• Soil bacterium
• Obligate Anaerobes
• Spore formers
• Do not have enzymes to protect from free radicals and superoxides

Clostridium botulinum

Occurrence

• Botulism
• Cosmopolitan. 
• Poor canning processes, food not cooked sufficiently to kill spores.
• Vegetative cells can then produce NEUROTOXIN (acts at the neuromuscular junction, prevents ACh from binding so muscle cannot contract-flaccid) under anaerobic conditions.
• Commerical canning cases are rare, more common in low acid or alkaline foods.
• Toxin destroyed by boiling vigorously for 3 minutes. (b/c it is a protein)

Clostridium botulinum

Reservoir

• Soil bacterium
• Intestinal tract of some herbivores and fish

Clostridium botulinum

MOT & IP

• MOT: Ingestion of preformed NEUROTOXIN without adequate heating during the canning process or before eating.

• IP: 1-4 days; shorter IP= worst case scenario & deaths

Clostridium botulinum

Disease process (DP) & Signs/Symptoms

• DP: affects nervous system primarily especially neuromuscular junction (NMJ)
• Usually an INTOXICATION and NOT an infection!

• SN/SX: ptosis (droopy eyelids), blurred vision & dry mouth are first SX. Descending symmetrical FLACCID PARALYSIS in ALERT person.
• Without treatment, 33% die in 3-7 days of respiratory paralysis; Good treatment 15% die

Clostridium botulinum

Diagnosis (DX) & Treatment (TX) & Prophy

• DX: Detection of toxin is most important b/c spores are so common
• TX: Respiratory support; botulism antitoxin
• RX: PCN in infants b/c it is an INFECTION in them (intoxication in adults)
• NO immunity
• Prophy: Can foods at proper temperature, pressure, & adequate time.; Boil home canned vegetables with stirring for at least 3 minutes

Clostridium botulinum

Wound Botulism

• Rarest type
• Spores contaminate ANAEROBIC wound (eg. puncture) and germinate.
• Vegetative cells produce exotoxin & cause disease.
• May occur in neonate if cord is cut with unsterile instrument.

Clostridium botulinum

Infant Botulism

• 1st recognized in 1976.
• Occurs in infants under 12 months resulting in flaccid paralysis (floppy baby sydnrome)
• Spores ingested (raw honey) & germinate in gut.= INFECTION b/c they do not have as many coliform bacteria as adults do to fight it.
• Accounts for 5% of SIDS.
• TX: Respiratory support, botulinum antitoxin, PCN to kill vegetative cells

Clostridium tetani

Occurrence

• Tetanus (Lockjaw)
• Infection that is rare in US 50-90 cases/yr.
• Common in Asia, Africa, South America 500,000 cases/yr.

Clostridium tetani

Reservoir & MOT

• Res: Intestine of animals including Homo sapiens (normal harmless inhabitant); soil contaminated with feces mainly herbivores.
• Not very invasive- does not get through gut wall.

• MOT: Introduction of spores usually through puncture wounds, IV drug use, but trivial injuries are rarely at risk.

Clostridum tetani

IP & CFR

• IP: 3-21 days, may be months; Short IP=worst case scenario
• CFR (case fatality rate) =30-90%

Clostridium tetani

Disease Process

• Spores germinate in anaerobic wounds. Vegetative cells produce TETANOSPASMIN (exotoxin) which is absorbed into neurons from MEP then migrates through the nerves to CNS. Tetanospasmin binds to neurons preventing release of inhibitory neurotransmitters (GABA & Glycine). Results in uncontrolled contractions of muscles especially masseter (b/c nerves are short). 
• Tetanus neonatorium may occur in neonates if umbillical cord or circumcision are done with non-sterile instruments.

Clostridium tetani

TX, Immunity, & Prophylaxis

• TX: respiratory support, antitoxin to neuralize toxin (=Tetanus Immune Globin)
• RX: PCN to kill any vegetative cells so there is no more source of toxin.
• Imm: Tetanus toxoid provides immunity for 10 years. Usually first given to kids 7+ as DTaP (Diphtheria, Tetanus and Pertussus). Need booster every 10 years or if high risk injury occurs. Today recommendation is for Td for anyone over 7 years old.
• Prophy: Incidence is low b/c schools require vaccination.

Clostridium perfringens

Cause

• Gas Gangrene & food poisoning
• Anaerobic wound contaminated with spores from soil or animal feces. 
• Vegetative cells produce enzymes that kill & digest host tissues.
•  Bacteria ferment CHO in necrotic tissues (esp. muscle tissue b/c there is lots of glycogen which is a CHO). 
• Gases produced as result of fermentation, may rip & tear tissues. Bacteria spread through tissues so affected area enlarges. 
• Associated with corned beef.

Clostridium perfringens

TX

• Wound debridement
• Surgical removal of foreign objects and necrotic tissues
• Antitoxins
• May use Hyperbaric Chamber to push O into cells @ extreme pressure & Oxygen (kills bacterium b/c it is an obligate anaerobe).

• (C. diff)
• Major problem in hospitals or in people who have to take antibiotics for a long period of time

• Anthrax
• Gram (+) bacillus
• Encapsulated
• Spore-forming
• Non-motile
• Facultative anaerobe- most obligate aerobes
• Koch used this bacterium as his model to develop his postulates
• Pasteur used it to prove the need for vaccinations

Bacillus anthracis

Occurrence

• Most cases occur in herbivores from Africa, Asia, Haiti & Middle Eastern countries
• Products like animal hides may contain spores
• In US less than 10 human cases/yr. due to effective control measures but epizootic outbreaks occur regularly.
• The practice of vaccinating workers involved in industrial processing of imported animal products & decline of using fibers of animal origin are primary factors in the current low incidence of human anthrax in US.

Bacillus anthracis

MOT, IP, & Resevoir

• MOT: Direct contact with broken skin, inhalation, or ingestion
• IP: 2-5 days
• Res: Soil, infected domestic herbivorous animals or their hides

Bacillus anthracis

Cutaneous Anthrax

• 95% of human infections are of this type.
• Exposure of broken skin to contaminated soil, infected animal hides, goat hair, wool, etc.
• SN/SX: Painless papule (slightly raised area) progressing to an ulcer then to a black lesion called an ESCHAR
• CFR: If no TX, 20% will die

Bacillus anthracis

Pulmonary Anthrax

• a.k.a. Woolsorter's Disease
• Inhaled spores germinate in lungs
• Vegetative cells grow & produce exotoxins resulting in toxemia causing capillary thrombosis and cardiovascular shock. 
• Septicemia causes death within a few hours.
• Regardless of TX with antibiotics, this form is virtually always fatal b/c of effect of the exotoxins

Bacillus anthracis

Gastrointestinal Anthrax

• Rarest form of disease & has not been reported in the US
• Occurs in underdeveloped countries when food (milk, cheese, meat) contaminated with spores is ingested.
• Exotoxin produced in the digestive tract causes necrotic lesions of ileum and/or L.I.
• CFR 25-50%
• If bacterium reaches the lymph &/or bloodstream, fatal septicemia develops within hours

Bacillus anthracis

Virulence factors & DX

• A polypeptide capsule which prevents phagocytosis and an exotoxin which is a combo. of 3 proteins: EF (edema factor-increases capillary permeability), PA (protective antigen), and LF (lethal factor).
• The exotoxin also helps prevent phagocytosis
• DX: The bacterium can be cultured from soil, cutaneous lesions, respiratory tract or blood. Determine the presence of exotoxin.

Bacillus anthracis

RX, Imm., & Prophylaxis

• RX: Cipro, PCN, Doxycycline, Erythromycin
• Immunity: Permanent with recovery; Toxoid avail. for humans which is a surface protein of the bacterium. A live, avirulent spore (Sterne strain) vaccine is used to vaccinate livestock animals.
• Prophy: Sterilization of hides, hair & bone products of herbivorous livestock; burn carcasses of livestock that die of anthrax; administer immunization to susceptible hosts.

• Diphtheria
• Occ:Unimmunized kids younger than 15. US 4 cases/yr. from 1980-83
• Res: Humans
• MOT: aerosols (eg. sneezing)
• SN/SX: Bacteria grow on mucous mem. of nose & pharynx causing a PSEUDOMEMBRANE that consists of bacteria, epithelial cells & WBCs to form in pharynx. Exotoxin causes destruction of cells of heart & kidney
• TX: PCN, antitoxin
• Imm: DPT vacc. as a child (schools require). Booster in form of Td.

• Leprosy or Hansen's disease
• 11 million cases worldwide; US 200-300/yr. -- 84% HI, CA, NY, TX (Endemic in Hawaii)
• Leprosarium in Carville, LA (closed in 2001)
• Res: Humans & Dasypus novemcinctus (9-banded armadillo)
• MOT: Repeated direct contact- communicable (hard to get)
• IP: 3-5 years+
• OBLIGATE INTRACELLUAR PARASITE

Mycobacterium leprae

SN/SX, Types

• SN/SX: Bacterium invades skin & Schwann cells (form myelin sheath in PNS)
• Tuberculoid (neural) leprosy: Type 4 Hypersensitivity (Delayed type) to surface Ag of bacterium resulting in nerve damage and loss of skin sensations. Very mild form of the disease.
• Lepromatous (progressive) disease: occurs when hypersensitivity reaction is weak or absent. Bacterium grows in skin destroying fingers, toes, face, etc.

Mycobacterium leprae

DX & TX

• DX: Identification of Acid-Fast bacilli from lesions, won't grow in culture, LEPTOMIN test (similar to TB skin test)
• TX: Dapsone (sulfa drug)- 1940s; Rifampin- 1960s; Clofazimine
• Notorious for resistance to antibiotics, so Rifampin is restricted for Mycobacterium sp. and a couple of other things ONLY!
• NO immunity

Mycobacterium tuberculosis

• Tuberculosis
• 4-5 million die each year worldwide; 24,000 new cases/yr. in US
• Occurs from crowded living conditions, poor nutrition, and lack of drugs.
• Incidence in US increasing slowly b/c of AIDS.
• Most susceptible groups= kids under 5 (underdeveloped immune system), aged, AIDS
• Res: M. tuberculosis= humans; M. bovis= cows; M. avium= birds
• MOT: Aerosols, broken skin/ mucous membrane, raw milk (causes intestinal infection)
• IP: 1-3 months

Mycobacterium tuberculosis

DP ,SN/SX, Types

• May infect any body tissue: lungs if inhaled (most common), gut if ingested
• Spreads from gut through lymphatics to anywhere.
• Cell-mediated Immunity is most important response by immune system (= Type 4 (Delayed) Hypersensitivity Reaction). 
• Chronic, granulomatous disease: body responds to inflammation by producing CT to wall-off the infected area- called a tubercle.
• Primary TB: the tubercles

Mycobacterium tuberculosis

DX, TX, Imm.

• Chest X-ray (for tubercles); TB Skin Test: PPD (Purified tuberculin Protein Derivative) which is injected in skin & will cause intense inflammatory response in those who have or have had TB. This test not good in first 3-7 wks. of disease- have to culture sputum.
• TX: Isoniazid (INH)-1954 specific for TB; Streptomycin-1950; Rifampin-1960s *main drug to treat TB
• Before Rifampin it took 18-24 mo. now 6-9 mo.
• Microbe is very resistant to antibiotics so they use 2-3 drugs at the same time. Hospitalization not necessary today.
• Imm: vaccine available but no recommended in US b/c no longer able to do TB skin test as DX aide, instead give INH prophy if someone close to you gets disease.

• Listeriosis
• Discovered in 1926, found in gut of up to 10% humans, as well as 37 mammal & 17 avian species
• INTRACELLULAR parasite causing rare sporadic outbreaks.
• MOT: ingesting contaminated foods: deli meats, soft cheeses, raw milk
• In healthy individuals causes flu-like SX but may spread causing septicemia (CFR 50%), meningitis (CFR 70%)
• Pregnant women 20x more likely to suffer disease resulting in 80% fetal mortality. Immune suppressed, cancer (esp. leukemia), diabetes mellitus & elderly are very susceptible
• TX: ampicillin gentamicin, TMP-SMX (sulfa drug), LISTEX (a just approved bacteriophage to control  the bacterium in soft cheeses.