Leprosy microbiology very short & concise

leprossy medical information

1. 1) Leprosy (Hansen's disease)
• A chronic disease caused by
✓ Mycobacterium leprae
✓ Mycobacterium lepromatosis (16S rRNA gene analysis; discovered in 2008)
• Primarily a granulomatous disease of the peripheral nerves in the mucosa/skin.
• Leprosy-manifestation:
1) Cellular immune responses that lead to tissues damage.
2) Peripheral neuropathy with potentially long-term consequences.
• In an endemic area, an individual should be regarded as having leprosy if he or she shows ONE (1)
of the following cardinal signs:
1) Hypopigmentation
2) Sensory loss
3) Thickened nerves
• About 95% of people are naturally immune
• Sufferers become non- infectious after 2 weeks of effective treatment.
• Untreated leprosy progresses to cause permanent damage to the nerves, skin, eyes and limbs.
• Naturally occurring infections occur in non-human primates including the African chimpanzee,
Sooty mangabey, and Cynomolgus macaque.
• It can be transmitted to humans by Nine-banded armadillos.
Mycobacterium leprae and Mycobacterium lepromatosis

• An intracellular, acid-fast, aerobic, bacilli.
• Large amount of wax in the cell membrane (Characteristic of Mycobacterium species).
• Extremely long time to reproduce inside of cells (about 12-14 days as compared to minutes to hours for most
bacteria).
• Grow best at 26.7oC-30.00C, (So cooler areas of the body tend to develop the infection).
• Grow very well in Macrophages and Schwann cells.
• Immune response – CMI (Cell Mediated Immunity)
• Uncultivable in the laboratory.
• Can be grown on certain animals (Footpads of mice and Nine-banded armadillo).


• Types of leprosy:
3 types of diseases depending on the effectiveness of the CMI response:
1) Tuberculoid (Paucibacillary) leprosy
2) Intermediate (Borderline)
3) Lepromatous (Multibacillary) leprosy.




Leprosy, Tetanus, Botulism Pathogenesis of leprosy
• How the infection produces the symptoms of the disease is Not known.
• Transmission of leprosy is prolonged close contact and through nasal droplet.
• The incubation period from a few weeks to 30 years (Average 3-5 years).
• The major target for infection is Schwann cells (SCs) that leads to injury of the nerve and demyelination;
consequently, is loss of axonal conductance.

2. Symptoms and Signs:
1) Tuberculoid leprosy
• In Tuberculoid leprosy (more benign form), there is a ‘Strong’ response of CMI.
• The disease is localized, affecting primarily the skin and nerves (The damaged nerve may become
enlarged).
• Either spontaneous resolution in a few years, persists or advances to Lepromatous forms.
• It progresses more slowly than the Lepromatous form (Average duration is 18 years).

• Histopathology:
Skin lesions from Tuberculoid patients are characterized by :-
❖ Inflammatory infiltrate containing well-formed granulomas
❖ Differentiated macrophages, epithelioid and giant cells
❖ A predominance of CD4+ T cells at the lesion site, and
❖ Low number or absent of bacteria.

2) Lepromatous leprosy
• In Lepromatous leprosy, little or no immunity (CMI response) develops and the disease is more
generalized.
• Greater number of skin lesions.
• Characterized by development of masses of granulation tissues.
• Progression leads to aseptic necrosis (tissue death from lack of blood).
• As the disease progresses, nerve involvement leads to anaesthetic areas and limb weakness.
• Presented with lepromas (skin nodules), and disfigurement of many areas, including the face.
• Large no of CD8+ T cells in situ.
• CD4:CD8 ratio of approximately 1:2.
• Enormous number of bacteria in the lesions.








Investigation

1) Lepromin Test:

• An extract sample of
inactivated Hansen's Bacillus
is injected just under the skin,
usually on the forearm, so
that a small lump pushes the
skin upward.
• Read after 48 hrs and after 21
days.
• Positive reaction means:

✓ Induration >10mm of
diameter after 48hrs, or
✓ Nodule > 5mm of
diameter after 21 days.

• Lepromin skin test can be
used to differentiate the 2
forms of leprosy.

✓ Tuberculoid Leprosy :
Lepromin POSITIVE
✓ Lepromatous Leprosy :
Lepromin NEGATIVE
Laboratory Diagnosis

1) Specimens:
• Skin scrapping
• Tissue biopsies


Detection of organism
• AFB staining of the skin scrapping
or tissue biopsies



Isolation
• On certain animals (Footpads of
mice and Nine-banded armadillo).
Treatment

• Multidrug Therapy (MDT) for
Lepromatous leprosy consists
of
• Rifampicin, Dapsone, and
Clofazimine taken over 12
months.
• Dosages adjusted appropriately
for children and adults.
• Single dose MDT for single
lesion leprosy consists of
Rifampicin, Ofloxacin, and
Minocycline.

Prevention

• In a recent trial, a single dose
of rifampicin reduced the rate
at which contacts acquired
leprosy in the two years after
contact by 57%.

3. 2) Tetanus
• Prolonged contraction of skeletal muscle fibres.
• The muscle spasm is caused by Tetanospasmin (A neurotoxin produced Clostridium tetani).
• Muscle spasms develop in the jaw (“Lockjaw") and elsewhere in the body.
• Infection occurs through deep wound contamination.
Organism : Clostridium tetani
• Obligate anaerobe.
• Gram-positive, resembles tennis rackets or drumsticks.
• It is heat-sensitive.
• Motile
• Forms terminal spore.
• The spores are extremely hardy; resistant to heat and most antiseptics.
• The spores are distributed widely in manure-treated soils (can remain infectious for more than 40 years),
in the gastrointestinal tract of animals, and can be found on human skin.

❖ C. tetani produces 2 types of exotoxins:
✓ Tetanospasmin -- a neurotoxin (a polypeptides), that causes spasm.
✓ Tetanolysin ( hemolysin) that causes destruction of tissues

Pathogenesis of Tetanus
1) C. tetani is non-invasive organism.
2) The infection remains strictly localized in the area of necrotic tissue (wound, burn, injury, umbilical stump,
surgical suture), where the spores have been introduced.
3) Tetanospasmin is produced by the organisms during
4) Germination of the spores and development of vegetative
5) Tetanospasmin released in the wound is absorbed into the circulation and binds to peripheral nerve terminals
of Lower motor neurons all over the body in 2-14 days.
6) It is then transported within the axon of the motor neuron by retrograde axonal transport to the spinal cord
and/or brainstem.
7) In the synaptic cleft of the spinal cord/ or brainstem, it is rapidly fixed to gangliosides at the presynaptic
inhibitory motor nerve ending and is taken up into the axon (by Transcytosis).
8) The toxin blocks the release of inhibitory neurotransmitters (glycine and gamma-aminobutyric acid-
GABA, a neurotransmitter that inhibits motor neurons,across the synaptic cleft, which is required to check
the nervous impulse).
9) As the result, a generalize muscular spasm (characteristic of tetanus) is produced (Normal inhibitory action
is inhibited).
10) This results in continuous muscular spasms (hyperreflexia and seizures).
11) The spasms can be so powerful that they tear the muscles or cause fractures of the spine.

4. Symptoms & Signs
• The incubation period (The time between infection and the first sign of symptoms) is typically 7 to 21 days.
• Tetanus often begins with mild spasms in the jaw muscles (lockjaw).
• The spasms can also affect the chest, neck, back, and abdominal muscles.
• Back muscle spasms often cause arching, called Opisthotonos.
• Sometimes the spasms affect muscles that help with breathing, which can lead to breathing problems.
• Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups (This is called tetany).
• These episodes can cause fractures and muscle tears

Other symptoms:
✓ Drooling
✓ Excessive sweating
✓ Fever
✓ Hand or foot spasms
✓ Irritability
✓ Swallowing difficulty
✓ Uncontrolled urination or defecation.

Complications:
• Airway obstruction
• Respiratory arrest
• Heart failure
• Pneumonia
• Fractures
• Brain damage due to lack of oxygen during spasms.

Diagnosis

• Diagnose of tetanus is based on
clinical features of muscle spasms,
stiffness and pain, and of immunization
history
• Laboratory tests generally are not
helpful for diagnosing tetanus.
• Anaerobic culture of tissues from
contaminated wounds may yield C.
tetani.
Treatment

Treatment may include:-

• Antibiotics, including Penicillin, Clindamycin, Erythromycin, or Metronidazole
(Metronidazole has been most successful).
• Tetanus immune globulin is given to reverse the toxic effects (It should not wait
for culture result before administering in suspected cases).
• Bed rest with a non-stimulating environment (dim light, reduced noise, and
stable temperature).
• Muscle relaxants such as diazepam
• Sedatives
• Surgery to clean the wound and remove the source of the poison
(debridement)
• Breathing support with oxygen, a breathing tube, and a breathing machine
may be necessary.





Prognosis

• Without treatment, 1 out of 4 infected people
die.
• The death rate for newborns with untreated
tetanus is even higher.
• With proper treatment, less than 10% of infected
patients die.
• Wounds on the head or face seem to be more
dangerous than those on other parts of the
body.
• If the person survives the acute illness, recovery
is generally complete.
• Uncorrected episodes of hypoxia caused by
muscle spasms in the throat may lead to
irreversible brain damage.

Prevention

• Tetanus vaccine (Tetanus toxin inactivated with formaldehyde).
• Given in combined DPT vaccine.
• Side effects are rare, fever, pain at the injection site, unexplained
crying in infants, and irritability in older children or adults.
• Severe reactions are extremely rare, anaphylaxis, seizures and
encephalopathy.
• All infants are recommended to receive the vaccine at 2, 4, 6, and
15 months of age.
• A fifth booster dose should be given at 4–6 years of age.
• After that, it should be given every 10 years.
• However, if a bite, scratch, or puncture occurs more than five years
after the last dose of vaccine, the patients should receive another
dose of vaccine.

3) Botulism
• Is a rare but fatal, paralytic illness.
• Foodborne botulism is an intoxication caused by consuming food contaminated with the botulinum
toxin.
• Wound botulism occurs when spores enter a wound under the skin, and, in the absence of oxygen are
activated and release toxin.
• Infant botulism occurs when gastro-intestinal tract is colonized by spores.

Organism - Clostridium botulinum
• Gram-positive, rod-shaped, obligate anaerobe.
• They have oval, subterminal endospores and is commonly found in soil.
• They produce neurotoxins, subdivided into types A-G.
• Only types A, B, E, and F cause disease in humans.
• The “Gold standard" for determining toxin type is a mouse bioassay.
• The genes for types A, B, E, and F can now be readily differentiated using Real-time polymerase chain
reaction (PCR).

Pathogenesis of Botulism
1) The bacterial spores release botulinum toxin when exposed to low oxygen levels and certain temperatures.
2) The toxin blocks the release of acetylcholine from motor nerve endings in the Lower motor neuron, and this
resulted in flaccid paralysis of the muscles and symptoms of blurred vision, ptosis, nausea, vomiting,
diarrhea and/or constipation, cramps, and respiratory difficulty.

5. Symptoms and Signs
There are 3 major types of botulism that differ in how they are acquired

Diagnosis
• May include a brain scan, spinal fluid
examination, nerve conduction test
[Electromyography (EMG)].
• Detect of botulinum toxin in the patient's blood,
serum, or stool. (Confirmatory test).
• Culture
• Detection of the toxin is done by:
✓ ELISA
✓ Electrochemiluminescent test
✓ Mouse inoculation test

Mouse inoculation test
• This is done by injecting the patient's serum or
stool into the peritoneal cavity of mice.
• An equal amount of serum or stool from the
patient is treated with multivalent antitoxin and
injected in other mice.
•
If the antitoxin-treated serum- or stool-injected
mice live while those injected with untreated
serum or stool die, then this is a positive test for
botulism and is called the mouse inoculation
test.

❖ The bacteria can also be isolated from the stool of
people with food-borne and infant botulism, but
this is not a definitive test.
❖ However, stool cultures can help differentiate
botulism from E. coli, Salmonella, and other
infectious agents.
Treatment
• An antitoxin that blocks the action of neurotoxin circulating in
the blood.
• The trivalent antitoxin (effective against three neurotoxins: A,
B, and E).
• Physicians may remove whatever contaminated food is still
in the gut by inducing vomiting or by using enemas.
• Wounds should be treated, usually surgically, to remove the
source of the toxin-producing bacteria.
• Patients who survive an episode of botulism poisoning may
experience fatigue and shortness of breath for years, and
long-term therapy may be needed to aid recovery.
• Untreated botulism has a mortality rate (death rate) of about
50%. Appropriately treated patients with botulism currently
still have a mortality rate of about 3%-5%.
• Some patients may experience various degrees of paralysis
for many months.
• The respiratory failure and paralysis that occur with severe
botulism may require a patient to be on a breathing machine
(ventilator) for weeks and may require intensive medical and
nursing care.
• After several weeks, the paralysis slowly improves as axons
in the nerves are regenerated.

Food-borne botulism

• Usually caused by eating
contaminated home-canned
foods (Never taste-test food
that may have gone bad) (The
illness can be fatal in 3 to 10
days if not treated.
• Incubation period is from 18 to
36 hours, (4 hours - 8 hours
after eating the contaminated
food).
Wound botulism

• Due to Clostridium
botulinum infecting a
wound and releasing
the neurotoxin
Infant botulism

• The baby consumes spores of the bacteria which
then grow in the baby's intestine and release the
neurotoxin.
• The infants appear lethargic, weak, and floppy, feed
poorly, become constipated, and have a weak cry
and poor muscle tone (In infants, constipation is
often the first symptom to occur).
• Botulism symptoms include double vision, droopy
eyelids, trouble speaking and swallowing, difficulty
breathing and constipation.
• If untreated, these symptoms may progress to cause
paralysis in various parts of the body, often seen as a
descending paralysis of the arms, legs, trunk, and
breathing muscles.