Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

Sexually differentiated regulation of gnRH release by gonadal steroid hormones in sheep.

Exposure of the sheep fetus to testosterone from day 30 to day 90 of a 147 day gestation causes the neurones that control GnRH secretion, the GnRH neuronal network, to become organized in a sex-specific manner. After androgen exposure in utero, GnRH neurones are activated in a sexually differentiated pattern by gonadal steroid hormones. Specifically, follicular phase concentrations of oestrogen trigger a GnRH 'surge' in ewes, but not in rams or females treated with androgen during fetal life. Furthermore, progesterone is a less potent inhibitor of GnRH release in rams or females treated with androgen during fetal life. The reasons for the sexual differentiation of these steroid feedback mechanisms probably reside in a dimorphism in steroid-sensitive neural inputs to GnRH neurones. The density of neurones containing oestrogen receptor alpha is sexually differentiated in areas of the ovine brain that are known to be involved in the steroidal regulation of GnRH. Furthermore, neurones in these regions are activated in a gender-specific pattern. A determination of the neural phenotype of these steroid-sensitive cells will form a basis for understanding the mechanisms by which the GnRH neuronal network is organized and activated in a sexually differentiated manner.