Tuberculosis (TB) Treatment and Vaccine

What is the treatment for tuberculosis?

A person with a positive skin test, a normal chest X-ray, and no symptoms most likely has only a few TB germs in an inactive state and is not contagious. Nevertheless, treatment with an antibiotic may be recommended for this person to prevent the TB from turning into an active infection. The antibiotic used for this purpose is called isoniazid (INH). If taken for six to 12 months, it will prevent the TB from becoming active in the future. In fact, if a person with a positive skin test does not take INH, there is only a 5%-10% lifelong risk that the TB will become active.

Taking isoniazid can be inadvisable (contraindicated) during pregnancy or for those suffering from alcoholism or liver disease. Also, isoniazid can have side effects. The side effects occur infrequently, but a rash can develop, and the individual can feel tired or irritable. Liver damage from isoniazid is a rare occurrence and typically reverses once the drug is stopped. Very rarely, however, especially in older people, the liver damage (known as INH hepatitis) can even be fatal. It is important therefore, for the doctor to monitor a patient's liver by periodically ordering blood tests called "liver function tests" during the course of INH therapy. Another side effect of INH is a decreased sensation in the extremities referred to as a peripheral neuropathy. This can be avoided by taking vitamin B6 (pyridoxine), and this is often prescribed along with INH.

A person with a positive skin test along with an abnormal chest X-ray and sputum evidencing TB bacteria has active TB and is contagious. As already mentioned, active TB usually is accompanied by symptoms, such as a cough, fever, weight loss, and fatigue.

Active TB is treated with a combination of medications along with isoniazid. Rifampin (Rifadin, rifampicin), ethambutol (Myambutol), and pyrazinamide are the drugs commonly used to treat active TB in conjunction with isoniazid (INH). Four drugs are often taken for the first two months of therapy to help kill any potentially resistant strains of bacteria. Then the number is usually reduced to two drugs for the remainder of the treatment based on drug-sensitivity testing that is usually available by this time in the course of the illness. Current studies are adding a fluoroquinolone (moxifloxacin [Avelox]) medication for a shorter period of time to the regimen. However, data regarding outcomes of this addition are still pending. Streptomycin, a drug that is given by injection, may be used as well, particularly when the disease is extensive and/or the patients do not take their oral medications reliably (termed "poor compliance"). Treatment usually lasts for many months and sometimes for years. Successful treatment of TB is dependent largely on the compliance of the patient. Indeed, the failure of a patient to take the medications as prescribed is the most important cause of failure to cure the TB infection. In some locations, the health department demands direct monitoring of patient compliance with therapy, including requiring the medication only be given to the patient one dose at a time, and requiring the patient to swallow the medication in the presence of the health department personnel (directly observed therapy).

Several new agents are being investigated for the treatment of TB, such as nitroimidazo-oxazine, sutezolid, and delamanid. Bedaquiline (Sirturo) is available in the U.S. for treatment of MDR TB. Treatment of MDR TB often requires multidrug therapy of 18-24 months' duration, which is expensive, toxic, and of limited effectiveness. These newer agents will hopefully improve our ability to treat this disease.

Surgery on the lungs may be indicated to help cure TB when medication has failed, but in this day and age, surgery for TB (multidrug-resistant TB) is unusual. Treatment with appropriate antibiotics will usually cure the TB. Without treatment, however, tuberculosis can be a lethal infection. Therefore, early diagnosis is important. Those individuals who have been exposed to a person with TB, or suspect that they have been, should be examined by a doctor for signs of TB and screened with a TB skin test.

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What is drug-resistant TB?

Drug-resistant TB (TB that does not respond to drug treatment) has become a very serious problem in recent years in certain populations. For example, INH-resistant TB is seen among patients from Southeast Asia. The presence of INH-like substances in the cough syrups in that part of the world may play a role in causing the INH resistance. Drug-resistant cases are also often seen in prison populations. However, the major reason for the development of resistance is poorly managed TB care. This can result from poor patient compliance, inappropriate dosing or prescribing of medication, poorly formulated medications, and/or an inadequate supply of medication. Multidrug-resistant tuberculosis (MDR TB) refers to organisms that are resistant to at least two of the first-line drugs, INH and rifampin. More recently, extensively (extremely) drug-resistant tuberculosis (XDR TB) has emerged. These bacteria are also resistant to three or more of the second-line treatment drugs.

XDR TB is seen throughout the world but is most frequently seen in the countries of the former Soviet Union and Asia.

Preventing XDR TB from spreading is essential. The World Health Organization (WHO) recommends improving basic TB care to prevent emergence of resistance and the development of proper laboratories for detection of resistant cases. When drug-resistant cases are found, prompt, appropriate treatment is required. This will prevent further transmission. Collaboration of HIV and TB care will also help limit the spread of tuberculosis, both sensitive and resistant strains.

Improved techniques of drug susceptibility testing (DST) may optimize strategies for therapy. More effective therapy with the onset of treatment will hopefully stem the tide of increased resistant organisms.

Is there a vaccine against tuberculosis?

Bacille Calmette Guérin, also known as BCG, is a vaccine given throughout many parts of the world. It is derived from an atypical Mycobacterium (a relative of TB) but offers some protection from developing active tuberculosis, especially in infants and children. This vaccination is believed to be important in parts of the world where TB is quite common. This is not the case in the United States, and the vaccine is not routinely administered in the U.S. When BCG has been administered, future PPD and Tine skin tests (tests used to determine if a person is infected with Mycobacterium tuberculosis) remain positive and can cause some confusion when trying to diagnose TB. It is also important to realize that even with a BCG vaccine in childhood, tuberculosis can still occur in an adult exposed to the tuberculosis bacteria, which calls into question the real utility and effectiveness of this vaccination.

A new blood test is now available that can help distinguish between a prior BCG vaccine and a positive PPD due to TB infection (QuantiFERON-TB Gold). This test involves mixing the patient's blood with substances that produce a TB-like immune response. After a period of time, the immune cells, if infected with TB, produce interferon-gamma, a protein produced by the body to defend against an infection. This test, like most other tests, is not perfect, but with the proper clinical information can help distinguish a real TB infection from a positive reaction on the test due to a prior BCG vaccine.

What's in the future for TB?

Conceivably, TB could have been eliminated by effective treatment, vaccinations, and public-health measures by the year 2000. However, the emergence of HIV changed the whole picture. Because of HIV, a tremendous increase in the frequency (incidence) of TB occurred in the '80s and throughout the '90s. This increase in TB happened because suppression of the body's immune (defense) system by HIV allowed TB to occur as a so-called opportunistic infection. With the increasing HIV epidemic in Africa, serious concerns are being raised about the development of MDR TB and XDR TB in this population. Hopefully, control of HIV in the future will check this resurgence of tuberculosis.

The epidemic of HIV and TB has been a deadly combination especially on the African continent. A recent study comparing prophylactic regimens for prevention of active TB in HIV-infected individuals has shown effectiveness, however, the distribution of medication for both of these disease in the third world remains problematic.

Medically reviewed by Robert Cox, MD; American Board of Internal Medicine with subspecialty in Infectious Disease

REFERENCES:

Cuevas, et al. "A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis." PloS Medicine 8.7 (2011).

Cuevas, et. al. "LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis; A Multi-Country Cross-Sectional Evaluation." PloS Medicine 8.7 (2011).

Lawn, et al. "Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test." The Lancet Infectious Diseases 13.4 (2013): 349-361.

Marais, et al. "Progress and challenges in childhood tuberculosis." The Lancet Infectious Diseases 13.4 (2013): 287-289.

Martinson, N.A., et al. "New Regimens to Prevent Tuberculosis in Adults With HIV Infection." NEJM 365 July 7, 2011: 11-20.

McConnell, Hargreaves. "Tuberculosis 2013 Series." The Lancet Infectious Diseases 13.4 (2013): 284-285.

United States. Centers for Disease Control and Prevention. "Guidelines for the Investigation of Contacts of Persons With Infectious Tuberculosis and Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States." MMWR 54(No. RR-17) 2005.

United States. Centers for Disease Control and Prevention. "Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection -- United States, 2010." MMWR 59 (No. RR-5) June 25, 2010: 1-25.

Zumla, et al. "Zero deaths from tuberculosis; progress, reality, and hope." The Lancet Infectious Diseases 13.4 (2013): 285-287.

Reviewed on 4/6/2017 12:00:00 AM

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