PRISM Cohort Studies and Entomological Surveys

PRISM Website at Makerere University

Brief Summary & Objectives: The Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) study is the dedicated East Africa International Center of Excellence for Malaria Research. The data presented in ClinEpiDB include the longitudinal cohort and entomological surveillance component of the PRISM study. Overall Prism Study Objectives include:

• Perform comprehensive surveillance studies aimed to improve understanding of malaria and measure the impact of population-level control interventions

• Comprehensive approach to surveillance brings together expertise from multiple disciplines to collect data across multiple levels, reflecting the complex nature of interactions between the mosquito vector, malaria parasite and human host

• Studies are conducted in three sites, ranging from areas of relatively low transmission intensity to areas with some of the highest transmission intensities recorded in the world

• A strong emphasis is placed on local training and capacity building, transfer of technology, and building strong relationships between researchers and policymakers.

Geographic Location/Study Sites: Uganda, Walukuba (Jinja District), Kihihi (Kanungu District), Nagongera (Tororo District)

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Dates of Data Collection: August 2011-June 2016

Units of Data Collection: Individuals, Households, Clinical Visits, Light Trap Collections

Methodology, Study Design Type: Longitudinal Cohort & Entomological Surveillance

Methodology, Study Design Details:

Household Cohort Study and Entomological Surveillance Eligibility Criteria: All households in each sub-county were enumerated and mapped (households were defined as any single permanent or semi-permanent dwelling acting as the primary residence for a person or group of people that generally cook and eat together). Using a computerized number generator, random samples of households from each sub-county were approached consecutively, and 100 households were enrolled per site from August – September 2011 into both the entomologic surveys and cohort studies if they met the following criteria:

• At least one household resident 0.5-10 years of age

• At least one adult resident available for providing informed consent

• 300 households (100 per site) were enrolled Aug-Sept 2011 and an additional 31 households were enrolled Aug-Sept 2013 to replace households withdrawn during the 1st two years of follow-up. Household surveys were conducted at the time of enrollment to collect information on household demographics, characteristics and socioeconomic factors.

Cohort Study Eligibility Criteria: All children and up to one primary caregiver from each household were enrolled into the cohort study if they met the following eligibility criteria:

• Documented age between 6 months and <10 years for children

• Full time resident of the household

• No intention to move out of the sub-county for the next two years

• Agreement to come to a dedicated study clinic located within the sub-county for any febrile illness

• Agreement to avoid antimalarial medications administered outside this study

• Provision of written informed consent from parent or guardian

Cohorts were dynamic: all newly eligible children were enrolled and study participants reaching 11 years of age were excluded from further follow-up.

Study participants were withdrawn from the study based on:

• Permanent movement out of the sub-county

• Inability to be located for > 4 months

• Withdrawal of informed consent

• Inability to comply with the study schedule and procedures

• Child reaching 11 years of age

• A household was withdrawn when all cohort study participants from the household were withdrawn.

Methodology, Target Populations: Comprehensive surveillance studies were conducted in Walukuba, Jinja District; Kihihi, Kanungu District; Nagongera, Tororo District. To generate a sampling frame for study recruitment all households within the sub-counties were enumerated and mapped from January – June 2011.

Methodology, Data Collection:

Entomological surveys: Surveys were conducted once a month in each household participating in the cohort studies. Mosquitoes were collected using miniature CDC light traps with the light positioned 1 meter above the floor at the foot end of the bed where a cohort study participant slept. Traps were set at 19.00h and collected at 07.00h the following morning by field workers.

• Female Anopheles mosquitoes were counted and identified taxonomically to species level (A. gambia s.l, A. funestus, or “other”) based on morphological criteria according to established taxonomic keys.

• In a random subset of female Anopheles mosquitoes the proportion infected with sporozoites were measured using an ELISA technique.

Population Level Vector Control Interventions:

• Universal Long-lasting insecticide treated bednet (LLIN)campaigns were carried out in Walukuba in November 2013, Kihihi in June 2014 and Nagongera in November 2013.

• District wide indoor residual spraying (IRS) of insecticide was conducted only in Nagongera. Administered December 2014 - February 2015, June - July 2015, November - December 2015 and June - July 2016. With 96.9%, 95.6%, 96.8% proportion of households sprayed respectively (data not available for June - July 2016).

Cohort Study Enrollment: At enrollment all child participants and their parent or guardian underwent a standardized evaluation including a medical history, physical examination, and collection of blood for hemoglobin measurement and thick/thin blood smear, and were provided with a long lasting insecticide treated bednet (ITN).

Cohort Study Follow-Up: Study participants received all medical care free of charge at a designated study clinics open every day, and were encouraged to come to the clinic any time they became ill.

For any participant presenting to the clinic with documented fever (tympanic temp >38C) or history of fever in the previous 24 hr, blood was obtained by finger prick for a thick blood smear. Smear-positive patients were diagnosed with malaria, hemoglobin measurements were obtained, and a thin blood smear was performed for parasite species identification. Episodes of uncomplicated malaria were treated with artemether + lumefantrine (AL). Complicated malaria (severe malaria or danger signs) or recurrent malaria within 14 d of prior therapy was treated with quinine or IV artesunate.

Routine evaluations including thick blood smears and hemoglobin measurements were performed every ~3 months. In subset of children starting in December 2014, routine blood smears were done every month.

 

Case Report Forms and Data Dictionaries:

Case Report Forms (CRFs):

 

• Household screening form - Used to screen households prior to enrolling household members in study

• Individual screening form - Used to screen individuals prior to enrolling participants in study

• Enrollment form - Used to enroll participants in study and collect first visit information

• Clinical visit form - Used to collect information each time participants were seen in the clinic

• Updated clinical visit form (Oct-2015) - Used to collect information when participants were seen in the clinic, revised from the original version

• Hospital admission form - Used to collect information on the course of illness if a participant was hospitalized

• Complicated malaria treatment record form - Used to collect information regarding malaria diagnosis and treatment

• Subject withdrawal form - Used to collect information regarding participant withdrawal from the study

• Subject death record form - Used to collect information regarding the death of a participant

Data Dictionaries:

 

• Longitudinal cohort data dictionary - Contains the variables and possible values for each question asked on the household screening form (HSF), individual screening form (ISF), enrollment form (ENR), clinical visit form (CVF), hospital admission form (HAF), subject withdrawal form (SWF), subject death record form (SDR), and complicated malaria treatment record form (CMTR)

• Household and laboratory sample data dictionary - Contains the variables and possible values for questions asked about the household (household members, household characteristics, and bednet usage) and lab results

• Entomology data dictionary - Contains the variables and possible values for questions asked about mosquitos collected at different households

Processing Conducted: Data files were provided to ClinEpiDB as flat, tab-delimited text files. These datasets were merged by unique ID and redundant or administrative columns were dropped from presentation on ClinEpiDB.org. All dates were obfuscated per participant 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 the study team and the Infectious Diseases Research Collaboration (IDRC) for administrative and technical support. We are grateful to the study participants who participated in this study and their families.

Financial Support: Funding was provided by the National Institutes of Health as part of the International Centers of Excellence in Malaria Research (ICEMR) program (U19AI089674).

Ethics Statement: Ethical approval was obtained from the Makerere University School of Medicine Research and Ethics Committee, the Uganda National Council for Science and Technology, the London School of Hygiene & Tropical Medicine Ethics Committee, the Durham University School of Biological and Biomedical Sciences Ethics Committee, the University of California, San Francisco Committee on Human Research and The University of Pennsylvania.

Last updated: June 27th, 2018