10. Tetanus _ botulinum 1

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► Meningitis

is characterised by the acute onset of fever and stiff neck. Aseptic menngitis may be caused by a variety of microbial agents. During initial 24 h of the course of aseptic meningitis, an affected person’s CSF is characterised by which of the following? decreased protein content elevated glucose concentration lymphocytosis polymorphonuclear leukocytosis Eosinophilia

* * * * *


19 yr old student brought to emergency dept because the patient was difficult to arouse in the morning.He has had a flu-like illness with fever,muscle and joint aches for 12h. Temp is 39.5c,pulse -120/min,BP 90/60mm Hg. There is diffuse petechial rash over the trunk and extremities,He has a stiff neck that cant be passively flexed. ► Which of the following is the most likely pathogen?

► Coxsackie ► Echovirus


influenzae ► Neisseria meningitidis ► Streptococcus pneumoniae

► Haemophilus


organisms Strept pneumoniae, Neisseria meningitidis & Haemophilus influenzae cause vast majority of cases of bacterial meningitis.What is the MOST IMP pathogenic component they share? ► A Protein A ► B Capsule ► C Endotoxin ► D Beta lactamase

A 20 yr old man has sevre headache ,vomiting that began yesterday. He is now confused,. On examination, his temp is 39c and his neck is stiff.Spinal fluid reveals no bacteria on Gram stain, 25 lymphs,normal protein and normal glucose. Culture of the spinal fluid on blood agar shows no bacterial colonies. ► ? DIAGNOSIS ► Most common agent

► Patient

is 20yrs old woman with sudden onset of fever to 104F ,severe head ache. Phy exam reveals nuchal rigidity. U suspect meningitis, spinal tap done. Gram stain reveals many neutophils + GN diplococci ► Of the following bacteria, which one is Most likely the cause? ► Pseudomonas aeruginosa ► Neisseria meningitidis ► Streptococus pnemumniae ► Haemophilus influenzae


20yrs old man had a severe head trauma during a bike accident 3 days back.,had spinal fluid leaking from nose and develops severe head ache. His temp is 39c, and has nuchal rigidity. LP done, spinal fluid cloudy,contains 5000 WBC/microlitre,90% are polyps. Which ONE is the most likely result observed in the laboratory analysis of spinal fluid?

► GN

rods grew anaerobically ► Motile spirochaete that formed beta haemolytic colonies on blood agar ► GPC –alpha hemolytic on blood agar ► GPC grew only in presence of 6.5% NaCL ► GPB grew on CA with X and V factors ► No organism was seen using Gram stain but tissue stains revealed cytoplasmic inclusion bodies



Following statements about Clostridia are true EXCEPT A pathogenic Clostridia are found in soil and normal flora of colon B Antibiotic associated colitis is due to a toxin produced by Cl difficile C Anaerobic conditions at the wound site are not required to cause tetanus because spores will form in the presence of oxygen D Botulism caused by ingesting preformed toxin can be prevented by boiling food prior to cooking

► Each

of the following statements TRUE about Cl tetani Except ► A gram positive spore forming rod ► Pathogenesis due to prodn of exotoxin that blocks inhibitory neurotransmitters ► Facultative ,grow on blood agar plate in presence of room air ► Natural habitat primarily is the soil

Tetanus - Clostridium tetani
Description: ► Straight, slender rod with rounded ends ► Gram positive ► The fully developed spores gives the organism the appearance of a drumstick with a large round end
► obligate ► Motile


and has numerous peritrichous flagella

► grows

well in cooked meat broth and produces a thin spreading film when grown on enriched blood agar ► spores are highly resistant to adverse conditions ► spores of some strains resist boiling in water for up to 3h ► they may resist dry heat at 160 degrees for 1 h and 5% phenol for 2 weeks or more ► iodine (1%) in water is said to kill the spores within a few hours

Toxin: ► produces an oxygen labile haemolysin (tetanolysin) but the organism's neurotoxin (tetanospasmin) is the essential pathogenic product ► tetanospasmin is toxic to humans and various animals when injected parenterally, but it is not toxic by the oral route ► when tetanus occurs naturally, the tetanus bacilli stay at the site of the initial infection ► not generally invasive, but the toxin diffuses to affect the relevant level of the spinal cord (local tetanus) and then to affect the entire system (generalized tetanus)

the toxin is absorbed from the site of its production in an infective focus ► is transmitted to the Central Nervous System (CNS) via motor nerves and apparently specifically by motor fibres. ► some toxin may be delivered from an infective focus via blood to all nerves in the body and the subsequent transmission to the Central Nervous System depends upon uptake through neuromuscular nerve endings and intraaxonal transport
► ► ►

the first signs of human tetanus is to be in the head and

neck, attributed to the shorter length of the cranial nerves

the toxin appears to act by interfering with the normal inhibition of motor impulses exercised by the upper motor neuron over the lower, producing an increase in tonus and tonic spasms

Occurrence of tetanus bacilli: ► occurs in the intestine of humans and animals ► derived primarily from animal faeces and indirectly via soil ► especially prevalent in manured soil Pathogenesis: ► if washed spores are injected into an animal, they fail to germinate and are removed by phagocytosis ► germination and outgrowth of tetanus spores depend upon reduced oxygen tension in devitalized tissue and non-viable material in a wound so that the Eh is significantly lowered

► cases

of tetanus have been reported in which the infection was apparently assoicated with a superficial abrasion, a contaminated splinter or a minor thorn prick ► in some cases, the site of infection is assumed to be in the external auditory meatus; thus otogenic tetanus may be attributable to over-zealous cleansing of the meatus with a small stick ► in other patients, the site of infection remains undiscovered, and this is referred to as

cryptogenic tetanus

► tetanus

uterus in cases of septic abortion

infection may also occur in or near the

Localized: ► Persistent spasm of the musculature at the site of primary infection. ► Disease remains confined to the injury site. Cephalic : ► Variant of localized tetanus ► Primary site of infection is head ► Dysfunction of one or more of the cranial nervesVII ► Prognosis is poor

Clinical features of tetanus:

Generalized tetanus: ► Most common type ► Most common symptom is spasm of masseter muscle ► Results in contraction of facial muscles- lock jaw ► Persistent back spasms Neonatal tetanus (tetanus neonatarum): ► Infection typically originates from the umbilical stump ► Then progress to generalized tetanus ► Prognosis is very poor ► Mortality rate exceeds 90%

Laboratory Diagnosis ► Simple light microscopy is often unsuccessful ► Immunoflourescence microscopy with a specific stain is possible but is not generally available ► Direct culture of unheated material on blood agar incubated anaerobically is often the best method of detection ► Material from the wound or from a mixed sporing subculture may be heated at various temperatures and for various times to exclude non-sporing bacteria ► The heated specimens are then seeded onto solid media and incubated aerobically ► Tetanus may be produced in mice by subcutaneous injection of an anaerobic culture prepared from wound material

► The

patient remains conscious and requires skilled sedation and constant nursing ► If generalized spasms are worrying, the patient is and ventilated mechanically until the toxin that has been taken up has decayed : this may take some weeks ► Vaccine: DPT toxoid ► Anti tetanus antiserum (HTIG) also available - only neutralizes toxin in bloodstream ► Combined immunization suggested

Clostridium botulinum
Description: ► Strict anaerobic, Gram positive bacillus ► Motile with peritrichous flagella ► Spores are oval and subterminal ► It is widely distributed saprophyte occurring in soil, vegetables, fruits, leaves, silage, manure, the mud of lakes and sea mud ► Its optimum growth temperature is about 35 degrees

Morphology of Cl.botulinum

occurrence of C. botulinum in nature, ► Ability to produce a potent neurotoxin in food and resistance of its spores to inactivation ► Combine to make it a formidable pathogen of humans and a range of animals and birds ► Insufficient heating in the process of preserving foods is an important factor in the causation of botulism ► Great care must be taken in canning factories to ensure that adequate heating is achieved in all parts of the can contents
► Widespread

Toxins of C.botulism: Toxins are among the most poisonous natural substances known ► Classified into seven types (A-G) with types A,B and E most frequently associated with human disease Human Botulism: ► Botulism is a severe, often fatal, form of food poisoning characterized by pronounced neurotoxic effects ► The disease has been caused by a wide range of foods ► Usually preserved hams, large sausages, home-preserved meats and vegetables, canned products such as fish, liver paste and even hazelnut puree and honey

► Foods

exhibit signs of spoilage ► Preformed toxin in the food is absorbed

responsible for botulism may not

from the intestinal tract. ► Although it is protein, it's not inactivated by the intestinal proteolytic enzymes. ► The toxin primarily affects the cholinergic system and seems to block release of acetylcholine, chiefly at points in the peripheral nervous system

► Introduced

in contaminated foods (nonacid canned vegetables, smoked meats). (does not destroy endospores)  anaerobic conditions produced  endospores germinate  organisms multiply  secrete neurotoxin  consumed with food.
Causes no change in color, odor, taste of food & can withstand boiling 10 min.

► Processing


Disease: Inc. pd. 2-3 days. ► Neurotoxin enters GI tract  bloodstream  CNS where interferes with release acetylcholene  no impulses transmitted to muscles  flaccid paralysis ► Onset: May or may not have GI disturbances  headache, blurred or double vision  difficulty speaking, swallowing  respiratory failure  convulsions  death. ► Mortality rate 60 - 70%. ► Vaccine: none ► Antiserum available - only neutralizes toxin in bloodstream.

Clinical Features: ► The period between ingestion of the toxin and the appearance of signs and symptoms is usually 1-2 days, but it may be much longer ► they may be initial nausea and vomiting ► the oculomotor muslces are affected and the patient may have diplopia and drooping

eyelids with a squint.

► There

may be vertigo and blurred vision

► There

is progressive descending motor loss with flaccid paralysis but no loss of consciousness or sensation, though weakness and sleepiness are often described ► The patient is thirsty, with a dry mouth and tongue ► There are difficulties in speech and swallowing, with later problems of breathing and despair ► There may be abdominal pain and restlessness ► Death is due to respiratory or cardiac failure

Infant botulism: ► Infants consume endospore (ex: in honey)  germinates in GI tract due to lack normal flora  produces neurotoxin  blood  CNS

Infant and wound botulism

Laboratory Diagnosis: ► The organism or its toxin may be detected in the suspected food and toxin may be demonstrated in the patient's blood by toxin-antitoxin neutralization test in mice ► Samples of vomit or faeces may also yield such evidence

Treatment: ► The priorities are – 1) To remove unabsorbed toxin from the stomach and intestinal tract 2) To neutralize unfixed toxin by giving polyvalent antitoxin 3) To give relevant intensive care and support

Control: ► Home canning of foodstuffs should be avoided and commercial canning must be strictly controlled

Acid fruits must be bottled safely in the home with heating at 100 degrees, since low pH is inhibitory to its growth
A prophylactic dose of polyvalent antitoxin should be given intramuscularly to all persons who have eaten food suspected of causing botulism Active immunization should be considered for laboratory staff who might have to handle the organism or who might have to handle specimens containing the organism or its toxin




a) b)

d) e) f) g)

A house wife who lives in a small farm is brought to the emergency room complaining of double vision and difficulty in talking. With in the past two hours she noted a dry mouth and a generalized weakness night she served home canned green beans as part of the meal.she tasted the beans before they were bioled. None of the other family members are ill. On examination there is symmetrical descending paralysis of cranial nerves, upper extremities , and trunk. the correct diagnosis is which of the following Tetanus Strychnine poisoning Botulism Morphine overdose Ricin intoxication Fungal food poisoning Staphylococcal food poisoning


A 45 year old man who immigrated to USA five years ago sustained a puncture injury to the lower part of his right leg when his rotary lawn mower threw a small stick into the leg.6 days latter he noticed spasm in the muscles of his right leg; on day 7 the spasms increased. Today –day 8 –he had generalized muscle spasms particularly noticeable in the muscles of his jaw. He was unable to open his jaw and came to the emergency room. In the emergency department you see a man who is alert lying quietly in the bed. A door slams down the hall and suddenly he has generalized muscle spasms with arching of his back. The correct diagnosis is which of the following.
Botulism Anthrax Gas gangrene Tetanus Toixc shock syndrome

A. B. C. D.


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