Dr Felix James
Earliest description of this disease can be found from the records on tablets of Babylo-Assyrian (668-626 BC), writings of Rig Veda, Old testament of Hebrews, Writings in Greek form days of Homer, Ossuary relics of Tuberculous lesions in neolithic man and egyptian mummies.
The disease description with cough, fever, blood spitting and emaciation was called as Leo ping in China, Rajyakshma in India, Pthisis by Hippocrates (460 – 377BC).
Development of Anatomy led to observation of small, rounded, whitish gray bodies called tubercles by Sylvius (1614 – 1672). The pathological alterations in the lung was described by Morgagni (1682 – 1771). Schoelein was the person who coined the term ‘tuberculosis’ in the year 1839. Robert Koch in the year 1882, established that tuberculosis in man and animals are caused by tiny, slender, rod shaped bacilli and called them ‘tubercle bacilli’. The discovery of X-ray by Roengten in 1895 revolutionised the method of diagnosis of the disease. Sanatorium for treatment this disease was first established in Germany by Brehmer (1853). In India started at Ajmer (1906), Almora (1908), Madanapalle (1908).
Calmette and Guerin accidentally found that the cultures of bovine Tuberculosis growing in glycerine potato medium altering their characters by addition of ox bile. They showed loss of virulence after 231 subcultures in glycerol ox bile potato medium
The incidence and mortality were high when the disease affected susceptible groups as they offered favourable condition for the spread of disease. Industrial revolution, overcrowding, poor sanitation, poor housing, poor nutrition, over work, stressful condition in cities lowered natural resistance and the incidence of the disease was more. Improved standards of living, better housing, less crowding, better sanitation, good nutrition, shorter working hours reduced the incidence of the disease.
England and Wales:
346 / 1,00,000 in mid 19th century
126 / 1,00,000 at beginning of this century
31 / 1,00,000 in 1951
6.7/ 1,00,000 in 1960
United states of America
250 / 1,00,000 before the discovery of bacilli
100 / 1,00,000 at beginning of the century
33 / 1,00,000 by 1946
12 / 1,00,000 by 1951
1.5 / 1,00,000 by 1975
800 / 1,00,000 hospital death early part of century
400 / 1,00,000 – Calcutta and Madras – early part of century
200 / 1,00,000 by 1949
64.1 / 1,00,000 by 1953
WHO studies reveal a global incidence of 3.5 to 4 million cases per year ( 90% from the developing countries – late 1990), which is only a fraction of the actual fact. Estimated 8 million new cases of which 97% belongs to developing countries in 1997 (Asia – 5 million, Africa – 1.6 million, middle east – 0.6 million, Latin America – 0.4 million.
It is estimated that 2 million deaths shall occur due to tuberculosis with 98% from the developing countries. It is predicted that the annual incidence rate shall increase by 40% by 2020.
Till 1985, in industrialised world records were reliable and predictable, there was decline of cases except during war years, from first half of the century. After 1985, the rate of decline ceased and there was increase in number of cases in USA, UK and other countries. In developed countries the affected population include elderly, immigrants from third world countries, members of ethnic communities and immuno-compromised individuals. In developing counties it mainly affects adults.
Pathogenesis And Immunity:
Infection begin when mycobacterium tuberculosis enters the host through droplet nuclei. Majority are trapped in upper airways and expelled by ciliated mucosal cells. Usually fewer than 10% of agent reaches the alveoli. Non specifically activated macrophages ingest the bacilli. Invasion of macrophages by mycobacterium leads to association of C2a with bacterial cell wall and C3b opsonisation of bacteria and recognition by macrophages. The balance between bactericidal activity of macrophage and the virulence of the bacillus (linked to bacterium’s lipid rich cell wall and to its glycolipid capsule, both confer resistance to complement and free radicals of phagocyte) determines the events following phagocytosis. The number of invading bacilli also has a role.
The genes that confer virulence to Mycobacterium tuberculosis have been identified. Kat-G encode for catalase which is protective against oxidative stress. RpoV main stigma factor. Defect in these two genes result in loss of virulence.
Studies and observations suggest that genetic factors play a key role in innate non immune resistance to infection with mycobacterium tuberculosis. The existance of this resistance is suggested by the differing degrees of susceptibility to tuberculosis in different populations
Initial stages of host-bacterial interaction:
Either the host’s macrophages contain bacillary multiplication by producing proteolytic enzymes and cytokines or the bacilli begin to multiply. If bacteria begin to multiply then the macrophages are killed by lysis. Non activated monocytes attracted from blood stream to the site by various chemotactic factors ingest the bacilli released from lysed macrophages. These phases are usually symptomless.
2-4 weeks after infection:
There develops two additional host response to infection, namely,
1) tissue damaging response
2) macrophage activation response.
Tissue damaging response is the result of delayed type hypersensitivity reaction to various bacillary antigens. It destroys non activated macrophages that contain multiplying bacilli.
Macrophage activating response is a cell mediated phenomenon resulting in the activation of macrophages that are capable of killing and digesting tubercle bacilli. Although both of these response can inhibit mycobacterial growth, the balance between these 2 determining the form of tuberculosis to be developed.
With the development of specific immunity between the accumulation of large numbers of activated macrophages at the site of primary lesion, granulomatous lesions (tubercles) are formed, consisting of lymphocytes, activated macrophages like epitheloid cells, giant cells. Initially the newly developed tissue damaging response is the only event capable of limiting mycobacterial growth with in the macrophages. The response mediated by bacterial products not only destroys macrophages but also produces early solid necrosis in the center of the tubercle.
Although Mycobacterium tuberculosis can survive, its growth is inhibited within this necrotic environment by low oxygen tension and low pH. At this point some lesion may heal by fibrosis and calcification, while other undergo further evolution.
Cell mediated immunity develop and is critical when bacillary antigens processed by macrophages stimulate T-lymphocytes to release a variety of lymphokines, which activates local macrophages. These activated macrophages aggregate around the lesions center and effectively neutralize tuberculosis bacilli without causing further cell destruction. The central part of lesion, the necrotic material resemble soft cheese (caseous necrosis). Viable bacilli may remain dormant inside macrophages or in necrotic material for years or throughout patients life time. Healed lesions in lung parenchyma and hilar lymph nodes may later be calcified and called as Ranke complex.
In minority of cases the macrophage activating response is weak, and mycobacterial growth can be inhibited only by intensified DTH reactions, which lead to tissue destruction. Lesions tend to enlarge further leading to liquefaction of caseous material and destruction of bronchial wall and blood vessels, which lead to formation of CAVITIES. Liquefied caseous material with large number of Bacilli drained through bronchi within the cavity spread to the environment and facilitate the spread of bacilli.
It occurs as a result of initial infection with Mycobacterium tuberculosis. In areas of high prevalence, children are usually affected and the infection is localized to middle and lower zones of lungs. It is accompanied by hilar and para tracheal lymphadenopathy. In majority of cases the lesions heals spontaneously and later may be evident as a small calcified nodule (Ghons Lesion).
In children and persons with impaired immunity i.e. affected with HIV or malnourished individuals primary pulmonary tuberculosis may develop clinical illness.
The initial lesion increases in size and can evolve in different ways:
1. Penetration of bacilli to pleural space leading to Pleural Effusion.
2. Primary site enlarges and central portion undergoes cavitation
3. Segmental or lobar collapse due to compression by enlarged lymph node
4. Obstruction emphysema and bronchiectasis from partial collapse.
5. Haematogenous spread leading to miliary tuberculosis.
6. Granulomatous lesions in multiple organs.
Post Primary Disease:
Also called as adult type or reactivation or secondary tuberculosis. It results from endogenous reactivation of latent infection or is usually localized to the apical or posterior segments of upper lobes, where high oxygen concentration favours the growth of mycobacterial tuberculosis.
Signs and symptoms:
It starts as non specific or insidious symptoms like fever and night sweats, weight loss, anorexia, general malaise and weakness. Cough eventually develops initially as non productive and later productive sputum. Blood streaking of sputum is frequently documented associated with massive hemoptysis due to erosion of a fully patent vessel.
Rhonchi due to partial bronchial obstruction and classic amphoric breath sounds in areas with large cavities may be heard. Low grade intermittent fever with wasting associated with pallor and finger clubbing in certain cases. Haematoloty shows mild anaemia and leucocytosis.
Extra Pulmonary Tuberculosis:
1. Lymph node tuberculosis or tuberculosis lymphadenitis:
It is the commonest extra pulmonary presentation frequently among the HIV patients. It is presented as a painless swelling of lymph node commonly at cervical and supraclavicular sites. Usually discrete at early phase but later become inflamed and caseous with a fistulous tract draining caseous material. Systemic symptoms are limited to HIV infected persons and concomitant lung disease may or may not be present. The diagnosis is by FNABC or surgical biopsy. AFB are seen in 50% of cases. Sputum culture is positive in 70-80%of cases. The histologic examination shows granulomatous lesion.
2. Pleural tuberculosis:
Common in primary tuberculosis due to penetration by tuberculosis bacilli. Depending on extent of reactivity the lesion can be small, or become sufficiently large in order to produce symptoms. The symptoms include fever, pleuritic chest pain and dyspnoea. The physical findings of pleural effusion like dullness on percussion absence of breath sounds are seen. X-ray chest reveals effusion. Thoracocentesis establishes final diagnosis and is also used as a therapeutic measure. FNABC reveals tuberculous bacteria. Tuberculous empyema is a less common complication.
3. Tuberculosis of upper air way:
Complication of advanced pulmonary cavitatory tuberculosis may involve larynx, pharynx and epiglottis. The symptoms include hoarseness and dysphagia and chronic productive cough. Carcinoma can have similar features but usually painless.
4. Genito urinary tuberculosis:
It occurs in 15% of all cases of extra pulmonary tuberculosis due to Haematogenous spread from the primary lesion and may involve any part of Genito urinary tract. The local symptoms like urinary frequency, dysuria, haematuria and flank pain predominate. It may be asymptomatic and may be discovered only after disease has developed. Urine examination reveals pyuria, haematuria. IVP helps in diagnosis. Calcification and urethral stricture are suggestive findings and lead to hydronephrosis and renal damage. Culture of three morning samples yields a definitve diagnosis.
5. Skeletal tuberculosis:
It is facilitated by reactivation of hematogenous foci or spread from adjacent paravertebral lymph nodes. The weight bearing nodes (spine, hip and knees in this order are affected most commonly. The spinal tuberculosis (Pott’s disease or tuberculous spondylitis) often involve two or more adjacent vertebral bodies. In children the upper thoracic spine is the commonest site and in adults the lower thoracic spine and lumbar vertebrae.
Pathogenesis: from anterior superior or inferior angle of vertebral body, the lesions reaches the adjacent body, also destroying the intervertebral disc. With advanced disease collapse of vertebral bodies results in Kyphosis (GIBBUS). A paraverebral cold absess may also form and in thoracic region this may attach to the chest wall as a mass. Lower spine may reach inguinal or present as psoas abscess.
MRI or CT scan helps in diagnosis. Aspiration or bone biopsy confirms diagnosis by culture and histologic findings.
The complication include paraplegia. Para paresis due to large abscess is a medical emergency and require drainage. Tuberculosis of hip joint causes pan and limping. Tuberculosis of knee joint causes pain and swelling and sometimes after a trauma. If the disease goes unrecognized it may lead to joint deformity.
The treatment include chemotherapy and surgery
6. Tuberculous meningitis and tuberculoma
Tuberculosis of central nervous system accounts for 5% of extra pulmonary cases. Usually seen in young children and in patients infected with HIV. It occurs due to hematogenous spread to subarachnoid space and due to old lesion in miliary patern found.
The case may present as head ache, confusion, lethargy, altered Sensorium and neck rigidity. The disease evolves over 1-2 weeks, a course longer than bacterial meningitis. Paresis of cranial nerves (ocular nerves in particular) and involvement of cerebral arteries may produce focal ischaemia. Hydrocephalus is common.
Lumbar puncture is the corner stone of diagnosis. The CSF shows high leucoctyic count, protein content, and low glucose concentration.
The control of tuberculosis:
Tuberculosis control means reduction in prevalence and incidence of disease in the community. The WHO defines that tuberculosis control is said to be achieved when the prevalence of natural infection in the age group 0-14 years is of the order of 1 per cent. This is abut 40% in India.
A case is defined by WHO as a patient whose sputum is positive for tubercle bacilli, and such cases are the target of case finding.
Case Finding Tools:
1. SPUTUM EXAMINATION: sputum smear examination by direct microscopy is now considered the method of choice. The reliability, cheapness, and ease of direct microscopic examination has made it number one case finding method all over the world. Studies have shown that examination of two consecutive specimens is sufficient to detect a large number of infectious cases in the community. Under India’s District Tuberculosis Programme (DTP), the first priority is given to direct smear examination of sputum of patients, who, of their volition, attend hospitals and health centres with the following persistent chest symptoms
a. Persistent cough of about 3 or 4 weeks duration
b. Continous fever
c. Chest pain
2. Sputum culture: culture of sputum is only second in importance in a case finding programme. It is not only difficult, tedious, lengthy and expensive but also needs special training and expertise. This method of examination is offered only to patients presenting themselves with chest symptoms whose sputum smear is negative by direct microscopic examination.
3. Mass miniature radiography: This method has been stopped as a general measure of case finding, because of high cost, lack of definitiveness, high proportion of erroneous interpretation and very low yield of cases commensurate with the effort involved
4. Tuberculin test: As the diagnostic value of tuberculin test is invalidated, this test has little value as a case finding tool.
Directly Observed Treatment, Short Course (Dots)
Compliance with tuberculosis treatment regimens is limited by their complexity and duration, a lack of symptoms in some patients and medication side effects. In 1993, at least 20 percent of patients with pulmonary tuberculosis did not complete therapy. Noncompliant patients are 10 times more likely than compliant patients to transmit multidrug-resistant tuberculosis, to require prolonged treatment and to experience disease progression or relapse; they are also more likely to die as a result of their infection. Noncompliance is more likely to be a factor in men, homeless persons, drug addicts, alcoholics, HIV-infected patients, patients with mental and physical disabilities, and patients who have previously failed treatment.
Predicting noncompliance in advance is notoriously unreliable. Thus, directly observed therapy, in which patients are observed swallowing each dose of medication, should be strongly considered in patients with latent tuberculosis infection who are being treated with twice- or thrice-weekly regimens and in all patients who are being treated for active tuberculosis.
When directly observed therapy is used, treatment completion rates range from 85 to 96.5 percent. In the first two years after directly observed therapy became more widely used, there was a 21 percent decrease in all tuberculosis cases and a 39 percent decrease in multidrug-resistant tuberculosis cases.
Local public health departments offer directly observed therapy services at minimal or no cost. Community health care providers are responsible for identifying and referring appropriate candidates for these services.
The case has to be individualized and proper similimum has to be selected
The following medicines have been given in the synthesis repertory for this condition.
1. GENERALS – TUBERCULOSIS
aven.; bac.; bell.; brom.; calc.; chinin-ar.; ferr-i.; hippoz.; iodof.; lap-a.; led.; myrt-c.; nat-ar.; phos.; pyrog.; spong.; teucr-s.; tub.; urea;
2. GENERALS – INFLAMMATION – Glands; of – tubercular ; merc-k-i (merc-k-i.;mercurius biniodatus cum kali iodatum) – grimmer collected works
3. GENERALS – HISTORY; personal – tuberculosis; of bac.;tub.;
4. GENERALS – FAMILY HISTORY of – tuberculosis bac.; carc.; tub
5. GENERALS – CANCEROUS affections – tubercular base; on kali-i.
6. FEVER – INTERMITTENT – tuberculosis, in bapt.;
7. FEVER – CONSTANTLY HIGH TEMPERATURE – accompanied by – diarrhea – children; in tuberculous lob-e.;lobelia erinus (Clarke)
8. FEVER – AFTERNOON – tuberculosis, early ars-i.;
9. SLEEP – SLEEPLESSNESS – tuberculosis, in iod.; sang.;
10. EXTREMITIES – PAIN – Joints – tubercular family history dros.;
11. CHEST – PHTHISIS pulmonalis
acet-ac.; acet-ac.; agar.; agar.; aloe; alumn.; am-c.; am-m.; ant-ar.; ant-t.; arg-met.; arg-met.; arn.; ars.; ars-i.; ars-s-f.; arum-t.; aur.; aur-ar.; aur-m.; aur-m-n.; bac.; bac-t.; bals-p.; bar-m.; berb.; beta; blatta-o.; brom.; bufo; calag.; calc.; calc.; calc-i.; calc-p.; calc-s.; calc-sil.; carb-an.; carb-v.; carbn-s.; carc.; card-m.; card-m.; cetr.; chinin-ar.; chlor.; chlor.; coc-c.; con.; con.; cur.; dros.; dros.; dulc.; elaps; elaps; erio.; eupi.; ferr.; ferr-ar.; ferr-i.; ferr-p.; fl-ac.; gad.; gal-ac.;b gal-ac.; graph.; guaj.; guaj.; guajol.; ham.; helx.; hep.; hippoz.; ichth.; iod.; kali-ar.; kali-bi.; kali-c.; kali-n.; kali-n.; kali-p.; kali-s.; kali-sil.; kreos.; lac-d.; lach.; lachn.;b lachn.; lec.;b led.; lyc.; lycps-v.; mag-c.; mang.; med.; merc.; mill.; myrt-c.; naphtin.; nat-ar.; nat-cac.; nat-m.; nat-p.; nat-s.; nit-ac.; ol-j.; ol-j.; ox-ac.; petr.; ph-ac.; phel.; phel.; phos.; pix; plb.; psor.; ptel.;h puls.; pyrog.; pyrog.; rumx.; rumx.; sabal; salv.; samb.; samb.; sang.; sarr.; senec.; senec.; seneg.; sep.; sil.; slag; spong.; stann.; stann-i.; stict.; still.; sul-ac.; sul-ac.; sul-i.; sulph.; tarent-c.; teucr-s.;gm1 teucr-s.; ther.; thyr.; tub.; tub.; tub-a.; tub-d.;al verb.; zinc.; zinc-i.; zinc-p.;
12. CHEST – CANCER – Mammae – accompanied by – ulcers – tubercular ulcers; bell-p.
13. EXPECTORATION – TUBERCLES hep.; mag-c.; phos.; sil.; spong.;
14. EXPECTORATION – CALCAREOUS tubercles sars.;
15. COUGH – TUBERCULOUS persons, in phos.;
16. COUGH – TALL, slender, tuberculous subjects; in phos.;
17. RESPIRATION – ASTHMATIC – tuberculosis family history dros.;
18. LARYNX AND TRACHEA – INFLAMMATION – Larynx – tubercular sel.;
19. FEMALE GENITALIA/SEX – MENSES – suppressed – tuberculosis, in lob.; lyc.; senec.; solid.; solid.; ust.;
20. FEMALE GENITALIA/SEX – LEUKORRHEA – tuberculous women; in ferr.;
21. MALE GENITALIA/SEX – POLLUTIONS – tuberculosis, in calc.;
22. RECTUM – DIARRHEA – tuberculosis; during arg-n.; ars.; chin.; chin.; coto; ferr.; phos.;
23. ABDOMEN – INFLAMMATION – tuberculosis abrot.;b
24. EXTERNAL THROAT – GOITRE – exophthalmic – tuberculosis in family; with dros.;
25. FACE – ERUPTIONS – acne – tubercular children; in tub.;
26. EYE – INFLAMMATION – Iris – tubercular bar-i.; tub.;
27. HEAD – INFLAMMATION – meninges – tubercular apis; calc.; iod.; lyc.; merc.; nat-m.; sil.; sulph.; tub.; zinc.; zinc.;
28. MIND – FEAR – tuberculosis; of calc.
1. Harrison’s Principles of internal medicine 15th edition
2. The oxford text book of medicine 3rd edition
3. Davidson’s Principles and practice of medicine
4. Clinical medicine – K.V.Krishnadas
5. Text book of medicine – K.V. Krishnadas
6. Repertory of homoeopathic materia medica – J.T.Kent
7. Synthesis Repertorium Homoeopathicum syntheticum – Frederick schroyens
8. Park’s text book of Preventive and Social Medicine – K.Park
9. websites of WHO and Centre for Disease Control United States of America
10. Text book on microbiology – Ananthanarayanan and Jayaram Panicker
Dr Felix James BHMS,MD(Hom)
Medical Officer, Dept. of Homoeopathy, Govt. of Kerala