BackgroundIn malaria-endemic countries, large proportions of infected individuals are asymptomatic, constituting a reservoir of parasites for infection of newly hatched mosquitoes. This study evaluated the impact of screening and treatment of asymptomatic carriers of Plasmodium falciparum.MethodsEighteen villages were randomized (1:1) to study arms and inhabitants participated in four community screening campaigns: three before the rainy season ~1 month apart, and the fourth after the rains at ~12 months. On day 1 of campaigns 1–3, asymptomatic carriers in the intervention arm were identified by rapid diagnostic test and treated with artemether-lumefantrine. Outcomes were symptomatic malaria with parasite density >5,000/μL per person-year in children < 5 years and change in haemoglobin between days 1 and 28 of campaign 1.ResultsAt 12 months, the number of symptomatic malaria episodes with a parasite density >5,000/μL per person-year in children < 5 years was not significantly different between arms (1.69 vs 1.60, p = 0.3482). Mean haemoglobin change in asymptomatic carriers during campaign 1 was greater in the intervention vs control arm (+0.53 g/dL vs -0.21 g/dL, p < 0.0001). ANCOVA demonstrated that mean asymptomatic carriage at the cluster level was lower in the intervention vs control arm at day 1 of campaigns 2 (5.0% vs 34.9%, p < 0.0001) and 3 (3.5% vs 31.5%, p < 0.0001), but showed only a small difference at day 1 of campaign 4 (34.6% vs 37.6%, p = 0.2982). Mean gametocyte carriage was lower in the intervention vs control arm at day 1 of campaigns 2 and 3 (0.7% vs 5.4%, p < 0.0001; 0.5% vs 5.8%, p < 0.0001), but was similar at day 1 of campaign 4 (4.9% vs 5.1%, p = 0.7208).ConclusionsSystematic screening and treatment of asymptomatic carriers at the community level did not reduce clinical malaria incidence in the subsequent transmission season, indicating greater levels of parasite clearance are required to achieve a sustained impact in this setting.
We have examined the action of endothelin on healthy and diseased human epicardial coronary arteries to assess its possible role in coronary vascular disorders such as vasospasm and atherosclerosis. Endothelin (10(-10) mol l-1-10(-7) mol l-1) produced dose-dependent contractions in both normal and diseased vessels. The level of constriction was significantly greatly in healthy vessels at 10(-8) mol l-1 endothelin. A greater response was recorded in smaller, more distal vessel segments, irrespective of the pathology of the tissue. Endothelium denudation of disease-free segments had no significant effect on the response to endothelin. In the presence of a threshold dose of endothelin (10(-9) mol l-1), there was no measurable increase in the tension generated by potassium chloride, the thromboxane-mimetic U46619, noradrenaline and histamine. However, the response to 5-HT showed a large increase in arteries from four patients (440-147%) but slight or no increase in arteries from another three patients. We conclude that the interaction with other vasoconstrictor substances is a possible mechanism whereby endothelin may be involved in coronary artery vasospasm. In addition, endothelin may also be involved in the regulation of vascular tone of the small vessels of the heart.
The performance of the saphenous vein as a bypass conduit in myocardial revascularisation may, in part, be determined by its vascular reactivity. The present study investigates whether the choice of peri-operative storage solution influences the response of this vessel to a range of vasoconstrictors and vasodilators. Saphenous vein ring segments (210) were obtained from 24 patients undergoing coronary artery bypass surgery, and following a 1 h incubation in either (1) heparinised blood, (2) heparinised saline, (3) 199-TC solution, (4) St. Thomas' cardioplegic solution or (5) plasma-lyte solution, rings of vein were set up as organ bath preparations. The relative magnitude of control constrictor response was: noradrenaline = 5-hydroxytryptamine > or = dopamine > histamine > acetylcholine. There was a significantly different (P < 0.05) enhanced response to noradrenaline and 5-hydroxytryptamine in segments stored in heparinised saline compared to 199-TC; similarly, dopamine and noradrenaline responses were significantly potentiated (P < 0.05) following storage in heparinised saline compared to cardioplegia. Storage in plasma-lyte enhanced the response significantly storage in heparinised saline compared to cardioplegia. Storage in plasma-lyte enhanced the response significantly (P < 0.05) to acetylcholine alone. None of the solutions had a significant effect on the potency (EC50) of the constrictors. Relaxations of pre-constricted segments were recorded to acetylcholine and sodium nitroprusside, but there was no difference in efficacy or potency in these responses following storage in the different solutions. This study demonstrates that the choice of peri-operative storage solution may influence the vascular reactivity of the human saphenous vein.
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