Browsing by Author "Johnson BA"

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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; Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Weill Cornell Medicine, New York, New York, USA.; University of Michigan, Ann Arbor, Michigan, USA.; Tufts School of Medicine, Medford, Massachusetts, USA.; Epilepsy Care Team, Chikankata Hospital, Mazabuka, Zambia.; National Institute of Health, Bethesda, Maryland, USA.; Icahn School of Medicine, New York, New York, USA.; University College London, London, UK.; University of Zambia, Lusaka, Zambia.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Boston Children's Hospital, Boston, Massachusetts, USA.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Epilepsy Division, Department of Neurology, University of Rochester, Rochester, New York, USA.; Center for Health + Technology, University of Rochester Medical Center, Rochester, New York, USA.; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.; Zambian College of Medicine & Surgery, Lusaka, Zambia.; US Army Brooke Army Medical Center, Fort Sam Houston, Texas, USA.; University of Rochester Medical Center, Rochester, New York, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case-Control Study.
(2024-Mar-01) Bearden DR; Mwanza-Kabaghe S; Bositis CM; Dallah I; Johnson BA; Siddiqi OK; Elafros MA; Gelbard HA; Okulicz JF; Kalungwana L; Musonda N; Theodore WH; Mwenechanya M; Mathews M; Sikazwe IT; Birbeck GL; Greater Lawrence Family Health Center, Lawrence, MA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Neurology, University of Michigan, Ann Arbor, MI.; University of Rochester, Center for Health and Technology, Rochester, NY.; Department of Biostatistics, University of Rochester, Rochester, NY.; Department of Psychology, University of Zambia, Lusaka, Zambia.; University of Zambia School of Medicine, Lusaka, Zambia.; University of Zambia, University Teaching Hospitals, Lusaka, Zambia.; San Antonio Military Medical Center, Infectious Diseases Service, HIV Medical Evaluation Unit, San Antonio, TX.; Department of Neurology, University of Rochester, Rochester, NY.; Department of Educational Psychology, University of Zambia, Lusaka, Zambia.; Epilepsy Division, US National Institute of Health, Bethesda, MD; and.; Department of Neurology, Beth Israel Deaconess Medical Center, Global Neurology Program, Boston, MA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. METHODS: We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm 3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. RESULTS: We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm 3 (OR 3.6, P < 0.001) increased risk of seizures. CONCLUSIONS: Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.
Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia.
(2020-Dec) Navis A; Dallah I; Mabeta C; Musukuma K; Siddiqi OK; Bositis CM; Koralnik IJ; Gelbard HA; Theodore WH; Okulicz JF; Johnson BA; Sikazwe I; Bearden DR; Birbeck GL; Department of Biostatistics, Center for AIDS Research, University of Rochester, Rochester, NY, USA.; National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.; Department of Neurology, University of Rochester, Rochester, NY, USA.; Department of Internal Medicine, Center for Vaccines and Virology Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Infectious Disease Service, Brooke Army Medical Center, Joint Base San Antonio-Ft Sam Houston, Houston, TX, USA.; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; Greater Lawrence Family Health Center, Lawrence, MA, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Departments of Neurology, Pediatrics, Neuroscience and Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Chikankata Epilepsy Care Team, Mazabuka, Zambia.
OBJECTIVE: Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. METHODS: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. RESULTS: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm SIGNIFICANCE: EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm
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; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.; University Teaching Hospitals Neurology Research Office, Lusaka, Zambia.; Department of Biostatistics, University of Rochester, Rochester, New York, USA.; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Department of Neurology, University of Rochester, Rochester, New York, USA.; Department of Medicine, San Antonio Military Medical Center, San Antonio, Texas, USA.; Department of Psychology, University of Zambia, Lusaka, Zambia.; Zambian College of Medicine and Surgery, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Clinical Epilepsy Section, US National Institute of Health, Bethesda, Maryland, USA.; Department of Imaging Sciences, University of Rochester, Rochester, New York, USA.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Family and Community Medicine, University of California San Francisco, San Francisco, California, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Mortality & recurrent seizure risk after new-onset seizure in HIV-positive Zambian adults.
(2018-Dec-07) Elafros MA; Johnson BA; Siddiqi OK; Okulicz JF; Sikazwe I; Bositis CM; Potchen MJ; Koralnik IJ; Theodore WH; Kalungwana L; Birbeck GL; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, NINDS NIH Building 10 Room 7D-43, Bethesda, MD, 20892, USA.; Greater Lawrence Family Health Center, 34 Haverhill St, Lawrence, MA, 01841, USA.; Infectious Disease Service, Brooke Army Medical Center, 3851 Roger Brooke Dr., Fort Sam Houston, San Antonio, TX, 78234, USA.; Epilepsy Division, Department of Neurology, University of Rochester School of Medicine & Dentistry, 265 Crittenden Blvd, CU420694, Rochester, NY, 14642-0694, USA.; Department of Biostatistics and Computational Biology, University of Rochester, 265 Crittenden Boulevard, CU 420-630, Rochester, NY, 14642-0630, USA.; Department of Psychology, University of Zambia, P.O. BOX 32379, 10101, Lusaka, Zambia.; Global Neurology Program, Division of Neuroimmunology, Department of Neurology, E/CLS 1017B Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA.; Department of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison Street, Suite 1106, Chicago, IL, 60612, USA.; Epilepsy Care Team, Chikankata Hospital, Private Bag S2, Mazabuka, Zambia.; Center for Infectious Disease Research in Zambia, 5032 Great North Road, P.O. Box 34681, Lusaka, Zambia.; Neuroradiology Division, Department of Imaging Sciences, University of Rochester Medical Center, 601 Elmwood Ave, Box 648, Rochester, NY, 14642, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; Department of Neurology, Johns Hopkins Hospital, Sheik Zayed Tower, Room 6005, 1800 Orleans Street, Baltimore, MD, 21287, USA. melafro1@jhmi.edu.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Recurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa. METHODS: HIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence. Seizure etiology was evaluated, and recurrent seizures and medication usage were assessed during clinic visits. Due to unexpectedly high mortality rates, predictors of death were evaluated using proportional hazards with Gray's test to compare cumulative incidence functions for recurrent seizure across groups adjusting for the competing outcome of death. RESULTS: 95 patients were enrolled (mean age 37 years, 43% female, 83% with Karnofsky > 50) and followed for a mean of 293 days (median 241 (IQR: 29-532)). At presentation, 50 (53%) were in status epilepticus. The majority (91, 85%) had advanced HIV disease and 65 (68%) were not on combined antiretroviral therapy (cART). After extensive workup, seizure etiology remained unknown in 16 (17%). Average time to cART initiation after enrollment was 61 days. During follow up, 37 (39%) died and 23 (24%) had recurrent seizure. Most deaths (25/37, 68%) occurred in the first 60 days post-index seizure. Individuals with advanced HIV were more likely to die (HR: 19.1 [95% CI: 1.1-333.4]) as were those whose seizure etiology remained unknown (HR: 2.2 [95% CI: 1.1-4.4]). Among participants that survived from enrolment to the end of data collection on 10 May 2013 (n = 58), 20 (34%) experienced recurrent seizures. CONCLUSIONS: New-onset seizure among HIV-positive Zambian adults is associated with high mortality despite good functional status prior to presentation. Advanced HIV infection and failure to identify an underlying seizure etiology are associated with greater mortality. Recurrent seizures occur in over a third of survivors within only 2 years of follow-up. This provides evidence to support AED initiation after first seizure in HIV-positive individuals with advanced HIV disease at the time of presentation though the risks of AED-cART interactions remain a concern and warrant further study.