Phase III, Open-label, Community-based, Cluster Randomised Controlled Trial to Evaluate the Efficacy, Cost-effectiveness, and Acceptability of Attractive Targeted Sugar Baits (ATSB) for Malaria Burden Reduction in Western Kenya
Phase: NA
Conditions: Malaria
Sponsor: Liverpool School of Tropical Medicine

ATSB-Kenya Protocol (v1.1-31May21) 
1 
Title: Phase III, open-label, community-based, cluster randomised controlled trial 
to evaluate the efficacy, cost-effectiveness, and acceptability of Attractive 
Targeted Sugar Baits (ATSB) for malaria burden reduction in western Kenya  
Short Title: ATSB Study 
Trial Identifiers: 
KEMRI SERU#: 4189 
CDC IRB#: 00008118 
LSTM REC#: 21-027 
Clinicaltrials.gov 
 
 
 
 
Co-Principal Investigators: 
Aaron Samuels, MD, MHS, Centers for Disease Control and Prevention (CDC), Director, CDC-Kenya 
Malaria Research Program, P.O. Box 1578, Kisumu 40100. Mobile: +254.724.255.633; Email: 
amsamuels@cdc.gov  
 
Eric Ochomo, PhD, Kenya Medical Research Institute (KEMRI), Centre for Global Health Research 
(CGHR) Entomology Section Head, P.O. Box 1578, Kisumu 40100. Mobile: +254.723.845.457; 
Email: eochomo@kemricdc.org   
Chief Investigator: 
Feiko ter Kuile, MD, PhD, Professor in Tropical Epidemiology, Liverpool School of Tropical 
Medicine (LSTM), Pembroke Place, Liverpool L3 5QA, UK. Mobile: +44 7846 377; Email: 
feiko.terkuile@lstmed.ac.uk 
Co-investigators: See Page 7 
 
 
 
 
 
Funder: Integrated Vector Control Consortium (IVCC), UK, which is funded through a grant by the 
Bill and Melinda Gates Foundation 
Sponsor: Liverpool School of Tropical Medicine (LSTM); Pembroke Place, Liverpool L3 5QA, UK 
Phone: +44 0151 7053794; Email: lstmgov@lstmed.ac.uk   
 
 
 
 
 
Trial Registration Information: Clinicaltrials.gov <#####> 
Trial Sponsor: Liverpool School of Tropical Medicine (LSTM) 
 
Revision Chronology 
Date 
Protocol Version 
Details of 
Changes 
Authors 
Signature of the PI 
31 May 2021 
v1.1 
Original 
AS, EO, 
JG, ML, 
JJ, FTK 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement: This document contains confidential information that must not be disclosed to anyone 
other than the sponsor, the investigator team, host institution, relevant ethics committee and regulatory authorities 
 

ATSB-Kenya Protocol (v1.1-31May21) 
2 
TABLE OF CONTENTS 
 
1 
Acronyms ........................................................................................................................................ 6 
2 
Administrative information ............................................................................................................. 7 
2.1 
Title of Research Proposal ...................................................................................................... 7 
2.2 
Investigators and collaborators .............................................................................................. 7 
 
Co-Principal investigators ............................................................................................... 7 
 
Chief Investigator ............................................................................................................ 7 
 
Co-investigators .............................................................................................................. 7 
 
Non-Engaged collaborators ............................................................................................ 7 
 
Institutions ...................................................................................................................... 7 
2.3 
Protocol summaries ................................................................................................................ 8 
 
Technical summary ......................................................................................................... 8 
 
Lay Summary ................................................................................................................... 8 
 
Trial Registration data ..................................................................................................... 9 
3 
Introduction .................................................................................................................................. 12 
3.1 
ATSB background and literature review ............................................................................... 12 
3.2 
Addressing residual outdoor malaria transmission .............................................................. 12 
3.3 
ATSBs ..................................................................................................................................... 13 
3.4 
Field experience with ATSB in Mali ....................................................................................... 13 
3.5 
Field experience with ATSB in western Kenya ...................................................................... 14 
4 
Justification for the study ............................................................................................................. 14 
5 
Objectives and outcomes.............................................................................................................. 15 
5.1 
Primary objective and outcome ............................................................................................ 15 
5.2 
Secondary objectives and outcomes .................................................................................... 15 
 
Efficacy .......................................................................................................................... 15 
 
Safety ............................................................................................................................ 16 
 
Ethnographic evaluation ............................................................................................... 16 
 
Health economics .......................................................................................................... 16 
6 
Trial design and design considerations ......................................................................................... 16 
6.1 
Overview of study design ...................................................................................................... 16 
6.2 
Design Considerations........................................................................................................... 17 
 
Superiority trial to detect at least a 30% reduction ...................................................... 17 
 
Duration of trial, interim analysis and criteria for early termination ........................... 17 
 
Measures to avoid contamination ................................................................................ 17 
 
Assessment of community effects. ............................................................................... 18 
6.3 
Overview of activities and procedures ................................................................................. 19 
 
Creation of clusters ....................................................................................................... 19 
 
Baseline data collection ................................................................................................ 19 
 
Epidemiological data ..................................................................................................... 19 
 
Rapid ethnographic methods ........................................................................................ 21 
 
Sensitization of the population ..................................................................................... 21 
 
LLIN distribution ............................................................................................................ 21 
 
ATSB deployment and monitoring and maintenance ................................................... 21 
 
Entomological monitoring............................................................................................. 22 

ATSB-Kenya Protocol (v1.1-31May21) 
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Health-economic data ................................................................................................... 22 
 
Collection of environmental parameters ...................................................................... 22 
 
Human safety monitoring ............................................................................................. 22 
7 
Method: Participants, interventions, and outcomes .................................................................... 23 
7.1 
Study site ............................................................................................................................... 23 
7.2 
Eligibility criteria.................................................................................................................... 23 
 
Eligibility criteria for clusters......................................................................................... 24 
 
Eligibility criteria for participants in the cohort study .................................................. 24 
 
Eligibility criteria for households for ATSB deployment ............................................... 24 
 
Eligibility criteria for households for entomological monitoring .................................. 24 
 
Eligibility criteria for human landing catches ................................................................ 25 
 
Eligibility criteria for participants in rapid ethnographic methods evaluation 
(community members) ................................................................................................................. 25 
 
Eligibility criteria for participants in rapid ethnographic methods evaluation (ATSB 
monitoring assistants) ................................................................................................................... 25 
7.3 
Withdrawal/follow-up .......................................................................................................... 25 
7.4 
Baseline characteristics ......................................................................................................... 26 
7.5 
Intervention (ATSBs) ............................................................................................................. 26 
 
ATSB .............................................................................................................................. 26 
 
Control cluster interventions ........................................................................................ 28 
 
Other malaria control interventions ............................................................................. 28 
7.6 
Adherence and protocol deviations ...................................................................................... 29 
 
Cluster-level adherence ................................................................................................ 29 
 
Household-level adherence .......................................................................................... 29 
 
Individual-level adherence to antimalarial treatment among cohort members .......... 29 
 
Protocol deviations ....................................................................................................... 29 
7.7 
Sample size ............................................................................................................................ 30 
 
Malaria case incidence cohort ...................................................................................... 30 
 
Continous malaria indicator survey to assess malaria parasite prevalence ................. 31 
 
Entomological monitoring............................................................................................. 31 
 
Rapid ethnographic methods ........................................................................................ 32 
8 
Methods: Assignment of interventions ........................................................................................ 32 
8.1 
Allocation and randomization ............................................................................................... 32 
8.2 
Blinding ................................................................................................................................. 33 
9 
Methods: Data collection, management and analysis .................................................................. 34 
9.1 
Data collection ...................................................................................................................... 34 
 
COVID-19 mitigation efforts .......................................................................................... 34 
 
Cohort study to assess the incidence of clinical malaria .............................................. 34 
 
Continuous household survey....................................................................................... 36 
 
Passive case detection .................................................................................................. 37 
 
Entomological monitoring............................................................................................. 37 
 
ATSB Intervention monitoring ...................................................................................... 39 
 
Rapid ethnographic methods ........................................................................................ 39 
 
Economic evaluation ..................................................................................................... 41 
9.2 
Data management ................................................................................................................ 42 
 
ATSB monitoring, cohort and cMIS case report forms ................................................. 42 
 
Passive case detection .................................................................................................. 42 
 
Rapid ethnographic methods: FGD and IDI data .......................................................... 42 

ATSB-Kenya Protocol (v1.1-31May21) 
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Entomological monitoring............................................................................................. 42 
 
Economic evaluation ..................................................................................................... 43 
9.3 
Biological samples ................................................................................................................. 43 
 
Blood samples ............................................................................................................... 43 
 
Entomological samples ................................................................................................. 43 
 
Sample storage and shipping ........................................................................................ 43 
9.4 
Statistical methods ................................................................................................................ 44 
 
Interim analysis ............................................................................................................. 44 
 
General principles ......................................................................................................... 45 
 
Analysis of the primary outcome .................................................................................. 46 
 
Other efficacy outcome analyses .................................................................................. 48 
 
Analysis of entomological data ..................................................................................... 49 
 
Focus group discussions and in-depth interviews ........................................................ 49 
 
Economic evaluation ..................................................................................................... 50 
 
Harms ............................................................................................................................ 50 
10 Methods: Monitoring .................................................................................................................... 50 
10.1 
Trial Governance ................................................................................................................... 50 
 
Trial steering committee ............................................................................................... 50 
 
Data safety and monitoring committees ...................................................................... 50 
10.2 
Trial monitoring and auditing ............................................................................................... 51 
 
Trial monitoring ............................................................................................................. 51 
 
Auditing ......................................................................................................................... 51 
 
Role of sponsor ............................................................................................................. 51 
10.3 
Safety monitoring and reporting .......................................................................................... 51 
 
Adverse events and serious adverse events ................................................................. 51 
10.4 
Quality assurance .................................................................................................................. 51 
 
Quality assurance field-based activities ........................................................................ 51 
 
Quality assurance data .................................................................................................. 52 
10.5 
Data collection methods & storage ...................................................................................... 53 
 
Methodologies for data collection/generation ............................................................ 53 
 
Data quality and standards ........................................................................................... 53 
 
Managing, storing, and curating data ........................................................................... 53 
 
Data preservation strategy and standards.................................................................... 53 
11 Ethics and dissemination .............................................................................................................. 53 
11.1 
Declaration of Helsinki .......................................................................................................... 53 
11.2 
Research ethics and regulatory approval ............................................................................. 54 
 
Ethical review and approval of study protocol ............................................................. 54 
 
Protocol amendments................................................................................................... 54 
 
Regulatory approval ...................................................................................................... 54 
 
Inclusion of vulnerable subjects: children and pregnant women ................................. 54 
 
Consent procedures ...................................................................................................... 54 
11.3 
Risks and benefits ................................................................................................................. 55 
 
Risks to study participants ............................................................................................ 55 
 
Risks to the population or environment ....................................................................... 57 
 
Adequacy of protection against risk ............................................................................. 58 
 
Potential benefits of the research to participants ........................................................ 59 
 
Health care during the trial ........................................................................................... 59 
 
Trial insurance ............................................................................................................... 60 

ATSB-Kenya Protocol (v1.1-31May21) 
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Post-trial care ................................................................................................................ 60 
11.4 
Declaration of interest .......................................................................................................... 60 
11.5 
Access to source data/documents ........................................................................................ 60 
11.6 
Expenses reimbursement and other payments to participants ........................................... 60 
11.7 
Dissemination and application of the results ....................................................................... 60 
11.8 
Authorship and publications ................................................................................................. 61 
11.9 
Data Sharing Statement ........................................................................................................ 61 
12 Timeframe and duration of the study ........................................................................................... 62 
13 Roles of the investigators.............................................................................................................. 63 
13.1 
Investigators .......................................................................................................................... 63 
13.2 
Non-Engaged Collaborators .................................................................................................. 64 
14 Financial aspects and conflict of interest ...................................................................................... 64 
14.1 
Funding for the trial .............................................................................................................. 64 
14.2 
Provision of ATSB .................................................................................................................. 64 
14.3 
Budget ................................................................................................................................... 64 
 
Budget table .................................................................................................................. 64 
 
Budget justification ....................................................................................................... 65 
15 References .................................................................................................................................... 66 
16 Annexes ......................................................................................................................................... 68 
16.1 
Annex I. Dinotefuran safety data sheet ................................................................................ 68 
16.2 
Annex II: Denatonium benzoate safety data sheet ............................................................... 75 
16.3 
Annex III: ATSB Stations: Disposal options assessment ........................................................ 80 
16.4 
Annex IV: ATSB human and environmental safety assessment report .............................. 109 
 

ATSB-Kenya Protocol (v1.1-31May21) 
6 
1 ACRONYMS 
ACT 
Artemisinin-based combination therapy 
AE 
Adverse event 
ANC 
Antenatal care 
ATSB 
Attractive targeted sugar bait 
CDC 
(US) Centers for Disease Control and Prevention 
cMIS 
Continuous Malaria Indicator Survey 
CRCT 
Cluster randomized controlled trial  
CS ELISA 
Circumsporozoite citrate synthase enzyme-linked immunosorbent assay  
DBS 
Dried blood spot 
DHIS2 
District health information system II 
DSMB 
Data safety monitoring board 
EIR 
Entomological inoculation rate 
GPS 
Global positioning system 
hCG 
Human chorionic gonadotropin 
HH 
Household 
HRP2 
Histidine-rich protein-2 
FGD 
Focus group discussion 
ICC 
Intracluster correlation coefficient 
ICER 
Incremental cost-effectiveness ratio 
IDI 
In-depth interview 
IPTp 
Intermittent preventative treatment in pregnancy  
IRS 
Indoor residual spray  
IVCC 
Innovative Vector Control Consortium  
KAP 
Knowledge, attitudes, and practices  
KEMRI 
Kenya Medical Research Institute 
LLIN 
Long-lasting insecticidal net 
LSTM 
Liverpool School of Tropical Medicine 
MACEPA 
Malaria Control and Evaluation Partnership in Africa 
MPAC 
Malaria Policy and Advocacy Committee  
NIH 
National Institutes of Health  
NIRS 
Near-infrared spectroscopy  
PCR 
Polymerase chain reaction  
pLDH 
Plasmodium lactate dehydrogenase 
RDT 
Rapid diagnostic test 
SAE 
Serious adverse event 
SEB 
Styrene ethylene/butylene styrene  
UV 
Ultraviolet  
VCAG 
Vector Control Advisory Group 
WHO 
World Health Organization  
 
 

ATSB-Kenya Protocol (v1.1-31May21) 
7 
2 ADMINISTRATIVE INFORMATION 
2.1 TITLE OF RESEARCH PROPOSAL 
Phase III, open-label, community-based, cluster randomised controlled trial to evaluate the efficacy, 
cost-effectiveness, and acceptability of Attractive Targeted Sugar Baits (ATSB) for malaria burden 
reduction in western Kenya 
2.2 INVESTIGATORS AND COLLABORATORS 
 Co-Principal investigators 
Dr Aaron Samuels 1,3 
Dr Eric Ochomo 2 
 Chief Investigator 
Prof Feiko ter Kuile 2,3 
 Co-investigators 
Dr Julia Janssen1 
Dr John Gimnig1 
Dr Simon Kariuki2 
Mr Kephas Otieno2 
Dr Caroline Ogwang2 
Dr Maia Lesosky3 
Dr. George Okello2 
 Non-Engaged collaborators 
Dr Megan Littrell4 
Dr Kennedy Odhiambo Oruenjo5 
2.3 INSTITUTIONS 
1. 
Centers for Disease Control and Prevention (CDC) 
2. 
Kenya Medical Research Institute (KEMRI) 
3. 
Liverpool School of Tropical Medicine (LSTM) 
4. 
PATH 
5. 
Siaya County Ministry of Health, Kenya Ministry of Health 
 

ATSB-Kenya Protocol (v1.1-31May21) 
8 
2.4 PROTOCOL SUMMARIES 
 Technical summary 
The effectiveness of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in 
western Kenya are threatened by insecticide resistance and vector behaviour changes toward early 
evening and outdoor biting malaria vectors. New tools to control malaria are needed to reduce and 
even interrupt malaria transmission. Attractive Targeted Sugar Bait (ATSB) is a promising new 
intervention designed to attract and kill mosquitoes, including those that IRS and LLINs do not 
effectively target. The ATSB ‘bait stations’ are A4-sized panels containing thickened fruit syrup laced 
with a neonicotinoid insecticide (dinotefuran) to attract and kill the foraging vectors. Entomological 
field trials in western Mali showed that ATSBs successfully reduce mosquito densities and longevity 
and thus have the potential to reduce malaria transmission. We will conduct a parallel, open-label 
cluster-randomised controlled trial in 80 village clusters (40 per arm) to evaluate the impact of ATSBs 
on the burden of malaria. During two years, households in half of these village-clusters will receive 
two or three ATSB bait stations per household structure on exterior walls approximately 1.8 meters 
above the ground. ATSBs will be replaced every six months. The primary outcome will be the 
incidence of clinical malaria in children aged 1-15 years enrolled in a prospective cohort of 5,376 
participants followed monthly for about six months each during a 2-year period (2,240 person-years) 
(this protocol). Secondary outcomes include malaria infection prevalence assessed by rapid 
diagnostic tests through household surveys and the case burden of clinical malaria assessed by 
passive facility-based and community-based surveillance (separate protocols). The study includes 
entomological monitoring and nested acceptability, feasibility and health-economics studies. The 
stand-alone trial in western Kenya is a part of a multi-country ATSB consortium conducting similar 
trials in Zambia and Mali.  
 Lay Summary 
Increasing insecticide resistance and changes in the malaria-transmitting mosquitoes' behaviour 
toward early evening and outdoor biting threatens the effectiveness of the current tools to reduce 
the malaria-transmitting mosquito. A new tool, the Attractive Targeted Sugar Bait (ATSB), is 
designed to attract and kill mosquitoes using a sugar attractant laced with insecticide, including 
those that escape the killing effect of conventional tools, such as indoor spraying with insecticide 
and insecticide-treated bednets. It reduces the lifespan and density of the malaria-transmitting 
mosquito population and can reduce malaria transmission when deployed at scale. We will conduct 
a large trial involving about 80 village-clusters. During a 2-year period, in half of these villages, 
households will receive two or three ATSB ‘bait stations’ per household structure every six months 
to hang outside on their exterior walls. The study aims to reduce the burden of malaria by reducing 
the number of malaria-infected mosquitoes in the area. This will be assessed by comparing the 
number of clinical episodes of malaria among 5,376 children aged 1-15 years in the intervention and 
control villages. The children will be visited at home every month for six months each. The study also 
includes nested studies assessing the impact ATSBs on mosquito densities and behaviour, 
acceptability and feasibility studies of ATSB deployment, and assessing the cost-effectiveness of the 
intervention. The study will take about three years, including about six months to collect baseline 
data before the ATSBs are used, two years of intervention and six months for data analysis and 
reporting. Similar studies will be conducted in Zambia and Mali. 
 

ATSB-Kenya Protocol (v1.1-31May21) 
9 
 Trial Registration data 
Data Category 
Information 
Primary registry and 
trial identifying number 
Clinicaltrials.gov: [#####] 
 
Date of registration in 
primary registry 
[#####] 
Secondary identifying 
numbers 
Kenya SERU: 4189 
CDC IRB: 00008118 
UK LSTM REC: 21-027 
Source(s) of monetary 
or material support 
Integrated Vector Control Consortium (IVCC), UK, which is funded through a grant by the Bill 
and Melinda Gates Foundation 
Primary sponsor 
Liverpool School of Tropical Medicine (LSTM); Pembroke Place, Liverpool L3 5QA, UK 
Phone: +44 0151 7053794; Email: lstmgov@lstmed.ac.uk 
Secondary sponsor(s)  
NA 
Contact for public 
queries 
 
Aaron Samuels, MD, MHS, Malaria Branch, Division of Parasitic Diseases and Malaria, 
Center for Global Health, Centers for Disease Control and Prevention, Kisumu, Kenya and 
Atlanta, GA, USA. Tel: +254.724.255.633 E-mail: amsamuels@cdc.gov   
 
Dr Eric Ochomo, PhD, Centre for Global Health Research (CGHR), Kenya Medical Research 
Institute (KEMRI), Kisumu, Kenya. Tel: +254 723 845 457; E-mail: eochomo@kemricdc.org 
 
Prof Feiko ter Kuile, MD, PhD, Department of Clinical Sciences, Liverpool School of Tropical 
Medicine (LSTM), United Kingdom. Tel: +44 151 705 3287, E-mail: 
feiko.terKuile@lstmed.ac.uk 
Contact for scientific 
queries 
 
Aaron Samuels, MD, MHS, Malaria Branch, Division of Parasitic Diseases and Malaria, 
Center for Global Health, Centers for Disease Control and Prevention, Kisumu, Kenya and 
Atlanta, GA, USA. Tel: +254.724.255.633 E-mail: amsamuels@cdc.gov   
 
Dr Eric Ochomo, PhD, Centre for Global Health Research (CGHR), Kenya Medical Research 
Institute (KEMRI), Kisumu, Kenya. Tel: +254 723 845 457; E-mail: kemricdc.org 
 
Prof Feiko ter Kuile, MD, PhD, Department of Clinical Sciences, Liverpool School of Tropical 
Medicine (LSTM), United Kingdom. Tel: +44 151 705 3287, E-mail: 
feiko.terKuile@lstmed.ac.uk  
Public title 
Attractive Targeted Sugar Baits (ATSB) for malaria burden reduction in western Kenya: a cluster-
randomized trial  
Scientific title 
Phase III, open-label, community-based, cluster-randomized controlled trial to evaluate the 
efficacy, cost-effectiveness, and acceptability of Attractive Targeted Sugar Baits (ATSB) for malaria 
burden reduction in western Kenya    
Countries of recruitment 
Kenya 
Health condition(s) or 
problem(s) studied 
Vector transmission of malaria 
Intervention(s) 
Attractive Targeted Sugar Baits (ATSBs) 
Study type 
Interventional 
Allocation: cluster randomized; intervention model: parallel assignment; arms: 2; allocation 
ratio: 1:1; restricted randomization. Masking: none  
Primary purpose: Prevention 
Phase-III 
Date first enrolment 
[dd mmm yyyy] 
Target sample size 
80 village-clusters, 40 per study arm; cohort 2,400 person-years (1,200 per arm) 
Recruitment status 
Not yet recruiting 
Primary Objective 
To determine if ATSB deployment plus universal LLIN coverage is superior to universal LLIN 
coverage alone in reducing the case burden of clinical malaria in western Kenya  
Eligibility criteria 
Eligibility criteria for clusters 
 
Inclusion criteria clusters 
o 
A grouping of contiguous rural villages in Alego-Usonga and Rarieda sub-counties 
of Siaya County 
o 
A minimum of 200 households  
 
Exclusion criteria clusters 
o 
Hard to reach in the rainy season 
o 
Refusal to participate by village elders 

ATSB-Kenya Protocol (v1.1-31May21) 
10 
Data Category 
Information 
Eligibility criteria for participants in the cohort study 
 
Inclusion criteria cohort  
o 
A resident of a household within the core area of a study cluster, defined as living 
in the household in the recent four months and planning to live in the same 
household for the next 6.5 months 
o 
Aged ≥ 1 year and < 15 years at the time of enrollment 
o 
Written informed consent and/or assent 
 
Exclusion criteria cohort 
o 
A confirmed or suspected pregnancy. Pregnant women are excluded because 
they are eligible for intermittent preventive treatment of malaria in pregnancy 
(IPTp).  
o 
Taking daily cotrimoxazole prophylaxis (because this has antimalarial effects) 
o 
Known sickle cell disease (because they received antimalarial prophylaxis) 
o 
Contraindication to artemether-lumefantrine, the medication used for parasite 
clearance  
Eligibility criteria for households for ATSB deployment  
 
Inclusion criteria 
o 
Households located within one of the 40 clusters (core or buffer area) randomly 
allocated to the trial intervention arm with a least one permanent resident 
 
Exclusion criteria 
o 
Refusal of consent by the head-of-household to deploy ATSB on the outer walls 
(intervention villages only) 
o 
Vacated compounds 
Eligibility criteria for households for entomological monitoring 
 
Inclusion criteria households for entomological monitoring 
o 
Household located within the core area of the cluster  
o 
Head of household or his/her representative is at least 18 years of age  
o 
Written informed consent for the collection of entomological data by the head of 
household or representative 
 
Exclusion criteria households for entomological monitoring 
o 
No residents sleeping in the household during the planned night of monitoring 
Eligibility criteria for human landing catches  
 
Inclusion criteria human landing catches  
o 
Men aged 18 to 49 years 
o 
Willingness and ability to work late at night for up to 7 hours at a time 
o 
Willingness to take and tolerate a treatment regimen of the appropriate Kenya 
Ministry of Health (MoH) recommended antimalarial and chemoprophylaxis with 
250 mg of mefloquine weekly to prevent malaria starting two weeks before the 
start of and until four weeks after completing HLCs 
o 
Written informed consent 
 
Exclusion criteria human landing catches 
o 
Refusal/inability to work late at night for up to 7 hours at a time 
o 
Unwillingness to take or intolerance/allergy to appropriate MoH treatment 
regimen or chemoprophylaxis 
Eligibility criteria for participants in rapid ethnographic methods evaluation (community 
members)  
 
Inclusion criteria ethnographic evaluation (community) 
o 
A resident of a household within an intervention area defined as an ATSB area 
during the main trial or an ASB area during any preliminary studies 
o 
Resides in a household at the time of ASB/ATSB deployment, where the 
ASB/ATSB was installed for at least one month.  
o 
18 years of age or older if participating in focus group discussions; 15 years of age 
or older if participating in in-depth interviews 
 
Exclusion criteria ethnographic evaluation (community)  
o 
Unable to provide consent 
Eligibility criteria for participants in rapid ethnographic methods evaluation (ATSB monitoring 
assistants) 
 
Inclusion criteria ethnographic evaluation (ATSB monitoring assistants) 
o 
Serving as an ATSB monitoring assistant with experience installing ATSBs and 
monitoring the deployment  

ATSB-Kenya Protocol (v1.1-31May21) 
11 
Data Category 
Information 
o 
Eighteen years of age or older 
 
Exclusion criteria ethnographic evaluation (ATSB monitoring assistants) 
o 
Less than one month experience (i.e. is new to the job) 
o 
Unable to provide consent 
Primary objective and outcome 
 
To determine if ATSB deployment plus universal LLIN 
coverage is superior to universal LLIN coverage alone 
in reducing the case burden of clinical malaria in 
western Kenya  
 
The incidence rate of clinical malaria by the end of year-2, 
defined as current fever (axillary temperature of ≥37.5°C) or 
history of fever in last 48 hours and a positive rapid diagnostic 
test (RDT, pLDH or HRP2), in children aged 1-<15 years 
enrolled in the cohort study 
Secondary objectives and outcomes 
Efficacy 
 
To determine if ATSB deployment plus universal LLIN 
coverage compared to universal LLIN coverage alone 
is superior in reducing malaria infection 
 
The time to first malaria infection assessed by PCR by the end 
of year-2, in children aged 1-<15 years enrolled in a cohort 
study 
 
The incidence rate of malaria infection detected by RDT 
(pLDH) by the end of year-2, in children aged 1-<15 years 
enrolled in a cohort study  
 
The prevalence of malaria infection diagnosed by RDT in 
continuous household surveys in participants aged ≥1 month. 
 
The incidence rate of RDT or microscopy confirmed 
clinical malaria assessed through passive surveillance 
at health facilities and community-based surveillance 
by Community Health Volunteers serving the village-
clusters  
 
The incidence rate of RDT or microscopy confirmed clinical 
malaria assessed through passive surveillance at health 
facilities and community-based surveillance by Community 
Health Volunteers serving the village-clusters  
 
To determine if the rate of overall illness events 
differs in the ATSB deployment plus universal LLIN 
coverage arm when compared to the control arm 
 
The incidence rate of non-malaria illness in the cohort study  
 
The incidence rate of all-cause sick visits assessed through 
passive surveillance at health facilities and community-based 
surveillance by community health volunteers 
 
To determine if ATSB deployment plus universal LLIN 
coverage compared to universal LLIN coverage alone 
reduces malaria transmission or affects insecticide 
resistance  
 
Entomological outcomes including malaria vector densities, 
the proportion of females older than three gonotrophic cycles, 
sporozoite rate, EIR and markers of insecticide resistance 
 
Antibodies against merozoite surface protein-1 (MSP-1), 
circumsporozoite proteins (CSP) and other malaria antigens 
 
Molecular measurements including, but not limited to, 24-
single-nucleotide polymorphisms (24-SNP) barcodes for the 
complexity of infection  
 
Mosquito salivary antigens for biting rates 
Safety 
 
Assess the safety of ATSBs on humans  
 
Adverse events associated with Adverse events associated 
with misuse or loss of ATSBs. 
 
Assess the safety of ATSBs on non-target insects  
 
Continued entomological monitoring of non-target insect 
populations  
Ethnographic evaluation 
 
To understand the acceptability and potential factors 
that influence ATSB coverage  
 
The proportion of ATSBs that have been moved/removed  
 
The proportion of household heads who perceive ATSBs as 
safe and effective 
 
Assess the acceptability of ATSBs by communities 
and other stakeholders  
 
Identification of potential barriers to uptake and consistent 
ATSB coverage,  
 
Assessment of the impact of ATSBs on the coverage and use of 
existing malaria control interventions (e.g. LLIN, IRS, 
treatment-seeking behaviour) 
Health economics 
 
Estimate the cost-effectiveness of deploying ATSBs 
for malaria control. 
 
Incremental cost-effectiveness of ATSB above the standard of 
care measured through costing of intervention and efficacy 
outcomes  

ATSB-Kenya Protocol (v1.1-31May21) 
12 
3 INTRODUCTION 
3.1 ATSB BACKGROUND AND LITERATURE REVIEW 
The current malaria vector control tools, long-lasting insecticidal nets (LLINs) and indoor residual 
spraying (IRS) are critically important and have saved many lives [1]. However, their effectiveness in 
western Kenya is threatened by insecticide resistance and vector behaviour changes toward more 
early evening and outdoor biting malaria vectors. LLINs and IRS specifically target indoor-biting and 
indoor-resting mosquitoes. Malaria vectors exhibit different behavioural characteristics that mitigate 
the effectiveness of vector control strategies. For example, traditionally, An. gambiae s.s. has been 
regarded as human-biting with late-night indoor-feeding and indoor-resting behaviours, while An. 
Arabiensi is found more often in drier environments and is more zoophagic with outdoor biting and 
resting behaviours. Following LLINs and IRS's widespread scale-up, the dominant African vectors' 
distributions and behaviours changed with An. gambiae s.s. and An. Funestus (also an indoor human 
biter) diminishing in abundance relative to An. arabiensis [2]. Subsequently, shifts towards earlier 
evening biting by An. Gambiae s.s. (before people enter houses to sleep under LLINs) and later biting 
by An. Funestus (biting in the morning after sunrise [3, 4]) are examples of behavioural plasticity 
enabling these species to avoid contact with the LLIN and IRS insecticides.  
There is a need for interventions that supplement and complement LLINs and IRS by killing 
mosquitoes outside houses using other biologic mechanisms (e.g., targeting sugar feeding 
behaviour). [5-7]. Furthermore, insecticides are required with novel modes of action that may 
restore sensitivity to pyrethroids by killing both pyrethroid-resistant and sensitive mosquitoes.  
Attractive Targeted Sugar Bait (ATSB) (the name was recently 
changed from Attractive Toxic Sugar Bait to highlight that it 
targets malaria vectors) is a promising new intervention that 
potentially fills the need for outdoor interventions with novel 
killing effects. ATSB ‘bait stations’ are A4-sized panels 
containing thickened fruit syrup laced with a neonicotinoid 
insecticide (dinotefuran) to attract and kill the foraging 
vectors. Entomological field trials in Mali showed that ATSBs 
successfully reduce mosquito densities and longevity and thus 
have the potential to reduce malaria transmission [8].  
Large scale efficacy studies are now needed to establish 
the efficacy of ATSB for controlling malaria transmission. We will propose a parallel, open-label 
cluster-randomized controlled trial in 80 village clusters (40 per arm) to evaluate the impact of ATSBs 
on the burden of malaria in western Kenya, where sustained malaria transmission occurs despite the 
scale-up of LLINs or IRS.  
3.2 ADDRESSING RESIDUAL OUTDOOR MALARIA TRANSMISSION 
LLINs and IRS are not well-suited for malaria vectors that avoid contact with indoor insecticides, 
frequently bite animals, and rest outdoors or remain within houses only briefly when they enter [5, 
6]. These behaviours allow residual populations of vector mosquitoes to survive, expand, and 
increasingly contribute to malaria transmission, despite high LLIN and IRS coverage [6]. These 
vectors can sustain endemic transmission even if they rarely bite humans. An. arabiensis is a 
 
Figure 1: ATSB station 
 

ATSB-Kenya Protocol (v1.1-31May21) 
13 
particularly important source of persistent residual transmission. This mosquito prefers to feed on 
animals, often bites and rests outside, and has limited indoor exposure [5, 6].  
In addition to the biological need for female Anopheles species to take a blood meal to obtain 
protein necessary for egg production, both male and female Anopheles must feed regularly on liquid 
and carbohydrates (sugars) to survive. Common sources of liquid and sugar meals include plant 
tissue and floral nectar. Mosquitoes are guided to sugar sources by chemical attractants. ATSBs are 
designed to attract the mosquito with a source of liquid and sugar. Because the sugar is laced with a 
toxicant, it kills the mosquito when ingested [9]. A limited number of studies have shown that using 
sugar sources to attract mosquitoes to an ingestion toxicant is a relatively simple and inexpensive 
strategy for mosquito control [10], even in sugar-rich environments [11]. 
Early studies examined the effect of spraying ingestion toxicants on attractive flowers to use their 
scent as bait. While these flowers effectively attract the target mosquitoes, the impact on non-target 
insects, especially pollinators, can be devastating. Furthermore, this approach is not suitable in areas 
with a lack of flowering vegetation [9].  
3.3 ATSBS 
Westham Co., based in Israel, recently developed a bait station containing a fruit syrup to attract 
mosquitoes, sugar to stimulate feeding, and an active ingredient (the neonicotinoid, dinotefuran) to 
kill the foraging vectors. The bait station contains a commonly used bittering agent called Bitrex 
(https://www.bitrex.com/en-us) that deters human and animal consumption of the bait. The bait 
stations also contain a pH regulator (citric acid), preservative (sodium benzoate), and thickener 
(xanthan gum). They have a protective membrane that covers and protects the bait from rain and 
dust but allows mosquitoes to feed through it (See Figure 1: ATSB station, page 12). The protective 
membrane will enable mosquitoes to feed, but it serves as a barrier to non-target organisms. Field 
studies to-date have also shown that the ATSB has a minimal impact on non-target organisms (NTOs) 
and humans. This includes evidence specifically for the toxicant that will be used, dinotefuran [12]. 
The Westham ATSB can remain effective in the field for at least six months and has a shelf life 
greater than three years with no specific storage requirements. This ATSB is now being produced at 
an industrial scale, uses simple and widely available ingredients, and limits environmental 
contamination with insecticides.  
ATSBs may be an essential vector control tool in the context of insecticide resistance. Insecticide 
resistance for the six insecticide classes currently used in LLINs and IRS threatens malaria prevention 
efforts. Resistance to pyrethroids (used in LLINs and IRS) is commonly reported 
(http://www.irmapper.com). If pyrethroids lose most of their efficacy, more than 55% of vector 
control benefits could be lost [13]. ATSBs can help mitigate insecticide resistance to these contact 
insecticides because they can use ingestion toxicants from very different chemical classes. Many 
existing ingestion toxicants may be used in a bait station, facilitating resistance management 
strategies, such as rotation or combination approaches.  
3.4 FIELD EXPERIENCE WITH ATSB IN MALI 
Proof of concept studies from Mali demonstrated that the ATSBs had the desired impact on 
mosquito vector populations [8]. Outdoor use of ATSBs was found to reduce vector abundance by 
57.4%, and the older mosquito population surviving long enough to transmit malaria by 97.1-100%. 
Preventing Anopheles mosquitoes from living long enough for the ingested malaria gametocytes to 
mature to sporozoites is key to preventing onward transmission. The studies in Mali also established 

ATSB-Kenya Protocol (v1.1-31May21) 
14 
an optimal deployment pattern. They showed that two ATSBs installed on opposite exterior walls of 
sleeping structures at a height of 1.8 meters were associated with a target mosquito feeding rate of 
at least 30% and a >90% reduction in vector populations [8].  
3.5 FIELD EXPERIENCE WITH ATSB IN WESTERN KENYA 
In western Kenya, similar entomological validation studies are ongoing under a separate protocol 
(SSC-3613; CDC IRB # 7112; LSTM REC # 18.015).  
The initial entomological validation trial in Kenya was carried out between Nov 2020 and Jan 2021 
with Attractive Sugar Bait stations (ASBs), which are like ATSB but without the toxin and contain a 
fluorescent dye. Preliminary results indicate that three ASBs hung on the exterior walls resulted in 
cumulative mosquito feeding rates of up to 30 % among An. gambiae and 60% among An. funestus 
during the first month of ASB deployment. The estimated daily feeding rate was 7% for An. gambiae 
and 11% for An. funestus, which for both species is above the 2.5% threshold estimated by 
mathematical models to result in a 30% reduction in malaria incidence.  
Additionally, the team assessed natural sugar feeding rates for these malaria vectors and found the 
average rate was 38% and 27% among An. funestus male and female mosquitoes, respectively, and 
26% and 13% among male and female An. gambiae mosquitoes, respectively. A larger pilot study 
(SSC-3613; CDC IRB # 7112; LSTM REC # 18.015) is planned for May-June of 2021, comparing feeding 
rates when deploying two versus three bait stations per structure. The information will be used to 
inform the final number of bait stations required in the larger efficacy trial described in the current 
protocol. 
4 JUSTIFICATION FOR THE STUDY 
Malaria prevention tools currently deployed at scale have been highly effective in reducing malaria, 
but in high transmission areas, these are insufficient to further reduce and ultimately interrupt 
transmission. The ATSB is a new tool designed to attract and kill mosquitoes, including those that IRS 
and LLINs do not effectively target. Modelling studies suggest that ATSBs could significantly reduce 
mosquito populations across a range of different transmission intensities and have great potential to 
further reduce malaria transmission in areas with high uptake of indoor vector control tools (e.g. 
LLINS and/or IRS) [7, 14]. To accelerate the evaluation of ATSBs as a potential public health strategy, 
Figure 2: Timeline for the ATSB New Paradigm Initiative 2014–2024 
2014
Proof of product
The Westham 
ATSB was 
selected for the 
New Paradigm 
Initiative based 
on initial data 
suggesting 
potential for high 
impact and short 
time to market. 
2015-2021
Proof of 
concept -
Impact on 
mosquito 
vectors
Lab studies and 
field 
experiements 
conducted in Mali 
demonstrated 
that the ATSB 
has the desired 
entomological 
outcomes. 
2021-2023
Proof of 
concept -
Impact on 
mlaria burden
Large-scale field 
trials required to 
demonstrate 
epidemiological 
impact and 
associated 
entomological 
performance.
To be 
demonstrated in 
3 study sites.
2024
WHO policy & 
product listing
WHO VCAG has 
reviewed all 
available 
evidence.
WHO MPAC 
releases a policy 
statement in 
support of ATSB 
deployment.
ATSB device is 
prequalified & 
listed. 

ATSB-Kenya Protocol (v1.1-31May21) 
15 
larger scale and multi-site studies are now needed to assess the impact on malaria infection and 
transmission outcomes (Figure 2).  
The results of this study will be submitted to the WHO Vector Control Advisory Group (VCAG), the 
advisory body to the WHO on new vector control classes for malaria and other vector-borne 
diseases. VCAG will review the ATSB public health value iteratively and provide regular updates to 
the Malaria Policy Advisory Committee (MPAC). MPAC will provide a recommendation to WHO 
based on available evidence. WHO will then formulate the recommendation and operational 
guidance for the product, and subsequent products in this product class will be eligible for WHO 
prequalification listing [15]. Many countries and donors will not purchase or import products that do 
not have a listing.  
5 OBJECTIVES AND OUTCOMES 
Table 1: Objectives and outcomes 
5.1 PRIMARY OBJECTIVE AND OUTCOME 
Primary objective 
Primary endpoint 
To determine if ATSB deployment plus universal 
LLIN coverage is superior to universal LLIN 
coverage alone in reducing the case burden of 
clinical malaria in western Kenya  
 
The incidence rate of clinical malaria by the 
end of year-2, defined as current fever 
(axillary temperature of ≥37.5°C) or history of 
fever in last 48 hours and a positive rapid 
diagnostic test (RDT, pLDH or HRP2), in 
children aged 1-<15 years enrolled in the 
cohort study 
5.2 SECONDARY OBJECTIVES AND OUTCOMES 
 Efficacy  
Secondary objectives 
Secondary endpoints 
To determine if ATSB deployment plus universal 
LLIN coverage compared to universal LLIN 
coverage alone is superior in reducing malaria 
infection 
 
The time to first malaria infection assessed by 
PCR by the end of year-2, in children aged 1-
<15 years enrolled in a cohort study 
 
The incidence rate of malaria infection 
detected by RDT (pLDH) by the end of year-2, 
in children aged 1-<15 years enrolled in a 
cohort study  
 
The prevalence of malaria infection 
diagnosed by RDT in continuous household 
surveys in participants aged ≥1 month. 
To determine in ATSB deployment plus universal 
LLIN coverage compared to universal LLIN 
coverage alone reduces the clinical case burden 
in health facilities and communities 
 
The incidence rate of RDT or microscopy 
confirmed clinical malaria assessed through 
passive surveillance at health facilities and 
community-based surveillance by Community 
Health Volunteers serving the village-clusters  

ATSB-Kenya Protocol (v1.1-31May21) 
16 
To determine if the rate of overall illness events 
differs in the ATSB deployment plus universal 
LLIN coverage arm when compared to the control 
arm 
 
The incidence rate of non-malaria illness in 
the cohort study  
 
The incidence rate of all-cause sick visits 
assessed through passive surveillance at 
health facilities and community-based 
surveillance by community health volunteers 
To determine if ATSB deployment plus universal 
LLIN coverage compared to universal LLIN 
coverage alone reduces malaria transmission or 
affects insecticide resistance  
 
Entomological outcomes including malaria 
vector densities, the proportion of females 
older than three gonotrophic cycles, 
sporozoite rate, EIR and markers of 
insecticide resistance 
 
Antibodies against merozoite surface protein-
1 (MSP-1), circumsporozoite proteins (CSP) 
and other malaria antigens 
 
Molecular measurements including, but not 
limited to, 24-single-nucleotide 
polymorphisms (24-SNP) barcodes for the 
complexity of infection  
 
Mosquito salivary antigens for biting rates 
 Safety 
Assess the safety of ATSBs on humans  
 
Adverse events associated with misuse or 
loss of ATSBs. 
Assess the safety of ATSBs on non-target insects  
 
Continued entomological monitoring of non-
target insect populations  
 Ethnographic evaluation 
To understand the acceptability and potential 
factors that influence ATSB coverage  
 
The proportion of ATSBs that have been 
moved/removed  
 
The proportion of household heads who 
perceive ATSBs as safe and effective 
Assess the acceptability of ATSBs by communities 
and other stakeholders  
 
Identification of potential barriers to uptake 
and consistent ATSB coverage,  
 
Assessment of the impact of ATSBs on the 
coverage and use of existing malaria control 
interventions (e.g. LLIN, IRS, treatment-
seeking behaviour) 
 Health economics 
Estimate the cost-effectiveness of deploying 
ATSBs for malaria control. 
 
Incremental cost-effectiveness of ATSB above 
the standard of care measured through 
costing of intervention and efficacy outcomes  
6 TRIAL DESIGN AND DESIGN CONSIDERATIONS 
6.1 OVERVIEW OF STUDY DESIGN 
This will be a phase III, open-label two-arm cluster randomized controlled superiority trial (CRCT) 
with a 1:1 allocation ratio to compare ATSB + LLINs vs LLINs alone (standard of care).  

ATSB-Kenya Protocol (v1.1-31May21) 
17 
During the baseline year, 100 clusters will be followed for 1-year. Clusters consist of approximately 1 
to 3 contiguous villages to achieve an optimal cluster size of between 200-400 households per 
cluster. Clusters are divided into core and buffer areas, as described in Section 6.2.3, Measures to 
avoid contamination, page 17. The sampling frame for measuring baseline and main study outcomes 
will be restricted to permanent residents residing in households within each cluster's core area to 
reduce contamination. After the baseline period, 80 out of the 100 clusters will be allocated to one 
of the two arms using restricted randomization based on the optimal combination of options that 
minimizes imbalance in baseline predictors between study arms. 
The study is designed to detect a ≥30% reduction in the primary outcome over two years, which is 
the incidence of clinical malaria in a cohort of children aged 1-15 years, defined as current fever 
(axillary temperature of ≥37.5⁰C) or history of a fever in the last 48 hours and a positive RDT. The 
WHO considers this effect size to be the minimal reduction required worthy of a WHO 
recommendation. The prevalence surveys will also be powered to detect a 30% reduction in malaria 
prevalence by RDT each year.  
6.2 DESIGN CONSIDERATIONS 
 Superiority trial to detect at least a 30% reduction 
The study is designed as a superiority trial to detect at least a 30% reduction compared to the 
current standard of care (universal coverage of LLINs) over a two-year period, which is the minimum 
reduction considered worthy of a WHO recommendation and large-scale deployment.   
 Duration of trial, interim analysis and criteria for early termination 
This study in Kenya is part of three similar trials conducted in Kenya (this protocol), Zambia and Mali. 
The purpose of these trials is to inform the assessment of public health value  by WHO’s Vector 
Control Advisory Group (VCAG). This requires at least a single year of data, but ideally, two years [16-
18]. This trial in Kenya is designed to have two interim and one final analysis, i.e. a total of three 
looks. The main purpose of these interim analyses is to inform WHO’s recommendation making 
process in a timely manner. In brief, the interim analyses will occur either after 50% and 75% of 
person-time have completed (i.e., after about 1 and 1.5 years respectively), or after 50% (n=372) and 
75% (n=558) of the total number of expected primary outcome events over two years in the control 
arm (n=744) have occurred (whichever comes first). The number of events will be tracked by an 
independent statistician not involved in the trial. Whether the interim analysis results will lead to the 
early stoppage of this trial, e.g., for futility or overwhelming evidence of efficacy, will depend on the 
overall evidence from the three trials. Please see Section 9.4.1, Interim analysis, page 44, for details 
of the interim analysis's purpose and procedures. 
 Measures to avoid contamination 
Contamination or spillover effects between study arms may bias results towards the null. Therefore, 
the study will use a “fried egg” design. In interventions clusters, ATSBs will be deployed throughout 
the entire cluster. However, the effect will only be obtained from households located in the core of 
the cluster. Excluding measurement for the primary outcome in buffer zones will ensure that 
households in control villages are excluded that may benefit from a community effect from proximal 
households in neighbouring intervention villages. 
The core area is defined as an area that is at least 300 to 600 meters from the perimeter of the 
cluster (i.e. at least 600 to 1200 meters between core areas of contiguous clusters), based on 
findings on the design of a recent cluster-randomized trial in Tanzania [19].  

ATSB-Kenya Protocol (v1.1-31May21) 
18 
The buffer zones will be uniformly applied to each study cluster, including control clusters that do 
not border an intervention cluster or vice versa. This will be done to avoid the potential confounding 
factor of household distance from the cluster centre. For example, cluster borders may consist of a 
river or stream. The presence of water may result in a relatively higher or lower risk of malaria 
infection exposure compared to the core area, or the household density may differ between core 
and buffer areas, etc.  
The boundaries for the core and buffer areas are based on recent mapping and census data.  
Only the analysis of the data from the cohort study (primary outcome), parasite prevalence survey, 
and entomological monitoring will use the “fried egg” approach. The analysis of the passive facility-
based or community-based surveillance data cannot use the fried-egg approach because only data 
on the village of residence, and not the geo-location of a household, is available in the routine 
clinical or CHV registers.  
 Assessment of community effects.  
Should funds permit, additional participants from the buffer zones may be enrolled in the cohort 
study or continuous household surveys to examine the community effect, i.e. the degree to which 
intervention effects wane by distance and/or spill over into neighbouring control clusters. See 
Section 7.8, Sample size, page 30, for further details on sample size and sampling.  
Figure 3: Buffer zone and core zone for sampling within each study cluster at trial sites with contiguous and non-
contiguous cluster configurations 
 
 
Notes: The core area for sampling will include 
all areas 300 to 600 meters from the cluster 
boundary, resulting in a 600 to 1200-meter 
buffer zone between the core intervention 
and core control clusters. ATSBs will be 
deployed throughout the entire intervention 
cluster, including the buffer zone. Buffer 
zones will be applied to all clusters 
(contiguous and non-contiguous).  
 
Contiguous clusters 
≥300-  
600m 
Non-contiguous 
≥300-
600m 
>300 to 
600m 
 

ATSB-Kenya Protocol (v1.1-31May21) 
19 
6.3 OVERVIEW OF ACTIVITIES AND PROCEDURES 
The following list provides a general overview of planned research activities, with a full description 
included in Section 9, Methods: Data collection, management and analysis, pages 34 to 42. Please 
refer to Figure 4: Overview of activities and procedures in intervention and control areas, page 20, 
for a graphical overview of activities and to Table 8: Timeline, page 62, for a timeline of the planned 
activities.  
 Creation of clusters  
Clusters have been created using data from a recent mapping and census exercise conducted in the 
study areas (Rarieda and Alego-Usonga sub-Counties of Siaya County). A total of 100 clusters were 
created from either a single village or multiple combined villages to achieve an optimal cluster size 
ranging between 200–400 households per cluster. Within each cluster, a core and buffer area have 
been delineated (see Section 6.2.3, Measures to avoid contamination, page 17). Additionally, these 
data are used to inform the denominator for the measurement of the incidence from passive case 
detection.  
 Baseline data collection 
The baseline malaria incidence, prevalence, and contextual data will be collected in a cohort study 
(6.3.3.1, below) and household survey (6.3.3.3, below) conducted in 100 clusters prior to ATSB 
deployment. This data will be used to inform the restricted randomization and select the 80 clusters 
for inclusion in the main trial. The incidence and prevalence data will also be used to confirm the 
necessary sample size for the cohort and household survey required for the main trial to assess 
impact. Baseline entomological data (including mosquito age structure, mosquito density, sporozoite 
rates, insecticide resistance, and EIR) will be collected in 30 randomly selected clusters to inform the 
restricted randomization.   
 Epidemiological data 
The epidemiological data sources for both the baseline and the main trial will include:    
 
Cohort study (active case detection) 
Participants aged 1 to <15 years who are usual residents of households within a core area of a study 
cluster will be randomly selected for enrolment into an active cohort (see section 9.1.2, Cohort study 
to assess the incidence of clinical malaria, page 34). All consented and enrolled cohort members will 
be given a presumptive treatment course of artemether-lumefantrine to clear any malaria 
infections. Parasite clearance will be confirmed two weeks after treatment. The scheduled monthly 
cohort visits will begin one month after the first day of this treatment. During monthly visits, study 
staff will collect a fingerprick (or heel prick in small infants) blood sample (about 250uL to 1 ml) for 
dried blood spots on filter paper. Should the cohort member report a fever in the last 48 hours or 
have an axillary temperature of ≥37.5°C at the time of the visit, the study staff member will perform 
a malaria RDT, and if positive, will treat the participant as per the Kenya Ministry of Health 
guidelines. A questionnaire will be administered to all cohort members and/or their caregivers to 
assess for illness, care-seeking, and LLIN usage, among other indicators. Several questions will be 
asked to monitor for any SAEs. A questionnaire assessing ATSB knowledge, attitudes and perceptions 
(KAP) will also be administered. Please see section 9.1.7, Rapid ethnographic methods, page 39, for 
more details.  
 

ATSB-Kenya Protocol (v1.1-31May21) 
20 
 
Figure 4: Overview of activities and procedures in intervention and control areas 
 
Transmission Season: Year-round with peaks in June-July 
Primary baseline data 
collection: 
 
Continuous 
malaria indicator 
survey  
 
Active cohort 
 
Health facility and 
CHV surveillance 
 
Entomological 
surveillance 
 
Qualitative 
assessment 
 
Ensure high 
ITN 
coverage in 
intervention 
and control 
Cohort 
 
Active infection detection to estimate clinical malaria and malaria infection incidence among the cohort 
with measurement every 4 weeks  
Baseline 
Rapid 
ethnographic 
methods 
Deploy ATSBs in 
intervention areas 
ATSB monitoring, maintenance and replacement in intervention areas to ensure continuous effective coverage.  
Human safety monitoring.  
Entomological data collection to determine ATSB impact on vector populations. 
Continuous collection of ATSB program cost data. 
Passive case detection at health facilities to estimate malaria case incidence among all ages 
Rapid 
ethnographic 
methods 
Results used to 
inform pre-trial 
and ongoing 
community 
engagement & 
Continuous HH survey: Parasite prevalence, coverage, ATSB KAP 
Main Trial (2-year follow-up period) 
Rapid 
ethnographic 
methods 

ATSB-Kenya Protocol (v1.1-31May21) 
21 
 
Passive surveillance of case burden (health facility and community-based surveillance) 
Data to estimate the all-age malaria case burden will be obtained using routine data collected in the 
Kenya Ministry of Health registers from outpatient health facilities, antenatal clinics, and CHVs 
serving the clusters' catchment areas. In brief, de-identified data are captured from the facility and 
CHV registers (paper-based register books). Village of residence data are collected in these registers 
and will be used to classify participants as coming from intervention or control clusters or outside 
the study area. Census data will be used to calculate the initial cluster population denominators. 
Census data collected by the CHVs annually may be used to update cluster denominators and 
sampling frames. Please see Section 9.1.4, Passive case detection, page 37, for more details. 
 
Continuous malaria indicator household surveys (cMIS)  
Malaria prevalence data will be obtained from ongoing continuous (year-round) malaria indicator 
surveys (cMIS) under an existing protocol (SSC 2773; LSTM Protocol 14.009; CDC Protocol 6733). As 
part of these surveys, fingerprick blood samples are collected for malaria RDTs and dried blood spots 
for later molecular and serological testing. Participants testing RDT positive are treated according to 
the Kenya Ministry of Health guidelines. A questionnaire is administered to the selected individual or 
their caretaker to evaluate key contextual variables, including human behavioural factors, 
demographic characteristics, and travel patterns. Please see Section 9.1.3, Continuous household 
survey, page 36 for more details. 
 Rapid ethnographic methods 
Qualitative research methods will be applied early in the study, including in-depth interviews (IDI) 
and focus group discussions (FGD) to assess community perceptions and attitudes regarding ATSB 
deployment. Initial qualitative work will inform the development of community engagement and 
communications plans. This work will be undertaken prior to the initial deployment of ATSBs. 
Subsequent work after ATSB deployment will examine knowledge, attitudes, and practices. Changes 
in communication strategies may be needed to ensure full coverage and adherence. Please see 
section 9.1.7, Rapid ethnographic methods, page 39, for more details.  
 Sensitization of the population  
Meetings will be held with the County and sub-County Health Management Teams and in the study 
villages to explain the interventions, the purpose of the study, and the need for randomizing 
communities to one of the two study arms. 
 LLIN distribution  
A Government of Kenya sponsored mass LLIN distribution campaign occurred in April 2021 within 
the study area to achieve universal access to LLINs (1 LLIN per 2 household members). Using data 
from the baseline cMIS survey, we will measure LLIN coverage and attrition prior to the main trial 
and perform top-up distributions in all clusters as warranted.  
 ATSB deployment and monitoring and maintenance 
 
Deployment 
ATSBs will be deployed according to the optimal protocol identified during the entomological 
validation studies. The deployment protocol will entail installing two or three bait stations per 
structure on exterior walls approximately 1.8 meters above the ground or as high as possible on 
shorter walls. Community-based staff will install the ATSBs according to manufacturer instructions. 
Consent will be obtained from both community leaders within selected clusters and individual heads 
of household. At the time of deployment, household owners will be educated on the importance of 

ATSB-Kenya Protocol (v1.1-31May21) 
22 
ensuring that the ATSBs remain on the exterior walls for the validity of the study and to avoid 
potential adverse effects on humans.  Household owners will be instructed to contact study staff if 
ATSBs are damaged or lost to allow for replacement. 
 
Continuous monitoring and maintenance of ATSBs  
A monitoring component will ensure that ATSB coverage remains high for the duration of the study. 
Community-based monitoring assistants will monitor all or a sample of bait stations about once per 
month and capture data on placement and condition. The bait stations will be replaced as required 
or every six months (the product's lifespan). Continuous monitoring will also include participant 
education, routine communication to ensure proper ATSB deployment and use, and the opportunity 
for household members to ask any questions or voice any concerns.  
 Entomological monitoring 
 
Monthly/quarterly mosquito catches 
Entomological data will be collected on a monthly basis from 10-12 households in each of 24 
randomly selected study clusters (12 intervention and 12 control; total= 240-288 houses per month). 
Collection of monthly mosquito catches will use UV light traps. Human landing catches will be 
performed quarterly in 4 houses in each of 12 randomly selected clusters (6 control and 6 
intervention clusters; total = 48 houses per quarter).   
 
Insecticide resistance monitoring 
Physiological and behavioural resistance to the ATSB toxin will be monitored annually by allowing 
adult mosquitoes reared from field-collected larvae or adult mosquitoes reared from the larvae of 
field-collected blood-fed or gravid adults to feed on the bait stations or according to other methods 
as they become available. As ATSBs employ an ingestion toxicant (in contrast to the contact 
insecticides used in LLINs and IRS), ATSBs have the potential to alter the physiological insecticide 
resistance profile in the mosquito population of insecticides used in LLINs and IRS. Thus, 
physiological resistance to insecticides used in IRS and LLINs will be assessed prospectively using 
WHO tube tests or CDC bottle bioassays. Additionally, a dinotefuran resistance assay is currently 
under development and may be used to monitor the development of resistance to dinotefuran 
during this trial.  
 Health-economic data 
ATSB product and delivery costs will be collected following a standardized procedure to estimate the 
financial and economic costs of the intervention. Costs will be classified as capital or recurrent and 
traded vs non-traded. Capital costs will be annuitized and discounted using a 3% rate. These costs 
will be expressed in a common currency and year (2019 US dollars). Additionally, they will be 
converted into purchasing power parity adjusted International Dollars for internal comparison. Costs 
will be combined with efficacy measures from the trial to estimate incremental cost-effectiveness 
measures.  
 Collection of environmental parameters  
Environmental parameters such as monthly rainfall and enhanced Vegetative Index (eVI) will be 
collected from online sites such as NASA’s MODIS data repository. 
 Human safety monitoring 
Systematic monitoring will assess safety by documenting the occurrence of any inadvertent 
exposures among the study participants to bait station contents (see 10.3, Safety monitoring and 
reporting, page 51).   

ATSB-Kenya Protocol (v1.1-31May21) 
23 
7 METHOD: PARTICIPANTS, INTERVENTIONS, AND OUTCOMES 
7.1 STUDY SITE 
The study will be performed in Rarieda and Alego-Usonga sub-Counties of Siaya County, western 
Kenya.  Malaria transmission is moderate to high and occurs year-round with peaks in June and July, 
and November and December following the long and short rains, respectively. Annual parasite 
prevalence from the continuous malaria indicator survey is estimated to be 36.5% by RDT among 
children under five years of age (unpublished data). In Siaya County, confirmed malaria incidence by 
passive case detection for 2016 was 585 per 1,000 population, and clinical (unconfirmed) malaria 
incidence rate was 261/1,000 (DHIS2 dashboard for Siaya County). The primary malaria vectors are 
Anopheles funestus and An. arabiensis. An. gambiae s.s. is a secondary vector. Malaria vector 
resistance to pyrethroid insecticides is documented in Kenya.  
7.2 RECRUITMENT 
Prior to the start of the study, we will hold community sensitization meetings with key leaders and 
stakeholders in the villages where the study will occur. Examples of key leaders and stakeholders 
include the county commissioner, chiefs and assistants, community advisory boards, village elders, 
community health volunteers, religious leaders, village reporters and youth. We will also hold 
“barazas” or community town halls. These meetings will serve to introduce the study and explain the 
purpose of the study, study components, who we might approach for enrolment and the general 
risks and benefits to the community at large. We will convene additional meetings with key leaders 
and stakeholders and hold additional barazas 2 to 4 times per year to provide a forum for questions 
and feedback.  
When enrolment begins, study staff will approach prospective participants at their homes. Staff who 
will be approaching prospective participants will be trained to communicate clearly to participants 
that there is no requirement to participate, no pressure to participate, and no consequence for not 
participating. 
If a prospective participant is undecided about enrollment on the day that study staff approach 
them, staff will be trained to leave the participant information sheet with the prospective participant 
and re-approach them within 1 to 3 days. At that time, if the prospective participant remains 
undecided, staff will explain to the prospective participant that if they want to enrol in the study at 
any later time, they can call the phone number provided  on the participant information sheet. 
7.3 ELIGIBILITY CRITERIA 
The trial population as a whole consists of all de facto and de jure residents present in intervention 
and control clusters (and associated buffer areas) during the study period. The village boundaries, 
household and population in the study area in Siaya County were mapped and enumerated under an 
approved protocol (KEMRI SSC# 1801; CDC IRB# 3308) “Household socioeconomic status and health 
facility surveillance for infectious diseases in western Kenya” (HDSS). For the baseline assessment, 
100 clusters were mapped. Eventually, 80 out of 100 baseline clusters will be selected for inclusion 
in the main trial using restricted randomisation to minimize imbalances in baseline predictors of the 
primary outcome (section 8.1, Allocation and randomization, page 32).   
The eligible populations for each evaluation are described in detail in the following sections.  

ATSB-Kenya Protocol (v1.1-31May21) 
24 
 Eligibility criteria for clusters 
 
Inclusion criteria clusters 
 
A grouping of contiguous rural villages in Alego-Usonga and Rarieda sub-counties of Siaya 
County 
 
A minimum of 200 households  
 
Exclusion criteria clusters 
 
Hard to reach in the rainy season 
 
Refusal to participate by village elders 
 Eligibility criteria for participants in the cohort study 
 
Inclusion criteria cohort  
 
A resident of a household within the core area of a study cluster, defined as living in the 
household in the recent four months and planning to live in the same household for the next 
6.5 months 
 
Aged ≥ 1 year and < 15 years at the time of enrollment 
 
Written informed consent and/or assent 
 
Exclusion criteria cohort 
 
A confirmed or suspected pregnancy. Pregnant women are excluded because they are 
eligible for intermittent preventive treatment of malaria in pregnancy (IPTp).  
 
Taking daily cotrimoxazole prophylaxis (because this has antimalarial effects) 
 
Known sickle cell disease (because they received antimalarial prophylaxis) 
 
Contraindication to artemether-lumefantrine, the medication used for parasite clearance  
 Eligibility criteria for households for ATSB deployment  
 
Inclusion criteria 
 
Households located within one of the 40 clusters (core or buffer area) randomly allocated to 
the trial intervention arm with a least one permanent resident 
 
Exclusion criteria 
 
Refusal of consent by the head-of-household to deploy ATSB on the outer walls 
(intervention villages only) 
 
Vacated compounds 
 Eligibility criteria for households for entomological monitoring 
 
Inclusion criteria households for entomological monitoring 
1. Household located within the core area of the cluster  
2. Head of household or his/her representative is at least 18 years of age  
3. Written informed consent for the collection of entomological data by the head of household 
or representative 
 
Exclusion criteria households for entomological monitoring 
 
No residents sleeping in the household during the planned night of monitoring 

ATSB-Kenya Protocol (v1.1-31May21) 
25 
 Eligibility criteria for human landing catches  
 
Inclusion criteria human landing catches  
 
Men aged 18 to 49 years 
 
Willingness and ability to work late at night for up to 7 hours at a time 
 
Willingness to take and tolerate a treatment regimen of the appropriate Kenya Ministry of 
Health (MoH) recommended antimalarial and chemoprophylaxis with 250 mg of mefloquine 
weekly to prevent malaria starting two weeks before the start of and until four weeks after 
completing HLCs 
 
Written informed consent 
 
Exclusion criteria human landing catches 
 
Refusal/inability to work late at night for up to 7 hours at a time 
 
Unwillingness to take or intolerance/allergy to appropriate MoH treatment regimen or 
chemoprophylaxis 
 Eligibility criteria for participants in rapid ethnographic methods evaluation 
(community members)  
 
Inclusion criteria ethnographic evaluation (community) 
 
A resident of a household within an intervention area defined as an ATSB area during the 
main trial or an ASB area during any preliminary studies 
 
Resides in a household at the time of ASB/ATSB deployment, where the ASB/ATSB was 
installed for at least one month.  
 
18 years of age or older if participating in focus group discussions; 15 years of age or older if 
participating in in-depth interviews 
 
Exclusion criteria ethnographic evaluation (community)  
 
Unable to provide consent 
 Eligibility criteria for participants in rapid ethnographic methods evaluation (ATSB 
monitoring assistants) 
 
Inclusion criteria ethnographic evaluation (ATSB monitoring assistants) 
 
Serving as an ATSB monitoring assistant with experience installing ATSBs and monitoring the 
deployment  
 
Eighteen years of age or older 
 
Exclusion criteria ethnographic evaluation (ATSB monitoring assistants) 
 
Less than one month experience (i.e. is new to the job) 
 
Unable to provide consent 
7.4 WITHDRAWAL/FOLLOW-UP  
Based on prior cohort studies in the area, we anticipate an approximate 20% refusal, LTFU, or 
withdrawal from each cohort. This is accounted for in the sample size calculations. The level of non-
participation in household surveys is expected to be less than 20%.   

ATSB-Kenya Protocol (v1.1-31May21) 
26 
7.5 BASELINE CHARACTERISTICS  
The study anticipates summarizing a number of baseline characteristics at the individual, household 
and cluster level (Table 2). 
Table 2: Baseline summary measures 
Characteristic 
Cohort  
Continuous household survey 
Cluster level 
Number of clusters 
N 
N 
Cluster Size 
Mean N HH (TOTAL HH) 
Mean N HH (TOTAL HH) 
Cluster Size 
Mean N residents (TOTAL N) 
Mean N residents (Total N) 
Cluster Size (sampling areas) 
Mean N residents (TOTAL N) 
Mean N residents (Total N) 
Cluster Size (buffer zones) 
Mean N residents (TOTAL N) 
Mean N residents (Total N) 
Baseline Incidence 
Mean incidence rate of clinical 
malaria in the baseline cohort 
per person-month (variance) 
Mean incidence rate of clinical 
malaria in the baseline cohort 
per person-month (variance) 
Baseline Prevalence 
 
Proportion positive by RDT for 
P. falciparum at baseline 
Household-level 
HH size 
Mean N residents (SD) 
Mean N residents (SD) 
LLIN ownership (at least one 
LLIN per household) 
Proportion HH with >=1 LLIN 
(First interview) 
Proportion HH with >=1 LLIN 
LLIN ownership (at least one 
LLIN per two people in the 
household) 
Proportion HH with >=1 LLIN 
per 2 residents (First 
interview) 
Proportion HH with >=1 LLIN 
per 2 residents  
 
 
 
Individual-level 
Age 
Mean age (SD) 
Proportion under five 
Sex 
Proportion of female 
Proportion of female 
HH size 
Mean hh size of participant’s 
HH (SD) 
Mean hh size of included hh 
(SD) 
Net Use 
Proportion Slept under the net 
night before the survey 
Proportion (tested population) 
slept under the net night 
before the survey 
7.6 INTERVENTION (ATSBS) 
 ATSB 
 
Deployment of ATSB in the study area 
We will use ATSBs from Westham Co. (Israel) containing Dinotefuran, a neonicotinoid insecticide 
effective at rapidly killing mosquitoes (See Section 11.3, Risks and Benefits, page 55 for safety 
information).  
ATSBs will be installed on all structures of consenting households in intervention areas that meet the 
following criteria: 
 
Complete roof with eaves 
 
At least three complete walls 
 
Wall length exceeds one meter 
 
Wall height exceeds 1.8 meters 

ATSB-Kenya Protocol (v1.1-31May21) 
27 
ATSBs will be affixed to each structure according to the instructions from the manufacturer as 
follows:  
 
Height of 1.8 meters or as high as possible above ground and out of the reach of children 
and animals 
 
Exterior walls of structures 
 
Wooden rods inserted on the top and bottom of the bait station to keep the station flat 
 
A string tied to the wooden rods to hang the bait station on two nails nailed into the 
household structure walls.  
 
ATSB membrane facing outwards and protected by eave   
The number of ATSBs (two or three) to be installed per 
structure will be determined during a field trial 
conducted from May 2021 to August 2021 (SSC Protocol 
3613; CDC IRB # 7112; LSTM REC # 18.015). A cadre of 
monitoring assistants will be recruited from participating 
communities. The monitoring assistants will receive 
training on how to unpack and correctly install the bait 
stations. The monitoring assistants will be responsible for 
providing individual-level household orientation for the 
ATSB. This orientation will include the following 
instructions:  
 
Do not remove the bait station for any reason 
 
Replace the bait station promptly should it fall 
down (provided it does not appear to have been 
damaged) 
 
Keep bait stations that may be temporarily uninstalled (e.g. awaiting assistance in 
reinstallation) out of reach from children and animals 
 
Contact the monitoring assistant if the bait station becomes damaged or goes missing 
 
Do not dispose of the bait stations. If, at any time, the household wishes to uninstall the 
stations, a monitoring assistant should be contacted for removal and proper disposal. 
When monitoring assistants visit households for bait station installation, they will provide an 
information sheet and seek informed consent (see ATSB Participant Information and Informed 
Consent Forms). ATSBs will be installed only at households where the head of the household or 
his/her representative provides informed consent. Household members will have the opportunity to 
ask questions and voice any concerns.   
Bait stations will be marked with a unique identifier. At the time of installation, the identifiers of 
ATSBs for a given household will be entered into a questionnaire allowing a linkage with data 
collected from that household. Data collection will include a household ID, household head name 
and contact information, as well as household GPS coordinates.  
 
Community sensitization 
Prior to ATSB deployment, community sensitization activities will be conducted to prepare 
communities for intervention and research activities. Community sensitization begins with the 
County and sub-County Health Management teams and the Division of National Malaria Program.  
Community sensitization activities will be informed by initial qualitative research activities 
undertaken to understand community member knowledge and perceptions regarding ATSBs based 
Figure 5 ATSB station in Mali 
 

ATSB-Kenya Protocol (v1.1-31May21) 
28 
on experiences from the validation studies. Community sensitization meetings (which may include 
‘barazas’) will be held in all intervention area communities. All community members will be invited 
to the meetings, and monitoring assistants and study staff, together with community leaders (e.g. 
elders, school teachers, religious leaders), will provide an overview of the ATSBs and instructions, as 
noted above. The community leaders and monitoring assistants, study staff, and community leaders 
will be trained about the ATSBs and will answer community member questions and address 
concerns. If they are unable to address specific questions or concerns, the monitoring assistants will 
refer these questions to the field coordinator. Where appropriate, local media may be used to 
disseminate messages to sensitize the community to the intervention and the research. This may 
include posters, pamphlets, or other printed materials. At each ATSB monitoring visit, and at the 
time of ATSB removal and replacement, household members will have the opportunity to ask 
questions and voice concerns to the ATSB monitors who will respond, capture this information, and 
report any questions that they are unable to respond to to the field supervisor who will then work to 
respond to the household.   
Sensitization meetings will also be held in control clusters to explain the trial and encourage 
appropriate care-seeking behaviour and usage of malaria prevention methods, including LLINs. 
 
Monitoring of ATSBs  
At the first visit during month 0, new ATSBs will be installed. At month 7, month 13, and month 19 
(every six months), all installed ATSBs will be replaced with new ATSBs. Full coverage of fully 
functional ATSBs will be maintained for the duration of the study. Community-based monitoring 
assistants will be trained and will be responsible for visiting intervention households monthly 
throughout the trial. Additionally, household heads in intervention areas will be instructed to 
contact monitoring assistants for a replacement bait station if one is damaged or missing in between 
monitoring visits.  
The monitoring assistants will be equipped with a supply of ATSBs and necessary materials for 
installing, replacing or re-hanging damaged or missing devices. During each monthly visit, the 
monitoring assistants will ensure eligible structures in study areas are covered with correctly 
installed ATSBs according to the manufacturer instructions. They will replace damaged or missing 
ATSBs as needed and record information about the ATSB condition in electronic data capture forms 
on a smartphone or tablet. The monitoring assistants will attempt to recover any missing ATSBs for 
proper disposal. They will respond to and record questions or concerns voiced by the household 
members to the field supervisor. At the end of their sixth month period, or if they are damaged or 
missing, they will be collected and incinerated in a high-temperature incinerator, per manufacturers 
instruction (see Section 16.3, Annex III: ATSB Stations: Disposal options assessment, page 80). 
 Control cluster interventions 
Between March and June 2021, the Government of Kenya is planning a mass LLIN distribution 
campaign throughout Siaya County (the study area is within Siaya County). Through our baseline 
continuous household survey (cMIS), we will evaluate LLIN coverage in all intervention and control 
clusters. Based on the findings, we may plan a “top-up” distribution to ensure equal coverage across 
arms.  
 Other malaria control interventions 
Community-case management of malaria by community health volunteers is an active intervention 
promoted by the Ministry of Health in this area. In this strategy, community health volunteers test 
and treat participants encountered in the households who complain of symptoms compatible with 

ATSB-Kenya Protocol (v1.1-31May21) 
29 
malaria. Additionally, in September 2019, the Kenya Ministry of Health began a phased 
implementation of GSK’s Mosquirix vaccine in children aged 5-17 months of age. Rarieda sub-county 
was chosen as an initial vaccinating sub-County, whereas Alego-Usonga was not. To control for the 
impact of RTS,S/AS01 on our study outcomes, we will ensure a balance of clusters between arms in 
Rarieda and Alego-Usonga sub-Counties. Additionally, we will record the vaccination status of all 
children <5 years of age from the maternal-child booklet or from vaccination cards. Where available, 
we will take a photograph of the child’s vaccination records. Where not available, we will use 
maternal recall. The Kenya Division of National Malaria Program (DNMP) does not currently have 
plans to perform IRS in Siaya County during the trial period. Should IRS be implemented in the trial 
area during the trial, the study team will monitor timing and coverage of the campaign at a 
household and cluster level but will not be responsible for regulating or “topping up” IRS should 
DNMP initiate spraying in the area. 
7.7 ADHERENCE AND PROTOCOL DEVIATIONS 
Both individual and cluster level adherence measures will be defined and pre-categorized prior to 
final analysis and used to categorize the per-protocol trial population. Since the intervention is 
deployed on a group basis rather than individually, adherence definitions will take account of this.  
 Cluster-level adherence 
In intervention clusters, adherence at the cluster level will be defined as a cluster where ATSBs were 
deployed and replaced according to the planned schedule. Non-adherence in intervention clusters 
will be defined as clusters where there was more than one-month delay in ATSB deployment during 
a two year period.  
 Household-level adherence 
Household-level adherence will be evaluated in the intervention cluster arms through ATSB 
monitoring visits. For each household, “expected ATSB-time” will be calculated by multiplying the 
total number of expected ATSBs hanging (2-3 ATSBs per structure) by the duration of time between 
visits (approximately four weeks). “Actual ATSB-time” will be calculated by multiplying the observed 
number of ATSBs during the monitoring visit by the duration of time they were hanging. The ratio of 
“actual ATSB-time” over “expected ATSB-time” will be expressed as a percentage and used as the 
measure to evaluate household-level adherence. For example, if a household has ten structures, and 
the intention is to have two ATSBs per structure, there should be 80 ATSB-weeks over four weeks 
(10x2x4). If the household had only one ATSB hanging on each structure between visits, the 
household would have an observed ATSB-time of 40 ATSB-weeks (10x1x4) and a household 
adherence of 50% (40/80).  
 Individual-level adherence to antimalarial treatment among cohort members 
A random subset of cohort participants who have recently been treated for malaria may be re-
visited within one week to assess adherence to the study medication. At this time, study staff will 
ask questions about the total number of doses taken and request to view the blister pack that 
contained the treatments that the participant took. 
 Protocol deviations 
Protocol deviations will be considered as the cluster and individual level using the above-described 
definitions for adherence. Protocol deviations related to failure to carry out other study procedures 
such as outcome assessment on a standardized schedule will not be considered reportable to DSMB 
unless they affect an entire cluster and delay primary outcome assessment by more than two 

ATSB-Kenya Protocol (v1.1-31May21) 
30 
months. Protocol deviations related to failure to deliver or replace ATSB will be summarized in the 
final trial reports and incorporated into the calculation of adherence. 
7.8 SAMPLE SIZE 
The number of study clusters identified for this study was driven by sample size considerations for 
the primary endpoint, malaria case incidence.  
 Malaria case incidence cohort 
 
Main trial 
The sample size was calculated using the ‘Tests for the Difference Between Two Poisson Rates in a 
Cluster Randomized Design’ module in PASS 2020 (©NCSS, Kaysville, Utah). The observed event rate 
in this age group was 1,128 per 1000 person-years in the control arm of a recently completed mass 
test-and-treat trial in this area. A more conservative event rate of 845/1000 will be used, which is 
25% lower than the previously observed event rate of 1,128/1000 person-years. This is done to 
account for an estimated 7.4% overall reduction in event rates in children 1-<15 years due to the 
implementation of the RTS,S/AS01E vaccine (vaccine efficacy 39.0%) in two-third of the study area in 
children 1-<5 years of age (28.6% of the sample study cohort) (0.39x0.67x0.286=0.074), plus a 
further 17.6% reduction in malaria due to unforeseen changes in environmental factors, or boosting 
of other malaria control measures such as the scaling up of integrated community-based case 
management. The coefficient of variation in this previous study was 0.4.  
A total sample size of 2,240 person-years (1,120 per arm, or 28 person-years per cluster) is required 
to detect a ≥30% reduction in the incidence of clinical malaria among children aged 1-<15 years (the 
primary outcome) from 845 per 1000 person-years in the control arm to 592 in the intervention arm 
over two years, allowing for 20% loss of person-time due to LTFU, or exclusion of person time after a 
clinical event treated with artemether-lumefantrine during a six month follow-up period resulting in 
1,760 person-years completed (22 person-years per cluster, 880 person-years per arm) (80 clusters 
[40 per arm], CV=0.4 in both arms, two-sided alpha=0.049, power=90%). No sample size inflation is 
required two allow for two interim analyses because a similar sample size is needed (2,240) for a 
study with a final two-sided alpha of 0.049 as for a study with a single analysis using a two-sided 
alpha of 0.05.  
The intention is to follow each child for 6.5 months. This includes two weeks of lead-in time that do 
not contribute to the analysis. These are the first two weeks after the initial presumptive treatment 
with artemether-lumefantrine to clear any existing parasitaemia. This will then be followed by six 
months of follow-up time that contribute to the analysis. We will use a more conservative average 
follow-up time of five months per participant to allow staggered enrolment of participants over 
time. This means that not all children towards the end of the 2-year trial will complete the full 6.5 
months. The 2,240 person-years will thus be obtained by sampling approximately 67.2 individuals for 
an average of five months each in 80 clusters (67.2x[5/12]x80=2,240).  
The same sample size will also have 80% power to detect a 26% reduction from 845 to 622 per 1000 
person-years with all other parameters kept the same, or 80% power to detect a 30% reduction if 
the CV was 0.488 instead of 0.4. Similarly, the study would have at least 80.0% power to detect a 
significant difference at the first interim analysis when 50% of the events have occurred in the 
control arm if the effect size is 41.2% instead of 30% (alpha=0.001, using Haybittle-Peto  type 
boundaries, see 9.4.1, Interim analysis, page 44). 

ATSB-Kenya Protocol (v1.1-31May21) 
31 
 
Baseline cohort 
The baseline cohort will be conducted during a period of approximately six months in 100 (instead of 
80) potential clusters before the deployment of ATSB. The sample size for the baseline cohort will be 
550 per year, obtained by following 11 participants per cluster for an average of five months each 
(11x[5/12]x100). The sample size is based on similar sample size considerations per cluster as for the 
main trial but adjusted to a six month instead of a 2-year period. The average of five months each 
(with a maximum follow-up time of 6.5 months per participant) is used to take a staggered 
enrolment into the cohort into account (i.e., not all participants will have contributed the full 6.5 
months before the start of the main trial).  
 Continuous malaria indicator survey to assess malaria parasite prevalence  
7.8.2.1.1 Main trial 
The continuous malaria indicator survey (cMIS), conducted under a separate protocol, provides 
adequate power to detect a 30% reduction in the all-age malaria prevalence detected by RDTs per 
year from 29.0% to 20.3%. The 29% prevalence is based on the observed all-age prevalence in 
Rarieda sub-county (29%) (representing two-thirds of the study area) and in Alego-Usonga (47.3%), 
representing one-third of the study area. The 47.3% in Alego-Usonga is based on cMIS data in 
neighbouring Karemo. The prevalence estimate in Rarieda is reduced from 29% to 27.7% to account 
for a 50% drop in malaria prevalence in children < 5years of age who will receive the RTS’s vaccine. 
Because this age group only represents 13.9% of the population, the anticipated impact of RTS,S on 
the all-age prevalence in Rarieda is modest. The pooled estimate of the RTS’s adjusted all-age 
prevalence of 27.7% in Rarieda and 47.3% in Aleg-Usonga is 34.1%. We propose to use a more 
conservative prevalence of 29% to allow a 15% reduction in malaria prevalence due to annual 
variations in environmental conditions (e.g. rainfall, temperature) (0.85 x34.1%=29%). This requires 
3,520 participants per year (44 per cluster, including 9 non-responders and 35 responders) 
(ICC=0.05, power=90%, two-sided alpha=0.05, and assuming 20% non-responders, e.g. refusals, not 
at home, etc.). The values for the intra-cluster correlation (ICC), parasite prevalence, and non-
response rates were estimated from the ongoing cMIS study. Where possible, households that are 
included in the first year will be excluded in the second year. Over 2-years, and assuming no overlap 
in participants between the first and second year, a sample size of 88 per clusters (including 18 non-
responders and 70 responders) would provide 80% power to detect a 23.7% reduction or 90% to 
detect a 27.3% reduction (ICC=0.05, alpha=0.05). Similarly, 70 responders per cluster after two years 
would provide 80% power to detect a 30% reduction if the ICC is 0.091 instead of 0.05, or 90% 
power if the ICC is 0.064.  
 
Baseline 
A similar annual sample size of 44 per cluster, including 9 non-responders and 35 responders, will be 
used in 100 clusters during the baseline year before the deployment of ATSBs in the intervention 
arms. 
 Entomological monitoring  
Twelve intervention clusters and 12 control clusters will be selected for entomological monitoring. 
Based on previous field research in Mali, large reductions in mosquito density are anticipated, up to 
90% (although density reductions may be dependent on the season due to seasonal fluctuations in 
abundance). A minimum reduction in density of 50% was used for sample size calculation.  
Ten 10 entomological collections per cluster per month are required to detect a 50% reduction in 
mosquito densities per CDC UV light trap (two-sided alpha=0.05, power=80%, ICC=0.38, 24 clusters 

ATSB-Kenya Protocol (v1.1-31May21) 
32 
[12 per arm]). For the impact of ATSBs on parity or sporozoite rates, all unfed mosquitoes captured 
alive will be used to estimate parity rates. All Anopheles mosquitoes collected during the study will 
be subjected to ELISA to estimate sporozoite infection rates. 
 Rapid ethnographic methods 
Focus group discussions (FGD) and in-depth interview (IDI) will be implemented at three discrete 
time periods: 1) before ATSB deployment, 2) at least one month after the first round of ATSB 
deployment, and 3) at least one month after a subsequent ATSB deployment. Each FGD will involve 
six to eight participants. FGDs will be segregated by sex and community members versus monitoring 
assistants. In the pre-ATSB deployment stage a total of six FGDs will be conducted; four among 
community members and two among monitoring assistants. In each of the post-ATSB deployment 
rounds, twelve FGDs will be conducted among community members and two among monitoring 
assistants. IDIs will be conducted among community residents. A total of eight will be conducted in 
the pre-ATSB deployment period, and then twelve each during the post-deployment rounds. 
8 METHODS: ASSIGNMENT OF INTERVENTIONS 
8.1 ALLOCATION AND RANDOMIZATION  
Restricted randomization will be used to allocate 80 of the 100 baseline clusters to intervention and 
control arms for the main trial to minimize any imbalance between study arms on key baseline 
characteristics. The steps to achieve restricted randomization will be conducted by a study team 
member who is not responsible for trial implementation. The steps are as follows: 
1. 
Establish balance criteria. The factors described in the table below may be considered for 
suitability as restriction criteria. 
2. 
Generate a list of at least 100,000 randomizations 
3. 
Check randomizations against balance criteria and drop those that do not fit 
4. 
Assess the number of randomizations left. There may be a need to relax criteria and start 
again if fewer than 10,000 acceptable randomizations remain.  
5. 
Test remaining set of potential randomizations for validity, specifically that all clusters are 
being independently assigned to study arms (e.g. check that no two clusters are always 
jointly assigned to the same arm).  
6. 
Randomly choose a randomisation.  
7. 
Flip a coin to determine if arm A or arm B is ATSB or control.  
8. 
Step 6 and 7 to be done in public with community participation.  
Table 3: Factors to consider for restricted randomisation 
Covariable/ 
endpoint 
Restriction criteria 
Data source 
Analytic method 
Malaria 
disease 
incidence 
The difference in mean clinical 
case incidence between trial 
arms (size of difference to be 
assessed when data are 
available) 
Baseline cohort 
The difference in disease 
incidence of cluster 
summaries between study 
arms  
Bednet use 
 
The difference in mean 
proportion of persons slept 
under any net night before 
survey between trial arms ≤5 
percentage points 
Baseline survey  
 
The difference in means of 
cluster summaries of the 
proportion of persons of all 
ages slept under any net night 
before survey between arms 

ATSB-Kenya Protocol (v1.1-31May21) 
33 
Population 
The total population size of the 
larger trial arm is no more than 
10% larger than the smaller arm 
Enumeration datasets 
Sum(pop size of clusters Arm 
large)/Sum(Pop size of 
clusters arm Small) less than 
1.10 
RTS,S/AS01 
vaccinating 
area 
Number of clusters in 
intervention and control arm 
balanced by vaccinating or non-
vaccinating areas for RTS,S/AS01 
Kenya National 
Vaccinations and 
Immunizations Programme 
(NVIP) 
N in Arm A== N in Arm B 
Housing 
density* 
The difference in mean housing 
density between trial arms ≤ 0.3 
SD of overall cluster level 
housing density 
Enumeration + cluster 
boundaries GIS files 
 
Or 
 
Remotely sensed data 
(GRUMP/WorldPop) plus 
Cluster boundaries GIS 
SD(cluster estimates of 
housing densities)*0.3 ≥ 
|mean(cluster estimates 
housing density Arm a) – 
mean(Cluster estimates of 
housing density Arm b)| 
HF location 
Number of clusters with a 
primary care facility exactly 
balanced across arms 
Study team 
documentation 
N in arm A == N of Arm B 
Altitude 
Differences in mean altitude of 
cluster centroids between trial 
arms ≤ 0.3 SD of overall cluster 
level mean altitude 
Digital Elevation Model 
(ASTER) combined with 
(GIS) shapefiles for cluster 
boundaries. 
SD(cluster estimates of 
altitude)*0.3 ≥ |mean(cluster 
estimates of altitude Arm a) – 
mean(Cluster estimates of 
altitude Arm b)| 
Entomological 
data collection 
The number of clusters with 
entomological data collection 
planned is exactly equal across 
study arms 
Study team self-report 
N in arm A == N in arm B 
*Either urbanization or housing density will be selected; these variables are likely collinear.  
8.2 BLINDING 
Allocation of study arms will not be blinded to the participants, the deliverers of the intervention, or 
the main investigators. Sham ATSBs will not be deployed in control areas because it is logistically not 
feasible to produce the number of ATSB stations needed for both intervention and control arm. The 
potential for bias among operator-dependent mosquito catches (indoor and outdoor aspirations) 
will be minimized using a standardized protocol. Additionally, the potential for bias in mosquito 
catches using CDC light traps is very low. The potential for changes in human behaviour affecting 
malaria control intervention coverage, namely LLIN use, will be minimized through comprehensive 
community engagement and communications. LLIN use will be promoted in intervention and control 
areas. Additionally, study teams will monitor LLIN use in intervention and control areas to document 
changes throughout the life of the study. Laboratory processing of mosquito and human blood 
specimens will be blinded.  
To further minimize bias, we will use an objective primary outcome measure and mask all laboratory 
staff to the treatment assignment of individual participants. The trial statistician will also be blinded 
regarding the allocation arm when the statistical analysis plan is developed and the analytical syntax 
is written, which will be validated and completed using dummy randomization codes. The actual 

ATSB-Kenya Protocol (v1.1-31May21) 
34 
allocation will only be provided to the study team after locking the database and approval of the 
statistical analysis plan by the independent DSMB before they review any trial results.  
9 METHODS: DATA COLLECTION, MANAGEMENT AND ANALYSIS 
9.1 DATA COLLECTION 
Outcomes are assessed using different sub-studies, including cohort studies, continuous household 
surveys, passive clinic- and CHV-based surveillance and ethnographic and economic studies; for an 
overview, see Section 5, Objectives and outcomes, page 15. The details of each of these components 
are outlined below. 
 COVID-19 mitigation efforts 
As a result of the COVID-19 pandemic, the Government of Kenya and the KEMRI SERU have 
developed guidelines to be followed within research trials to protect participants and study staff 
from SARS-CoV-2 transmissions (KEMRI-SERU section 3.2.5, Ref: KEMRI/SERU/REC/GUIDE/001 of 
22nd June 2020). These mitigation efforts are periodically updated by the Ministry of Health and 
KEMRI. We will adhere to the prevailing Ministry of Health and KEMRI guidelines at the time that the 
study commences and will adopt any new recommendations during the course of the trial. 
 Cohort study to assess the incidence of clinical malaria 
Households with participants aged 1 to <15 years of age will be randomly chosen from the 
household in the census database. A single resident aged 1 to <15 years will be selected from these 
households to be enrolled in the cohort. They will be followed for up to 6.5 months, including two 
weeks of lead-in time for parasite clearance and six months of subsequent follow-up, contributing to 
the analysis person time). The sampling frame of households may be updated based on findings 
from subsequent routine CHV censuses in the study area. A baseline cohort study will be conducted 
before the deployment of ATSB to inform the restricted randomisation, followed by a cohort study, 
to assess the impact of ATSB. The procedures in these cohorts will be similar, as outlined below. 
 
At recruitment/enrolment 
 
Informed consent will be administered to the parent/caregiver, and assent to the participant 
if he/she is 13-<15 years of age 
 
A fingerprick blood sample (~250µL or 1mL) will be collected to perform an RDT and to 
prepare approximately five dried blood spots (DBS) on filter paper for subsequent molecular 
and potentially serological testing and for evaluation of mosquito salivary antigens 
 
All cohort members will be treated with artemether-lumefantrine (AL; first-line antimalarial 
in Kenya) irrespective of their RDT result to clear any subpatent infections that may exist  
 
A questionnaire will be administered to the head of the household to assess household 
assets for the construction of socio-economic status (SES) categories and to assess 
household  malaria control measures (e.g. number of LLINs, housing construction) 
 
A questionnaire will be administered to the parent/caregiver and/or the participant to 
assess activities of interest, including medical and vaccination history, medication use, 
inclusion in other clinical trials, care-seeking behaviour, LLIN use, daily commuting and travel 
information, and information about the structure that the participant sleeps in  
o A photograph will be taken of vaccination history and pertinent medical records 
from the maternal child health booklet or other records 

ATSB-Kenya Protocol (v1.1-31May21) 
35 
o For participants enrolled in the HDSS or clinical studies, we will link the cohort data 
to their study/HDSS records 
 
For young women of childbearing age (12-14 years), pregnancy status will be evaluated in a 
private and confidential location through the following algorithm: 
o If the woman has had menarche, her last menstrual period was >=6 weeks ago, and 
if she has any suspicion that she may be pregnant, then she will be offered a urine 
pregnancy test 
o If she declines or is found to be pregnant, she will be considered ineligible for the 
cohort  
 
A photograph may be taken of the participant to create a study identification badge that the 
participant will keep for identification by study staff for scheduled and sick visits 
 
Parasite clearance confirmation visit (2 weeks after enrolment) 
 
Before this visit, the study team will call the cohort member to remind them of the 
upcoming visit and reschedule if necessary. Up to three visit attempts will be made to 
complete the parasite clearance confirmation visit.  
 
Two weeks after the enrolment visit, the household will be visited and a finger-prick blood 
sample (~250µL to 1mL) will be drawn to prepare five dried blood spots, and to prepare a 
blood smear for parasite clearance confirmation. 
 
If the participant is febrile at this visit, the staff member will review the RDT result from the 
enrolment visit.  
o If the enrolment visit RDT was negative, the participant will be re-tested with an RDT 
and if positive, the participant will be ineligible for the cohort and second-line 
antimalarial treatment will be administered as per national guidelines (e.g. 
dihydroartemisinin-piperaquine). If the RDT administered during this visit is 
negative, we will proceed with the blood smear. 
o If the enrolment visit RDT was positive, the blood smear will be expedited.   
 
If the participant is found to be positive for malaria by microscopy, we will consider the 
participant ineligible for the cohort and will withdraw him/her. A staff member will return to 
the house to convey this information and provide second-line antimalarial treatment as per 
national guidelines (e.g. dihydroartemisinin-piperaquine). 
 
At each monthly cohort visit (starting 4 weeks after enrolment)  
 
Prior to each follow-up visit, the cohort study team will call cohort members to remind them 
of the next visit and reschedule, if necessary, to minimize loss to follow-up. Up to three visits 
will be made to each cohort study household to complete a follow-up visit. 
 
At each of these visits, a finger finger-prick blood sample (~250µL to 1mL) will be drawn to 
prepare approximately five dried blood spots for testing, as indicated in the enrolment visit.  
 
If the participant has an axillary temperature of ≥37.5⁰ C or reported history of fever in the 
last 48 hours, a malaria RDT will be performed using blood from the same fingerprick. Those 
who test positive for malaria by RDT will be treated at the household according to the Kenya 
Ministry of Health Guidelines unless they already received appropriate antimalarial 
treatment from other sources in the previous seven days. Cohort members who do not have 
objective fevers or report a history of fever in the last 48 hours will not be tested for malaria 
by RDT.  
 
For women of childbearing age, pregnancy status will be evaluated as described in the 
enrolment visit section. Those in whom a pregnancy test is indicated but who decline and 
those who have a positive pregnancy test will be withdrawn from the cohort. These women 

ATSB-Kenya Protocol (v1.1-31May21) 
36 
may opt to be visited and evaluated for malaria, free of charge for the duration that they 
would have been in the cohort. 
 
A questionnaire will be administered on a tablet or smartphone to the participant or his/her 
parent/guardian, including questions about the history of recent illness (including AEs and 
SAEs), care-seeking, LLIN use, and travel and commuting history. If the cohort member 
sought care between scheduled visits, we will copy any relevant information from these 
health records to evaluate any malaria diagnostics performed and antimalarial treatment 
given 
 
A follow-up visit in four weeks time may be scheduled at this time. Parents/guardians and 
the participant will be reminded to call the study staff at the number provided on the 
consent form if the participant becomes ill before the next scheduled visit.  
 
The limited care provided by the study team includes any care related to study procedures, 
malaria illness, or other uncomplicated acute illnesses such as acute respiratory or 
gastrointestinal disease. The study will not be responsible for the care of pre-existing 
conditions or chronic or traumatic conditions diagnosed during the trial. 
 
Sick visits (participant initiated visits occurring between scheduled monthly visits) 
 
Study staff will tend to cohort participants for sick visits as described above  
 
During these sick visits, study staff will administer a “sick visit” questionnaire including 
questions about current illness and any associated care-seeking behaviour or medications 
ingested. 
 
Questions about physical interaction with or ingestion of ATSBs will also be included for AE 
and SAE monitoring.  
 
Will collect a finger- or heal-prick to collect 250 µL to 1 mL of blood to prepare 
approximately five dried blood spots on filter paper and for any other diagnostic tests that 
are clinically indicated based on the participant’s presentation  
 
In the setting of identifying that a cohort member sought care from outside of the study 
(identified either from a phone call or subsequent scheduled visit), study staff will attempt 
to gather records from the facility, CHV or pharmacy where the cohort member sought care   
PCR and serological testing of the DBS specimens collected during the study will not be used for care.  
 Continuous household survey  
 
Continuous malaria indicator survey (cMIS) 
Community malaria infection prevalence will be evaluated through an ongoing protocol involving 
participants of all ages, “Malaria Indicator Household Surveys to evaluate the impact of malaria 
transmission reduction activities in Siaya County, western Kenya: a continuous rotating panel 
survey”; short title, “Continuous Malaria Indicator Survey (cMIS)” [KEMRI SERU Protocol# 2773; CDC 
IRB# 6733; LSTM REC#  14.009; PATH RDC# 0777]. The survey will include malaria blood testing by 
RDT and PCR. The RDT result will dictate malaria treatment in the field, and PCR results will be 
processed at a later date to estimate the secondary outcome of infection prevalence by PCR. The 
individual and household questionnaires will capture information about malaria intervention 
coverage (e.g. LLIN ownership and use), housing characteristics, and household demographic 
information. The surveys will also measure a set of indicators regarding ATSB knowledge and 
perceptions. 
 
Brief description of cMIS procedures 
 
Households are randomly selected for household visits 

ATSB-Kenya Protocol (v1.1-31May21) 
37 
 
Staff members administer informed consent  
 
Staff members administer the cMIS questionnaire on a password protected study tablet, 
which includes questions about the history of illness, care-seeking, malaria prevention 
methods and coverage 
 
Study staff collect blood (250 µL to 1 mL) from a finger- or heal-prick to prepare 
approximately five blood spots on filter paper and to perform a rapid diagnostic test. If the 
RDT is positive, the study staff member treats the participant per Kenya Ministry of Health 
guidelines  
 Passive case detection  
Confirmed malaria case incidence data will be collected from outpatient health facilities, ANC clinics,  
and from CHVs providing diagnostic testing in the community through the Kenya Ministry of Health. 
These are routine surveillance data collected by the Ministry of Health and do not include personally 
identifiable information. Numbers of participants with suspected malaria, tested for malaria (RDT or 
microscopy), diagnosed with malaria and treated for malaria are recorded in the routine registries 
collected at these facilities and by CHVs.  
The population denominator for incidence calculations will be derived from the house-to-house 
enumeration and census. 
 Entomological monitoring  
Entomological monitoring activities will include routine indoor and outdoor mosquito collections 
using CDC UV light traps and human landing catches (HLC), monitoring for insecticide resistance, and 
ATSB durability.   
 
UV light traps 
1. Twelve intervention area and 12 control area clusters will be randomly selected for 
entomological monitoring using UV Light traps.  
2. Entomological field assistants will receive training in the study methods and procedures for 
mosquito collections.  
3. Informed consent will be administered to the head of household  
4. UV light trap collections will be conducted monthly for the duration of the trial. The 
household sampling frame generated during the census will be used to select a random 
sample of 10-12 households per cluster.  
5. Collections from clusters will be completed in pairs: one intervention and one control cluster 
pair. If feasible, collections from all 10-12 households in each of the 2 clusters will be 
completed in one night. If this is not feasible, collections will be completed over two nights 
from 5-6 households per cluster per night.  
6. In each selected household, a UV light trap will be hung at the foot of a bed or sleeping 
space by the entomology field team between 1700-1800HRS in the evening. The UVLT 
should be set next to a bed or sleeping space with a net hanging over it. The house owners 
will be instructed not to touch it until removed by the team the next morning 
7.  An additional light trap will be set up outdoors 
8. In the morning, the entomology field assistants will visit the household, ensure the UVLT is 
still running and then carefully remove the collection cup to ensure no mosquitoes escape.  
Mosquitoes will be returned to the KEMRI CGHR laboratory in Kisian or a field laboratory, 
where mosquitoes will be sorted and processed for further analyses. 

ATSB-Kenya Protocol (v1.1-31May21) 
38 
 
Human landing catches 
1. Six clusters not included in the monthly UVLT sampling will be randomly selected from each 
arm, and within each cluster, four households will be purposively selected for quarterly 
indoor and outdoor mosquito collections using human landing catches. Each household will 
participate in this collection for two nights. 
2. Selected households will be visited in advance of the collection night and provided 
information about the study. Informed consent will be sought from the head of the 
household or his/her representative. 
3. A team of 6 collectors will be consented per house. They will be divided into pairs, and each 
pair will work up to a 6-hour shift during the night. Collections will begin at 5 pm in the 
evening and continue through 11 am the following morning. 
4. Collectors will work for 45 minutes each hour and then take a 15-minute break to rest, take 
food if necessary and prepare for the next hour of collection. Each pair of collectors will 
work for 6 hours before a new shift will take over. 
5. Prior to the HLC, collectors will be trained to properly aspirate mosquitoes, ideally before 
they are bitten, and will have ample time during training to practice the technique so as to 
minimize bites during collections. 
6. The collectors will sit in fixed spots, one inside the house and one outside at least 5m away 
from the house. They will then expose their lower legs, and using a torch (flashlight) and a 
mouth aspirator, they will collect mosquitoes that land on their lower legs.  Collected 
mosquitoes will be placed in individually labelled paper cups with a separate cup for each 
hour of indoor collection and outdoor collections. 
7. Mosquitoes will be returned to the KEMRI CGHR laboratory in Kisian or a field laboratory in 
the study area where mosquitoes will be sorted and processed for further analyses. 
8. Collectors will be provided with mefloquine 250 mg weekly for prophylaxis, starting two 
weeks prior to the HLCs as per manufacturer guidelines. Research has shown that with 
proper prophylaxis, participants in human landing catch collections are at a reduced risk of 
malaria infection compared to non-participants living in the same community.[20] To further 
minimize risk to field workers, they will be instructed to wear long-sleeve shirts during the 
collections to prevent mosquitoes from landing and biting them on the arms (only the legs 
are exposed for the collections).  Collectors will also be provided with free malaria testing 
and treatment if they become ill during the course of the HLCs and for up to 4 weeks after.   
 
Insecticide resistance monitoring 
1. Insecticide resistance monitoring will be examined at the end of years one and two and will 
include testing dinotefuran, permethrin, and either deltamethrin or alphacypermethrin. 
2. An. gambiae s.l. mosquitoes will be collected as larvae while An. funestus will be collected as 
adults from inside houses. Fed/gravid An. funestus will be allowed to lay eggs. Immature 
mosquitoes collected as larvae or from adult An. funestus will be reared to the adult stage in 
the insectary at the KEMRI CGHR in Kisian. 
3. Adults that are 2-5 days old will be exposed to the insecticides using standard WHO tube 
tests to permethrin, deltamethrin and alphacypermethrin [21]. 
4. Twenty to twenty-five mosquitoes per tube (or bottle) will be run, and enough tubes/bottles 
will be run to have a minimum of 100 mosquitoes exposed (the total number of mosquitoes 
will be dependent on the amount able to be collected).  
5. WHO test papers for dinotefuran are not available. Resistance testing for this insecticide will 
be done using a topical application of a diagnostic concentration to the thorax of adult 
mosquitoes, and mortality will be recorded after 24 hours. 

ATSB-Kenya Protocol (v1.1-31May21) 
39 
 
Bait station durability 
1. To examine the durability of the bait stations during the first 6-month deployment, a 
selection of ATSBs will be randomly sampled from households within ATSB study clusters. 
Stations collected from households will be immediately replaced with new stations.   
2. The bait station will be placed in a 30cm x 30cm x 30cm cage and 100 female An. gambiae or 
An. arabiensis (collected as larvae and reared in the lab)  will be introduced into the cages 
after an appropriate period of starvation. 
3. Mortality will be recorded at 24 hours.  
4. The number of dead and live mosquitoes will be recorded at 48 hours. 
 
Entomological laboratory procedures 
1. Specimens will be processed to estimate species composition, density, age structure, 
sporozoite rate, and EIR estimation. 
2. Mosquitoes will initially be identified morphologically using standard dichotomous keys  
3. All female anopheline mosquitoes will be tested for the presence of Plasmodium spp. 
sporozoites using ELISA 
4. Mosquitoes identified as An. gambiae s.l. will be identified to species using standard PCR. A 
subset of An. funestus will be identified to species by standard PCR methods. 
5. A subset of live female mosquitoes collected by UVLT or HLC will be dissected and examined 
for dilatations in the ovarian duct as a proxy for age (each dilatation represents an egg batch 
laid). 
 ATSB Intervention monitoring  
1. ATSB monitoring assistants will be trained on proper installation, adjustment, and removal 
and transport of ATSBs on structure walls, administering an ATSB questionnaire, and 
responding to questions or concerns raised by household members. 
2. After administering informed consent and ATSB installation community-based, ATSB 
monitors will visit households in intervention clusters on a monthly basis 
3. ATSB monitors will complete a questionnaire programmed onto a tablet or electronic data 
capture form to assess the presence of each ATSB and/or whether it has incurred any 
damage 
4. If an ATSB has been damaged, the monitor may photograph the damaged ATSB 
5. Damaged or missing ATSBs will be replaced by ATSB monitors at each visit 
6. ATSB monitors will instruct the head of the household to contact the study team if an ATSB 
is damaged or is missing between each visit so that the ATSB monitor can return to replace it 
to ensure high ATSB coverage rates 
7. ATSB monitors will additionally respond to any questions or concerns that household 
members have about the ATSB or the trial. They will refer questions they are unable to 
answer to the field supervisor for further consideration and response. 
 Rapid ethnographic methods 
The qualitative component of this study is designed to understand potential factors that influence 
coverage, including 1) ASB and ATSB coverage, defined as the continuous and correct installation of 
the ATSBs, and 2) LLIN coverage, defined as routine use by household members each night (see 
Figure 6: Conceptual framework for the qualitative study, below). 

ATSB-Kenya Protocol (v1.1-31May21) 
40 
Figure 6: Conceptual framework for the qualitative study 
 
A series of three qualitative evaluations will be conducted as part of this trial: 1) after an 
entomological validation trial with ASBs, but before the main trial, 2) during the first year of the 
ATSB main trial, and 3) during the second year of the main ATSB trial. For the evaluation occurring 
during the main trial, these will be conducted at least 1-month after the introduction of the ATSBs. 
Focus group discussions (FGD) and in-depth interviews (IDI) will be conducted in intervention 
clusters (for the first evaluation, these will occur in areas where ASBs had been implemented for 
entomological validation trials) with the aim of understanding the potential factors influencing 
coverage. These qualitative methods will be applied as rapid ethnographic methods with a focus on 
rapidly available and actionable information to inform programmatic decisions. This includes guiding 
community engagement prior to the first ATSB deployment and informing strategies to ensure high 
community engagement and coverage levels throughout the trial. The FGDs will engage a set of 
community members as key informants in a discussion regarding community experiences with the 
ASBs and ATSBs. Separate FGDs will also be conducted with ASB and ATSB monitoring assistants 
serving as key informants on community experiences. The IDIs will be conducted with residents in 
intervention areas and will be used to explore in detail the experience of individual households with 
the ASBs and ATSBs. Additional messages will be created from these ethnographic methods to 
provide similar messages across arms to ensure LLIN usage and strengthen education and care-
seeking behaviour for malaria. 
 
Procedures for focus group discussions 
1. Field workers will receive training in the study design, research tools, and study procedures 
for the FGDs and IDIs.  
2. FGDs will be performed in each of the entomological validation clusters at baseline 
3. ATSB monitoring data will be used during the main trial to classify clusters as having a 
relatively high or low incidence of ATSB damage, removal or replacement.  
a. Three clusters classified as high incidence and three clusters classified as low 
incidence will be randomly selected 
b. A single village within each of these six clusters will be randomly selected 
Potential factors influencing 
coverage 
Coverage
Impact (trial outcomes)
Reduction in incidence & prevalence
ASBs & ATSBs continuously 
and correctly installed
-ASB & ATSB 
damage from 
elements (wind, 
rain), improper care 
(cleaning) & 
installation, other
-ASB & ATSB  
frequently 
unintentionally 
removed (e.g. due to 
wind, rain)
ASB& ATSBs 
purposefully 
removed due to: 
-Perceptions: 
risk, benefit, harm
-Preferences e.g. 
appearance
LLINs routinely 
used 
-Perceived 
malaria risk
- Perceived 
benefit of LLIN 
use

ATSB-Kenya Protocol (v1.1-31May21) 
41 
4. Within each of the clusters/villages selected for FGDs, two groups of six to eight community 
members will be purposively selected by community-based field monitoring assistants based 
on their activity within the community and exposure to views and experiences of community 
members (i.e. school teachers, religious leaders, village elders) 
5. Additionally, at each round, two sets of FGDs will be conducted with six to eight community-
based ATSB monitoring assistants selected by the research team as key informants with 
monitoring ATSBs and deploying them 
6. FGDs will be segregated by sex, and an equal number of FGDs with women and men will be 
conducted  
7. Participants selected for FGD will be brought together in a central but private location and 
provided with an overview of the study and an informed consent form. Those that provide 
informed consent will continue to participate in the discussion. 
8. The FGD will be closed to outside observers, limited only to consenting participants and the 
fieldworkers conducting the session.  
9. Two field workers will conduct the FGD. One fieldworker will lead the discussion, and the 
other will take notes. The discussion will be recorded for transcription.  
10. A semi-structured discussion guide will be used to guide the discussion (See separate file, 
ATSB Focus Group Discussion Guide (Community Members) and (Monitoring Assistants)).  
11. The discussion will last approximately 60 minutes.  
12. The recording of the discussion will be used to create a discussion transcript for data 
analysis.  
 
Procedures for in-depth-Interviews  
1. The first round of IDIs will be conducted among four key informants per each of the 
entomological validation and field trial study clusters. The four participants will be 
purposively selected using community-based field workers that assisted with the monitoring 
and implementation of the validation study. The field workers will be asked to select two 
households that experienced issues with the ASB, including damage, removal, or 
replacement, and two households that did not experience such issues.  
2. One fieldworker will visit each selected potential IDI participant and will provide information 
about the study. The participant will be asked to provide informed consent. The interview 
will be conducted with people who provide informed consent. 
3. The interviewer will use a semi-structured interview guide to guide a discussion that will last 
approximately 60 minutes.  
4. The interview will be recorded for transcription.  
5. The recording of the interview will be used to create a discussion transcript for data analysis.  
6. Subsequent rounds of IDIs will be conducted during the trial. Twelve IDIs will be conducted 
within the 6 study clusters identified for FGDs as described above. Informants will be 
identified according to the procedures noted above. Within each cluster, the study team will 
seek one informant from a household that experienced ATSB issues and one informant from 
a household that did not experience these issues. The interviews will be conducted 
according to the procedures outlined above.  
Data for FGDs and IDIs will be analysed thematically and may use software including Atlas.ti and 
NVivo for data organization and analysis. 
 Economic evaluation  
ATSB product and delivery cost data will be collected and combined with efficacy measures of 
clinical malaria incidence to produce incremental cost-effectiveness ratios (ICER). The ICER will 

ATSB-Kenya Protocol (v1.1-31May21) 
42 
represent the incremental cost-effectiveness of the use of ATSB in addition to standard of care 
malaria vector control (high/universal LLIN coverage) to estimate the financial and economic costs of 
the intervention. Cost data will be combined with efficacy estimates to produce cost-effectiveness 
estimates of this strategy from a provider perspective. 
 
Procedures 
Cost data collection will include a review of program records and reports, invoices, budgets, 
expenditure reports, as well as through interviews with intervention implementers to acquire 
information not recorded in existing program data. No interaction with study participants is required 
for provider perspective cost analysis. Interviews only with trial staff will be focused on resource use 
during the implementation of the study interventions. Where direct estimates of unit costs for 
inputs are not available through the above methods, data on costs will be supplemented with 
secondary source data such as is available from the WHO-CHOICE database, the World Bank, the 
International Monetary fund or other published literature. Economic costs will be estimated, 
meaning that costs from donated inputs will also be valued.  
 
Timeframe 
The collection of cost data will be conducted throughout the study period, with a review of cost data 
occurring quarterly throughout the scale-up and roll-out of the intervention and study. Final cost 
estimates and cost-effectiveness calculations will be done at the conclusion of the study.  
9.2 DATA MANAGEMENT 
The sections below provide details of data management for individual study components. All data 
will be stored on a secure, shared drive managed by KEMRI and backed up on a secure server at 
LSTM, Liverpool, UK. All investigators and the sponsor, IVCC, will have access to the data.  
 ATSB monitoring, cohort and cMIS case report forms 
The questionnaire will be administered using electronic data capture forms on mobile phones or 
tablets. The data will be sent to a cloud-based secure server on a daily basis. Data will be extracted 
from the server after each round of ATSB monitoring is completed. The extraction will be completed 
using Alteryx, Microsoft Excel, or Microsoft Access, and data will be loaded into a package for 
statistical analysis such as Stata and/or SAS and/or R.  
 Passive case detection 
Data entered into routine outpatient, ANC, and CHV MoH Registers will be extracted using ScanForm 
software and stored on a secure cloud-based server (under separate protocol).  
 Rapid ethnographic methods: FGD and IDI data 
Transcripts of all discussions and interviews will be created in Microsoft Word. Interviews will be 
translated into English during the process of transcription. Data coding and analysis will be 
completed using Microsoft Excel. 
 Entomological monitoring  
Field data will be recorded using electronic data capture forms on mobile phones or tablets. This will 
include details on the house structure (e.g., roof type, wall type, open or closed eaves), presence and 
use of LLINs, the timing of any IRS application within the last 12 months, and other factors that may 
affect mosquito density (e.g., cooking in the house, use of mosquito coils, presence of animals). 
Laboratory data will be entered using a standardized data entry form either directly on a PC or a 

ATSB-Kenya Protocol (v1.1-31May21) 
43 
tablet. Data will be imported into Microsoft Access, and data merging, cleaning, and analysis will be 
done using a standard statistical software package such as SAS, Stata or R. 
 Economic evaluation  
Data will be stored in the manner collected and collated into Microsoft Excel then transferred to R 
software for analysis. Transcripts of interviews with program staff will be created in Microsoft Word. 
All data will be backed up in a password-protected secure cloud storage setting to prevent data loss. 
9.3 BIOLOGICAL SAMPLES 
 Blood samples 
During cohort and cMIS household visits, a finger- or heal-prick blood sample (approximately 500 µL) 
will be taken to prepare dried blood spots (DBS) on filter paper. DBS will be used to evaluate malaria 
positivity or exposure through molecular and serological methods as well as exposure to mosquito 
biting at a later date and will not be used for clinical care. Should the participant be febrile at the 
time of the visit (axillary temperature ≥37.5°C) or report a fever in the previous 48 hours, a malaria 
RDT will also be performed. RDT results will be used for treatment decisions based on the Kenya 
Ministry of Health guidelines. In certain cases, to confirm parasite clearance, a blood smear may be 
prepared to perform light microscopy. 
Real-time quantitative PCR will be performed on cohort samples to evaluate the time to first 
infection and may be performed on a sub-sample of cMIS samples to evaluate malaria prevalence. 
Should funds be available, PCR may also be performed to assess parasite genetics, including 
complexity of infection analyses to evaluate the impact of ATSB on circulating parasite strains. 
Serological studies may be performed on cohort and cMIS samples to evaluate changes in exposure 
to malaria-associated with ATSB implementation as evaluated through antibody profiles of the 
participants. These may include IgG antibodies to antigens such as merozoite surface protein (MSP-
1,) apical membrane antigen (AMA-1), circumsporozoite antigen (CSP), and other antigens. 
Additionally, exposure to vector biting may be assessed by measuring antibodies to mosquito saliva 
antigens, including Sg6 in the blood. 
In other geographic areas such as Eritrea, HRP2 deletions have been identified. As the RDTs that are 
used in Kenya are based on HRP2 detection, the main trial outcomes rely on the detection of HRP2 
antigens. Preliminary data from the study site (unpublished data 2018) have not identified evidence 
of HRP2 deletions. We may assess HRP2 concentration levels and PfHRP2/3 deletions from both 
cohort and cMIS samples.     
 Entomological samples 
Collected mosquitoes will be returned to the laboratory for morphological identification, sporozoite 
ELISA testing, and, if necessary, species identification by PCR 
 Sample storage and shipping 
 
Storage 
All filter papers with DBS will be stored at the KEMRI CGHR campus in Kisian until the end of the 
study. All laboratory tests, as part of primary and secondary analyses, can be performed at the Kisian 
campus. For laboratory studies that may not be available at the Kisian campus, samples from 
participants who consent to shipment of samples may be shipped to laboratories at the CDC in the 
United States or to laboratories in the United Kingdom at the Liverpool School of Tropical Medicine. 

ATSB-Kenya Protocol (v1.1-31May21) 
44 
For participants who consent, samples will be stored for up to 25 years from the time that the study 
ends. This is because the technology for sequencing parasites for clonal diversity, resistance, and 
serological markers of exposure is rapidly advancing. It may prove useful to analyze stored samples 
at a later date. At the end of the 25-year period, all biological specimens will be destroyed. Remnants 
of samples shipped to another laboratory will be destroyed after the testing has been completed.  
 
Shipping 
All specimens to be shipped will be packaged, shipped, and transported according to the current 
edition of the International Air Transport Association (IATA) Dangerous Good Regulations as at the 
time of shipping. 
9.4 STATISTICAL METHODS  
 Interim analysis 
 
Purpose of the interim analysis 
The study is designed to have two interim and one final analysis, i.e. a total of three looks. The 
timing of the interim analysis is based on the number of cumulative events or person time 
accumulated as described in section 6.2.2, Duration of trial, interim analysis and criteria for early 
termination, page 17. In brief, the interim analyses will occur either after 50% and 75% of person-
time have completed (i.e., after about 1 and 1.5 years respectively), or after 50% (n=372) and 75% 
(n=558) of the total number of expected primary outcome events over two years in the control arm 
(n=744) have occurred (whichever comes first).   
The purpose of the interim analysis is to use the preliminary data to inform the assessment process 
by WHO’s Vector Control Advisory Group (VCAG) in a timely manner. This requires at least a single 
year of data, but ideally, two years [18]. This study in Kenya is part of three similar trials conducted 
in Kenya (this protocol), Zambia and Mali. The combined results will inform WHO’s recommendation 
process regarding ATSBs. Each of these three trials is designed to have an interim analysis. A decision 
to stop any of these three trials, including this one, early for overwhelming evidence of efficacy will 
depend on the overall evidence from the three trials and thus not only on the evidence generated 
from a single trial. It is thus possible that WHO’s VCAG, the DSMB and/or the trial steering 
committee will recommend continuing this trial in Kenya for the full two years even if statistically 
the stopping boundary is crossed (suggesting overwhelming evidence of efficacy) or there is 
evidence of futility. The possible rationale for any of these committees to recommend continuing 
the trial for a second year may involve continuing collecting more epidemiological, entomological, 
behavioural, and safety information and data for further subgroup analyses. This would allow 
determining the cumulative effects of the intervention over a two-year period as behavioural 
changes of the population (e.g., change in adherence to the deployment of ATSBs), year-to-year 
seasonal variation in malaria transmission, cumulative impact on mosquito densities and 
community-effects, etc., may impact on the results over time.  
However, it will also be possible that these committees recommend stopping the trial early if the 
committees agree that sufficient evidence is available after the first or second interim analysis to 
make a recommendation. This is the rationale to design the study to allow for two interim analyses. 
 
Procedures for interim analysis 
The interim analysis will be conducted on the primary endpoint using the intention-to-treat analysis 
population. First, the trial statistician will develop the analysis programs for the primary outcome 

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45 
and validate them using a test version of the study database with a dummy random treatment code.  
Then, these programs will be provided to the DSMB statistician before the scheduled DSMB meeting. 
The DSMB statistician receives a copy of the random treatment assignment code directly from the 
study statistician or a second independent statistician not involved with the trial analysis. The DSMB 
statistician would replace the dummy random treatment code with the actual allocation code and 
execute the programs. Finally, after reviewing the analysis output and verifying the results, the 
DSMB statistician would summarize the findings in a report addressed to the other members of the 
DSMB. 
 
Evidence of benefit 
The interim analysis will consider the using the Haybittle-Peto spending function to determine the 
test boundaries to preserve the overall two-sided type I error rate of α=0.05 at the final analysis. 
Overwhelming evidence of benefit will be defined as a p-value favouring the intervention arm of 
<0.001 after the first or only interim analysis and also a one-sided p-value of <0.001 after the second 
interim analysis. This test will be conducted using a multilevel regression model with a Poisson 
likelihood and a log link function which includes random cluster level intercepts. Other models will 
be considered if there is evidence of overdispersion for Poisson (e.g. negative binomial models). The 
final null-hypothesis significance testing will be based on an alpha level of 0.049 to control the trial's 
overall type-I error potential.  
 
Stopping for harm 
The trials do not include formal stopping rules based on harm. The intervention is not targeted to 
humans, and the expected risk to trial participants is expected to be minimal. However, this does not 
preclude the DSMB from stopping the trial for harm should unforeseen consequences of the ATSB or 
trial procedures lead to harms.    
 
Timing of final analysis 
The final analysis will be conducted either following an interim analysis should the trial end early or 
at the end of two years should no early stopping rule be invoked. 
 General principles 
 
Analysis populations 
9.4.2.1.1 Intention-to-treat population 
The primary analysis of the primary outcome (the incidence of clinical malaria in the cohort) will be 
conducted with the intention-to-treat analysis population, consisting of all eligible participants 
recruited and consented to participate in the study.  
9.4.2.1.2 Per-protocol analysis populations  
The per-protocol analysis populations will be those eligible, recruited, and consented participants 
whose cluster-level adherence meets the definition of adherence. Clusters (and those living in these 
clusters) will be excluded from the per-protocol population if they fulfil the criteria for non-
adherence to ATSB deployment as defined in section 7.7.1, Cluster-level adherence, page 29. The 
ATSB monitoring data, which are contemporaneously collected, may be used to inform the further 
definition of the per-protocol population in the statistical analysis plan 

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46 
9.4.2.1.3 Multiplicity 
Whilst the trial tests multiple secondary outcomes, no adjustment will be made of multiplicity 
because the study has two arms and a single primary outcome. Secondary outcomes are assumed to 
be on the same causal pathway as the primary outcome. 
 
Missing data 
9.4.2.2.1 Missing outcome data 
Significant effort will be made to reduce missing outcome data by revisiting cohort households 
multiple times and pre-scheduling follow up visits where possible. When missing data does arise due 
to failed monthly outcome assessment, no imputation will be used. Full reporting of the fraction of 
missing outcome assessments by study arm will be conducted for the intention-to-treat study 
population.  
9.4.2.2.2 Missing co-variables 
Missing baseline covariables (as defined in the SAP prior to data lock) will be imputed using simple 
imputation methods based on the covariable distributions, should the missing values for a particular 
covariable be less than 5%. For a continuous variable, missing values will be imputed from random 
values from a normal distribution with mean and SD calculated from the available sample. For a 
categorical variable, missing values will be imputed from random values from a uniform distribution 
with probabilities P1, P2, … Pk from the sample. The seed for the imputation will be set as a number 
with eight digitals (e.g. the date of the programming). If the missing values for a covariable are ≥5%, 
then they will be imputed using Markov chain Monte Carlo (MCMC) methods. 
 
Adjusting for cluster design and other correlated observations 
For all analyses, standard errors of effect estimates will be estimated with a random intercept at the 
cluster level to account for correlated observations at the cluster level as a result of the community 
randomized control trial study design.  
 Analysis of the primary outcome 
 
Definition of events and person-time to obtain incidence rates 
The primary outcome analysis will be based on a comparison of the unadjusted (crude) incidence 
rates between study arms using a multi-level (variance compartments model). The incidence rate 
will be defined as the total number of incident clinical malaria cases divided by the total person-time 
observed among each cohort.  
The person-time (i.e., the denominator) and events (i.e., the numerator) will be defined as follows: 
9.4.3.1.1 At the time of enrolment 
If the blood smear collected two weeks after cohort enrolment (parasite clearance) visit is negative, 
person-time accrual will begin two weeks after enrolment to account for the post-prophylactic effect 
of the full treatment course with artemether-lumefantrine 
9.4.3.1.2 After a positive RDT and malaria treatment  
Similarly, two weeks of person-time will be subtracted after each treatment provided during the 
follow-up. This scenario would result in an event in the numerator 
9.4.3.1.3 Visit following a positive malaria treatment  
At the next visit (one month later), if the participant fulfils the criteria for clinical malaria (mRDT 
positive with symptoms), he/she will again be treated, and two weeks of person-time will be 

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47 
removed. However, this will only be counted as an event (i.e. contribute to the numerator) if 
subsequent PCR testing for P. falciparum in the laboratory is positive. The rationale for this is based 
on the long tail of histidine-rich protein-2 (HRP2) antigenemia which can persist for weeks after 
active infections have cleared, resulting in false-positive mRDT results.  
9.4.3.1.4 Visit where participant’s overnight sleeping outside of the cluster of residence is 
documented 
If a person sleeps outside of their cluster of residence for a period to be defined in the Statistical 
Analysis Plan based on a consensus between the three trials in Kenya (this protocol), Zambia and 
Mali, person-time and events for that month will be excluded. If the participant is found to be RDT 
positive, this event will not count in the numerator 
9.4.3.1.5 Missed visits 
Missing outcomes due to participant absence at scheduled visits will result in the removal of the 
previous period of follow-up time. Participants who return to the study after an absence of at least 
one measurement period and immediately test positive for clinical malaria will not be counted as 
cases, nor will their follow-up time between the last ascertainment and their return to study be 
counted (see section 9.4.2.2.1, Missing outcome data, page 46). 
 
Computing of incidence rate ratios 
To obtain incidence rate ratios, a multi-level variance compartments model will be used, constructed 
on a generalized linear model framework with a Poisson likelihood and a log link function. Random 
intercepts will be included for each study cluster, and study arm as a fixed effect coded categorically 
as 0 for arm A and 1 for arm B. The primary outcome will also be checked for the distributional 
assumption that the mean and variance of the outcome are similar after conditioning on cluster (e.g. 
are the within-cluster mean and variance similar). If the variance is substantially larger, a negative 
binomial likelihood will be considered. Results will be presented as the incidence rate ratio (IRR), 
95% confidence intervals and p-value.  
 
Covariable adjusted analysis of the primary and secondary outcomes:  
A secondary co-variable adjusted analysis of the primary outcome will be conducted. Pre-specified 
covariables, developed and tested prior to final analysis, will be used. It is expected that these will 
also include the covariables used in restricted randomization (Table 4, below).  
Table 4: Potential co-variables to be used in restricted randomisation 
Variable 
Categorization  
(if applicable) 
Analysis 
Analysis Population 
Baseline prevalence 
Calculated at cluster 
level 
Clinical incidence, 
prevalence 
ITT, per-protocol 
Baseline incidence 
Calculated at cluster 
level 
Clinical incidence, 
prevalence 
ITT, per-protocol 
Rainfall (anomaly) 
Summarized monthly 
at cluster level (lagged 
one month preceding) 
as anomaly  
Clinical incidence, 
prevalence 
ITT, per-protocol 
Season 
 
Clinical incidence, 
prevalence 
ITT, per-protocol 
Year 
One vs Two 
Clinical incidence, 
prevalence 
ITT, per-protocol 

ATSB-Kenya Protocol (v1.1-31May21) 
48 
Age 
Under 60 months vs 
greater than 60 
months 
Clinical incidence, 
prevalence 
ITT, per-protocol 
 
Subgroup analysis of the primary outcome  
We will perform a series of subgroup analyses that may include the list of subgroups in Table 5 below.  
Imputation for these baseline missing covariables (see section 9.4.2.2.2, Missing co-variables, page 
46) will be carried out before categorizing. Assessment of the homogeneity of treatment effect by a 
subgroup variable will be conducted by the inclusion of the treatment, subgroup variable, and their 
interaction term as predictors in the adjusted models of the primary outcome and the p-value 
presented for the interaction term.  
Table 5: Subgroups 
Subgroup Name 
Categorization 
Rationale 
Housing type 
Closed eaves vs Non-closed 
eaves 
House structure may act as an 
effect modifier by eliminating 
indoor biting risk independent 
of ATSB deployment 
Gender 
Male vs Female 
The behavioural and 
occupational difference may 
act as an effect modifier 
One month lagged rainfall 
(Total m per m2 previous 
month) 
High vs. low (>= mean for 
study site (country) vs. < mean 
for study site (country)). 
High levels of absolute rainfall 
may reduce the impact of ATSB 
by increasing environmental 
carrying capacity for the 
mosquito population 
Season 
High vs low (four continuous 
months of the year with 
highest clinical malaria 
incidence at local health 
facilities during the trial) vs 
eight months with a lower 
incidence  
(Kenya only) 
Age 
<= 60 months of age vs > 60 
months of age, and possibly 
≥15 years of age 
Behavioural differences by age 
may act as an effect modifier 
 
 Other efficacy outcome analyses 
 
Analysis of secondary efficacy outcomes in the cohort  
9.4.4.1.1 Count outcomes 
Similar methods of analysis will be used to obtain crude and adjusted incidence ratios for secondary 
clinical outcomes. 
9.4.4.1.2 Time to first infection 
The time to the first infection assessed among the cohort by PCR will be analysed using a Cox-
proportional Hazards model. A shared frailty for study cluster and a ‘fixed’ effect coefficient for the 
study arm will be included. Results will be presented as the hazard ratio, 95% confidence intervals 
and p-values. The proportional hazards assumption will be checked using plotting and regressing the 
Schoenfeld residuals against time after model fitting. If the proportional hazards assumption is not 

ATSB-Kenya Protocol (v1.1-31May21) 
49 
met, consideration of dose-response models with time-varying adherence measures will be 
considered, or alternative accelerated failure time models may also be considered.  
 
Analysis of the prevalence survey data 
The prevalence outcomes will be analysed using multi-level variance components models 
constructed on a log-binomial model with robust variance estimation. Random intercepts will be 
included for each study cluster, and the study arm will be included as a fixed effect.  Model results 
will be presented as the risk ratio, 95% confidence intervals, and P-values. 
 
Analysis of the count data obtained by passive case detection  
The incidence data obtained from routine passive case detection in health facilities and through CHV 
in villages will be analysed using multi-level variance compartments models, constructed on a 
generalized linear model framework with a Poisson likelihood and a log link function. Random 
intercepts will be included for each study cluster, and the study arm will be included as a fixed effect. 
Denominator data to obtain person time for each cluster will be based on the enumeration data 
obtained from the census. Model results will be presented as incidence rates and incidence rate 
ratios, their associated 95% confidence intervals and p-value. Similar to the analysis of primary 
outcome, each count outcomes will also be checked for the distributional assumption that the mean 
and variance of the outcome are similar after conditioning on cluster (e.g. are the within-cluster 
mean and variance similar). If the variance is substantially larger, a negative binomial likelihood will 
be considered. 
 Analysis of entomological data 
Mosquito densities will be analysed by Poisson or negative binomial regression using generalized 
estimating equations to adjust for correlated observations at the cluster level. Separate models will 
be done for each species where adequate numbers have been collected. All models will assume an 
auto-regressive correlation structure where the degree of correlation decreases with increasing time 
between collections. Models will include potential confounders such as the use of LLINs, recent 
house spraying, the presence of open eaves, and climatic factors. Logistic regression models will be 
used to compare the impact of ATSBs on binary outcomes such as the sporozoite rates, parity rates, 
the proportion of mosquitoes with three or more ovarian dilatations, or the proportion of outdoor 
biting. The logistic regression models will adjust for correlated observations at the cluster level using 
assuming an auto-regressive correlation structure. 
 Focus group discussions and in-depth interviews  
Discussions during IDIs and FGDs will be recorded and subsequently transcribed. Qualitative data will 
be managed and analysed using directed content analysis whereby transcripts will be interrogated 
for specific and emergent themes. The interview guides and conceptual framework will be used to 
create an initial set of predetermined codes for the domains of potential barriers to high ATSB and 
LLIN coverage. Data will be coded and organized by theme and respondent type using Microsoft 
Excel or NVivo. Transcripts will be entered into an Excel file by transferring each codable unit to a 
separate cell on a line with additional cells containing information on the respondent (interview 
type, age, sex) for that unit of text. This process of data organization will allow the analyst to 
become familiar with the transcripts and refine the coding scheme as needed based on the data. 
Each unit of text will be assigned codes, and sub-codes entered in cells corresponding to the data. 
Excel Data functions, including Filter and Sort, will be used to organize data according to theme, 
review data within each assigned code, and make adjustments to coding. When coding is complete, 
a synthesis of data within each code will be drafted. Patterns among themes and across types of 
respondents will be identified and interpreted.  

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50 
 Economic evaluation 
Both financial and economic costs will be calculated. Costs will be classified as capital or recurrent 
and traded vs non-traded. Capital costs will be annuitized and discounted using a 3% rate. These 
costs will be expressed in a common currency and year (2019 US dollars). Additionally, they will be 
converted into purchasing power parity adjusted International Dollars for internal comparison. Costs 
will be combined with efficacy measures from the trial to estimate incremental cost-effectiveness 
measures. 
 Harms  
The main risks associated with the intervention are the risk of physical contact or ingestion of the 
bait by humans, animals, and/or non-target arthropods, particularly the local bee population. 
Continued entomological monitoring of non-target insect populations and ongoing monitoring of 
trial sites for misuse or product loss will be conducted. The statistical analyses of harms to study 
participants will consist of evaluating the number of AEs and SAEs related to physical contact or 
ingestion of the bait. analysed 
10 METHODS: MONITORING 
10.1 TRIAL GOVERNANCE 
 Trial steering committee 
The ATSB project is governed by a steering committee with members from the Bill and Melinda 
Gates Foundation, IVCC, Westham Co., PATH, the University of Bamako, and two external expert 
advisors (one epidemiologist and one entomologist). The steering committee meets quarterly to 
discuss all aspects of the project, including study protocol and procedures, additional external 
reviews and reviewers (e.g. WHO VCAG), product and production issues, timeline and deliverables, 
and review of available data. 
 Data safety and monitoring committees 
An independent data safety monitoring board (DSMB) will be established to monitor 
implementation. The board will consist of at least four independent experts in malaria vector 
control, entomology, the conduct of community trials, biostatistics, and epidemiology. The members 
of the DSMB will serve in an individual capacity and provide their expertise and recommendations. 
No independent member of the DSMB shall have any conflict of interest with the study team, the 
organizations funding or conducting the research, the results of the research, or the ATSB 
manufacturer (Westham Co.).  
The primary responsibilities of the DSMB will be to periodically review and evaluate the accumulated 
study data for participant safety, study conduct and progress, and, when appropriate, efficacy. The 
DSMB will be responsible for making recommendations to investigators and participating in research 
ethics committees concerning the continuation, modification, or termination of the trial. The DSMB 
will be guided by a charter. This charter will include statistical monitoring guidelines that will guide 
recommendations about the trial's termination or continuation. These procedures will include 
guidelines for termination for futility and termination for safety reasons (see Section 9.4.1, Interim 
Analysis, page 45).  

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51 
10.2 TRIAL MONITORING AND AUDITING 
 Trial monitoring 
External clinical trial monitoring visits are provided by the sponsor at trial initiation, and then 
regularly (at least yearly) thereafter and at trial closeout, or more frequently if so required; e.g. if the 
trial fieldwork is about 24 months, this means that the site is visited approximately four times by 
external monitors. The results from each monitoring visit will help inform whether more frequent or 
earlier repeat visits are required.  
 Auditing 
The independent trial monitoring process will be audited by a study staff from the sponsor’s 
research office at LSTM in Liverpool, UK. The auditor may choose to accompany the clinical monitor 
during at least one of the site visits to determine if more auditing visits are required. 
 Role of sponsor 
The sponsor reserves the right to suspend temporarily or prematurely discontinue this study at any 
time for reasons including, but not limited to, safety or ethical issues or severe non-compliance. If 
the sponsor determines such action is needed, it will discuss this with the investigator and the 
funder (IVCC). When feasible, the sponsor will provide advance notification to the investigator of the 
impending action prior to it taking effect. The sponsor will promptly inform the ethics committees 
and provide the reason for the suspension or termination. 
10.3 SAFETY MONITORING AND REPORTING  
 Adverse events and serious adverse events 
Adverse events (AEs) and serious adverse events (SAEs) will be recorded in the study cohort during 
home visits and sick visits.  Since this is not a trial involving a human intervention, these AEs and 
SAEs will not be reported in an expedited manner to the DSMB, sponsor, ethics committee or 
regulator. The exceptions are AEs or SAEs related to a physical interaction with ATSBs or ingestion of 
ATSB materials. Any ingestion of ATSB material will be considered an event that requires expedited 
reporting regardless of the seriousness of the event. Thus both SAEs or AEs related to physical 
interaction with ATSBs or ingestion of ATSB materials will be reported by the principal investigator to 
the DSMB, sponsor and ethics committee/institutional review boards within 72 hours. Study staff 
will be trained to report such events to the principal investigator in an expedited manner. 
Participants will also be instructed to contact the study staff if ingestion were to occur. All other AEs 
and SAEs not related to a physical interaction with ATSBs or ingestion of ATSB materials will be 
reported at the time of continuing review.  
10.4 QUALITY ASSURANCE  
 Quality assurance field-based activities 
Field coordinators will be employed to provide supervision to all field staff and ensure that human 
blood and mosquito specimens are collected, transported, and stored according to standard 
operating procedures.  
Additional staff will support passive routine data collection at health facilities. (see Section 9.1.4, 
Passive case detection, page 37)  

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52 
 Quality assurance data 
 Routine review of ATSB monitoring data 
The ATSB monitoring data will be reviewed on an ongoing basis (minimum quarterly basis) to assess 
the extent to which full coverage with ATSBs is achieved in intervention areas. This information will 
be used to take necessary action to address gaps in coverage.  
 Routine review of cohort data quality 
The cohort data will be reviewed on an ongoing basis (minimum quarterly basis) to assess data 
quality. Checks will be performed to ensure data completeness and assess consistency. Information 
from these data reviews will be used to take action to address data quality issues as needed.  
 Continuous household survey data review 
The household survey data will be reviewed for data completeness and consistency. Information 
from these data reviews will be used to take action to address data quality issues within the 
continuous household survey to ensure a minimum level of quality.  
 Routine review of health facility data 
The passive case detection data collected at health facilities will be reviewed on an ongoing basis 
(minimum quarterly basis) to assess data quality. Checks will be performed to ensure data 
completeness and assess consistency. These checks will include ensuring that the geographic 
location of cases is being recorded sufficiently to assign each case to the correct study arm. 
Information from these data reviews will be used to take action to address data quality issues within 
the passive case detection collection at facilities.  
 Review of qualitative study data 
Data from each of the two rounds of qualitative data collection will be analysed as data become 
available. Results from these studies will be used to address barriers to continuous coverage with 
ATSBs and LLINs (i.e. strengthened and targeted community engagement strategies).  
 Review of ATSB durability monitoring and insecticide resistance monitoring data 
Results from data collection to monitor ATSB durability and insecticide resistance will be analysed 
and reviewed as these data are collected. Results from these study components will be used to flag 
and address unanticipated issues with shorter than anticipated ATSB product life in the field (less 
than six months durability of the attractant and ingestion toxicant) and/or evidence of target vector 
resistance to the ATSB active ingredient.  
 Routine review of entomological monitoring data 
The entomological monitoring data collected monthly will be reviewed on an ongoing basis 
(minimum quarterly) to assess data quality. Checks will be performed to ensure data completeness 
and assess consistency. Information from these data reviews will be used to take action to address 
data quality issues within entomological data collection and entry.  
 Midterm analysis of entomological monitoring data 
The entomological monitoring data will be analysed after one year to examine trends in key 
entomological indicators, including trends in density and population age structure in intervention 
and control areas. Should this analysis suggest no entomological effect of the intervention, a 
comprehensive review of trial procedures, intervention coverage, contextual information (e.g. 
weather and rainfall trends), and data quality will be undertaken.  

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53 
10.5 DATA COLLECTION METHODS & STORAGE 
 Methodologies for data collection/generation 
Data will primarily be captured using mobile data collection tools such as tablets and smartphones. 
Routine MoH register data are collected on paper-based forms utilising ScanForm (QED®) software 
for semi-automated transcribing into an electronic database by taking images with android-based 
ScanForm App and using Optical Character Recognition, intelligent document recognition and data 
validation and human verification of information against source documents. Once validated, the 
data will be transferred to the target database along with a PDF of the original image of the CRFs, 
such that there is an electronic copy of all paper-based documents. For the electronic-only data 
capture, we will use tablets with integrated sim cards to transfer encrypted data to the ODK servers. 
This has worked well in previous studies.  
 Data quality and standards 
The quality of questionnaire data collection and data entry will be maximised through the training of 
field staff in the standardised questionnaire administration methodology. Field staff will be trained 
in the methodology for collecting data and will be expected to demonstrate competence before 
conducting fieldwork 
 Managing, storing, and curating data 
Verified and validated data will be stored on secure, highly fault-tolerant, storage area network 
servers. Locally, data will be backed-up on a continuous basis on a secure off-site server and on 
encrypted standalone hard drives.  
Once the data validation phase is completed by the central data manager, the database will be 
locked and transferred to a statistical programmer who will do further syntax-driven consistency 
checks and syntax-driven data cleaning. The statistical programmer will have access to the source 
data. He/she will then prepare the database for data analysis by the statistician by creating the final 
variables for data analysis, such as the creation of the composite endpoints. The final cleaned 
database will be available in Stata, SAS, R and other formats, with a corresponding data dictionary. 
 Data preservation strategy and standards 
The majority of the data collected will be captured using electronic data collection tools such as 
tablets or smartphones. The country-specific paper-based ICFs and the databases will be stored and 
archived at KEMRI’s Centre for Global Health Research (CHGR) in western Kenya. The research data 
will be stored in the long-term in the original electronic format, in a large unified database and a 
public database that contains all research data other than identifiable participant data. The public 
database will be updated when needed if the software becomes obsolescent to achieve long-term 
preservation. The data will be preserved in this way for ten years or longer if still being accessed at 
that stage. 
11 ETHICS AND DISSEMINATION 
11.1 DECLARATION OF HELSINKI 
This study will be conducted in compliance with the principles of the Declaration of Helsinki (1996), 
the principles of GCP, and in accordance with all applicable regulatory requirements in Kenya. 

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54 
11.2 RESEARCH ETHICS AND REGULATORY APPROVAL  
 Ethical review and approval of study protocol  
This protocol will be reviewed by the research ethics committee and institutional review boards at 
the KEMRI and LSTM. A reliance agreement based on KEMRI’s review will be submitted to the CDC.  
 Protocol amendments 
No changes will be made to the approved protocol without the agreement of the sponsor, Chief 
Investigator and Principal Investigators. All protocol amendments will be submitted to the research 
ethics committees at LSTM (sponsor) and KEMRI for approval before implementation in that 
country. Any change to the informed consent form, except for layout, spelling errors and formatting, 
must also be approved by the sponsor and KEMRI before the revised forms are implemented. 
 Regulatory approval 
Additionally, this study will be submitted to the National Commission for Science, Technology & 
Innovation (NACOSTI) and it will be registered with ClinicalTrials.gov. Import permits will be sought 
from and the Kenya Pest Control Products Board (PCPB) for ATSB shipments to the study site. 
 Inclusion of vulnerable subjects: children and pregnant women  
The cohort study will include children age 1-<15 years. Informed consent from the parent or 
guardian will be obtained before participants are enrolled. Additional assent will be obtained for 
children age 13-<15 years (see 11.2.5, Consent procedures, below) per local guidelines.  
Pregnancy is an exclusion criterion because enrolment in the cohort requires presumptive clearance 
of any existing infections with artemether-lumefantrine. WHO does not yet recommend artemether-
lumefantrine for the case-management of confirmed malaria in the first trimester, nor does it 
recommend the presumptive treatment with ACTs at any time during pregnancy. It is possible that 
some girls aged 12-<15y could be pregnant. Pregnancy will be excluded by asking girls aged 12-<15y 
about their date of last menstrual period. If this is >=6 weeks, she will be asked if she could be 
pregnant. If she is unsure, a urine human Chorionic Gonadotropin (hCG) rapid pregnancy test will be 
offered. Any girl who is unsure about her pregnancy status and is hesitant to do a urine-based hCG 
pregnancy test will not be eligible for enrolment. Any study participant who is pregnant at screening 
or becomes pregnant during the study will be referred to the antenatal clinic for further follow-up 
and care. 
 Consent procedures 
 Consent and assent   
Written informed consent will be sought for all participants aged >= 18 years. For participants aged 
<18 years of age consent from the parent/guardian will also be required. Additional assent will be 
obtained for children age 13-17 years (13-<15 years in the cohort study, 15-17 in the in-depth 
interviews). Table 6 below summarises the consent/assent forms for each study component.  
The informed consent forms will consist of a participant information sheet (PIS) and a 
consent/assent statement for their signature or thumbprint. The consent/assent process will be 
initiated at the time of enrolment into the study and will continue throughout the participant’s 
participation. If the participant meets the study enrolment criteria following an initial screening for 
basic eligibility criteria, the full consent process will follow. The consenting/assenting procedures will 
be conducted by trained staff who will answer any questions the participants may have. Participants 
(and if applicable based on Table 6, their parent/guardian) will be given the option of reading the PIS 

ATSB-Kenya Protocol (v1.1-31May21) 
55 
in the local language, having the PIS read to them in the local language, or both. The PIS’s include a 
description of voluntary participation, the right to withdraw from the study at any time without 
having to give a reason, and the right not to answer specific questions or participate in a specific 
component of the research. The participant information sheets also address the risks, benefits, and 
purpose of the study.  
Table 6: Consent and assent for each study component 
Study component 
Inclusion ages 
Written consent/ assent  
ATSB installation 
18 years and older 
 
Consent 
Cohort study 
1-12 years 
 
Parent/guardian consent 
13-14 years 
 
Parent/guardian consent 
 
Child assent 
Focus group discussion 
18 years and older 
 
Consent 
In-depth interview 
18 years and older 
15-17 years 
 
Consent 
 
Parent/guardian consent 
 
Child assent 
Entomological monitoring (light 
traps at household level)  
18 years and older 
 
Consent 
Entomological monitoring (HLC) 
Males, 18 to 49 years old 
 
Consent 
No informed consent or assent will be sought for the passive surveillance studies as no identifiable data 
will be collected. The continuous malaria indicator household survey (cMIS) falls under a separate 
approved protocol (SSC #2773; LSTM Protocol #14.009; CDC Protocol #6733). 
Participation in the research study is voluntary. Participants refuse the installation of ATSBs on the 
exterior walls of their house. Participants electing not to participate in other components of the 
study may still receive ATSBs as part of the intervention.  
For illiterate participants, an independent witness will be present during the informed consent 
process. Any adult aged 18 or older who is independent (e.g. a family member, neighbour etc)  may 
act as a witness for the consent of illiterate participants. The witness will sign the consent form, 
while the participant or their parent/guardian will be asked to indicate consent by use of a 
thumbprint.  
A copy of the informed consent/assent document will be given to the participant and their 
parent/guardian for their records. Each consent statement will be co-signed by a staff member. A 
signed consent statement will be forwarded to a central location for storage within a secured 
cabinet under lock and key. Checks in the field by the principal investigator and project leaders will 
further ensure that the consent process is followed. 
11.3 RISKS AND BENEFITS 
 Risks to study participants 
 Exposure to insecticide 
The active ingredient in the ATSB, dinotefuran, is an insecticide manufactured by Mistui Chemicals 
Agro, Inc. in Tokyo, Japan. Dinotefuran is a neonicotinoid insecticide that is effective for mosquito 
control. The ATSB contains 100 grams of the sugar/fruit juice solution and 0.1% dinotefuran (0.1 
gram). The safety data sheet is provided in Annex I. Dinotefuran safety data sheet, page 68. A study 
of human health and environmental risk for dinotefuran deployed within the Westham Co. ATSB was 
commissioned in 2017. The results are provided in Annex IV: ATSB human and environmental safety 

ATSB-Kenya Protocol (v1.1-31May21) 
56 
assessment report, page 109. Briefly, the assessment found that the use of dinotefuran in ATSBs 
under normal conditions of use is not expected to present an unacceptable risk to users handling the 
product or to residents living in the community. The human health risks of potential exposure to 
dinotefuran are considered low. In the worst-case assessment whereby a child would get ahold of 
one or more products and deliberately break them open to ingest the sugar bait, ingestion of the 
contents of an entire ATSB is unlikely to lead to a significant poisoning incident. In fact, under the 
most conservative assumptions regarding human toxicity, a child consuming 20 bait stations may 
experience severe poisoning. However, the assessment deemed this highly unlikely.  
Given the amount of dinotefuran-laden bait required to induce severe poisoning based on weight, 
an acute poisoning event among livestock or other domesticated animals is highly unlikely. The risk 
to animals would be an issue if an animal such as a goat or dog would ingest the bait from hundreds 
of stations.  
To address the potential consumption of bait by humans or animals, Westham incorporated a widely 
used bittering agent called Bitrex into the bait. Bitrex (denatonium benzoate) is an additive for a 
number of household products in order to prevent a poisoning event (see Annex II: Denatonium 
benzoate safety data sheet, page 75 for more information).  
 Risks associated with blood sampling 
Table 7 below outlines the risks associated with each component of data collection. A primary risk 
associated with data collection is the risk involved in a finger/heal-prick for blood draws for malaria 
RDTs and dried blood spots. Finger and heal-prick blood draws can cause pain and redness or 
swelling at the finger or heal-prick area and carry a risk of infection at the site of the lancet puncture.  
 Risks associated with the protection of privacy and confidentiality 
Collection of household and individual identifying information is necessary for the follow-up 
procedures. Geolocations of all households involved in the intervention and surveys will be 
collected. The collection of this information poses a potential threat to the confidentiality of 
individual data. Interview forms will contain little information that would generally be considered to 
be sensitive. Notably, there is no stigma associated with malaria infection status in the study 
communities. However, there is a risk that the privacy of an individual could be compromised during 
the administration of a questionnaire.  
Table 7: Risks associated with each type of data collection  
Type of data 
collection 
Description  
Risk 
Census 
enumeration  
Household questionnaire 
No risk 
ATSB monitoring 
Monitoring visit once every two months to 
confirm installation and assess the condition of 
the ATSB 
No risk 
Cohort study 
enrollment and 
monitoring 
Brief questionnaire 
Fingerstick for RDT and dried blood spot 
collection 
Minimal risk from the 
finger stick  
Side effects of malaria 
treatment 
Inadvertent pregnancy 
disclosure 
Household survey 
Household questionnaire 
Fingerstick for RDT and dried blood spot 
collection 
Minimal risk from the 
finger stick 

ATSB-Kenya Protocol (v1.1-31May21) 
57 
Side effects of malaria 
treatment 
Inadvertent pregnancy 
disclosure  
Focus group 
discussion 
Semi-structured group discussion with 
recording and transcription of the conversation  
No risk 
In-depth interview 
Semi-structured interview with recording and 
transcription of the conversation  
No risk  
Entomological 
monitoring  
Mosquito traps will be placed inside and 
outside of homes and will trap mosquitoes 
during peak biting hours beginning in the early 
evening through the early morning.   
No risk    
Entomological 
Monitoring 
Indoor and outdoor human landing catches 
through the night 
Minimal risk of mosquito 
bites and malaria 
infection 
Economic 
evaluation 
Collection of intervention cost data 
No risk  
 Risks to the population or environment  
The main environmental concern with the use of dinotefuran is the potential harm for non-target 
arthropods such as bees which are known to be sensitive to neonicotinoids like dinotefuran. The 
assessment summarizes a feeding study that examined feeding rates using a sample of over 3,700 
species from 7 orders and 27 suborders. The percentage of dissected samples that fed on the bait 
stations was shown to be very low, ranging from 0-2%. The study concluded that the ATSB design 
effectively limits exposure of the treated bait to non-target arthropods (see Annex IV: ATSB human 
and environmental safety assessment report, page 109).  
According to a US EPA fact sheet 
(https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-044312_01-Sep-
04.pdf), dinetofuran is water soluble and has a potential to leach into subsurface soil layers and/or 
enter rivers, ponds or lakes through surface runoff. However, dinetofuran is considered practically 
non-toxic to birds, mammals and fish on an acute basis though there were subacute effects on 
Japanese quail and mallard ducks including reduced numbers of eggs laid and reduced 14-day old 
survivors. Chronic toxicity testing on freshwater invertebrates showed no effects.  
Although there appears to be limited risk of effects on non-target organisms other than insects due 
to accidental release of dinetofuran into the environment, we will take measures to limit such 
releases.  First, the dinetofuran is contained within a bait station and only limited amounts are 
available to insects with piercing mouthparts (i.e. mosquitoes).  The main risk for accidental release 
is through damage to the bait stations or misuse by residents that receive them.  To minimize this, 
we will educate residents who receive bait stations on the importance of keeping the ATSBs on the 
exterior walls, both for the validity of the study and to protect against harm to people or the 
environment.  We will instruct residents to contact a study staff member in the event an ATSB is lost 
or damaged.  Second, we will conduct periodic spot checks on the bait stations and document the 
risk of accidental loss or intentional misuse.  Last, we will collect ATSBs after six months before 
replacement with new ones.  If, at any time, excessive damage or loss is observed, additional 
measures will be implemented to minimize the risk of future damage/loss of the ATSBs. 
 

ATSB-Kenya Protocol (v1.1-31May21) 
58 
 Adequacy of protection against risk 
 Protection against risks associated with exposure to the insecticide 
As outlined in Section 11.3.1, Risks to study participants, page 55, the main risks associated with the 
intervention are the risk of ingestion of the bait by humans, animals, and/or non-target anthropods, 
particularly the local bee population. The following measures will be taken to minimize the risk of 
exposure for all non-target organisms to the bait: 
 
ATSBs will be installed by trained monitoring assistants to ensure the proper installation of 
all ATSBs released into the community. The ATSB monitoring assistants will visit each 
household at least one time every month to verify that all ATSBs remain properly installed 
and will inspect the ATSBs for damage. Damaged ATSBs will be removed and replaced by the 
ATSB monitoring assistants. The ATSB monitoring assistants will attempt to recover and will 
safely dispose of any ATSBs (see below) that are not present at the time of the monitoring 
visit or that are reported missing by a participating household. 
 
ATSBs will be replaced every six months. The ATSB monitoring assistants will remove the 
ATSBs, and a field supervisor for disposal will collect all ATSBs to ensure that the products do 
not remain in the community. ATSBs will be incinerated in a high-temperature incinerator.  
 
Based on previous field research in Mali, manufacturer guidelines stipulate installing the 
ATSBs at a height of 1.8 meters. This is intended to minimize access to the bait from children 
and animals. This was shown to be successful in Mali (unpublished data). ATSBs will be 
installed at this height in all trial sites.  
 
Unused ATSBs and ATSBs that have been removed and are awaiting incineration will be 
stored in secure locations that prohibit access by children and animals. Conditions of storage 
may include rooms with locked doors and covered windows (glass, wood, metal, or screen 
covers) or locked boxes.  
 
Community sensitization activities will be implemented before and during the initial ATSB 
installation. These may include radio spots and presentations at community meetings that 
will include information on proper installation of ATSBs, instructions to keep ATSBs out of 
reach from children and animals and remove and report damaged ATSBs. It will also include 
contact information for community-based resources that can provide more information and 
assist with damaged or missing ATSBs.  
 
An informed consent form will be administered to all participants in the local language at the 
time of the ATSB installation. ATSBs will only be installed at households where the head of 
household or his/her representative provide consent. The information provided at the time 
of installation will include an overview of the potential risks to non-targets and instructions 
to 1) maintain the installation of the ATSBs at the height of 1.8 meters; 2) inform the contact 
provided (community-based ASTB monitoring assistant) should the bait station become 
damaged, missing, or if assistance is required to reinstall the bait station; and 3) to keep the 
ATSB away from the children and animals should the intended, or unintended removal of 
the bait station occur and if so, contact the community-based ATSB monitoring assistant 
(contact information provided).  
 Protection against the risks associated with blood sampling 
Trained and experienced staff will be used for the administration of the malaria RDT and collection 
of DBS. These health workers will follow detailed standard operating procedures designed to 
minimize the risk of pain, redness, swelling, and infection.   

ATSB-Kenya Protocol (v1.1-31May21) 
59 
An informed consent form will be administered to all participants in the local language for 
participation in each component of the study.  
 Protection of privacy and confidentiality 
Confidentiality of participant data and privacy of the participants will be preserved through the 
following measures:  
 
Interviews and testing will be conducted in a private place within the participant’s 
homestead.  
 
Focus group discussions will be closed to outside observers and will be held in a private 
location.  
 
Fieldworkers will receive training to maintain privacy during interviews and blood testing 
and preserve the confidentiality of all information collected.  
 
Identifying information will be recorded only in secure database software on password-
protected smartphones or tablets. Field workers will only have access to the data that they 
directly collect. Data will be cleared from their devices after all follow-up visits are complete. 
Data will be compiled by field supervisors or sent directly via secured mobile connections to 
central servers and will be stored only on password-protected computers in locked offices.  
 
Prior to data analysis, the data will be de-identified except for geo-location codes which are 
necessary for specific per-protocol analyses. The absence of individual identifying 
information will protect subject confidentiality.  
 
All paper records and blood specimens (DBS) will be stored in a locked location.  
 Potential benefits of the research to participants 
Participants will directly benefit from the top-up distribution of LLINs to ensure universal coverage 
throughout the study area. Furthermore, participants in the intervention area may benefit from the 
community-wide reductions in malaria transmission that are hypothesized to occur with the ATSB 
intervention. Participants in the study cohort will benefit from monthly testing and treatment for 
malaria infection. Participants in the household survey will benefit from malaria testing and 
treatment.  
Participants may also indirectly benefit as the information gained from this research will be used to 
inform a WHO recommendation regarding the use of the ATSB to further reduce malaria 
transmission above and beyond reduction achieved through universal LLIN coverage. The research 
will benefit the scientific and malaria control communities more generally by providing evidence on 
the efficacy of the ATSB as a potential tool to address residual malaria transmission. These types of 
new tools will be required to continue reducing malaria transmission and ultimately achieve 
elimination. Ancillary and post-trial care 
 Health care during the trial 
Care directed to immediate adverse events related to trial procedures (such as taking biological 
samples) will be provided free of charge by the study in the study hospitals.  For cohort participants, 
care will be provided to evaluate, diagnose and treat acute illness. The study will not be able to 
support care for trauma or chronic illness that was existing prior to or after the commencement of 
the study that cannot, in any way, be reasonably attributed to trial participation. The intervention is 
targeting the vector and is not anticipated to have an impact on participants. 

ATSB-Kenya Protocol (v1.1-31May21) 
60 
 Trial insurance 
The sponsor will take out trial insurance such that participants enrolled in the intervention study are 
covered by indemnity for negligent harm and non-negligent harm associated with the protocol. This 
will include cover for additional health care, compensation or damages whether awarded voluntarily 
by the Sponsor or by claims pursued through the courts. The ATSB manufacturer's liability is limited 
to claims arising from faulty manufacturing of the commercial product and not to any aspects of the 
study conduct.  
 Post-trial care 
The study budget is not able to fund post-study care or implementation of ATSBs. However, the 
investigators work in close collaboration with local and international policymakers (e.g. WHO) and 
funders (e.g. President’s Malaria Initiative [PMI]) to ensure that policymakers and funders are 
informed early of germane research findings. If the evidence supports the efficacy of the ATSB, we 
will advocate with the Division of National Malaria Programme and its partners, including PMI, for 
continued implementation of the ATSBs in intervention and control areas with supportive 
monitoring and disposal. 
11.4 DECLARATION OF INTEREST 
None of the investigators has paid consultancies with the companies involved in the trial or other 
competing interest for the overall trial or in each study site.  
11.5 ACCESS TO SOURCE DATA/DOCUMENTS 
In addition to the clinical monitors, authorized representatives of the funder, sponsor/CRO, an 
IEC/IRB, or regulatory authority may visit the study site to perform audits or inspections, including 
source data verification. The investigator agrees to allow the sponsor and CRO representatives, 
including the monitor and study safety monitor, the DSMB, the IRB/IEC and regulatory authority, 
direct access to source data and other relevant documents. 
11.6 EXPENSES REIMBURSEMENT AND OTHER PAYMENTS TO PARTICIPANTS 
No payment for household visits will be provided to participants. A transport reimbursement of 400 
Kenya shillings will be provided for sick visits when a parent/guardian must travel to a clinic to see 
study staff. Those who participate in human landing catches (HLCs) will be compensated up to 1000 
Kenya shillings for their time.  
11.7 DISSEMINATION AND APPLICATION OF THE RESULTS 
The purpose of this study is to provide a body of evidence to the VCAG in order to make a 
recommendation on the use of ATSBs in the year 2022. Data from this study will be combined with 
data from two other study sites where a similar protocol is being implemented. The outcome of 
these studies will guide recommendations for implementation or further testing to be performed on 
the Westham Co. ATSB product. The findings of this study will be directly applicable to western 
Kenya as this is an area of high malaria endemicity with presumed outdoor biting for which the 
ATSBs were specifically designed to be deployed. 
After study completion, study staff will hold “barazas” (town halls) and other community meetings 
within the involved counties to present the results of the study. 

ATSB-Kenya Protocol (v1.1-31May21) 
61 
11.8 AUTHORSHIP AND PUBLICATIONS 
Potential authors include all professionals that have participated in the trial for a minimum of six 
months. Authorship of any presentations or publications arising from this study will also be governed 
by the principles for authorship criteria of the International Committee of Medical Journal Editors 
has designed.[22] Disputes regarding authorship will be settled by the publications committee, with 
further involvement of the independent chair of the TSC if so required. The manufacturers of the 
ATSBs will be provided with a draft of the manuscript but will have no role in the review, data 
interpretation, or writing of the article. 
11.9 DATA SHARING STATEMENT 
Biological samples and data will be shared using material and data transfer agreements with the 
collaborating institutions (see 2.2.4 Non-Engaged collaborators, page 7) to minimize the risk of 
unauthorized analysis beyond the scope of the agreed parameters. 
The full protocol will be available on request to any interested professional and may be published in 
a peer-reviewed journal or deposited in an online repository. Individual, de-identified participant 
data will be made available for meta-analyses as soon as the data analysis is completed, with the 
understanding that the meta-analysis results will not be published before the individual trial results 
without the prior agreement of the investigators. The de-identified data set of the complete 
participant-level data will be available for sharing purposes, such as via the WWARN repository 
platform (http://www.wwarn.org/working-together/sharing-data/accessing-data). A Data Access 
Committee will consider all requests for data for secondary analysis to ensure that the use of data is 
within the terms of consent and ethics approval. 

ATSB-Kenya Protocol (v1.1-31May21) 
62 
12 TIMEFRAME AND DURATION OF THE STUDY 
Table 8 summarises the timeframe for each study component. 
Table 8: Timeline 
  
2021 
2022 
2023 
2024 
  
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
Qualitative study  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Launch of community 
engagement 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Baseline Passive 
Surveillance 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Baseline Household Survey 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Baseline Cohort 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
LLIN distribution 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
ATSB installation (every 6 
months) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Collect ATSBs for disposal 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Main Trial Passive 
Surveillance 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Main Trial Household 
Survey 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Main Trial Cohort 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Final Reporting 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 

ATSB-Kenya Protocol (v1.1-31May21) 
63 
13 ROLES OF THE INVESTIGATORS 
13.1 INVESTIGATORS 
Dr Aaron Samuels is the Director of the CDC-Kenya Malaria Research Program based in Kisumu, 
Kenya. He will serve as the co-PI on this study, with a particular focus on the epidemiological aspects 
of the study. He will be engaged with participants and will have access to personally identifiable 
information. He will be responsible for the local design, methodology, and conduct, and the analysis 
and reporting of the study. He will provide coordination and technical advice to the epidemiology 
staff and serve as a liaison to the non-engaged collaborators and other institutions. 
Dr Eric Ochomo is the KEMRI-CGHR Entomology Section Head in Kisumu, Kenya. He will also serve as 
a co-PI on this study, with a particular focus on the entomological aspects of the study. He will be 
responsible for the local design, methodology, and conduct and the analysis and reporting of the 
study. He will provide coordination and technical advice to the entomology staff and serve as a 
liaison to the non-engaged collaborators and other institutions. 
Dr Feiko ter Kuile is a Professor of Tropical Epidemiology at LSTM and is based part-time in Kisumu, 
Kenya. He will be the Chief Investigator of this trial and provide technical advice and support 
pertaining to study design, methodology, conduct, analyses, and manuscript writing. 
Dr Simon Kariuki is the KEMRI-CGHR Malaria Branch Chief and Chief Research Officer in Kisumu, 
Kenya. He will provide high-level technical support to the epidemiological, entomological and 
laboratory components of the trial design, methodology and conduct. He will also play a supervisory 
role. 
Dr John Gimnig is an Entomologist in the CDC Entomology Branch in Atlanta, GA, USA. He will 
provide higher-level technical advice and support as it pertains to the entomological study design, 
methodology, conduct, analyses, and manuscript writing. Dr Gimnig will also provide on-ground 
technical support to staff. 
Kephas Otieno is the KEMRI-CGHR Malaria Laboratory Section Head. He will provide technical 
oversight to the laboratory components of the study, including the methodology and 
implementation of these components. 
Benard Abong’o is an entomologist working for the KEMRI-CGHR Entomology Section of the Malaria 
Branch. He will provide study coordination and responsibilities and technical advice towards the 
design, methodology, and implementation of the entomological components of the study. 
Dr Julia Janssen is a medical doctor and Epidemic Intelligence Officer Fellow at the US CDC. She will 
assist with local design, methodology, and conduct, and the analysis and reporting of the study. She 
will be engaged and provide coordination and technical advice to the epidemiology staff and serve 
as a liaison to the non-engaged collaborators and other institutions. 
Dr. Caroline Ogwang is a Medical Doctor at KEMRI. She will serve as the Trial Manager for the 
epidemiological aspects of the trial. She will be engaged in trainings and direct supervision of staff, 
and ensure that the protocol and SOPs are followed. She will be involved in data analysis, report 
writing, manuscript preparation and dissemination of findings. She will also coordinate 
communications between the engaged and collaborating institutions as well as the Kenya Ministry of 
Health. 

ATSB-Kenya Protocol (v1.1-31May21) 
64 
Dr. Maia Lesosky is PhD in biostatistics and will serve as the site-specific statistician for the ATSB trial 
in Kenya. She will be involved in development of the statistical analysis plan, data cleaning, analysis 
and report and manuscript development. 
Dr. George Okello is a PhD level behavioural scientist. He will be leading the qualitative components 
of the trial including assisting with the development of the methodology, conduct, analyses and 
report writing. He will be providing direct and technical oversight and supervision of the staff 
implementing the qualitative components. 
13.2 NON-ENGAGED COLLABORATORS 
Kennedy Odhiambo Oruenjo is the County Director of Public Health, Sanitation and Health Planning 
for Siaya County, Kenya. He will provide critical communications with the study, the ministry, other 
programs working int eh study area, as well as the communities. He will assist with community 
sensitization and acceptance. He will additionally assist with study findings and interpretations for 
dissemination, including manuscript and presentation dissemination. 
Dr Megan Littrell is an Epidemiologist with PATH based in Washington, D.C., USA. She will provide 
technical advice into the overall study design, methodology, conduct, analyses, and manuscript 
writing. She will also serve as the liaison with the DSMB, Trial Steering Committee, VCAG, IVCC and 
Westham Co. 
14 FINANCIAL ASPECTS AND CONFLICT OF INTEREST 
14.1 FUNDING FOR THE TRIAL 
This study is funded by the Innovative Vector Control Consortium (IVCC) based in Liverpool, UK, 
which is funded by the Bill & Melinda Gates Foundation. 
IVCC provided support in the design of the trial through their independent expert scientific advisory 
committee. Support was also provided by the Design, Analyze, Communicate (DAC) team from the 
Bill & Melinda Gates Foundation. Guidelines provided by WHO’s Vector Control Advisory Group 
(VCAG) were also taken into account in the design of the study.[18] 
IVCC will reserve the right to review any draft manuscripts of the trial but will not have any role 
during the execution, analysis, interpretation of the data. 
14.2 PROVISION OF ATSB 
ATSB will be provided by Westham Co., Israel. 
14.3 BUDGET 
 Budget table 
Table 9: Budget 
Description 
Cost KSH (100 KSH to 1 USD) 
Cost USD 
Personnel 
214,883,682 
$2,148,836.82 
Supplies 
84,783,550 
$847,835.50 
Equipment 
2,750,000 
$27,500.00 
Other Direct Costs 
34,175,747 
$341,757.47 

ATSB-Kenya Protocol (v1.1-31May21) 
65 
Travel  
23,155,552 
$231,555.52 
Subtotal 
359,748,531 
$3,597,485.31 
Total Indirect Costs 15% (to 
KEMRI and LSTM UK) 
53,962,280 
$539,622.80 
Total 
413,710,811 
$4,137,108.11 
 Budget justification  
The overall budget includes the costs to write the protocols, obtain clearance from all governing 
bodies, prepare the study site for the study, implement the study, analyze the data, and disseminate 
the data at local and international fora, and publish manuscripts over a four-year period. 
Personnel: This includes the entomological and epidemiological staff who will be performing the 
field monitoring of the cohort, continuous household survey, outpatient health facility surveillance, 
ATSB monitoring and entomological monitoring. Additionally, it includes the salaries for study 
coordinators and support staff, such as administrators and drivers. 
Supplies: This includes the costs of the RDTs, filter papers, LLINs, antimalarials, laboratory reagents 
for PCR, software licenses, and airtime. 
Equipment: This includes a freezer for the storage of samples. 
Other Direct Costs: This includes the costs of tablets and laptops for data collection, the costs of 
local travel to the communities, including motorbike and transport fees, ethical review processing, 
sponsorship governance, and CME training. 
Travel: This includes international travel fees for the Entomology co-PI to attend international 
conferences in each of the years of the study and travel for consultants from the USA and UK to 
provide technical expertise to the study. It also includes domestic travel to present to the Kenya 
Ministry of Health (National Malaria Control Program) in Nairobi. 
Indirect costs: These include the indirect costs necessary for operating on the KEMRI-CGHR platform 
and for support to the LSTM offices in the UK. 
 
 

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66 
15 REFERENCES 
1. 
Huho B, Briet O, Seyoum A, Sikaala C, Bayoh N, Gimnig J, et al. Consistently high estimates 
for the proportion of human exposure to malaria vector populations occurring indoors in rural 
Africa. International journal of epidemiology. 2013;42(1):235-47. Epub 2013/02/12. doi: 
10.1093/ije/dys214. PubMed PMID: 23396849; PubMed Central PMCID: PMCPMC3600624. 
2. 
Amek N, Bayoh N, Hamel M, Lindblade KA, Gimnig JE, Odhiambo F, et al. Spatial and 
temporal dynamics of malaria transmission in rural Western Kenya. Parasit Vectors. 2012;5:86. Epub 
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16.2 ANNEX II: DENATONIUM BENZOATE SAFETY DATA SHEET  
 
 
 
 

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16.3 ANNEX III: ATSB STATIONS: DISPOSAL OPTIONS ASSESSMENT 
 
 

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16.4 ANNEX IV: ATSB HUMAN AND ENVIRONMENTAL SAFETY ASSESSMENT REPORT 
 
 
 

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