Malaria
Conditions
Keywords
long-lasting insecticidal net, pyriproxyfen, piperonyl butoxide, alpha-cypermethrin, deltamethrin
Brief summary
In Uganda, the National Malaria Control Division (NMCD) and implementing partners plan to deliver long-lasting insecticidal nets (LLINs) nationwide in 2020-21, through a mass distribution campaign supported by generous contributions from international donors. LLINs will be distributed free-of-charge to all Ugandan households, aiming to achieve universal coverage. The Against Malaria Foundation has agreed to provide LLINs treated with a pyrethroid insecticide plus pyriproxyfen (PPF) (Royal Guard, Disease Control Technology) and LLINs treated with a pyrethroid insecticide plus piperonyl butoxide (PBO) (PermaNet 3.0, Vestergaard), presenting an opportunity to rigorously evaluate and compare these two LLINs at scale across Uganda. In collaboration with the MOH, the investigators propose to embed a cluster-randomised trial to compare the impact of LLINs with PPF to LLINs with PBO into Uganda's 2020 LLIN distribution campaign. The primary objective of the study is: To evaluate the impact of LLINs treated with a pyrethroid insecticide plus pyriproxyfen (PPF LLINs), as compared to LLINs treated with a pyrethroid plus piperonyl butoxide (PBO LLINs), on malaria incidence in Uganda. The study will test the hypothesis that malaria incidence will be lower in intervention clusters (randomised to receive PPF LLINs) than in control clusters (randomised to receive PBO LLINs).
Detailed description
This rigorous, cluster-randomised trial will evaluate the impact of long-lasting insecticidal nets (LLINs) distributed in Uganda through the 2020-21 national universal coverage campaign. A cluster has been defined as the catchment area of a Malaria Reference Centre (MRC). A total of 64 clusters have been included in the study, covering 32 high malaria burden districts in Uganda where IRS is not being implemented. Clusters have been randomised in a 1:1 ratio in blocks of two by district to receive one of two types of LLINs: (1) pyriproxyfen (PPF) LLINs (Royal Guard) \[n=32\] and (2) piperonyl butoxide (PBO) LLINs (PermaNet 3.0) \[n=32\]. The intervention, including delivery of the LLINs and social and behaviour change communication (SBCC), will be led by the Ugandan National Malaria Control Division (NMCD) and other stakeholders. Currently, LLINs are scheduled to be delivered in the study areas from October 2020 to January 2021. The evaluation will include health facility surveillance at the MRCs to generate continuous estimates of malaria incidence for each MRC catchment area, cross-sectional community surveys at baseline (if additional resources are available), and at 12- and 24-months after LLIN distribution to gather information on net survivorship and use, and parasite prevalence in children 2-10 years of age, entomology surveys, and assessment of net durability and efficacy. The primary outcome of the trial will be malaria incidence as estimated using the health facility surveillance. For each cluster the study will use a 'fried egg' approach for delivering the intervention ('egg white') and measuring our outcomes ('egg yolk'). The 'white' of the egg will include one sub-county per cluster, where the MRC is located. PPF LLINs and PBO LLINs will be distributed to the designated sub-county, as allocated in the randomisation. The 'yolk' of the egg will be the catchment area directly surrounding each MRC, where care-seeking at the MRC is expected to be high (i.e. if someone within the catchment area develops malaria, they are likely to seek care at the MRC). To determine the population of the MRC catchment areas, and to generate a sampling frame for the community surveys, the investigators will do the following: (1) define the catchment area of each MRC before the onset of the trial using data on village of residence from patients attending the MRCs, (2) map and enumerate all households within the MRC catchment areas before the 12-month community survey, and (3) conduct a census survey within each MRC catchment area to generate an accurate estimate of the study population in which study outcomes will be measured concurrently with the 12-month community survey.
Interventions
OTHERlong lasting insecticidal nets with alpha-cypermethrin + pyriproxyfen (PPF LLIN, Royal Guard))
Next-generation bed net combining insecticides with different modes of action
OTHERlong lasting insecticidal nets with deltamethrin + piperonyl butoxide (PBO LLIN, PermaNet 3.0))
Next-generation bed net combining an insecticide with a synergist
BEHAVIORALSocial behaviour change communication
SBCC activities will use digital and other platforms, similar to those used for the COVID-19 response, including the following: (1) LLIN launch on television and radio; (2) regional advocacy meetings on Zoom; (3) mass media platforms (for advertisements, mini skits, DJ mentions, radio spots, interactive talks); (4) social media platforms; (5) VHTs; (6) operation hotlines and toll-free call centres; (7) community mobilisation (megaphones); and (8) use of appropriate information, education, and communication materials. Communication will include messages about COVID-19, malaria, and use, care, repair and repurposing of LLINs.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
cluster-randomised trial
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
A) Primary outcome: All patients who present to the outpatient departments of the MRCs B) Community surveys for secondary outcomes: Inclusion Criteria: * At least one adult aged 18 years or older present * Adult is a usual resident who slept in the sampled household on the night before the survey * Agreement of the adult resident to provide informed consent for the household survey
Exclusion criteria
* Dwelling destroyed or not found * Household vacant * No adult resident home on more than 3 occasions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Malaria Incidence | 24 months following LLIN distribution | Number of cases of laboratory-confirmed malaria diagnosed at the MRC among patients residing in the catchment areas per unit time/the population of the catchment areas |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Parasitaemia | 12 months following LLIN distribution | Proportion of children aged 2-10 years at the time of cross-sectional surveys with blood smears positive for parasites by microscopy |
| Prevalence of Anaemia | 12 months following LLIN distribution | Proportion of children aged 2-4 years with haemoglobin \< 11 g/dL at the time of cross-sectional surveys |
| Proportion of Households That Owned at Least One LLIN | 12 months following LLIN distribution | Proportion of households with at least one LLIN at the time of cross-sectional surveys |
| Proportion of Households That Owned at Least One LLIN for Every Two Occupants | 12 months following LLIN distribution | Proportion of households with at least one LLIN per every two occupants at the time of cross-sectional surveys |
| Proportion of Household Residents Who Slept Under an LLIN the Previous Night | 12 months following LLIN distribution | Proportion of households residents who report sleeping under LLIN the previous night at the time of cross-sectional surveys |
Countries
Uganda
Participant flow
Recruitment details
Households from each of the 64 clusters was randomly selected for participation in each of the community surveys. Within each cluster (MRC target area), households were randomly sampled from a list of households enumerated by the study team, until 50 households with children aged 2-10 years were sampled per cluster.
Pre-assignment details
Only participants in the MRC target areas who participated in cross sectional surveys were considered enrolled while all other persons living in the target areas were not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Royal Guard alpha-cypermethrin + pyriproxyfen (PPF)
long lasting insecticidal nets with alpha-cypermethrin + pyriproxyfen (PPF LLIN, Royal Guard)): Next-generation bed net combining insecticides with different modes of action
Social behaviour change communication: SBCC activities will use digital and other platforms, similar to those used for the COVID-19 response, including the following: (1) LLIN launch on television and radio; (2) regional advocacy meetings on Zoom; (3) mass media platforms (for advertisements, mini skits, DJ mentions, radio spots, interactive talks); (4) social media platforms; (5) VHTs; (6) operation hotlines and toll-free call centres; (7) community mobilisation (megaphones); and (8) use of appropriate information, education, and communication materials. Communication will include messages about COVID-19, malaria, and use, care, repair and repurposing of LLINs. | 92,648 |
| PermaNet 3.0 deltamethrin + piperonyl butoxide (PBO)
long lasting insecticidal nets with deltamethrin + piperonyl butoxide (PBO LLIN, PermaNet 3.0)): Next-generation bed net combining an insecticide with a synergist
Social behaviour change communication: SBCC activities will use digital and other platforms, similar to those used for the COVID-19 response, including the following: (1) LLIN launch on television and radio; (2) regional advocacy meetings on Zoom; (3) mass media platforms (for advertisements, mini skits, DJ mentions, radio spots, interactive talks); (4) social media platforms; (5) VHTs; (6) operation hotlines and toll-free call centres; (7) community mobilisation (megaphones); and (8) use of appropriate information, education, and communication materials. Communication will include messages about COVID-19, malaria, and use, care, repair and repurposing of LLINs. | 99,132 |
| Total | 191,780 |
Baseline characteristics
| Characteristic | Royal Guard | PermaNet 3.0 | Total |
|---|---|---|---|
| Age, Continuous | 19.7 years STANDARD_DEVIATION 17.6 | 19.9 years STANDARD_DEVIATION 17.3 | 19.8 years STANDARD_DEVIATION 17.4 |
| Incidence of malaria in residence of all ages from MRC target areas | 15621 episodes of malaria over 3 months | 16763 episodes of malaria over 3 months | 32384 episodes of malaria over 3 months |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 92648 Participants | 99132 Participants | 191780 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 46324 Participants | 49566 Participants | 95890 Participants |
| Sex: Female, Male Male | 46324 Participants | 49566 Participants | 95890 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Malaria Incidence
Number of cases of laboratory-confirmed malaria diagnosed at the MRC among patients residing in the catchment areas per unit time/the population of the catchment areas
Time frame: 24 months following LLIN distribution
Population: estimated number of residents of all ages from MRC target areas; these estimates came from routine surveillance data that did not involve consent or enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Malaria Incidence | 90466 episodes of malaria over 24 months |
| PermaNet 3.0 | Malaria Incidence | 95898 episodes of malaria over 24 months |
Secondary
Prevalence of Anaemia
Proportion of children aged 2-4 years with haemoglobin \< 11 g/dL at the time of cross-sectional surveys
Time frame: 12 months following LLIN distribution
Population: children 2-4 years of age enrolled in cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Prevalence of Anaemia | 347 participants with hemoglobin <11g/dL |
| PermaNet 3.0 | Prevalence of Anaemia | 385 participants with hemoglobin <11g/dL |
Secondary
Prevalence of Anaemia
Proportion of children aged 2-4 years with haemoglobin \< 11 g/dL at the time of cross-sectional surveys
Time frame: 24 months following LLIN distribution
Population: children 2-4 years of age enrolled in cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Prevalence of Anaemia | 178 participants with hemoglobin <11g/dL |
| PermaNet 3.0 | Prevalence of Anaemia | 191 participants with hemoglobin <11g/dL |
Secondary
Prevalence of Parasitaemia
Proportion of children aged 2-10 years at the time of cross-sectional surveys with blood smears positive for parasites by microscopy
Time frame: 12 months following LLIN distribution
Population: children 2-10 years of age enrolled in cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Prevalence of Parasitaemia | 654 participants with parasitemia |
| PermaNet 3.0 | Prevalence of Parasitaemia | 521 participants with parasitemia |
Secondary
Prevalence of Parasitaemia
Proportion children aged 2-10 years at the time of cross-sectional surveys with blood smears positive for parasites by microscopy
Time frame: 24 months following LLIN distribution
Population: children 2-10 years of age enrolled in cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Prevalence of Parasitaemia | 651 participants with parasitemia |
| PermaNet 3.0 | Prevalence of Parasitaemia | 602 participants with parasitemia |
Secondary
Proportion of Household Residents Who Slept Under an LLIN the Previous Night
Proportion of households residents who report sleeping under LLIN the previous night at the time of cross-sectional surveys
Time frame: 12 months following LLIN distribution
Population: household residents enrolled in 12 month cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Proportion of Household Residents Who Slept Under an LLIN the Previous Night | 6045 residents reported sleeping under LLIN |
| PermaNet 3.0 | Proportion of Household Residents Who Slept Under an LLIN the Previous Night | 6121 residents reported sleeping under LLIN |
Secondary
Proportion of Household Residents Who Slept Under an LLIN the Previous Night
Proportion of households residents who report sleeping under LLIN the previous night at the time of cross-sectional surveys
Time frame: 24 months following LLIN distribution
Population: household residents enrolled in 24 month cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Proportion of Household Residents Who Slept Under an LLIN the Previous Night | 5117 residents reporting sleeping under LLIN |
| PermaNet 3.0 | Proportion of Household Residents Who Slept Under an LLIN the Previous Night | 5341 residents reporting sleeping under LLIN |
Secondary
Proportion of Households That Owned at Least One LLIN
Proportion of households with at least one LLIN at the time of cross-sectional surveys
Time frame: 12 months following LLIN distribution
Population: households enrolled in 12 month cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Proportion of Households That Owned at Least One LLIN | 1571 households with at least 1 LLIN |
| PermaNet 3.0 | Proportion of Households That Owned at Least One LLIN | 1628 households with at least 1 LLIN |
Secondary
Proportion of Households That Owned at Least One LLIN
Proportion of households with at least one LLIN at the time of cross-sectional surveys
Time frame: 24 months following LLIN distribution
Population: households enrolled in 24 month cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Proportion of Households That Owned at Least One LLIN | 1345 households with at least 1 LLIN |
| PermaNet 3.0 | Proportion of Households That Owned at Least One LLIN | 1384 households with at least 1 LLIN |
Secondary
Proportion of Households That Owned at Least One LLIN for Every Two Occupants
Proportion of households with at least one LLIN per every two occupants at the time of cross-sectional surveys
Time frame: 12 months following LLIN distribution
Population: households enrolled in 12 month cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Proportion of Households That Owned at Least One LLIN for Every Two Occupants | 987 households with at least 1 LLIN/2persons |
| PermaNet 3.0 | Proportion of Households That Owned at Least One LLIN for Every Two Occupants | 1060 households with at least 1 LLIN/2persons |
Secondary
Proportion of Households That Owned at Least One LLIN for Every Two Occupants
Proportion of households with at least one LLIN per every two occupants at the time of cross-sectional surveys
Time frame: 24 months following LLIN distribution
Population: households enrolled in 24 month cross-sectional surveys
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Royal Guard | Proportion of Households That Owned at Least One LLIN for Every Two Occupants | 650 households with at least 1LLIN/2persons |
| PermaNet 3.0 | Proportion of Households That Owned at Least One LLIN for Every Two Occupants | 695 households with at least 1LLIN/2persons |