1.1 A brief history of tuberculosis in development of diagnosis and treatment


Tuberculosis (from Latin, Tuberculum – tubercle) – general infectious disease caused by Mycobacterium tuberculosis. From the Greek word (phthysis – consumption –“exhaustion of a body” the word phthisiology is derived – scientific study of tuberculosis.

The ancient times medicine was based on believe that diseases to be natural phenomena and sought remedies from earthly sources. Dietary enrichments of various forms were popular, including milk from various sources. At the same time primitive empiric healers were predisposed to attribute the diseases to the displeasure of deities or other supernatural events. Consequences of these belief systems included attempted remedy by religious ritual, exorcism, fasting, and – when it was believed that a fellow member of the community was responsible – expulsion or execution. Because of the supernatural component, members of the religious hierarchy or the royalty [who were empowered by god(s)] became important healers, typically to the detriment of the patient but to the benefit of their institutional coffers. Various remedies were used at that times such as bleeding, purging, emetics, or other interventions. For the tuberculosis patients they were morbid at best and mortal in the extreme. At the same time, the attempts of objective study of tuberculosis and search for effective means of treatment were constantly made.

Hippocrates 400-350 B.C. The first systemic description of the clinical manifestations and epidemiologic features of phthisis was recorded in the Hippocratic Collection. In his book “The causes and symptoms of chronic diseases” gave a very accurate description of the disease, which later refer to tuberculosis and mentioned that fever, sweating, fatigue and lassitude were symptoms of tuberculosis. The long empirical period of observation and diagnostics of the disease, when, on words of Hippocrates, “… the judgments are done by means of eyes, ear, nose, mouth and other ways, known for us, i.e. by sight, touch, hearing, by sense of smell and taste “, was replaced by a clinico-anatomic direction, which promoted rational understanding of illness.

Girolamus Fracastorius (1483-1553) is credited to have originated the “germ theory” and believed that tuberculosis was contagious. He systematically described three major modes of transmitting infection in his book “De contagioni”:

  1. spread by direct contact;
  2. spread by intermediary (e.g. fomites);
  3. infection at a distance.

He also mentioned about antiseptics on the treatment of tuberculosis.

Andreas Vesalius (1514-1564) made the pioneering efforts of postmortem examinations. This method of study facilitated the understanding of the pathological findings such as lung cavities, empyema among others.

Franciscus Sylvius de la Boe (1614-1672) for the first time associated small hard nodules discovered in various tissues at autopsy with the symptoms of consumption.

John Jacob Monget in 1700 gave the description of classical milliary tuberculosis.

Benjamin Marten (1704-1782) in his book “A new Theory of consumption” conjectured that tuberculosis could be caused by “certain species of Animalcula or wonderfully minute living creatures”, which, once they had gained a foothold in the body, could generate the lesions and symptoms of the disease.

Gaspard Laurent Bayle (1774-1816) performed a prodigious number of autopsies on phthistic patient. Notably, the necropsies were accompanied by detailed antemortem histories of the illness, enabling physicians to make heretofore clinico-pathological correlations.

Rene Theophile Hyacinthe Laenecc (1781-1826), the French doctor carried out the large clinico – anatomic study and stated in 1819 the doctrine about a tuberculosis in ” the Treatise about auscultation or recognition of lung and heart diseases”. In Treatise he for the first time has entered the term a tuberculosis. Laenecc gave the description close to our conception about tuberculum as a source of tuberculosis, noted existence of isolated “infiltrative tuberculum”. He united various morphological displays in the uniform doctrine about phthisis. Scrofulous [tuberculous] changes of lymphatic nodes, contact disease of bronchi, the cavity formed as a result of tissue softening and which is looking like cheese (caseosis). Laenecc managed to see connection existing between various displays of tubercular character in organs, and to combine into one disease, known in that time damage of the lung and lymphatic system.

Jean Antone Villeman French physician of military service began a series of experiments in 1865 that before 20 years of Koch.s discovery of Mycobacterium tuberculosis. Taking lung tissue and blood and pus from cavities of tuberculosis patients, Villemin inoculated rabbits and was able to demonstrate disseminated tuberculosis in all.

On 24th March 1882 Robert Koch announced the discovery of the tubercle bacillus (bacterium of Koch). So, it was Robert Koch – German scientist who finally demystified the secret of the cause of tuberculosis. Koch postulated (Koch’s Postulates): In order to prove that tuberculosis is brought about by the tubercle bacillus:

  1. the bacilli must be isolated from the body…
  2. cultured so long in pure culture that they are freed from any diseased production of the animal organism which may still be adhering to the bacilli…
  3. the isolated bacilli must bring about the transfer of the disease to other animals.

Koch’s development of tuberculin and its application as diagnosticum for definition tuberculosis infection, and also improvement by Ziehl and Neelsen of coloring at MBT at microscopy made possible reliable diagnostic of tuberculosis infection. With the Wilhelm Conrad Roentgen (1845-1923), the technique of radiological imaging became available different organs, including lungs.

Calmette, a physician, and Gueren, a veterinarian, chose M.bovis in their culture medium, they add ox bile. They found that the bile also reduced the virulence of M.bovis strain. After 231 serial passages, these attenuated organisms were shown to offer significant protection in animal models and were introduced as a human vaccine (BCG) in the early 1920s. The end of XIX and beginning of XX centures were the period of many scientific discoveries. The conceptions about tuberculosis also have undergone significant changes. The scientific studies of tuberculosis already were based on exact knowledge of methods of diagnostics of the causative agent and unity of tubercular disease with its localization in various organs. In parallel with study of diagnostics and pathogenesis of tuberculosis the attempts of effective treatment of tuberculosis were done. Manipulation of climatological variables has been employed in the treatment of many illnesses including tuberculosis, throughout history. A variant of climate therapy was the issue of the type of air to which the patient should be exposed. Arising in the same era as sanatorium/rest care, vide variety of surgery manipulations were the last major thrust of clinicians to cure tuberculosis before the modern era of chemotherapy. To surgical methods of treatment concern: extrapleural pneumothorax, oleothorax, thoracoplasty, surgery on the peripheral nerves. Widely applied lung resections are: limited cuneiform resections, segmentectomy, lobectomy and pulmonectomy – removal the whole lung.

Introduction in 1950s and 1960s of numerous antituberculosis drugs: isoniazid (H) the aminglycosides, viomycin, capreomycin, pyrazinamid (Z), ethionamide, cycloserine, ethambutol (E), and rifampicin, ensure effective and predicatble treatment of tuberculosis. Now phthiatria is armed with a number of of treatment methods, effective at the various forms of tuberculosis.

Simple or more complex schemes, based on various principles and simultaneous assignment of several antituberculosis preparations strengthen therapeutical effect and prevent development of drug resistance and. Surgical interventions, for example, are made in conditions of a sanatorium-hygienic mode and are combined with chemotherapy.

Prevention of tuberculosis is the important section of struggle with it. The purpose is to warn distribution of the infection among the population and first of all among children, to prevent disease and development of its far advanced and irreversible forms of process among infected. In the far past, when the reasons of disease were not still known, could not have places and its rational preventive maintenance. In some countries, for example in Persia and Italy, because of significant distribution of tuberculosis attempts were made to isolate the patients, forbade to them to communicate with the population, to enter a marriage. Further, as the infective nature of tuberculosis was found out, has ripened necessity for wider sanitary – preventive measures.

In Spain in 1751, in Italy in 1782, and then in Portugal and in other countries the laws were issued on obligatory registration of all patients with phthisis and their hospitalization, disinfection of their dwellings, destruction of clothes, home belongings. For default of the specified decisions of the doctors taxed with the penalty or sent from the country, and persons, guilty of concealment, and property of the patients subjected to the prison conclusion. But such attempts could not be successful because of large quantity of the patients. An obstacle for the tuberculosis prevention, is its long and chronic current, and also lot of the factors of the household, economic, moral and psychological order connected to the large material spending. At the same time there was obvious a necessity of development of effective widespread measures of public, sanitary and personal prevention in conditions of communal life. The tuberculosis dispensaries were organized to carry out some of these measures. Such establishments were organized in France (in Lille) under the initiative Kallmette, in Edinburgh under the initiative R. Philip, etc. However quantity of such establishments was insufficient earlier and remains the same now.

That is the historical way of development of science and struggle with tuberculosis. In this brief section, the separate and most important stages are submitted only. But already from the given materials there is obvious a significant development of theoretical knowledge in the given area and sharply increased efficiency of medical and preventive measures. These successes are achieved by works of many scientists of various countries. Among them the large merit belongs also to Russian researchers and public health organizes, from which many were the pioneers in development of major problems of tuberculosis.

The Russian surgeon, brilliant clinician and scientist N.I.Pirogov (1810-1881) has played a important role in development and extention of conception about tuberculosis as sysrtimic. N.I.Pirogov has described a clinicopathologic picture of a sharp generalized tuberculosis, has noted an opportunity of simultaneous existence of milliary eruptions and of confluent changes at the same patient. He first has paid attention to gigantic cells in tubercular nodules, received then name of Langhance. Observing heavy generalized forms of tuberculosis, N/I/Pirogoc wrote: ” I believe in hygiene … The future belongs to preventive medicine. This science, going hand in hand with state, will bring doubtless benefit to mankind “.

In 1888 the Russian scientist Mechnikov I.I. has informed, soon after discovery of MBT by Koch that in cultures, except of typical Koch’s mycobacterium there are polymorphic forms. The polymorphism becomes apparent by development of rode like, granular and coccus forms.

After October revolution (1917) in Russia organization of struggle with tuberculosis were transferred from charity to a state basis. In process of reconstruction of national economy and economic development of the Soviet Union, on the basis of the state decisions the large funds were allocated for organization of specialized antituberculosis service and for scientific solutions of problems of prevention and treatment of tuberculosis, training of the highly skilled staff of experts. New medical speciality – phthisiatria gradually was developing and specialized antituberculosis service, in that time unique in the world was created.

The clinical classification of tuberculosis was created, for registration of the tuberculosis patients. The clinical classification was as base for creation of the system for early revealing and complex treatment of the tuberculosis patients under the supevision of tubercular dispensary in hospital, sanatorium, in a health resort and in polyclinic without separation of the patient from habitual activity. The technique mass antitubercular vaccination and revaccination was introduced into practice.

A.I.Abrikosov, V.U.Shtevko, A.I.Strukov, A.N. Chistovich, V.I.Pusik and their numerous followers have made large contribution to study of pathogenesis and pathological anatomy, morphogenesis of tuberculosis. The primary complex in intestinal tract was described. It was found out, that the large or smaller degree bacillema can arise independently in parallel with the lung lymphatic focus before or after their formation (A.I.Chistovich, N.N.Georgadze, M.D.Krilov, Z.A.Lebedeva etc.).

Russian pediatritians led by the professor A.A.Kisel have created in 30th of the XX century the doctrine about chronic tubercular intoxication. Later in 40-50 years, the doctrine was created about early tubercular intoxication of children, infected by tuberculosis for the first time (N.O.Vasilevich, A.I.Kudrjavceva, E.Z.Sorkina). This period of intoxication is designated by rather early morphological and bacteriological displays of tubercular infection in bone marrow, in lymphatic nodes.

By the professor A.I. Kagramanov the presence of bacillemia with small morphological displays in various organs and systems not accessible to x-ray diagnosis is proved at post mortem examinations of children who have died not from a tuberculosis,. Significant expansion of concepts about the beginning of tuberculosis, about dissemination of MBT from the primary focus, before or simultaneously with its formation. The knowledge about early bacilemia has formed the basis after discovery of antituberculosis preparations for prevention application.

The large importance acquire with scientific development of methods of struggle with tuberculosis. The large collectives in antituberculosis scientific-research institutes constantly study pathogenesis of tuberculosis, its early forms; new drugs and methods of treatment of tuberculosis. In medical institutes, and also at medical faculties of Universities the chairs of tuberculosis are created, which task is training the medical students to diagnostics and treatment of tuberculosis. At the same time collectives of such faculties conduct scientific work. At creation of the Russian Peoples friendship University the course of tuberculosis was created at the medical faculty in 1964. Its first head was professor, doctor med.sci, honored scientist Z.A. Lebedeva (1963-1980), which before was the outstanding scientific and public figure After it(her) a rate headed Ivanova Z.A. From 2003 rates heads V.A. Koshechkin. At the clinical base of the course attending physician, (registrar) from Africa, Asia, Latin America specialize in phthisiology The scientific work is carried out in the field of tuberculosis. The basic direction of scientific studies is investigation of diseases, accompanying tuberculosis.

The battle with tuberculosis is not ended.
Today, after more than 40 years after introduction chemotherapy of tuberculosis in practice new cases of the disease in the world are counted in total much more, than before. In many industrialized countries, sufficient funding, resources, high living standards, and wide spread chemotherapy in the last 40 years, have helped to reduce tuberculosis to a relatively minor problem. But in poorer coun¬tries it remains almost as big a problem as ever. Indeed, as their populations have increased and their tuberculosis rates have only slightly decreased, there are probably more tuberculosis patients in the world today than there were 20 years ago.

World Health Organization (WHO) has estimated that the total number of cases in the world will rise from 7.5 million in 1990 to 10.2 million in the year 2000. Total deaths will rise from 2.5 to 3.5 million. The rise will be due partly to increases in population in developing countries and partly to the spread of the HIV and drug resistant MBT. The number of deaths caused by tuberculosis annually essentially exceeds number of cases of death caused by any other pathogenic microorganism. Tuberculosis, affects mainly adult people in the most productive period of life, entails enormous economic costs.

WHO is world coordinating center in fight with tuberculosis. In a base for fight with tuberculosis the organization of national tuberculosis programs (NTP) are laid. Treatment of tuberculosis is the cornerstone of any NTP. The modern treatment strategy is based on standardized short-course chemotherapy regimens and proper case management to ensure completion of treatment and cure. Standardized treatment is a component of the tuberculosis control policy package, set out in WHO’s expanded framework for effective fight with tuberculosis, and of the internationally recommended strategy for tuberculosis control known as “DOTS (Direct Observation Treatment Short-course).

Each doctor, without dependence from his specialty, should know principles of preventive measures, diagnostics and treatment of tuberculosis.

A qualified doctor should in proper time suspect tuberculosis at the patient and in according to the circumstances carry out competent diagnostics and if there are indications send the patient to phthisiatrists or to an extra pulmonary tuberculosis expert.

In each country if this country is a member-state of WHO, there is a nation-wide program of struggle with tuberculosis. Any doctor should know, how the struggle with tuberculosis is organized in his country, basic directions of this program, establishments which are responsible for its performance and whenever possible to participate in this program.

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