Browsing by Author "Elafros MA"

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A qualitative study of factors resulting in care delays for adults with meningitis in Zambia.
(2022-Dec-02) Elafros MA; Bwalya C; Muchanga G; Mwale M; Namukanga N; Birbeck GL; Chomba M; Mugala-Mulenga A; Kvalsund MP; Sikazwe I; Saylor DR; Winch PJ; Department of Neurology, University of Michigan, Ann Arbor, 48109 Michigan, USA.; Department of Neurology, University of Rochester, Rochester, 14642 New York, USA.; Department of Internal Medicine, University of Zambia, School of Medicine, 10101 Lusaka, Zambia.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205 Maryland, USA.; Maryland Global Initiatives Corporation (MGIC), Lusaka, Zambia.; University Teaching Hospitals Children's Hospital, 10101 Lusaka, Zambia.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; University of Lusaka, 10101 Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, 10101 Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Meningitis causes significant mortality in regions with high comorbid HIV and TB. Improved outcomes are hindered by limited understanding of factors that delay adequate care. METHODS: In-depth interviews of patients admitted to the University Teaching Hospital with suspected meningitis, their caregivers, doctors and nurses were conducted. Patient/caregiver interviews explored meningitis understanding, treatment prior to admission and experiences since admission. Provider interviews addressed current and prior experiences with meningitis patients and hospital barriers to care. A conceptual framework based on the Three Delays Model identified factors that delayed care. RESULTS: Twenty-six patient/caregiver, eight doctor and eight nurse interviews occurred. Four delays were identified: in-home care; transportation to a health facility; clinic/first-level hospital care; and third-level hospital. Overcrowding and costly diagnostic testing delayed outpatient care; 23% of patients began with treatment inside the home due to prior negative experiences with biomedical care. Admission occurred after multiple clinic visits, where subsequent delays occurred during testing and treatment. CONCLUSIONS: Delays in care from home to hospital impair quality meningitis care in Zambia. Interventions to improve outcomes must address patient, community and health systems factors. Patient/caregiver education regarding signs of meningitis and indications for care-seeking are warranted to reduce treatment delays.
A qualitative study of patient, caregiver, doctor and nurse views of factors influencing lumbar puncture uptake in Zambia.
(2022-Apr-04) Elafros MA; Belessiotis-Richards C; Birbeck GL; Bond V; Sikazwe I; Kvalsund MP; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, 10101, Zambia.; Department of Neurology, University of Michigan, Ann Arbor, MI 48105, USA.; University Teaching Hospitals, Children's Hospital, Lusaka, 10101, Zambia.; Camden and Islington NHS Foundation Trust, London, NW1 OPE, UK.; Department of Neurology, University of Rochester, Rochester, NY 14642, USA.; Department of Psychiatry, University College London, London, W1T 7BN, UK.; Centre for Infectious Disease Research in Zambia, Lusaka, 10101, Zambia.; Zambart, School of Public Health, University of Zambia, Lusaka, 10101, Zambia.; Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Uptake of lumbar puncture (LP) remains low in regions with a high prevalence of central nervous system (CNS) infections like Zambia. Efforts to improve uptake are hindered by limited understanding of factors influencing LP uptake. METHODS: Semistructured qualitative interviews were conducted with patients with suspected CNS infection, caregivers, doctors and nurses at the University Teaching Hospitals in 2016. Questions focused on LP experiences, knowledge, the consent process and health system barriers to LP among patients with an LP indication. Interviews were transcribed, translated to English and analysed using a thematic approach. RESULTS: We recruited 24 adult patients, 36 caregivers of adult patients, 63 caregivers of paediatric patients, 20 doctors and 30 nurses (173 in total). LP barriers arose from both patients/caregivers and health providers and included community apprehension about LP, proxy (family) consensus consent practices, competing clinical demands, wariness of patient/caregiver responses, limitations in consumables and time to complete the LP. This could result in consent not being obtained correctly. LP enablers included patient/caregiver perceived LP utility, provider comfort with LP and in-person counselling. CONCLUSIONS: LP uptake is a complex sociocultural process influenced by patient, healthcare and community-level factors. Interventions to improve uptake must address multiple barriers to be successful.
Acute EEG findings in HIV-infected Zambian adults with new-onset seizure.
(2015-Mar-31) Siddiqi OK; Elafros MA; Sikazwe I; Birbeck GL; Kalungwana L; Potchen MJ; Bositis CM; Koralnik IJ; Theodore WH; From the Global Neurology Program (O.K.S., I.J.K.), Division of Neuroimmunology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine, Lusaka; International Neurologic and Psychiatric Epidemiology Program (M.A.E.) and College of Human Medicine (M.A.E.), Michigan State University, East Lansing; Epilepsy Division, Department of Neurology (G.L.B.), and Neuroradiology Division, Department of Imaging Sciences (M.J.P.), University of Rochester, NY; Chikankata Epilepsy Care Team (G.L.B.), Mazabuka; Centre for Infectious Disease Research in Zambia (I.S.), Lusaka; Department of Psychiatry (L.K.), University of Zambia, Lusaka; Greater Lawrence Family Health Center (C.M.B.), MA; and Clinical Epilepsy Section (W.H.T.), NINDS, NIH, Bethesda, MD. osiddiqi@bidmc.harvard.edu.; From the Global Neurology Program (O.K.S., I.J.K.), Division of Neuroimmunology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine, Lusaka; International Neurologic and Psychiatric Epidemiology Program (M.A.E.) and College of Human Medicine (M.A.E.), Michigan State University, East Lansing; Epilepsy Division, Department of Neurology (G.L.B.), and Neuroradiology Division, Department of Imaging Sciences (M.J.P.), University of Rochester, NY; Chikankata Epilepsy Care Team (G.L.B.), Mazabuka; Centre for Infectious Disease Research in Zambia (I.S.), Lusaka; Department of Psychiatry (L.K.), University of Zambia, Lusaka; Greater Lawrence Family Health Center (C.M.B.), MA; and Clinical Epilepsy Section (W.H.T.), NINDS, NIH, Bethesda, MD.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline clinical characteristics associated with EEG abnormalities, and evaluate the relationship between EEG abnormalities and recurrent seizure. METHODS: Eighty-one HIV-infected adults with new-onset seizure had EEG recordings during their index admission. Baseline characteristics assessed included HIV stage, seizure semiology, serum and CSF studies, neuroimaging, cognitive function based on the Zambian Mini-Mental State Examination and International HIV Dementia Scale, and psychiatric symptoms using the Shona Symptom Questionnaire. We evaluated the relationship between baseline characteristics and EEG abnormalities. Patients were followed for seizure recurrence, and the association between acute EEG abnormalities and seizure recurrence was assessed. Death was a secondary outcome. RESULTS: Fifty-five patients had abnormal EEGs (68%): 18 (22%) had interictal spikes (12) or a recorded seizure (6). Among baseline clinical characteristics, more advanced HIV disease (p = 0.039) and any imaging abnormality (p = 0.027) were associated with abnormal EEGs. Cortical (p = 0.008) and white matter (p = 0.004) abnormalities were associated with slow posterior dominant rhythm. Patients were followed for a median of 303 days (interquartile range 103-560). Twenty-four (30%) died and 23 (28%) had recurrent seizures. EEG abnormalities were not associated with recurrent seizure. There was a nonsignificant association between seizures recorded during EEG and death (67% vs 26%, p = 0.051). CONCLUSIONS: EEG abnormalities are common in this population, particularly in patients with imaging abnormalities and advanced HIV. Acute EEG abnormalities were not associated with recurrent seizure, but high mortality rates during follow-up limited this analysis.
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.
Cognitive impairment and psychiatric morbidity in HIV+ Zambians with new-onset seizure.
(2014-Dec) Kalungwana L; Elafros MA; Siddiqi OK; Bositis CM; Sikazwe I; Koralnik IJ; Theodore WH; Birbeck GL; Department of Psychology, University of Zambia, Lusaka, Zambia; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia; Division of NeuroVirology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Greater Lawrence Family Health Center, Lawrence, Massachusetts; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Neurology, Epilepsy Division, University of Rochester, Rochester, New York; Chikankata Epilepsy Care Team, Mazabuka, Zambia gretchen_birbeck@urmc.rochester.edu.; Department of Psychology, University of Zambia, Lusaka, Zambia; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia; Division of NeuroVirology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Greater Lawrence Family Health Center, Lawrence, Massachusetts; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Neurology, Epilepsy Division, University of Rochester, Rochester, New York; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
A prospective cohort study of new-onset seizure in people with human immunodeficiency virus (HIV) in Zambia is ongoing to determine the incidence of subsequent epilepsy and risk factors for epileptogenesis in this population. At enrollment, we evaluated this cohort for cognitive impairment and psychiatric morbidity. Over 50% of participants had cognitive impairment and significant psychiatric morbidity. Most participants had advanced HIV disease based on CD4+ T-cell count and World Health Organization stage, but we found no association between cognitive impairment or psychiatric morbidity and HIV disease staging.
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 layered stigma from comorbid HIV and epilepsy among Zambian adults.
(2018-Dec) Elafros MA; Gardiner JC; Sikazwe I; Okulicz JF; Paneth N; Chomba E; Birbeck GL; University Teaching Hospital, Department of Paediatrics and Child Health, Nationalist Way, Lusaka, Zambia.; Infectious Disease Service, Brooke Army Medical Center, 3851 Roger Brooke Dr., Fort Sam Houston, TX 78234, USA.; Epilepsy Care Team, Chikankata Hospital, Private Bag S2, Mazabuka, Zambia.; Centre for Infectious Disease Research in Zambia, 532 Great North Road, PO Box 24681, Lusaka, Zambia.; Department of Epidemiology and Biostatistics, Michigan State University, 909 Fee Road, Room B629, East Lansing, MI 48824, USA.; Strong Epilepsy Center, Department of Neurology, University of Rochester, 265 Crittenden Blvd, CU420694, Rochester, NY 14642, USA.; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, 909 Fee Road, Room 324, East Lansing, MI 48824, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND AND PURPOSE: Stigma hinders care for patients with neurologic illness. Layered stigma due to comorbid disease is common yet poorly characterized due to lack of instruments. Epilepsy and HIV are prototypical stigmatized conditions widespread in sub-Saharan Africa. METHODS: We assessed layered stigma among people with HIV and epilepsy (n = 21), epilepsy only (n = 88), and HIV only (n = 40) in Zambia. Epilepsy-associated stigma was assessed using the Stigma Scale of Epilepsy and Jacoby's Stigma Scale. HIV-related stigma was assessed using the HIV/AIDS Stigma Instrument-People Living with HIV/AIDS and Jacoby's Stigma Scale. Stigma was compared across groups using RESULTS: 55% (60/109) with epilepsy reported some epilepsy-associated stigma and 20% (12/61) with HIV reported HIV self-stigmatization. Those with HIV and epilepsy were more likely to associate seizures with fear (OR 6.1 [95% CI: 1.3-27.9]) and epilepsy with dependence (OR 4.6 [1.1-19.6]), controlling for age, gender, marital status, and employment. Those with comorbid disease were more likely to report they were "no longer a person" and felt "blamed" for their HIV. Controlling for age and gender, the difference in depersonalization remained (OR: 6.4 [1.1-36.1]). CONCLUSION: Individuals carrying the burden of one stigmatized condition may be more vulnerable to stigma from a comorbid disease.
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; Lusaka Apex Medical School, Medical Radiation Sciences, Lusaka, Zambia.; HIV Evaluation Unit, Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, USA.; Department of Imaging Sciences, University of Rochester, Rochester, NY, USA.; HIV Prevention, Care and Treatment Program, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Department of Neurology, University of Rochester, Rochester, NY, USA.; Epilepsy Care Team, Chikankata Hospital, Mazabuka, Zambia.; Department of Psychology, University of Zambia (UNZA), Lusaka, Zambia.; Clinical Epilepsy Unit, United States National Institutes of Health (US NIH), Bethesda, MD, USA.; Center for Virology and Vaccine Research, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Global Neurology Center, Division of Neuroimmunology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia, Lusaka, Zambia.; College of Human Medicine, Michigan State University (MSU), East Lansing, MI, USA.; Greater Lawrence Family Health Center, Lawrence, MA, USA.
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.
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.
Neuroimaging abnormalities and seizure recurrence in a prospective cohort study of zambians with human immunodeficiency virus and first seizure.
(2014-Oct-23) Potchen MJ; Siddiqi OK; Elafros MA; Koralnik IJ; Theodore WH; Sikazwe I; Kalungwana L; Bositis CM; Birbeck GL; College of Human Medicine, Michigan State University , East Lansing, MI, USA.; Epilepsy Division, Department of Neurology, University of Rochester , NY, USA ; Chikankata Epilepsy Care Team , Mazabuka, Zambia.; Clinical Epilepsy Section, United States National Institutes of Health , Bethesda, MD, USA.; Greater Lawrence Family Health Center , Lawrence, MA, USA.; Centre for Infectious Disease Research in Zambia , Lusaka, Zambia.; Division of NeuroVirology, Beth Israel Deaconess Medical Center , Boston, MA, USA.; Department of Psychology, University of Zambia , Lusaka, Zambia.; Neuroradiology Division Department of Imaging Sciences, University of Rochester , NY, USA.; Department of Internal Medicine, University of Zambia , Lusaka, Zambia ; Division of NeuroVirology, Beth Israel Deaconess Medical Center , Boston, MA, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
In HIV-positive individuals with first seizure, we describe neuroimaging findings, detail clinical and demographic risk factors for imaging abnormalities, and evaluate the relationship between imaging abnormalities and seizure recurrence to determine if imaging abnormalities predict recurrent seizures. Among 43 participants (mean 37.4 years, 56% were male), 16 (37%) were on antiretroviral drugs, 32 (79%) had advanced HIV disease, and (28) 66% had multiple seizures and/or status epilepticus at enrollment. Among those with cerebrospinal fluid studies, 14/31 (44%) had opportunistic infections (OIs). During follow-up, 9 (21%) died and 15 (35%) experienced recurrent seizures. Edema was associated with OIs (odds ratio: 8.79; confidence interval: 1.03-236) and subcortical atrophy with poorer scores on the International HIV Dementia Scale) (5.2 vs. 9.3; P=0.002). Imaging abnormalities were not associated with seizure recurrence or death (P>0.05). Seizure recurrence occurred in at least a third and over 20% died during follow-up. Imaging was not predictive of recurrent seizure or death, but imaging abnormalities may offer additional diagnostic insights in terms of OI risk and cognitive impairment.
New-onset seizure in HIV-infected adult Zambians: A search for causes and consequences.
(2017-Jan-31) Siddiqi OK; Elafros MA; Bositis CM; Koralnik IJ; Theodore WH; Okulicz JF; Kalungwana L; Potchen MJ; Sikazwe I; Birbeck GL; From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.; From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia. gretchen_birbeck@urmc.rochester.edu.
OBJECTIVE: To identify the etiology of new-onset seizure in HIV-infected Zambian adults and identify risk factors for seizure recurrence. METHODS: A prospective cohort study enrolling HIV-infected adults with new-onset seizure within 2 weeks of index seizure obtained clinical, laboratory, and neuroimaging data to determine seizure etiology. Participants were followed to identify risk factors for seizure recurrence. Risk factors for mortality were examined as mortality rates were unexpectedly high. RESULTS: Eighty-one patients with CSF for analysis were enrolled and followed for a median of 306 days (interquartile range 61-636). Most (91%) were at WHO stage III/IV and 66 (81%) had a pre-seizure Karnofsky score ≥50. Prolonged or multiple seizures occurred in 46 (57%), including 12 (15%) with status epilepticus. Seizure etiologies included CNS opportunistic infections (OI) in 21 (26%), hyponatremia in 23 (28%), and other infections in 8 (10%). OIs included Cryptococcus (17%), JC virus (7%) and 5% each for tuberculosis, cytomegalovirus, and varicella-zoster virus. No etiology could be identified in 16 (20%). Thirty (37%) patients died during follow-up and 20 (25%) had recurrent seizures with survival being the only identifiable risk factor. CONCLUSIONS: HIV-infected adults with new-onset seizure in Zambia often have advanced HIV disease with OI being the most frequent seizure etiology. Seizure recurrence is common but no risk factors for recurrence other than survival were identified. These findings suggest an urgent need for immune reconstitution in this population. Initiating treatment for seizure prophylaxis where only enzyme-inducing antiepileptic medications are available could threaten antiretroviral efficacy.
Patient-Reported Adverse Effects Associated with Combination Antiretroviral Therapy and Coadministered Enzyme-Inducing Antiepileptic Drugs.
(2017-Jun) Elafros MA; Birbeck GL; Gardiner JC; Siddiqi OK; Sikazwe I; Paneth N; Bositis CM; Okulicz JF; Infectious Disease Service, San Antonio Military Medical Center, San Antonio, Texas.; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan.; Global Neurology Program, Division of Neuroimmunology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.; Department of Neurology, University of Rochester, Rochester, New York.; Greater Lawrence Family Health Center, Lawrence, Massachusetts.; Department of Internal Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.; Epilepsy Care Team, Chikankata Hospital, Mazabuka, Zambia.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
AbstractConcurrent treatment with combination antiretroviral therapy (cART) and an enzyme-inducing antiepileptic drug (EI-AED) is common in resource-limited settings; however, the incidence and impact of adverse effects in cotreated patients is largely unknown. Symptoms of adverse effects were assessed by both spontaneous report and checklist for 145 human immunodeficiency virus (HIV)-infected Zambian adults initiating various treatment combinations, such as cART with an EI-AED (