Multi-drug-resistant tuberculosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Ammu Susheela, M.D. [3]
Overview
Multi-drug resistant tuberculosis (MDR-TB) is defined as TB that is resistant at least to isoniazid (INH) and rifampicin (RMP). Isolates that are multiply-resistant to any other combination of anti-TB drugs but not to INH and RMP are not classed as MDR-TB.
Historical Perspective
Mycobacterium tuberculosis was first described by Robert Koch in 1882 and in 1970 drug-resistant tuberculosis was first reported. Since then, several drugs and strategies have been implemented to control the disease. Cases in US have decreased, however worldwide MDR-TB is increasing in developing countries.
Classification
Classification of drug resistant tuberculosis is based on drug susceptibility , pathophysiology, clinical classification and molecular classification. According to drug susceptibility it is classified as monoresistance, poly resistance, multidrug resistance, extensive drug resistance and rifampicin resistance. Clinically it is classified as acquired and primary resistance. The restriction fragment length polymorphism helps for molecular classification into unique and cluster type.
Pathophysiology
Tuberculosis is a granulomatous infection tansmitted mainly through droplets and can have pulmonary and extra pulmonary manifestations. Multi drug resistant strains of tuberculosis have been emerging at an alarming rate and they might be developed due to primaryy resistance or acquired resistance. These resistance are mainly through genetic mutations in genes like inhA, katG and rpob genes. These molecular pathophysiology can be detected through pyrosequencing, DNAsequencing and electrophoresis.
Causes
Mycobacterium tuberculosis is the bacterium responsible for tuberculosis. It is an aerobic, non-encapsulated, non-motile, acid-fast bacillus. M. tuberculosis belongs to the Mycobacterium tuberculosis complex, that also includes bacteria, such as M. bovis and M. africanum. The bacterium has a very slow rate of replication, and its genetic variations account for the geographical distribution of different strains, and are involved in drug resistance. M. tuberculosis has tropism for different kinds of human cells, with preference for cells of the lung. It may infect different species, yet human beings are its frequent natural reservoir.
Differential Diagnosis
Pulmonary tuberculosis must be differentiated from other diseases that cause cough, fever, night sweats, hemoptysis and weight loss, such as: brucellosis, bronchogenic carcinoma, Hodgkin lymphoma, bacterial pneumonia, sarcoidosis, mycoplasmal pneumonia.
Epidemiology and Demographics
Risk Factors
Risk factors for multi-drug resistant tuberculosis include exposure to an individual with MDR-TB, previous TB treatment, HIV infection, and a low socioeconomic status.
Screening
Screening for tuberculosis is generally done with using a mantoux tuberculin skin test, also known as a tuberculin skin test or a PPD. The test involves injecting a small amount of a purified protein derivative of the tuberculosis bacterium intradermally, and watching for a reaction in the following days.
Natural history, complications and prognosis
Tuberculosis has been classified as primary and post primary infection. It can have pulmonary and extra pulmonary manifestations as well as severe parenchymal, vascular, pleural and chest wall complications. The post primary infection can be due to a recent infection or reactivation of an old infection. Further multi drug resistant strains can develop through acquired resistance through inadequate treatment / treatment failure as well as slow gradual genetic mutation resulting in primary resistance. These are transmitted to healthy people resulting in emerging multi drug resistant strains. They can be rifampicin resistant, multi drug resistant, extensively drug resistant and totally drug resistant. The more the number of drugs the strain is resistant to , the poorer is the prognosis.
Diagnosis
History and Symptoms
The general symptoms of MDR-TB will be the same as drug suceptible tuberculosis, these include weakness, weight loss, fever, and night sweats. Symptoms of pulmonary tuberculosis include cough, chest pain, and hemoptysis. Tuberculosis is particularly difficult to diagnose in children, as these may not present with common findings.
Physical Examination
A physical examination can provide valuable information about the patient’s overall condition and other factors that may affect how tuberculosis is treated, such as HIV infection or other illnesses. The most common physical findings include fever, decreased breath sounds, tachypnea and tachycardia. Physical findings will depend on the location of the tuberculosis infection.
Laboratory findings
Routine laboratory exams are usually in the normal ranges. The presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates TB disease and a positive culture for M. tuberculosis confirms the diagnosis. Other laboratory test include peritoneal fluid or CSF analysis, urinalysis, and Interferon-Gamma release assays. The Xpert MTB/RIF test is a molecular test that detects the DNA of the M. tuberculosis and resistance to rifampin. The use of this test has increased in the past years.
Chest X-Ray
An X-ray is a very important diagnostic tool in pulmonary tuberculosis. Chest X-ray findings include parenchymal infiltrates, hiliar adenopathy, cavitation, nodules and pleural effusion. The most common location of a pulmonary tuberculosis lesion is the upper lobes.
CT
The majority of patients with pulmonary tuberculosis will have abnormal findings in a chest CT, which include micronodules, interlobular septal thickening, cavitation and consolidation. CT scan is more sensitive than an X-ray to detect lymphadenopathies.
MRI
MRI is used for the assessment of extrapulmonary tuberculosis, such as CNS tuberculosis, osteoarticular tuberculosis, Pott's disease, and parotid gland tuberculosis.
Other Imaging findings
The abreugraphy is a smaller variant of the chest X-ray that allows the identification of lung abnormalities that may suggest the diagnosis of TB. With the decrease of incidence of TB, the abreugraphy is no longer recommended in most countries for low risk populations. However, depending on the screening resources of each country, it may be used for the screening of high-risk groups, such as HIV-positive patients and alcoholics.
Other Diagnostic Studies
Other diagnostic studies that could be performed in a patient with tuberculosis are the adenosine deaminase test and Nucleic Acid Amplification Test(NAAT).