Surveillance
COHORTS

The PRISM Cohorts Study are three concurrent, dynamic population-based cohorts to estimate the incidence of malaria and other indicators of malaria morbidity in children living in three well defined epidemiological settings of varying malaria transmission intensities. Study participants are recruited from randomly selected households located in our catchment areas and followed for two years.

The studies are conducted in three sub-counties located in Uganda: Nagongera sub-county, located in Tororo district in Eastern Uganda, Walukuba sub-county, located in Jinja district in Eastern Uganda and Kihihi sub-county, located in Kanungu district in south-western Uganda. Study clinics will be set up at the UMSP sentinel site health center IV facilities which serve each of the sub-counties.

Nagongera sub-county, is predominantly a rural setting considered to be of very high malaria transmission. Entomology studies conducted in Nagongera in 2001-02 estimated the entomological inoculation rate (EIR) to be 562 infective bites per person per year . Recent demographic data from this sub-county comes from a survey done by our group in 2009 and data from our ongoing sentinel surveillance project. The total population of Nagongera sub-county is 37,714, with children aged 1 to 10 years constituting 37% of the population. Nagongera Health Center IV is the largest public health facility in the sub county and treated an average of 2044 patients per month in 2010 (umsp.muucsf.org).

Also located in the eastern part of the country, Walukuba is a peri-urban sub-county in Jinja district. The district, with an estimated population of 387,600, is an area of medium malaria transmission with an estimated EIR of 6 infective bites per person per year. The Walukuba health center IV is the largest public health facility in the sub-county and treated an average of 3,198 patients per month in 2010 (umsp.muucsf.org).

Kihihi is a rural sub-county in Kanungu district. The district has an estimated population of 204700 and is an area of relatively low malaria transmission intensity with an EIR estimated to be 6 infective bites per person per year. The largest healthcare point in Kihihi sub-county is Kihihi health center IV, a public health facility that treated an average of 1,945 patients per month in 2010 (umsp.muucsf.org)

Map of Uganda showing the three selected UMSP sentinel sites

Primary Objective
To estimate the incidence of malaria among children and adults living in three different epidemiological settings with varying levels of malaria transmission intensity.

Secondary objectives
1. To measure the prevalence of asymptomatic parasitaemia and anaemia among children and adults living in three settings of varying malaria transmission intensity.

2. To determine the age- and exposure-dependent acquisition of antibody responses to malaria antigens

3. To measure associations between antimalarial antibodies and protection from malaria.

Objectives of immunology studies
1. To perform detailed analyses of malaria-specific T cells using multiparameter flow cytometry, and examine the relationship between this response and malaria incidence, controlling for both age and exposure intensity measured at the level of individual households. We hypothesize that T cell correlates of protection can be identified after controlling for these confounding variables, and that biological age, independent of exposure history, is an important determinant of the development of T cell immunity to malaria.

2. To use whole genome expression profiling and multiplex cytokine analysis to identify age-based differences in the response to acute febrile malaria, and determine whether this acute-phase immune response predicts the magnitude, functional quality, and durability of the ensuing adaptive T cell response.

SURVEYS

The PRISM Surveys project conducts cross-sectional surveys in communities and primary schools twice a year for at least 2 years in the 3 different sites. The surveys will be timed to correspond to the high and low malaria transmission seasons, when possible. In the community surveys, 200 households will be recruited from a list randomly generated from a census database at each site. The community surveys will consist of three components: (1) a household survey targeting heads of households, (2) a women’s survey targeting all women of child-bearing age (15-49 years), and (3) clinical surveys of all children under fifteen years of age, and of one household member within the age category 15-24 years, 25-34 years, 35-44 years, 45-54 years, and > 55 years. The clinical surveys will include a fingerprick blood sample for measurement of hemoglobin, thick and thin blood smear, rapid diagnostic test (RDT) for malaria, and filter paper blood sample. The school surveys will be conducted in 3 randomly selected primary schools per site. A total of 100 randomly selected children will be recruited in each school. The school surveys will include only the clinical assessments including measurement of temperature, and a fingerprick blood sample for measurement of hemoglobin, thick and thin blood smear, RDT for malaria, and filter paper blood sample.

General objective:
To estimate indicators of malaria morbidity and coverage of key control interventions in three different epidemiological settings, to help identify optimal strategies for malaria surveillance in Uganda

Specific objectives:
1. To estimate the prevalence of malaria parasitemia and anemia in three different epidemiological settings

2. To compare estimates of the prevalence of malaria parasitemia and anemia as determined in school surveys with those estimated through ‘gold standard’ community surveys

3. To estimate the all-cause mortality rate in children under five in three different epidemiological settings

4. To estimate the malaria-specific mortality rate among children under five of years of age using verbal autopsy procedures in three different epidemiological settings

5. To determine coverage of key malaria control interventions (ITNs, IRS, IPTp and treatment with ACTs) in three different epidemiological settings

6. To measure associations between antimalarial antibodies and estimates of malaria parasite prevalence and anemia in school and community surveys

ENTOMOLOGY

The PRISM Entomology studies, propose to estimate malaria transmission intensity, as measured by EIR, using three different methodologies including human landing catches (the gold standard), CDC light traps, and pyrethrum spray catches combined with exit trap collections. The study will be conducted in three different study sites, all of which were included in the original survey conducted Okello and colleagues in Uganda (Tororo, Jinja, and Kanungu ). The study will provide important information about the degree of malaria transmission in Uganda, and whether it is as intense today. In addition, we aim to compare the alternative collection methods to the gold standard in the anticipation that one of these techniques can be used to estimate transmission effectively, allowing us to confine human-landing catches to the history books.

The information collected in this study will complement and support other studies which will describe the clinical pattern of infection and morbidity, as well as the level of antimalarial drug resistance in the parasite populations and insecticide resistance in local vector populations, in the same sites. The collection and integration of these diverse data sets will provide a robust characterisation of malaria in the study sites and establish an essential framework for developing future interventions against this disease.

This work will capture the intensity and variability of malaria transmission in the study sites and the distribution and nature of larval breeding sites. This information will also provide specimens for determining the level and nature of the susceptibility of mosquitoes to insecticides. In addition, it will also allow the team to develop mathematical models which describe the nature of malaria transmission in the study area and can be used for determining the most effective way in which to combine interventions against malaria in the future.

Study Objectives:
1. To estimate the malaria transmission intensity, as measured by the EIR, in the 3 study areas

2. To compare the relative ability of human landing catches, CDC light trap collections and pyrethrum spray collections and exit traps combined to measure human biting rates

3. To estimate the proportion of bites by malaria vectors which occur outdoors relative to those received indoors

4. To estimate R0 in the study sites by measuring the human-landing rate, proportion of blood-fed mosquitoes that have fed on people (human biting index) and mosquito population survival (parity rate)

5. To determine the distribution of larval breeding sites during the study

6. To collect mosquitoes for determination the susceptibility of malaria vectors to insecticides commonly used for malaria control