Haemophilus

Haemophilus influenzae Haemophilus ducreyi

Haemophilus General Overview

 Gram-negative bacilli liking blood (as per genus name)  Obligate Parasites of Man and Animals  Major pathogens for which humans are natural hosts Haemophilus influenzae
Acute pyogenic, normally invasive infections Chronic infections with H. influenzae as 2o pathogen

Haemophilus ducreyi
STD; Soft chancre (chancroid)

Chancroid painful genital ulcer with accompanying painful swollen inguinal lymph nodes which later rupture releasing pus

Syphilitic chancre painless, bilateral adenopathy without pus

Genital Herpes initially as painful blisters which later rupture with associated systemic symptoms Lymphogranuloma Venereum (LGV) ulcer disappears when lymphnodes inflame, LN are painless and suppurative

Haemophilus influenzae Diseases

Gardnerella vaginalis
Clue cells vaginal epithelial cells that contain bacilli within the cytoplasm

Signs and symptoms: burning or itching of labia, dysuria, fishy odor foul-smelling vaginal discharge Metronidazole drug of choice

Bordetella pertussis
Fastidious hard to grow like H. influenzae NOT INVASIVE, meaning never goes into the bloodstream. It does all its damage where it lands in the respiratory tract

Bordetella pertussis
Virulence Factors
 Fimbriae for attachment like H. influenzae  Endotoxin role similar to H. influenzae  Big difference between the two is that Bordetella pertussis produces a bunch of different types of exotoxins
Pertussis toxin
Increases cAMP in lung cells Increased cAMP = increased secretion Excessive mucous and fluid build-up

Adenylate Cyclase Toxin

Also increases cAMP

Dermonecrotic Toxin Tracheal cytotoxin

Bordetella pertussis
Pathogenesis
 Respiratory droplet exposure  Enter respiratory tract  Attach to ciliated epithelial cells  Endotoxin inhibits cilia clearance  Replication on outside of respiratory cells  Cells eventually die and release toxin
This is an important point to understand when we talk about approaches to antibacterial therapy. The cells must die and release their toxins to cause the symptoms of the disease

Bordetella pertussis
Clinical Infection Whooping cough Epidemiology
Humans only reservoir 60,000,000 cases annually world wide 2000-6000 cases annually in US Occur primarily in nonimmune children Adults with waning immunity milder disease
Misdiagnosed as cold or flu

Bordetella pertussis
Three stages of Whooping Cough

Catarrhal stage
First stage as bacteria just start to die and release toxin
Mild cold symptoms, coughing, sneezing

Child is not that sick so parent thinks they have a common cold and dont isolate from other children This is the MOST contagious stage since many bacteria still alive in respiratory tract and all the coughing and sneezing spread live bacteria easily to other children

Bordetella pertussis
Paroxysmal stage
Maximum cell death and toxin release Severe Cough
40 50 cough spells/day 20-30 coughs in a row with no chance to breath Coughing causes stomach upset and vomiting

Mucous build-up in Lungs

Air blockage can in rare cases lead to death Secondary pneumonia is biggest threat  Caused by other bacterial pathogens H. influenzae, S. aureus, and S. pneumoniae

Bordetella pertussis
Convalescent stage
Coughing spells diminish slowly
decrease in number of spells and severity

Possible CNS complications in some children. The pathogenesis is not clear

Bordetella pertussis
Treatment Self-limiting in majority of children Supportive treatment Antibiotics only speed up the process. Erythromycin (Macrolides)
No effect on disease Reduces number of live bacteria Reduces the incidence of secondary pneumonia Prophylaxis of contacts important

Bordetella pertussis
Vaccination (DPT diphtheria, pertussis, tetanus)
Has own unique problems different from the H. influenzae CNS toxicity was major stumbling block
Blamed on whole cell pertussis prep in the DPT vaccine Many parents avoided vaccine and apathy led to wide spread outbreaks

New genetic engineered noncellular preparations have helped to alleviate fear in parents However, only effective in 80-85% of children Therefore, we still need to give antibiotics to contacts

Legionella sp.
Legionnaires Disease Pontiac Fever

Genus Legionella
Best-studied species is L. pneumophila
accounts for ~ 85% of infections motile, Gram-negative, aerobic rod complex nutritional requirements

~ 50 species in genus, > half implicated in human disease

L. micdadei: mild, febrile, flu-like illness called Pontiac fever
self-limiting, little or no tissue damage

Legionella pneumophila
Ubiquitous in soil and freshwater
incidence increased dramatically with installation of central A/C in large buildings grows in A/C cooling towers aerosols from A/C machinery inhaled contaminated inhalation therapy devices dust, liquid aerosols from construction sites whirlpool spas colonization of hot water tanks if > 40C

Legionnaires Disease
Susceptibility
healthy are relatively resistant impairment of respiratory defenses (heavy alcohol use, smoking, old age) increases susceptibility hospital patients with underlying immune defects also susceptible

Legionnaires Disease
Fever, disorientation, lethargy Severe pneumonia progressing to multisystemic disease Considerable lung damage X-rays reveal patches of fluid accumulation Most invading bacteria found inside phagocytes, growing inside phagosomes Extensive lysis of phagocytes

Treatment and Prevention

Drug of choice is erythromycin (why?) Also azithromcyin, levofloxacin Prevention: disinfection of water systems

Yersinia pestis
Gram-negative rod Intracellular pathogen Zoonotic infection Epidemiology
World-wide problem India has had latest scare (100s infected) Sporadic cases in the U.S., southwestern mostly Usually associated with contact with squirrels and other urban animals

Yersinia pestis
Clinical Syndromes (Bubonic Plague)
Flea bite Bacilli travel to lymph nodes Infection results in swelling and pain (Bubo seen in picture below) High fever, chills, headache, nausea

Yersinia pestis
Clinical Syndromes (Septicemic Plague)
Can penetrate and invade bloodstream
All organs infected Lungs (secondary pneumonic plague) Danger to close contacts

50-75% mortality when it goes to bloodstream

Endotoxin shock primary problem
Intravascular coagulation Multi-organ failure bruising on skinthis is how it got the name the black death See the same thing with Neisseria meningitidis

Yersinia pestis
Clinical Syndromes (Primary Pneumonic Plague)
Spread via respiratory droplets 1 bacilli can cause disease in patient Severe hemorrhaging Death in hours 100% mortality if untreated, or late treatment

Diagnosis and Treatment

Symptoms and patient history key Must act fast with treatment

Brucella species
Medically important species named for the livestock they commonly come from
Brucella abortus (cattle) Brucella suis (pigs) Brucella melitensis (goats)

General characteristics
Intracellular pathogen Classic Zoonotic pathogen

Brucella species
Epidemiology
Worldwide prevalence Causes serious problems in herds (abortions) Routes of Transmission to humans are varied
Unpasteurized Milk (not a real problem in U.S.) Slaughterhouse, veterinarians, livestock handler
Contact with infected tissue, blood, urine Inhalation

Brucella species
Clinical syndrome (undulant fever)
Cyclic undulant fever that lasts for several weeks Enlarged lymph nodes Fatigue Can be chronic long lasting

Diagnosis
Tough because clinical symptoms are so nonspecific History of patient is most important
Where do they work Where have the traveled (drank unpasteurized milk)

Difficult to culture (takes 6 weeks) Looking for antibodies in serum also used to diagnose, but tricky

Brucella species
Treatment
Tetracycline is drug of choice Bacteriostatic protein synthesis inhibitor Good intracellular penetration Relapses are still common though

Prevention
No vaccine for humans, some for animals Kill infected animals and herds
1000s in killed in Yellowstone National Park

Pasteurize milk and wear protective clothing

Francisella tularensis
General characteristics are very similar to Brucella species
Intracellular pathogen Zoonotic

Franciscella tularensis
Epidemiology
Worldwide prevalence, widespread in U.S. Found in >100 species of animals (RABBITS) Insect vector important too, and is something we dont see with Brucella Routes of Transmission
Infected tissue (rabbit fever) Inhalation Ingestion Insect bites

Franciscella tularensis
Clinical syndromes (depends on route of transmission)
Ulceroglandular
Most common form of disease (80% of cases) Ulcer at site of inoculation Commonly seen in hunters that kill rabbits and skin them This would be the form seen from insect bite as well

Oculoglandular
Rub the eye and introduce bacteria into eye Ulcers in conjuctiva of eye

Pneumonic
Highest mortality (10% if untreated) Usually primary inhalation, secondary spread from other forms

Typhoidal
Ingested contaminated meat or water

Franciscella tularensis
Diagnosis
Clinical history of patient and symptoms
Did they hunt? Insect bite? Skin a rabbit?

Rarely cultured, hard to grow and dangerous to lab personnel

Treatment
Gentamicin (bactericidal)..tetracycline alternative Relapses common

Prevention
Protect against inoculation Vaccination of lab personnel only

Pasteurella multocida
Similar general characteristics to Brucella and Francisella Veterinary problem
Both domestic and wild animals Respiratory/GI during stress (shipping fever) Cholera in poultry Hemorrhagic septicemia and pneumonia cattle

Human disease
Cellulitis from animal bites

Pasteurella multocida
Human disease
Cellulitis from animal bites
within 24 hours is key for differential diagnosis

Pneumonia from inhalation Septicemia and death, this can occur in infants that are licked by infected dogs or cats in the face

Diagnosis and treatment

Patient history Time of bite critical to differentiate from Gram positive pathogens that take longer to show symptoms Penicillin very effective, rare for gram-negative bacteria