Streptococcus pneumonia
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Streptococcus pneumonia

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Streptococcus pneumonia

Streptococcus pneumonia

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Streptococcus pneumonia Streptococcus pneumonia Presentation Transcript

  • Microbial Diseases of the Upper Respiratory SystemLaryngitis: S. pneumoniae, S.pyogenes, virusesTonsillitis: S. pneumoniae, S.pyogenes, virusesSinusitis: BacteriaEpiglottitis: H. influenzae Dr.T.V.Rao MD 2
  • History0 In 1881, the organism, discovered by Leo Escolar, then known as the pneumococcus for its role as an etiologic agent of pneumonia, was first isolated simultaneously and independently by the U.S Army physician George Sternberg and the French chemist Louis Pasteur. Dr.T.V.Rao MD 3
  • Pneumococcal disease: a major health threat0 Streptococcus pneumoniae is the leading bacterial cause of infection worldwide:- asymptomatic colonisation- common infections (otitis media, )- life-threating infections (sepsis, meningitis, )0 Despite the introduction of antimicrobial drugs over the past few decades it remains a significant threat to health Dr.T.V.Rao MD 4
  • S. pneumoniae0 leading cause of pneumonia 0 particularly young and old 0 after damage to upper respiratory tract *e.g.following viral infection0 bacteremia0 meningitis0 middle ear infections (otitis media) Dr.T.V.Rao MD 5
  • DISEASES CAUSED BY STREPTOCOCCUS PNEUMONIAE PNEUMOCOCCAL INFECTIONNon-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) Dr.T.V.Rao MD 6 Musher, in Principles and Practice of Infectious Diseases, 1995
  • Streptococcus pneumoniae0 Most common cause of both pneumonia overall and fatal pneumonia.0 Antibiotic resistance has developed worldwide and is most frequent in pneumococcal serotypes that are most prevalent in children (types/groups 6, 14, 19, and 23).0 The incidence of pneumococcal disease is the highest in children < 2 years of age and in adults > 65 years of age.0 Penicillin (penicillin G/amoxicillin) remains the drug of choice for strains that are fully sensitive0 Cefotaxime and ceftriaxone are the first-line alternatives in cases with higher levels of resistance. Dr.T.V.Rao MD 7
  • Streptococcus pneumoniae0 Streptococcus pneumoniae cells are Gram-positive, lancet- shaped cocci (elongated cocci with a slightly pointed outer curvature). Usually, they are seen as pairs of cocci (diplococci), but they may also occur singly and in short chains. When cultured on blood agar, they Dr.T.V.Rao MD 8 are alpha hemolytic
  • Streptococcus pneumoniae 0 Individual cells are between 0.5 and 1.25 micrometers in diameter. They do not form spores, and they are nonmotile. Like other streptococci, they lack catalase and ferment glucose to lactic acid Dr.T.V.Rao MD 9
  • Streptococcus pneumoniae • leading cause pneumonia – particularly young and old – after damage to upper respiratory tract *e.g. following viral infection • bacteremia S. pneumoniae - diplococci • meningitis • middle ear infections (otitis media)0 capsule:0 pneumolysin:0 Surface protein adhesinand secretory IgA protease.0 Teichoic acid and the Peptidoglycan fragment, phosphorylchorine . Dr.T.V.Rao MD 10
  • PNEUMOCOCCUS:Nasopharyngeal carriage may occur in up to 60% of healthy pre-schoolchildren and upTRANSMISSION AND COLONISATION to 30% of healthy older children and adults Nasal cavity Asymptomatic carrier Nasopharynx: site of colonisation Aerosol Inhalation Trachea Patient with pneumococcal disease Dr.T.V.Rao MD Fedson, Musher, in Vaccines, 1994 11 2.4 Dissemination Musher, in Principles and Practice of Infectious Diseases, 1995
  • PNEUMOCOCCUS: PATHOGENESIS Dr.T.V.Rao MD 12 Salyers, Whitt, in Bacterial Pathogenesis, 1994
  • Pneumococcal cell surface Dr.T.V.Rao MD 13
  • Genome of S. pneumoniae0 The genome of S. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs, depending on the strain. It has a core set of 1553 genes, plus 154 genes in its virulome, which contribute to virulence, and 176 genes that maintain a noninvasive phenotype. Genetic information can vary up to 10% between strains.[5] Dr.T.V.Rao MD 14
  • S. pneumoniae TIGR4 genome R6 D39 Comparativegenome hybridizations Dr.T.V.Rao MD 15 Science 2001
  • The capsule# Composition: polysaccharide# Virulence factor: avoiding phagocytosis# Induce type-specific immune response# More than 90 different serotypes Dr.T.V.Rao MD 16
  • Serotyping0 The quelling reaction (swelling reaction) forms the basis of serotyping and relies on the swelling of the capsule upon binding of homologous antibody. The test consists of mixing a loopful of colony with equal quantity of specific antiserum and then examining microscopically at 1000X for capsular swelling Dr.T.V.Rao MD 17
  • Summary Figure (Identification Scheme) Note: Strep. viridans GRAM POSITIVE COCCI are alpha hemolytic and negat ive for all t he tests below Catalase + Staphylococcus (Clusters) - (pairs & chains) Streptococcus Coagulase Hemolysis +S. aureus - S. epidermidis • BETA: Bacitracin + S .pyogenes (group A) hemolytic nonhem olytic (usua lly) CAMP/Hippurate + S. agalactiae (group B)mannitol mannitol (2) ALPHA: Optochin/Bile Solubility + S. pneumoniae yellow white • GAMMA: Bile Es culin + 6.5% NaCl + Group D* Enterococcus Bile Esc ulin + 6.5% NaCl - Group D* Non-Enterococcus (*can also be beta or alpha hemolytic) Dr.T.V.Rao MD 18
  • S. pneumoniae0 hemolytic0 pneumolysin 0 degrades red blood cells under aerobic conditions grows well on sheep blood agar0 No group antigen Dr.T.V.Rao MD 19
  • Hemolysis Streptococcus pneumoniae are Alphahemylotic alpha betagamma Dr.T.V.Rao MD 20
  • Bile solubility test Streptex antiserum optochin sensitive Not optochin sensitive Quellung reaction• using antisera• capsule "fixed" Dr.T.V.Rao MD 21• visible microscopically Latex agglutination - streptococci
  • Optochin Test0 The minimum criteria for identification and distinction of pneumococci from other streptococci are bile or optochin sensitivity, Gram-positive staining, and hemolytic activity. Dr.T.V.Rao MD 22
  • Not optochin sensitive optochin sensitiveDr.T.V.Rao MD 23
  • PNEUMOCOCCAL CARRIER STATE0 Disease occurs in persons who are already asymptomatic carriers0 Carrier rates 38%-60% in preschool children 29%-35% in grammar school children 9%-25% in junior high school students 18%-29% in adults with children at home 6% in adults with no children at home Virtually all children <2 of age become carriers Dr.T.V.Rao MD 24
  • Pathogenesis: the route to infection Colonisation of the respiratory tractInnate and adaptive immune system Replication in the nasopharynx Viral infections, malnutrition Spread to adjacent sites mucosal damage pneumonia middle-ear otitis sinusitis Dr.T.V.Rao MD 25 blood meningitis
  • Pneumococcus: colonisation and transmission0 Exclusively a human pathogen, part of the normal microbial flora of the upper respiratory tract0 Transmission: by droplet secretions0 Temporal pattern: winter-early spring0 Communicability: Unknown. Probably as long as organism in respiratory secretions Dr.T.V.Rao MD 26
  • Dr.T.V.Rao MD 27
  • Streptococcus pneumoniae: Symptoms and Signs0 Classic description 0 sudden onset of chills and pleuritic chest pain 0 followed by fever and then cough productive of rusty sputum.0 Varies greatly. 0 Respiratory tract symptoms may be absent, especially among patients with bacteremic disease. 0 Lack of fever is not uncommon and indicates a poor prognosis. 0 Gastrointestinal symptoms such as nausea, vomiting, or diarrhea are present in 15 to 20% Dr.T.V.Rao MD 28
  • Types of infection non-invasive invasiveotitis (25-50%) pneumoniasinusitis sepsisrecurrent bronchitis meningitis Dr.T.V.Rao MD 29
  • PNEUMOCOCCAL DISEASE: MENINGITIS0Meningitis 0 Inflammation of the meninges (membranes surrounding the brain) 0 Can be caused by a range of microorganisms, as well as be a manifestation of some non-infectious diseases0Pneumococcal meningitis 0 Invasive pneumococcal disease 0 Generally, pneumococci invade the CNS from the blood stream0Signs and symptoms1 0 Early stages: fever, irritability, neck stiffness, drowsiness 0 Later stages: headache, seizures, coma0The signs and symptoms are not specific to pneumococcal disease Dr.T.V.Rao MD 30 1 Salyers, Whitt, in Bacterial Pathogenesis, 1994
  • PNEUMOCOCCAL DISEASE: PNEUMONIA a major Complication0 Bacteraemia in 15−30% of patients with pneumonia − 0 high mortality despite appropriate antibiotic therapy 0 overall case fatality rate 15−20% for pneumococcal − bacteraemia 0 higher case fatality rates (30−40%) for elderly persons and − other vulnerable groups0 Spread of pneumococci in the blood to other normally sterile sites can cause other invasive pneumococcal diseases (e.g. meningitis) 0 Empyema (pus in the pleural cavity) in about 2% of cases 1 Salyers, Whitt, in Bacterial Pathogenesis, 1994 Dr.T.V.Rao MD 2 Fedson, Musher, in Vaccines, 1994 31 3 Musher, Clin Infect Dis, 1992
  • Asplenic patients at risk with Pneumococcal Infections0 Asplenic patients and those with impaired splenic function are at risk for a fulminant sepsis syndrome usually due to Streptococcus pneumoniae0 The combined use of pneumococcal polysaccharide immunization and early administration of oral empiric antibiotic therapy for fever offers a high level of protection against postsplenectomy sepsis Dr.T.V.Rao MD 32
  • HIV infection andPneumococcal Infection 0 Adults infected with HIV have high rates of invasive pneumococcal disease. 0 Persons infected with HIV are particularly susceptible to invasive pneumococcal disease, with a 50- to 100- fold higher incidence than the general U.S. population Dr.T.V.Rao MD 33
  • PNEUMOCOCCAL PNEUMONIA MORTALITY 8%-10% Overall healthy young adults (non bacteriemic) < 1% Bacteriemic pneumonia: 15%-20% High-risk groups: 50% Elderly > 70 years: 30%-40% Young adults (<45 years): <8% Dr.T.V.Rao MD 34
  • Treatment0 Treatment is usually with Beta-lactam antibiotics. In the 1960s, nearly all strains of S. pneumoniae were susceptible to penicillin, but since that time, there has been an increasing prevalence of resistance, especially in areas of high antibiotic use. A varying proportion of penicillin-resistant strains may also be resistant to erythromycin, macrolides, and clindamycin and the quinolones. Dr.T.V.Rao MD 35
  • ORAL ANTIBIOTICS0 Amoxicillin: first choice in < 5 years0 Alternatives: co-amoxiclav, azithromycin, cefaclor, erythromycin, clarithromycin0 > 5 years. 0 Macrolide antibiotics should be used if either mycoplasma or chlamydia pneumonia is suspected 0 Amoxicillin should be used as first line treatment at any age if S pneumoniae is thought to be the likely pathogen. Dr.T.V.Rao MD 36
  • IV antibiotics0Indications of Intravenous antibiotics 0 Unable to take oral antibiotics (for example, because of vomiting) 0 presents with severe signs and symptoms.0Antibiotics: 0 co-amoxiclav, cefuroxime, and cefotaxime. Dr.T.V.Rao MD 37
  • Vancomycin is helpful in resistant strains 0 Most remain susceptible to vancomycin, which is a less desirable antibiotic because of dosing and tissue penetration issues. Susceptibility testing is routine, with empiric antibiotic treatment, guided by resistance patterns in the community in which the organism was acquired, pending the results. Dr.T.V.Rao MD 38
  • PNEUMOCOCCAL POLYSACCHARIDE VACCINEs0 14-valent pneumococcal vaccine licensed in 19770 23-valent preparation licensed in 19830 23-valent vaccines cover 85%-90% of serotypes that cause invasive pneumococcal infections0 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 33F0 6 serotypes most frequently associated with drug- resistant infection: 6B, 9V, 14, 19A, and 23F Dr.T.V.Rao MD 39
  • Pneumococcal vaccines Protective immunity is conferred by anti-capsular type-specific antibodiesAntibodies against pneumococcal surface proteins conferprotection in animal models. In humans this role is to be determinedCurrently licensed in Europe: 2 types of pneumococcal vaccines Old 23-valent Pneumococcal Polysaccharide Vaccine (PPV23) New 7-valent Pneumococcal Conjugated Vaccine (PCV7) Dr.T.V.Rao MD 40
  • 23-valent Pneumococcal Polysaccharide Vaccine PPV2325 µg of purified capsular polysaccharide antigen serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33FCovers 85-90% of invasive pneumococcal diseaseRelatively good antibody responses (60–70%) followinga single intramuscular/subcutaneous immunization inmost healthy adults Dr.T.V.Rao MD 41
  • PPV23 Negative aspects0 immune response mediocre in children <2 years and in immunocompromised individuals (HIV/AIDS)0 does not induce immunological memory which is required for subsequent booster responses Dr.T.V.Rao MD 42
  • PPV23 Recommendations0 For healthy adults ≥ 65 years of age, particularly those living in institutions- Based on data from observational studies:significant protective effect against IPD, but not pneumonia- Based on data from randomised controlled trials: failed to show a beneficial effect of the vaccine0 Persons ≥ 2 years at higher risk of PID (asplenic, immunocompromised, …) Dr.T.V.Rao MD 43
  • 7-valent Pneumococcal Conjugated Vaccine PCV7• Seven S. pneumoniae capsular polysaccharide antigens, conjugated to nontoxic diphtheria toxin (cross-reactive material, CRM(197)• CRM(197): inert but immunogenic variant of diphtheria toxoid also used as a carrier molecule in one H.influenzae type b conjugate vaccine Dr.T.V.Rao MD 44
  • PCV7. Characteristics0 higher antibody levels and a more efficient immune response in infants0 significant immunological memory0 >90% effective against invasive disease0 less effective against other forms of the disease (non-invasive pneumonia, otitis media, …) Dr.T.V.Rao MD 45
  • PCV7. Effectiveness (Wyeth Lab. Prevnar®,USA or Prevenar®, Europe) ® ®0 serotypes 4, 6B, 9V, 14, 18C, 19F, 23F0 serotypes included: most prevalent in invasive diseases and antibiotic resistance potential coverage of serotypes causing PID: 85% for the USA 70-75% for Europe ≈ 65% for Latin America ≈ 50% for Asia Dr.T.V.Rao MD 46
  • PPV7. Efficacy in invasive disease Pre-licensed study Northern Carolina Kaiser Permanent Trial - 37,816 children enrolled & 4 doses of vaccine or control - efficacy against vaccine serotype disease: 97.4% (19F) - efficacy against all serotypes IPD: 89.1%Black S, et al. Efficacy, safety and immunogenicity of the heptavalent pneumococcal conjugate vaccine inchildren. Pediatric Infect Dis J. 2000;19:187-195 r.T.V.Rao MD D 47
  • PCV7. Safety and schedule02, 4, 6 months, booster 12-14 months0Possible interference with other conjugate vaccines (meningococcal) when administered together0 Safe0 Adverse reactions: fever Dr.T.V.Rao MD 48
  • CDC RECOMMENDATIONS0 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 49
  • CDC RECOMMENDATIONS0 Persons >2 years living in special environments or social settings, such as: Nursing homes Chronic-care facilities Alaskan Natives Certain Native American populations Dr.T.V.Rao MD 50
  • PNEUMOCOCCAL DISEASE: CONCLUSIONS0Pneumococcal disease 0 Major cause of morbidity and mortality worldwide 0 Diagnosis not always made and difficult to establish 0 Treatment may be complicated by antibiotic resistance 0 Management can be costly0Prevention by vaccination is a priority in populations who are at risk: 0 The elderly 0 Patients with chronic cardiovascular, pulmonary, renal, hepatic and metabolic disorders 0 Patients who are immunocompromised 0 Patients with asplenia Dr.T.V.Rao MD 51
  • 0 Programme created by Dr.T.V.Rao MD for e-learning resources for Medical and Paramedical Students in Developing world 0 Email 0 doctortvrao@gmail.com Dr.T.V.Rao MD 52