Incidence of motor neuron disease/amyotrophic lateral sclerosis in South Africa: a 4-year prospective study.

BACKGROUND AND PURPOSE: Little is known about the epidemiological features of amyotrophic lateral sclerosis (ALS) in sub-Saharan Africa, and data from the region are limited to clinical series or case reports. The aim of the study was to investigate the incidence rate and presentation of ALS in an ethnically diverse region of South Africa. METHODS: We performed a 4-year prospective incidence study in the Western Cape Province of South Africa between 1 July 2014 and 30 June 2018, and used a two-source capture-recapture method for case ascertainment. Age- and sex-adjusted incidence rates (ASAIRs) were calculated using the 2010 US population as the reference. RESULTS: A total of 203 incident cases were identified over the study period, resulting in a crude incidence rate (IR) of 1.09 [95% confidence interval (CI) 0.94-1.24] per 100 000 person-years in the at-risk population (aged >15 years). Capture-recapture analysis resulted in an estimated IR of 1.11 (95% CI 1.01-1.22) per 100 000 person-years. The ASAIR was 1.67 (95% CI 1.09-2.26) overall; 1.99 (95% CI 1.60-2.39) for men and 1.37 (95% CI 1.06-1.68) for women. When analysed separately, there was a substantial difference in ASAIRs between the different population groups, with the highest in the European ancestry group (2.62; 95% CI 2.49-2.75), the lowest in the African ancestry group (0.56, 95% CI 0.0-1.23), and an ASAIR in between these two in the mixed ancestry group (1.09, 95% CI 0.80-1.37). CONCLUSION: The overall incidence of ALS in the Western Cape Province of South Africa appears to be lower than in North African and Western countries, but higher than in Asian countries. As suggested by previous epidemiological studies, ALS may be less frequent in people of African ancestry.

A proposed management algorithm for late-onset efavirenz neurotoxicity.

A high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causing inhibition of a pathway that plays an important role in slow EFV metabolisers. Concomitant INH use therefore affects plasma levels of EFV. EFV is well known to cause neuropsychiatric side-effects on initiation, and a recent adult case series described late-onset neurotoxicity in the form of subacute ataxia and encephalopathy in patients treated with EFV for a median of 2 years, in association with toxic plasma levels of the drug. We have seen an increase in cases of EFV toxicity presenting to our neurology referral unit. All cases have been in the context of recent initiation of concomitant INH. We therefore conducted a retrospective case record audit to describe these seven cases with the additional advantage of tertiary-level assessment. We outline the clinical features and investigation results, as well as outcomes after EFV was stopped. Our main objectives are to highlight the probable role of concomitant INH use in the development of this syndrome, and to suggest that only limited work-up may be warranted in suspected cases.

HIV-associated neurocognitive disorders: antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes.

BACKGROUND: The human immunodeficiency virus (HIV) can give rise to a spectrum of neuropsychological impairments known collectively as HIV-associated neurocognitive disorders (HAND). Although antiretroviral therapy (ART) has reduced the incidence of HIV dementia, the prevalence of milder forms of HAND has increased. It has been postulated that incomplete central nervous system (CNS) viral suppression or potential drug toxicity, both of which could be related to the CNS penetration effectiveness (CPE) of ART regimens, may contribute to this phenomenon. OBJECTIVE: This study compared cognitive outcomes in clade C-infected HIV patients in South Africa treated for 1 year with ART regimens with differing CPE scores. METHODS: We assessed 111 HIV-positive patients with varying levels of cognitive function at baseline (pre-ART) and then a year later. A neuropsychological battery was administered at both visits to derive global deficit scores. ART regimen data were collected at the follow-up visit. Some participants remained ART-naïve during this period, thus providing a non-treatment control group. RESULTS: Significantly more ART recipients maintained or improved cognitive function compared with patients not on ART (p=0.017). There was no significant difference in cognitive outcomes between higher and lower CPE regimen groups (p=0.473). CONCLUSIONS: ART preserves or improves cognition in HIV-infected patients after 1 year, irrespective of the regimen's CPE. South Africa's current low CPE-scored first-line regimen performed as well as higher CPE-scored regimens. These findings are reassuring for South Africa, but larger, longer-term studies would be more definitive.