Pharmacokinetics of TKM-130803 in Sierra Leonean patients with Ebola virus disease: plasma concentrations exceed target levels, with drug accumulation in the most severe patients.

BACKGROUND: TKM-130803 is a specific anti-EBOV therapeutic comprised of two small interfering RNAs (siRNA) siLpol-2 and siVP35-2. The pharmacokinetics (PK) of these siRNAs was defined in Ebola virus disease (EVD) patients, with reference to efficacy (ET) and toxicology thresholds (TT). The relationship between PK and patient survival was explored. METHODS: Pharmacokinetic (PK) and pharmacodynamic (PD) data were available for seven participants with EVD in Sierra Leone who received 0·3 mg/kg of TKM-130803 by intravenous infusion over 2 h daily for up to 7 days. Plasma concentration of siRNA was compared to survival at 14 days. PK data were fitted to two-compartment models then Monte Carlo simulated PK profiles were compared to ET (Cmax 0·04-0·57 ng/mL and mean concentration 1·43 ng/mL), and TT (3000 ng/mL). FINDINGS: Viral loads (VL) were not significantly different at treatment onset or during treatment (p = 0·1) in subjects who survived or died. siRNA was in quantitative excess of virus genomes throughout treatment, but the 95% percentile exceeded TT. The maximum AUC for which the 95% percentile remained under TT was a continuous infusion of 0·15 mg/kg/day. Plasma concentration of both siRNAs were higher in subjects who died compared to subjects who survived (p<0·025 both siRNAs). INTERPRETATION: TKM-130803 was circulating in molar excess of circulating virus; a level considered needed for efficacy. Given extremely high viral loads it seems likely that the patients died because they were physiologically beyond the point of no return. Subjects who died exhibited some indication of impaired drug clearance, justifying caution in dosing strategies for such patients. This analysis has given a useful insight into the pharmacokinetics of the siRNA in the disease state and illustrates the value of designing PKPD studies into future clinical trials in epidemic situations. FUNDING: This work was supported by the Wellcome Trust of Great Britain (grant number 106491/Z/14/Z and 097997/Z/11/A) and by the EU FP7 project PREPARE (602525). The PHE laboratory was funded by the UK Department for International Development. The funders had no role in trial design, data collection or analysis. The views expressed are those of the authors and not necessarily those of Public Health England, the Department of Health, or the EU. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.

Ebola virus disease: What clinicians in the United States need to know.

In March 2014 the World Health Organization was notified of an outbreak of Ebola virus disease (EVD) in the forest region of Guinea. As of May 2015, the outbreak had become the most devastating EVD epidemic in history with more than 27,000 cases and more than 11,000 deaths. The introduction of EVD into noncontiguous countries, including the United States, from infected travelers highlights the importance of preparedness of all health care providers. Early identification and rapid isolation of patients suspected with EVD is critical to limiting the spread of Ebola virus. Additionally, enhanced understanding of EVD case definitions, clinical presentation, treatment procedures, and infection control strategies will improve the ability of health care workers to provide safe care for patients with EVD.

Ebola: a holistic approach is required to achieve effective management and control.

The current Ebola outbreak in West Africa has already caused substantial mortality and dire human and economic consequences. It continues to represent an alarming public health threat in the region and beyond and jeopardizes the provision of health care and other services in the affected countries. The scale of the epidemic has accelerated research efforts for diagnostics, treatment, and prevention galvanized through increased availability of funding. Our knowledge relating to the virus, disease pathogenesis, risk factors, dynamics of transmission, and epidemic control is increasing, and sociocultural factors have emerged as critical determinants for the success and failure of control efforts. However, there is a long way to go. In this review we summarize the current knowledge, examine the sociocultural context in West Africa, and outline priority areas for future research.

[Ocular symptoms and treatment of Ebola virus disease]. / Az Ebola-vírusos betegség szemészeti tünetei és kezelése.

Ocular signs and symptoms of Ebola infection initially suggest banal conjunctivitis, but in advanced cases severe haemorrhagic conjunctivitis appears and, in the final stage of the disease, retinal and chorioidal haemorrhages may occur which can cause even blindness. Although the viral infection accompanied by ocular symptoms of a non-specific conjunctivitis, the high fever present from the onset of the disease should raise the suspicion of Ebola infection. There is no causal therapy know so far, and the only adjunctive treatment may be delivered by an ophthalmologist. Because the virus can be detected in the tear, it can theoretically be the mediator of the infection and, therefore, ophthalmological examinations should be carried out with the highest caution. In case of suspected Ebola infection the nearest competent healthcare authority should be immediately alerted in order to take further actions.

Perception and attitude towards Ebola Virus Disease among traditional healers in Ibadan, Nigeria.

BACKGROUND: Nigeria experienced her first outbreak of Ebola Virus Disease (EVD) in the second-half of 2014. Since its first occurrence in Zaire and Sudan in 1976, most studies on EVD were clinically based and were carried out using biomedical approaches. No empirical social science/behavioural-oriented study exists on the deadly EVD in Nigeria. OBJECTIVE: This study examined the traditional healers' perception and attitude towards Ebola virus disease in Ibadan metropolis. STUDY DESIGN: Purposive sampling method was used to select a total of 23 traditional healers who specialized in different areas of traditional medicine (such as herbs selling, faith healing, divination, and general practice). In-depth interview (IDI) method was employed in the study. RESULTS: The study found some misconceptions about the disease while the dominant attitude among the healers was that of avoidance and caution on safety. CONCLUSION: The healers' interpretations of the disease rested on the culture and individual experiences. There is thus a need to take the local cultural perceptions of the Ebola Virus Disease into consideration when controlling the disease in the future.