Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: report from a field study

BACKGROUND: Nifurtimox-eflornithine combination therapy (NECT) for the treatment of second stage gambiense human African trypanosomiasis (HAT) was added to the World Health Organization's Essential Medicines List in 2009 after demonstration of its non-inferior efficacy compared to eflornithine therapy. A study of NECT use in the field showed acceptable safety and high efficacy until hospital discharge in a wide population, including children, pregnant and breastfeeding women, and patients with a HAT treatment history. We present here the effectiveness results after the 24-month follow-up visit. METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, open label, single arm phase IIIb study, second stage gambiense HAT patients were treated with NECT in the Democratic Republic of Congo. Clinical cure was defined 24 months after treatment as survival without clinical and/or parasitological signs of HAT. Of the 629 included patients, 619 (98.4%) were discharged alive after treatment and were examined for the presence of trypanosomes, white blood cell count in cerebro-spinal fluid, and disease symptoms. The clinical cure rate of 94.1% was comparable for all subpopulations analyzed at the 24-month follow-up visit. Self-reported adverse events during follow-up were few and concerned mainly nervous system disorders, infections, and gastro-intestinal disorders. Overall, 28 patients (4.3%) died during the course of the trial. The death of 16 of the 18 patients who died during the follow-up period was assessed as unlikely or not related to NECT. Within 24 months, eight patients (1.3%) relapsed and received rescue treatment. Sixteen patients were completely lost to follow-up. CONCLUSIONS/SIGNIFICANCE: NECT treatment administered under field conditions was effective and sufficiently well tolerated, no major concern arose for children or pregnant or breastfeeding women. Patients with a previous HAT treatment history had the same response as those who were naive. In conclusion, NECT was confirmed as effective and appropriate for use in a broad population, including vulnerable subpopulations. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, number NCT00906880

Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial

BACKGROUND: Fexinidazole has been reported as an effective oral monotherapy against non-severe gambiense human African trypanosomiasis in a recent trial in adults. We aimed to assess the safety and efficacy of fexinidazole in children across all disease stages of gambiense human African trypanosomiasis. METHODS: We did a multicentre, single-arm, open-label, phase 2-3 trial at eight district hospitals in the Democratic Republic of the Congo. We recruited children with a Karnofsky score of more than 50, those aged 6 years to younger than 15 years, weighing 20 kg or more, and with confirmed gambiense human African trypanosomiasis (any stage). Children weighing 20 kg or more and less than 35 kg received oral fexinidazole of 1200 mg (two x 600 mg tablets) once per day for 4 days (days 1-4) followed by 600 mg (one x 600 mg tablet) once per day for 6 days (days 5-10). Children weighing 35 kg or more received oral fexinidazole of 1800 mg (three x 600 mg tablets) once per day for 4 days (days 1-4), followed by 1200 mg (two x 600 mg tablets) once per day for 6 days (days 5-10). The primary endpoint was fexinidazole treatment success rate 12 months after end of treatment. A rate greater than 80% was deemed acceptable and a target value of 92% was aimed for. Safety was assessed through routine monitoring. This study is completed and registered with ClinicalTrials.gov, number NCT02184689. FINDINGS: Between May 3, 2014, and Nov 22, 2016, we screened a total of 130 paediatric patients, of whom 125 (96%) received at least one dose of fexinidazole. All 125 patients (69 [55%] patients with stage 1, 19 [15%] with early stage 2, and 37 [30%] with late stage 2 gambiense human African trypanosomiasis) completed the 10-day treatment. Treatment success rate at 12 months was 97.6% (95% CI 93.1-99.5; 122 of 125 patients). The primary endpoint was met and the targeted value of 92% was exceeded. Treatment success at 12 months was elevated across all disease stages: 98.6% (95% CI 92.2-99.9; 68 of 69 patients) in stage 1, 94.7% (74.0-99.9; 18 of 19 patients) in early stage 2, and 97.3% (85.8-99.9; 36 of 37 patients) in late stage 2 gambiense human African trypanosomiasis. No new safety issues were observed beyond those found in adult trials. Overall, 116 (93%) of 125 patients reported 586 treatment-emergent adverse events, mainly mild or moderate. The most frequently reported treatment-emergent adverse events of interest during hospital admission were vomiting (86 [69%] of 125) and headache (41 [33%]). Seven (6%) of 125 patients had severe malaria, which was often accompanied by anaemia that was unrelated to fexinidazole. One patient died following dyspnoea and injury due to traumatic aggression 172 days after end of treatment, which was considered unrelated to fexinidazole or gambiense human African trypanosomiasis. INTERPRETATION: Oral fexinidazole is a safe and effective first-line treatment option across all gambiense human African trypanosomiasis disease stages in paediatric patients. FUNDING: Through the Drugs for Neglected Diseases initiative: the Bill & Melinda Gates Foundation (USA), the Republic and Canton of Geneva (Switzerland), the Dutch Ministry of Foreign Affairs (Netherlands), the Norwegian Agency for Development Cooperation (Norway), the Federal Ministry of Education and Research through KfW (Germany), the Brian Mercer Charitable Trust (UK), and other private foundations and individuals from the human African trypanosomiasis campaign. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Should I Get Screened for Sleeping Sickness? A Qualitative Study in Kasai Province, Democratic Republic of Congo

Active screening strategies are common disease control interventions in the context of poor and remote rural communities with no direct access to healthcare facilities. For such activities to be as effective as possible, it is necessary that they are well adapted to local socio-economic and cultural settings. Our aim was to gain insight into the barriers communities in the Kasai-Oriental province of the Democratic Republic of Congo experience in relation to their participation in active screening activities for African sleeping sickness. Participation rates seem to be especially low in this province compared to other endemic regions in the country. We found several important factors to be in play, a number of which could be addressed by adapting the operational procedures of the mobile teams that perform the active screening activities (e.g., improved confidentiality during the screening procedure). However, more profound considerations were found in the form of regional beliefs related to the treatment of the disease. Although not based on rational grounds, these prohibitions seem to pose a significant barrier in a person's decision to seek diagnosis and treatment. A better understanding of these prohibitions and their origin could lead to improved participation rates for sleeping sickness screening in Kasai-Oriental

An experience of developing mission critical software for BIRD attitude control using UML

The cry for quality and software release schedules are nightmares for the software engineers. The unification of last decade techniques in the Unified Modeling Language (UML) give a rise for stable platform for software modelling. We show how the UML fit the software engineering process and report the experience made with UML during the development of the BIRD attitude control system

''Europe is no longer Europe'': montaging borderlands of help for a radical politics of place

In this paper, we position the societal expectation of the ‘grateful refugee’ in the larger European script of placing migrant help and integration. We ask how might we re-imagine geographies of migrant ‘help’ so as to break with the dominant ontologies of places as sites embedded within the nation-state and the accompanying relations of power which displace the migrant in a perpetual penumbra of gratefulness? By montaging a series of contrapuntal vignettes of borderlands producing Europe, we examine the moral geographies of help and debt and how geographical imaginations of place and place-identities of practices of refugee-help today are entangled with mid-20th century wartime aid. Drawing inspiration from the negritude movement, we argue that such ‘untimely articulations’ produce ‘sites of décalage’ where Europe (as manifesting in such entangled moral geo-histories of help) is no longer Europe, suggesting an initial vocabulary for a radical politics of place