REACTIVE TARGETED PARASITE ELIMINATION (TPE) Study Title: Evaluating the effectiveness and feasibility of reactive targeted parasite elimination vs. reactive case detection as a community- level intervention in response to a passively identified index case in Swaziland Funded by: The Bill and Melinda Gates Foundation Principal Investigators: Michelle Hsiang, Roly Gosling, Simon Kunene ClinicalTrials.gov Number: NCT02315690 Protocol Version 1.10, 30 March 2016 Table of Contents Study summary ........................................................................................................................................................................................... 5 Study personnel and institutions ........................................................................................................................................................ 6 Principal Investigators......................................................................................................................................................................... 6 Other Key Personnel and Collaborators ...................................................................................................................................... 6 Study members and responsibilities.......................................................................................................................................... 10 Administrative contacts .................................................................................................................................................................. 14 Institutional review boards ............................................................................................................................................................ 14 Primary Funder ................................................................................................................................................................................... 15 Abbreviations & acronyms .................................................................................................................................................................. 16 1 Background ....................................................................................................................................................................................... 17 1.1 Malaria in Swaziland ....................................................................................................................................................... 17 1.2 Challenges for Malaria Elimination ........................................................................................................................... 17 1.3 Reactive case detection (RACD) ................................................................................................................................. 17 1.4 Targeted parasite elimination (TPE) ......................................................................................................................... 19 1.5 RACD vs. reactive TPE ..................................................................................................................................................... 19 1.6 Drug regimens .................................................................................................................................................................... 20 2 Rationale ............................................................................................................................................................................................ 21 3 Study aims ......................................................................................................................................................................................... 23 4 Study design & methods.............................................................................................................................................................. 24 4.1 Overview .............................................................................................................................................................................. 24 4.2 Study site and study population ................................................................................................................................ 24 4.3 Randomization of localities (clusters) ...................................................................................................................... 24 4.4 Target Areas ........................................................................................................................................................................ 28 4.5 Inclusion and exclusion criteria .................................................................................................................................. 30 5 Baseline Preventative Interventions – LLINs and IRS ...................................................................................................... 31 6 Enrollment ......................................................................................................................................................................................... 31 6.1 Sensitization ........................................................................................................................................................................ 31 6.2 Identification of Target Areas (through immediate case notification and Case investigation of the index case) ....................................................................................................................................................................................... 32 6.3 Informed consent ............................................................................................................................................................. 32 7 Study intervention.......................................................................................................................................................................... 33 7.1 Household-level questionnaire................................................................................................................................... 33 7.2 RACD arm - Perform RDT and refer secondary cases to health facilities ................................................. 34 7.3 TPE arm - Administration of DP .................................................................................................................................. 34 7.4 Management of sick participants .............................................................................................................................. 35 7.5 Adherence assessment .................................................................................................................................................. 35 8 Adverse event monitoring .......................................................................................................................................................... 37 8.1 Overview .............................................................................................................................................................................. 37 Swaziland TPE protocol V1.10, 30 March 2016 2 8.2 Definitions ........................................................................................................................................................................... 37 8.3 Passive identification of SAEs ...................................................................................................................................... 37 8.4 SAE report forms............................................................................................................................................................... 37 8.5 Expedited reporting of SAEs and SUSARs ............................................................................................................... 38 8.6 Management of participants with SAEs .................................................................................................................. 38 9 Follow-up surveys ........................................................................................................................................................................... 38 9.1 Overview .............................................................................................................................................................................. 38 9.2 Follow-up blood survey at 6-9 months ................................................................................................................... 38 9.3 End-line survey (at the end of the study, expected mid 2017) .................................................................... 39 10 Acceptability Assessment ............................................................................................................................................................ 39 10.1 Background and Rationale ......................................................................................................................................... 39 10.2 Aims of the Acceptability Assessment .................................................................................................................. 40 10.3 Methods for the Acceptability Assessment ........................................................................................................ 40 11 Cost-effectiveness