Tuberculosis

thumbnail image: Tuberculosis 

Introduction


Tuberculosis is responsible for an enormous burden of disease worldwide, particularly in poorer regions of the world, and where human immunodeficiency virus (HIV) is common. Some of the first clinical trials tested tuberculosis treatments, and thus systematic reviews are core to helping establish the evidence-base. In the past, Cochrane Reviews have helped the World Health Organization clarify the key components of the global directly observed treatment, short-course (DOTs) strategy, have assisted in promoting other approaches to improve adherence, and have evaluated a variety of preventive and treatment strategies. Cochrane Reviews have also helped to clarify aspects of clinical management of the disease, including the use of steroids in tuberculous meningitis; and to identify interventions that don’t work, such as Mycobacterium vaccae immunotherapy. They have also evaluated the addition of new interventions such as fluoroquinolones to existing regimens, and whether nutritional supplementation is effective. The reviews have helped us to understand how treatments and prevention strategies need to be modified in populations where HIV is common.

PREVENTION

Isoniazid for preventing tuberculosis in non-HIV infected persons
Although isoniazid is commonly used for treating tuberculosis, it is also effective as preventive therapy. This review estimates the effect of six- and 12-month courses of isoniazid for preventing tuberculosis in HIV-negative people at increased risk of developing active tuberculosis.

Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV-infected children
Children with human immunodeficiency virus (HIV) are at an increased risk of acquiring tuberculosis. Even with treatment, HIV-infected children with tuberculosis have a worse outcome than children with tuberculosis only. This review evaluates the impact of tuberculosis preventive therapy on tuberculosis incidence and death in HIV-infected children.

Mycobacterium vaccae immunotherapy for treating tuberculosis
Some authorities have advocated Mycobacterium vaccae immunotherapy for treating tuberculosis and other infections caused by mycobacteria. This review evaluates M. vaccae immunotherapy as an adjunct to chemotherapy for people with tuberculosis.

DIAGNOSIS

Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults 
Accurate and rapid detection of tuberculosis and drug resistance are critical for improving patient care and decreasing the spread of TB. Xpert® MTB/RIF assay (Xpert) is a rapid, automated test that can detect both TB and rifampicin resistance, within two hours after starting the test, with minimal hands-on technical time, but is more expensive than conventional sputum microscopy. This review assessed the diagnostic accuracy of Xpert for pulmonary TB (TB detection), both where Xpert was used as an initial test replacing microscopy, and where Xpert was used as an add-on test following a negative smear microscopy result. It also assessed the diagnostic accuracy of Xpert for rifampicin resistance detection where Xpert was used as the initial test, replacing conventional culture-based drug susceptibility testing. The assessment was made in the adult population suspected of having pulmonary TB or multidrug-resistant TB (MDR-TB), with or without HIV infection. Most studies were performed in high TB burden countries.

TREATMENT WITH DRUGS

Rifabutin for treating pulmonary tuberculosis
Rifamycins are an essential component of modern short-course regimens for treating tuberculosis. Rifabutin has favourable pharmacokinetic and pharmacodynamic properties and is less prone to drug−drug interactions than rifampicin. It could contribute to shortening of therapy or simplify treatment in human immunodeficiency virus (HIV)-positive people who also need antiretroviral drugs. This review compares combination drug regimens containing rifabutin with those containing rifampicin for treating pulmonary tuberculosis.

Regimens of less than six months for treating tuberculosis
The World Health Organization recommends six months of treatment in tuberculosis programmes. This review assesses the effects of regimens lasting less than six months compared with longer regimens in the treatment of active tuberculosis.

Interventions for treating tuberculous pericarditis
Tuberculous pericarditis – tuberculosis infection of the pericardial membrane (pericardium) covering the heart – is becoming more common. The infection can result in fluid around the heart or fibrosis of the pericardium, which can be fatal. The review evaluates, in people with tuberculous pericarditis, the effects on death, life-threatening conditions, and persistent disability of six-month antituberculous drug regimens compared with regimens of nine months or more; corticosteroids; pericardial drainage; and pericardiectomy.

Fully intermittent dosing with drugs for treating tuberculosis in adults
The number of people infected with tuberculosis continues to rise worldwide. Rifampicin-containing treatment regimens can achieve high cure rates. Intermittent drug treatment delivered in the community has the potential to improve adherence to treatment. This review compares the effectiveness of rifampicin-containing short-course chemotherapy regimens, given two or three times a week, with similar regimens given daily in adult patients with pulmonary tuberculosis.

Fluoroquinolones for treating tuberculosis
Fluoroquinolones are sometimes used to treat multiple-drug-resistant and drug-sensitive tuberculosis. This review assesses fluoroquinolones as additional or substitute components to antituberculous drug regimens for drug-sensitive and drug-resistant tuberculosis.

Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis
The emergence and spread of multiple-drug-resistant tuberculosis (MDR-TB), caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, is a potential threat to global tuberculosis control. Treatment is prolonged, expensive, more toxic than treatment of susceptible tuberculosis, and often unsuccessful. Experts are still undecided on the management of people exposed to MDR-TB. This review evaluates antituberculous drugs given to people exposed to MDR-TB in preventing active tuberculosis.

Corticosteroids for tuberculous pleurisy
Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent, raising doubt as to whether such treatment is worthwhile. Concern also exists regarding the potential adverse effects of corticosteroids, especially in HIV-positive people. This review evaluates the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion.

Corticosteroids for managing tuberculous meningitis
Tuberculous meningitis, a serious form of tuberculosis that affects the meninges covering the brain and spinal cord, is associated with high mortality and disability among survivors. Corticosteroids have been used as an adjunct to antituberculous drugs to improve the outcome, but their role is controversial. This review will evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis.

Treatment of latent tuberculosis infection in HIV infected persons
Individuals with human immunodeficiency virus (HIV) infection are at an increased risk of developing active tuberculosis. It is known that treatment of latent tuberculosis infection (LTBI), also referred to as tuberculosis preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in HIV-negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified. This review determines the effectiveness of tuberculosis preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected people.

OTHER TYPES OF TREATMENT, INCLUDING NUTRITION

Routine surgery in addition to chemotherapy for treating spinal tuberculosis
Tuberculosis is generally curable with chemotherapy, but there is controversy in the literature about the need for surgical intervention in the one to two per cent of people with tuberculosis of the spine. This review compares chemotherapy plus surgery with chemotherapy alone for treating people diagnosed with active tuberculosis of the spine.

Nutritional supplements for people being treated for active tuberculosis
Tuberculosis and malnutrition are linked in a complex relationship. The infection may cause under-nutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there are no evidence-based nutritional guidance for adults and children being treated for tuberculosis. This review assesses the effects of oral nutritional supplements (food, protein/energy supplements or micronutrients) on tuberculosis treatment outcomes and recovery in people on antituberculous drug therapy for active tuberculosis.

Low level laser therapy for treating tuberculosis
The main treatment for tuberculosis is antituberculous drugs. Low level laser therapy is used as an adjunct to antituberculous drugs, predominantly in the former Soviet Union and India. This review compares low level laser therapy plus antituberculous drugs with antituberculous drugs alone for treating tuberculosis.

DELIVERY STRATEGIES

Reminder systems and late patient tracers in the diagnosis and management of tuberculosis
Reminder systems and late patient tracers as strategies to improve patients' adherence to tuberculosis screening, diagnosis, and treatment are used in some countries, but their effectiveness has not previously been systematically reviewed. This review assesses the effects of reminder systems and late patient tracers on a range of outcomes relating to the diagnosis and management of tuberculosis. These include completion of diagnostics, commencement of treatment in people referred for curative or prophylactic treatment of tuberculosis, completion of treatment in people starting curative or prophylactic treatment for tuberculosis, and cure in people being treated for active tuberculosis.

Directly observed therapy for treating tuberculosis
For tuberculosis treatment, policies have been introduced to encourage adherence to treatment regimens. One such policy is directly observed therapy (DOT), which involves people directly observing patients taking their antituberculous drugs. This review compares DOT with self administration of treatment or different DOT options for people requiring treatment for clinically active tuberculosis or prevention of active disease.

Patient education and counselling for promoting adherence to treatment for tuberculosis
Non-adherence to tuberculosis treatment can lead to prolonged periods of infectiousness, relapse, emergence of drug-resistance, and increased morbidity and mortality. This review assesses whether patient education or counselling, or both, promotes adherence to tuberculosis treatment.

Material incentives and enablers in the management of tuberculosis
Patient adherence to medications, particularly for conditions requiring prolonged treatment such as tuberculosis, is frequently less than ideal, and can result in poor treatment outcomes. Material incentives (given as cash, vouchers and tokens), have been used to improve adherence. This review assesses the effects of material incentives in people undergoing diagnostic testing, or receiving prophylactic or curative therapy, for tuberculosis.

Active case finding in contacts of people with tuberculosis
Tuberculosis is a major global health challenge that is caused by bacteria which is spread by airborne droplets. Mostly patients are identified in high-burden countries when they visit health care facilities ('passive case finding'). Contacts of tuberculosis patients are a high-risk group for developing the disease. Actively screening contacts of people with confirmed tuberculosis may improve case detection rates and control of the disease. This review aims to compare whether active case finding among contacts of people with confirmed tuberculosis increases case detection compared to usual practice.

Acknowledgements: With thanks to Paul Garner for drafting the introduction and comments/edits in 2010 and 2013; and Bridget Jones for supplying the list of reviews and comments/edits for the update in 2013.

Image credit: ISM/Science Photo Library, M270/0274

Date published: 10 March 2010; updated 31 January 2013 with new and updated reviews.

Contact: Cochrane Editorial Unit (editorial-unit@cochrane.org)

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