Correction: Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.

[This corrects the article DOI: 10.1371/journal.pntd.0005969.].

Temporary disengagement and re-engagement in human immunodeficiency virus care in a rural county serving pastoralist communities in Kenya: a retrospective cohort study.

BACKGROUND: Pastoralist communities are known to be hard to reach. The magnitude of temporary disengagement from human immunodeficiency virus (HIV) care is understudied. METHODS: We conducted a retrospective cohort study of temporary disengagement (2 weeks late for a next appointment), virologic response, lost to follow-up (6 months late) and re-engagement in care among patients who started antiretroviral therapy between 2014 and 2016 in Baringo County, Kenya. Predictors of re-engagement after disengagement were estimated using logistic regression. RESULTS: Of 342 patients, 76.9% disengaged at least once (range 0-7). Of 218 patients with a viral load (VL), 78.0% had a suppressed VL. Those with a history of temporary disengagement from care were less likely to suppress their VL (p=0.002). Six patients had treatment failure (two consecutive VLs >1000 copies/mm3) and all had disengaged at least once. After disengagement from care, male patients (adjusted odds ratio [aOR] 0.3 [95% confidence interval {CI} 0.2 to 0.6]; p<0.001) and patients with World Health Organization stage III-IV (aOR 0.3 [95% CI 0.1 to 0.5; p<0.001) were less likely to re-engage in care. CONCLUSIONS: Temporary disengagement was frequent in this pastoralist setting. This indicator is often overlooked, as most studies only report binary outcomes, such as retention in care. Innovative strategies are required to achieve HIV control in rural settings like this pastoralist setting.

Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.

BACKGROUND: Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa. METHODS: We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom. FINDINGS: None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of 'test' antivenom IgGs to bind venom proteins were not substantially different from that of the 'gold standard' antivenoms. The least effective antivenoms had the lowest IgG content/vial. CONCLUSIONS: Manufacture-stated preclinical efficacy statements guide decision making by physicians and antivenom purchasers in sub-Saharan Africa. This is because of the lack of both clinical data on the efficacy of most of the many antivenoms used to treat patients and independent preclinical assessment. Our preclinical efficacy assessment of antivenoms available in Kenya identifies important limitations for two of the most commonly-used antivenoms, and that no antivenom is preclinically effective against all the regionally important snakes. The potential implication to snakebite treatment is of serious concern in Kenya and elsewhere in sub-Saharan Africa, and underscores the dilemma physicians face, the need for clinical data on antivenom efficacy and the medical and societal value of establishing independent preclinical antivenom-efficacy testing facilities throughout the continent.