Addition of @entity506 to XXXX for treatment of @entity3964 @entity311 in Gambian @entity1 causes a significant but short-lived reduction in infectiousness for mosquitoes.

@entity1 @entity5427 @entity458 @entity3964 @entity506 @entity311 @entity503 @entity313
OBJECTIVES: Combination therapy using existing anti-malarials together with @entity506 ( @entity5427 ) has been advocated as a method to slow the spread of drug resistance. We assessed the effect on @entity3964 transmissibility of the addition of @entity5427 to @entity503 (CQ) in an area of The Gambia where resistance to CQ is increasing. METHODS: Gambian @entity1 with acute uncomplicated @entity3964 @entity311 were treated with either CQ monotherapy (n=120) or the combination of CQ plus three doses of @entity5427 ( @entity5427 ; n=352). Post-treatment @entity458 was assessed during a 4-week follow-up period. Experimental infections of @entity313 s.s. mosquitoes were performed with blood from @entity1 who were carrying gametocytes 7 days after starting treatment (n=69). RESULTS: The addition of @entity5427 significantly reduced post-treatment prevalence and mean density of gametocytes in the first 14 days (day 7: 43.7% vs. 12.4%, 62.4/microl vs. 6.2/microl; day 14: 32.9% vs. 3.7%; 21.9/microl vs. 5.2/microl; CQ vs. @entity5427 ), although by day 28 the benefits of the combination were substantially less marked (40.5% vs. 21.8%; 23.0/microl vs. 63.1/microl; CQ vs. @entity5427 ). The duration of gametocyte carriage over the study period was significantly lower in the @entity5427 group (5.2 days vs. 1.5 days; CQ vs. @entity5427 ). The estimated infectious proportion of @entity1 at day 7 was also lower in the combination group (19.2% vs. 3.4%; CQ vs. @entity5427 ), as were the proportion of mosquitoes infected and mean oocyst density (11.5% vs. 0.9%; 0.3 vs. 0.01; CQ vs. @entity5427 ). Treatment failure was associated with threefold and twofold higher gametocyte carriage rates during follow-up in CQ and @entity5427 groups, respectively (P<0.001 in both cases), and 26-fold and 2.3-fold higher intensity of infection at day 7 among CQ- and @entity5427 -treated @entity1 , respectively (P=0.002 and 0.30, respectively). CONCLUSION: The benefits of adding @entity5427 to CQ monotherapy in lowering gametocyte prevalence and density were transient, suggesting that the addition of @entity5427 delayed, but did not prevent, the emergence of gametocytes. This is consistent with our finding that treatment failure, and thus the presence of CQ-resistant parasites, was significantly associated with a higher gametocyte carriage rate in both treatment groups. At day 7, CQ monotherapy significantly favoured transmission of resistant infections, which showed an 11-fold greater intensity of transmission compared with infections that were successfully treated. In contrast, the combination of @entity5427 did not significantly favour resistant infections at day 7. We conclude that significant transmission-reduction is achieved by the combination but is not maintained because of the recrudescence of CQ-resistant parasites.
