1 Introduction:
Tuberculosis or TB is a bacterial disease.The most common microorganism that causes TB is mycobacterium tuberculosis. This organism was discovered in 1882.Robert koch was the scientist who made the discovery. This organism has slow growth and a very thick capsule outside that protects it from threats and hence it is one of the most toughest organism causing very tough infections. There are a few other organisms that cause the disease as well. America was considered to be one of the countries that have been safe from the disease up untill 1990 s when the disease was discovered in the congested city areas especially those affected by aids. This has become the new public health challenge for the america . The TB attacks lungs usually and it is the most common of the sites affected by TB. The same organism causes the infection in the lungs but does have the capability to travel to any part of the body by entring into blood. TB spreads from one person to another by the cough or sneezing from a sick person who has the germ in his sputum of the air carries the droplets.our body's immune system, that has the role of defending our bodies against the infections normally does destry these organisms upon entry into the body.
Some times our defence system doesn't kill the organisms but creates a think wall arround the bacteria thus limiting their affect and hence saving the body from active disease although the organism does stay inside the walls capable of creating infection if given chance by the decrease in immunity during diseases like aids. This situation is called latent TB in which the person has the capacity to spread the infection but isnt suffering from the disease itself.
Sometimes, If our immune system does not effectively kill the bacteria's these organisms create thick walls arround themselves and remain dormant for years and wait till they find decreased immunity in the host and a chance to cause infection, thus attacking the host either inside the lungs or any other area. Many diseases are the cause of increased latent TB such as Aids , diabetes mellitus and at times simple nourashment problems caused by physical and some times mental illness.Most of the times Tb starts in the lungs and person suffers from symptoms of lung disease but it can often involve lymph nodes(small glands that help getting rid of the waste and infections) or some times it can effect bones intestines etc. meningitis(the inflamation of brain and its membranes) is one serious disease that can be caused by the same bacteria. Although it is very rare.
Tuberculosis is one of the most ancient disseases .In neolithic times (8000 BC) there Were incidents of the same disease affecting bones and skeleton called Pots disease .The records are also found in Egyptian and pre Columbian new worlds (1000 BC) During times of Hippocrates (400 BC) it was known to be a contagious disease, the disease which can spread from one man to another. They used to call it phthisis(which meant to waste away). There are clear evidences of increase in the number of people suffering from disease during time of population growth in urban areas especially in European countries . Industrial revolution of 1750 has witnessed about 25 % of population eradicated by this disease. In the early 20th century it was the main cause of death in America.
(CDC) The US Centers for Disease Control and Prevention, has been recording detailed epidemiologic information on tuberculosis (TB) since 1953. Due to basic infection controle practices and other factors it was observed that the infection rate (incidence) of TB has droped since the beginning of 20th century A resurgence of tuberculosis was observed from the data collected in 1985. This increase was observed in ethnic minorities and more so in the population suffering from other diseases like Aids. Since than there are increases efforts in TB control activities in America and world wide.
AIDS causes immunity problems and hence it is often related with TB as an opportunistic infection attacking the vulnerable hosts. It is found to be co existing usually with Aids. Globally, coinfection with HIV is highest in South Africa, India, and Nigeria.
Aids affected persons are 20 times more vulnerable to TB as compared to normal person with intact immune systems. Correspondingly, TB is the leading cause of mortality among persons infected with HIV.
Worldwide, TB is most common in Africa, the West Pacific, and Eastern Europe. These areas are full of factors causing and helping TB ,that includes limited financial resources and poor food supplies ,poor sanitation, and living conditions. Aids and multidrug resistant TB are other contributing factors. Despite aggressive measures to cut down the rate of growth of this disease these factors have contributed in continuous rise in the number of cases annually
Epidemiology:
TB death rate has fallen from 35% 1990.
Of the 22 TB high burden countries, 13 countries are on track to meet the 2015 Millennium Development Goal target (halt and reverse the incidence of TB by 2015
Estimated TB incidence, prevalence , 2008
Prevalence in india
Widely different results have been observed by Annual Risk of TB Infection (ARTI) studies undertaken in certain countries . During 2000-2003 four zones in india were selected to study and they showed ARTI rates ranging from 1.0 % in the southern zone to 1.9% in the northern zones . ARTI surveys are being repeated in these zones to verify the results but the results are not yet available. A study in west Sumatra Indonesia In Indonesia in 2206 , revealed an incidence rate of 1.3 % While a limited ARTI survey done in 2008 in DPR Korea indicates that the incidence rates for Korea estimated by WHO may need to be revised upwards and might be double the number suggested initially . Nepal was also involved in an ARTI survey for three ecological zones and in Kathmandu valley from 2006-2007, revealed a ratio of 0.86%, substantially lower compared to previous rate of 2.1%.Bhutan and Sri Lanka in 2009.are expected to undergo similar surveys .
TB disease incidence, prevalence and mortality
Where these surveys do indeed contribute to more accurate estimates of the burden of disease on different countries, still uncertainties exist regarding the current estimates for TB disease incidence rates , prevalence and mortality rates among individual countries of the Region. The routine notification data use for as a measure of disease incidence ,is certainly the right way to the future. However we do require to strengthen all aspects of TB surveillance system, focusing primarily on quality of data entry, detail compilation and timely reporting, and giving attention to precise accurate analysis and interpretation of the data.WHO Regional Office for South-East Asia (SEARO)has decided to organize a series of trainings focusing the areas like managing information for action (MIFA) in four of selected Member countries during 2007-2008. Meanwhile ,there is definitely a need to continue and support well-designed population-based surveys through out the Region, particularly in the higher TB burden countries, till such time that the routine case notifications might begin and be used to correctly reflect actual TB prevalence trends.
4: TB in India
TB is one of the most ancient and most important diseases. The Vedas and Ayurvedic Samhitas have clear mentions of the disease. The exact identification of the first reported case In India might not be possible yet we can find out the details of the first open air sanatorium for treatment and isolation of TB patients which was founded in 1906 in Tiluania, near Ajmer,and that followed by one in Almora two years later. The first non-missionary sanatorium was built near Shimla in year 1909 . Upon the earlier work done by Dr Louis Hart from 1908, the United Mission Tuberculosis Sanatorium (UMTS) which was built in 1912 in Madanapalle, south India. Dr Frimodt Moller who was the first Medical Superintendent did play a significant role in India's fight against TB . He did training of TB workers, and started the TB surveys (1939)along with introduction of BCG vaccination (1948).In 1917 the first TB dispensary was opened in Bombay which was the first real achievement against the fight with this disease. Later on madras also started a TB dispensary . Soon anti-TB societies were formed in Lucknow and Ajmer.
It was advised by dr langkaster that government should take active role in fighting this emerging and high incidence disease in india. India became a member of the International Union Against Tuberculosis (IUAT) in 1929 largly due to his suggestions. In year 1937, Her Excellency Lady Linlithgow had issued a public appeal for anti-TB funds collection on behalf of the government. Nearly a crore (10 million )of rupees was collected; from the original collection 5% of the money was kept by the center and the balance was distributed to the provinces and states. TBI (Tb association of india was formed with this retained fund along with With the help King George V Thanksgiving (Anti-TB) Fund, in February 1939. The provinces and states who received money also started their TB independent associations. The BTA Bengal TB Association, however, was functioning from 1929 and it hadits maintained dispensaries in Calcutta and Howrah. Its activitis benefited greatly this funding. In 1946 only 6000 beds were available for the treatment of TB patients. According to the estimates given by The Bhore Committee there were about two and a half million patients who need treatment and annual deaths are about half a million . India was a huge country , which included Pakistan and Bangladesh in those days, the efforts of NGOs that were not centrally monitored or funded were not adequate. There was no option but The government to intervene. However, diagnosis was a serious unresolved issue, while treatment, remained inadequate. It was by 1925,when chest radiology started detecting a deep-seated area of TB affected consolidation and thoracic surgeons started to demand X-rays. By 1945, the functions of the apparatus were enhanced and new technological advances helped the medical professionals to take help of and embody the MMR version.
Untill middle of the 20th century there were no really effective drugs or the combinations of any drugs that could controle the disease .Good food, open air and dry climate remained the main stay of medical treatment and the physician was handicapped in having any real intervention for the disease. Understandably treatment used to be the second priority where diagnosis was the main interest for the physicians at that time . In 1939, the TAI recommended the Organized Home Treatment Scheme as the best compromise under the prevailing circumstances.
Second world war started in that time and logically Fighting diseases was accepted as back seat passenger. However, a new TB Division situated in the Directorate General of Health Services (DGHS), was established in New Delhi in 1946,while an advisor was selected As TB head in it. TB started receiving a a prominent place in the planning. Since the government was not only concerned with TB but with other significant diseases and improving health infrastructure, there was constituted a committee under the chairmanship of Sir Joseph Bhore. Its secretary was Rao Bahadur KCKE Raja, who as the Director General of Health Services (DGHS)had done a lot of efforts against the TB disease during his tenure . The Bhore Committee, had published the report in 1946, and they placed organized domiciliary service on the forefront ofant TB programme. setting up of a seperate clinic for each district along with the use of mobile clinics for rural areas were the main suggestions of the committee.
BCG vaccine, was named after the two scientists who worked on mycobacteria and developed the vaccine , stands for Bacillus Calmette Guerín. BCG work was initiated in India as a pilot project and was supposed to be the two centers in 1948. In 1949, the project was extended to schools in almost every state of India. Under the supervision of the International Tuberculosis Campaign, which had collected a significant amount of experience working on BCG in many countries, Madanapalle was selected for the pilot project and it was a small project with Dr Frimodt Moller in the lead. India started working on a mass BCG preparation Campaign in 1951. A large BCG Vaccine Production Center in the city of Guindy, Madras had been set up in 1948. WHO and UNICEF supported the two projects with man power and funding.
The researcher were intrigued by the whole new idea about the possibility of finding an effective new drug against the tuberculosis created a revolution in the field and a new wave of experimental work was initiated with researchers trying a range of experiments and combinations of drugs their dosages against the TB. Affordability was an issue that needed to be studied and tackled in this war against TB .At annual TB workers conference held in 1949 ,number of research papers were presented suggesting the effects of PAS and SM on the tuberculosis disease and distribution of SM in indian cities .1952 Drs Robitzek and Selikoff revealed that INH is a miracle drug against TB and it continues as such till date.
The management of this disease in India and globally will be revolutionized in time ,owing to these studies .The scientists soon learned that the bacillus itself was a tough one and even the most effective drugs and their combinations were failing to eradicate the presence of bacteria completely .This bacillus was expert in fighting the drugs by creating resistance to drugs over and above its innate survival abilities. The short lived effect of these treatments soon helped the workers to realize that in order to fight this infection single drugs are not sufficient and that extensive long treatment might be the required solution ranging upto 9-12 months and at times 18 months .this opened the doors to new problems among which patients compliance was the top one .There were a few patients who could afford and had the temperament to continue the treatment for this long period.. further research and studies were needed to look into these issues of the ways to keep track ,and compliance .there was a need to do further research in this field.
TRC was the tuberculosis research Centre situated in madras chenai . which was established by the government in 1956 and it was related to the chemotherapy in tuberculosis initially .it was supported by government of madras WHO and ICMR along with British medical research council BMRC . The Centre was created to focus on the provision of information at mass level to the public affected by the tuberculosis . It focused pulmonary tuberculosis and found out the traditional sanatorium treatment recommended for the treatment of the disease ,bed rest ,well balanced diet and good accommodation were all relatively less important factors ,provided the adequate medical treatment was initiated and maintained .it was also suggested that the family members of the TB patients do not necessarily have higher risk of getting infected and that the treatment could be conducted in their own homes instead of sanatoriums r. These findings revolutionized the global treatment centers .
5: First reported case of TB in India
The references to tuberculosis in Asian civilization is not clear yet first of these is found in the Vedas. (Rigveda, 1500 BCE) being the oldest , calls the disease as yaksma. The Atharvaveda mentions another name: balasa for that . Atharvaveda has a clear first description of scrofula .which is the disease affecting lymph nodes (glands) Sushruta Samhita, which was written about 600 BCE, has recommendations for disease to be treated with breast milk, ample meats, alcohol and bed rest. The Yajurveda has advice for sufferers to move to higher altitudes.
The Manu Smriti, had written about 1500 BCE, that sufferers of yaksma have impurity and prohibits Brahmans to marry a women that has a family history of the disease
6: Causative agent of TB:
Mycobacterium tuberculosis, a tubercle bacillus, is the causative agent of TB. It belongs to a group of closely related organisms—including M africanum, M bovis, and M microti —in the M tuberculosis complex. Robert Koch discovered and isolated M tuberculosis in 188
It's a small aerobic non motile bacillus .this bacteria divides in 16 to 20 hours as compared to normal division in one hour. It is one of the toughest organism and can resist ordinary disinfectants easily.it can survive in dry atmosphere for weeks. M Africanum is less common found normally in African countries.
M bovis was once a significant disease causing organism but the advent of pasteurization has caused great reduction in this type of infections. Other less common type of mycobectria are Mycobacterium leprae, Mycobacterium marinum, Mycobacterium avium and M. kansasii. Last two are nontuberculous bacteria which don't cause tuberculosis
7: Mode of transmission
Tuberculosis is airborne disease that means it spreads to other people when someone suffering from TB infection coughs or sneezes. Sometimes simple speaking and spiting causes the organism to spread to other people .Small aerosol droplets get trapped into the breath of the coughing person and the droplets size very small ie 0.5 to 5 micro meter ..As much as 40 000 droplets can be released in a single bout of cough. The mycobacterium has tough outer shell that protects it from harm even when its outside the host body and may survive for weeks in dormant condition. Active disease can be caused by any one of these particles because a small amount of bacteria can cause infection in tuberculosis unlike other infections that need load of microorganisms to cause disease.
The risk of infection increases in people who have prolonged contact or repeated contacts with the patients and it can reach upto 22 % infection rate .Normally a person who has active disease and is not taking treatment usually causes transmission to upto 15 persons in a year time.There are few other causes that increase the risk of getting the infection Others at risk include people in areas where TB is common, people who inject drugs using unsanitary needles, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and health care workers serving these high-risk clients.[46]
Transmission can only occur from people with active — not latent — TB.[1] The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain.[12] The chain of transmission can, therefore, be broken by isolating patients with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can transmit the disease to others.[47] TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis causes TB in cattle
8: Symptoms
Classic features associated with active TB are as follows:
Cough
Weight loss/anorexia
Fever
Night sweats
Hemoptysis
Chest pain
With regard to chest pain, a dull aching consistent with pericardial TB can lead to cardiac tamponade or constriction and presents similarly to congestive heart failure.
Genitourinary symptoms are less common in patients with TB. In women, dysuria, hematuria, and frequent urination may be present. In men, painful scrotal mass, prostatitis, orchitis, and epididymitis may be present.
Signs and symptoms of extrapulmonary TB may be nonspecific. They can include leukocytosis, anemia, and hyponatremia due to the release of ADH (antidiuretic hormone)-like hormone from affected lung tissue.
Elderly individuals with TB may not display typical signs and symptoms of TB infection because they may not mount a good immune response. Active TB infection in this age group may manifest as nonresolving pneumonitis.
Pulmonary tuberculosis (TB)
Typical symptoms of pulmonary TB include a productive cough, fever, and weight loss. Patients with pulmonary TB occasionally present with hemoptysis or chest pain. Other systemic symptoms include anorexia, fatigue, and night sweats.
Skeletal TB
The most common site of skeletal TB involvement is the spine (Pott disease). Symptoms include back pain or stiffness. Lower-extremity paralysis occurs in up to half of patients with undiagnosed Pott disease. Tuberculous arthritis usually involves only 1 joint. Although any joint may be involved, the hips and knees are affected most commonly, followed by the ankle, elbow, wrist, and shoulder. Pain may precede radiographic changes by weeks to months.
Genitourinary TB
Reported symptoms of genitourinary TB include flank pain, dysuria, and frequency. In men, genital TB may manifest as epididymitis or a scrotal mass. In women, genital TB may mimic pelvic inflammatory disease. TB is the cause of approximately 10% of sterility cases in women worldwide and of approximately 1% in industrialized countries.
Gastrointestinal TB
Any site along the gastrointestinal tract may become infected. Symptoms of gastrointestinal TB are referable to the site infected, including the following: nonhealing ulcers of the mouth or anus; difficulty swallowing (with esophageal disease); abdominal pain mimicking peptic ulcer disease (with stomach or duodenal infection); malabsorption (with infection of the small intestine); and pain, diarrhea, or hematochezia (with infection of the colon)
9: Distribution patterns:
Despite the fact that TB rates have declined in both sexes in the United States, certain differences exist. TB rates in women decline with age, but in men, rates increase with age. In addition, men are more likely than women to have a positive tuberculin skin test result. The reason for these differences may be social, rather than biologic, in nature.
Age predilection
Higher rates of TB infection are seen in young, nonwhite adults (peak incidence, 25-40 y) than in white adults. In addition, white adults manifest the disease later (peak incidence, age 70 y) than do nonwhite persons.
In the United States, more than 60% of TB cases occur in persons aged 25-64 years; however, the age-specific risk is highest in persons older than age 65 years.
TB is uncommon in children aged 5-15 years
The estimated sex prevalence for TB varies by source, from no sex prevalence to a male-to-female ratio in the United States of 2:1.
10: Diagnosis and prognosis
Radiography stays in the main place when diagnosis is dealt with. We need to consider a range of other conditions mimicking TB . We will study some of those before we proceed to other diagnostic studies.
TB is well-known for its ability to masquerade as other infectious and disease processes within the human body. For example, congenital TB can mimic congenital syphilis or cytomegalovirus (CMV) infection.
Specific dermatologic considerations in the identification of TB
Differentiate primary-inoculation TB from ulceroglandular complexes and mycobacterioses.
Differentiate TB verrucosa cutis from diseases such as North American blastomycosis, chromoblastomycosis, iododerma and bromoderma, chronic vegetative pyoderma, verruca vulgaris, verrucous carcinoma, verrucous atypical mycobacterial infection, and verrucous lupus vulgaris.
Differentiate miliary TB of the skin (which appears as small, noncharacteristic, erythematous, papular or purpuric lesions) from drug reactions)
Differentiate scrofuloderma from supportive lymphadenitis with sinus-tract formation, such as blastomycosis and coccidioidomycosis.
Differentiate TB cutis orificialis from glossitis, apotheosis, and deep fungal infections.
Differentiate lupus vulgaris from lupoid rosacea, deep fungal or atypical mycobacterial infection, chronic granulomatous disease, granulomatous rosacea, and Wegener granulomatosis.
Differentiate erythema induratum from nodular panniculitides (eg, Weber-Christian disease) and nodular vasculitides (eg, syphilitic gumma, nodular pernio).
Differentiate papulonecrotic tuberculid from other papulonecrotic entities, such as leukocytoclastic vasculitis, lymphomatoid papulosis, papular eczema, and prurigo simplex with neurotic excoriation.
Differentiate lichen scrofulosorum from keratosis spinulosa, lichenoid sarcoid, and lichenoid secondary syphilis.
obtain the following laboratory tests:
Sputum for acid fast smear and culture
Complete blood count (CBC)
Chemistries, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
Alkaline phosphatase
Total bilirubin
Uric acid
Creatinine
HIV serology in all patients with tuberculosis (TB) and unknown HIV status
For congenital TB, the best diagnostic test is the examination of the placenta for pathology, histology, and culture. Mycobacterial blood cultures of the newborn may also be helpful. Treatment may be necessary until placental culture results are negative.
If chest radiography findings suggest TB and sputum smear is positive for acid-fast bacilli, initiate treatment for TB.
Ziehl-Neelsen staining of sputum is a simple 5-step process that takes approximately 10 minutes to accomplish. While highly specific for mycobacteria, this stain is relatively insensitive, and detection requires at least 10,000 bacilli per mL; most clinical laboratories currently use a more sensitive auramine-rhodamine fluorescent stain (auramine O).
Routine culture uses a nonselective egg medium (Lowenstein-Jensen or Middlebrook 7H10) and often requires more than 3-4 weeks to grow because of the 22-hour doubling time of M tuberculosis. Radiometric broth culture (BACTEC radiometric system) of clinical specimens significantly reduced the time (10-14 d) for mycobacterial recovery. Newer broth culture media and systems for isolation are available for use in clinical laboratories based on a fluorescent rather than a radioactive indicator. The indicator is inhibited by oxygen; as mycobacteria metabolize substrates in the tubes and use the oxygen, the tube begins to fluoresce.]
Deoxyribonucleic acid (DNA) probes specific for mycobacterial ribosomal ribonucleic acid (RNA) identify species of clinically significant isolates after recovery. In tissue, polymerase chain reaction (PCR) amplification techniques can be used to detect M tuberculosis -specific DNA sequences and thus, small numbers of mycobacteria in clinical specimens.
Extrapulmonary involvement occurs in one fifth of all TB cases, although 60% of patients with extrapulmonary manifestations of TB have no evidence of pulmonary infection on chest radiograph or sputum culture. Ocular TB can be especially difficult to identify, owing to its mimicry and its lack of accessible sampling; a high index of suspicion is required.
The hallmark of extrapulmonary TB histopathology is the caseating granuloma, consisting of giant cells with central caseating necrosis. Rarely, if ever, are any TB bacilli seen.
Altered mental status, neck stiffness, decreased level of consciousness, increased intracranial pressure, and cranial nerve involvement can indicate tuberculosis meningitis or tuberculoma. TB can directly seed the meninges and, if suspected, performing a lumbar puncture for evaluation of the cerebrospinal fluid is necessary. In addition, a tuberculoma can be substantiated based on an increase in intracranial pressure and computed tomography (CT) scanning/magnetic resonance imaging (MRI).
If vertebral involvement (Pott disease) or brain involvement is suspected, it is important to consider that a delay in treatment could have severe repercussions for the patient (compression of the spinal cord and/or paraplegia); further evaluation is necessary with CT scanning or MRI.
Tuberculin sensitivity
Tuberculin sensitivity develops 2-10 weeks after infection and usually is lifelong.
Multidrug-resistant TB
Symptoms and radiographic findings do not differentiate MDR-TB from fully susceptible TB. Suspect MDR-TB if the patient has a history of previous treatment for TB, was born in or lived in a country with a high prevalence of MDR-TB, has a known exposure to a MDR-TB case, or is clinically progressing despite standard TB therapy. Susceptibilities should be repeated if cultures remain positive after 2 months, even when initial susceptibilities did not reveal any resistance.
Pregnancy
Pregnancy provides an opportunity to screen for TB; all pregnant women can undergo tuberculin skin testing. If skin-testing results are positive, chest radiography can be performed with lead shielding. Chest radiography should not be delayed during the first 3 months of pregnancy in patients with suggestive symptoms.
TB in children
Postnatal TB is contracted via the airborne route. The most common findings of postnatal TB include adenopathy and a lung infiltrate. However, the chest radiographic findings may be normal in infants with disseminated disease.
Chest radiographs in children with TB may show only hilar lymphadenopathy or a patchy infiltrate. Most children with TB can be treated with isoniazid and rifampin for 6 months, along with pyrazinamide for the first 2 months if the culture from the source case is fully susceptible. Gastric aspirates or biopsies are not necessary if positive cultures have been obtained from the source case
Prognosis
Among published studies involving DOT treatment of tuberculosis (TB), the rate of recurrence ranges from 0-14%.[19] In countries with low TB rates, recurrences usually occur within 12 months of treatment completion and are due to relapse.[20] In countries with higher TB rates, most recurrences after appropriate treatment are probably due to reinfection rather than relapse.[21]
Full resolution is generally expected with few complications in cases of non-MDR-TB and non-XDR-TB, when the drug regimen is completed.
Poor prognostic markers include extrapulmonary involvement, an immunocompromised state, older age, and a history of previous treatment
11: treatment, precaution
Isolate patients with possible tuberculosis (TB) infection in a private room with negative pressure (air exhausted to outside or through a high-efficiency particulate air filter). Medical staff must wear high-efficiency disposable masks sufficient to filter the tubercle bacillus. Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 wk of treatment). Unfortunately, these measures are neither possible nor practical in countries where TB is a public health problem.
For initial empiric treatment of TB, start patients on a 4-drug regimen: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Once the TB isolate is known to be fully susceptible, ethambutol (or streptomycin, if it is used as a fourth drug) can be discontinued.
Patients with TB who are receiving pyrazinamide should undergo baseline or periodic serum uric acid assessments, and patients with TB who are receiving long-term ethambutol therapy should undergo baseline and periodic visual acuity and red-green color perception testing. The latter can be performed with a standard test, such as the Ishihara test for color blindness.
After 2 months of therapy (for a fully susceptible isolate), pyrazinamide can be stopped. Isoniazid plus rifampin are continued as daily or intermittent therapy for 4 more months. If isolated isoniazid resistance is documented, discontinue isoniazid and continue treatment with rifampin, pyrazinamide, and ethambutol for the entire 6 months. Therapy must be extended if the patient has cavitary disease and remains culture-positive after 2 months of treatment.
DOT is recommended for all patients. Patients on the above regimens as DOT can be switched to 2- to 3-times per week dosing after an initial 2 weeks of daily dosing. Patients on twice-weekly dosing must not miss any doses. Prescribe daily therapy for patients on self-administered medication.
Pregnancy
Active TB should be treated, even in women in the first stage of pregnancy. Isoniazid, rifampin, and ethambutol may be used. In the United States, pyrazinamide is reserved for women with suspected MDR-TB. Elsewhere in the world, pyrazinamide is commonly used in pregnant women with TB.
Preventive treatment is recommended during pregnancy, especially in the following situations:
Pregnant women with a positive tuberculin skin test result who are HIV seropositive or who have behavioral risk factors for HIV infection but who decline HIV testing
Pregnant women with a positive tuberculin skin test result who have been in close contact with a patient who is smear-positive for pulmonary TB
Pregnant women who have had a documented tuberculin skin test conversion in the past 2 years
Pregnant women are at an increased risk for isoniazid-induced hepatotoxicity and should undergo monthly ALT monitoring while on treatment. This risk continues 2-3 months into the postpartum period. Pyridoxine should also be administered to pregnant women receiving isoniazid. Breastfeeding can be continued during preventive therapy. Many experts recommend supplemental pyridoxine for the breastfed infant.
Lin et al have reported that women diagnosed with TB during pregnancy are at an increased risk of having babies who are of low birthweight and small for gestational age. However, preterm birth was not m Postnatal TB
Many experts increase the treatment duration to 9 or 12 months because of the possible impaired immune system in children younger than 12 months. BCG vaccine is not recommended in infants in the United States but is commonly used around the world.
Tuberculosis in children
Isoniazid tablets may be crushed and added to food. Isoniazid liquid without sorbitol should be used to avoid osmotic diarrhea, causing decreased absorption. Rifampin capsules may be opened and the powder added to food. If rifampin is not tolerated, it may be taken in divided doses 20 minutes after light meals.
Ethambutol is often avoided in young children because of difficulties monitoring visual acuity and color perception. However, studies show that ethambutol (15 mg/kg) is well tolerated and can prevent further resistance if the child is infected with a resistant strain. More common in women with TB
Human immunodeficiency virus
Individuals infected with HIV are at an increased risk for TB, beginning within the first year of HIV infection.[25] Based on historical data, the initiation of antiretroviral therapy (ART) decreases the risk of developing TB in these patients.
Treatment regimens for active or latent TB in patients with HIV infection are similar to the treatment of individuals who are HIV negative, but dose adjustments may be necessary.[43, 44] The most significant differences involve the avoidance of rifampin in patients who are on protease inhibitors. Rifabutin may be used in place of rifampin in such patients.
Patients with HIV and TB may develop a paradoxical response when starting antiretroviral therapy. This response has been attributed to a stronger immune response to M tuberculosis. Clinical findings include fever, worsening pulmonary infiltrates, and lymphadenopathy.
However, in an open-label, randomized trial, Abdool Karim et al concluded that the initiation of antiretroviral therapy during TB therapy significantly improved survival. The investigators looked at results from 642 patients with a TB/HIV coinfection, to determine the optimal initiation of antiretroviral agents.
In the study, the simultaneous initiation of antiretroviral therapy with TB therapy (429 patients) decreased the death rate over a sequential approach (213 patients), with a mortality rate of 5.4 deaths per 100 person-years (25 deaths) compared with 12.1 deaths per 100 person-years (27 deaths), respectively. The relative reduction was 56%. These results provide further impetus for the integration of TB and HIV services.[45]
Swaminathan et al compared intermittent (3 times/wk) antitubular treatment regimens in patients with HIV infection and newly diagnosed TB. Patients received either a 6-month, 4-drug regimen or a 9-month, 4-drug regimen. A significantly lower bacteriologic recurrence rate was observed in the 9-month group. Acquired rifampin resistance (ARR) was high, and neither mortality nor ARR was altered by lengthening Once multidrug-resistant tuberculosis (MDR-TB) is suspected due to relevant history or epidemiologic information and after sputum is cultured with anti-TB drug sensitivity, treatment is implemented. Treatment must be started empirically prior to culture results; once results are known modification of therapy is necessary according to susceptibilities. (Costs are many times higher for the treatment of MDR-TB.)
When initiating treatment, utilize at least 3-5 previously unused drugs in which there is in vitro susceptibility. The fluoroquinolone levofloxacin has been shown to be best suited long-term and should be included in the regimen.
The complexity of MDR-TB treatment lies in the futility of using isoniazid and rifampin. Isoniazid has the strongest antibactericidal action and significantly contributes to making patients rapidly noninfectious; rifampin has unique antibacterial properties against dormant bacilli that are no longer in the active phase of replication.
Never add a single new drug to a failing regimen.
Administer at least 3 (preferably 4-5) of the following medications according to drug susceptibilities: aminoglycosides (ie, streptomycin, amikacin, capreomycin, kanamycin); fluoroquinolone (ie, levofloxacin, ciprofloxacin, ofloxacin); thioamides such as ethionamide or prothionamide; pyrazinamide; ethambutol; cycloserine; terizodone; or para-aminosalicylic acid.
Consider rifabutin substitution for rifampin, as approximately 15% of rifampin-resistant strains are rifabutin sensitive.
Do not use intermittent therapy.
Surgery is recommended for patients with MDR-TB whose prognosis with medical treatment is poor. Surgery can be performed with a low mortality rate (< 3%), with prolonged periods of a chemotherapeutic regimen for more than 1 year after surgery.
All patients should be closely observed for 2 years after completion of treatment, with a low threshold for referral to TB centers.
Clusters of MDR-TB with 7-drug resistance have been reported and have a high infectivity rate.
Successful MDR-TB treatment is more likely in association with such factors as a lower prior patient exposure to anti-TB drugs, a higher number of anti-TB drugs to which the infection is still susceptible, and a shorter time since the first TB diagnosis (indicating a less advanced disease).
Continue treatment for MDR-TB for 18-24 months after sputum culture conversion. The drugs should be prescribed daily (no intermittent therapy), and the patient should always be on DOT. Weekend DOT may not be possible; therefore, giving self-administered oral drugs on Saturdays and Sundays may be reasonable.
In a study by Diacon et al, TMC207 added to standard therapy for MDR-TB reduced the time to conversion to a negative sputum culture compared with placebo and increased the proportion of patients with conversion of sputum culture (48% vs 9%).[46]
The diagnosis of XDR-TB is established with an isolate that is resistant to isoniazid, rifampin, at least 1 of the quinolones, and at least 1 injectable drug. Treatment options for XDR-TB are very limited, and XDR-TB carries a very high mortality rate. TB treatment
12: Policy: in India at federal governmental and at state level, role of international and national institutions WHO
