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June 2001: Volume 43, Number 6

Return of the MAC: Risks of Waterborne Mycobacterium avium
by Kelly R. Reynolds, MSPH, Ph.D.

As scientists continue to debate the human health significance of re-growth microorganisms in drinking water, the water treatment industry is being pressured to respond. Opportunistic bacteria (those that primarily infect persons with weakened immunity) are commonly present in source water and water that has been municipally treated and/or treated at the tap. Unfortunately, there's little data available to assess the health risks of opportunistic bacteria and their re-growth potential in various water sources. Furthermore, little is known about how, or if, it's necessary to completely eliminate opportunistic bacteria from drinking water. The following is a review of an opportunistic pathogen of primary concern -- Mycobacterium avium complex (MAC).

Properties of pathogen
There are 32 species of mycobacteria that are pathogenic to humans, including M. tuberculosis. The most commonly encountered mycobacterium pathogens, however, are species of MAC. MAC comprises several bacterial agents and over 20 recognized serotypes including, M. avium, M. avium subspecies paratuberculosis and salvaticum, and M. intracellulare. M. avium subspecies salvaticum causes infections in birds and mammals, especially deer while subspecies paratuberculosis causes a chronic enteritis in cattle and is suspected of causing inflammatory disease in humans. Only M. avium and M. intracellulare are confirmed pathogens in humans.

Many people have MAC populations growing in their stomachs or lungs with no adverse symptoms. In addition, the majority of drinking water source sites harbor MAC organisms. The U.S. Environmental Protection Agency has placed MAC on their top 10 list of waterborne health-related microbes in need of methods development for research on the assessment of health effects, occurrence in water and treatment.

Who is at risk?
Persons most at risk of MAC infections are immunocompromised populations, especially those previously infected with the human immunodeficiency virus (HIV). In HIV positive patients, MAC is the most common bacterial infection, occurring in as many as 43 percent of people within two years of being diagnosed with auto immune deficiency syndrome (AIDS). MAC may cause disseminated infections (spread throughout the body), characterized by night sweats, fever, weight loss, abdominal pain, fatigue, diarrhea and anemia. Disseminated infections usually occur only in advanced HIV illness with T-cell counts below 75 cubic millimeters (cu.mm).

In early-stage HIV disease, MAC may affect single organs, producing localized illness. Pulmonary diseases in the elderly and cervical lymphadenitis (inflammation of the lymph glands in the neck associated with pain and tenderness) in children have also been documented. Although rare, pulmonary disease may occur in non-immunocompromised persons due to MAC.

Infections from MAC aren't reportable diseases, thus little is known about its true incidence in the United States. Studies in the Houston and Atlanta metropolitan areas suggest an incident rate of one in 100,000 persons per year. Despite it's ubiquitous nature, incidence is decreasing among HIV positive patients due to new treatment options. Researchers warn, however, this trend may be altered due to increasing resistance of MAC organisms to anti-microbial agents.

MAC transmission in water
The primary transmission route for MAC hasn't been well defined, although it's now well accepted that the organism is acquired from environmental sources. Consumption of contaminated food or drink, or breathing air with soil particles containing MAC, have all been suggested as possible exposure routes to infection. Water is known to support the growth of MAC, and transmission can occur via contact, ingestion, aspiration or aerosolization of potable water. The risk of person-to-person spread appears to be minor.

MAC organisms are commonly found in bird droppings, soil and natural waters, including marine waters, lakes, rivers, streams, ponds and springs, and are frequently isolated from water distribution systems (piped waters). Occurrence studies of mycobacteria in water have found variable results. M. avium has been found to be present anywhere from less than 1-50 percent of drinking water samples. The infectious dose appears to be anywhere from 10-e4 to 10-e7 organisms. MAC organisms have been found in 69 percent of hospital hot water systems that were tested. A survey of bottled waters, public water supplies, and ice found no mycobacteria in bottled water or cisterns, but 54 percent of the ice samples and 35 percent of the public drinking-water samples from 21 states were positive.[1]

A survey of eight water treatment facilities over 18 months showed the overall, mycobacterial recovery from the systems was low (15 percent of samples, n = 528 water and 55 biofilm) and ranged from 10-to-700,000 colony forming units per liter (cfu/L).[2] Although water treatment substantially reduced the number of mycobacteria in raw waters (by 2-to-4 log units), numbers were substantially higher in the distribution system samples (average of 25,000-fold) than those collected immediately downstream from the treatment facilities. Thus, mycobacteria were growing in the distribution system.

MAC organisms are highly resistant to disinfectants compared to indicator bacteria, i.e., E. coli. Chlorine levels required for a 99.9 percent reduction of M. avium strains are 580-2,300 times greater than E. coli.[3] The bacteria were also highly resistant to monochloramine, chlorine dioxide and ozone. The levels of chlorine routinely used in drinking water treatment are, therefore, unlikely to be effective against MAC organism and may account for their presence in distribution systems. The same study discussed the increased resistance of aggregated bacterial cells, such as the condition likely in biofilm environments common to water distribution systems.

Preventing MAC infections
Diagnosis of MAC disease can be difficult and time consuming, requiring blood cultures and/or cell or tissue extraction from bone, stomach or lungs. The organism grows slowly and results may not be available for weeks. Detection of the organisms is complicated by the overgrowth of other microorganisms in growth media. Treatment is often initiated before definitive diagnosis and includes the use of combined medications such as clarithromycin or azithromycin and ciprofloxacin, ethambutol or rifabutin. High doses are required to keep the infection under control and are often associated with numerous side effects, including nausea, vomiting, diarrhea, rashes and abdominal pain. More severe side effects include hearing loss, eye inflammation, and damage to blood vessels or the liver. Treatment may be continued indefinitely for fear of re-colonization of the organism. For severely immunocompromised individuals, prophylactic treatment may be indicated.

Certain conventional municipal water treatment processes (sand filtration and coagulation-sedimentation, for example) appear to reduce the number of MAC organisms to low levels; however, treated waters are by no means sterile and re-growth in the distribution system and storage tanks is probable. Thus, complete avoidance of MAC organisms is difficult.

Given that MAC is found in most water systems, hospital water supplies, and even bottled water, persons at risk for opportunistic infections are advised to boil their drinking water. Although found on raw fruits and vegetables, MAC bacteria are killed at 176 degrees F, thus normal cooking procedures should eliminate the organism in food items. Fruits and vegetables consumed raw should be thoroughly rinsed and peeled.

Conclusion
Whether the water treatment industry should be concerned about opportunistic pathogens in drinking water is a matter of perspective. On one hand, we're talking about trying to control organisms that are ubiquitous in nature, where water is only a portion of the exposure route to individuals (one study of infected individuals found a much greater prevalence of MAC in the soil of potted plants than in drinking water).[4] On the other hand, large amounts of water are being consumed every day and at a much larger dose than a single contaminated food or soil particle.

In addition, although costly, we may have more practical control over the purity of our water than our food or other environmental exposure routes. Immunocompromised individuals are a growing population in the United States as people are living longer with chronic illnesses. The water treatment industry must consider the threat that opportunistic pathogens pose to immunocompromised individuals and whether a point-of-use device can address their drinking water treatment needs.

References
1. Covert, T.C., et al., "Occurrence of nontuberculous mycobacteria in environmental samples," Applied and Environmental Microbiology, 65(6): p. 2492-6, 1999.
2. Falkinham, J.O., C.D. Norton, and M.W. LeChevallier, "Factors Influencing Numbers of Mycobacterium avium, Mycobacterium intracellulare, and Other Mycobacteria in Drinking Water Distribution Systems," Applied and Environmental Microbiology, 67(3): p. 1225-31, 2001.
3. Taylor, R.H., et al., "Chlorine, chloramine, chlorine dioxide, and ozone susceptibility of Mycobacterium avium," Applied and Environmental Microbiology, 66(4): 1702-1705, 2000.
4. Yajko, D.M., et al., "Mycobacterium avium complex in water, food, and soil samples collected from the environment of HIV-infected individuals," Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology, 9(2): p. 176-82, 1995.

About the author
Dr. Kelly A. Reynolds is a research scientist at the University of Arizona with a focus on development of rapid methods for detecting human pathogenic viruses in drinking water. She holds a master of science degree in public health (MSPH) from the University of South Florida and doctorate in microbiology from the University of Arizona. Reynolds also has been a member of the WC&P Technical Review Committee since 1997.