Preclinical Assessment of the Treatment of Second-Stage African Trypanosomiasis with Cordycepin and Deoxycoformycin

There is an urgent need to substitute the highly toxic arsenic compounds still in use for treatment of the encephalitic stage of African trypanosomiasis, a disease caused by infection with Trypanosoma brucei. We exploited the inability of trypanosomes to engage in de novo purine synthesis as a therapeutic target. Cordycepin was selected from a trypanocidal screen of a 2200-compound library. When administered together with the adenosine deaminase inhibitor deoxycoformycin, cordycepin cured mice inoculated with the human pathogenic subspecies T. brucei rhodesiense or T. brucei gambiense even after parasites had penetrated into the brain. Successful treatment was achieved by intraperitoneal, oral or subcutaneous administration of the compounds. Treatment with the doublet also diminished infection-induced cerebral inflammation. Cordycepin induced programmed cell death of the parasites. Although parasites grown in vitro with low doses of cordycepin gradually developed resistance, the resistant parasites lost virulence and showed no cross-resistance to trypanocidal drugs in clinical use. Our data strongly support testing cordycepin and deoxycoformycin as an alternative for treatment of second-stage and/or melarsoprol-resistant HAT

Comparison of outcomes of a community-based education program executed with and without active community involvement

Objective : The aim of this study was to evaluate the applicability of a previously designed set of generic objectives for community-based education (CBE) emphasising community involvement. Methods : The study was designed as a non-blinded, randomised trial. Experimental and conventional groups of students following CBE programmes either closely or weakly matching the set of generic objectives were compared. Student groups were subjected to passive participatory observation. Students evaluated their programmes through questionnaires. The impact of student interventions was assessed by community compliance. Community perception of the programmes was evaluated through structured interviews with community representatives. Results : Students in experimental groups appreciated their programme more than students in conventional groups. High compliance and appreciation were recorded in communities hosting the modified programme. Most students in conventional groups judged their posting negatively, largely because of the high number of households to be visited. Health interventions performed by conventional groups lacked co-operation between students and the community. Communities hosting conventional groups felt their health needs were scarcely discussed and addressed. Conclusions The modification of an existing CBE programme to better match a set of generic CBE objectives emphasising community involvement had a positive effect on programme outcomes and levels of appreciation by both students and hosting communities. However, some confounding variables could not be controlled. Colleagues planning comparable studies may take advantage of the lessons we learned while performing this study