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Mycobacterium tuberculosis and Mycobacterium leprae

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TB has been known as Pthisis, King’s Evil, Pott’s disease, consumption, and the White Plague.

Egyptian mummies from 3500 BCE have the presence of Mycobacterium tuberculosis

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Started in Europe in 1600’s

Reigned for around 200 years

Named for the loss of skin color of those infected

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Infected the New World before the Europeans

10% deaths in the 19th century were due to TB

Isolated the infected in sanitariums, which served as waiting rooms for death

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Mycobacterium tuberculosis Mycobacterium

tuberculosis is the etiologic agent of tuberculosis  in humans.

Humans are the only reservoir for the bacterium.

Humans can also be infected by the consumption of unpasteurized milk.

This route of transmission can lead to the development of extrapulmonary TB,

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Cell Morphology

Weakly gram-positive, strongly acid-fast, aerobic bacilli (rod).

The rods are 2-4 micrometers in length and 0.2-0.5 um in width.

Lipid-rich cell wall, making the organism resistant to disinfectants, detergents, common antimicrobial drugs and traditional stains.

Capable of intracellular growth in inactivated alveolar macrophages.

Disease primarily from host response to infection.

Arranged in colonies

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SEM of M. tuberculosis

M. Tuberculosis (stained in purple)

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Humans are the only reservoirInhalation of droplet nuclei containing

M.tuberculosisReplication in lungs

(granuloma formation)Lymphohematogenous spread:

dissemination throughout body inside macrophages

Cell-mediate immune response leads to granuloma formation:

Latent infection Reactivation

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Granuloma formation:activated lymphocytes, macrophages, Langhans giant cells, fibroblasts and capillaries

Caseous necrosis: leads to liquefaction of necrotic tissue leads to cavitations in lungs

MTB in granuloma latent for years and then if immunity wanes the AFB can reactivate

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The photomicrograph shows a caseous granulomatous lesion in a lymph node and the causative agents are not decernible in the H&E stained section. The inserted image(right hand

corner) shows the section following a Ziehl-Neelsen acid-fast special stain viewed under an oil objective. The pink rod

microbes,the causative agents engulfed in the giant cells, are Mycobacteria tuberculosis.”

LYMPH NODE LUNGS TISSUE

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M. Tuberculosis in sputum

(stained in red)

M. tuberculosis: - Acid Fast Bacilli (AFB)- Risk group 3 bacterium- Humans are the only reservoir

Pathogenesis: - Inhalation of infectious droplet nuclei- unrestricted replication spreads throughout body- Cell-mediated immune response - Granuloma formation latent infection- Reactivation if immunity wanes

Public Health Risk- Pulmonary TB highest risk for spread- HIV link- MDR: multi-drug resistant strains

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TB infection is detected by the administration of a tuberculin skin test on the arm. A single needle is used to put some testing material, called tuberculin, under the skin. In two or three days, a nurse or a doctor will check to see if there is a reaction to the test. The test is "positive" if a bump about the size of a pencil eraser or bigger appears on the arm. This bump means a person probably has TB infection. A chest X-ray is done to see if someone with a positive skin tests (TB infection) also has TB disease.

People who are infected with TB do not feel sick, do not have any symptoms and have a normal chest X-ray cannot spread TB. However, they may develop TB disease at some time in the future. People with TB infection but are not yet sick can take medicine so that they will never develop TB disease.

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M. Tuberculosis in sputum

(stained in red)

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Extra-pulmonary TB: Symptoms depend on location of infectionGeneral symptoms: fatigue, fever, loss of appetite, weight loss.TB of lymph nodes: swelling of lymph nodesTB meningitis: neurological symptoms including headacheSpinal TB: Mobility impairments, pain

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•Mycobacterium tuberculosis is the bacterial specie that causes most cases of tuberculosis.•Like all bacteria, Mycobacterium tuberculosis is an extremely small organism, having a rod-like body that is only a few microns (1/10,000 of an inch) in length.•In many individuals, the body mounts an immune response to this infection that is successful in either clearing out the bacteria or walling them off so they exist in a dormant state.•the invading organisms proceed to destroy tissue and create lesions (tubercles) in the lungs.

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•Due to the notable slow growth rate of this bacteria, death for the victim can take many months or even years.•Within the lungs, Mycobacterium tuberculosis cells are ingested by specialized cells of the body's immune system known as macrophages.• Due to their unique waxy surface coating, the bacteria are not destroyed by this action as other invaders would be, but instead begin to replicate themselves within the macrophages. •Other immune cells then swarm to the site of infection to keep it from spreading further, resulting in the formation of a dense spherical mass termed a granuloma. •n others, the bacteria persist and remain viable, albeit in a dormant walled-off nodule. While the latter outcome does lead to an asymptomatic latent infection, this is nevertheless fully capable of causing tuberculosis later in life if the body's immune system becomes weakened or compromised.

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Proteins that are actively secreted during culture on synthetic media represent a particular group of great current interest.

At least eight proteins secreted by Mycobacterium tuberculosis have been isolated and characterized to various extents.

All of them contain typical signal sequences. The proteins of the antigen 85 complex, which form the main

subject of this review, are often the most common proteins in M. tuberculosis culture fluid.

The constituents denoted 85A, 85B, and 85C are encoded by three genes located at different sites in the mycobacterial genome and show extensive cross-reactivity as well as homology at amino acid and gene levels.

Secreted mycobacterial antigens are expected to be of particular significance in induction of various immune responses that are responsible for development of protective immunity in some individuals and for clinical symptoms and complications of the ensuing disease in others.

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M. tuberculosis requires oxygen to grow. It does not retain any bacteriological stain due to high lipid content in its wall, and thus is neither Gram-positive nor Gram-negative; hence Ziehl-Neelsen staining, or acid-fast staining, is used. While mycobacteria do not seem to fit the Gram-positive category from an empirical standpoint (i.e., they do not retain the crystal violet stain), they are classified as acid-fast Gram-positive bacteria due to their lack of an outer cell membrane.[1]

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M. tuberculosis divides every 15–20 hours, which is extremely slow compared to other bacteria, which tend to have division times measured in minutes (Escherichia coli can divide roughly 20 minutes).

M. tuberculosis is characterized by caseating granulomas containing Langhans giant cells, which have a "horseshoe" pattern of nuclei. Organisms are identified by their red color on acid-fast staining.

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The use of blood agar media for the recovery of M. tuberculosis was reported early in the last century but has been removed from contemporary microbiology manuals (4, 6). However, there have been more recent reports, including one from 1998 in which Arvand et al. isolated M. tuberculosis from a lymph node when investigating a diagnosis of cat scratch disease (1). Even earlier, a comparative study of different media conducted in 1977 suggested that penicillin blood agar would be at least as good as, if not better than, Löwenstein-Jensen medium for recovering M. tuberculosis (3).

The study of Drancourt et al. with clinical samples is very useful in once again highlighting the ability of these media to grow M. tuberculosis, in particular when this is not the organism being sought. Moreover, we agree with Drancourt et al. in highlighting the importance of handling in a secure manner culture media which are not specific for mycobacteria but require prolonged incubation, as we have already stated in our paper. Sealing the agar plates with adhesive tape (Micropore surgical tape; 3M, St. Paul, Minn.) is a simple way to avoid risks.

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Tuberculosis (TB) is the most common major infectious disease today. It is estimated that two billion people--or one-third of the world's population--are chronically infected without active symptoms. Nine million new cases of active disease are diagnosed annually, resulting in two million deaths. TB is predominantly a lung disease. It is caused by a microbe called Mycobacterium tuberculosis which infects lung cells, but it is still not clear how exactly this happens. Ludovic Tailleux, Olivier Neyrolles, and colleagues (from the Pasteur Institute, in collaboration with the Necker and Saint-Louis Hospitals, in Paris) have found that a molecule called DC-SIGN plays a crucial part.

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The researchers wanted to examine whether lung cells from patients with TB were different from those of healthy people or those with different lung diseases, and what that tells us about the way the infection spreads in the lung. In particular, they looked at the surface of the lung cells, because this is the part directly involved in the first contact with the Mycobacterium. As they report now in the international open-access medical journal PLoS Medicine, they studied 74 individuals, 40 of whom had TB, 25 had other inflammatory lung diseases, and 9 had neither active TB nor lung inflammation and served as healthy "controls." The patients underwent a procedure called broncho-alveolar lavage that washes out some of the secretions and cells from the lower respiratory tract. The researchers then analyzed the cells in different ways. They concentrated on a type of cell called a macrophage (the natural target of Mycobacterium) and found that macrophages from patients with TB had much more the DC-SIGN protein on their surface than macrophages from patients with other diseases or from the control individuals.

They then took macrophages from a control individual (which had very low levels of DC-SIGN) and infected them with Mycobaterium under laboratory conditions. They found that shortly after infection not only the infected cells but also some of their neighbours started to display DC-SIGN on their surface. They also found that having DC-SIGN on the surface made uninfected cells much more susceptible to infection.

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highly fatal form if not adequately treated. In fact, once the bacilli enter the bloodstream, they can travel to almost any organ of the body, including the lymph nodes, bones...

When still active, pulmonary tuberculosis is a constant threat to the patient, because blood-borne spread may occur at any time. Diffuse spread of tuberculosis in the lung (known as miliary tuberculosis)

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An Infection Of The Meninges That Cover The Brain Causes Tuberculous Meningitis; Before The Advent Of Specific Drugs, This Disease Was Always Fatal, Though Most Affected People Now Recover.

In Many Developing Countries, Tuberculous Meningitis Is Common.

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The global tuberculosis epidemic An estimated 14 million people worldwide are infected with

active tuberculosis (TB), which is a disease of poverty affecting mainly young adults in their most productive years. In 2009 there were 9.4 million new cases of TB and 1.7 million deaths, including 380,000 deaths from TB among people with HIV. The vast majority of deaths from TB are in the developing world.

The latest data released by the World Health Organization (WHO) in November 2010 show that the number of new cases continues to fall globally and in five of the six WHO regions. The exception is Southeast Asia, where incidence remains stable. In many countries TB prevalence is declining. Worldwide, deaths from TB fell by 35 percent between 1990 and 2009.

If current trends continue the world can meet the Millennium Development Goal target for incidence – that new cases should be falling by 2015 – and the Stop TB Partnership target to halve TB mortality by 2015 in comparison with 1990.

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Progress in tackling the global TB burden is associated with DOTS, the basic package that underpins the Stop TB Strategy, which was adopted by the WHO in 1993. The expansion of DOTS across the world since the mid-1990s is tracked through the proportion of estimated new TB cases that are detected – or “notified” – and successfully treated under DOTS.

In 2009 5.8 million cases of all kinds of TB were notified globally, equivalent to a 63 percent case detection rate compared with 61 percent in 2008.* Treatment success rates continue to be measured in terms of smear-positive pulmonary TB only. Of the 2.6 million cases notified in 2008, 86 per cent were successfully treated against the new 90 percent target included in the 2011-2015 update of the Global Plan to Stop TB.

A total of 41 million TB patients were successfully treated in DOTS programs between 1995 and 2009.

The Global Fund has helped to accelerate case detection and successful treatment in recent years, with 1.7 million additional cases of TB detected and treated by Global Fund-supported programs in 2010, compared with 1.4 million in 2009 and 1.3 million in 2008. Since the Global Fund’s inception in 2002, programs it has financed had supported DOTS for a total of 7.7 million people by December 2010.

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A child receiving a tuberculosis vaccine at school in Bulacan province, Philippines, c. 1952.

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The micro bacterial leprae generation time is 12 to14 days!

it is an Acid Fast Bacteria i.e the decolorizer used in its gram staining is a very strong acid and they are very resistant to even acid!

It presence is indicated by the appearance of red color in slide

Optimum temperature required for max growth is 30 degree.

It shows preference of growth in outer cooler places.

leprosy have never been grown in artificial media!

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LEPROSY

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Leprosy is a chronic infectious disease caused by mycobacterium leprae, an acid-fast, rod-shaped bacillus.

The disease mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract and also the eyes, apart from some other structures.

Leprosy has afflicted humanity since time immemorial. It once affected every continent and it has left behind a terrifying image in history and human memory - of mutilation, rejection and exclusion from society

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The bacterium that causes Leprosy is rod-shaped and called Mycobacterium leprae.

When Mycobacterium leprae enters the body, one of these things can happen:

1)Tuberculoid leprosy (TT) : The body's immune cells attempt to

seal off the infection from the rest of the body by surrounding the offending pathogen.

2)Lepromatous leprosy (LL) : • This is the more dangerous type, in

which the body's immune system is unable to mount a strong response to the invading organism. Hence, the organism multiplies freely in the skin. This type of leprosy is also called the multibacillary (MB) leprosy, because of the presence of large numbers of bacteria. Occasionally, the mucous membranes of the eyes, nose, and throat may be involved.

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Leprosy has struck fear into human beings for thousands of years, and was well recognized in the oldest civilizations of China, Egypt and India.

Since ancient times, leprosy has been regarded by the community as a contagious, mutilating and incurable disease.

There are many countries in Asia, Africa and Latin America with a significant number of leprosy cases. It is estimated that there are between one and two million people visibly and irreversibly disabled due to past and present leprosy who require to be cared for by the community in which they live.

When M.leprae was discovered by G.A. Hansen in 1873, it was the first bacterium to be identified as causing disease in man. However, treatment for leprosy only appeared in the late 1940s with the introduction of dapsone, and its derivatives.

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The most widely held belief was that the disease was transmitted by contact between cases of leprosy and healthy persons.

More recently the possibility of transmission by the respiratory route is gaining ground.

There are also other possibilities such as transmission through insects which cannot be completely ruled out

TRANSMISSION BY CONTACT:The term 'contact' in leprosy is generally not clearly defined. All that we know at present is that individuals who are in close association or proximity with leprosy patients have a greater chance of acquiring the disease.In general, closeness of contact is related to the dose of infection which in turn is related to the occurrence of disease. Of the various situations that promote close contact, contact within the household is the only one that is easily identified.TRANSMISSION THROUGH INSECTS:With the available evidence on intracutaneous inoculation as a successful method of transmission of M.leprae in the mouse footpad model and a similar situation possibly existing in human beings,

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"scaly skin."   Kingdom: Bacteria Phylum: Actinobacteria Order: Actinomycetales Suborder: Corynebacterineae Family: Mycobacteriaceae Genus: Mycobacterium Species: M. leprae   It's easy to look at a listing of the scientific classification, but why

does it belong to each of those groups? Here is a brief explanation...

Kingdom: Bacteria This organism belong to the kingdom bacteria because it fits the

typical characteristics of prokaryotic bacteria,

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Signs and Symptoms of LeprosySigns and symptoms of leprosy usually

appear three to five years after becoming infected with Mycobacterium leprae -- the bacteria responsible for the disease. Leprosy usually affects the skin and peripheral nerves. However, once signs and symptoms of leprosy begin, there can be a wide variety of symptoms and severity. The type of leprosy a person has is also a factor.

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It is important to note that not all people with leprosy lose their fingers and toes. With early diagnosis and leprosy treatment, many of these signs and symptoms of leprosy can be prevented. Many patients with tuberculoid disease can even self-heal without benefit of treatment. In order to prevent problems with fingers or toes, people should avoid injury and infections to these areas and take their medicines as prescribed.

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Mycobacterium Avium Complex (MAC) is not spread through person-to-person contact. This The most common TB Cousin, MAC, presents itself like many other illnesses. Avoiding contact with some source of MAC is virtually impossible. Animal, water, air, food, soil, tobacco products are all suspected vectors for the mycobacterium avium complex. MAC may be misdiagnosed as just another pulmonary exacerbation, or the flu. Common symptoms of infection include: Fever Chills Swollen GlansNigh sweats Fatigue

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Leprosy occurs in armadillos as well -Men are twice as likely to catch leprosy than women -In some folklore, they believe if you catch leprosy then your limbs will fall off

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Mycobacterium leprae Mycobacterium leprae

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