Lecture 16 Haemophilus-Bordetella

Lecture 16 Haemophilus-Bordetella - Haemophilus Lecture 16...

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Unformatted text preview: Haemophilus Lecture 16 Classification Classification Family Genus Species Pasteurellaceae Haemophilus H. influenzae H. influenzae bg aegyptius H. parainfluenzae H. aphrophilus H. ducreyi History: H. influenzae History: First described by Dr. Pfeiffer in 1892 Isolated from flu patient Proposed to be etiological agent of human influenza Subtyping: 1) According to serological reaction (capsule antigens): Serotypes a­f (type b most important human pathogen) 2) According to biochemical reaction: Biotypes I­VIII 3) According to clinical and other biological phenotypes: Biogroups e.g. H.influenzae biogroup aegypticus (causes Brazilian purpuric fever) H. influenzae H. influenzae Gram­neg H. influenzae H. influenzae General Characteristics Variable morphology (pleiomorphic), small rods/coccobaccilli­that can assemble into filaments fastidious Facultative anaerobe, fermenter Catalase positive non­spore forming Nonmotile H. influenzae H. influenzae Pathogenicity Capsular antigen (polyribitol phosphate, PRP, characteristic for Hib ) Outer membrane components (LPS) Adherence (fimbriae) IgA protease (against Ab mediated opsonization and complement activation) Three mechanism of antibody mediated host defense Three mechanism of antibody mediated host defense Evasion of acquired IR Evasion of acquired IR one example Expression of Ig binding proteins (Prot.A) Evasion of IgA in mucosal surfaces Evasion of IgA in mucosal surfaces IgA: -secreted as dimer -neutralizes pathogen (inhibits adhesion, toxins) IgA structure and bacterial targets IgA structure and bacterial targets 1) 3) 2) found mainly in extracellular pathogens IgA proteases IgA proteases New Concept! Co­Evolution New Concept! Co­Evolution IgA1 proteases are immunogenic and host develops Ab against them 30 different forms of protease have been found in Haemophilus influenzae Antigenic diversity helps evade host Ab H. Influenzae (all serotypes) Ear (Otitis) and sinus (Sinusitis) infections H. Influenzae (encapsuled only and mostly type b pre­vaccine era) Pulmonary disease Epiglottitis Meningitis (100% mortality if untreated) H. ducreyi Genital ulcers (STD)/Chancroid Diseases Diseases 7: base of tongue 3: epiglottis 1: vocal cords H. Influenzae / Diagnosis H. Influenzae / Diagnosis Microscopy of blood, CSF or bronchiolar lavage fluids (high bacterial numbers in CSF) Satellite phenomenon on blood agar plates Culture on chocolate agar Examples of tissue staining Examples of tissue staining Gram stains Sputum of patient with pneumonia (Coccobacillus shape) Brain tissue (overwhelming meningitis) Long filaments H. influenzae H. influenzae Laboratory diagnosis Nutritional requirements X factor (hemin) V factor (NAD or NADP) Chocolate agar (heated blood agar) in order to destroy inhibitor of V­factor and release Hemin Satellite phenomenon Satellite phenomenon Staph aureus secretes NAD which promotes growth of H.influenzae on regular blood agar H. influenzae H. influenzae Haemophilus spp. omnipresent (nasopharynx) most non­encapsulated=nontypeable (NTHi) few are encapsulated few cause invasive disease 95% of invasive disease caused by type b (prevaccine era) Now more cases caused by non­b H. influenzae and NTHi in U.S. Type b still a significant problem in developing countries Epidemiology Epidemiology: USA 2008 Epidemiology: USA 2008 This used to be about 20,000 before 1987 Humans (asymptomatic carrier) only known host Colonizes nasopharynx Spread via aerosolized dropletsof infected or asymptomatic subject Temporal pattern (peaks in Sept­Dec. and March­May); reason unknown H. influenzae Epidemiology/Transmission H. Influenzae type b H. Influenzae type b Epidemiology Pre­vaccine (introduced in 1987) H. influenzae H. influenzae Prevention Active immunization with polysaccharide­ protein conjugate vaccines capsular PRP (polyribitol phosphate) linked to protein (from other pathogen) 3 doses before 6 months followed by booster doses Induces protective antibody response Possible proteins used for Possible proteins used for conjugation No vaccine available of Hi type a H. influenzae H. influenzae Meningitis Treatment broad spectrum cephalosporins Less severe infections, e.g. sinusitis and otitis ampicillin (~35% are resistant) cephalosporins Prophylaxis use rifampin for children at risk Causes painful ulcers on genitals and selling of inguinal lymph nodes, symptomatic mostly in men Rare in the US, 6 million cases world wide Sexually transmitted disease Presence of chancre facilitates HIV infection 10% of cases; co­infection with T. pallidum Treatment using Cipro or Erythromycin H. ducreyi (Chancroid) H. ducreyi (Chancroid) Chancroid Chancroid Latex condoms Broad range of antibiotics are effective (e.g. erythromycin) Sometimes large, swollen lymph nodes need to be drained Ulcers contain large amount of bacteria and are thus contagious­ avoid contact to not spread bacteria to other body parts Chancroid Chancroid Prevention/Treatment Lecture 16 Lecture 16 Bordetella Classification Classification Family Alcaligenaceae Genus Bordetella 5 others B. pertussis B. parapertussis B. bronchiseptica Species Characteristics Bordetella Bordetella small gram negative coccobacillus capsule Non­motile after subculture: pleiomorphic bipolar metachromatic staining narrow zone of hemolysis Antigenic Structure Bordetella Bordetella Surface O antigen (LPS) heat stable protein Capsular antigen heat labile K antigens Bordetella Bordetella Physiology Strict aerobes tests used: urease (NEGATIVE) nitrate reduction (NEGATIVE) oxidase (POSITIVE) Laboratory Diagnosis Bordetella Bordetella Primary isolation nasopharyngeal swab on modified B­G (Bordet­ Gengou) Glycerin potatoe blood agar B. pertussis 3­4 days to grow identification by biochemical tests agglutination tests Nasopharyngeal swap Nasopharyngeal aspirate Diagnostic Diagnostic Pathogenic Factors Bordetella Bordetella Pertussis Toxin (A­B5 type toxin) ­leads to increase in intracellular cAMP levels, leading to increased secretion in epithelial cells (mucus build up in lungs) Pertactin and Filamentous Hemagglutinins (Adhesins that bind to ciliated epithelium in lungs) LPS Bordetella Bordetella Clinical Causative agent of pertussis (whooping cough) Infection by inhalation Stages Incubation Catarrhal (Inflammation of mucous membranes, especially of the nose and throat) Paroxysmal (A sudden attack, recurrence, or intensification of a disease) Convalescent Most contagious stage Whooping Cough Whooping Cough http://www.whoopingcough.net/sound%20of%20whooping%20cough%20with%20much% http://www.whoopingcough.net/cough­child­muchwhooping.wav Intense cough can be followed by episodes of vomiting Epidemiology Bordetella Bordetella Human only known host In US, 7­12,000 cases /yr most deaths in babies under 1 YO Infant mortality worldwide a reflection of health standards Cases of pertussis in USA Cases of pertussis in USA Epidemiology Bordetella Bordetella Pertussis mostly considered a pediatric disease but… Increase in adolescent and adult Increase in adolescent and adult cases of pertussis Red: 1988 Blue: 2002 Treatment/Prevention Bordetella Bordetella Treatment Erythromycin Suction (mucus build up in the lungs), O 2 subunit Vaccine (DTaP­Diphteria, tetanus, pertussis) , using pertussis toxin and/or pertactin components but problem of antigenic variation of bacteria Chemoprophylaxis – erythromycin in contact individuals Prevention Diseases and Vaccines… Diseases and Vaccines… Hib and Bordetella pertussis Hib and Bordetella pertussis cause mainly pediatric disease Highly preventable by childhood vaccinations! No demonstrated causal link between vaccinations and autism Some parents rely on herd immunity to protect their children 1992 Hib outbreak in Minnesota 1992 Hib outbreak in Minnesota 5 cases of Hib meningitis All hospitalized One death In 3 of 5 children parents did not vaccinate child Vaccination helps protect the Vaccination helps protect the unvaccinated/susceptible children/infants Effect of vaccines on public Effect of vaccines on public health ...
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