Browsing by Author "Koralnik IJ"

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Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.
(2023-Dec) Musukuma-Chifulo K; Ghebremichael M; Chilyabanyama ON; Bates M; Munsaka S; Simuyandi M; Chisenga C; Tembo J; Sinkala E; Koralnik IJ; Dang X; Chilengi R; Siddiqi OK
The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.
Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.
(2022-Jun) Ravishankar M; Dallah I; Mathews M; Bositis CM; Mwenechanya M; Kalungwana-Mambwe L; Bearden D; Navis A; Elafros MA; Gelbard H; Theodore WH; Koralnik IJ; Okulicz JF; Johnson BA; Belessiotis C; Ciccone O; Thornton N; Tsuboyama M; Siddiqi OK; Potchen MJ; Sikazwe I; Birbeck GL
OBJECTIVE: This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new-onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30-day mortality and cause of death are also reported. METHODS: Children living with HIV (CLWHIV) with new-onset seizures were prospectively evaluated at one large urban teaching hospital and two non-urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. RESULTS: From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2-10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non-accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty-two (30%) children died within 30 days of the index seizure. SIGNIFICANCE: Despite widespread ART roll out in Zambia, new-onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.
Epstein-Barr Virus Detection in the Central Nervous System of HIV-Infected Patients.
(2022-Sep-22) Musukuma-Chifulo K; Siddiqi OK; Chilyabanyama ON; Bates M; Chisenga CC; Simuyandi M; Sinkala E; Dang X; Koralnik IJ; Chilengi R; Munsaka S
Simply detecting Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) is insufficient to diagnose EBV-associated diseases. The current literature around EBV-DNA detection from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-positive non-lymphoma patients was systematically reviewed and a meta-analysis reporting the estimated pooled prevalence in this population when PCR methods are employed, targeting different sequence segments within the EBV genome, was conducted. Using a combination of three key concepts-Epstein-Barr virus detection, central nervous system disease, and human cerebrospinal fluid-and their MeSH terms, the PubMed database was searched. A total of 273 papers reporting the detection of EBV in CNS were screened, of which 13 met the inclusion criteria. The meta-analysis revealed a pooled prevalence of EBV-DNA in CSF of 20% (CI: 12-31%). The highest pooled prevalence was from studies conducted on the African population at 39% (CI: 27-51%). The investigation of the presence of EBV-DNA in the CSF was also very varied, with several gene targets used. While most patients from the articles included in this review and meta-analysis were symptomatic of CNS disorders, the pathogenicity of EBV in non-lymphoma HIV patients when detected in CSF has still not been determined. The presence of EBV-DNA in the CNS remains a concern, and further research is warranted to understand its significance in causing CNS disorders.
HIV and new onset seizures: slipping through the cracks in HIV care and treatment.
(2016-Feb) Sikazwe I; Elafros MA; Bositis CM; Siddiqi OK; Koralnik IJ; Kalungwana L; Theodore WH; Okulicz JF; Potchen MJ; Birbeck GL
OBJECTIVES: The aim of the study was to describe patient characteristics and outcomes among HIV-positive adults presenting to a Zambian tertiary care hospital with new-onset seizures. METHODS: From July 2011 to June 2013, adults with seizures and a known or probable diagnosis of HIV infection were screened for a cohort study. Demographic and clinical data were obtained, including information on engagement in HIV services and in-patient mortality. Analyses were conducted to identify characteristics associated with poor engagement in care and death. RESULTS: A total of 320 of 351 screened adults were HIV-positive, with 268 of 320 experiencing new-onset seizures. Of these, 114 of 268 (42.5%) were female, and their mean age was 36.8 years. Seventy-nine of the 268 patients (29.5%) were diagnosed with HIV infection during the index illness. Among those who were aware of their HIV-positive status, 59 of 156 (37.8%) had disengaged from care. Significant functional impairment (Karnofsky score < 50) was evident in 44.0% of patients. Cerebrospinal fluid was not obtained in 108 of 268 (40.3%). In-patient mortality outcomes were available for 214 patients, and 47 of these 214 (22.0%) died during hospitalization. Patients with significant functional impairment were more likely to undergo lumbar puncture (P = 0.046). Women and the functionally impaired were more likely to die (P = 0.04 and < 0.001, respectively). CONCLUSIONS: Despite the availability of care, less than half of HIV-infected people with new-onset seizures were actively engaged in care and in-patient mortality rates were high. In the absence of clinical contraindication, lumbar puncture should be performed to diagnose treatable conditions and reduce morbidity and mortality. Continued efforts are needed to expand community-based testing and improve HIV care retention rates. Qualitative studies are needed to elucidate factors contributing to lumbar puncture usage in this population.
Long-term outcomes after new onset seizure in children living with HIV: A cohort study.
(2024-Apr) Birbeck GL; Mwenechanya M; Ume-Ezeoke I; Mathews M; Bositis CM; Kalungwana L; Bearden D; Elafros M; Gelbard HA; Theodore WH; Koralnik IJ; Okulicz JF; Johnson BA; Musonda N; Siddiqi OK; Potchen MJ; Sikazwe I
OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.