Mycobacterial infections

BACKGROUND

A large group of bacteria, called mycobacteria, can cause infections in humans. These bacteria have waxy cell walls that help protect them against attacks and digestion. As a result, the unique outer coating of mycobacteria makes them difficult to destroy.

The most common types of mycobacterial infections include tuberculosis, leprosy, and mycobacterium avium complex.

Tuberculosis (TB) is a bacterial infection of the lungs that is caused by the microorganism Mycobacterium tuberculosis. Tuberculosis is transmitted through airborne droplets of infected mucus or phlegm (called sputum). Individuals can have the bacteria in their bodies without actually being infected or experiencing symptoms. This is called a latent TB infection. Individuals who have latent TB infections have healthy immune systems that are able to suppress the infection. Patients with latent TB do not require any medical treatment. Only 10% of individuals with latent TB ever develop the infection.

Leprosy is an infectious disease that is characterized by disfiguring skin sores and nerve damage. A mycobacterium, called Mycobacterium leprae, causes leprosy. This bacterium is present in the soil and on some armadillos.

There are two types of leprosy: tuberculoid and lepromatous. Both forms cause skin sores and nerve damage that leads to decreased sensations. However, lepromatous is more severe. Researchers believe that the lepromatous form is contagious and may be transmitted from person to person. The tuberculoid form is not contagious.

Mycobacterium avium complex (MAC) is a bacterial infection that is caused by either Mycobacterium avium or Mycobacterium intracellulare. MAC infections are classified under a subgroup of mycobacteria called nontuberculous mycobacteria (NTM). Because the bacteria that cause MAC are found almost everywhere in the environment, they are present in almost all humans. However, an infection only develops if the person has a weakened immune system. This type of infection is most common in HIV/AIDS patients.

Mycobacterial infections can be successfully treated with antibiotics. However, if left untreated, mycobacterial infections may spread to vital organs and become life threatening. Therefore, individuals should visit their healthcare providers to diagnose and treat an infection as soon as symptoms develop.

CAUSES

Tuberculosis: Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is highly contagious. It is transmitted when a person inhales airborne droplets of mucus from someone with the untreated, active form of the disease. These microscopic droplets may be present after an infected person coughs, sneezes, talks, or laughs.

Leprosy: Individuals can become infected with either form of leprosy after coming into contact with Mycobacterium leprae when they are exposed to soil or armadillos that carry the bacteria. Exposure may occur during gardening, hiking, or other outdoor activities.

The tuberculoid form of leprosy cannot pass from person to person. Instead, it can only be transmitted through direct contact with the bacteria in soil or on armadillos.

The lepromatous form, on the other hand, may be passed from person to person. However, researchers do not consider the disease to be highly contagious. Experts currently believe that the lepromatous form of leprosy is passed from person to person through mucus droplets that are released into the air from the mouth or nose of an infected person. Most cases of transmission occur after close, long-term contact with an infected individual. Individuals are most likely to catch leprosy from someone else if they live with an infected person. This means it is unlikely that an individual will develop leprosy after short-term or casual contact with an infected individual.

Contrary to popular belief, neither form of leprosy can be spread after touching someone who has the disease.

Mycobacterium avium complex (MAC): Individuals with weakened immune systems may develop mycobacterium avium complex after exposure to either Mycobacterium. avium or Mycobacterium intracellulare. These mycobacteria are so common that they are present in almost every human. The mycobacteria are found in water, soil, dust, and food. However, individuals who have healthy immune systems are able to prevent the bacteria from multiplying uncontrollably and causing an infection. Therefore, individuals with weakened immune systems or immune disorders, especially HIV/AIDS patients, have the greatest risk of developing MAC.

SIGNS AND SYMPTOMS

Tuberculosis: Latent tuberculosis (TB) infection is not contagious and causes no symptoms.

Symptoms of active TB may include cough, shortness of breath, inflamed membranes around the lungs (called pleurisy), fever, weight loss, night sweats, chills, and loss of appetite. The disease can cause serious breathing problems, which can be life threatening, especially if left untreated.

Leprosy: The tuberculoid form of leprosy causes a rash, consisting of one or more flat, whitish areas on the skin. Areas that are affected are usually numb because the mycobacterium damages the peripheral nerves, which are located outside of the brain and spinal cord.

Lepromatous leprosy is more disfiguring than tuberculoid leprosy. Lepromatous leprosy typically causes many small bumps (called nodules) or raised rashes on the skin. Symptoms of numbness and muscle weakness are generally much worse in patients who have lepromatous leprosy than patients who have tuberculoid leprosy. As a result of this decreased sensation, patients with lepromatous leprosy often develop blisters and skin wounds on the soles of the feet. Because patients cannot feel pain, these wounds often go unnoticed and eventually progress to disfiguring sores and eruptions.

If left untreated, leprosy may lead to serious complications, such as permanent nerve damage, physical deformities, eye damage that may lead to blindness, erectile dysfunction, infertility (in males), generalized inflammation that may be painful, chronically stuffy nose, and decreased quality of life. Without treatment, the inside of the nose may become damaged and scarred. Eventually, this may lead to complete collapse of the nose.

Mycobacterium avium complex (MAC): MAC infection can be limited to one part of the body, or it may enter the bloodstream and spread throughout the body. When several parts of the body are affected, the condition is typically called disseminated mycobacterium avium complex or DMAC.

In general, common symptoms of MAC include enlarged lymph nodes and fever. Other symptoms may include drenching sweats, diarrhea, weight loss, abdominal pain, fatigue, weakness, shortness of breath, inflamed mammary glands, inflamed muscle tissue, and skin abscess and lesions. The liver or spleen may also be enlarged. A brain abscess may also, causing symptoms such as headache, dizziness, aching neck, confusion, drowsiness, irritability, decreased responsiveness, seizures, and loss of coordination. Patients usually feel tired, weak, and have pale skin because the infection causes low levels of iron in the blood (called anemia), low levels of white blood cells, and thrombocytopenia (low levels of platelets).

The most common complication of DMAC is anemia, which may require a blood transfusion. This is because the bacteria need iron to survive. Depending on the organs involved, DMAC may become life threatening. For instance, if the infection spreads to the lungs, it may cause fatal respiratory failure.

DIAGNOSIS

General: An infection is suspected if a patient has a fever, swelling, and/or pain. Mycobacterial infections are diagnosed after the bacteria are identified in the patient's blood, sputum, skin, or bone marrow.

Tuberculosis: A Mantoux test is the standard diagnostic skin test for tuberculosis. During the test, a small amount of purified protein derivative (PPD) tuberculin is injected under the skin of the patient's forearm. The PPD contains a very small amount of tuberculosis proteins, called antigens. A patient with tuberculosis will have a delayed hypersensitivity reaction to the proteins. After 48 to 72 hours, a healthcare provider checks the arm for a reaction. A positive response is indicated by a hard, raised bump at the injection site.

However, the test cannot determine if the infection is active or latent. Patients with active or latent tuberculosis will have positive test results. The test also cannot tell the difference between a TB infection and a TB vaccination. Therefore, additional tests, such as a chest X-ray, sputum culture, or both, are usually performed to determine if the patient has an active TB infection.

Leprosy: Leprosy is diagnosed after a skin scraping test. During the procedure, a small sample of skin cells are removed from an area of affected skin. The sample is then analyzed in a laboratory. If the Mycobacterium leprae is present, the patient has leprosy.

Once leprosy is diagnosed, a lepromin skin test can be used to distinguish between tuberculoid and lepromatous leprosy. During the procedure, an extract of inactivated leprosy-causing bacteria is injected under the patient's skin. The healthcare provider observes the injection site three days and 28 days after the injection. Patients with tuberculoid leprosy will develop an area of red and swollen skin at the injection site, indicating a positive reaction to the test. Patients with lepromatous leprosy will not experience any reaction to the injection.

Mycobacterium avium complex: Blood and bone marrow cultures are the most sensitive diagnostic tests for MAC. Since bone marrow cultures are more invasive, a blood culture is most often used to make a diagnosis. During a blood culture, a sample of the patient's blood is placed in a special laboratory preparation, and then it is incubated in a controlled environment for one to two weeks. If the disease-causing bacterium is present, a positive diagnosis is made.

A bone marrow culture is an invasive procedure that is only used when all other tests are negative, but the doctor suspects MAC. First, a bone marrow biopsy is performed to obtain a tissue sample. Patients receive sedatives to help them relax, and an anesthetic is injected to numb the skin around the biopsy site. During the biopsy procedure, a needle is inserted into the marrow in the back of the pelvis, and a small sample is removed. The sample is then placed in a special laboratory preparation and incubated in a controlled environment for one to two weeks. If the disease-causing bacterium is present, a positive diagnosis is made. The biopsy site is usually sore for one to two days after the procedure, and bruising may occur. Serious complications may include bleeding and infection.

TREATMENT

General: Mycobacterial infections are curable. They are treated with medications called antibiotics.

Patients should take medications exactly as prescribed. Even if symptoms appear to go away, patients should take all of their medication because there may still be bacteria in the body. Stopping medication early may allow the infection to return. Also, stopping medication early may lead to antibiotic resistance. The few remaining bacteria in the body that survive most of the antibiotic therapy are the most difficult to kill. If the bacteria become resistant to treatment, the medications will no longer be effective if taken in the future. Therefore, antibiotic resistance limits treatment options and increases the risk of a fatal outcome.

Patients should tell their healthcare providers if they are taking any other drugs (prescription or over-the-counter), herbs, or supplements because they may interact with treatment.

Tuberculosis: Patients with latent tuberculosis do not require any medical treatment.

Patients with active tuberculosis typically receive a combination of four different antibiotics: isoniazid (Nydrazid© or INH), rifampin (Rifadin©), ethambutol (Myambutol©), and pyrazinamide.

Depending on the severity of the infection, one or two of the four drugs may be discontinued after a few months of treatment. In general, treatment lasts six to 12 months. After a few weeks of treatment, the individual will not be contagious and symptoms may start to improve. However, medication should not be stopped early.

Medications should be taken on an empty stomach, either one hour before or two hours after a meal, with a full glass of water. Wait at least one hour before taking an antacid, as antacids may interfere with the antibiotics used to treat TB. Common side effects of drugs that are used to treat tuberculosis may include diarrhea, dizziness, drowsiness, gas, headache, heartburn, upset stomach, cramps, and trouble sleeping.

Leprosy: Patients with either type of leprosy receive a combination of antibiotics, called multidrug therapy (MDT). These medications cure the infection, but they do not reverse nerve damage or physical disfiguration that has already occurred. The standard combination is dapsone, rifampin (Rifadin© or Rimactane©), and clofazimine (Lamprene©). Dapsone usually does not cause serious side effects. Rifampin is a stronger drug that may cause more serious side effects that may lead to liver damage. Symptoms of liver damage may include yellowing of the skin or eyes (jaundice) or fatigue.

Other antibiotics have also been used to treat leprosy. Examples include ethionamide (Trecator-SC©), minocycline (Dynacin©, Minocin©, or Myrac©), clarithromycin (Biaxin©), and ofloxacin (Floxin©).

Patients with leprosy may develop sores on their heels, which in severe cases, may lead to decreased tissue on the feet. In some cases, tissue from other parts of the body may be surgically removed from one part of the body, such as the leg, and transplanted to the heels.

Some patients with leprosy may develop a collapsed nose. In such cases, surgery may be performed to reconstruct the nose.

Patients should discuss the potential health benefits and risks of surgery before making a decision about medical treatment.

Mycobacterium avium complex (MAC): In order to control MAC, the patient's immune system must be restored. For instance, all HIV patients who are not taking anti-HIV drugs, called antiretrovirals, should begin treatment to help boost their immune systems.

In general, MAC infections are treated with two or three antimicrobials for life in order to prevent the infection from recurring. These medications are given to both HIV-negative and HIV-positive patients that have MAC infections. Commonly prescribed antibiotics include clarithromycin (Biaxin©), ethambutol (Myambutol©), and azithromycin (Zithromax©). HIV patients who have disseminated (DMAC) infections usually receive a combination of newer macrolide antibiotics (clarithromycin, azithromycin) with ethambutol and rifabutin (Mycobutin©).

INTEGRATIVE THERAPIES

Strong scientific evidence:

Iodine: Iodine is an element that the human body needs to make thyroid hormones. Iodine is commonly used in topical disinfectant preparations for cleaning wounds, sterilizing skin before surgical/invasive procedures, or sterilizing catheter entry sites. Iodine has been shown to help prevent the transmission of bacteria. Betadine solution, for example, contains povidone-iodine. Other topical disinfectants include alcohol and antibiotics, and iodine is sometimes used in combination with these. Commercially prepared iodine products are recommended in order to assure appropriate concentrations.

Reactions to iodine can be severe, and deaths have occurred after exposure to iodine. Avoid iodine-based products if allergic to iodine. Do no use for more than 14 days. Avoid lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), fluid in the lungs, bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate or burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

Probiotics: Probiotics are beneficial bacteria that are sometimes called friendly germs. They help maintain a healthy intestine and aid in digestion. They also help keep harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a course of antibiotics may reduce the adverse effects of antibiotics in the intestinal environment. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics.

Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.

Unclear or conflicting scientific evidence:

Astragalus: In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. One clinical trial suggests that astragalus may help treat active tuberculosis. Further well-designed clinical trials are required before recommendations can be made.

Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid if taking anticoagulants or herbs or supplements with similar effects. Avoid with inflammation (swelling), fever, stroke, organ transplant, or autoimmune diseases. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously if taking blood sugar drugs, diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.

Beta-sitosterol: Beta-sitosterol is found in plant-based foods such as fruits, vegetables, soybeans, breads, peanuts, and peanut products. It is also found in bourbon and oils. Beta-sitosterol has been studied as an adjunctive treatment for active tuberculosis. However, additional studies are needed before a firm conclusion can be made.

Avoid if allergic or hypersensitive to beta-sitosterol, beta-sitosterol glucoside, or pine. Use cautiously with asthma, breathing disorders, diabetes, primary biliary cirrhosis (destruction of the small bile duct in the liver), ileostomy, neurodegenerative disorders, diverticular disease (bulging of the colon), short bowel syndrome, celiac disease, or sitosterolemia. Use cautiously with a history of gallstones. Avoid if pregnant or breastfeeding.

Chlorophyll: Chlorophyll is a type of protein that is responsible for the green pigment in plants. Preliminary evidence suggests that chlorophyll intake during chemotherapy treatment in patients with tuberculosis may improve immune parameters and free radical indices, such as malonic dialdehyde. Additional study is needed in this area.

Avoid if allergic or hypersensitive to chlorophyll or any of its metabolites. Use cautiously with photosensitivity, compromised liver function, diabetes, or gastrointestinal conditions or obstructions. Use cautiously if taking immunosuppressant agents or antidiabetes agents. Avoid if pregnant or breastfeeding.

L-carnitine: A preliminary study suggests that the antibiotic properties of acetyl-L-carnitine may help patients with tuberculosis fight against the infection. Additional study is needed to confirm these findings.

Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, high blood pressure, alcohol-induced liver cirrhosis, or diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.

Thymus extract: Thymus extracts for nutritional supplements are usually derived from young calves (bovine). Although inconclusive, preliminary evidence suggests that thymus extract may improve effectiveness of antibacterial therapy in patients with active tuberculosis. Well-designed clinical trials are required before recommendations can be made

Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to the potential for exposure to the virus that causes "mad cow disease." Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid with thymic tumors, myasthenia gravis (neuromuscular disorder), or untreated hypothyroidism. Avoid if taking immunosuppressants or hormonal therapy. Avoid if pregnant or breastfeeding. Thymic extract increases human sperm motility and progression.

Zinc: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. A few studies have examined the efficacy of zinc treatment in leprosy. Studies of zinc taken by mouth report positive results, while one study of topical zinc reports negative results. Further research is needed before a conclusion can be drawn.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used since studies cannot rule out the possibility of harm to the fetus.

PREVENTION

Immune system health: Individuals who have strong immune systems are less likely to acquire infections. Healthcare professionals recommend eating a balanced diet that consists of plenty of fresh fruits and vegetables. Adequate amounts of sleep and exercise regularly also help keep the immune system healthy.

HIV/AIDS patients should take anti-HIV medications exactly as prescribed. These medications suppress the virus and help boost the immune system.

Avoid/minimize exposure: Individuals should also avoid or minimize contact with individuals who have active tuberculosis. Individuals should avoid close, long-term contact with others who have lepromatous leprosy. Patients should also avoid touching armadillos because some carry Mycobacterium leprae. For this reason, individuals should also avoid eating undercooked armadillo.

Practicing good hygiene and regularly washing the hands with soap and water may help reduce the risk of acquiring infections.

Prompt treatment: Patients who have symptoms of mycobacterial infections should visit their healthcare providers as soon as possible. Patients who receive prompt treatment are less likely to experience serious complications.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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