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Background: Mycobacterium avium complex (MAC) is an uncommon clinical pathogen, especially in the central nervous system (CNS), and carries a poor prognosis. MAC infections commonly present as immune reconstitution disease (IRD) in HIV patients. Herein, we report a case of intracranial infection caused by MAC in an AIDS patient without disseminated MAC (DMAC) and immune reconstitution inflammatory syndrome (IRIS)., Case Presentation: A 31-year-old HIV-positive male presented us with progressively worsening CNS symptoms, and neuroimaging revealed ring-enhancing lesions. The intracranial lesions worsened after the empirical therapy for toxoplasma encephalitis and fungal infection. Due to the rapid progression of the disease, the patient died. Mycobacterium avium was the only pathogen in brain tissue after cultures and molecular biology tests., Conclusion: MAC infection in CNS is challenging to diagnose in HIV patients. Our findings emphasize that obtaining tissue samples and applying molecular biology methods is essential to help diagnose the patient as soon as possible to receive adequate treatment., (© 2024. The Author(s).)

Abstract: Microorganisms belonging to the Mycobacterium avium complex (MAC) are ubiquitous in the environment, but only a minority of infected persons develop disease. An underlying lung disease or immune deficiency is a prerequisite for clinical manifestation. However, disseminated MAC disease primarily manifests in people living with human immunodeficiency virus (HIV) in the severe immunodeficiency stage with a whole host of clinical symptoms. We present two cases of disseminated M. avium infection in people living with HIV in the stage of severe immunodeficiency. Both patients exhibited distinct disease progression, with the absence of pulmonary symptoms being a common characteristic. The first patient predominantly experienced high fever, accompanied by diarrhea and severe anemia. The normothermia in the second patient was incongruent with the presence of marked cachexia, severe abdominal pain, and magnetic resonance imaging evidence of abdominal lymph node involvement. The causative agent was isolated from both sputum and stools. The patients underwent treatment that comprised aminoglycoside, macrolide, ethambutol, and rifampicin. Although both patients achieved optimal viral suppression of HIV, the immunologic response to antiretroviral therapy was suboptimal. The first patient died in the setting of severe immunodeficiency due to the development of decompensated liver cirrhosis, while the second patient demonstrated a slight reverse course of the disease., (Copyright © 2024 Copyright: © 2024 International Journal of Mycobacteriology.)

Background: Disseminated Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis infections have almost similar clinical presentations but require different therapeutic management. Materials & methods: A duplex PCR was designed based on the sequence variation between the genes encoding catalase-peroxidase (KatG) of M. avium complex and M. tuberculosis , so as to discriminate MAC, M. tuberculosis and mixed mycobacterial (MAC + M. tuberculosis ) infections in HIV patients. Results: An accurate, single-step differential diagnosis of disseminated mycobacterial infections in HIV patients was achieved with specific detection of a single band each for M. avium (120 bp) and M. tuberculosis  (90 bp) and two bands for the mixed (120 and 90 bp) infections. Conclusion: katG gene-based duplex PCR can facilitate quick differential diagnosis of disseminated MAC and M. tuberculosis infections in HIV patients.

A 66-year-old woman with HIV-1 infection recently commenced on antiretroviral therapy (CD4+ 25 cells/mm 3 was referred to the Dermatology Clinic the following month due to a well-demarcated nodule in the extensor surface of the left arm with evident fluctuation but only slight pain on palpation, with no increase in temperature. Surgical drainage was performed with aspiration of yellowish-green exudate, with no characteristic smell. In culture of cutaneous exudate, Mycobacterium intracellulare was isolated. Upon careful review of the laboratory tests that were in progress at discharge, the same agent was isolated in one of the bronchoalveolar lavage cultures. The diagnosis of cutaneous abscess caused by M. intracellulare from hematogenous dissemination of lung infection was made. The patient was treated with clarithromycin, ethambutol and rifabutin for 24 months. M. intracellulare species and Mycobacterium avium constitute the Mycobacterium avium-intracellulare complex (MAC), responsible for the majority of human infections by atypical mycobacteria. They are ubiquitous bacteria and MAC infection mainly affect immunocompromised patients, with M. intracellulare being isolated in <5% of HIV patients with MAC infection. Cutaneous infection is rare and may present clinically with erythematous plaques, chronic ulcers or abscesses. When present, skin involvement is usually secondary to pulmonary infection.

Competing Interests: Competing interests: None declared.

A 37-year-old man with AIDS presented with altered mental status four weeks after stopping his medications for Mycobacterium avium-intracellulare (MAI). He had low CD4 cell count and severe hypercalcemia. Bone marrow biopsy revealed bone marrow infiltration by granulomas positive for acid-fast bacilli and cultures grew MAI. His hypercalcemia continued to worsen with the initiation of MAI therapy but we were able to treat it successfully with pamidronate and calcitonin., (Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: The aim of this study is to differentially identify MAC by PCR in patients with AIDS and disseminated mycobacteriosis., Methods: A cross sectional study was conducted in Mexico to identify MAC by Molecular Biology. Two sets of primers were synthesized: MAV and MIN, for M. avium and M. intracellulare, respectively. Whole-cell DNAs obtained from 29 clinical isolates and clinical serum specimens from other 24 patients with AIDS and disseminated mycobacterial infection were extracted and amplified by PCR with the MAV and MIN primers. The MAV and MIN primers each amplified one highly specific 1.3-kb segment of the homologous DNA, respectively., Results: Twenty-nine DNAs from MAC clinical isolates identified by Gen-Probe AccuProbes were amplified with the MAV primers. Of the 24 clinical samples, 3 were positive for M. avium and 6 for M. tuberculosis., Conclusions: Our results demonstrated that PCR technique could be applied for the differentiation of M. avium and M. intracellulare by specific 16S rRNA primers. In patients with advanced stage AIDS and in whom disseminated mycobacteriosis is suspected, the presence of anemia (even with negative cultures), elevated alkaline phosphatase and a median CD4 count of 15.9/mL, the diagnosis of infection by MAC should be strongly considered; we suggest that in accordance with our findings, a more precise stratification of patients in terms of their CD4 T cell counts is warranted.

To evaluate the existing evidence regarding treatment regimens for Mycobacterium avium complex (MAC), a systematic review of the available therapeutic studies was conducted to assess treatment outcomes. A random-effects meta-analysis was used to assess treatment outcomes. Subgroup analyses were also conducted by separating studies based on each characteristic independently. Twenty-eight trials met the inclusion criteria. Our meta-analysis showed that the estimated pooled treatment success rate for patients with MAC disease was 39 % [95 % confidence interval (CI) 38-41 %]. The rates of failure, relapse, death, and default were 27 % (95 % CI 25-29 %), 6 % (95 % CI 5-7 %), 17 % (95 % CI 15-18 %), and 12 % (95 % CI 11-13 %), respectively. The proportion of patients treated successfully did not differ significantly on the basis of the study characteristics. However, studies with treatment regimens containing macrolides had significantly higher pooled success proportions (42 %, 95 % CI 40-44 %) than that of other studies (28 %, 95 % CI 24-32 %). Substantial heterogeneity in the study characteristics prevented more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. This review underscored the importance of strong patient support and treatment follow-up systems to develop successful MAC treatment programs.

Immune reconstitution inflammatory syndrome is a clinical entity with a broad presentation, described in both HIV and non-HIV-infected patients. We report a case of Mycobacterium avium-complex pericarditis as a rare but life-threatening manifestation of this syndrome in a patient with AIDS.

A 66-year-old man with human immunodeficiency virus (HIV) infection was admitted for treatment of Pneumocystis pneumonia. Upon admission, a tumor mass adjacent to the thoracic descending aorta was revealed on computed tomography. Histology revealed an exudative granuloma with histiocytes packed with numerous acid-fast bacilli. Mycobacterium avium was isolated from the tissue. A genetic examination of the isolates demonstrated this strain to be located in the cluster consisting of strains that cause systemic infection. The patient's baseline CD4+ cell count was 9/μL and the HIV-RNA viral load was 43,800 copies/mL. This case suggests the possibility of a localized onset of disseminated M. avium infection.

Objective: To estimate the prevalence of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium avium (M. avium) infections in HIV-positive patients suspected to have pulmonary and extrapulmonary mycobacterial co-infection using PCR technique., Methods: Totally 50 samples comprising sputum, pleural fluid and CSF taken from HIV positive patients suspected to have mycobacterial infection, were processed. The demographic information and results of acid fast staining and culture were recorded for each patient. The PCR for detecting of M. tuberculosis comprised of specific primers targeting IS6110 gene sequence. For detecting of M. avium, PCR with primers that amplifies the mig gene were used., Results: From 50 samples processed, 45 were sputum (90%), 3 pleural fluid (6%) and 2 CSF (4%). In total, 8 (16%) were culture positive, 7 had positive acid fast staining (14 %) and 13 samples (26%) were positive using PCR technique. All the positive samples were sputum and belonged to patients with pulmonary infection. Of these, 9 were positive for M. tuberculosis (69.2%) and 4 were identified as M. avium (30.8%), which 2 out of 13 positive samples showed mixed infections by both mycobacteria., Conclusions: The PCR shows the highest detection rate (26%) of mycobacteria compared with culture and acid fast staining. The majority of infections were with M. tuberculosis (18%) and this shows the importance of this mycobacterial co-infection in HIV positive patients in the region of study., (Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Mycobacterium avium complex (MAC) is an opportunistic pathogen in AIDS patients and pigs, and causes dissemination through primary intestinal lesions. However, its pathogenesis is not well understood. In this article, we hypothesize that pigs can provide a suitable experimental model of disseminated MAC disease. We compared the initial route of infection, the characteristics of the pathogenic strains, the immunological status of the hosts, and the histological characteristics. The route of infection and infective strains are similar in AIDS patients and pigs. Pigs can respond to infection by the formation of systemic epithelioid granuloma with sufficient cell-mediated immunity. However, there are differences in immunological status and histological features between AIDS patients and pigs. Therefore, pigs might be used as an appropriate animal model because of their good cell mediated immunity triggered by systemic mycobacterial infection. In conclusion, MAC infections in AIDS patients and pigs show similarities in terms of the initial route of infection and the genetic characteristics of the pathogenic strains., (2011 Elsevier Ltd. All rights reserved.)

Pathogenesis by mycobacteria requires the exploitation of host-cell signaling pathways to enhance intracellular survival and persistence of the pathogen. Among patients with end-stage acquired immune-deficiency syndrome, disseminated infection with Mycobacterium avium, a member of the M. avium complex (MAC), is the most common bacterial infection. The virulence and intrinsic multidrug resistance of this pathogen has been attributed in part to its unique cell wall, which is a complex array of hydrocarbon chains containing the arabinogalactan-peptidoglycan mycolic acid core found in all mycobacteria, surrounded by a second electron-dense layer made up, in part, of serovar-specific glycopeptidolipids (GPLs) found only in MAC. Via cell-surface receptors, M. avium, an intra-macrophage (mφ) pathogen, can modulate various host signaling pathways such as the mitogen-activated protein kinase and nuclear factor κB pathways. The modulation of specific mφ signaling cascades can result in the regulation of pro- and anti-inflammatory cytokine production, and the process of phagolysosome fusion. The outcome of this M. avium-host mφ interaction could result in host disease or death of the invading pathogen. This review will focus on the immunomodulation aspects of M. avium pathogenesis as well as the role of GPLs as virulence factors.

An AIDS patient was admitted to a tertiary care hospital in central India with fever, weight loss, breathlessness, night sweats, diarrhoea, BMI 14 kg/m2, Hemoglobin 8 gm% and CD4 counts 120 cells/cumm. His blood culture by BACTEC 460 TB system revealed Mycobacterium avium bacteremia and stool culture grew Mycobacterium avium and mycobacterium wolinskyi.

Duodenal infection by Mycobacterium avium-intracellulare is a common opportunistic disease in HIV-infected patients. Individuals with CD4 counts <50 cells/mm3 are at highest risk. The main symptoms are diarrhea, abdominal pain, weight loss, and fever. Endoscopic examination shows various abnormalities including disseminated nodules that may be yellowish, whitish, or pinkish in color. Other mucosal lesions may be found such as erosion, erythema, or friable edematous aspect. Since these findings are non-specific, it is important to obtain biopsy specimens for histological and microbiological examination. The most common histologic features are atrophic mucosa resembling Whipple's disease with strongly positive PAS staining. The presence of BARR in macrophages is typical of MAI. Diagnosis is based on identification of the bacteria using either conventional culture techniques or polymerase chain reaction (PCR). Differential diagnosis includes other gastrointestinal infections associated with AIDS, i.e., microsporidiosis, cryptosporidiosis, giardiosis, anguillulosis, CMV, and isoporosis. The course of the disease is usually unfavorable even with antibiotic treatment. The purpose of this report is to describe a case of duodenitis due to atypical mycobacterial infection in a 30-year-old woman who was seropositive for human immunodeficiency virus. She was hospitalized due to fever with deterioration of her general condition (more than 10% of body weight loss) and chronic abdominal pain with inflammation. Diagnosis of MAI was confirmed by biopsy and Ziehl-Neelsen coloration. The patient was treated with rifampicine, isoniazide, ethambutol, and pyrazinamide in association with stavudine, lamuvidine and efavirenz. Despite improvement of general condition, fever persisted and the patient died after 40 days of treatment.

Pleural involvement in nontuberculous mycobacterium infection has rarely been reported. We present a case of a patient with advanced AIDS, not on antiretroviral therapy, who presented with massive pleural empyema and splenic and liver abscess secondary to Mycobacterium avium-intracellulare complex. She was a 42-year-old female who was admitted with fever, chills, weight loss, and productive cough of 3 weeks duration. Her pleural fluid cultures were positive for Mycobacterium avium-intracellulare complex, and no other organism was identified. Our patient had good outcome after treatment with antitubercular agents (isoniazid, rifabutin, and clarithromycin).

Background: Mycobacterium avium complex (MAC) often causes disseminated infection in patients at an advanced stage of HIV infection; however, peritonitis associated with disseminated MAC infection is rare., Methods: In this report, we describe five cases of MAC peritonitis in AIDS patients at our hospital, and analyze these cases alongside 11 previously published cases found in the literature., Results: Most of the AIDS patients with MAC peritonitis had CD4 counts of <50 cells/microl and elevated alkaline phosphatase levels. Other than ascites, MAC was also isolated from other sterile and non-sterile sites. Of note, six patients (37.5%) presented with chylous ascites., Conclusions: Despite therapy, MAC peritonitis is associated with a grave outcome.

It can be difficult to establish the clinical significance of the isolation of non-tuberculous mycobacteria (NTM) from the sputum of HIV-infected patients. In this observational study, we have investigated factors associated with having NTM infection. During the period of the study, 10 patients had NTM infection and 14 had NTM colonization. Factors associated with having NTM infections were: CD4 lymphocyte count <50 cells/mL (odds ratio [OR] 10; 95% confidence interval [CI] 1.4-69.3), haemoglobin <11 g/dL (OR 7.2; 95% CI 1.08-47.9), weight loss (OR 9; 95% CI 1.3-63.9), duration of symptoms for more than a month (OR 54; 95% CI 4.2-692.5), the presence of acid fast bacilli (AFB) in sputum (OR 30.3; 95% CI 2.6-348.9) and repeated positive NTM cultures in other sputum samples (OR 4.3; 95% CI 1.6-11.7). In conclusion, we must suspect NTM infection in patients with long-standing symptoms, anaemia, low CD4 lymphocyte count, several positive sputum cultures and when AFB are seen.

Clinical relevance of nontuberculous mycobacteria (NTM) isolated from 180 chronically ill patients and 385 healthy controls in Zambia was evaluated to examine the contribution of these isolates to tuberculosis (TB)-like disease. The proportion of NTM-positive sputum samples was significantly higher in the patient group than in controls; 11% and 6%, respectively (p<0.05). NTM-associated lung disease was diagnosed for 1 patient, and a probable diagnosis was made for 3 patients. NTM-positive patients and controls were more likely to report vomiting and diarrhea and were more frequently underweight than the NTM-negative patients and controls. Chest radiographs of NTM-positive patients showed deviations consistent with TB more frequently than those of controls. The most frequently isolated NTM was Mycobacterium avium complex. Multiple, not previously identified mycobacteria (55 of 171 NTM) were isolated from both groups. NTM probably play an important role in the etiology of TB-like diseases in Zambia.

Data on nontuberculous mycobacterial (NTM) disease in sub-Saharan Africa are limited. During 2006-2008, we identified 3 HIV-infected patients in northern Tanzania who had invasive NTM; 2 were infected with "Mycobacterium sherrisii" and 1 with M. avium complex sequevar MAC-D. Invasive NTM disease is present in HIV-infected patients in sub-Saharan Africa.

Background: Despite the impact of highly active antiretroviral therapy (HAART), mycobacterial infections in patients with AIDS remain a frequent complication. In disseminated cases, both tuberculous and non-tuberculous mycobacterial infections may involve the gastrointestinal system and cause abdominal pain and diarrhea. While there have been cases of small bowel perforation in AIDS patients with Mycobacterium tuberculosis (MTB) infection, no case of bowel perforation in non-tuberculous mycobacterial (NTM) infection has been reported to date., Case Report: We report a case of spontaneous perforation of the terminal ileum in an AIDS patient with disseminated non-tuberculous mycobacterial infection who was responding to HAART., Conclusions: Non-tuberculous mycobacteria can lead to spontaneous bowel perforation in patients with AIDS who are responding to HAART.

Background: Mycobacterium avium-intracellulare (MAI) is a well-described pathogen in patients with acquired immune deficiency syndrome (AIDS). However, peritonitis and severe sepsis as a complication of disseminated MAI is rare. We report a case that represents the first successful use of recombinant human activated protein C (rhAPC) in the treatment of severe sepsis secondary to mycobacterial infection and only the second reported case of MAI peritonitis with no known predisposing factor other than AIDS., Methods: Case report and review of the pertinent literature., Results: A 36-year-old man with AIDS presented to the emergency department with acute-onset right-sided abdominal pain, fever, and chills. Abdominal computed tomography revealed multiple rim-enhancing fluid collections. Despite immediate surgical drainage and debridement and appropriate antimicrobial therapy targeting the non-tuberculous acid-fast bacilli found in intraperitoneal fluid, the patient developed severe sepsis and septic shock. Clinical improvement occurred after infusion of recombinant human activated protein C (rhAPC) and specific antimicrobial chemotherapy directed against MAI., Conclusions: Treatment with rhAPC decreases the mortality rate of bacterial sepsis of abdominal origin and may confer a similar benefit in the treatment of abdominal mycobacterial sepsis.

Disseminated Mycobacterium avium complex (MAC) infection is a severe complication of advanced HIV/AIDS disease. Disseminated infection due to MAC appeared later in the natural history of HIV disease and was an independent predictor of mortality in patients before the extended use of highly active antiretroviral therapy (HAART). The use of combination schemes, including three or four antimicrobial agents followed by secondary prophylaxis and HAARTs, improved the survival and reduced mortality rates. However, subjects who ignore their serological status for HIV, or who are not receiving or do not tolerate HAART, are at high risk of developing disseminated MAC disease. In addition, patients who show a good immunological and virological response to HAART can develop episodes of immune reconstitution inflammatory syndrome associated with MAC, including supurative lymphadenitis and subcutaneous or soft-tissue abscesses. In this article, we describe the epidemiological, clinical, immunological, therapeutic and preventive aspects of MAC infection in HIV-seropositive patients in the pre- and post-HAART era.

The advent of highly active anti-retroviral therapy (HAART) has reduced both the morbidity and incidence of acquired immunodeficiency syndrome (AIDS)-related central nervous system (CNS) diseases. However, some patients seem to suffer paradoxical clinical deterioration after starting HAART, known as immune reconstitution inflammatory syndrome (IRIS). We report a rare case of probable Mycobacterium avium complex (MAC) infection of the brain in a patient with AIDS who had been treated effectively for probable pulmonary and cerebral MAC infection, with both lesions recurring after significant decreases in plasma human immunodeficiency virus type-1 viral load following initiation of HAART. This case appears to represent the first precise clinicopathological description of severe ventriculo-encephalitis in CNS MAC-related IRIS.

Mycobacterium avium complex (MAC) continues to be a challenging problem in some patients with advanced human immunodeficiency virus (HIV) infection despite the availability of potent chemotherapeutic agents. The use of adjunctive immunomodulatory therapy has shown promise in vitro, but there is currently limited supportive clinical evidence [Kemper CA, Bermudez LE, Derenski SC. Immunomodulatory treatment of Mycobacterium avium complex bacteraemia in patients with AIDS by use of recombinant granulocyte-macrophage colony-stimulating factor. J Infect Dis 1998;177:914-20; Kedzierska K, Johnson M, Mijch A, Cooke I, Rainbird M, Roberts S, et al. Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type-1 infected monocytes/macrophages in vitro and in vivo. J Infect Dis 2000;181:390-94]. We report the resolution of MAC disease resistant to traditional therapy, in an HIV-infected individual, following the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Objectives: HIV-infected patients responding to combination antiretroviral therapy (ART) after experiencing severe immunodeficiency may exhibit persistent immune defects and occasionally experience opportunistic infections (OIs) despite increased CD4 T-cell counts. The investigation of immune defects in such patients was examined in this study., Methods: CD4 effector memory T-cell (T(em)-cell) function [assessed by blood cytomegalovirus (CMV) interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) counts] and B-cell dysregulation [assessed by serum immunoglobulin A (IgA) and IgE levels] were examined in 27 patients with increased CD4 T-cell counts after receiving ART for over 2 years. Two of these patients and one other had developed OIs on ART and are described in detail., Results: Serum levels of IgA and IgE were higher than reference intervals (P<0.001) and CMV IFN-gamma ELISPOT counts were lower than those in non-HIV-infected controls (P<0.001) in the HIV-infected patients. Low CMV IFN-gamma ELISPOT counts were associated with high IgA levels (r=-0.5, P=0.01, Spearman's correlation test) and segregated with high IgE levels (P=0.06, Fisher's test). CMV IFN-gamma ELISPOT counts and serum IgA and IgE levels did not change significantly over a median time of 35 (range 8-60) months after the first measurement, whereas CD4 T-cell counts increased. All three patients who experienced OIs had repeatedly low CMV IFN-gamma ELISPOT counts and increased serum levels of IgA and/or IgE., Conclusion: Low CD4 T(em)-cell function and B-cell dysregulation are immune defects that may persist independently of changes in the CD4 T-cell count in HIV-1-infected patients responding to ART and are associated with an increased risk of developing an OI.

Objective: To compare changes in CD4+, CD8+ and total lymphocyte counts after initiation of highly active antiretroviral therapy (HAART) between HIV-infected patients with and without a recent history of Mycobacterium avium complex (MAC) infection., Method: Matched exposed-non-exposed retrospective cohort study., Results: Fifty-one patients with a recent history of MAC infection (MAC+) started a combination of at least three antiretroviral drugs. They were individually matched to 145 patients without any history of MAC infection (MAC-) according to CD4+ T-cell count (+/- 30 cells/mm3), previous experience of antiretroviral treatment, AIDS clinical stage at the time of HAART initiation (baseline), age (+/- 10 years) and gender. MAC+ and MAC- patients presented comparable median levels of total lymphocytes (488 vs 688/mm3, P=0.09), CD4+ (11 vs 16/mm3, P=0.15), CD8+ count (359 vs 386/mm3, P=0.39) and plasma HIV RNA (5.3 vs 5.1 log10 copies/ml, P=0.22) at baseline. After 6 months on HAART, the median increase of CD4+ T-cell count was 28 cells/mm3 (interquartile range [IQR]: 1-63) in MAC+ and 72 cells/mm3 (IQR: 34-120) in MAC- patients (P<0.0001), whereas the percentage of CD4+ T cells was not significantly different between the two groups (P=0.13). Comparable differences were observed for total lymphocytes and CD8+ T cells (P<0.001). The 6 months decline of plasma HIV RNA was not significantly different according to MAC exposure (-1.6 in MAC+ vs -1.8 log10 copies/ml in MAC- patients, P=0.65). Results were confirmed after adjustment for other characteristics than the matching variables and after taking into account potential informative bias due to unbalanced number of deaths between the two groups., Conclusion: MAC infection at the time of HAART initiation is an important deleterious factor for immune reconstitution. A better understanding of the underlying mechanism and an evaluation of additional treatment strategies are necessary to help immune restoration in such circumstances.

Three mycobacterial isolates, one from the blood of an HIV-infected patient and two consecutive isolates from a woman with unknown HIV status, had been identified as belonging to the Mycobacterium avium complex by conventional procedures. In both patients, using genetic analysis procedures such as PCR-restriction enzyme analysis (PRA) of the hsp65 gene, a commercially available reverse hybridization-based assay (INNO-LiPA mycobacteria) and/or sequencing analysis of the 16S-23S internal transcribed spacer (ITS), the presence of Mycobacterium lentiflavum was also demonstrated. At the time of detection, both cases were also infected with M. avium, suggesting an underestimation of infection with M. lentiflavum and co-infection with different Mycobacterium species.

The use of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has been associated with a marked reduction in the incidence of most opportunistic infections. From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count < 100.0 cell/mL were investigated. Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). The TCD4+ count at the time of M. avium bacteremia ranged from 7 cells/microL (average of 48.5 cell/microL), while in M. tuberculosis bacteremia it ranged from 50.0 cells/microL (average of 80.0 cell/microL). The prevalence of M. avium bacteremia in our study follows the expected decline in opportunistic infections observed after the introduction of HAART; however, mycobacteremia by M. tuberculosis still indicates a high prevalence of tuberculosis infection in AIDS patients.

Mycobacterium avium complex (MAC) is a group of ubiquitous and opportunistic bacterial pathogens included on the U.S. Environmental Protection Agency Drinking Water Contaminant Candidate List. The risk of contracting a disseminated MAC infection is primarily limited to the immunocompromised, including those with advanced acquired immunodeficiency syndrome (AIDS). These infections likely result from exposures to MAC-contaminated tap water, food, or soil, although the epidemiologic evidence is insufficient to implicate a specific medium. The objective of this study was to assess tap water exposure to MAC in the U.S. population with advanced AIDS, defined here as having fewer than 100 CD4(+) cells/mm(3) of blood. Using limited data on the detection of MAC and self-reported post-tap treatment practices, two exposure models were developed to simulate the likelihood of exposure to MAC via tap water consumption in this sensitive population. The first model integrated data from studies that described sources of water for consumption and post-tap treatment rates in cohorts infected with human immunodeficiency virus (HIV(+)). The second model used data from a study that categorized the fraction of water intake consisting of tap water that was not further treated. Approximately 1500 individuals with advanced AIDS were estimated to ingest tap water with detectable concentrations of MAC organisms daily. Additional studies on tap-water use in U.S. HIV(+) populations are needed to confirm these findings. Longitudinal and cross-sectional studies on the occurrence of MAC in tap water, particularly in regions with large HIV(+)/AIDS populations, would help address some of the uncertainty in these exposure estimates.

Cutaneous infections with Mycobacterium avium intracellulare (MAI) are uncommon in healthy patients but may arise in those with underlying immunocompromise, including patients with HIV. Their clinical manifestations are protean. We report an AIDS patient with a cutaneous MAI infection that clinically and histopathologically mimicked histoid leprosy, a presentation not previously described in this population.

The role that colonization with Mycobacterium avium plays in the development of disseminated disease is unclear. In this study, we determined whether all M. avium strains isolated from the portals of M. avium infection are capable of crossing the mucosal border and causing infection. The patients in this study were enrolled in AIDS Clinical Trial Group protocol 341. The patients were divided into 3 groups; 2 groups differed in their immunological and clinical risk for M. avium disease. A third group (n=22 patients) had culture-documented disseminated M. avium complex disease at the time of entry in the study. Eight of 22 patients had M. avium isolated from both a colonized site and blood or bone marrow specimens. All 8 patients had distinct M. avium strains; 2 patients had a polyclonal infection. The virulence properties of 13 strains were determined, including invasion of gastrointestinal cells and replication in macrophages. There were significant differences in the virulence properties, and these differences may provide insight into the interplay between microbial pathogenesis and host defense.

From July 1995 to August 1998, mycobacterial blood cultures were obtained from 1032 HIV-infected patients seen at the Centro de Referência e Treinamento de AIDS (CRTA), Hospital São Paulo (HSP), and Centro de Referência de AIDS de Santos (CRAS). Overall, 179 episodes of mycobacteraemia were detected: 111 (62.0%) at CRTA, 50 (27.9%) at HSP, and 18 (10.1%) at CRAS. The frequency of positive cultures declined sharply from 22.6% in 1995 to 6.9% in 1998, consistent with the decrease in opportunistic infections following the publicly funded distribution of highly active antiretroviral therapy. In 1995, mycobacteraemia was more frequently due to Mycobacterium avium complex (59.2%) than Mycobacterium tuberculosis (28.6%), whereas in 1998 the relative frequencies were reversed (28.6 vs. 64.3% respectively), probably justified by the increased virulence of M. tuberculosis and the greater risk of invasive infection in less-immunocompromised patients, including patients unaware they are infected with HIV.

This multicenter, randomized, open-label phase 3 clinical trial compared the safety and efficacy of 3 clarithromycin-containing combination regimens for the treatment of disseminated Mycobacterium avium complex (MAC) disease in persons with acquired immunodeficiency syndrome. A total of 160 eligible patients with bacteremic MAC disease were randomized to receive clarithromycin with either ethambutol (C+E), rifabutin (C+R), or both (C+E+R) for 48 weeks. After 12 weeks of treatment, the proportion of subjects with a complete microbiologic response was not statistically significantly different among treatment arms: the proportion was 40% in the C+E group, 42% in the C+R group, and 51% in the C+E+R group (P=.454). The proportion of patients with complete or partial responses who experienced a relapse while receiving C+R (24%) was significantly higher than that of patients receiving C+E+R (6%; P=.027) and marginally higher than that of patients receiving C+E (7%; P=.057). Subjects in the C+E+R group had improved survival, compared with the C+E group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.83) and the C+R group (HR, 0.49; 95% CI, 0.26-0.92).

Background: We evaluated the efficacy of abdominal ultrasound (US) and fine-needle aspiration biopsy (FNAB) in the diagnosis of disseminated mycobacteriosis (DM) in acquired immunodeficiency syndrome (AIDS)., Methods: Twelve AIDS patients (nine male, three female; age range, 22-43 years) with DM underwent abdominal US within 2 days after admission with 3.5- to 5-MHz convex probes and a 7.5-MHz linear probe. All patients underwent FNAB of one or two enlarged abdominal lymph nodes. Eight patients underwent FNAB of the spleen. The aspirated specimens were stained with acid fast for quick examination and cultured for isolation of mycobacteria., Results: Abdominal US showed enlarged, hypoechoic, round or oval, abdominal lymph nodes (diameter, 10-35 mm; mean, 18 mm) in all patients; splenomegaly (spleen diameter, 14-22 cm; mean, 16.8 mm) in all patients; numerous splenic abscesses (diameter, 3-20 mm) in nine patients; hepatomegaly (right hepatic lobe thickness, 14.5-17 cm) in all patients; small intestinal wall thickening in five patients (maximum bowel wall thickness, 7-15 mm); mild to moderate ascites in six patients; pleural effusion in four patients; bilateral enlargement of the kidneys with hyperechogenicity of the cortex in three patients; and a retroperitoneal tubercular abscess in one patient. No complication occurred after FNAB of lymph nodes and spleens. Fast-acid stain of spleen and/or lymph node FNAB specimens allowed early diagnosis of mycobacteriosis in 12 of 12 cases (100%). Cultures of lymph node aspirates grew mycobacteria in six of 12 patients (50%). Spleen aspirates grew mycobacteria in nine of nine patients (100%). Blood cultures were positive in four of 12 patients (33%). Mycobacterium tuberculosis was diagnosed in six patients and M. avium in five., Conclusion: Abdominal US features can suggest DM in AIDS patients. Spleen and/or lymph node FNAB indicated the specific diagnosis in 100% of patients.

Purpose: To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS)., Study Design: Case report and literature review., Participants: A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis., Methods: The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC)., Results: Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease., Conclusions: This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.

Objective: Evaluate the incidence of mycobacterial disease and the colonization of the respiratory and gastrointestinal tracts by Mycobacterium avium complex (MAC) bacteria in AIDS patients., Inclusion Criteria: HIV-positive individuals with at least one CD(4)(+) count < 100 cells/mm(3)., Exclusion Criteria: Mycobacterial disease and MAC prophylaxis. Stool, sputum, and blood cultures were prospectively obtained every month from September, 1997, to December, 1999. The incidence was calculated using Poisson regression. Survival was estimated by the Kaplan Meier method and the Cox proportional hazard model., Results: We followed-up 79 patients during a median period of 428 days. Blood cultures (n = 742) were negative for all mycobacteria. Positive cultures (25 samples) were obtained from non-sterile sites: Stools (19/703 specimens = 2.7%) and sputum (14/742 specimens = 1.9%). MAC was isolated in 7/703 stool samples (1%) and 1/32 sputum specimens (0.1%). The incidence of patient colonization with MAC was 0.09 /year (CI=0.05-0.18). CD4 counts in patients colonized with MAC were below 100 cells/mm(3) in only 2 out of 8 cases. Restoration of CD(4)(+) counts >100 cells/mm(3) (HR = 0.18; CI = 0.05-0.70) predicted a lower risk of death (P<0.05) but was not protective for MAC colonization (HR=0.52;CI =0.62-4.35, P=0.55)., Conclusion: The absence of DMAC infection in colonized individuals argues in favor of a HAART protective effect against; DMAC; however, restoration of CD(4) counts did not protect patients against MAC colonization.

We describe 3 patients who developed atypical manifestations of Mycobacterium avium complex (MAC) infection >10 months (range, 3-16 months) after attaining sustained CD4(+) T cell counts of >100 cells/microL while receiving antiretroviral therapy and not receiving MAC prophylaxis. The common features of these cases include the degree of immune reconstitution, the unusual locations of the infections, and the absence of a systemic inflammatory response. The low rate of these unusual MAC infections does not warrant continuation of primary or secondary prophylaxis after presumed immune reconstitution.

Sixty-nine blood samples from 47 patients infected with human immunodeficiency virus were analyzed by using PCR to detect Mycobacterium avium. The sensitivity can be up to 95.7%, depending on the detection method used and the number of blood samples analyzed from each patient. The procedure can be helpful in the diagnosis of mycobacterial disease.