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Haemophilus, Brucella and Bordetella

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

2 Parvobacteria Haemophilus influenzae
Invasive disease - meningitis, bacteraemia, osteomyelitis Non-invasive disease –respiratory tract. Bordetella pertussis Whooping Cough Brucella spp. Brucellosis Yersinia spp. Diarrhoea and systemic disease Pasteurella Wound infection after dog/cat bites Francisella Tularaemia Legionella Pneumonia

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

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

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10 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

11 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

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13 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

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

15 Clinical Manifestations
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

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

17 Epiglottitis in an adult

18 Cellulitis Reddish-blue hue, typically on cheek

19 Haemophilus influenzae type b periorbital cellulitis

20 Non-typable H. influenzae
Otitis media Sinusitis Conjunctivitis Exacerbations of COPD Pneumonia Especially in elderly with pre-existing lung disease

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

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

23 Prevention HiB vaccine introduced in Ireland in 1992
Scheduled doses at 2, 4 and 6 months Uptake >90% Still about 40 cases/year 6 vaccine failures in (Fitzgerald et al. 2005)

24 Haemophilus influenzae Type B Disease by Age Group: 1990 to 2000

25 Number of invasive H. influenzae type b (Hib) cases in
Ireland, (Based on reports received at NDSC up to 28/11/2003)

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27 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

28 Whooping cough - Epidemiology
Estimated 285,000 deaths in 2001 worldwide 131 cases in Ireland in 2002 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

29 Data from HPSC

30 Virulence factors Filamentous Hemagglutinin (Fha) Pertussis Toxin (PT)
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

31 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

32 Pathogenesis Ciliostatsis and damage to epithelium mediated by TCT
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

33 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

34 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

35 Complications Pneumonia Neurological damage
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.

36 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

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38 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

39 Vaccination Whole-cell pertussis vaccination is associated with rare serious events such as acute encephalopathy, estimated to occur at 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

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41 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 B. abortus is still prevalent in cattle in Republic and Northern Ireland

42 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

43 B. melitensis Primary hosts are sheep and goat
Sir David Bruce ( ) 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              

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45 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. Invades mucous membranes and transported (free or in phagocytes) to lymph nodes enter phagocytic cells. Spread via circulation to other organs liver, spleen, bone marrow, kidney: cause granulomas .

46 Clinical presentation
Extremely variable. Any system can be affected In the acute form (<8 weeks from illness onset) nonspecific and "flu-like," including fever, sweats, malaise, anorexia, headache, myalgia, and back pain. Lymphadenopathy, splenomegaly Chronic (>1 year from illness onset), may include chronic fatigue syndrome-like, depressive episodes, and arthritis.

47 Laboratory Diagnosis B. melitensis: blood cultures B. abortus:
serology SAT, Coombs Four-fold rise in titre

48 Treatment Tetracycline +/- rifampicin for 6 weeks

49 Yersinia species Y. pestis Causes plague –bubonic/pneumonic
Transmitted by flea bite, occasionally from aeroslisation periodic disease outbreaks in rodent populations, hungry infected fleas that have lost their normal hosts seek other sources of blood Rat-borne epidemics continue to occur in some developing countries, particularly in rural areas. Potential bioterrorist agent

50 Yersinae pestis

51 Yersinia pestis on blood agar

52 Protective clothing worn in 14th century
Europe during the Black Death

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56 Xenopsylla cheopis - Oriental rat flea

57 FIGURE 226-3. Transmission of plague
FIGURE Transmission of plague. The wide arrows indicate common modes of transmission, the medium arrows indicate occasional transmission, and the thin arrows indicate rare kinds of transmission.

58 Clinical features Bubonic plague: Septicemic plague: Pneumonic plague:
enlarged, tender lymph nodes, fever, chills and prostration Septicemic plague: fever, chills, prostration, abdominal pain, shock and bleeding into skin and other organs Pneumonic plague: fever, chills, cough and difficulty breathing; rapid shock and death if not treated early TREATMENT Streptomycin/gentamicin, ciprofloxacin, doxycycline

59 Plague axillary bubo (CDC Public Health Image Library No:2061)

60 Plague inguinal bubo CDC Public Health Image Library No:2044

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62 Peripheral blood smear of septicaemic plague showing
FIGURE Peripheral blood smear of septicemic plague patient showing large numbers of bipolar-staining bacilli. (Courtesy of the Centers for Disease Control and Prevention, Fort Collins, CO.) Peripheral blood smear of septicaemic plague showing bipolar staining bacilli

63 Y. pseudotuberculosis Y. enterocolitica
Both can cause abdominal symptoms Occurs most often in young children. Fever, abdominal pain, and diarrhoea, which is often bloody May mimic appendicitis Eating contaminated food, especially raw or undercooked pork Outbreaks are described Usually self-limited Tetracyclines

64 Pasteurella multocida
Cause of animal bite infections Present in dog/cat oropharynx Treat with penicillin

65 Dog and cat bites Common Nearly all infections are mixed Aerobes
S. aureus, streptococci, Pasteurella etc. and anerobes Consider tetanus and rabies

66 Antimicrobial prophylaxis
Debride and irrigate Tetanus prophylaxis Antimicrobial prophylaxis Co-amoxyclav for 5- 7 days Especially for severe early infections late (>8 h) presentation Wounds of face, hand, genitals Bone or joint involvement Immunosuppressed host

67 Francisella tularensis
Small, fastidious Gram-negative bacillus Zoonoses Predominantly North America – type A Potential bioterrorist agent – no person-person spread Transmission: Bite of an infected arthropod Contact with infected animals (small rodents) Aerosol Clinical: Mainly ulceroglandular or respiratory

68 Tularaemia skin ulcer (from HPA)

69 Treatment Gentamicin/streptomycin Ciprofloxacin Doxycycline


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