Exposure to parasitic infections determines features and phenotypes of active convulsive epilepsy in Africa

Background: Epilepsy affects 70 million people worldwide, 80% of whom are in low-and-middle income countries (LMICs). Infections of the central nervous system (CNS) contribute considerably to the burden of epilepsy in LMICs, but the nature and presentation of epilepsy following these infections is not fully understood. We examined if epilepsy foutcomes are associated with the exposure to parasitic infections. Methods: This was a case-comparison study nested in a cross-sectional survey of people with active convulsive epilepsy, with cases as those exposed to parasitic infections, and comparison as those unexposed. Associations of exposure to parasites with clinical and electroencephalographic features of epilepsy were done using a modified mixed effects Poisson regression model across five sites in Africa. Multiplicative and additive scale (RERI) interactions were explored to determine the effect of co-infections on epilepsy features. Population attributable fractions (PAF) were calculated to determine the proportion of severe clinical and electroencephalographic features of epilepsy attributable to CNS infections. Results: A total of 997 participants with active convulsive epilepsy from the five African sites were analyzed, 51% of whom were males. Exposure to parasitic infections was associated with more frequent seizures in adult epilepsy (relative risk (RR)=2.58, 95% confidence interval (95%CI):1.71-3.89). In children, exposure to any parasite was associated with convulsive status epilepticus (RR=4.68, (95%CI: 3.79-5.78), intellectual disabilities (RR=2.13, 95%CI: 1.35-3.34) and neurological deficits (RR=1.92, 95%CI: 1.42-2.61). Toxoplasma gondii and Onchocerca volvulus interacted synergistically to increase the risk of status epilepticus (RERI=0.91, 95%CI=0.48-1.35) in the data pooled across the sites. Exposure to parasitic infections contributed to 30% of severe features of epilepsy as shown by PAF. Conclusions: Parasitic infections may determine features and phenotypes of epilepsy through synergistic or antagonistic interactions, which can be different in children and adults. Interventions to control or manage infections may reduce complications and improve prognosis in epilepsy

Exposure to parasitic infections determines features and phenotypes of active convulsive epilepsy in Africa

Background: Epilepsy affects 70 million people worldwide, 80% of whom are in low-and-middle income countries (LMICs). Infections of the central nervous system (CNS) contribute considerably to the burden of epilepsy in LMICs, but the nature and presentation of epilepsy following these infections is not fully understood. We examined if epilepsy foutcomes are associated with the exposure to parasitic infections. Methods: This was a case-comparison study nested in a cross-sectional survey of people with active convulsive epilepsy, with cases as those exposed to parasitic infections, and comparison as those unexposed. Associations of exposure to parasites with clinical and electroencephalographic features of epilepsy were done using a modified mixed effects Poisson regression model across five sites in Africa. Multiplicative and additive scale (RERI) interactions were explored to determine the effect of co-infections on epilepsy features. Population attributable fractions (PAF) were calculated to determine the proportion of severe clinical and electroencephalographic features of epilepsy attributable to CNS infections. Results: A total of 997 participants with active convulsive epilepsy from the five African sites were analyzed, 51% of whom were males. Exposure to parasitic infections was associated with more frequent seizures in adult epilepsy (relative risk (RR)=2.58, 95% confidence interval (95%CI):1.71-3.89). In children, exposure to any parasite was associated with convulsive status epilepticus (RR=4.68, (95%CI: 3.79-5.78), intellectual disabilities (RR=2.13, 95%CI: 1.35-3.34) and neurological deficits (RR=1.92, 95%CI: 1.42-2.61). Toxoplasma gondii and Onchocerca volvulus interacted synergistically to increase the risk of status epilepticus (RERI=0.91, 95%CI=0.48-1.35) in the data pooled across the sites. Exposure to parasitic infections contributed to 30% of severe features of epilepsy as shown by PAF. Conclusions: Parasitic infections may determine features and phenotypes of epilepsy through synergistic or antagonistic interactions, which can be different in children and adults. Interventions to control or manage infections may reduce complications and improve prognosis in epilepsy

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated