MYCOBACTERIUM AVIUM INTRACELLULARE INFECTION
Historically, Mycobacterium tuberculosis infection was common throughout the world, particularly in underprivileged societies. Fortunately, the advent of antitubercular regimens dramatically eradicated the illness. A distinct cohort of nontuberculous mycobacterial pathogens was revealed to exist, however. Nontuberculous mycobacterial illness is predominantly caused by Mycobacterium avium-intracellulare (MAC) and Mycobacterium kansasii, with over 140 distinct species identified. Interestingly, before antiretroviral therapy was available for AIDS, MAC infection was more common in developed nations than underprivileged nations; this fact prompted the hypothesis that bacillus Calmette-Guérin vaccination or a history of tuberculosis may confer immunity. Intradermal reactivity rates were demonstrated to be equal in MAC patients in both developed and underdeveloped nations, however. The pathogenesis of the disease is poorly understood, but several mechanisms have been revealed.
Potable soil and water act as the main reservoirs and
surfaces for biofilms that harbor MAC and other non-tuberculous mycobacterial
species. MAC has been isolated from residential drinking water, faucets,
show-erheads, Jacuzzis, water fountains, swimming pools, domesticated farm
animals, foodstuffs, soil composts, and potting mix. Biofilms consist of
complex communities of bacteria, viruses, fungi, protozoa, and other organisms,
all held within a mucous layer of self- secreted polysaccharides, proteins, and
even DNA. MAC may exist within these other host cells within the polysaccharide
matrix, making routine disinfectants ineffective. When protozoa are present on
a biofilm surface, MAC has the opportunity to intracellularly parasitize them.
Host cells provide nutrients and protection form the innate immune system and
antibiotics. The characteristic slow growth allows time for antibiotic
metabolism, so that higher antibiotic concentra- tions are needed to achieve
eradication. Thus infection is slow to develop. However, disease will begin to
ensue once the host immune system begins to phagocytize the infected cells and
ultimately produce symptoms. Inherited and acquired host immune systems have
been implicated. Th1 cell and macrophage pathway abnormalities, primary
immunodeficiency or autoantibodies to interferon-gamma, and lymphopenia due to
hematologic malignant disease or HIV infection are among the mechanisms
elucidated so far. No single cause of infection has been identified in patients
who do not have HIV infection or AIDS. Dissemination of disease ensues via
hematogenous and lymphatic spread.
MAC is routinely aerosolized, promoting pulmonary
infection in individuals with or without preexisting lung disease (e.g., cystic
fibrosis, interstitial lung disease, emphysema). Children may demonstrate
superficial lymphadenitis, particularly along the cervical chain. Soft tissue
and cutaneous infections (e.g., in a wound) occur following direct contact with
the specific reservoir. Immunocompromised individuals, such as those of
advanced age, those with hematologic malignant disease, solid-organ transplant
recipients, those taking immunosuppressive therapy (e.g., anti–tumor necrosis
factor alpha agents), and those with AIDS (particularly those with a CD4 count
< 50 cells/mL) are at increased risk to develop MAC infection and
disseminated disease. Fortunately, MAC has not been demonstrated to be
contagious.
Pulmonary symptoms consist of either a dry or a
productive cough, lethargy, dyspnea, chest discomfort, and, rarely, hemoptysis.
The presence of fever, weight loss, and night sweats may suggest disseminated
disease. Bone marrow infiltration may manifest with leukopenia or anemia.
Lymphatic involvement presents as lymph-adenopathy or hepatosplenomegaly,
sometimes with transaminitis. Intestinal involvement manifests with diffuse,
dull, intermittent abdominal discomfort without evidence of obstruction. AIDS
patients with a CD4 cell count of less than 50 cells/mL may develop acute or
chronic diarrhea.
The cornerstone of diagnosis rests primarily with
mycobacterial culture-specific media from sputum in pulmonary disease or from
other tissue specimens. In disseminated disease with gastrointestinal
involvement, imaging may reveal bowel wall thickening. Endoscopic biopsy is
warranted and may reveal MAC involvement. Infrequently, MAC may present with a
nonspecific peritonitis with or without high-protein ascites; laparoscopic
investigation may be needed in such cases when cytologic studies of the ascites
are inconclusive. Both tuberculosis and MAC may manifest with hepatic lesions
and demonstrate granulomas or caseating histologic findings. Hence, culture is
critical for differentiation. MAC disease causing AIDS cholangiopathy is rare
and has been limited to case reports only.
In pulmonary disease, medication is the first-line therapy; in cases where medical treatment fails or there is isolated disease, surgical resection may be needed. Disseminated disease will only benefit from medical therapy. Early days of macrolide monotherapy promoted drug resistance. Hence, multidrug regimens with typical antitubercular agents (rifabutin, ethambutol, isoniazid) are the mainstay of treatment. Given the potential for drug-drug interactions in HIV patients taking antiretroviral medication, rifabutin is one of the recommended agents. Upon treatment initiation, cultures are taken monthly. Treatment continues until cultures are negative for at least 12 months. Lack of a therapeutic response at 6 months of therapy or a relapse following therapy should trigger repeat mycobacterial culture to assess sensitivity and susceptibility.
