Mycobacterium avium- intracellulare complex
PKGhatak,MD
Mycobacterium avium-intracellulare complex (MAC) is a combination of two species of Non-Mycobacterium tuberculosis (NMB). In the past, other NMB species were lumped into this complex.
MAC bacteria exhibit characteristics so very similar and produce almost identical human diseases that the diseases cannot be differentiated clinically and only by the use of genome probe tests actual species diagnosis is made with ease.
MAC is ubiquitous in nature, many MACs are present in water, soil, house dust, plumbing, tap water, etc. Both healthy and immunosuppressed people carry MAC in the respiratory and GI tracts and produce no inflammation or diseases. In fact, it is not easy to establish a pulmonary disease due to MAC unless tissue invasion and recovery of MAC are demonstrable in the biopsy tissues. Person-to-person transmission does not happen.
People with immunosuppression are living longer and the incidence of MAC infection is rising. HIV infected patients, until recent years, were devastated by MAC and are still susceptible to M.avium infection. Elderly women are particularly susceptible to M.intercellulare. The actual reason for their susceptibility is not known. It was thought that modesty in earlier English women prevented them to cough in public resulted in retaining sputum in the airways and that was responsible for repeated infections and the development of nodular bronchiectasis. This is known as Lady Windermere syndrome.
In a rare instances, multiple family members develop cervical lymphadenitis by MAC due to congenital deficiency of IFN-y receptor expression or the gene. Patients with gastroesophageal reflux, gastric acid suppression by medications and gastric aspirations are susceptible to M.intercellulare pulmonary infection. Globally MAC is a major problem in poor nations where MTB is common and often MAC are misdiagnosed as drug resistant MTB. In France, New Zealand, and the U.K. MAC incidence is increasing.
Manifestations of MAC infection.
The clinical picture is better described under immunocompetent and in immunosuppressed populations.
In immunocompetent people.
These manifestations are encountered – Cavitary pulmonary infection, Nodal bronchiectasis and Hypersensitive pneumonitis. And cervical lymphadenitis in children.
Cavitary pulmonary infection.
The clinical picture of this entity is similar to M.kansasii infection. The only way to differentiate between the two is to use a newer species identification test like a genome probe test.
Similarly, the clinical pictures of nodular bronchiectasis and hypersensitive pneumonitis are similar to M.kansasii infection.
MAC can infect children. Cervical lymph nodes are commonly infected. In a rare instances, other lymph nodes in the axilla, hila of lungs and groin are infected.
Extrapulmonary MAC infection sites are flat bones, breasts, bone marrow, skin, muscles, brain, and GI tract in immunosuppressed people.
Pulmonary manifestations of MAC.
In immune competent.
Cavitary pneumonia, nodular bronchiectasis, hypersensitive pneumonitis.
In children with cervical lymph nodes.
In immunosuppressed people.
Multi-organ infections besides lungs are bone marrow, spleen, retroperitoneal lymph nodes, kidneys, liver and occasionally brain and meninges.
Diagnosis of MAC.
Chest Radiographs.
The chest x-ray is not sensitive enough to an early diagnosis of MAC. High -resolution-CT scan (HRCT) shows the lesions much more clearly. Fibro-cavitary changes in the upper lung zones. In elderly women fibronodular bronchiectasis and nodules in the right middle lobe. In addition, atelectasis, consolidation, ground-glass opacities on CT appear as a tree in early spring with the emerging buds – Tree-Bud appearance. In hypersensitive pneumonitis, centrilobular nodules, ground-glass opacities, and hyperinflation coalesced alveoli due to trapped air during expiration indicating expiatory bronchial obstruction.
In HIV patients abdominal CT reveals retroperitoneal and periaortic lymphadenitis, enlarged spleen, and liver.
Biopsy.
Infected tissues are biopsied by a method suitable to patients in order to minimize tissue damage by the biopsy process. Commonly bronchoscopic transbronchial lung biopsy is practiced. Other methods are CT-guided needle biopsy, Transthoracic video assisted tissue biopsy and open lung biopsy.
Culture for MAC.
Blood, urine, pus, lung tissue, node biopsy, bone marrow, and liver biopsy tissues are stained by Ziel Nielsen stain for Acid-fast bacteria (AFB) and cultured in rapid growing culture media.
In tissues with only a few AFB Nuclear, acid amplification tests followed by genome probe tests are done.
Histology.
In HIV positive cases inflammatory nodes are few, but AFB is plentiful and appears as sheets of macrophages loaded with AFB.
Cervical lymph nodes.
Both caseating and non-caseating granuloma with sinuous tracts of eosinophilic necrosis and scatted nuclear debris are present. Langhans giant cells surrounding nodules are easily identified and neutrophils are rare and lymphocytes are few. AFB is present in a few numbers.
In immunocompetent patients.
Typical non-caseating granuloma and significant numbers of AFB are present.
Treatment.
Drugs used in Pulmonary tuberculosis (MTB) are generally resistant in MAC cases.
Macrolides are the mainstay of therapy, at minimum three drugs are prescribed for 12 months. The usual protocol includes macrolides. rifamycin and ethambutol. Other drugs with variable effectiveness are clofozinidine, fluoroquinolones, aminoglycosides, and inhaled liposomal amikacin.
Various combinations of drugs are used based on the sensitivity test results and response noted in a patient. From treatment centers to nurses- observed intermittent therapy is used to maximize effectiveness and compliance.
Surgery.
Cervical lymphadenitis is best treated with surgical excision. In general drug treatment is not required.
In resistant pulmonary MAC, lobectomy may be required, in addition to a maximum tolerable dose of drugs.
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