Molecular Diagnosis of Central Nervous System Opportunistic Infections in HIV-Infected Zambian Adults

Abstract

CNS OIs are frequent, potentially treatable complications of AIDS in Zambia. Multiple pathogens often coexist in CSF. EBV is the most prevalent CNS organism in isolation and in coinfection. Whether it is associated with CNS disease or a marker of inflammation requires further investigation. More comprehensive testing for CNS pathogens could improve treatment and patient outcomes in Zambia.

Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort

“…Similar to three other recent publications, cryptococcal meningitis was more common than all other identified etiologies of meningitis combined. [8][9][10] Thereafter, a confirmed diagnosis was difficult to ascertain. The prevalence of aseptic meningitis was 23% (71 of 314).…”

“…2 Clearly bacterial meningitis is infrequent in our patient population, and in Zambia among those with HIV. 8 In the general population in Malawi, Cryptococcus is nearly 2.3 times more common than all causes of bacterial meningitis combined in adults, 9 with similar national epidemiology in South Africa. 10 With these results, in both the general population and the population of inpatients with advanced HIV disease, and knowing that the cost of ceftriaxone 2 g (US$2) is the same as the cryptococcal antigen lateral flow assay (CrAg LFA, $2 Immy, Inc.), one might consider an algorithm for those HIV-infected patients initially presenting with meningitis, involving an initial cryptococcal antigen point-of-care test in the blood.…”

“…In Malawi, South Africa, Uganda, Zambia, and Zimbabwe, cryptococcal meningitis is the predominant etiology of meningitis followed by tuberculosis (TB) meningitis (TBM) in adults. [3][4][5][6][7][8] In both South Africa and Malawi, Cryptococcus is more common than all causes of bacterial meningitis combined. 9,10 In Ethiopia, the most common neurologic manifestation has been thought to be cerebral toxoplasmosis, followed by TBM and Cryptococcus, 11 although recent studies suggest a very large burden of cryptococcosis among those with advanced HIV.…”

New-onset seizure in HIV-infected adult Zambians

“…9 CSF DNA PCR testing was conducted for Mycobacterium tuberculosis, Epstein-Barr virus (EBV), JC virus, varicella-zoster virus, cytomegalovirus, herpes simplex virus type 1, herpes simplex virus type 2, and Toxoplasma gondii on a Rotorgene 6000 (Corbett Life Sciences, Sydney, Australia) real-time thermocycler as previously described. 10 The presence of a CNS OI was defined as positive CSF or serum CrAg, amplification of DNA from CSF PCR with the exception of EBV, or neuroimaging consistent with a specific CNS OI and confirmed by serum studies or response to treatment. Amplification of CSF EBV was not considered to be a CNS OI as its pathologic role in the CNS is unclear.…”

“…The pathologic significance of EBV in the CSF of HIV-infected patients remains an open question. 10,[13][14][15] Cryptococcal meningitis (17%) was the most frequently detected CNS OI. The mechanism whereby cryptococcal meningitis may cause seizures is not fully understood.…”