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Table of Contents   
CASE REPORT  
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 194-196
Disseminated Mycobacterium avium intracellulare complex (MAC) disease in a retropositive patient caused by noncompliance of HAART


1 Department of Microbiology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India

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Date of Web Publication3-May-2016
 

   Abstract 

Mycobacterium avium intracellulare complex (MAC) is the most common mycobacterial cause [after Mycobacterium tuberculosis(MTB)] of an opportunistic disease in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients with low CD4+ cell count. We report a case of disseminated MAC disease in a 46-year-old retropositive patient, noncompliant to highly active antiretroviral therapy (HAART), with CD4+ T-lymphocyte count of 10 cells/mm3. MAC was isolated in culture from multiple specimens including bone marrow aspirate, blood culture, and bronchoalveolar lavage (BAL) fluid. The patient was successfully treated with the following second-line antitubercular therapies: clarithromycin, rifabutin, and ethambutol.

Keywords: Highly active antiretroviral therapy (HAART), human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), Mycobacterium avium intracellulare complex (MAC), noncompliance of HAART, nontuberculous mycobacteria (NTM)

How to cite this article:
Dhar K, Shenoy VP, Vishwanath S, Prabhu M. Disseminated Mycobacterium avium intracellulare complex (MAC) disease in a retropositive patient caused by noncompliance of HAART. Ann Trop Med Public Health 2016;9:194-6

How to cite this URL:
Dhar K, Shenoy VP, Vishwanath S, Prabhu M. Disseminated Mycobacterium avium intracellulare complex (MAC) disease in a retropositive patient caused by noncompliance of HAART. Ann Trop Med Public Health [serial online] 2016 [cited 2019 Dec 13];9:194-6. Available from: http://www.atmph.org/text.asp?2016/9/3/194/179100

   Introduction Top


Mycobacterium avium and Mycobacterium intracellulare [M. avium complex (MAC)] are ubiquitous, soil- and water-related, environmental mycobacteria with no interhuman transmission. MAC is the most common mycobacterial cause [after Mycobacterium tuberculosis (MTB)] of an opportunistic disease in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients with low CD4+ cell count.[1] The most serious presentation of MAC/AIDS-related disease is the disseminated disease with multiorgan involvement. There are clinical signs of suspect such as fever of unknown origin, visceral enlargement, and elevated alkaline phosphatase, but the diagnosis of disseminated MAC infection requires the isolation of the mycobacteria (usually blood or bone marrow cultures) and prompt identification through biochemical methods or modern laboratory procedures such as DNA probes.[2] With the advent of a highly active antiretroviral therapy (HAART), the incidence of MAC decreased substantially in the developed countries, but it is still a frequent opportunistic AIDS-related disease in patients without HAART or those on irregular therapy more so in the developing countries such as India.


   Case Report Top


A 46-year-old male from Mangalore having retropositive illness for last 10 years with CD4+ T-cell count of 10/mm 3 and viral load of 125,000 copies/mL on irregular HAART, was admitted to the medicine ward with complaints of fever and cough since 10 days. On examination, vitals were stable while chest auscultation revealed bilateral rhonchi. He had stopped taking previous antiretroviral therapy medications. On three occasions, sputum was sent for the detection of acid-fast bacilli (AFB) by fluorescence microscopy, all of which turned out to be negative for AFB. Then, he showed slight improvement over the next week. However, his hemoglobin level was decreasing from 10.4 mg/dL to 7.8 mg/dL within a week. In view of that bone marrow aspirate as well as bronchoalveolar lavage (BAL) fluid was sent for AFB staining and mycobacterial culture. No AFB was observed by fluorescence microscopy of both BAL and bone marrow aspirate, whereas bone marrow cytology revealed increased histiocytes and 11% lymphocytes with myeloid: erythroid ratio of 6:1 suggestive of HIV associated changes with tuberculosis. Furthermore, bone marrow aspirate was negative for MTBcomplex by nested polymerase chain reaction (PCR) (target gene – IS6110). However, with bone marrow and BAL culture report awaited, he was discharged after 11 days of hospital stay with an advice to take antiretroviral therapy medications – Tab. Duovir (Lamivudine 150 mg, Zidovudine 300 mg) twice a day, Tab. Synthivan (Atazanavir 300 mg, Ritonavir 100 mg) once a day, and Tab. Sulfamethoxazole–Trimethoprim (800 + 160 mg) once a day.

After 1 month, he was once again admitted with similar complaints of fever and cough since past 2 weeks. On examination, vitals were stable, but pallor was present and bilateral rhonchi were heard over bilateral lung fields on auscultation. Chest x-ray [Figure 1] revealed patches over lower zones of bilateral lung fields that are suggestive of pulmonary tuberculosis. The patient's blood sample was sent for mycobacterial culture. Other baseline lab reports were normal. Meanwhile, BAL fluid grew nontuberculous mycobacteria (NTM) by Mycobacteria Growth Indicator Tube (MGIT 960, BD) and the isolate was negative for MPT64 antigen test for MTB complex. The isolate was identified as MAC by GenoType Mycobacterium CM (for common mycobacteria) (Hain Lifescience GmbH, Nehren, Germany). Hence, he was diagnosed to have disseminated atypical mycobacterial infection. In view of that, he was started on clarithromycin 500 mg twice a day, rifabutin 150 mg once a day, and ethambutol 800 mg once a day. He showed clinical improvement during his 2 weeks stay at the hospital, and he was discharged with an advice to continue anti-retroviral therapy and anti-MAC therapy. At the time of discharge from the hospital his CD4+ count was 97 cells/mm 3.
Figure 1: Chest radiograph (before therapy) showing opacities over bilateral lower zones of lung

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One month later, the blood culture grew NTM in BacT Alert MB (bioMerieux) which was once again identified as MAC by GenoType Mycobacterium CM. Besides, bone marrow aspirate also grew the same by conventional culture. While at the follow–up, he was asked to take ART strictly along with the antitubercular drugs. One month after his discharge, his symptoms had subsided and the repeat chest x-ray showed resolved patches over bilateral lung fields [Figure 2].
Figure 2: Chest radiograph (after therapy) showing disappearance of opacities over bilateral lower zones of lung

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   Discussion Top


Environmental mycobacteria or NTM are relatively infrequent agents of human disease, other than that in HIV/AIDS patients.[1] NTM affects mainly HIV-infected patients or predisposed hosts and produce disease in organs with underlying conditions. Specifically, MAC may cause a pulmonary disease resembling tuberculosis (TB) in HIV-infected patients with or without prior lung disorders such as bronchiectasis, chronic obstructive pulmonary disease (COPD), and pneumoconiosis or residual granulomatous lesions produced by TB and mycoses.[3],[4] MAC is the most frequent etiological agent of NTM disease associated with AIDS.[5]

There appears to exist an ecological imbalance between a more aggressive pathogen, such as MTB, and the less virulent MAC. In the developing world, TB jeopardizes the human host and the barrier of more complex methodology for the identification of NTM veils the real incidence rates.[6] Nevertheless, MAC is often identified as the pathogen especially in HIV-infected patients with less than 50 CD4+ cells/μL.[7] Moreover, it is more common with HIV-infected patients who have irregular HAART or discontinued therapy. The prospective risk of MAC bacteremia was approximately 60% within 1 year for the patients with colonization in either the respiratory tract or gastrointestinal (GI) tract.[1] In AIDS patients, MAC disease is a later complication that affects patients with a CD4+ T-cell count less than 50 cells/mm 3.[1],[7] MAC presents as a disseminated and bacteremic disease in which the most typical symptoms include prolonged fever, frequently of unknown origin; fatigue; significant weight loss; abdominal pain; diarrhea; and hepatosplenomegaly.[8],[9],[10] Approximately, 40% of patients will have diarrhea and 20% develop intractable abdominal cramps.[1] In addition, disseminated MAC infection is a major cause of wasting syndrome in patients with AIDS.[1] Karne et al. reported a case of brain abscess caused by MAC in a retropositive patient with CD4+ count of 14 cells/mm 3.[11]

The patient presented in this case report had both bone marrow culture and blood culture positive for MAC that indicates persistent disseminated disease. For HIV positive patients, one of the most common cause of relapsing fever is recurrent MAC disease.[1],[2] The retropositive case discussed here had multiple predisposing factors for having MAC disease notably the noncompliance for HAART and low CD4+ T-cell count. However, in the absence of a positive blood culture in the face of recurrent fever and low CD4+ counts, other possibilities, such as lymphoma or disseminated cytomegalovirus (CMV) infection, should be considered as well.

Many HIV/AIDS patients are not receiving HAART for different reasons in the developing countries such as undiagnosed HIV seropositivity, refusal of therapy, and lack of therapy. Besides, the increase in the incidence of MAC infection among HIV/AIDS patients may be attributed to more effective management of other opportunistic infections previously associated with a high risk of mortality, and with better surveillance, and reporting of successful treatment regimens. As a result of this, more patients with low CD4+ counts are surviving longer, thus increasing the risk of acquiring MAC. Unfortunately, disseminated MAC disease has been shown to be an independent risk factor for the increased mortality rate in HIV/AIDS patients.[5]


   Conclusion Top


As disseminated MAC is a lethal disease in AIDS patients when it is not promptly diagnosed and treated, it is imperative to maintain a high index of suspicion during the management of patients with late-stage AIDS or persistent pyrexia of unknown origin given the proven clinical benefit of prophylactic therapy and available treatment regimens. It signifies the paramount importance of investigating for NTM. Where appropriate, prophylaxis or treatment for MAC should be promptly initiated to improve the quality of life and increase the survival time.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Corti M, Palmero D. Mycobacterium avium complex infection in HIV/AIDS patients. Expert Rev Anti Infect Ther 2008;6:351-63.  Back to cited text no. 1
    
2.
Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al.; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367-416.  Back to cited text no. 2
    
3.
Cassidy PM, Hedberg K, Saulson A, McNelly E, Winthrop KL. Nontuberculous mycobacterial disease prevalence and risk factors: A changing epidemiology. Clin Infect Dis 2009;49:e124-9.  Back to cited text no. 3
    
4.
Ringshausen FC, Apel RM, Bange FC, de Roux A, Pletz MW, Rademacher J, et al. Burden and trends of hospitalisations associated with pulmonary non-tuberculous mycobacterial infections in Germany, 2005-2011. BMC Infect Dis 2013;13:231.  Back to cited text no. 4
    
5.
Horsburgh CR Jr, Selik RM. The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS). Am Rev Respir Dis 1989;139:4-7.  Back to cited text no. 5
    
6.
Horsburgh CR Jr. Epidemiology of Mycobacterium avium complex In: Korvick JA, Benson CA, editors. Mycobacterium Avium Complex Infection: Progress in Research and Treatment. NY, USA: Marcel Dekker; 1996. p. 1-22.   Back to cited text no. 6
    
7.
Chaisson RE, Moore RD, Richman DD, Keruly J, Creagh T. Incidence and natural history of Mycobacterium avium- complex infections in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. Am Rev Respir Dis 1992;146:285-9.  Back to cited text no. 7
    
8.
Benson CA, Ellner JJ. Mycobacterium avium complex infection and AIDS: Advances in theory and practice. Clin Infect Dis 1993;17:7-20.  Back to cited text no. 8
    
9.
Havlik JA Jr, Horsburgh CR Jr, Metchock B, Williams PP, Fann SA, Thompson SE 3rd. Disseminated Mycobacterium avium complex infection: Clinical identification and epidemiologic trends. J Infect Dis 1992;165:577-80.  Back to cited text no. 9
    
10.
Karakousis PC, Moore RD, Chaisson RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infect Dis 2004;4:557-65.  Back to cited text no. 10
    
11.
Karne SS, Sangle SA, Kiyawat DS, Dharmashale SN, Kadam DB, Bhardwaj RS. Mycobacterium avium-intracellulare brain abscess in HIV- positive patient. Ann Indian Acad Neurol 2012;15:54-5.  Back to cited text no. 11
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Correspondence Address:
Vishnu Prasad Shenoy
Department of Microbiology, Kasturba Medical College, Manipal University, Manipal, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.179100

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