Human African trypanosomiasis is a neglected tropical disease that is usually fatal without treatment. WHO has revised its rhodesiense human African trypanosomiasis treatment guidelines on the basis of an independent systematic literature review and following the GRADE methodology. This Review reports on the decision-making process and summarises the new recommendations and their potential implications for health-care professionals and policy makers. Due to data scarcity, all recommendations are conditional and based on very low certainty of evidence. Fexinidazole replaces suramin and melarsoprol as the first-line therapy in individuals aged 6 years and older with a bodyweight of 20 kg or more. As fexinidazole is effective in both stages of rhodesiense human African trypanosomiasis, a lumbar puncture for staging is no longer required. In settings in which first-choice drugs are not readily available, immediate interim treatment with pentamidine is suggested. The introduction of oral fexinidazole represents an advancement in the management of rhodesiense human African trypanosomiasis considering the life-threatening adverse reactions individuals can have to melarsoprol. However, children below the age or weight limits remain ineligible for treatment with fexinidazole.
Most SARS-CoV-2 antigen-detecting rapid diagnostic tests require nasopharyngeal sampling, which is frequently perceived as uncomfortable and requires healthcare professionals, thus limiting scale-u...
Staphylococcus aureus (S. aureus) strains that produce the toxin Panton-Valentine leukocidin (PVL; PVL-SA) frequently cause recurrent skin and soft tissue infections (SSTI). PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps, but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA suffer from recurring infections whereas others are asymptomatic. We thus aimed to (a) investigate how PVL exerts its pathogenicity on neutrophils and (b) identify factors that could help to explain the predisposition of patients with recurring infections. We provide genetic and pharmacological evidence that PVL-induced NET formation is independent of NADPH-oxidase and reactive oxygen species (ROS) production. Moreover, through NET proteome analysis we identified that the protein content of PVL-induced NETs is different from NETs induced by mitogen or the microbial toxin nigericin. The abundance of the proteins cathelicidin (CAMP), elastase (NE), and proteinase 3 (PRTN3) was lower on PVL-induced NETs, and as such they were unable to kill S. aureus. Furthermore, we found that neutrophils from affected patients express higher levels of CD45, one of the PVL receptors, and are more susceptible to be killed at a low PVL concentration than control neutrophils. Neutrophils from patients that suffer from recurring PVL-positive infections may thus be more sensitive to PVL-induced NET formation, which might impair their ability to combat the infection.
Background: The Syrian conflict has led to a dramatic increase of Old World cutaneous leishmaniasis (CL), triggered by continuous population displacements, disrupted control programmes, poor shelter and sanitation. Methods: A retrospective patient record study was conducted at the Institute of Tropical Medicine and International Health in Berlin. Records of all refugees from Syria treated for CL between January 2015 and March 2020 were reviewed. Results: Twenty refugees from Syria were treated. Seventeen refugees (85%) had complex lesions, mainly due to previous therapy failure or localization on the face. A long disease duration (50% > 1 year), pronounced facial scarring (20%), recurrences (20%), or worsening of existing lesions (20%) were observed. Nine patients (45%) had been pretreated in Syria. Complete remission was achieved in 10 of 16 patients (63%) treated with perilesional antimony. Eight patients (40%) required systemic treatment, thereof four (20%) repeated systemic treatment. Eight patients (40%) reported a delay of therapy ≥3 months in Germany, thereof one patient with a delay of 12 months and one patient with a delay of 32 months. Conclusion: Between 2015 and 2020, Syrian refugees presented with severe morbidities of CL frequently requiring systemic and even consecutive systemic treatments. We assume a combination of socioeconomic and environmental factors associated with the ongoing Syrian conflict and migration to be responsible for the complex clinical presentations in this case series. More attention should be drawn to the situation of Syrian refugees with CL in countries where they are displaced to.