Clostridiums

• LargeLarge, straightstraight or slightly curved roads with rounded endsrounded ends. Bulging spore

• Mostly motile (with peritrichous flagella)

• AnaerobicAnaerobic (only some tolerate O2)

ClostridiumsClostridiums

• Usually saprophyticsaprophytic• Usually proteolyticproteolytic and fermenterfermenter (Important

in the process of decomposition of animal proteins)

• Most of the species are highly toxigenictoxigenic

• Living normally in soil soil or animal GI animal GI

DiseasesDiseases• C. tetaniC. tetani causes tetanus.• C. botulinumC. botulinum causes botulism.• C. perfringensC. perfringens, C. septicum & ……causes

gas gangrene and other infections.• C. difficileC. difficile causes pseudomembranous

colitis and antibiotic associated diarrhoea.

Clostridiums tetani

PeritricusPeritricus flagellaTerminal sporeHighly resistant spores (but glutaraldehyde is

effective.)

Toxins: Tetanolysin (Tetanospasmin) - Oxygen labile haemolysin.

Colonies: Tiny colonies Tiny colonies growing in a net of fine filamentousfilamentous

TetanospasminTetanospasmin

• - NeuroNeuromuscularmuscular pathogenic effect.–Gene encoded on a plasmidplasmid.

– Tiny lethal dose required, but only effective in humans parentrallyparentrally (not oralnot oral).

The site of infection

• BacilliBacilli remain at the site of infectionsite of infection, toxin causes localized localized or generalized generalized tetanustetanus.• Spread is haematogenoushaematogenous.• Spore germination Spore germination is favoured by

necrotic tissue and poor blood poor blood supplysupply in the wound.

PathogenesisPathogenesis

• Tetanus toxin (tetanospasmin)It is carried intra-axonally (retrograde) to the

central nervous system, where it binds to ganglioside receptors and blocks release of inhibitory mediators (e.g. glycine, Gamma-aminobutiric acid) at spinal synapses leading to hyper reflection and spastic paralysis.

Clinical findingsClinical findings

• Gradual onsetGradual onset• Incubation periodIncubation period: 4-5 days – several

weeks• Violent muscle spasms in the site of

infection.

Clinical findingsClinical findings

• Lockjaw (trismus) Lockjaw (trismus) due to rigid contraction of the jaw muscles, a characteristic known as

“risus sardonicus”

Clinical findingsClinical findings (cont.)

• Extreme arching of the backExtreme arching of the back (Opisthotonos)

• Low blood pressureLow blood pressure, SweatingSweating, tachycardiatachycardia, arrhythmiaarrhythmia and autonomic instability.

• Respiratory failureRespiratory failure.

Neonatal tetanus

TransmissionTransmission

• Highest incidence in developing Highest incidence in developing countriescountries, associated with a fertile soil and warm climate.

• Previous association with non-sterile ear non-sterile ear piercing piercing and …...

Laboratory Diagnosis:

• Gram stains Gram stains of wound smears: don't often prove useful!• Direct culture Direct culture on blood agar. • An anaerobically prepared culture

may be injected injected into mice mice, with control mice control mice protected by antitoxinantitoxin.

• Antitoxin (does have a low effect)• Penicillin• Respiratory support• Muscle relaxants

Treatment

Prevention

• Immunization with toxoid in childhood (2, 4, 6, 12 months ages) and every 10 years thereafter.

• When trauma occurs deeply:1. Wound should be cleaned and debrided.2. Tetanus toxoid booster should be given.3. Tetanus immune globulin should be given.4. Penicillin administered.

Clostridium botulinumClostridium botulinum

• Strictly anaerobic G+ bacillus but tolerates traces of oxygen (>2%) due to superoxide dismutase (SOD).• Motile with peritrichous flagella.

Clostridium botulinumClostridium botulinum

• Oval & sub-terminal Oval & sub-terminal spores.

• Widely distributed saprophytesaprophyte: soil, manure, fruits, veg.

• Optimum growth @35 C35 C.

• Lipase negative

• Growth between pH of 4.8 and 7 • Can't use lactose as a primary carbon

source.

BotulinBotulin• As a neurotoxinneurotoxin (types A-G)• Antigenically different but pharmacologically

identical. • A, B & E are most common. • 1 gram killd 1 million people• Type A exhibits an LD50 of 40-56 ng in monkeys

BotulinBotulin• FoundFound in all sorts of food all sorts of food (sausages to honey)• Resistant Resistant to proteolytic enzymes proteolytic enzymes (absorbed

through the GI tract). • Type A&B - soil source, type E - marine

source.• The toxin binds irreversibly to the presynaptic

nerve endings, where acetylcholineacetylcholine release is inhibitedinhibited.

PhenotypesPhenotypes

• C. botulinumC. botulinum recognises four physiologicalphysiological & hosthost groups (I-IV):

1.Group I (proteolytic) 2.II (non-proteolytic): most outbreaks of human human

botulismbotulism3. Group III: mainly cause diseases in animalsanimals.4. Group IV: No human or animalNo human or animal disease.

ControlControl

• Highly resistant sporesHighly resistant spores (can survive 100 C for several hours), can be killed by moist heat 120c for 15 mins.

• ProblemsProblems occur in canning factories canning factories where the contents of the can are not adequately heated.

• The spores survive radiationspores survive radiation.

Pathogenesis

• Botulinus toxinAbsorbing from the gut ---> Carrying

via the blood to peripheral nerve synapses ---> Blocking release of acetylcholine ---> Paralysis

Clinical findings

• Incubation periodIncubation period: 1-2 days • Symptoms: Symptoms: - - Initial nausea, vomiting, dysphagia, and

abdominal pain - Oculomotor palsy, ptosis, diplopia. - Descending motor paralysis - Progressive thirst (dry mouth and tongue)

Clinical findingsClinical findings

• Death due to cardiac/respiratory failure.• Floppy child syndrome:Floppy child syndrome: Children <6

months (a flaccid paralysis due to toxin production in the gut.)

• It has been attributed to the presence of C. botulinum spores in honey given to babies with the feed.

TransmissionTransmission

• In soilsoil ---> Alkaline vegetables/meatAlkaline vegetables/meat ---> canned/vacuum-packed ---> Spore germination Spore germination ---> ToxinToxin production ---> ingestion ingestion

Laboratory diagnosis:

• Refer to a reference lab: Toxin maybe demonstrated by

toxin-antitoxin neutralization test in mice.

Treatment

• Remove unabsorbed toxin Remove unabsorbed toxin from the stomach and GI tract.

• Neutralize unfixed toxin Neutralize unfixed toxin by giving polyvalent antitoxin.

• Give ICU careICU care & supportsupport.

Control• Of commercial food preparationfood preparation.

• ThoseThose who have had a suspectedsuspected contact, a prophylactic dose of polyvalent antitoxin polyvalent antitoxin should be given.

Invasive clusteridumsInvasive clusteridums

• Include 30% 30% of clusteridums

• Produce wide range of lethallethal, hemolytichemolytic and necroticnecrotic toxins and enzymes.