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JAMA. 2002;288:157-158.

MMWR. 2002;51:501-502

Persons with advanced human immunodeficiency virus (HIV)-1 infection are susceptible to disseminated mycobacterial infections. In the United States, most such infections are caused by Mycobacterium avium or M. intracellulare (i.e., M. avium complex [MAC]). In less developed countries, M. tuberculosis is equally or more prevalent than MAC in persons with HIV-1 infection.¹ Other mycobacterial species have been reported to cause disseminated infection in HIV-infected persons, including Simiae-Avium (SAV) group mycobacteria. SAV group organisms share characteristics of M. avium and M. simiae.² Although disseminated (i.e., the isolation of a mycobacterial species from the blood) infection with M. simiae has been reported in HIV-infected persons,^3-6 another distinct species within the SAV group, M. triplex, was characterized in 1996.⁷ Two cases of disseminated infection caused by M. triplex have been reported in HIV-1-positive persons.^8-9 This report describes four HIV-infected patients from Bangkok, Thailand, and Lilongwe, Malawi, who were infected with SAV group organisms. Because different mycobacterial species are not susceptible uniformly to antimycobacterial agents, accurate identification of mycobacterial species causing an infection is crucial for directing appropriate therapy.

These infections were detected during prospective blood culture studies of febrile, adult inpatients in these two countries.^{1, 10} The Bangkok study was conducted at an infectious diseases hospital during February-March 1997¹⁰; the Lilongwe study was conducted at a general hospital during August-September 1997.¹ In both studies, adults (aged 18 years) admitted consecutively with fever (oral temperature 100°F [38°C] in Bangkok and axillary temperature 99°F [37.5°C] in Malawi) were recruited within 12 hours of hospital admission. After informed consent was obtained, patients gave a full medical history and underwent a comprehensive physical examination. Blood was drawn for HIV-1 testing and mycobacterial culture. All mycobacterial isolates were sent to Duke University Medical Center for confirmation and identification. M. tuberculosis complex and M. avium complex isolates were identified by using AccuPROBE (Gen-Probe, San Diego, California) DNA probes and biochemical tests. Isolates of uncommon Mycobacterium spp. (e.g., M. simiae) were sent to North Carolina State Public Health Laboratory and the Mycobacteria Reference Laboratory at CDC for further characterization and confirmation by high performance liquid chromatography analysis of mycolic acids. Personnel at both laboratories read all chromatograms visually. Susceptibilities of the isolates to antituberculous drugs were performed at CDC using methodology established for M. tuberculosis. Of 480 patients evaluated, four (two from Bangkok and two from Lilongwe) were found to have disseminated infection with SAV group mycobacteria, later identified as M. simiae.

Bangkok, Thailand

Both patients had positive serology for HIV-1 antibody. Neither was receiving antiretroviral or antimycobacterial therapy. Patient 1, a man aged 32 years, presented with fever, cachexia, and diarrhea of 3 months' duration. Physical examination revealed oral candidiasis and lymphadenopathy. Patient 2, a man aged 36 years, presented with fever, cachexia, and cough and shortness of breath of 1 weeks' duration. Physical examination revealed lymphadenopathy. Additional laboratory studies on this patient revealed hematocrit 16% (normal: 39%-49%) and positive cerebrospinal fluid cryptococcal antigen. Both patients were treated with broad-spectrum antimicrobials for possible underlying bacterial infection and were discharged from the hospital.

Lilongwe, Malawi

Both patients had positive serology for HIV-1 antibody. Neither was receiving antiretroviral or antimycobacterial therapy. Patient 3, a man aged 28 years, presented with chronic fever and cough of 7 months' duration. Physical examination revealed cachexia and skin lesions. No lymphadenopathy was noted. Patient 4, a man aged 36 years, presented with fever, chronic fever, and diarrhea of 5 months' duration. Physical examination revealed oral candidiasis. No lymphadenopathy was detected. Both patients were treated with penicillin and chloramphenicol for underlying bacterial infection and were discharged from the hospital.

Susceptibility Testing

All four isolates were available for susceptibility testing. These isolates were resistant to all first-line drugs (isoniazid, rifampin, streptomycin, ethambutol, and pyrazinamide) used for treating M. tuberculosis infection and to alternative drugs (e.g., kanamycin and ciprofloxacin) used for treating atypical mycobacteria and multidrug-resistant tuberculosis (MDR-TB).

Reported by:

LB Reller, Clinical Microbiology Laboratory, Duke Univ Medical Center, Durham, North Carolina. LK Archibald, MD, WR Jarvis, MD, Div of Healthcare Quality Promotion; Div of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases; LA Grohskopf, MD, EIS Officer, CDC.

CDC Editorial Note:

Advances in laboratory methodology have enabled more rapid and reliable differentiation of mycobacterial species commonly associated with clinical illness (e.g., M. tuberculosis and MAC), and the identification of new or emerging species (e.g., M. triplex). However, ambiguities in determining specific mycobacteria species might occur in regions of the world where diagnostic resources are limited or not available. In addition, no standard susceptibility testing panel has been established for these organisms. These limitations might lead to difficulties in the clinical management of patients with disseminated mycobacterial infection.

The clinical manifestations of disseminated mycobacterial infection are nonspecific and are not indicative of the infecting species. Therefore, as with other mycobacterial infections, diagnosis and specific therapy should be guided by laboratory testing, including species identification and susceptibility testing whenever possible, rather than clinical findings alone.

The findings in this report are subject to at least three limitations. First, neither CD4 lymphocyte nor HIV-1 viral load data were obtained. However, because each patient had a marker of symptomatic HIV-1 infection (oral candidiasis, Kaposi's sarcoma, or positive cerebrospinal fluid cryptococcal antigen), all probably had clinical evidence of advanced immune deficiency. Second, because these patients had multiple conditions that could have produced their nonspecific symptoms and physical findings, it is unclear whether SAV mycobacteria were the cause of their symptoms. Further study and characterization of the SAV group of mycobacteria and of the clinical illness with which they are associated are required to better ascertain the prevalence and clinical significance of these mycobacterial infections. Finally, no information was available on treatment or postdischarge outcome for these patients.

Awareness of M. simiae and other SAV mycobacteria as potential causes of disseminated infection in patients with AIDS is important for several reasons. Because of the phenotypic similarity between SAV mycobacteria and other mycobacterial species, patients infected with SAV mycobacteria might go unrecognized and be presumed to be infected with other Mycobacterium species (e.g., M. tuberculosis), particularly in resource-poor settings without access to adequate laboratory testing. This might lead to ineffective treatment, because not all species are susceptible to all agents. Also, if these isolates were assumed to be M. tuberculosis, they could be misclassified as MDR-TB.

Because of the lack of data and of clinical experience with M. simiae and other SAV group mycobacteria, the best treatment is unknown. Infections with other mycobacteria, particularly M. tuberculosis, require treatment for prolonged periods with multiple agents to which the organisms are susceptible; not adhering to these principles promotes the development of drug-resistant organisms. Additional investigation is needed to determine whether similar hazards exist when SAV mycobacteria are treated with ineffective agents or otherwise suboptimal therapy.

Acknowledgments

This report is based on data contributed by S Tansuphasawadikul, B Eampokalap, A Chaovavanich, Bamrasnaradura Hospital, Nonthaburi; S Rheanpumikankit, Field Epidemiology Training Program, Ministry of Health, Thailand. P Kazembe, O Nwanyanwu, H Dobbie, Lilongwe Central Hospital, Lilongwe; Ministry of Health, Malawi. LF Turner, North Carolina Dept of Health and Human Svcs, State Laboratory of Public Health, Raleigh, North Carolina.

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