Historical review, epidemiological situation, etiopathogenesis and pathological anatomy of Tuberculosis
Tuberculosis is caused by two bacteria: Mycobacterium tuberculosis and mycobacterium bovis. The disease spreads when infected people with the active form of the illness coug or sneeze. It spreads most rapidly among people living in over crowded conditions. M.bovis causes T.B in Cattles and is spread to humans in milk and meat. It is estimated that there were about 800,000 deaths in the U.K between 1850 and 1950 as a result of T.B transmitted from Cattle. However, most people wit T.B are infected with M.tuberculosis. They have a persistent cough and as part of their defence, cells release hormone-like compounds which cost fever and suppress the appetite, as a result sufferers lose weight and often look emaciated.
In the U.K, the incidence of T.B decrease steeply well before the introduction of the vaccine in 1950s, this was because of improvement in housing conditions and diet. The antibiotic, streptomycin was introduced in the 1940s and this hasten the decrease in incidence of T.B, this pattern was repeated throughout the developed world. T.B once thought to be practically eradicated, but now it is showing a resurgence due in part to the following factors.
- Some strains of T.B bacteria which are resistant to drugs
- The AIDS pendemic
- poor housing and rising homelessness in inner cities in the developed world.
- The breakdown of T.B control programs particularly in the U.S.A. Partial treatment of T.B increases the chance of drug resistance in microbacteria.
T.B attacks many of the poorest and socially disadvantaged communities because it is spread by air borne droplets and people who sleep close together in large numbers are particularly at risk. The disease primarily attack the homeless and people who live in poor substandard housing and for this reason, prevalent in the 19th century. Those with low immunity, due to malnutrition for being HIV positive are also particularly vulnerable. In 1995, T.B killed more people worldwide than any other disease. It is estimated that 1/3rd of the world's population is infected with M.tuberculosis. The bacteria is attacked by the microphages in the lungs byt it is not killed.. It is predicted that 300 million people may become infected within the next 5 years and without proper treatment, each person may infect 10-15 others every year. Transmission is easily achieved and the bacteria may remain in the Lungs or in the Lymphoid tissues for years until they become very active.
T.B is often the first opportunistic infection to strike HIV positive people, HIV infection may re-activate dormant infections of M.tuberculosis. T.B is now the leading cause of death of HIV positive. The HIV pandemic has been followed very closely by the T.B pandemic. There are high rates of incidence, all across the developing world and in the countries of the former solviet union. Very high rates are also found in areas of destitution in developed countries, where the incidence in part of some inner cities is as high as in countries like Tanzania. The recent epidemic of T.B in the USA happened as the result of neglect and poverty, especially in parts of New York, where the Public health system almost collapse. Social factors such as homelessness, neglect of primary health care and Urban decay, contributed to the spread of T.B and this need to be addressed if the Pandemic is to be curbed.
Once someone appears with the symptoms of T.B, the sputum (mucus and pus) from the lungs is collected for analysis, the identification of M.tuberculosis can be made very qucikly by microscopy. If T.B is confirmed, then sufferers should be isolated whiel they are in the most infectious state (which is at 2-4 weeks). This is particularly the case if they have an infection of a drug resistant strain. T he treatment involves using several drugs to ensure that all the bacteria are killed, not just a few. Otherwise, drug resistance forms are left behind to continue the infection. The treatment is a long one of 6 months to 2 years but many people do not complete their cause of drugs as they think that when they feel better, they are cured. However, it takes months to kill microbacterium because they are slow growing. They are intracellular parasites surviving inside cells of the immune system, where they are metabolically inactive, therefore, difficult to trat with drugs.
Strains of drug resistant M.Tuberculosis were identified when treatment with antibiotics such as Streptomycin began in the 1950s. Antibiotics act as selective agents, killing drug sensitive strains and leaving resistant ones behind. Drug resistance happen as a result of mutation, this is a random event occurring with a frequecy of 1 in every 1000 bacteria. If 3 or 4 drugs are sued in treatment, then the chance of resistance occurring to all of them is reduced to (1/1000)3 or (1/1000)4 . If T.B is not treated or the person stops the treatment before the bacteria are completely eliminated, bacteria spread throughout the body, increasing the likelihood that mutations will arise. Premature stoping treatment can mean that M.tubercuosis develop resistance to all the drugs being used. Patients under poorly managed treatment programs, return home to infect others. Multiple drug resistant forms of T.B (MDR-T.B) now exist. In 1995, a HIV unit in London reported an outbreak of MDR-T.B with a form of M.tuberculosis that was resistance to 5 of the major drugs used to treat the disease including isoniazid, the most successful. The W.H.O promotes a scheme to ensure that patients complete their coarse of drugs D.O.T.S (Direct Observation treatment short course), involves health workers or responsible family members, making sure that patients, take their drugs regularly for 6-8 months. The drugs widely used are isoniazid and rifampicin, often in combination with others. This drug therapy, cures 95% of all patients and is twice as effective as other strategies, helping to reduce the spread of MDR strains.
Contact tracing and the subsequent testing of contacts for the bacterium is an essential part of controlling T.B contacts are screened for symptoms of T.B infection but the diagnosis can take up to 2 weeks. The spread of the disease among children is prevented, to a large extent of vaccination. The BCG vaccine is derived from M.bovis and protects up to 70% to 80% of the teenagers in the U.K, its effectiveness decreasing with age, unless there is exposure to T.B. Studies of the effectiveness of BCG in protecting Adults and children gives conflicting results. It appears that the vaccine is effective in some parts of the world, and less effective in some other parts e.g India. Many of the world's T.B victims were not vaccinated. An infective method of control is the dual approach of milk pasturization and T.B testing of cattle. Any cattle found to test positive are destroyed. These measures have reduced the incidence of T.B caused by M.bovis considerably, so that it is hardly a hazard to health in countries where these controls operate.
Tuberculosis, as an illness, is known since ancient times. The principal clinical manifestations of tuberculosis are described still by Hippocrate, Gallen, Avizenna. The fact that tuberculsis is infectious disease was confirmed by Fracastoro in the 16th Century. It was Morton who published the first monography "Phthisiology or a treatise on the Phthisis" (R. Morton, 1689) and named a science of tuberculosis "phthisiology" (from the Greek word "phthisis"-which means exhaustio. In the 17th century, the French anatomist sylviy, describing the hurt lungs of patients who had died of Phthisis, used the word "hump" (tuberculum). However, it was only in the 19th century in France that pathologists and therapeutists G. Bayle, and then R. Laennec proved the hump and caseous necrosis to be specific morphological substratum of tuberculosis. In 1865, the French physician B. Villemin experimentally proved the infectious nature of tuberculosis, though he could not reveal the pathogene. In 1882, the German bacteriologist Robert Koch discovered the pathogen of tuberculosis, which was named bacillus of Koch (BK)). He was also the first who obtained tuberculin with the hope to successful treatment of tuberculosis patients. These expectations of the scientist did not come true, nevertheless, for the purpose of diagnostics, tubercuin has been used for over 100 years.
M.I. Pyrohov studied clinico-morphological properties of tuberculosis of various localization and for the first time described typhoid form of miliar tuberculosis, histologic structure of tuberculous granuloma. Further study of pathomorphological alterations at lungs tuberculosis was proceeded by A.I. Abrykosov and A.I. Strukov.
In 1887, R. Philip in Edinburgh (Scotland) founded the world first antituberculosis dispansery. This new institution offered the patients not only medical but also social help, which later on laid the foundation of the organization of antituberculosis service also in his country. In 1882, in Rome, C. Forlanini offered artificial Pneumothorax for treating lung tuberculosis patients. In 1895, Wilhelm Kondrat Roentgen discovered X-rays, which have been widely used in medicine up to today. In 1909, the first free hospital for tuberculosis patients was opened in Moscow. An important achievement of the start of the 20th century was the creation by the French scientists Calmette, Guerin). Since 1935, mass vaccination began. At the same time in 1924, Abre in Brazile introduced the method of fluorographic observation of the population for active revealing lung tuberculosis patients. In 1944, the American bacteriologist from Odesa S. Waksman obtained streptomycin, for which he was awarded the Nobel Prize (1952). PASA, tibon, GINA preparations (the most effective of them-isoniazidum, synthesized in Fox's laboratory, GB, 1951) came into practice somewhat later, and since 1965 rifampincinum, the most effective antimycobacterial medicine has been used.
World Epidemiological situation
More than 6 billion people live on our planet now. Me than 2 billion of them suffer from various diseases. Every fifth earthman lives in extreme need and poverty, which has become the main death reason in the world. Today, tuberculosis is the most widely spread infectious disease which ranks first as to the death rate among the people from infectious pathology. Moreover, new misfortunes are added. In 2001 A.D, there are 30-40 million carriers of the human immunodeficiency virus in the world and 10 million AIDS patients, who increase the number of tuberculosis patients considerably. According to the data of the World Health Organization, half of the globe population is infected with tuberculosis mycobacteria. In some countries, infectiousness of the population with tuberculosis reaches 80-90%. In some European countries such as Ukraine, every year, each tuberculosis patient can infect 10-15 and more persons of which 5-10% will catch the disease.
Every year, 7-10 million people fall ill with tuberculosis all over the world, including 4-4.5 million- with bacterial secretion and about 3 million, adults die of it (of these, 97% in the developing countries) and approximately 300 thousand children. The total number of tuberculosis patients reaches 50-60 million. Nowadays, tuberculosis is the most menacing illness for the whole mankind. It kills more patients worldwide than all the infectious and parasitic illnesses taken together. Present tuberculosis epidemic has acquired the global scales. In many parts of the world, tuberculosis epidemic is beyond the control. The highest tuberculosis statistics of sickness is noted in African and Asian regions, in the countries of the Pacific Ocean coast. Tuberculosis epidemic situation got worse in the countries of Europe too, especially in the countries of the former socialist community.
In 1998, the lowest tuberculosis index was registered in the highly developed countries, such as Malta (4.2), Sweden (5), Norway (5.5), Iceland (6.2), Italy (8.4 per 100000 of the population), the highest- in Romania (114.6), in the former Soviet Union, as in Kyrgysta (127.8), Kazakhstan (126.4), Georgia (124.4), Turkmenistan (86.1 per 100, 000 of the population).
Etiopathogenesis and pathological anatomy of tuberculosis
The stimulus of tuberculosis belongs to the wide group of mycobacterium, related with lower organisms such as actinomyces (from Greek words acti-ray and myces-fungus). there are different names of the stimulus of tuberculosis: Koch's bacillus, mycobacterium of tuberculosis. Tuberculosis is an infectious disease and its stimulus is mycobacterium of tuberculosis (MBT): genus Mycobacterium, kind Mycobacteriacea, class Actinomycetales. To the genus Mycobacterium, kind Mycobacteriacea, there belong aerobe stiff gram-positive lineal or curved mycobacterium resistance to acid and spirit. They grown slowly or very slowly (saprophytic quite quickly).
Mycobacterium are widely approximately 50 classes of them are found out, a class includes approximately 200 kinds: typical is Mycobacterium tuberculosis. According to the mark proper pathogenic and saprophytic kinds are distinguished. Atypical mycobacterium (by classification of Runyon, 1959), depending on the color of colonies and speed of growth, they are divided into 4 groups:
- Photochromogenic-cause pigmentations of colonies at light (M.kansasii, M.marinum);
- Scotochromogenic-the most widely spread group, cause yellowish and orange pigmentation int he dark (M.aquae, M.flavescens, M.scrofulaceum, M.gordonae ad M.paraffinicum);
- nonphotochromogenic-not causing pigmentations or cause it in a small amount (M.xenopi, M.avium, M.intracellularae, M.gastri, M.nonphotochromogenicum, M.terrae, M.triviale);
- quickly grown- (M.phlei, M.smegmatis, M.fortuitum, M.marinum).
Among the pathogenic mycobacterium, depending on their pathogenecity for humans and animals there are distinguished the following kinds: M. tuberculosis-human tubercle bacillus, M.bovis-bovine tubercle bacillus, M.africanum (African) [found in western tropic Africa: it has the qualities typical for the previous kinds].
M.tuberculosis-thin or slightly curved bacillus measuring 1.0-10.0 X 0.2-0.6 um with slightly curved tips, in cytoplasm there are granulose formations, without spores and capsules. Gram-positive aerobes. Their main feature is resistance to acid, alkali and spirit, which is caused by the presence of lipid fraction, mycoly tic acid, in particular. They produce fissiparity, approximately in 14-18 hours. Under the influence of environment, changes of living the morphological, cultural and biological qualities of mycobacterium tuberculosis change. They sometimes produce qualities of granules, filterable and L-form formations-the process is called persistence. The recurrence from persisting forms to bacterial is called reversion. usage of antimycobacterium drugs leads to medical resistance to MBT. The infection of fetus usually occurs in two ways: hematogenic, transplacental or within aspiration and swallowing amniotic waters, mucus of genitals if a pregnant woman is ill. In hematogenic way of infection, MBT penetrate from a mother to a child through umbilical vein, piercing to liver or Auranti venosus duct to heart and lung. In hematogenic way of infection, primary effect is formed in the liver or fetus.
There are three types (species) of pathogenic MBT: human (M.tuberculosis), bovine (M.bovis) and African (M.africanum). All of them are very stable in the environment, in particular, they are preserved in the soil for 1-2 years, in basins-up to 5 months, in the road dust-up to 10 days, i premises at the dissipated sunlight-up to a month and a half, in excrements and on pasture-grounds up to a year, in butter, cheese kept in a fridge- 8-10 months, on books pages-3 months. At the temperature of 200 celsius, MBT preserve their vital activity during 7 years. Boiling liquid sputum kills MBT in 5 minutes. Under the action of the sun rays, MBT die in an hour and a half, and that of ultraviolet radiation-in 2-3 minutes. Atypical (conditional pathogenic) MBT under certain conditions can be pathogenic for a man and cause mycobacteriosis-an illness similar to tuberculosis. Human tuberculosis in 85-97% of cases occurs as a result of the infestation with human, in 2-15% with bovine and very rarely-with avain MBT type. Sick people and animals, secreting MBT, are the source of human tuberculosis infestation. A pathogen, depending on the Organ hurt, is secreted into the environment with sputum, excrements, urine, milk, sperm etc. Infestation occurs most often by aerogenic (90%), contact (5-6%), rarelier alimentary (1-2%) and extremely rarely by intrauterine way. Principally, those are children, rarely teenagers and adults who face tuberculosis infection for the first time. MBT, having penetrated into the respiratory tract, can by the system of mucocyliar clearance-gleaning epithelium, with mucus, be excreted out of bronchi, thus preventing their contact with alveolar macrophages. Otherwise, at initial infestation MBT encounter with polynuclears and phagocytes and undergo phagocytosus. Macrophages go to ruin and MBT and their fragments are excreted into intercellular space, joined with J-protein and enzyme-mediators (interleukine1) which activates T-lymphocytes. The later, in their turn, excrete mediators-lymphokines (interleukine 2) which speed up the migration of macrophages, their fermentative activity according to MBT. The mediators mentioned above also activate B-lymphocytes, which are transformed into plasmatic cells, capable of producing immunoglobulins-specific antibodies against MBT antigens. However, the role of humoral immunity has not been fully elucidated yet. The mechanisms of cell immunity, carried out by sensibilized T-lymphocytes, particularly, their sub-population and correlation (T-helpers activate macrophages, T-suppressors depress them, T-killers can stick to the cells that phagocytized MBT and destroy them together with the infect) are more important. The substances secreted at increased macrophage enzyme activity promote the development of inflammation reaction, and under the action of MBT phosphotides macrophages turn into epitheloid and gigantic Pyrohov-Langhance cells, a tuberculosis granuloma is formed. Alongside with it, the destruction of mycobacteria togetehre with macrophages and the surrounding tissues by T-killers occurs, resulting in caseous necrosis. Dry caseous is mainly formed in the center of the tuberculosis granuloma and is an unfavorable medium for MBT reproduction. Further dynamics of the infection process depends upon the scale of the bacterial population and the perfection of the immune systems of the organism.
At a small number of MBT, in the process of the development of the immunity, their multiplication slows down, the inflammatory reaction weakens, the specific granuloma sclerotizes and mycobacteria transforms into persisting forms, which maintain relative acquired immunity. Positive tuberculin reaction is an indication of immunologic reconstruction, which manifests itself in 3-12 weeks after infestation and lasts to the end of one's life. Under certain unfavorable conditions, in months-years, persisting MBT forms can reverse into cirulent ones, that results into reactivation of specific inflammation process and the development of the secondary forms of tuberculosis.
At intensive multiplication of a considerable population of mycobacteria, the activity of T-helpers decreases, the activation of macrophages is inhibited and the number of T-suppressors increases, gradually tuberculosis process progresses and the primary forms of tuberculosis develop. The primary tuberculosis emerges after a veering of tuberculin reactions, it is characterized by an expressed hypersensitivity of an organisms with an obligatory lesion of the lymphatic system and a bent to infection spread hematogenously and lymphogenously, not seldom with a hurt of cereous membranes and the presence of paraspecific reactions.
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