PRISM2 ICEMR Border Cohort

Related studies:

PRISM2 ICEMR Cohort
PRISM ICEMR Cohort

Background:

Uganda is emblematic of other high burden African countries, where progress in reducing the burden of malaria has been slow and difficult to sustain despite the scale up of proven control
interventions. Uganda was the first country to implement universal distribution of free long lasting insecticidal nets (LLINs) starting in 2014, with repeated campaigns every 3-4 years. Uganda
also has one of the largest indoor residual spraying of insecticide (IRS) programs, focusing on selected high transmission districts using different formulations of insecticides rotated every few years.

The success of this intensive approach to vector control has been well documented in Tororo District, a historically high transmission area of southeastern Uganda. IRS was first implemented in Tororo
District in December 2014, initially using a carbamate (Bendiocarb), then switching to an organophosphate (Actellic) in 2016. Comparing key malaria indicators measured from 2011-2014 (prior to IRS)
with indicators in 2017-2019 (after two rounds of universal LLIN distribution and 5 years of sustained IRS), a 500-fold decrease in malaria transmission intensity, a 60-fold decrease in
the incidence of symptomatic malaria, and a 5-fold decrease in parasite prevalence among children 0.5 to 10 years of age were documented. In addition, over this time frame there was a marked shift in the predominant
vector species from An. gambiae s.s. to An. arabiensis.

However, a marked resurgence of malaria cases in 2020 was documented using health facility-based data from 5 districts of Uganda (including Tororo), reaching pre-IRS levels within 1-2 years.
This coincided with a change to clothianidin-based formulations of IRS (Fludora Fusion/SumiShield) in 2019-2020.

To quantify the magnitude of the resurgence, investigate causes, and evaluate the impact of a shift back to IRS with Actellic in 2023, the PRISM Border
Cohort study assessed changes in malaria metrics in regions within and near Tororo District.

Objectives: To better quantify the magnitude of the malaria resurgence in Tororo and to investigate potential causes, the PRISM Border Cohort compared temporal changes in malaria incidence,
prevalence, and entomological measures between September 2020 and September 2023 in a cohort of 667 residents living in two areas within Tororo District and in neighboring Busia District,
where IRS has never been implemented. In addition, the study assessed changes after the formulation of IRS in Tororo District was shifted back to an organophosphate (Actellic) in March 2023.

Methodology:

Geographic Location/Study Sites: Tororo and Busia Districts, Uganda

Dates of Data Collection: August 2020 – September 2023

Study Design: Prospective cohort study

Eligibility Criteria:

Households were randomly selected from an enumeration list for screening and enrolled if they met the following criteria:

At least two members aged 5 years or younger reside in the household
No more than 7 permanent residents currently reside in the household
The household has no plans to move from the study catchment area in the next 2 years
The household expressed willingness to participate in entomological surveillance studies

All permanent residents from enrolled households were screened and enrolled in the cohort study if they met the following criteria:

The selected household was considered their primary residence
The resident agreed to come to the study clinic for any febrile illness and scheduled routine visits
The resident agreed to avoid antimalarial medications outside the study
The resident (for parent or guardian in the case of children) provided written informed consent

Data Collection:
At enrollment, a baseline evaluation was conducted including a detailed medical history, focused physical examination, and blood collection by venipuncture for hemoglobin measurement,
thick blood smear, and storage for future molecular studies. A household survey was conducted to collect information on characteristics of the household and LLIN ownership; all household
members were provided access to an LLIN after the survey. A wealth index was generated for each household using principal components analysis based on common assets and categorized into tertiles.

The cohort was dynamic, such that over the course of the study any permanent residents that joined a household were screened for enrollment. Cohort study participants were encouraged to come to
a dedicated study clinic open 7 days per week for all their medical care.

Routine visits were conducted every 4 weeks and included a standardized evaluation and collection of blood by finger prick/heel stick (if < 6 months of age) or venipuncture (if aged 6 months and older)
for thick blood smear, hemoglobin measurement (every 12 weeks), and storage for future molecular studies. Study participants who missed their scheduled routine visits were visited at home and requested
to come to the study clinic as soon as possible.

Study participants found to have a fever (tympanic temperature > 38.0˚C) or history of fever in the previous 24 hours at the time of any clinic visit had a thick blood smear read immediately.
If the thick blood smear was positive by light microscopy, the patient was diagnosed with malaria and managed according to national guidelines.

All enrolled participants were followed through September 30th, 2023 unless they were prematurely withdrawn. Participants were withdrawn if they: 1) moved out of the cohort household;
2) were unable to be located for > 4 months; 3) withdrew informed consent; or 4) were unable to comply with the study schedule and procedures.

Mosquito collections were conducted every 2 weeks in all rooms of study houses where cohort study participants slept using CDC light traps positioned 1 m above the floor.
Traps were set at 7 PM and contents collected at 7 AM the following morning. Entomology technicians assessed whether cohort study participants reported sleeping under an LLIN each morning
when trap contents were collected.

Study Documentation:

Study protocol:

PRISM2 Border Cohort Study Protocol

Data collection forms: (used to collect raw data)

PRISM2 Border Cohort Household Screening CRF
PRISM2 Border Cohort Individual Screening CRF
PRISM2 Border Cohort Enrollment CRF
PRISM2 Border Cohort Clinical Visit CRF
PRISM2 Border Cohort Hospitalization CRF
PRISM2 Border Cohort Subject Withdrawal CRF
PRISM2 Border Cohort Subject Death CRF
PRISM2 Border Cohort Travel CRF
PRISM2 Border Cohort Mosquito Collection & LLIN Adherence CRF
PRISM2 Border Cohort Human Landing Catches CRF
PRISM2 Border Cohort DBS from Bloodfed Mosquitoes CRF
PRISM2 Border Cohort Oocyst Detection CRF
PRISM2 Border Cohort Membrane feeding CRF
PRISM2 Border Cohort Visitor CRF

Data Dictionaries:

PRISM2 Border Cohort Cross-sectional survey Data Dictionary
PRISM2 Border Cohort Household Questionnaire Data Dictionary
PRISM2 Border Cohort Household Screening Data Dictionary (HSF)
PRISM2 Border Cohort Individual Screening Data Dictionary (ISF)
PRISM2 Border Cohort Enrollment Data Dictionary (ENR)
PRISM2 Border Cohort Clinical Visit Data Dictionary (CVF)
PRISM2 Border Cohort Hospitalization Data Dictionary (HAF)
PRISM2 Border Cohort Subject Withdrawal Data Dictionary (SWF)
PRISM2 Border Cohort Subject Death Data Dictionary (SDR)
PRISM2 Border Cohort Travel Data Dictionary (TF)
PRISM2 Border Cohort Mosquito Collection & LLIN Adherence Data Dictionary (LAF)
PRISM2 Border Cohort Human Landing Catches Data Dictionary (HLC)
PRISM2 Border Cohort DBS from Bloodfed Mosquitoes Data Dictionary (DBS)
PRISM2 Border Cohort Oocyst Detection Data Dictionary (ODF)
PRISM2 Border Cohort Membrane feeding Data Dictionary (MMF)
PRISM2 Border Cohort Visitor Data Dictionary (VF)

ClinEpiDB Data Integration: Data files were provided to ClinEpiDB as .dta files. All dates were obfuscated through the application of a random number algorithm
that shifted dates no more than seven days to comply with the ethical conduct of human subjects research.

Acknowledgements: We thank all the study team members for successfully conducting the PRISM studies over the years and the Tororo and Busia district
administrations for their support. We are grateful to the study participants who participated in this study and their families.

Financial Support: The PRISM2 Border Cohort study was funded by the US National Institutes of Health as part of the International Centers of Excellence
in Malaria Research (ICEMR) program (U19AI089674). The funders played no role in the design of the study; in the collection, analyses, and interpretation of data;
in the writing of the manuscript; or in the decision to submit the manuscript for publication.

Ethics Statement: Ethical approval was obtained from the Makerere University School of Medicine Research and Ethics Committee (REF 2019–134),
the Uganda National Council for Science and Technology (HS 2700), the London School of Hygiene & Tropical Medicine Ethics Committee (17777), and the
University of California, San Francisco Committee on Human Research (257790). Written informed consent was obtained for all participants prior to
enrollment into the cohort study.

Last Updated: July 11, 2024The Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda 2 (PRISM2) Border Cohort is a dynamic prospective cohort study. Households were recruited if they had at least
2 members under the age of 5, no more than 7 residents, and no plans to move in the next 2 years. Mosquito collections were performed every 2 weeks, routine clinic visits occurred every 4 weeks,
and participants attended a study clinic any time they became ill.