Tuberculosis: epidemiology, transmission, and treatment

Tuberculosis

Prevalence and Statistics. In the early part of the past century, one in every 5 persons in the U.S. had active tuberculosis or TB, the leading killer of the period and referred to as the "captain of all men of death (Jerant 2000)." Public health authorities and increased public awareness dramatically reduced the incidence by almost 75% from 1953 or to only 9.3% for every 100,000 population in 1985. But at the start of 1986, figures went up again at 10.5 cases per 100,000 people by 1992. The new resurgence was attributed to the emergence of the human immunodeficiency or HIV / AIDS epidemic, the entry of large waves of immigrants from countries with high prevalence of tuberculosis, an increase in multi-drug-resistant myco-bacterial organisms and the decline in the efficiency of local TB control programs (Jerant). In addition to those whose immunity was compromised, at-risk groups also increased in number and these included minorities, the poor, alcoholics, immigrants from Third-World countries, prisoners, the aged, nursing home residents and the homeless (Harisinghani 2000).

This incidence of M. tuberculosis in the U.S. has steadily declined since 1992 and has remained significantly low to this time (Martin and Lazarus 2000). Further reductions on the level, however, appeared feasible only along with global efforts to eradicate the disease in potential reservoir (Jerant 2000). In the meantime, M TB continues to plague some Asian and sub-Saharan African countries, which have more than 300 cases per 100,000 population. Almost up to 50% of those infected with HIV / AIDS are co-infected with M. tuberculosis. Thus, tuberculosis continues to rise and afflict the rest of the world, especially developing countries, where pulmonary TB is still common particularly among the socio-economically disadvantaged population, the aging groups, the chronically debilitated and prisoners (Karam). It is said to be present in one-third of the world's population, with approximately 8 million new cases and 2.6 to 2.9 million succumbing to it every year around the world (Martin and Lazarus). The World Health Organization predicted that close to 12 million cases shall have developed each year by 2005.

Diagnosis, Symptoms, Features. Tuberculosis can affect any organ system and become very serious if left untreated. It tends to progress from its primary site and develops symptoms similar to those of other diseases (Harisinghani 2000). Its two types are the primary pulmonary TB and the post-primary TB. With the use of radiography, Primary TB manifests as parenchymal disease, lymphadenopathy, pleural effusion, military disease, or lobar or segmental atelectasis, while post-primary TB initially manifests as a patchy, ill-defined segmental consolidation. Radiographic methods, such as computed tomography or CT and magnetic resonance imaging or MRI can reliably detect tuberculous spondylitis, tuberculous arthritis, gastrointestinal and genitourinary tuberculosis and TB of the central nervous system. Early and accurate diagnosis and prompt and appropriate therapy reduce morbidity (Harisinghani). Primary care physicians make the significant and critical first steps in containing the incidence and the emergence of drug resistance to TB (Martin and Lazarus 2000).

A tuberculosis, M bovis and M. africanum are microbes that comprise the Mycobacterium tuberculosis complex that may cause TB in human beings. A diagnosis of "tuberculosis infection" is made after a positive TB skin test is made without evidence of active disease (Martin and Lazarus 2000), while a "tuberculosis disease" diagnosis is made for cases of positive acid-fast smear or culture for M. tuberculosis or radiographic and clinical presentation of TB. The traditional diagnosis of tuberculosis, made on the basis of clinical findings and radiographs and confirmed by findings of sputum or tissue smear tests, has remained the gold standard. But the introduction of DNA probes, polymerase chain reaction or PRC and the liquid media have made more sensitive and faster diagnosis possible, although increased sensitivity does not always mean or result in increased specificity.

Primary TB infection usually starts in the lower lobes after droplets of the nuclei have been inhaled. It can occur in almost any organ during the first weeks of infection, during which there are minimal or no symptoms. These first signs and symptoms include fever, dry and scant sputum and, at times, retrosternal pain or erythema nodosum (Martin and Lazarus 2000). Clinical pneumonia occurs in 5-10% of afflicted adults and higher among children and HIV / AIDS sufferers. Secondary TB is a reactivation of the disease that accounts for 90% of those not simultaneously infected with HIV / AIDS. The M. tuberculosis microbes tend to stay dormant and reactivate after primary infection and, in early stages, it has no symptoms or signs. TB is suspected with protean manifestations, especially when there is extra-pulmonary involvement or when the patient suffers from fever of unknown origin, night sweats or unexplained loss of weight. A study conducted in British Columbia identified and summarized the TB symptoms of 142 adult and 76 elderly subjects as cough, 77%; weight loss, 62%; fever, 49%; night sweats, 45%; non-respiratory complaints, 44%; chest pains, 33%; dyspnea, 29%; hemoptysis, 25%; anorexia, 24%;.chills, 19% and no symptoms, 7%. Persons carrying the M. tuberculosis microbes, which develop generally, are quite capable of spreading the infection. When diagnosed, one such person will exhibit a raised level of sedimentation rate, marked leukocytosis, hyponatremia and hypercalcemia (Martin and Lazarus).

Chest films of a person with Primary TB will show a lobar infiltrate, characteristically with ipsilateral hilar adenopathy (Martin and Lazarus 2000), often as a consequence of adenitis. In a few patients, primary M. TB may progress and result in pleurisy and pleural effusion, progressive caseous pneumonia, extensive bronchopneumonia or a hematogenous spread. Studies revealed that primary M. TB is not always or initially recognizable on chest films in more than half of all hospitalized adult TB cases.

On the other hand, chest radiograph findings of a patient with secondary TB will show fibronodular changes, often in the upper lobes, or an apparent cavity or volume loss (Martin and Lazarus 2000). One cause of a misdiagnosis is the presence of granulomatous changes or calcifications without first ruling out M. tuberculosis. Reactivation of the disease is suspected or arrived at with the appearance of lower-lobe infiltrates, adenopathy, pulmonary masses, isolated or associated pleural effusion, pneumothorax, alveolar fillings or other respiratory distresses.

Chest radiograph is used in combination with the tuberculin skin test in detecting TB (Martin and Lazarus 2000). There have been attempts to develop a sensitive and specific serologic assay for M. tuberculosis for many decades, although one has remained elusive. A suitable procedure will be particularly helpful in detecting M. tuberculosis in children and adult patients with extra-pulmonary infection or when there are problems obtaining specimens. The standard skin test is the Mantoux test, which uses an injection of 5 TU of purified protein derivative tuberculin, usually.1 ml and made intra-dermally. The induration is assessed 48 to 72 hours later. Records showed that approximately 20% of patients with active TB could have negative skin tests and that some populations could have higher incidence of false negative skin tests. Negative skin tests would not rule TB out and a positive skin test alone would not establish its presence.

Computed tomography or CT is more sensitive than x-ray in detecting cavities, lymphadenopathy, military disease, bronchiectasis, bronchial stenosis, bronchopleural fistula and pleural effusion (Martin and Lazarus 2000). It is specifically useful when there are no available chest films or the chest findings are inconsistent as guide for diagnostic evaluations, such as bronchoscopy, extensive fibrosis, scarring or post-surgical changes. High-resolution CT or HRCT, on the other hand, can detect occult abscesses, cavities and the extent of a pleural disease. Another method, magnetic resonance imaging or MRI, is also a preferred mode for diagnosing extra-pulmonary ailments, such as skeletal and intracranial TB.

The greater effectiveness of HRCT was the subject of a study, involving 102 patients whose x-ray findings suggested pulmonary TB (Karam) and who were subjected to HRCT. The subject patients were enrolled under the cross-sectional study at the Maseeh Daneshvary Hospital chest clinic from February to November 1999. A questionnaire was prepared as an information gathering tool and combined with medical records of signs and symptoms and x-ray findings and laboratory results (Martin and Lazarus 2000). An HRCT was performed and then the patients were admitted into the hospital for further tests and workup. The criteria for the final diagnosis were positive smear and culture results for tuberculosis bacilli, positive smear and/or BAL culture results and positive pathologic TBLB results

HRCT findings showed that 74.5% of them had active PTB. Further clinical tests confirmed the disease in 52 patients or 51% of the total. HRCT also confirmed the centrilobular nodule and "tree-in-bud" signs of their earlier diagnosis by x-ray. HRCT's sensitivity was 96% and the negative predictive value was placed at 93%. The study concluded that HRCT is powerful and reliable in diagnosing TB and can be used even before obtaining myco-bacteriologic results (Karam).

All the patients under study were subjected to an HRCT with Siemens Somatom Plus CT scanner and with the use of contrast media selectively administered in assessing the mediastinum in patients exhibiting the pathology (Martin and Lazarus 2000). From the lung apices to the hemi-diaphragms, 1.5-mm thick sections were taken at 10-mm intervals. The images were prospectively reconstructed with the use of a high-resolution bone algorithm in diagnosing the lung lesions. The HRCT results were then compared with the results of clinical and para-clinical work-up on the patients. The analysis and comparison of rank values were performed using the chi-square P-values less than 0.05, and the sensitivity, specificity, positive and negative predictive value were likewise computed.

Results showed that 61 of the patients were negative for sputum smear and culture, 9 were positive for both, 5 negative for sputum smear and culture positive and 27 diagnosed according to BAL and TBLB results (Martin and Lazarus 2000, Karam). All of the patients had x-ray or chest radiographs suggesting active PTB through infiltration or cavitation in the upper lobes. HRCT findings concluded that 76 of the patients or 74.5% had active PTB who required work-up confirmation and established a strong positive correlation. The sensitivity of HRCT was placed at a high 96%. Binomial tests were also performed between the final diagnosis and each characteristic "tree-in-bud" and centrilobular appearances radiologic manifestation in determining the diagnostic yield of each characteristic radiologic manifestation obtained from the CT scan. Analysis revealed that neither was individually diagnostic, but their combination accurately confirmed a diagnosis of PTB (Martin and Lazarus, Karam).

Radiography or x-ray in conjunction with skin testing is the standard initial screening method not only when results seem unreliable, the skin test reading is impractical or when there are significant risks of transmission in undiagnosed cases as in institutional settings, like hospitals, jails and long-term facilities (Leung 1999).

Post-primary TB is usually a disease of adolescents and adults, the earliest findings being a heterogeneous, poorly marginated opacity in the apical or posterior portion of the upper lobes. In 40% of cases, chest x-rays revealed cavitation, particularly in cases complicated with extensive fibrosis and structural distortion (Martin and Lazarus 2000, Karam). The most common complication of tuberculous cavitation is endobronchial spread, which is radiographically detectable at 19% but up to 98% by HRCT. In some cases, HRCT may detect indicators of active disease not intercepted or captured by chest radiographs. The higher level of sensitivity of the HRCT may lead to prompt and accurate diagnosis even while microbiology results are pending.

Treatment - Latent tuberculosis infection is usually indicated, whatever the patient's age and for patients who belong to the high-risk groups. There are no standard recommendations for patients in the lower-risk groups but health care workers weigh the benefits against the risks, especially for patients older than 35 (Jerant 2000). Pregnant women with PTB are usually subjected to treatment until after delivery, but those belonging to the high-risk groups or recently infected are often given isoniazid as soon as the active disease is excluded (Jerant). Usual dosage is 5-300 mg isoniazid per kilogram body weight a day for nine months. The nine-month program is preferred to the previous six months' treatment schedule on account of the findings of randomized trials among HIV / AIDS-negative patients. The findings showed that treatment for 9 months was more effective than 6 months. A regimen of 12 months also showed minimal benefit. A twice weekly dosage also seemed acceptable when compliance with the daily dosage becomes difficult or questionable.

The nine-month treatment regimen already has stated advantages, but the six-month regimen exhibited protection and appeared superior in certain tests, which used placebo in HIV / AIDS-negative and HIV / AIDS-positive patients (Jerant 2000). In view of the wide variations of patient responses and compliance and local health department resources, health authorities recommend the six-month instead of the nine-month regimen if the six-month treatment would produce more favorable outcomes and prove more cost-effective. These authorities and the American Academy of Pediatrics, however, stress on the nine-month duration of treatment for children. Pyridoxine or hexa-betalin is often prescribed at a dosage of 10-50 mg a day to reduce the likelihood of drug-related peripheral neuropathy with the use of isoniazid for all children six years and older. Pyridoxine is likewise advised for patients with neuropathic conditions, such as diabetes, alcoholism and malnutrition, pregnancy and for patients on anticonvulsant therapy.