Review 2: "The Transmission Blocking Activity of Artemisinin-Combination, Non-Artemisinin, and 8-Aminoquinoline Antimalarial Therapies: A Pooled Analysis of Individual Participant Data"

RR\ID Evidence Scale rating by reviewer:

• Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: It is interesting and useful to combine the recent trials of the effect of different ACTs on gametocyte prevalence and density, proportion of infected mosquitoes and mean oocyst density. The number of participants per study was relatively low, so combining them improves the power of the findings. The paper has been carefully compiled with explanations of the similarities and differences between the trials, with useful graphics such as Figure 1 to show when outcomes were assessed. The trials were done in similar fashion with consistent methods for assessing outcomes such as infectivity.  In fact all the graphics used are very clear and show the differences between the ACTs.  There are apparently a large number of supplementary files which I wanted to consult but could not find a link to. 

The results of the comparisons between DHA-PPQ, SP-AQ, PY-AS, AS-AQ and AL are all clear, especially in Fig 6. I don't find it valid to combine all the Non-ACT-PQ and compare with ACT-PQ.  Non-ACT-PQ includes only SP-AQ with PQ (N=20) if I am not mistaken (Table 1).  ACT-PQ includes AL, AL-AQ, DHA-PPQ, AS-AQ and PY-AS with high heterogeneity between their effects (without PQ) and many more participants (N=142). I don't think that you can conclude from this that PQ should be added to 'ACT'. The statement in lines 364 to 366 that "adding a single low dose of PQ ...to any ACT accelerated the clearance of gametocytes and led to significantly greater reduction in mosquito infection rate..." needs more statistical justification. It likely depends on the ACT, but without access to the data on separate ACTs with and without PQ in valid comparisons I cannot assess.  Similarly calling the last graph in Fig 6 "ACT-TQ" is a bit misleading when it is only DHA-PPQ in this group. 

There is so much valuable information in this paper, much of which is apparently in supplementary files. I think it could be split into two or more papers, with the first main findings comparing the ACTs, and the PQ and TQ addition in a separate analysis.  This would allow inclusion of more of the relevant data in the main text, such as the mosquito infection data (lines 296 to 298).

I rate this preprint as 'reliable' because of the strength of the results for the different ACTs (without PQ), despite the concerns about the PQ addition data and the pooling of the different ACTs in this comparison.