anatomic asplenia• Sickle cell disease• HIV infection• Out-of-home group child care• Certain racial and ethnic groupsDR.T.V.RAO MD 15
    • SIGNIFICANT DISEASE BURDEN IN CHILDRENDisease severity Estimated number of cases per year (US) 1,400 Meningitis Invasive 17,000 Increases Bacteremia 71,000 Pneumonia Noninvasive 5–7 million Otitis media Prevalence DR.T.V.RAO MD MMWR. 1997;46:1-24. 16
    • Bacterial Pneumonia• Common etiological agents: Streptococcus pneumoniae• Clinical presentation: Abrupt onset with fever, cough, production of purulent sputum, dyspnea, and Pleuritic chest pain• Recommended diagnostics: Chest X-ray, blood culture, FBC, gram stain of sputum, sputum culture and sensitivity• Common findings: X-ray may show pneumonic consolidation, infiltrates, or pleural effusion; leukocytosis; blood cultures may be positiveDR.T.V.RAO MD 17
    • ACUTE OTITIS MEDIA• From colonisation to invasion of middle ear through the eustachian tube• Facilitated by previous viral infection• Mostly in young children with immature immune defence• Day-care centre (DCC) attendance and prior antibiotic treatment are risk factorsDR.T.V.RAO MD 19
    • INVASIVE PNEUMOCOCCAL DISEASE (IPD)• Bacterial growth in normally sterile fluids • Blood (pneumonia, meningitis, endocarditis) • CSF (meningitis) • Joint fluids (artritis) • Pleural fluid (pleuritis) • Peritoneal fluid (peritonitis)DR.T.V.RAO MD 20
    • PNEUMOCOCCAL DISEASE: PNEUMONIA AND COMPLICATIONS•Complications • Bacteraemia in 15-30% of patients with pneumonia 1,2 • high mortality despite appropriate antibiotic therapy • overall case fatality rate 15-20% for pneumococcal bacteraemia • higher case fatality rates (30-40%) for elderly persons and other vulnerable groups • Spread of pneumococci in the blood to other normally sterile sites can cause other invasive pneumococcal diseases (e.g. meningitis) • Empyema (pus in the pleural cavity) in about 2%Whitt, incases 3 1 Salyers, of Bacterial Pathogenesis, 1994 2 Fedson, Musher, in Vaccines, 1994 3 Musher, Clin Infect Dis, 1992
    • IMPACT OF COMPETITION• Pneumococcal strains also compete with each other. The increase in the prevalence of previously uncommon serotypes in populations in which the pneumococcal CPS conjugate vaccine is extensively used (a phenomenon that is referred to as serotype replacement) suggests that nonvaccine pneumococcal types are being out-competed by the serotypes that are present in the vaccine. One mechanism that could underlie this intra-species competition is the strain-specific activity of pneumococcal Bacteriocins, which are known as pneumocins.
    • DIAGNOSIS OF STREPTOCOCCUS PNEUMONIA• Chest X-ray• Culture and staining• Biochemical tests of isolated organism
    • CULTURING OF S.PNEUMONIAE• Streptococcus pneumoniae is a fastidious bacterium, growing best in 5% carbon dioxide. Nearly 20% of fresh clinical isolates require fully anaerobic conditions. In all cases, growth requires a source of catalase (e.g. blood) to neutralize the large amount of hydrogen peroxide produced by the bacteria. In complex media containing blood, at 37°C, the bacterium has a doubling time of 20-30 minute• On agar, pneumococci grow as glistening colonies, about 1 mm in diameter. Two serotypes, types 3 and 37, are mucoid. Pneumococci spontaneously undergo a genetically determined, phase variation from opaque to transparent colonies at a rate of 1 in 10 5 . The transparent colony type is adapted to colonization of the nasopharynx, whereas the opaque variant is suited for survival in blood. The chemical basis for the difference in colony appearance is not known, but significant difference in surface protein expression between the two types has been shown.DR.T.V.RAO MD 24
    • CULTURING OF S.PNEUMONIAE (CONT)• Streptococcus pneumoniae is a fermentative aerotolerant anaerobe. It is usually cultured in media that contain blood. On blood agar, colonies characteristically produce a zone of alpha (green) haemolysis, which differentiates S. pneumoniae from the group A (beta haemolytic) streptococcus, but not from commensal alpha haemolytic (viridans) streptococci which are co-inhabitants of the upper respiratory tract. Special tests such as inulin fermentation, bile solubility, and optochin (an antibiotic) sensitivity must be routinely employed to differentiate the pneumococcus from Streptococcus viridansDR.T.V.RAO MD 25
    • DRUG-RESISTANT S.PNEUMONIAE• Mortality associated with S. pneumoniae dropped with advent of penicillin in the 1940’s• During the 1960’s, isolates of S.Pneumoniae moderately resistant to penicillin appeared• Isolates with high-level resistance emerged in the 1970’s• 60-fold increase in 1992 vs 1987• Prevalence of drug-resistant strains continues to increase -- up to 35% in some communities DR.T.V.RAO MD 26
    • RATIONALE FOR VACCINATION AGAINST STREPTOCOCCUS PNEUMONIA• Prevention of life- threatening and prevalent pneumococcal disease• Reduction of disease transmission• Reduction of carriage• Reduction of antibiotic resistance• Retention of antibiotic effectivenessDR.T.V.RAO MD 28
    • NEW PROTEIN-CONJUGATED VACCINES• T cell-dependent immune response• Immunological memory• Booster response• Immunogenic also in young children• 7-11 of 90 serotypes• Protects against invasive disease in all age groups (type-specific)• Protects against AOM (type-specific)• Effective against carriage• Licensed in USA February 2000 & European approval February 2001 DR.T.V.RAO MD 29
    • PNEUMOCOCCAL POLYSACCHARIDE VACCINE• 14-valent pneumococcal vaccine licensed in 1977• 23-valent preparation licensed in 1983• 23-valent vaccines cover 85%-90% of serotypes that cause invasive pneumococcal infections• 23-valent vaccines contain serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F• 6 serotypes most frequently associated with drug-resistant infection: 6B, 9V, 14, 19A, and 23FDR.T.V.RAO MD 30
    • ADVERSE REACTIONS TO PNEUMOCOCCAL VACCINELow incidence of adverse reactions• ~50% of patients experience mild, local reactions, usually lasting <48 hours• More severe local reactions, moderate systemic reactions, and severe systemic reactions are rare• ~33% of 7531 vaccine recipients had local reactions and none had severe febrile or anaphylactic reactionsCDC. MMWR.February 1989;38:64-68, 73-76CDC. MMWR. April 1997;46(RR-8):1-24Fine et al. Arch Intern Med. 1994;154:2666-2677 DR.T.V.RAO MD 31
    • CDC RECOMMENDATIONS• All adults >65 years• Immunocompetent persons >2 years with: Chronic cardiovascular disease Chronic pulmonary disease Diabetes mellitus Alcoholism Chronic liver disease CSF leaksDR.T.V.RAO MD 32
    • CDC RECOMMENDATIONS• Persons >2 years living in special environments or social settings, such as: Nursing homes Chronic-care facilities Alaskan Natives Certain Native American populationsDR.T.V.RAO MD 33
    • DURATION OF PROTECTION • Full antibody response occurs in 2-3 week • Antibody levels remain elevated for at least 5 years • May decrease to preimmunization levels within 10 years • May decline within 3-5 years in children, within 5-10 years in elderly, splenectomy and renal dialysis patients, transplant recipients • Duration of protection suggests revaccination for some patients CDC.MMWR.February 1989;38:64-68, 73-76DR.T.V.RAO MD 34
    • REVACCINATION GUIDELINES Revaccinate persons who: • Are >65 years of age, if vaccinated >5 years earlier and aged <65 years when first vaccinated • Are 2-64 years and at high risk for serious pneumococcal infection • Are at high risk and have shown a rapid decline in antibody levels, if first vaccinated >5 years earlier Revaccination is not routinely recommended for most patientsDR.T.V.RAO MD 35
    • CDC RECOMMENDATIONS• Immunocompromised persons >2 years with: Functional or anatomic asplenia HIV, AIDS Leukemia, lymphoma, Hodgkin’s disease, multiple myeloma Generalized malignancy Chronic renal failure, nephrotic syndrome Receiving immunosuppressive chemotherapy, radiation Organ and bone marrow transplant patients DR.T.V.RAO MD 36
    • REVACCINATION OF THE ELDERLY• Protection by pneumococcal polysaccharide vaccine may not be lifelong• One-time revaccination after >5 years is recommended for persons >65 years vaccinated at <65 yearsJacksonMD al. JAMA. 1999;281:243-248DR.T.V.RAO et 37
    • ACCELERATING NEW VACCINE DEVELOPMENT AGAINST PNEUMONIA AND OTHER PNEUMOCOCCAL DISEASESCurrent pneumococcalconjugate vaccines areeffective against the specificserotypes included in thevaccines, but do not protectagainst all pneumococcalserotypes. Furthermore, theyare complicated and relativelyexpensive to produce, whichmakes it difficult for poorercountries in urgent need to beable to afford them withoutassistance.DR.T.V.RAO MD 38
    • PATH is an international non-profitorganization that createssustainable, culturally relevantsolutions, enabling communitiesworldwide to break longstandingcycles of poor health. Bycollaborating with diverse public-and private-sector partners, we helpprovide appropriate healthtechnologies and vital strategies thatchange the way people think andact. Our work improves global healthand well-being.DR.T.V.RAO MD 39
    • • PATH is pursuing a number of approaches to develop pneumococcal vaccines that will be effective and affordable in the countries that most urgently need them. The pneumococcal vaccine project at PATH partners with scientists and manufacturers to advance their research toward preventing this childhood disease.• One approach that holds particular promise is the development of “common protein” vaccines. Vaccines containing proteins that are common to all pneumococcus serotypes could provide broad protection to children worldwide. PATH is also partnering to develop an inactivated whole cell vaccine against pneumococcus that could provide affordable and broad protection for children.DR.T.V.RAO MD 40
    • IMPORTANT FOR MODELLING: VACCINE EFFECT ON ANTIBIOTIC RESISTANCE• Reduction of antibiotics consumption (15-20% Israel)• Reduction of carriage of antibiotic-resistant bacteria • Vaccine types = child serotypes = resistant types• Herd immunity: decreased carriage in siblings• Reduction of infection with antibiotic resistant bacteria• But the bacteria will fight back • Serotype replacement to non-vaccine types • They will eventually also become resistantDR.T.V.RAO MD 41
    • PNEUMOCOCCAL DISEASE: MUCH NEGLECTED INDEVELOPING WORLD CAUSES MORBIDITY AND MORTALITY •Pneumococcal disease • Major cause of morbidity and mortality worldwide • Diagnosis not always made and difficult to establish • Treatment may be complicated by antibiotic resistance • Management can be costly •Prevention by vaccination is a priority in populations who are at risk: • The elderly • Patients with chronic cardiovascular, pulmonary, renal, hepatic and metabolic disorders • Patients who are immunocompromised • Patients with asplenia
    • • Programme created by Dr.T.V.Rao MD for Medical and Health Care Workers in the Developing World • Email • doctortvrao@gmail.comDR.T.V.RAO MD 43