Bordetella Pertussis and Respiratory Tract Infections - PDF

Gram-Negative Rods Related to the Respiratory Tract Bordetella pertussis Acinetobacter baumannii Dr. Nada A. Abdelrahim 1  Four medically important Gram-negative rods, typically associated with respiratory tract:- ❖Haemophilus influenzae ❖Bordetella pertussis ❖Acinetob...

Gram-Negative Rods Related to the Respiratory Tract Bordetella pertussis Acinetobacter baumannii Dr. Nada A. Abdelrahim 1  Four medically important Gram-negative rods, typically associated with respiratory tract:- ❖Haemophilus influenzae ❖Bordetella pertussis ❖Acinetobacter baumannii ❖LegioneIla pneumophila (See Table on Next Slide) H. influenzae & B. pertussis are found Only in Humans, whereas L. pneumophila is found primarily in environmental water sources A. baumannii is found in environmental water sources but also colonizes skin & upper respiratory tract 2 3 Bordetella pertussis 4  Bordetella pertussis causes Whooping Cough (Pertussis) B. pertussis is a Small, Coccobacillary, Encapsulated Gram-negative Rod A young boy coughing due to pertussis 5  Pathogenesis & Epidemiology B. pertussis (pathogen only for humans) is transmitted by airborne droplets produced during severe coughing episodes Organisms attach to ciliated epithelium of the upper respiratory tract, but do not invade underlying tissue Decreased cilia activity & subsequent death of ciliated epithelial cells are important aspects of pathogenesis Pertussis is a highly contagious disease that occurs primarily in infants & young children and has worldwide distribution Number of cases has declined in US (because use of vaccine is widespread) Outbreaks of pertussis during years 2005, 2010 & 2012 has led to concern about waning immunity to the vaccine & to the recommendation that an additional booster immunization be given 6  Several Factors play a role in the Pathogenesis: (1) Attachment of organism to cilia of epithelial cells is mediated by protein on pili called filamentous hemagglutinin o Antibody against filamentous hemagglutinin inhibits attachment & protects against disease (2) Pertussis toxin stimulates adenylate cyclase by catalyzing addition of adenosine diphosphate ribose (a process called ADP-ribosylation) to inhibitory subunit of G protein complex (Gi protein) o This results in prolonged stimulation of adenylate cyclase & consequent rise in cAMP & in cyclic AMP–dependent protein kinase activity 7 o This results in edema of respiratory mucosa that contributes to the severe cough of pertussis o Toxin also has domain that mediates its binding to receptors on surface of respiratory tract epithelial cells. It is an A-B subunit toxin o Pertussis toxin also causes striking lymphocytosis in the blood of patients with pertussis o The toxin inhibits signal transduction by chemokine receptors, resulting in failure of lymphocytes to enter lymphoid tissue (Spleen & Lymph Nodes) o Because lymphocytes do not enter lymphoid tissue, there is increase in their number in blood o Inhibition of signal transduction by chemokine receptors is also caused by ADP-ribosylation of Gi protein 8 (3) Organisms also synthesize & export Adenylate Cyclase o This enzyme (when taken up by phagocytic cells [e.g., neutrophils]) can inhibit their bactericidal activity o Bacterial mutants that lack cyclase activity are Avirulent (4) Tracheal cytotoxin is a fragment of the bacterial peptidoglycan that damages ciliated cells of respiratory tract o Tracheal cytotoxin appears to act in concert with endotoxin to induce nitric oxide (which kills the ciliated epithelial cells) 9  Clinical Findings Whooping cough is an Acute Tracheobronchitis that begins with Mild URT tract symptoms followed by Severe Paroxysmal Cough (lasts from 1 to 4 weeks) Paroxysmal Pattern is characterized by: series of hacking coughs, accompanied by production of copious amounts of mucus, that end with an inspiratory “whoop” as air rushes past the narrowed glottis Despite the severity of symptoms, the organism is restricted to the respiratory tract (blood cultures are negative) Pronounced Leukocytosis with up to 70% lymphocytes is seen Although Central Nervous System Anoxia & Exhaustion can occur as a result of the severe coughing, Death is due mainly to Pneumonia 10  Classic picture of Whooping Cough (described earlier) occurs primarily in Young Children In adults, B. pertussis infection often manifests as Paroxysmal Cough of varying severity lasting weeks Characteristic Whoop is often Absent, leading to difficulty in recognizing the cough as caused by this organism In the correct clinical setting, Adults with Cough Lasting Several Weeks (often called the 100-Day Cough) should be evaluated for infection with B. pertussis 11  Laboratory Features Diagnosis of whooping cough can usually be made clinically Only occasionally is the laboratory required to investigate B. pertussis infection Specimens: Preferably Nasopharyngeal Secretions collected by Aspiration or a correctly taken Pernasal Swab taken during the paroxysmal stage Morphology: B. pertussis is Small, Non-Motile, Capsulated Gram-negative coccobacillus It may occur Singly or in Chains, and may show Bipolar Staining 12 Bordetella pertussis G –ve coccobacilli 13 14  Bordetella species are Strict Aerobes ❖ Specimens for the isolation of B. pertussis must be cultured as soon as possible Medium of choice for Bordetellae Bordet-Gengou medium (contains high percentage of blood [20%–30%] to inactivate inhibitors in agar) Culture: BGM or Charcoal Cephalexin Blood Agar when incubated for 2–6 days at 35–37 ºC in Moist Aerobic Atmosphere, they produce Small Pearly-Grey, Shiny (Mercury-Like), usually Mucoid colonies Identification can be made by: agglutination with specific antiserum or by fluorescent antibody staining The organism grows very slowly in culture, so Direct Fluorescent-Antibody Staining of nasopharyngeal specimens can be used for diagnosis 15 Bordet Gengou Agar with Blood Showing colonies of Bordetella pertussis 16  PCR–based tests are highly specific & sensitive & should be used if available Isolation in patients with prolonged cough is often difficult: Serologic tests that detect antibody in patient’s serum can be used for diagnosis in those patients Bordetella parapertussis grows more rapidly & forms larger colonies than B. pertussis It produces Pigment in the Medium and is able to Grow Aerobically on blood agar & nutrient agar 17  B. pertussis is Oxidase Positive & Urease Negative B. parapertussis is Oxidase Negative & Slowly Urease Positive (after 24 h) Bordetella species can be serotyped in specialist microbiology laboratory Antimicrobials with activity against B. pertussis include: Erythromycin Chloramphenicol Tetracycline & Cotrimoxazole Protection against whooping cough is by prophylactic vaccination 18  Treatment Azithromycin is the drug of choice Azithromycin reduces number of organisms in throat & decreases risk of secondary complications But has little effect on the course of the disease at the “prolonged cough” stage (because the toxins already damaged the respiratory mucosa) Supportive care (e.g., oxygen therapy & suction of mucus) during the paroxysmal stage is important (especially in infants) 19  Prevention Two types of vaccines: 1) Acellular Vaccine containing purified proteins from Bordetellae 2) Killed Vaccine containing inactivated Bordetella pertussis The Acellular Vaccine contains 5 antigens purified from Bordetellae (used currently in the US) Main Immunogen in this vaccine is Inactivated Pertussis Toxin (Pertussis Toxoid) Toxoid in the vaccine is Pertussis Toxin that is inactivated genetically by introducing two amino acid changes (which eliminates its ADP-ribosylating activity but retains its antigenicity) It is the first vaccine to contain a Genetically Inactivated Toxoid 20  Other Pertussis Antigens in Acellular Vaccine are: o Filamentous Hemagglutinin o Pertactin o Fimbriae Types 2 & 3 Acellular Vaccine has Fewer Side Effects than the Killed Vaccine Acellular Vaccine has Shorter Duration of Immunity than the Killed Vaccine The pertussis vaccine is usually given combined with diphtheria and tetanus toxoids (DTaP) in three doses beginning at 2 months of age. Booster at 12 to 15 months of age & Another at the time of entering school are recommended Because outbreaks of pertussis usually occurrs among Teenagers, a Booster for those between 10 and 18 years old is recommended This vaccine (called Boostrix) contains Diphtheria & Tetanus Toxoids also21  Another vaccine (called Adacel) also contains Diphtheria & Tetanus Toxoids A Pertussis Booster Dose is recommended for Adults as well To Protect Newborns, Pregnant Women should receive Pertussis Vaccine Anti-pertussis IgG will pass the placenta & protect the newborn The Killed Vaccine is no longer used in the US (because it is suspected of causing various side effects, including Post-Vaccine Encephalopathy at a rate of about one case per million doses administered) The Killed Vaccine is in use in many other countries 22  Azithromycin is useful in prevention of disease in Exposed, Unimmunized Individuals It should also be given to Immunized Children Younger than 4 years who have been exposed (because vaccine-induced immunity is not completely protective) 23 Acinetobacter baumannii 24  Acinetobacter species are Gram-negative coccobacillary rods Found commonly in Soil & Water, but they can be part of the normal flora Are Opportunists that readily colonize patients with compromised host defenses Acinetobacter baumannii is the species usually involved in human infection It causes disease mostly in Hospital Setting (associated with respiratory therapy equipment [ventilator-associated pneumonia] & indwelling catheters) Sepsis, Pneumonia & UTIs are the most frequent manifestations A. baumannii is remarkably Antibiotic Resistant Some isolates are Resistant to All Known Antibiotics Imipenem is the drug of choice for infections caused by susceptible strains Colistin is useful in Carbapenem-Resistant Strains Previous Genus names for this organism include Herellea & Mima 25 26