Though age old stigma with tuberculosis has educed but people still have misconceptions about the disease, its contagiousness and the way it can affect others.

Clear communication is the keystone of patient diagnosis and it begins with telling the correct diagnosis and counseling the patient and family.

It is preferable to counsel the family together to begin with, to educate them and to dispel myths and to gain their support towards regular compliance by the patient.

Counseling and motivation during each visit are the keys to successful completion of treatment.

Counseling and motivation

• Explain the salient features of the disease to the patient and his family members.
• Answer their queries with concern.
• It is a good idea to develop a one to one relationship with the patient and to know about his social and economic situation.

• Stress upon strict following of the regime and ask the other members of family to keep a record and enforce the regime.

• Cos of the treatment should be clearly explained if patient buys his own medicine.
• If patient cannot afford the treatemtn he sould be referred to  nearest goverment set up that povides anti TB drugs
• Patient should be told that  he will improve gradually and shall become asymptomatic at the end of 2-3 months, but should go on taking his medicines regularly in the prescribed doses for the prescribed period.

• Side effect should be explained and reported as soon as noted.

Tuberculois needs to be treated aggressively and patient needs to participate actively in the treatment.

They are activated by IL-15.

They have the appearance on light microscopy of large lymphocytes with numerous cytoplasmic granules and are sometimes called large granular lymphocytes. The granules contain substances that facilitate target cell lysis including perforin (a pore-forming protein) and granzymes. They classically express the CD16 and CD56 cell-surface markers.

NK cells attack virus-infected or abnormal cells expressing low levels of class I MHC molecules, while CD8+ T cells are MHC-restricted and attack cells with high level of class I MHC complexed to antigen.

NK cells insert perforin into the cells they are attacking and secrete granzymes through the pore. Granzymes attack the cell causing apoptosis.

NK cells can also kill cells through antibody-dependent cellular cytotoxicity where IgG bound to target cells interacts with Fc receptors (CD16) on NK cells causing release of lytic enzymes. NK cells are numerous in skin biopsies of patients with graft versus host disease following bone marrow transplant. They are also expanded in large granular lymphocyte (LGL) syndrome and in some patient with Felty’s syndrome.

mmune response can be segregated into four main types

Type I – IgE-mediated immediate hypersensitivity (e.g., allergic rhinitis or hayfever)
Type II – Antibody-mediated tissue injury, (e.g., autoimmune hemolytic anemia)
Type III –Immune complex (antigen-antibody) formation (e.g., serum sickness, Arthus skin reaction).
Type IV – Delayed-type hypersensitivity (e.g., immune response to mycobacterial antigens, positive PPD skin test)

MHC stands for major histocompatibility complex, a group of genes located on human chromosome 6. The products of MHC gene loci can be classified into two categories-class I and class II MHC molecules.

• Class I MHC molecules are expressed on the surface of all nucleated cells.

• Class II MHC molecules are found mostly on specialized cells called antigen-presenting cells.

Unlike macrophage, neutrophils, and B cells, T cells classically cannot recognize free soluble antigen. T cells can only “see” antigen via their surface T cell receptor, which will only bind to antigen bound to (“presented by”) an MHC molecule on the surface of a cell.

T cells “see” only pieces of large antigens because the antigen-binding groove in a MHC molecule can only accommodate a small peptide. Large protein antigens are digested (“processed”) prior to insertion in the groove.

An exception to the above involves stimulation of T cells by superantigens. A superantigen is typically a molecule of bacterial or viral origin that directly interacts with MHC class II molecules outside of the antigen-binding groove and then with the Vβ region in the T cell receptor.

The result is direct T cell activation of large amounts of T cells, all of which contain a specific Vβ region in the T cell receptor.

Therefore, the systemic host response to a superantigen can be substantial. Examples include toxic shock syndrome caused by a staphylococcal exotoxin that acts as a T cell superantigen.

Tuberculin is a glycerol extract of the tubercle bacillus. Purified protein derivative (PPD) tuberculin is a precipitate of non-species-specific molecules obtained from filtrates of sterilized, concentrated cultures.

The test is named after Charles Mantoux, a French physician who developed on the work of Koch.

Procedure

A standard dose of 5 Tuberculin units (0.1 mL) is injected intradermally and read 48 to 72 hours later. A person who has been exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins.

The reaction is read by measuring the diameter of induration (palpable raised hardened area) across the forearm (perpendicular to the long axis) in millimeters. If there is no induration, the result should be recorded as “0 mm”.

Erythema (redness) should not be measured.

If a person has had a history of a positive tuberculin skin test, another skin test is not needed.

Interpretation of tuberculin reaction

The results of this test must be interpreted carefully. The person’s medical risk factors determine at which increment (5 mm, 10 mm, or 15 mm) of induration the result is considered positive.

A positive result indicates an exposure with mycobacterium tuberculosis.

Normally generalised interpretation of Mantoux test are

Induration 0-5 mm  – Negative

Induration 6-9 mm  – Weak positive

Induration > 10 mm – Positive

However depending upon risk factors the interpretation is considered positive as follows

Induration of 5 mm or more is positive in

• HIV-positive person
• Recent contacts of TB case
• Persons with nodular or fibrotic changes on chest x-ray consistent with old healed TB
• Patients with organ transplants and other immunosuppressed patients

Induration of 10 mm or more is positive in

• Recent arrivals (less than 5 years) from high-prevalence countries
• Injection drug users
• Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters, etc.)
• Mycobacteriology lab personnel
• Persons with clinical conditions that place them at high risk (e.g., diabetes, prolonged corticosteroid therapy, leukemia, end-stage renal disease, chronic malabsorption syndromes, low body weight, etc)
• Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories

Induration of 15 mm or more is positive in

• Persons with no known risk factors for TB

False positive result

A false positive result may be caused by nontuberculous mycobacteria or previous administration of BCG vaccine. Prior vaccination with BCG may result in a false-positive result for many years afterwards.

False negative result

Those that are immunologically compromised, especially those with HIV and low CD4 T cell counts, frequently show negative results from the PPD test. This is because the immune system needs to be functional to mount a response to the protein derivative injected under the skin.

Patients with highly active TB infection may also show false negative results.

Anergy testing

In cases of anergy, a lack of reaction by the body’s defence mechanisms when it comes into contact with foreign substances, the tuberculin reaction will occur weakly, thus compromising the value of Mantoux testing. For example, anergy is present in AIDS, a disease which strongly depresses the immune system. Therefore, anergy testing is advised in cases where suspicion is warranted that it is present. However, routine anergy skin testing is not recommended.

This induration is a result of the hypersensitivity that the individual develops to the bacilli. Hence a positive Mantoux test only indicates that the individual got infected with Mycobacterium tuberculosis sometime during his life. It should not be misinterpreted as a sign of tuberculous disease and ATT should not be started in adults solely on the basis of a positive Mantoux test.

More than 50 percent of Indian adults are Mantoux positive, indicating a high prevalence of infection with Mycobacterium tuberculosis. 90 percent of those infected do not develop pulmonary TB in their lifetime. It is clear that a positive Mantoux test does not indicate and is not a sign of disease in adults.

A test is either positive or negative depending on whether the induration is less than or more than 10 mm in diameter. There is no added significance of a “strongly positive” reaction.

The radiological opacities in a chest x-ray are a result of the pathological processes taking place in the lungs. TB causes alveolar consolidation, necrosis, cavitation and fibrosis, features, which it shares with a variety of lung diseases.

TB also shares its radiological features with many other pulmonary diseases. There is no radiological feature that is absolutely typical of pulmonary TB and other diseases may mimic TB radiologically. The following features, however, when seen on a chest skiagram, suggest a diagnosis of TB:

• Unilateral or bilateral upper zone opacities with or without associated fibrosis.
• Cavity lesions.
• Opacities with or without cavitation in apical segments of either lower lobe.
• Mediastinal and unilateral hilar lymphadenopathy.
• Bilateral miliary mottling.
• Pleural effusion.

TB, even after a complete cure, usually leaves behind residual opacities in the patient’s chest x-ray for life. That is why, when a previously treated patient presents with recurrence of respiratory symptoms, ATT should not be started on a radiological basis alone, without sputum smear or culture positivity for AFB.

Most patients with a cavity on an x-ray chest are smear positive for AFB. Thereafter, when the sputum of a patient with cavitary lesions on the x-ray is persistently negative, consider other diagnosis.

Computed tomography

Although computed tomography  should not be routinely ordered when investigating pulmonary tuberculosis.

However, in rare situations it can be used to define mediastinal and pulmonary lesions more clearly. Wherever computed tomography is resorted to, it must be complemented, wherever possible, with a guided fine needle aspiration biopsy to arrive at a definite pathological or microbiological diagnosis.

It stops variceal bleed in 80 percent of patients and can be repeated if bleeding recurs. However, if there is active bleeding, sclerotherapy is hazardous and first the bleeding should be controlled by balloon tamponade.

Banding: Here, the varices are sucked into an endoscope accessory, allowing them to be occluded with a tight rubber band. The occluded varice subsequently sloughs with variceal obliteration.

Balloon tamponade: This is done with Sengstaken-Blakemore tube which possesses two balloons and exerts pressure in lower esophagus and fundus of the stomach. The tube is passed through the mouth and its presence in the stomach is checked by auscultating over the upper abdomen while injecting air into the stomach. The gentle traction is used to maintain pressure on the varices. Initially gastric balloon only is inflated, which would control the bleeding. If esophageal balloon also required to be inflated, it is important to deflate it for 10 mins every three hours to prevent esophageal mucosal damage. This usually stops the variceal bleed, but only allows for time for more definite therapy.

Transaction: Transaction of the varices can be done easily with a stapling gun. This is used when bleeding cannot be controlled by other measures. It carriers a small risk of subsequent esophageal stenosis.

Shunt surgery: Portocaval shunts also give excellent results with low morbidity and mortality and is a one time procedure unlike sclerotherapy which may have to be repeated. However, the incidence of hepatic encephalopathy is high and death could result from liver failure. Hence it is only used when other measures fail and offered only to patients with good liver functions.

Common side effects: Hepatitis, peripheral neuropathy
Uncommon side effects: Cutaneous reactions, arthralgia, drug induced lupus, optic neuritis, convulsions, mental symptoms aplastic anaemia, haemolytic anaemia agranulocytosis, gynaecomastia.

Rifampicin

Common side effects: Anorexia, nausea, vomiting, epigastric pain, hepatitis
Uncommon side effects: Anaemia, cutaneous reaction, flue like syndrome, shortness of breath, acute renal failure, shock, thrombocytopaenic purpura, haemolytic anaemia.

Pyrazinamide

Common side effects: Arthralgia (21 percent cases) hepatitis, anorexia, nausea, vomiting.
Uncommon side effects: Cutaneous reaction, hyperuricemia, sideroblastic anaemia.

Ethambutol

Common side effects: Retrobulbar neuritis, arthralga
Uncommon side effects: Cutaneous reactions, peripheral neuropathy.

Streptomycin

Common side effects: Cutaneous reactions, auditory and vestibular toxicity resulting in giddiness, numbness and tinnitus.
Uncommon side effects: Vertigo, ataxia and deafness-if streptomycin is continued despite early symptoms

Stop immediately and don’t reuse in case following reactions occur

• Rifampicin – Acute haemolytic anaemia, shock, acute renal failure or thrombocytopaenic purpura.

• Ethambutol – Retrobulbar neuritis.
• Streptomycin – Deafness or ataxia.
• Thiacetazone – Severe skin rashes or agranulocytosis.

A patient of tuberculosis is likely to have infected some of his own family members prior to reporting to you.

Of those infected, some may develop the disease.

Only sputum smear positive patients are likely to spread infection. Those patients who do not expectorate the bacilli in their sputum, will not spread the infection to their family members.

A family contact survey is necessary only when the patient’s sputum smear is positive for acid fast bacilli.

In case of a child, it is necessary to survey the family to see who may have infected the child. A well taken history and corroborative symptoms usually identify the adult.

He or she may then be investigated in some detail.

All contacts living at home.  should be surveyed. The survey should include all the elderly members of the household, as also, all the domestic workers who stay with the family.

There is no need to do a family contact survey of a smear negative patient.

Erythrocyte sedimentation rate (ESR)

ESR is o a non-specific investigation which may become rapid in a large variety of clinical conditions ranging from anaemia to any chronic infectious, inflammatory or malignant disease.

ESR has absolutely no diagnostic value for TB and should not be given any weightage at all towards its diagnosis as a standalone criteria. But in conjunction with other clinical parameters, its raised value can indicate possibility of tuberculosis

Sputum examination

Examination of the sputum is the only way by which a definitive diagnosis of pulmonary tuberculosis can be made. You can be absolutely certain that your patient has pulmonary TB only when his sputum smear is positive for AFB. The importance of this investigation cannot be overstated. Vigorous efforts should be made to isolate AFB in sputum before initiating treatment.

Useful tips

• The patient should preferably give samples on three days. In case of inconvenience, a ‘spot’ sample to the laboratory on the first day, return the next day with an early morning sample and give a third, ‘spot’ sample, the same day. The chances of finding AFB in sputum are much higher with 3 samples than with 2 or 1 sample

• Give clear instructions to the patient to give sputum and not saliva for examination. Instruct the patient to produce the specimen by a vigorous cough and give the thick, white, yellow or green sputum thus expectorated from the lower respiratory tract.

• It is preferable to transfer the sample to the laboratory on the same day in a clean, wide mouth glass container.

• Send samples to a reliable laboratory that routinely handles a large number of sputum specimens every day.

• Wherever there is a high index of suspicion, but the first two samples are negative for AFB by smear, and a reliable laboratory is available, send the third sample for both smear and culture examination.

Common reasons for a negative report

• Poor or no instructions by doctors to patients

• Poor staining the smear also contributes towards underdetection of AFB in sputum.

• Too few or no bacilli in the sputum

The patient whose sputum smear is persistently negative may have some other disease. However, if you still strongly suspect pulmonary TB clinically and radiologically, repeating sputum smear examination after 3-4 weeks may be worthwhile.

Complement System On Attack

Complement components have immunologic activity both individually and in an activation cascade leading to a polymer formed by C5, C6, C7, C8, and C9 (the membrane attack complex, or MAC), which results in lysis of target cell membrane.

Early classic complement components (especially C3 products) act as opsonins and assist in the phagocytosis of bacterial particles by neutrophils and macrophages.

Certain complement split products (C3a and C5a) are chemotactic for phagocytic neutrophils and also act as “anaphylatoxins,” which directly stimulate mast cells and basophils to release histamine resulting in increasedvascular permeability.

Deficiency of early complement components is associated with increased pyogenic infections (C3 deficiency) and an increased incidence of autoimmune diseases, possibly owing to impaired clearance of immune complexes. The MAC appears especially important in host defense against Neisseria infection. Deficiency of any one of the terminal complement components can result in recurrent infections with Neisseria.

The complement system can be activated by three pathways:

Classical-IgM and IgG binding to antigen forming immune complexes that can bind Clq activating Clr and Cls to cleave c4. other proteins including c-reactive protein (binds Clq), serum amyloid P, and C4 nephritic factor can activate this pathway.

Alternative-activated by lipopolysaccharide on microbial cell surfaces in the absence of antibody. C3 and factor B bind to cell surface forming C3bBb, which functions to cleave more C3 molecules. This is part of the innare immune system. IgA complexes and C3 nephritic factor can also activate this pathway.

Lectin-mannan-binding lectin is secreted by the liver and binds to microbial ligands. This activates mannan-binding lectin-associated proteases that are related to Clr and Cls and can cleave C4 resulting in complement activation.

Neutrophil granulocyte migrates from the blood vessel to the matrix for phagocytosis

Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of white blood cells in mammals and form an essential part of the immune system. Neutrophils are important in phagocytosing and digesting foreign particles at sites of inflammation and antigen entry. Neutrophils kill and dissolve microbes by

• Release of enzymes and bactericidal products from their intracytoplasmic granules
• By generation of toxic oxygen radicals and hypohalous acids.

Clinical deficiency of leukocytes manifests as recurrent skin and soft tissue infections with pyogenic organism and sepsis.

eosinophils (acidophils), are white blood cells that are one of the immune system components responsible for combating infection and parasites. Eosinophils are active in immunity against parasites, especially helminths, Eosinophils are specialized leukocytes whose granules contain numerous toxic products, including major basic protein, eosinophil peroxidase, and eosinophil cationic protein.

These products are especially toxic to helminthes. Activated eosinophils also produce large quantities of leukotriene C4 (LTC4) and TGF-β that promote increased venular permeability and fibroblast-dependent fibrosis, respectively.