GTS-MACS Study

GTS-MACS Study

Full title

Development of Geospatio-Temporal Surveillance and Characterisation of Malaria in the Changing Climatic Conditions in Eastern Uganda Study

Study overview

Malaria transmission is influenced by environmental conditions that affect mosquito survival, breeding and contact with human populations. Changes in temperature, rainfall and humidity may alter when and where malaria transmission occurs, potentially extending transmission seasons or increasing malaria incidence in previously lower-risk areas.

At the same time, the emergence of Plasmodium falciparum parasites with reduced susceptibility to commonly used antimalarial medicines threatens progress in malaria control.

The GTS-MACS Study combines epidemiological surveillance, geographical mapping, climate information, parasite-clearance monitoring and molecular laboratory investigations to characterise malaria in Eastern, Northern and Northeastern Uganda.

Study objectives

The study aims to:

Study design

GTS-MACS is a multidisciplinary observational research programme with three interconnected components:

  1. Geospatial and temporal surveillance of malaria cases.
  2. Clinical monitoring of parasite clearance following malaria treatment.
  3. Molecular surveillance of antimalarial drug-resistance markers.

The study combines routine health-facility data, participant information, laboratory results, geographical data and climatic variables.

Geospatial and temporal surveillance

The geospatial component examines how malaria cases are distributed across geographical locations and how these patterns change over time.

Malaria data are analysed alongside environmental variables such as:

This information is used to produce malaria-risk maps and identify geographical areas where climate-related conditions may be contributing to increased or sustained malaria transmission.

The mapping component is intended to help malaria programmes allocate resources more effectively and target surveillance, prevention and treatment activities toward the most affected communities.

Parasite-clearance component

Children with uncomplicated malaria who receive artemether-lumefantrine are monitored to determine how quickly malaria parasites disappear from their blood.

The study particularly examines the presence or absence of parasites on day three after treatment begins. Delayed parasite clearance can provide an early warning of reduced parasite susceptibility to artemisinin-based medicines.

Parasite-clearance findings are considered together with molecular-resistance results to provide a broader understanding of treatment response. The presence of parasites on day three does not, by itself, confirm treatment resistance and must be interpreted alongside adherence, medicine exposure, parasite density and genetic findings.

Molecular-surveillance component

The molecular component examines Plasmodium falciparum genetic mutations associated with reduced susceptibility or resistance to antimalarial medicines.

The genes investigated include:

Blood samples collected from children with confirmed malaria are stored as dried blood spots. Parasite DNA is extracted and analysed using Molecular Inversion Probes and high-throughput sequencing.

Study population

The published molecular-surveillance component enrolled children aged two months to 12 years who attended participating hospitals with uncomplicated malaria.

Children were eligible when malaria was:

Participation required informed consent from a parent or caregiver and assent from children where applicable.

Study sites

The molecular-surveillance component included four Ugandan hospitals:

These sites represent areas with differing malaria-transmission patterns in Eastern, Northeastern and Northern Uganda.

Data and sample collection

Study data include:

For molecular analysis, blood was collected by venepuncture and applied to filter paper to produce dried blood spots. Samples were transported to the Uganda Ministry of Health’s Central Public Health Laboratory for DNA extraction, sequencing and analysis.

Molecular-surveillance sample

Between February and August 2024, the study collected 200 dried blood-spot samples:

Sequencing success varied among sites because some samples contained very low parasite densities.

Preliminary and published findings

The study generated a malaria epidemiological map demonstrating variations in malaria distribution in relation to temperature, rainfall and humidity.

The molecular component detected Pfk13 mutations associated with emerging partial artemisinin resistance. The A675V mutation was identified at varying levels, including approximately:

The Pfk13 C469Y mutation was also detected across the study locations. Other important mutations, including R561H and C580Y, were not detected in the analysed samples.

These molecular findings suggest that resistance-associated parasite populations differ geographically and require continued surveillance.

Antifolate-resistance findings

The study found a high prevalence of mutations in the Pfdhfr and Pfdhps genes. These mutations are associated with resistance to sulfadoxine-pyrimethamine.

The widespread presence of combinations of these mutations suggests substantial antifolate-drug resistance across the study areas. This is particularly important because sulfadoxine-pyrimethamine continues to have a role in malaria prevention for selected populations, including pregnant women.

Other resistance markers

The Pfcrt K76T mutation associated with chloroquine resistance was uncommon. Most samples carried the wild-type allele, potentially reflecting reduced selection pressure following the withdrawal of chloroquine from routine malaria treatment.

Most Pfmdr1 markers were also predominantly wild type, although some geographical variation was observed. These markers require continued monitoring because changes may affect parasite susceptibility to partner medicines such as lumefantrine.

The findings were published in Malaria Journal in June 2025. Read the molecular-surveillance publication.

Interpretation of the findings

The detection of resistance-associated mutations does not automatically mean that every child carrying these parasites will experience treatment failure. Molecular markers are warning indicators that should be interpreted alongside parasite-clearance rates and therapeutic-efficacy studies.

The geographical variation observed by GTS-MACS demonstrates the importance of conducting surveillance at regional and district levels. National estimates may conceal important local differences in parasite populations, treatment response and malaria-transmission intensity.

The relatively small number of samples successfully sequenced at some sites, particularly Soroti, limits the generalisability of the resistance estimates. Larger and repeated studies are therefore required to confirm trends.

Importance of the study

GTS-MACS provides a framework for bringing together information that is often analysed separately:

This integrated approach can help health authorities anticipate changes in malaria transmission, identify resistance hotspots and design interventions suited to particular districts and communities.

The project is also strengthening national capacity in molecular surveillance, geographical information systems, data analysis and climate-sensitive disease monitoring.

Capacity-building activities

In addition to its research objectives, GTS-MACS has supported the development of:

Preliminary findings have been shared with researchers, healthcare providers and policymakers through scientific meetings, online dissemination activities and conferences. Read the Busitema University project update.

Study leadership

The Principal Investigator is Professor Peter Olupot-Olupot, who conceptualised the study and led its design and implementation.

The research team includes investigators from Mbale Clinical Research Institute and Busitema University, including:

Additional site, laboratory and technical investigators contributed from participating hospitals, the Central Public Health Laboratory and the Infectious Diseases Research Collaboration.

Collaborating institutions

The participating and collaborating organisations include:

Funding

The study has received support from:

Ethical and regulatory approval

The study received approval from:

Parents or caregivers provided informed consent before children participated. Assent was obtained from children who were old enough to provide it.

Study status

GTS-MACS is an ongoing study. The UNCST record lists the study period as February 2024 to February 2027.

The geospatial mapping component and an initial phase of molecular-resistance analysis have been completed. Parasite-clearance analysis, continued surveillance, validation of findings and dissemination activities form part of the ongoing research programme. View the UNCST study record.

Key publication

Comprehensive analysis of molecular markers linked to antimalarial drug resistance in Plasmodium falciparum in Northern, Northeastern and Eastern Uganda – Malaria Journal

About

Ms. Adyango Catherine is a Human Resource Manager and Senior Grants Professional with over 15 years of experience in managing multimillion-dollar donor portfolios, project operations, and organizational systems strengthening. She currently serves as Human resource Manager at Mbale Clinical Research Institute (MCRI), where she leads in Human resource management,  donor compliance, project operations, and institutional capacity building.

At MCRI, Catherine has combined her expertise in grant management and human resources to establish efficient systems that support both research and staff welfare. She played a pivotal role in championing organizational culture reforms, developing HR policies, strengthening staff welfare schemes, and promoting inclusive recruitment processes. She also streamlined adoption of a Human Resource Management Information System (HRMIS/ESS), which reduced administrative bottlenecks and improved efficiency across teams.

Her academic background includes a Postgraduate Diploma in Human Resource Management (Uganda Management Institute), an MSc in Health Services Management, and a bachelor’s degree in business administration & management. Catherine is also pursuing ACCA training, demonstrating her commitment to continuous professional growth.

Catherine’s career reflects a strong commitment to strategic leadership, staff development, and inclusive programming, with a proven ability to balance donor expectations and human resource needs. Her work at MCRI has significantly contributed to building sustainable research capacity, enhancing compliance systems, and creating a supportive work environment that empowers both researchers and administrative staff.

About

Denis Amorut serves as the Study Site Coordinator at the Mbale Clinical Research Institute’s Soroti Site. He is a qualified Registered Nurse with a Bachelor of Science in Health Services Management from the Islamic University in Uganda and a Diploma in Comprehensive Nursing from Soroti School of Registered Comprehensive Nursing. Additionally, he is currently pursuing an Advanced Postgraduate Diploma in Clinical Research & Quality Assurance at James Lind Institute, showcasing his commitment to advancing his expertise in clinical research. Denis has an extensive professional background with 12 years in clinical nursing practice and 11 years dedicated to clinical research. He is registered with the Uganda Midwives and Nurses Council, highlighting his professional standing in the healthcare sector.
 
Throughout his career, Denis has held significant positions such as Trial Manager since November 2021 and previously as Study Site Coordinator at Soroti Regional Referral and Teaching Hospital from 2008 to October 2021. He also serves as a member of the Medicine and Therapeutic Committee at the same hospital since 2018. Denis has enriched his knowledge and skills through numerous online courses and certifications in areas like research ethics, data management for clinical studies, Good Clinical Practice (GCP), and managing health emergencies like Covid-19. His involvement in various research studies, including the TRACT study, and his roles in hospital committees further demonstrate his dedication to both practice and research in healthcare, focusing on improving patient care through evidence-based practices.

About

Ms. Linda Isabirye serves as the Public and Community Engagement Officer at MCRI, where her role encompasses a variety of tasks aimed at enhancing the Institute’s interaction with both internal and external communities. Her work is divided into two primary focuses: public engagement, where she communicates the Institute’s research and ideas to the public, and community engagement, where she assists others in conducting research and achieving their objectives.

In her community engagement efforts, Linda is involved in developing and sustaining a public engagement and involvement framework for the research program. She identifies local opportunities for community collaboration, nurturing relationships with MCRI’s research scientists, staff, and the broader community.

With over two years of experience, she has worked extensively with diverse community stakeholders. Her responsibilities include coordinating activities for the Community Advisory Board (CAB), designing, and overseeing the execution of Community Engagement (CE) initiatives. These initiatives are crucial for identifying, recruiting, and retaining volunteers, engaging community leadership, and supporting the formation and operation of community peer groups. This includes working with study participants, family support groups, and youth and adolescent groups, among others.

About

Rita Muhindo holds a MSc. Molecular Biology from Staffordshire University, UK. She attained her BSc. Biomedical Laboratory Science and Technology degree from Makerere University and an Advanced Diploma in Health Services Management from Islamic University in Uganda. She joined Mbale Clinical Research Institute in July 2011 as a laboratory technologist participating in setting up various laboratory assays for all clinical trials at the MCRI.

She is currently the laboratory manager of MCRI, a role which involves supervision all laboratory research activities at MCRI main and satellite laboratories. She has over twelve years of experience in managing laboratory clinical research and diagnostics service delivery across several key disciplines including molecular, immunology, hematology, microbiology and clinical chemistry.

She has keen interest in understanding the prevalence of red cell polymorphisms present in Ugandan donor populations. Her main focus of her MSc project was on the prevalence of Glucose-6-Phosphate dehydrogenase deficiency, α-thalassaemia and Haemoglobin S among Ugandan donors. Rita is also keen to explore the effects of these polymorphisms on the resolution of severe anaemia.

About

Dr. Charles Benard Okalebo is a highly qualified professional with a B. Pharm, an MPH, and currently a fellow in Infectious Disease and Field Epidemiology under the EDCTP-funded IDEA fellowship. His background as a pharmacist and public health specialist, combined with his role as a Quality Assurance Officer, has provided him with extensive experience in clinical research. This diverse training has honed his skills in assessing healthcare gaps, identifying problems, and designing projects to address these deficiencies. Dr. Okalebo values accuracy, integrity, quality, and career growth above all.
 
He is an experienced and determined professional in conducting clinical trials for both infectious and non-infectious diseases. With eight years in the research field, he has served as a Pharmacist and Quality Assurance Officer at the Mbale Clinical Research Institute, focusing on various types of clinical trials related to infectious diseases. His involvement spans across all phases of clinical trials (I-III), including protocol design, review, and implementation; navigating regulatory approval processes; managing investigational medicinal products (IMP); monitoring studies; establishing and implementing Quality Management processes; pharmacovigilance; and leading training sessions on the ethical conduct of research. The trials he has participated in include TRACT (ISRCTN84086586), GASTROSAM (ISRCTN76149273), PAC (ISRCTN11594437), FLACSAM (ISRCTN18051843), MIMBLE (ISRCTN10309022), and TABS (ISRCTN49726849) studies.
 
Dr. Okalebo is a dedicated researcher with a keen interest in advancing his career in pharmaco-epidemiology, statistics, and pharmacovigilance.

About

Felix Opio joined the Mbale Clinical Research Institute (MCRI) in April 2014 as Data Manager under the REACH (Realizing Effectiveness Across Continents with Hydroxyurea) ClinicalTrials.gov NCT01966731) which is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, long-term risks and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries (Mable Uganda,Kilifi Kenya, Luanda Angola and Kinshasa DRC).

He holds a Bachelor of Science in Computer Science from Gulu University, a post graduate diploma in Monitoring and Evaluation from Uganda Management Institute (UMI), Certificate in Project Management Professional from Devimpact Institute Kenya and various other certification in Clinical database development.

He Has 9 years of experience in Clinical Database design and Management, He is Currently overseeing data management work for the REACH study and all the day to day activities of the Project, He is also a member of the internal Clinical Trial Monitoring Unit and A chairperson Procurement Committee for Mbale Clinical Research Institute.

About

Ebitu Caleb Daniel serves as an I.T Support Officer at the Mbale Clinical Research Institute. He is recognized as an accomplished network and systems administrator, who takes pleasure in applying his skills to support and contribute to the technological advancement of research within the institution.
 
Ebitu graduated from Uganda Christian University Mukono with a Bachelor’s degree in Computer Science. Over the years, he has also acquired various certifications including CCNA, Information Security, Google Cloud Developer, PMP (Telecom), and Federated Identity Management.

About

Laban has accumulated over four years of experience in managing research financial processes since joining the Mbale Clinical Research Institute on July 1, 2019, as an Accounts Assistant. This experience complements his extensive background of over ten years in the banking sector, where he has previously worked for two banks in roles involving people management, cash management, internal controls, and accountability.

He holds a Bachelor’s degree in Business Studies, specializing in Accounting, from the Islamic University of Uganda. He is currently pursuing a Certificate of Public Accountants (CPA) from the Institute of Certified Public Accountants of Uganda (ICPAU), with only two papers remaining to complete the course.

Driven by an ambition to advance his career in accounting and expand his experience in research-related accounting managed by well-established systems and processes, he believes that MCRI is the ideal place for his professional growth.