Essential notes on gram positive bacteria Flashcards
Mycoplasma/Mollicutes
The Mycoplasma are perhaps better (alternatively) named as the Mollicutes, which derives
from the Greek meaning soft skinned (mollis =soft, cutis=skin). The reason for this is that
they completely lack a cell wall and possess only a plasma membrane.
Therefore these bacteria stain Gram negative but sequencing of their genes reveals that
they are clearly phylogenetically related to the low GC Gram positives ( Firmicutes,
Lactobacillus-Clostridium branch).
The lack of a cell wall means that they are sensitive to osmotic lysis.
Plasma membrane is strengthened by inclusion of sterols.
Mycoplasma are pleomorphic – meaning that they have variation in the size and shape of
cells - big, small, long, branched……
The coccoid cells 0.12µm -0.25µm in diameter are probably the smallest living cells.
Because of their small size and their ability to squeeze into different shapes and spaces,
they are hard to remove from tissue culture growth medium and animal products by filtration,
this makes them common contaminants in tissue culture used in research and industry.
All mycoplasma are parasites of eukaryotes but many can be grown in lab media. Most
species require sterols in the lab media to facilitate growth. They are often characterised by
fried egg shaped colonies on solid agar media.
Mycoplasma Genomics – Mycoplasma have small genomes – for example, Mycoplasma
genitalium has the smallest known genome of any self-replicating organism measuring only
580 kbp and encoding 472 genes.
Close to the smallest amount of DNA capable of encoding a free-living cell
There are a number of genera within the Mycoplasmas
Mycoplasmas - Parasites of animal mucous membranes. Over 60 species recognised.
Ureaplasma (T-Strain Mycoplasmas) - microaerophilic. Require cholesterol and urea for
growth. May be associated with nongonococcal urethritis.
Acholeplasma - widely distributed animal parasites. Able to grow in absence of sterols.
Common contaminants of cell lines in tissue culture.
Anaeroplasma - strict anaerobes. Inhabit bovine or ovine rumen.
Spiroplasma - helical, motile. parasites on arthropods and plants (eg citrus stubborn and
corn stunt diseases), but a few cause disease in animals
Below are some details on some important human pathogen species.
Mycoplasma pneumonia – Causes a respiratory tract infection which can result in primary
atypical pneumonia in humans, PAP, sometimes called “walking pneumonia“. Diagnosis by
pathchy diffuse X-Ray, serological tests or culture. Treatment is with anitibiotics that do not
target the cell wall (because mycoplasma don’t have one!) eg. Erythromycin, doxycycline
(not children), azithromycin
GENITAL MYCOPLASMAS - Mycoplasma genitalium, M. hominis and Ureaplasma
urealyticum. Causes of non-gonnococcal (non-chlamydial) urethritis NGU. May also be
associated with infertility in men. Woman – associated with cervicitis and endometritis and
serologically with tubal factor infertility. Detection relies on molecular techniques (PCR) due
to difficulty in culturing. Treated with doxycycline/erythromycin and/or azithromycin
(sometimes moxifloxacin). Drug resistance is rising.
Mycoplasma penetrans - Infects humans in the urogenital and respiratory tracts.
Penetrates into human cells , Intracellular replication and persistence for months/years
Associated with HIV infection.
Streptococci
Spherical cells divide only in one plain and so form chains
Require complex media for growth
Unable to make haem group of cytochromes or catalase
Grown on blood agar (good source of catalase)
Grouping of Streptococci I: Hemolysis
Beta - complete hemolysis -> clear zone
α- incomplete hemolysis of red blood cells to produce a greenish-brown zone
γ- hemolytic - no hemolysis
Grouping of Streptococci II: Antigenically/Serologically
Lancefield Groups of ß-hemolytic Streps
Named after Rebecca Lancefield
A, B, C, D… based on the specific carbohydrate antigen extracted by heating cells to 150°C
Group A - S.pyogenes
Group B - Cattle and humans eg S. agalactiae
Group D - Intestinal tract of man and animals Enterococcus
Etc etc
Group A Strep. = Streptococcus pyogenes
beta haemolytic. Sensitive to bacitracin
It causes many of the streptococcal diseases of humans.
Antigenicity of M-proteins in the cell wall provides sub-classification of group A
into over 100 sub-serotypes.
Habitat: 5 - 30% of healthy people may be carriers of group A, beta hemolytic
Streps in their throat and nasopharynx; however numbers usually low.
Group A streps can cause Strep throat, impetigo skin infection, cellulitis and necrotizing
faciitis.
Also scarlet fever, usually result of Strep sore throat caused by a pyrogenic toxin-producing
organism
- toxin (A, B and C) encoded by a phage.
Symptoms- Fever, susceptibility to endotoxic shock, erythematous
rash.
Non-supporative diseases may also include:
Rheumatic fever.
It occurs in a small percentage of individuals, 2 - 3 weeks after an untreated pharyngeal
infection that was caused by a hemolytic group A Strep.
Joints and heart affected.
May be an immunological reaction - antibody to Strep also binding to heart/joint tissue.
And Glomerulonephritis.
Most cases of glomerulonephritis occur about a week after group A Strep infection (skin or
throat).
Also thought to be an immunolgical reaction in which a Strep-directed antibody reacts with
the glomerular basement membrane; or antibody-antigen complexes are deposited onto
basement membrane.
Leads to loss of protein (blood initially in urine) through kidneys and hypertension.
Can lead to kidney failure.
Other Streptococci
Group B Streptococci: S. agalactiae is the predominant species in this Lancefield
group
Present in vaginal flora of up to 25% of woman.
May cause serious infections in newborn - septicaemia, pneumonia,
meningitis with high fatality rates
Diagnostic tests include the hippurate test and the CAMP test
Group D Streptococci - faecal flora - enterococci.
Urinary and wound infections.
Major problem of vancomycin-resistance.
α-hemolytic Streptococci
Viridans group:
Strep. Viridans is not a species but a large group of bacteria include many species that are
normal inhabitants of throat and nasopharynx of humans.
One example of a viridans species is S..mutans which causes dental caries
Viridans Strep are a significant cause of bacterial endocarditis - infection of heart valve -
invariably fatal if not treated.
Streptococcus pneumoniae
Lancet shaped organism - usually arranged in pairs (Diplococcus).
Virulent organisms are encapsulated. -resist phagocytosis.
Subdivided into 90 types on the basis of antigenicity of capsular polysaccaride.
Habitat: normal commensal of the upper respiratory tract.
Can cause acute lung inflammation.
Chills, fever and pleural pain. Alveoli fill with exudate.
Bacteremia occurs in 25%. Pneumococci may invade other tissues,
eg. sinuses, middle ear and meninges.
Accounts for about one million deaths per annum worldwide. Has a 10 - 20% mortality
Diagnosis can involve direct smears of sputum are examined for G+, encapsulated cocci.
Quellung test - encapsulated bacteria + type-specific antibody -> capsular swelling - capsule
becomes more visible and refractile due to antiboby attachment.
Growth of organism on blood agar – a-hemolytic mucoid colonies, sunken in center -
(autolytic enzymes).
Colonies are soluble in bile (10% deoxycholate drop onto colony - colony dissolves) and
sensitive to optochin.
Treatment and vaccination
Can be treated with penicillin. However, strains of multiple-resistant pneumococci have
appeared and are becoming increasingly common in some parts of the world.
These are presently treated with vancomycin but there are fears that resistance will spread
from enterococci.
Staphlylococci
Gram+ non-motile cocci (>30 species) often occurring in clusters like bunches of grapes
(contrast to chains for streptococcus)
Catalase positive (also distinguishes from Streptococcus)
Staphylococcus aureus
B-hemolytic and coagulase positive
Diseases
Pneumonia and septicaemia in new-born and immunocompromised patients (e.g. burns
units).
Skin infections. Organism invades subcutaneous tissue with the aid of lipases - inflammation
-> white blood cells -> organisms releases leucocidins that kill white blood cells forming pus -
> organisms releases coagulase - > fibrin barrier -> boils, carbuncles. Also impetigo.
Septic arthritis- joint infection
Osteomyelitis – bone infection
Endocarditis – heart tissue,valves
Wound infections, absesses. Common hospital acquired infection - can be transmitted by
hospital personnel, but usually patient.
Major cause of nosocomial infections.
Scalded skin syndrome (SSSS) – caused by S.aureus carrying a phage encoded exfoliatin
toxin. Occurs after initial infection in the mouth, nasal cavities, throat, or umbilicus
Toxic shock syndrome due to infection and production of a super-antigen that stimulates T
cells en masse.
Aside leucocidins, coagulase, exfoliatins and toxic shock syndrome superantigen, S.aureus
produces protein A which binds to immunoglobulins contributing to both adherance and antiphagocytic activity.
S.aureus is also a major cause of food poisoning. -caused by ingestion of preformed toxin
- food contaminated from humans allowing bacterial growth and enterotoxin production.
-onset and recovery both occur within few hours
Very rapid - acts on emitic receptor site -> vomiting and inhibits water absorption →
‘explosive’ diarrhoea.
Treatment
S.aureus naturally produces penicillinase (-lactamases). Usually sensitive to synthetic
(beta-lactamase resistant) penicillins such as oxacillin, methicillin.
In UK and other countries, many hospitals have been colonised with methicillin drug
resistance S. aureus (MRSA) due to production of altered penicillin binding proteins and
penicilinase - plasmid mediated. Rates of MRSA infection in hospitals increased greatly in
the 1990’s but have since stabilised.
Many MRSA strains are resistant to multiple antibiotics – can presently be treated with the
glycopeptide antibiotic, vancomycin. However, vancomycin-resistant MRSA have been
identified which represents a future problem for treatment.
Staphylococcus epidermidis
Non-hemolytic, coagulase negative staphylococcus
major component skin flora, also in gut and respiratory tract but can cause opportunistic
infections.
Major cause of nosocomial infections
e.g. infection in catheters, shunts and prosthetic heart valves
The endospore forming bacteria
Main genera: Bacillus - aerobic or facultative anaerobes
Clostridium – anaerobic
Form a distinctive type of dormant cell - the endospore.
Usually formed when a population reaches conditions of nutrient limitation.
Highly resistant to heat, uv, toxic chemicals, ionising radiation.
Spores have incredible longevity maybe remaining viable for millions of years.
Heat resistance is used for selection.
Typical G + cell wall, but stain variably.
Typical habitat is soil.
Spore has numerous layers. From outside to in:
Exosporium – thin delicate layer of mostly protein
Spore coat(s) – multiple layers of spore specific proteins
Cortex – loosely packed peptidoglycan
Spore protoplast or core – normal cell wall, plasma membrane, cytoplasm and nucleoid
Properties of the Core include:
- Dipicolinate
- Dehydrated –10-30% water content of the vegetative cell –gives heat and stress
resistance
- pH is more acidic than vegetative cell
- Abundant small acid-soluble spore proteins, SASPs – give resistance to dry heat,
dessication, UV. These also form a carbon source during outgrowth
Pathogenic Bacillus
Bacillus anthracis
Agent of anthrax. Disease of sheep, goats & cattle that is also transmissable to
humans. Isolated by Koch in 1877 – “first” bacterial pathogen. Survive in soil for 30 years or
more.
Three general manifestations/routes of infection of human disease.
1. Cutaneous Anthrax
Most common form (2000ish cases per year)
Animal workers mostly
Spores germinate in skin abrasions
Skin ulcer – black eschar – can become systemic
Untreated 20% mortality, responds well to antibiotic
2. Gastrointestinal Anthrax
Caused by ingestion of undercooked contaminated meat.
2 types - oral-pharyngeal (most rare) and abdominal (rare)
Abdominal
Spores germinate in lower gastrointestinal tract
primary intestinal lesion forms
Symptoms - nausea, severe abdominal pain, vomiting, bloody diarrhoea
Intestinal perforation or anthrax toxemia are the usual causes of death
Mortality very high
3. Pulmonary anthrax
Inhalation of spores
Spores are mopped up by macrophages and trafficked to the draining lymph nodes
Germination in the lymph nodes may take up to 60 days
Anthrax bacilli replicate in the lymph nodes and disease immediately follows. Capsule
inhibits phagocytosis.
Hemorrhage, edema, and necrosis are the results of bacterial exotoxins released during
replication.
Symptoms- flu-like with fever, myalgia, cough, headache, vomiting, chills, abdominal pain,
and chest pain. Cyanosis and hypotension result in death
80% mortality in 2 to 4 days whether antibiotics given or not. Inhalational anthrax is 99%
lethal in unvaccinated individuals.
An ideal agent for biological warfare!
Virulence mechanisms
Capsule made of poly-D-glutamate polypeptide. Smooth mucoid colonies.
pX02 plasmid.
Toxin encoded on plasmid pX01. 3 parts - PA (binding domain)
- EF (Edema factor)
- LF (Lethal factor)
Diagnosis -G+ rod. Central (non-staining spore) occurs in soil and in culture, but not in
clinical samples. Sometimes occur in chains. Identified in blood, skin lesions, or respiratory
secretions or by measuring specific antibodies in the blood or masuring DNA in samples by
PCR
Treatment - penicillin, doxycycline, and fluoroquinolones (such as ciprofloxacin).
Prevention Pasteur demonstrated efficacy of vaccine. Several modern vccines based on an
avirulent strain of B. anthracis which lacks the plasmid pX02 plasmid.
Control also relies on sterilisation of wool etc. from areas where anthrax is endemic
Bacillus cereus
First recognised as a cause of food poisoning in 1955
Two types of poisoning
Short-incubation or emetic , occurs between 1 and 6 hours after eating
Symptoms – nausea, vomiting and abdominal pain
Caused by heat stable enterotoxin which cannot be destroyed by cooking
Long-incubation or diarrheal, ocurrs 6-18 hours after eating
Symptoms – diarrhoea
Caused by an enterotoxin that can be destroyed by cooking. Toxin activates
intestinal adenylate cyclase and causes intestinal fluid secretion.
Pathogenic Clostridia
Pathogenic Clostridia
Natural habitat is soil and the intestinal tract of man and animals. Invasive capability of
pathogenic clostridia varies considerably.
At one end the organisms remain at the site of inoculation (tetanus) or may not even enter
tissue at all (botulism) whereas at the other extreme (gangrene) the organisms elaborate
destructive enzymes that allow progressive invasion of necrotic tissue.
C. Botulinum - Botulism
C. botulinum is found in soil, water and decaying vegetation.
Fatal food poisoning that follows ingestion of preformed toxin from growth of organism in
food.
Animals are frequently affected from feeds.
Endospores are very resistant to heat and may withstand boiling for several minutes
Anaerobic conditions (incompletely sterilised canning) may germinate spores - grow into
vegetative cells and eventually produce the deadly toxin.
Toxin acts by inhibiting release of acetylcholine from motorneurons causing flaccid paralysis.
Toxin (Botox) can be used clinically to relieve muscle contractions or cosmetically.
C.botulinum may occasionally infect wounds.
Also, infant botulism can result from ingestion of spores in soil and dust - germinate in
intestine (anaerobic).
Diagnosis of botulism
Clinical picture. ELISA for the toxin in suspect food or injection into mice. Culture may
be attempted.
Prevention
Antitoxin is given to suspected cases. In contrast to spores, toxin is heat labile
therefore cooking inactivates.
C. tetani - Tetanus
Spores are introduced into the body through wound.
Wounding producing necrotic (dead) cells allows anaerobic conditions to develop and spores
to germinate leading to formation of the toxin.
2 types of tetanus
* Generalised tetanus
* Neonatal tetanus occurs if umbilical stump becomes infected - from soil or
bindings containing spores. High fatality rate >200,000 deaths each year
Tetanus – Pathogenesis
* Toxin migrates along peripheral nerve axons to the CNS (site of action)
* Symptoms take 3-21 days to develop.
* Toxin blocks glycine release from inhibitory interneurons leading to uncontrolled
release of acetylcholine from motorneurons and spastic paralysis.
* Since spasms often involve neck and jaws disease is referred to as lockjaw (teeth
have to be knocked out).
* Death results from muscular spasms affecting respiration. 50% mortality.
* Symptoms last 3-4 weeks, complete recovery not for months (if at all!)
Diagnosis
Diagnosis is usually by clinical picture, although organism can be isolated - G+, drumstick
shaped due to terminal spore. Haemolytic toxin production can be demonstrated by growth
on agar plates half spread with antitoxin - prevents haemolysis.
Prevention and treatment
Prevention is by immunity produced by vaccination with formalin-inactivated toxin (in DPT
triple vaccine). Tetanus toxoid vaccine has 100% efficacy!!!
Following injury, non-immunised persons are given human tetanus immunoglobulins
C. perfringens - Gas Gangrene
Normal flora in GI and vagina
Caused by C. perfringens usually although several other species of clostridia may also
cause gangrene.
Results from contamination of wounds with spores of clostridia.
Able to grow in anaerobic conditions in deep necrotic wounds with reduced blood supply.
After germination organisms secrete exotoxins causing more tissue damage, resulting in
rapid spread of the organisms. Carbohydrate may be fermented resulting in the production of
large quantities of gas (unpleasant odour) in tissue - constrict blood vessels.
* surgery
* battlefield casualties.
* motor vehicle crashes
* farm injuries.
* Post-abortal sepsis
Diagnosis and Identification:
Usually on clinical picture (smell from protein digestion is characteristic). X-ray for gas. Since
other organisms (eg. bacteroides) can produce similar infections, definitive diagnosis
requires isolation and identification so culture attempted.
Organisms producing alpha toxin (phospholipase or lecithinase) will hydrolyse lecithin in egg
yolk medium -> opaque area around colony. This can be neutralised by presence of
antitoxin antibody in media - Nagler reaction.
Prevention and Treatment
Cleansing of wounds. Antibiotics have limited effect in necrotic areas. Surgery may be
necessary to remove affected parts.
C.perfringens is also a significant cause of food poisoning in man and animals.
C.difficile - Pseudomembranous Colitis
Severe colitis following antibiotic therapy leading to overgrowth of Clostridium difficile which
may be normal flora of many people.
Produces toxins.
20% of cases of antibiotic-associated diarrhoea are caused by Clostridium difficile
C difficile is recognized as the most common nosocomial gastrointestinal infection.
Two major enterotoxins have been identified: toxin A, and toxin B.
Diagnosis. Most common test is an ELISA test for toxins A and B in the stools
Treatment. Stop the causative antibiotic therapy. Anti diarrhoea drugs and administer
antibiotics effective against the C.difficile like metronidazole, vancomycin.
Listeria monocytogenes
Listeria monocytogenes
There are several species of listeria.
L.monocytogenes is an important cause of disease in man and animals.
The bacterium itself is a short, gram positive, non-spore forming, facultatively aerobic rod.
It has tumbling motility at room temperature but not at 37ͦC. It is a catalase positive and
produces beta-hemolytic colonies on blood agar. Media that detect the phospholipase
activity of the bacterium can distinguish the pathogenic from the non-pathogenic listeria
species.
Listeriosis disease
Disease split in to two types
* Perinatal
– Early onset- intrauterine infection, sepsis and death before birth
– Late onset – infected at birth, meningitis and sepsis within 2-3 weeks.
Significant mortality
* Adult
– In immunocompetent individuals it causes ”flu-like symptoms” and gastric
upset- resolution in a couple of weeks
– In immunocompromised individuals it causes meningo-encephalitis and
bacteraemia
–
Treatment – penicillin and gentamicin (latter does not enter host cells so need both to kill this
intracellular pathogen)
Source of infection
Main reservoir of infection is infected animals, silage, infected humans.
Normal route of infection is gastrointestinal.
Infection and outbreaks are associated with dairy products – especially soft unpasteurised
cheeses, packaged meat like luncheon meat and fruit and vegetables.
Avoidance of infection is by pasteurisation of dairy foodstuffs and cooking of food.
Pathogenesis
Listeria is an intracellular pathogen that actively enters non-phagocytic cells (eg. Fibroblasts)
or is passively enters phagocytic cells. It escapes the phagosome using phospholipases and
listeriolysin. It is intra-cytoplasmically motile by generation of an actin tail that is important to
drive cell-to-cell spread.
Streptomyces
These are abundant soil organisms that have mycelial growth and
generate spores at the ends of terminal hyphae. They are strict aerobes that are nutritionally
versatile and produce many antibiotics (Eg, Streptomycin, erythromycin)
Nocardia
These are Gram +ve, catalase positive, acid-fast (because they have mycolic acid cell walls)
filamentous or coccobacilliary bacteria.
Nocardiosis disease
Nocardiosis is caused by infection with organisms of the Nocardia asteroides complex which
consists:
Nocardia abscessus
Nocardia farcinia
Nocardia nova
Less frequently N.brasiliensis and other species cause infection
Pathogenic and non-pathogenic Nocardia are found widely in the soil.
Nocardiosis caused by breathing in bacteria leading to pulmonary infection
and pneumonia. Infection may spread to other tissues such as brain and skin
Most common in immunocompromised individuals – HIV, alcoholics, immunosuppressed etc
It can also cause skin lesions from direct inoculation of scratches.
Diagnosis
Usually by Gram and acid-fast stains of smears
from sputum, pus, biopsy material etc
Grows on most media forming heaped waxy colony morphology
Treatment is with antibiotics eg. amikacin.
Corynebacteria
Diverse group of Gram +, aerobic, non-motile club-shaped rods
Koryne (Greek) = club
Animal pathogens, plant pathogens and saprophytes.
Corynebacterium diptheriae
Diptheria disease
An upper respiratory tract disease characterized by sore throat, low-grade fever, and
an adherent membrane of the tonsils, pharynx, and/or nose
Infection is spread by droplets or by contact. Toxigenic strains produce a toxin
which is absorbed onto the mucous membrane and causes destruction of epithelium
and local inflammation. The necrotic epithelium becomes embedded in the exuded
fibrin and immune cells so that a greyish “pseudomembrane” is formed.
* Symptoms include the pseudomembrane, a bull neck, conjunctivitis and systemic
action of toxin leads to lesions in kidney, heart, nervous system -> acute nephritis,
serious weakness of the heart, and paralysis.
* 5 – 10% mortality even with treatment
Diphtheria toxin is encoded by a lysogenic phage. It has A (catalytic) and B (receptorbinding) domains which lead to ADP-ribosylation of elongation factor EF2, preventing protein
synthesis. The lethal dose for humans is about 0.1 μg/kg
Inactivated toxoid used as vaccine.
Antitoxin used for treatment.
Toxin used for Elek diagnostic test.
Mycobacteria
Mycobacteria
Unicellular rods that stain acid-fast due to a waxy, mycolic acid rich cell wall (like Nocardia
and Corynebacteria)
Mycobacterium tuberculosis
Causative agent of TB which kills 40000 people every week, 2 billion people are infected.
High incidence in HIV infected individuals but a “disease of poverty”.
TB Disease
Maybe two thirds of exposed people (close contacts) are resistant to infection as they never
become positive by skin test immunoreactivity (Heaf, Mantoux, Elispot). Of those people that
become infected 90% never develop disease although may remain infected for a lifetime. 5%
of infected people develop primary active TB within the first 2 years and 5% will develop
“reactivation” TB at some point later in life perhaps decades later.
Exposure is normally via the respiratory route and aerosols travel to the alveoli of lungs. The
bacteria are engulfed by alveolar macrophages which if activated due to an aquired immune
response(e.g. healthy adult), host may clear bacteria, or at least contain infection.
If the macrophage is unactivated (e.g. infant or naïve adult), the bacteria survive and
replicate in macrophages, attract more cells (PMN’s, T-cells), damage tissue, and form
granulomatous tubercle.
This granuloma may contain infection and stop the development of disease. However, it is
also the mechanism of transmission as continued replication of the contained bacteria and
development of a caseous necrotic centre may lead to cavitation into the airways and
coughing up of the bacteria (ie transmission).
An intact inflammatory immune response is thus required for both protection and (counterintuitively) for transmission
Clinical manifestion of TB
Fever, weight loss/“consumption”, weakness, persistent cough
Pulmonary TB is the most frequent but 15% of TB spreads to extrapulmonary sites eg.
Central nervous system
Lymphatic system
Genitourinary systems
Bones and joints
Disseminated (miliary TB)
Control
BCG vaccination is one of the most widely administered vaccine. BCG is an attenuated live
vaccine derived from M. bovis by serial passage until avirulent. BCG protects against
disseminated disease in children, and protects against leprosy but its efficacy in adults is
poor in most studies.
Diagnosis is by lung X-ray for lesions, by microscopy of sputum looking for acid fast rods
And culture of sputum samples on medium containing egg (Lowenstein Jenson) or oleic acid
and albumin. Takes about 6 weeks!! PCR of sputum can also be used if available.
Treatment involves multidrug therapy for a minimum of 6 months using a combination of
antibiotics (frontline - isoniazid, rifampicin, ethambutol, pyrazinamide).
Resistant strains of TB are increasingly common with some strains resistant to 7 antibiotics
including all 4 frontline drugs (XDR TB)
Mycobacterium leprae
Leprosy disease
Leprosy has been greater reduced by concerted efforts to treat infections. 15 million affected
in 1985, now less than 0.2 million. However, transmission of leprosy remains and we still
understand relatively little about M.leprae because it is difficult to study. The bacterium is
non-cultivatable but can be grown in 9 banded armadillos and in mouse footpads.
It is an intracellular parasite which can grow in macrophages and other cells such as
schwann cells.
Transmission is still a mystery but probably occurs by cantact with droplet from the nasopharynx. Most people who come in contact with leprosy patients do not get
infected. >5 year incubation to symptoms
Disease
95% of infected individuals do not develop clinical disease.
2 clinical manifestations of disease
Tuberculoid- very few bacilli in the tissue, usually a mild disease
with few skin lesions
Host response - strong cellular immune response, low antibody. Competent tuberculoid
granulomas form to contain infection.
Lepromatous- severe disease with massive numbers of bacilli in the tissue. Multiple lesions
–skin nodules packed full of bacteria
Nerve damage is common leading to paralysis and anaesthesia. Can lead to loss of fingers,
toes, nasal deformation, eventually death
Host response - poor cellular immune response, high antibody
Foam cell granulomas indicate poor host resistance
Control of Leprosy
Vaccination with BCG has been shown to be effective
Drug Treatment
Dapsone is the most used antibiotic
For lepromatous leprosy treatment may be for life.
Resistance to Dapsone is becoming increasingly common
-like in tuberculosis the answer is multidrug therapy, combining dapsone with
rifampicin, clofazimine
