Sleeping sickness at the crossroads

Human African trypanosomiasis (HAT; sleeping sickness) is a disease with truly historic dimensions [...

The orchid flora and distribution of species on the island of Vis (eastern Adriatic, Croatia)

Floristic investigations were carried out on the island of Vis during spring 2004. Two hundred and sixty three vascular plants were recorded, including 23 taxa of Orchidaceae. The island is a new locality for the orchids Cephalanthera longifolia, O.scolopax, Orchis purpurea and Spiranthes spiralis. On the basis of our investigations and the floristic data published so far, there are 27 taxa of orchids on the island of Vis. The distribution of the observed orchids was mapped by GPS. Some nature conservation considerations complete the investigations

Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).

BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense

Fexinidazole for human African trypanosomiasis, the fruit of a successful public-private partnership

After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenges of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 microM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030

Microclimate and the Zoonotic Cycle of Tick-Borne Encephalitis Virus in Switzerland

The focal distribution of tick-borne encephalitis virus (TBEV; Flaviviridae, Flavivirus) appears to depend mainly on cofeeding transmission between infected Ixodes ricinus L. nymphs and uninfected larvae. To better understand the role of cofeeding ticks in the transmission of TBEV, we investigated tick infestation of rodents and the influence of microclimate on the seasonality of questing I. ricinus ticks. A 3-yr study was carried out at four sites, including two confirmed TBEV foci. Free-living ticks and rodents were collected monthly, and microclimatic data were recorded. A decrease in questing nymph density was observed in 2007, associated with low relative humidity and high temperatures in spring. One site, Thun, did not show this decrease, probably because of microclimatic conditions in spring that favored the questing nymph population. During the same year, the proportion of rodents carrying cofeeding ticks was lower at sites where the questing nymph density decreased, although the proportion of infested hosts was similar among years. TBEV was detected in 0.1% of questing ticks, and in 8.6 and 50.0% of larval ticks feeding on two rodents. TBEV was detected at all but one site, where the proportion of hosts with cofeeding ticks was the lowest. The proportion of hosts with cofeeding ticks seemed to be one of the factors that distinguished a TBEV focus from a non-TBEV focus. The enzootic cycle of TBEV might be disrupted when dry and hot springs occur during consecutive year

Transparent reporting of recruitment and informed consent approaches in clinical trials recruiting children with minor parents in sub-Saharan Africa: a secondary analysis based on a systematic review

BACKGROUND: Standardised checklists of items to be addressed in clinical study protocols and publications are promoting transparency in research. However, particular specifications for exceptional cases, such as children with minor parents are missing. This study aimed to examine the level of transparency regarding recruitment and informed consent approaches in publications of clinical trials recruiting children with minor parents in sub-Saharan Africa. We thereby focused particularly on the transparency about consenting persons (i.e. proxy decision-makers) and assessed the need to expand reporting guidelines for such exceptional cases. METHODS: We conducted a secondary analysis of clinical trial publications previously identified through a systematic review. Multiple scientific databases were searched up to March 2019. Clinical trial publications addressing consent and potentially recruiting children with minor parents in sub-Saharan Africa were included. 44 of the in total 4382 screened articles met our inclusion criteria. A descriptive analysis was performed. RESULTS: None of the included articles provided full evidence on whether any recruited children had minor parents and how consent was obtained for them. Four proxy decision-maker types were identified (parents; parents or guardians; guardians; or caregivers), with further descriptions provided rarely and mostly in referenced clinical trial registrations or protocols. Also, terminology describing proxy decision-makers was often used inconsistently. CONCLUSIONS: Reporting the minimum maternal age alongside maternal data provided in baseline demographics can increase transparency on the recruitment of children with minor mothers. The CONSORT checklist should require clinical trial publications to state or reference exceptional informed consent procedures applied for special population groups. A standardized definition of proxy decision-maker types in international clinical trial guidelines would facilitate correct and transparent informed consent for children and children with minor parents. STUDY REGISTRATION: CRD42018074220

The good clinical practice guideline and its interpretation - perceptions of clinical trial teams in sub-Saharan Africa

To explore the advantages and challenges of working with the Good Clinical Practice (GCP)-International Conference of Harmonization (ICH) E6 guideline and its interpretation from the perspective of clinical trial teams based in sub-Saharan Africa.; We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal and thematically analysed the responses.; Clinical trial teams perceived working with ICH-GCP as highly advantageous and regarded ICH-GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one-third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH-GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously.; Clinical trial teams in sub-Saharan Africa perceived GCP as a helpful guideline, despite having been developed by northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers

Challenges and insights in the exploration of the low abundance human ocular surface microbiome.

PURPOSE The low microbial abundance on the ocular surface results in challenges in the characterization of its microbiome. The purpose of this study was to reveal factors introducing bias in the pipeline from sample collection to data analysis of low-abundant microbiomes. METHODS Lower conjunctiva and lower lid swabs were collected from six participants using either standard cotton or flocked nylon swabs. Microbial DNA was isolated with two different kits (with or without prior host DNA depletion and mechanical lysis), followed by whole-metagenome shotgun sequencing with a high sequencing depth set at 60 million reads per sample. The relative microbial compositions were generated using the two different tools MetaPhlan3 and Kraken2. RESULTS The total amount of extracted DNA was increased by using nylon flocked swabs on the lower conjunctiva. In total, 269 microbial species were detected. The most abundant bacterial phyla were Actinobacteria, Firmicutes and Proteobacteria. Depending on the DNA extraction kit and tool used for profiling, the microbial composition and the relative abundance of viruses varied. CONCLUSION The microbial composition on the ocular surface is not dependent on the swab type, but on the DNA extraction method and profiling tool. These factors have to be considered in further studies about the ocular surface microbiome and other sparsely colonized microbiomes in order to improve data reproducibility. Understanding challenges and biases in the characterization of the ocular surface microbiome may set the basis for microbiome-altering interventions for treatment of ocular surface associated diseases

Genomic detection of a secondary family burial in a single jar coffin in early Medieval Korea

Abstract Objectives Family relationship is a key to understand the structure of past societies but its archeological reconstruction mostly stays circumstantial. Archaeogenetic information, especially genome-wide data, provide an objective approach to accurately reconstruct the familial relationship of ancient individuals, thus allowing a robust test of an archaeology-driven hypothesis of kinship. In this study, we applied this approach to disentangle the genetic relationship of early Medieval individuals from Korea, who were secondarily co-buried in a single jar coffin. Materials and Methods We obtained genome-wide data of six early Medieval Korean individuals from a jar coffin. We inferred the genetic relatedness between these individuals and characterized their genetic profiles using well-established population genetics methods. Results Congruent with the unusual pattern of multiple individuals in a single jar coffin, genome-wide analysis of these individuals shows that they form an extended family, including a couple, their two children and both paternal and maternal relatives. We show that these early Medieval Koreans have a genetic profile similar to present-day Koreans. Discussion We show that an unusual case of the secondary multiple burial in a single jar coffin reflects family relationship among the co-buried individuals. We find both paternal and maternal relatives co-buried with the nuclear family, which may suggest a family structure with limited gender bias. We find the genetic profile of early Medieval Koreans similar to that of present-day Koreans, showing that the genetic root of the present-day Koreans goes back at least 1500?years in the Korean peninsula.1 Introduction 2 Materials and methods 2.1 Archeological context of the Gunsan jar coffin 2.2 Permission for destructive analyses of skeletal elements 2.3 Skeletal analysis 2.4 Sampling of skeletal materials 2.5 Ancient DNA laboratory work and sequencing 2.6 Ancient DNA sequencing data processing and authentication 2.7 Reprocessing of whole genome sequences of present-day Koreans 2.8 Data set compilation 2.9 Principal component analysis 2.10 Genetic kinship analysis 2.11 Runs of homozygosity analysis 2.12 F-statistics and qpWave/qpAdm analysis 3 Results 3.1 | Ancient genome-wide data production 3.2 | A familial relationship of individuals from a single jar coffin 3.3 | The genetic profile of early medieval Koreans 4 Discussio

Clinical study on the melarsoprol-related encephalopathic syndrome: risk factors and HLA association

Melarsoprol administration for the treatment of late-stage human African trypanosomiasis (HAT) is associated with the development of an unpredictable and badly characterized encephalopathic syndrome (ES), probably of immune origin, that kills approximately 50% of those affected. We investigated the characteristics and clinical risk factors for ES, as well as the association between the Human Leukocyte Antigen (HLA) complex and the risk for ES in a case-control study. Late-stage Gambiense HAT patients treated with melarsoprol and developing ES (69 cases) were compared to patients not suffering from the syndrome (207 controls). Patients were enrolled in six HAT treatment centres in Angola and in the Democratic Republic of Congo. Standardized clinical data was obtained from all participants before melarsoprol was initiated. Class I (HLA-A, HLA-B, HLA-Cw) and II (HLA-DR) alleles were determined by PCR-SSOP methods in 62 ES cases and 189 controls. The principal ES pattern consisted in convulsions followed by a coma, whereas ES with exclusively mental changes was not observed. Oedema, bone pain, apathy, and a depressed humour were associated with a higher risk of ES, while abdominal pain, coma, respiratory distress, and a Babinski sign were associated with higher ES-associated mortality. Haplotype C*14/B*15 was associated with an elevated risk for ES (OR: 6.64; p-value: 0.008). Haplotypes A*23/C*14, A*23/B*15 and DR*07/B*58 also showed a weaker association with ES. This result supports the hypothesis that a genetically determined peculiar type of immune response confers susceptibility for ES