Mycobacterium Avium Meningitis in HIV Patients in North India

E ditor: Central nervous system (CNS) infections caused by nontuberculosis mycobacteria (NTM) are rare. They may manifest as meningitis, meningoencephalitis, and occasionally as encephalitis or abscesses. ^1,2 Mycobacterium avium has been implicated as the most common NTM responsible for CNS infections. ³ The data on NTM infections from the developing countries are scanty as M. tuberculosis is usually incriminated as the causative organism for most mycobacterial infections due to lack of proper identification to the species level. Since the improper diagnosis leads to adverse treatment outcomes, there is a need to look for M. avium infections in immunocompromised patients presenting with mycobacterial infections at extrapulmonary sites such as the CNS. We have already standardized a multitargeted polymerase chain reaction (PCR) (MPCR) using primers specific for M. tuberculosis and M. avium. ⁴ Evaluation of the MPCR on cerebrospinal fluid samples from HIV-positive patients with history suggestive of CNS infections is being reported here.

Cerebrospinal fluid samples (n=114) from HIV patients with a history suggestive of acute or chronic meningitis were included in the study. DNA extraction was carried out by the phenol chloroform extraction method as described previously. ⁵ All the samples were subjected to MPCR using primers specific for the M. avium and M. tuberculosis complex (IS6110). ⁶ Medical records of all the positive cases were reviewed to note details such as age, sex, CD4 count, and outcome.

MPCR was positive for M. tuberculosis in 58% of patients (55/114) while MPCR was positive for M. avium in 13.6% of patients (12/114). Coinfection of M. tuberculosis and M. avium was noted in three patients. Table 1 summarizes the profile of patients with M. tuberculosis and M. avium CNS infections. All the patients with M. avium infection were adult males (median age 35 years, CD4 count 63/μl). More than 50% of these HIV patients were on antiretroviral therapy. The majority of the patients also received empirical category 1 antitubercular treatment. Two cases were treated using amphotericin B, of which one was serologically confirmed as cryptococcal meningitis.

Central nervous system infection due to NTMs accounts for 2% of all the infections in AIDS patient. ⁷ Mycobacterium avium complex (MAC) is the most common agent isolated from these infections and is frequently associated with disseminated disease. The majority of the data regarding M. avium causing CNS infections is drawn from isolated case reports, retrospective studies of culture positive cases, and autopsy data. ^{3,8 –10} Retrospective neuropathological studies also have shown evidence of M. avium infection in AIDS patients. ¹¹

In a review of cases of NTM meningitis published between 1982 and 1994, Flor et al. described 31 cases of M. avium meningitis in AIDS patients. ³ Cegielski and Wallace reported 48 cases of MAC infections (that accounted for 60% of all NTMs in their series) in AIDS patients, and these included both meningitis and meningoencephalitis cases. ¹² The present series of 12 cases of M. avium CNS infection is perhaps the largest series reported from India so far. Due to the ubiquitous nature of the organism, higher infection rates are observed in immunocompromised individuals such as patients with HIV/AIDS. The scanty data from developing countries on M. avium infections in HIV patients can be attributed either to lack of awareness or lack of facilities for definitive diagnosis.

In an endemic country such as India, with an increasing number of AIDS patients, the CNS infections due to M. avium may be higher and prospective studies looking for these infections are needed to determine the true burden of this disease. Our experience highlights the need to look for M. avium infections in AIDS patients presenting with neurological symptoms in whom TBM has been ruled out. Molecular techniques such as PCR may be beneficial over conventional techniques in the demonstration of NTMs such as M. avium.