Discussion
ADVERSE EVENTS, CPS, ADVERSE EVENT, INFLAMMATORY RESPONSES
Here, we conducted the first trial using the Nevertheless, this immunization regimen was almost certainly still sub-optimal for inducing protective responses. Firstly, the unexpected bloodstage multiplication of NF135 parasites observed under mefloquine prophylaxis meant that all participants in cohort A required rescue treatment with atovaquone/proguanil following their first immunization and a proportion also following their second. Measurement of atovaquone in these participants’ blood immediately prior to their second and third immunizations revealed higher residual concentrations than anticipated based on the previously reported half-life of 2 to 3 days, and these concentrations were higher than the predicted ICThe drug susceptibility profile of NF135 differed from that based on its in vitro profile. Despite the similar mefloquine in vitro ICHigher numbers of adverse events occurred after NF135 immunizations compared to previous NF54 CPS trials, contrary to previous observations in participants challenged with five NF135-infected mosquitoes [A further potential safety concern is the occurrence of a cardiac serious adverse event, but it is questionable whether this can be attributed specifically to The unfavorable tolerability and drug susceptibility profile of NF135 preclude its further development as a strain for immunization under the CPS approach evaluated here. Whereas concomitant use of non-steroid anti-inflammatory drugs to decrease inflammatory responses associated with the high liver-to-blood inoculum could potentially improve tolerability [