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Haemophilus , Brucella and Bordetella

Haemophilus , Brucella and Bordetella. Dr. Brian O’Connell. Parvobacteria. Parvobacteria. Gram stain of Haemophilus influenzae. Gram stain of E. coli. H. influenzae. Small, non-sporing, non-motile bacterium

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Haemophilus , Brucella and Bordetella

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  1. Haemophilus, Brucella and Bordetella Dr. Brian O’Connell

  2. Parvobacteria

  3. Parvobacteria Gram stain of Haemophilus influenzae Gram stain of E. coli

  4. H. influenzae • Small, non-sporing, non-motile bacterium • Encapsulated strains isolated from cerebrospinal fluid are gram-negative coccobacilli • Non encapsulated organisms from sputum are pleomorphic • Requires preformed growth factors that are present in blood, specifically • X factor (i.e., hemin – from iron containing pigments) • V factor (NAD or NADP). • Usually grown on chocolate blood agar

  5. Gram stain of H. influenzae from a CSF

  6. Gram stain of H. influenzae from sputum

  7. Epidemiology: • Only found in humans • Normally found in the pharynx (conjunctiva, genital tract) • Spread by airborne droplets or direct contact with respiratory secretions • Both extra and intracellular pathogen

  8. Virulence and Immunity • Some strains are encapsulated with polyribosylribitolphosphate (PRP) • Subdivides H. influenzae into groups a-f • Type B is a major virulence factor • 95 percent of bloodstream and meningeal Haemophilus infections in children are caused by type B organisms • Encapsulated organisms penetrate the epithelium of the nasopharynx and invade the blood capillaries directly • Resist phagocytosis and complement-mediated lysis in the the nonimmune host

  9. The age incidence of H. influenzae meningitis is inversely proportional to the titre of bactericidal antibody in the blood • Passively acquired from the mother or actively formed • In children aged 2 months to 3 years, antibody levels are minimal

  10. Relation of the age incidence of bacterial meningitis caused by Haemophilus influenzae to bactericidal antibody titres in the blood

  11. Clinical Manifestations- invasive disease • Hib • Bacteraemia • Meningitis • No particular features to distinguish HiB meningitis from other causes • May be fulminant but usually presents with several days of mild URTI followed by deterioration • Mortality <5% but neurologic sequelae are common • Septic arthritis • Previously common in children <2 years • Single weight-bearing joint

  12. Epiglottitis • Acute respiratory obstruction caused by cellulitis of supraglottic tissues • Usually children aged between 2 and 7 but also occasionally occurs in adults • Sore throat, fever, pooling of secretions, restless, anxious, sitting in characteristic position – sitting up, tongue sticking out, drooling, inspiratory stridor

  13. Epiglottitis in an adult

  14. Cellulitis • Reddish-blue hue, typically on cheek

  15. Haemophilus influenzae type b periorbital cellulitis

  16. Clinical manifestations- mucosal disease • Non-typable H. influenzae • Otitis media • Sinusitis • Conjunctivitis • Exacerbations of COPD • Pneumonia • Especially in elderly with pre-existing lung disease

  17. Laboratory Diagnosis • Gram stain • Pleomorphic gram-negative coccobacilli • Culture • Chocolate agar • Confirm by growth around X and V discs

  18. Treatment • Hib • Third-generation cephalosporin e.g. cefotaxime until susceptibility confirmed • Between 5 and 20% of strains produce -lactamase • Non-typable strains • Amoxicillin, co-amoxyclav

  19. Prevention • HiB vaccine introduced in Ireland in 1992 • Scheduled doses at 2, 4 and 6 months • Uptake >90% • Still about 40 cases/year • 6 true vaccine failures (TVF) in 2004, 11 in 2005 (Fitzgerald et al. 2005) • Introduction of booster dose at 12-15 months in 2008

  20. Haemophilus influenzae Type B Disease by Age Group: 1987 to 2005

  21. One true vaccine failures in 2010.

  22. Bordetella pertussis • Gram-negative coccobacillus • Nutritionally fastidious, normally cultivated on medium containing blood • Primarily a human pathogen • Other members of the genus Bordetella can cause disease in animals • Causes Pertussis (Whooping cough) • Serious, highly communicable acute tracheobronchitis

  23. Whooping cough - Epidemiology • Estimated 285,000 deaths in 2001 worldwide • Cases in Ireland • 8296 cases in U.S. • Previously mainly in children • Now a number of reports of increasing pertussis in adults because of the limited duration of protection from pertussis vaccine

  24. Data from HPSC

  25. Virulence factors • 4 important steps in development of disease: attachment, (2) evasion of host defenses, (3) local damage, and (4) systemic manifestations • Filamentous Hemagglutinin (Fha) • ability to agglutinate RBCs • Binds to galactose on sulfated glycolipids (in membranes of ciliated cells) • Antibodies to Fha protect against infection • Pertussis Toxin (PT) • may act as an adhesin and toxin • Two toxin subunits (S2 and S3) mediate adherence • Anti-Pt-antibody prevents colonization of ciliated cells, protects vs infection

  26. Adenylate cyclase toxin (ACT) • Mainly cell-associated, can be released • activated adenylate cyclase leads to impaired white cell function • Tracheal cytotoxin (TCT) • Peptidoglycan fragment • Released by lysis • Kills ciliated cells • Stimulates release of IL-1 (produces fever) • Dermonecrotic toxin (DNT) • Causes smooth muscle contraction leading to ischaemic necrosis

  27. Pathogenesis Attachment to respiratory epithelium mediated by FHA and possibly PT Ciliostatsis and damage to epithelium mediated by TCT Inhibition of phagocytsosis mediated by ACT, PT and DNT Systemaic manifestations probably manifested by PT

  28. Clinical manifestations:Pertussis (whooping cough) • Spread by aerosol/direct contact • Early symptoms - nonspecific- seldom diagnosed until paroxysmal stage- most contagious early • Stages- Incubation period: 7-10 days- Catarrhal stage: • Symptoms like common cold, lasts 1-2 weeks • Paroxysmal stage: • dry nonproductive cough, paroxysmal • excess mucus production, vomiting, convulsions, cyanosis, paroxysms separated by inspiratory whoop • Lasts 4-6 weeks

  29. Children who are too young to be fully vaccinated and those who have not completed the primary vaccination series are at highest risk for severe illness

  30. Complications • Pneumonia • Either caused by B. pertussis or secondary bacterial infection • Bronchiectasis • Neurological damage • Seizures in 1.4%, encephalopathy 0.2% (seizures and mental retardation) • Raised intrathoracic and intrabdominal pressure leading to intracranial bleeds, conjunctival haemorrhages, petichiae, pneumothorax, inguinal hernia etc.

  31. Laboratory Diagnosis • Leucocytosis with absolute lymphocytosis at end of catarrhal and beginning of paroxysmal stage • Culture: pernasal swab early in course of illness, plate on Bordet-Genou or charcoal medium • PCR • Serology

  32. Management and Prevention • effect of antimicrobial therapy on the severity and duration of the illness is debated but erythromycin x 14 days (clarythromycin and azithromycin are alternatives) is recommended as it may reduce the spread of disease • Antimicrobial prophylaxis (erythromycin x 14 d) should be offered to all family members and other close contacts • There is no evidence of any benefit from chemoprophylaxis given more than 21 days from the date of onset of the primary case. • Chemoprophylaxis should be considered if a case has a household contact who is at greatest risk from pertussis – primarily young

  33. Vaccination • Whole-cell pertussis vaccination is associated with rare serious events such as acute encephalopathy, estimated to occur at 0.0-10.5 per million doses • 1996 several new acellular pertussis vaccines developed • multicomponent vaccines contain combinations of pertussis toxoid, filamentous hemagglutinin, pertactin, and the two types of fimbriae • fewer side effects than the whole cell vaccine • Protection declines with time (little protection at 10 yrs) • Booster recommended at 11-14 yrs

  34. Pertussis in Ireland

  35. Brucella species • Gram-negative coccobacillus • Facultative intracellular parasites • Six species • B. abortus - cattle • B. suis - pigs • B. melitensis - goats • B. canis - dogs • B. ovis - sheep • B. neotomae - desert wood rats • Cause zoonoses worldwide • Ireland was declared free of brucellosis in cattle on July 1st 2009

  36. B. abortus • Disease in cattle- causes abortion, mammary infection (not mastitis)- transmission to humans by ingestion (infected milk) or inhalation (aborted material) • Disease in humans- long incubation period (weeks, months)- malaise, chills, fever, sweats- weakness, myalgia, headache- nervous symptoms (psychoneurosis)- difficult to diagnose due to vagueness of symptoms

  37. Sir David Bruce (1855-1931) isolated the bacterium of Malta fever in 1887. • B. melitensis • Primary hosts are sheep and goat • Disease in goat similar to B. abortus in cattle • Early localization in mammary gland, shedding in milk leads to human infection • Gastroenteritis- Malta/Mediterranean fever • potential agent of bioterrorism

  38. Pathogenesis • Ingestion. • Most common. • Inhalation. • Certain occupations e.g. laboratory workers, abbattoir workers. • Enter the body through skin wounds. • Slaughterhouses or meat packing plants or for veterinarians. • Laboratory • inhalation of aerosols (estimated infectious dose of 10-100 organisms) • Common laboratory-acquired infection • Accounts for 10% of LAIs in US • 11% of deaths associated with occupational exposure

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