School-based Treatment with ACT to Reduce Transmission: Evaluation of the community impact of intermittent preventive treatment for malaria in Uganda

Lead Research Organisation: London Sch of Hygiene and Trop Medicine
Department Name: Infectious and Tropical Diseases

Abstract

Despite global commitment to malaria control and substantial increases in funding, the burden of malaria in Africa remains high. Currently, malaria control is targeted at children under five years and pregnant women. School-aged children remain relatively uncovered leaving them at risk for illness and death, and with the potential to transmit malaria to other members of the community. Intermittent preventive treatment (IPT), administering antimalarial treatment at predefined intervals regardless of infection status, has been shown to benefit pregnant women, infants, and young children, and has become an important malaria control strategy. Initial studies conducted in Uganda and elsewhere in Africa suggest that school-aged children also benefit from IPT, but the community benefits of IPT and impact on malaria transmission are unproven.

We propose to evaluate the impact of IPT for malaria in Ugandan schoolchildren on indicators of health and malaria transmission in the community. We will select 36 primary schools in Kanungu district to participate in the study; 18 schools will be randomly assigned to receive the IPT intervention, and 18 will be assigned to standard care (no intervention). Dihydroartemisinin-piperaquine (DP), a highly effective and long-acting, artemisinin-based combination therapy (ACT) will be provided to eligible children attending intervention schools once a term (3 times per year) for one year. In addition, all children in both the intervention and standard care schools will receive annual deworming, according to national guidelines.

Outcomes will be measured using surveys of communities, schoolchildren, and mosquito vectors.
Community and school surveys will be conducted at baseline and approximately two months after the third (and final) round of treatment. The community surveys will consist of a household questionnaire and a laboratory evaluation of all household members; 180 residents from randomly selected households from each of the 36 clusters will be included. For the school surveys, 64 randomly selected children from each of the 36 schools will be included. In both community and school surveys, a finger-prick blood sample will be obtained to evaluate for malaria parasites and to measure blood counts (haemoglobin). Mosquitos will also be collected from eight randomly selected households from each of the 36 clusters. Each house will be sampled once a month for the duration of the study.

The primary outcomes for the trial will be the proportion of people that are infected with malaria parasites and the entomologic inoculation rate (estimated number of infective mosquito bites per person per year) in the community. We will also determine the proportion of schoolchildren that are infected with malaria parasites.

A qualitative study will run alongside the main trial to investigate perceptions of the IPT intervention, and the potential feasibility of integrating the intervention into health service and school systems in Uganda. Results from this work will help to inform the design of future Information, Education, and Communication programmes if the intervention was taken to scale. We will also conduct mathematical modelling to determine the potential impact of the intervention in other epidemiological settings.

Given the potential contribution by school-aged children to malaria transmission in the community, and the likelihood of operational success and sustainability of school-based interventions, the question of whether IPT targeted to schoolchildren could reduce malaria transmission at a population level is highly relevant. This trial will address that question, and includes health service research and modelling to help guide future research and implementation of the intervention, and help shape policies in Uganda and elsewhere in Africa.

Technical Summary

We propose to evaluate the impact of intermittent preventive treatment (IPT) for malaria in Ugandan schoolchildren on indicators of health and malaria transmission in the community, using a cluster randomised design. The unit of randomisation for the trial will be a primary school. A cluster will be defined as the school plus surrounding catchment area, including households located within a 500m radius. We will select 36 primary schools in Kanungu district to participate in the study; 18 schools will be randomly assigned to receive the IPT intervention, and 18 will be assigned to standard care (no intervention). Dihydroartemisinin-piperaquine (DP), a highly effective artemisinin-based combination therapy (ACT) will be provided to eligible children attending intervention schools once a term (3 times per year) for one year. In addition, all children in the intervention and standard care schools will receive annual deworming, according to national guidelines. Outcomes will be measured using surveys of communities, schoolchildren, and mosquito vectors. Community and school surveys will be conducted at baseline and approximately two months after the third (and final) round of treatment.

The primary objective of the study is to evaluate the impact of IPT for malaria, as compared with the current standard of care, on community-level indicators of malaria transmission. We will test the hypothesis that malaria transmission, as measured by the prevalence of asexual parasitaemia and the entomological inoculation rate (EIR), will be lower in communities surrounding the intervention schools, than those surrounding the standard care schools.

To guide future research and implementation of the intervention, our proposal includes health service research to evaluate perceptions of the intervention and the potential feasibility of taking the programme to scale, and mathematical modelling to determine the potential impact of the intervention in other epidemiological settings.

Planned Impact

Introduction

Malaria remains one of the most important global health challenges. The economic and social burden of malaria is great, and malaria and poverty are closely linked. Malaria control efforts typically target children under five years and pregnant women. However, malaria remains a problem in older children, contributing to poor school performance, and putting school-aged children at risk for illness and death. Older children also serve as a reservoir for parasites, with the potential to transmit malaria to other members of the community.

Intermittent preventive treatment (IPT), providing antimalarial treatment at predefined intervals regardless of infection status, is becoming an important malaria control strategy. In this study, we propose to evaluate the impact of IPT for malaria in Ugandan schoolchildren on community-level indicators of malaria transmission. Treatment with dihydroartemisinin-piperaquine, a highly effective and long-acting, artemisinin-based combination therapy (ACT) will be provided to eligible children attending intervention schools once a term, for a total of three treatments over one year. If the intervention is successful, it will decrease malaria transmission in the community, as well as improve health of schoolchildren. To guide future research and implementation of the intervention, our proposal also includes health service research to evaluate perceptions of the intervention and the potential feasibility of taking the programme to scale, and mathematical modelling to determine the potential impact of the intervention in other epidemiological settings.


Who might benefit from this research?

This research will directly benefit those involved in with the study, including schoolchildren, teachers, and primary schools. Others associated with the study, including members of the students' households, and members of the communities surrounding the participating schools, also stand to benefit. Local, district, and national officials involved in health and education, Uganda's National Malaria Control Programme, and other organizations such as non-governmental organizations (NGOs) that are involved in malaria research and control, are also expected to benefit from this research, in Uganda, elsewhere in Africa, and globally. The study proposed here is designed to evaluate the efficacy of the IPT intervention in a controlled setting, delivered by research study staff. We envision that future studies could assess the effectiveness of the intervention in programmatic settings, with the intervention delivered by teachers or school nurses, informed by the implementation research and modelling incorporated in this study. The impact of future studies that lead on from our research could be far reaching, with national, international and global impact.


How might they benefit from this research?

Anticipated economic and social impacts of this research include increased health and well-being, increased school performance, improved effectiveness of primary schools, improved economic prosperity, enhanced quality of life, strengthened links between the education and health sectors, and opportunities for evidence based policy making. Schoolchildren participating in the study are expected to benefit directly through improved health and well-being, and increased school performance. If the intervention decreases malaria transmission, the health of other community members also stands to improve. Increased school attendance and student performance may enhance the effectiveness of primary schools. Decreasing the burden of malaria could contribute to economic prosperity and enhanced quality of life for the community. This research aims to build the links between education and health sectors, and stands to provide evidence to guide future policy decision making, which would benefit officials involved in health and education, and organizations involved in malaria research and control.

Publications

10 25 50
 
Description ACT Consortium strategic reserve funding
Amount $169,048 (USD)
Funding ID ITGB502010 
Organisation London School of Hygiene and Tropical Medicine (LSHTM) 
Department ACT Consortium
Sector Academic/University
Country United Kingdom
Start 08/2014 
End 05/2015
 
Description START-IPT Investigators 
Organisation Durham University
Country United Kingdom 
Sector Academic/University 
PI Contribution PI and coordinator of Co-Investigators and institutions, which are working together to achieve the objectives of the START-IPT project.
Collaborator Contribution Partners at the Infectious Diseases Research Collaboration (IDRC) in Uganda made large contributions to developing the grant application and study design, and are managing the trial on the ground in Uganda, working closely with the PI. Partners at the University of California San Francisco made large contributions to developing the grant application and study design, and provide ongoing expertise on intervention design, implementation and interpretation of results. UCSF oversees and manages the collaboration between START-IPT and related project "PRISM", facilitating effective communication between project staff. Partners at the University of Durham made large contributions to developing the grant application and study design, are leading the entomological surveys in the project, and will contribute to interpretation of trial results. Partners at Imperial College London will contribute to the statistical and mathematical modelling work of the project, and interpretation of trial results. Partners at Makerere University made large contributions to developing the grant application and study design, and are working closely with IDRC in Uganda to assist in trial management and implementation. They will contribute to interpretation of results.
Impact All project outputs stem from this collaboration, as the core project collaboration between research investigators. The collaboration is multi-disciplinary, with the following disciplines represented: Clinical, Entomology, Operational, Mathematical Modelling, Statistics, Epidemiology.
Start Year 2013
 
Description START-IPT Investigators 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution PI and coordinator of Co-Investigators and institutions, which are working together to achieve the objectives of the START-IPT project.
Collaborator Contribution Partners at the Infectious Diseases Research Collaboration (IDRC) in Uganda made large contributions to developing the grant application and study design, and are managing the trial on the ground in Uganda, working closely with the PI. Partners at the University of California San Francisco made large contributions to developing the grant application and study design, and provide ongoing expertise on intervention design, implementation and interpretation of results. UCSF oversees and manages the collaboration between START-IPT and related project "PRISM", facilitating effective communication between project staff. Partners at the University of Durham made large contributions to developing the grant application and study design, are leading the entomological surveys in the project, and will contribute to interpretation of trial results. Partners at Imperial College London will contribute to the statistical and mathematical modelling work of the project, and interpretation of trial results. Partners at Makerere University made large contributions to developing the grant application and study design, and are working closely with IDRC in Uganda to assist in trial management and implementation. They will contribute to interpretation of results.
Impact All project outputs stem from this collaboration, as the core project collaboration between research investigators. The collaboration is multi-disciplinary, with the following disciplines represented: Clinical, Entomology, Operational, Mathematical Modelling, Statistics, Epidemiology.
Start Year 2013
 
Description START-IPT Investigators 
Organisation Infectious Diseases Research Collaboration (IDRC)
Country Uganda 
Sector Charity/Non Profit 
PI Contribution PI and coordinator of Co-Investigators and institutions, which are working together to achieve the objectives of the START-IPT project.
Collaborator Contribution Partners at the Infectious Diseases Research Collaboration (IDRC) in Uganda made large contributions to developing the grant application and study design, and are managing the trial on the ground in Uganda, working closely with the PI. Partners at the University of California San Francisco made large contributions to developing the grant application and study design, and provide ongoing expertise on intervention design, implementation and interpretation of results. UCSF oversees and manages the collaboration between START-IPT and related project "PRISM", facilitating effective communication between project staff. Partners at the University of Durham made large contributions to developing the grant application and study design, are leading the entomological surveys in the project, and will contribute to interpretation of trial results. Partners at Imperial College London will contribute to the statistical and mathematical modelling work of the project, and interpretation of trial results. Partners at Makerere University made large contributions to developing the grant application and study design, and are working closely with IDRC in Uganda to assist in trial management and implementation. They will contribute to interpretation of results.
Impact All project outputs stem from this collaboration, as the core project collaboration between research investigators. The collaboration is multi-disciplinary, with the following disciplines represented: Clinical, Entomology, Operational, Mathematical Modelling, Statistics, Epidemiology.
Start Year 2013
 
Description START-IPT Investigators 
Organisation Makerere University
Country Uganda 
Sector Academic/University 
PI Contribution PI and coordinator of Co-Investigators and institutions, which are working together to achieve the objectives of the START-IPT project.
Collaborator Contribution Partners at the Infectious Diseases Research Collaboration (IDRC) in Uganda made large contributions to developing the grant application and study design, and are managing the trial on the ground in Uganda, working closely with the PI. Partners at the University of California San Francisco made large contributions to developing the grant application and study design, and provide ongoing expertise on intervention design, implementation and interpretation of results. UCSF oversees and manages the collaboration between START-IPT and related project "PRISM", facilitating effective communication between project staff. Partners at the University of Durham made large contributions to developing the grant application and study design, are leading the entomological surveys in the project, and will contribute to interpretation of trial results. Partners at Imperial College London will contribute to the statistical and mathematical modelling work of the project, and interpretation of trial results. Partners at Makerere University made large contributions to developing the grant application and study design, and are working closely with IDRC in Uganda to assist in trial management and implementation. They will contribute to interpretation of results.
Impact All project outputs stem from this collaboration, as the core project collaboration between research investigators. The collaboration is multi-disciplinary, with the following disciplines represented: Clinical, Entomology, Operational, Mathematical Modelling, Statistics, Epidemiology.
Start Year 2013
 
Description START-IPT Investigators 
Organisation University of California, San Francisco
Country United States 
Sector Academic/University 
PI Contribution PI and coordinator of Co-Investigators and institutions, which are working together to achieve the objectives of the START-IPT project.
Collaborator Contribution Partners at the Infectious Diseases Research Collaboration (IDRC) in Uganda made large contributions to developing the grant application and study design, and are managing the trial on the ground in Uganda, working closely with the PI. Partners at the University of California San Francisco made large contributions to developing the grant application and study design, and provide ongoing expertise on intervention design, implementation and interpretation of results. UCSF oversees and manages the collaboration between START-IPT and related project "PRISM", facilitating effective communication between project staff. Partners at the University of Durham made large contributions to developing the grant application and study design, are leading the entomological surveys in the project, and will contribute to interpretation of trial results. Partners at Imperial College London will contribute to the statistical and mathematical modelling work of the project, and interpretation of trial results. Partners at Makerere University made large contributions to developing the grant application and study design, and are working closely with IDRC in Uganda to assist in trial management and implementation. They will contribute to interpretation of results.
Impact All project outputs stem from this collaboration, as the core project collaboration between research investigators. The collaboration is multi-disciplinary, with the following disciplines represented: Clinical, Entomology, Operational, Mathematical Modelling, Statistics, Epidemiology.
Start Year 2013
 
Description START-IPT study collaborator 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution We have produced models of Intermittent Preventive Treatment for malaria in school children, to assist the design of a trial and give an estimate of likely effect.
Collaborator Contribution Design and carrying out a cluster-randomized trial of Intermittent Preventive Treatment for malaria in school children in Uganda.
Impact Informed trial design. The collaboration is multi disciplinary, including mathematical modellers, clinicians, epidemiologists.
Start Year 2014
 
Description ASTMH Oral Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Catherine Maiteki from IDRC presented one oral presentation entitled " School-based Treatment with ACT to Reduce Transmission of Malaria", reporting the results of the main trial. The intended purpose of this activity was to present the final results to an academic audience in order to generate useful discussion and disseminate results more widely.
Year(s) Of Engagement Activity 2016
 
Description ASTMH Poster Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Samuel Gonahasa from IDRC presented a scientific research poster at the American Society for Tropical Medicine and Hygiene (ASTMH) Annual Meeting in Philadelphia, October 2015, entitled: 'School-based treatment with ACT to reduce transmission (START-IPT): Evaluation of the community impact of intermittent preventive treatment for malaria in Ugandan children'. The intended purpose of this activity was to present findings to an academic audience in order to generate useful discussion and disseminate results more widely.
Year(s) Of Engagement Activity 2015
 
Description ASTMH Poster Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Susan Nayiga from IDRC presented a scientific research poster at the American Society for Tropical Medicine and Hygiene (ASTMH) Annual Meeting in Philadelphia, October 2015, entitled: 'Lessons for integrating intermittent preventive treatment for malaria in school systems in low income settings: experiences from Uganda'. The intended purpose of this activity was to present findings to an academic audience in order to generate useful discussion and disseminate results more widely.
Year(s) Of Engagement Activity 2015
 
Description ASTMH Poster Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Samuel Gonahasa from IDRC presented a scientific research poster at the American Society for Tropical Medicine and Hygiene (ASTMH) Annual Meeting in Philadelphia, October 2015, entitled: 'Risk of QTc prolongation with repeated dosing of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in Ugandan schoolchildren'. The intended purpose of this activity was to present findings to an academic audience in order to generate useful discussion and disseminate results more widely.
Year(s) Of Engagement Activity 2015
 
Description Community sensitisation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Meetings were held with communities in the research sites and with village leaders and other key stakeholders to communicate the nature of the research and to establish a dialogue with the local communities. Representatives from the project presented their work to the community groups, responded to their questions and concerns, and gained their feedback. It is beneficial for the local communities in our research sites to understand why our teams are there and the importance of the research. This raises awareness of malaria in the local areas and encourages prevention measures. Support of the local communities also makes it easier to run the project, therefore increasing the chances of study success.

It is beneficial for the local communities in our research sites to understand why our teams are there and the importance of the research. This raises awareness of malaria in the local areas and encourages prevention measures. Support of the local communities also makes it easier to run the project, therefore increasing the chances of study success.
Year(s) Of Engagement Activity 2013,2014,2015
 
Description IDRC Stakeholder Dissemination Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Dr Catherine Maiteki from IDRC presented one oral presentation entitled " School-based Treatment with ACT to Reduce Transmission of Malaria", reporting the results of the main trial. The audience comprised internation malaria scientists (various disciplines) and policymakers, primarily from Uganda. The presentation resulted in various scientific discussions about the study and its potential implications for future research and policy.
Year(s) Of Engagement Activity 2016
 
Description Scientific Presentation, YIRS Uganda 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Ms. Susan Nayiga presented an abstract at the Young Investigators Research Symposium (YIRS) held in Kampala, Uganda, in Jan 2016, entitled: 'Lessons for integrating IPT for malaria in school systems'. The symposium is held annually at the Infectious Diseases Research Collaboration (IDRC) and brings together young scientists, senior scientists and mentors from the London School of Hygiene and Tropical Medicine, University of California San Francisco and Makerere University to discuss ongoing research in infectious diseases, including malaria, HIV and TB.
Year(s) Of Engagement Activity 2016
 
Description Scientific Presentation, YIRS Uganda 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Catherine Maiteki presented an abstract at the YIRS entitled: 'School-based Treatment with ACT to Reduce Transmission of Malaria'. Areas covered included; the intervention roll out, evaluation and preliminary results. The symposium is held annually at the Infectious Diseases Research Collaboration (IDRC) and brings together young scientists, senior scientists and mentors from the London School of Hygiene and Tropical Medicine, University of California San Francisco and Makerere University to discuss ongoing research in infectious diseases, including malaria, HIV and TB.
Year(s) Of Engagement Activity 2016
 
Description Scientific Presentation, YIRS Uganda 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Samuel Gonahasa presented an abstract at the Young Investigators Research Symposium held in Kampala, Uganda, in Jan 2015, entitled: 'Risk of cardiotoxicity with repeated dosing of DP for IPT in schoolchildren'. The symposium is held annually at the Infectious Diseases Research Collaboration (IDRC) and brings together young scientists, senior scientists and mentors from the London School of Hygiene and Tropical Medicine, University of California San Francisco and Makerere University to discuss ongoing research in infectious diseases, including malaria, HIV and TB.
Year(s) Of Engagement Activity 2015
 
Description Scientific Presentation, YIRS Uganda 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Catherine Maiteke presented an abstract at the Young Investigators Research Symposium held in Kampala, Uganda, in Jan 2015, entitled: 'School-based treatment with ACT to reduce transmission of malaria'. The symposium is held annually at the Infectious Diseases Research Collaboration (IDRC) and brings together young scientists, senior scientists and mentors from the London School of Hygiene and Tropical Medicine, University of California San Francisco and Makerere University to discuss ongoing research in infectious diseases, including malaria, HIV and TB.
Year(s) Of Engagement Activity 2015
 
Description Scientific Talk - Malaria Centre Retreat 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Catherine Maiteki from IDRC presented two oral presentations at LSHTM's annual Malaria Centre Retreat entitled " School-based Treatment with ACT to Reduce Transmission of Malaria", reporting the results of the main trial, and 'Cardiac Monitoring and pharmacokinetic studies', reporting the results of the cardiac monitoring sub-study. The audience comprised malaria scientists (various disciplines) from LSHTM and external collaborators from around the world. Presentation resulted in various scientific discussions about the study and its results with other malaria scientists, from a wide range of scientific disciplines.
Year(s) Of Engagement Activity 2016
 
Description Scientific talk, Malaria Centre Retreat 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The PI gave a summary presentation on START-IPT at the Annual Malaria Centre Retreat, Brighton, March 2014. The audience comprised malaria scientists (various disciplines) from LSHTM and external collaborators from around the world. The presentation resulted in various scientific discussions about the study and its protocol with other malaria scientists, from a wide range of scientific disciplines.

Presentation resulted in various scientific discussions about the study and its protocol with other malaria scientists, from a wide range of scientific disciplines.
Year(s) Of Engagement Activity 2014
 
Description Stakeholder dissemination 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact Meetings were held with local stakeholders in Uganda (from government offices, MOH, policy makers, local universities, district level health and education officials) at the start of the project and at update meetings. Updates were presented on project progress, and a dialogue was opened to gain feedback and recommendations from the stakeholders to inform ongoing project work. Recommendations from local stakeholders fed directly into project decisions.

Recommendations from local stakeholders feed directly into project decisions.
Year(s) Of Engagement Activity 2013,2014,2015
 
Description World Health Organisation, Evidence Review Group meeting on The Cardiotoxicity of Antimalarials 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Dr Pras Jagannathan from Stanford University presented the combined results of studies led by IDRC in Uganda, focusing on the safety of chemoprevention with dihydroartemisinin-piperaquine (DP) in various populations (pregnant women, very young children, schoolchildren), including the results from the START-IPT trial. The WHO ERG meeting included scientists from a variety of disciplines, members of WHO and other policy makers. The purpose of the meeting was to generate recommendations for consideration by the WHO Malaria Policy Advisory Committee and the WHO Advisory Committee on Safety of Medicinal Products.
Year(s) Of Engagement Activity 2016
 
Description World Health Organisation, Global Malaria Partnership 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Dr Samuel Gonahasa from IDRC presented one oral presentation entitled " School-based Treatment with ACT to Reduce Transmission of Malaria", reporting the results of the main trial. The audience included Dr Pedro Alonso, the director of WHO's GMP and other key members of the WHO. The intended purpose of this activity was to raise awareness of ongoing research in Uganda, and to present the final results to WHO GMP.
Year(s) Of Engagement Activity 2016