Review 3: "Dramatic Resurgence of Malaria after 7 Years of Intensive Vector Control Interventions in Eastern Uganda"

RR:C19 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: This is a clear and informative study, well written and comprehensive. Kamya et al describe an observational study to confirm the causal influences for a resurgence of malaria in a district where IRS has been in place for nearly a decade. Combining epidemiological and entomological data, the authors conclude that the change in IRS insecticide  allowed an increase in density of resistant An. funestus  replacing the less effective vector An. arabiensis. Where no IRS had been implemented, the vector species composition was not altered and thus, although remaining high, malaria incidence and prevalence did not show the same pattern of resurgence and decrease after the potentially ineffective insecticide was replaced.

General typo note: many end of sentence references are listed after the full stop.

• L81 – Uganda has universal distribution of LLINs – any info on usage?

• L83 -  ‘one of the largest IRS programmes…’  - in relation to?  Is there a reference?

• L87 – ‘our group’ replace with name of institute

• L100 – [comment] – did the authors suspect the cause of the resurgence was to do with the change in IRS insecticide when the investigation was started? Was the reversion back to the organophosphate IRS a consequence of the study – or is this a retrospective study done more as an observation of how the different formulations may have had an impact?

• L123 – why was the IRS compound changed to Actellic in 2016? Part of a considered rotations scheme? (same question for the change to clothianidin 2020)

• L127 – the decision to revert to Actellic was made due to this study?

• L133 – did the use of PBO nets from 2020 have an impact on malaria in Busia?

• L139 – how many sites are regularly assessed/surveyed and how often? (for spatial and temporal trends) or are these based on cases presented at the health centre?

• L222 - italicise  ‘Anopheles’

• L227 – why was IR assessed in mosquitoes from neighbouring district and not the district where the study was conducted?

• L511 – other contributing factors could also be explored relating to the vector biology and ecology – the study indicates that it was a lack of control of An. funestus that may have caused much of the resurgence – and An. funestus has quite different behaviour from An. gambiae and An. arabiensis. For example, larval sites can be permanent or semi-permanent compared to the more transient larval sites of An. gambiae and An. funestus can replace An. arabiensis  in a process of temporal succession as the species prefers sites with more emergent vegetation compared to a more open larval sites of An. arabiensis, so some consideration of the surrounding environment (agriculture, swamps etc) would be useful for context – as well as other factors thar may influence the vectors – was rainfall lower over the study period? – potentially reducing An. gambiae but having little impact on An. funestus…