PCR testing reveals high prevalence of CNS infections among people living with HIV in Zambia with CNS symptoms

Over a third of patients died

Michael Carter
Published: 30 April 2014

There is a high prevalence of central nervous system (CNS) opportunistic infections among people living with HIV in Zambia who present with CNS symptoms, investigators report in the online edition of Clinical Infectious Diseases. At least one pathogen was detected in 57% of patients. The mortality rate was high, with over a third of individuals dying after their admission to hospital.

Enhanced screening for CNS pathogens “would save lives” write the authors.

They undertook the study because little is known about the prevalence of CNS infections among patients in sub-Saharan Africa.

The cross-sectional study involved 331 adults living with HIV in Lusaka, Zambia, who presented for emergency care with CNS symptoms. Cerebrospinal fluid (CSF) samples were obtained from each patient. PCR testing was used to detect a number of CNS pathogens, including tuberculosis (TB), Epstein-Barr virus (EBV), JC virus (JCV), varicella zoster virus (VZV), cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), HSV-2 and toxoplasmosis gondii (TG).

The patients had severe immune suppression. The median CD4 count was just 89 cells/mm3. A quarter of patients were diagnosed with HIV at the time of their presentation. Just over a third of patients (36%) were taking antiretroviral therapy. But the duration of this treatment was short, a median of 240 days.

Cryptococcal antigen testing was performed for the 56% of patients who were able to pay the $10 for this test.Overall, CNS pathogens were detected in 189 patients (57%). Of these 189 patients, 64% had one and 36% had multiple pathogens detected.

The most common pathogen was EBV, detected in 28% of patients. Cryptococcus was also highly prevalent (19%), as was TB (14%). JCV was detected in 6% of patients, a similar proportion having VZV. Pneumococcal and meningococcal meningitis were detected in 2% and 1% of patients, respectively. HSV-1 was rare (2%) and no cases of toxoplasmosis or HSV-2 were detected.

A quarter of patients who underwent cryptococcal antigen testing had a positive result.

Seizures occurred in 24% of patients. They were most commonly seen in people with cryptococcus (27%), JCV (25%), VZV (23%) and HSV-1 (20%). They also occurred in patients with EBV (17%), CMV (15%) and TB (12%).

Outcomes were poor. A total of 117 patients (35%) died during hospitalisation. The mortality rate was higher among patients with a CNS pathogen than among patients without this diagnosis (41% vs 27%, p = 0.01).

The mortality rate among patients with EBV in cerebrospinal fluid was 41%, and 39% of those with cryptococcal meningitis died. Mortality was also high (45%) among patients with TB infection in CNS.

Recent diagnosis with HIV was associated with a significantly increased risk of mortality (p = 0.03).

“PCR uncovered the presence of multiple pathogens that would have otherwise remained undetected,” comment the authors. “There was a high prevalence of co-infection in the CSF, indicative of severe immunosuppression in this population. These findings may reflect late presentation of patients to health facilities.”

The authors believe their study highlighted a number of factors that could improve patient care and outcomes. These include earlier diagnosis of HIV and the more widespread use of cryptococcal antigen testing. They also suggest use of PCR technologies to detected EBV, TB, CMV, VZV and HSV “may improve patient survival”.

Reference

Siddiqi OK et al. Molecular diagnosis of central nervous system opportunistic infection in HIV-positive Zambian adults. Clin Infect Dis, online edition, 2014.

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