A Community Setting Study of Malaria After Systematic Treatment of Symptomatic Carriers of P. Falciparum With COA566 (Coartem®)

Data is presented per cluster. Change in hemoglobin levels from day 1 to day 28 was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each asymptomatic carrier from Community Screening Campaign 1 (CSC1), \> 6 months of age, at day 1 and at day 28.

Time frame: Day 1 and day 28 of period 1

Population: The number of units represents the number of clusters that include all randomized, \> 6 months of age participants for which CSC1 was conducted, data was available and census data were obtained as per protocol.

Data is presented per cluster. Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000s) per person-year in infants and children (\<5 years) in post Community Screening Campaign (CSC) at month 12 was detected by Rapid Diagnostic Test (RDT) (using a blood sample from each participant) and later confirmed to have a parasite density ≥5000/uL by microscopy. Number of SMRC5000: sum of all SMRC5000 for all infants and children (\<5 years) in post CSC. Person-year observed: sum of duration (in days) for all infants and children (\<5 years) in post CSC present in study /365.25. Number of SMRC5000 per person-year = number of SMRC5000/person-year observed.

Time frame: Month 12 of period 1

Population: The number of units represents the number of clusters that include all randomized infants and children (\<5 years) for which CSCs 1, 2, and 3 were conducted, data was available, and census data were obtained as per protocol.

Anemia status based on Community Screening Campaign 1 (CSC1)/Day 1 in infants and children (\>6 months and \<5 years) was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) \<5 g/dL = severe anemia, Hb 5 to \<8 g/dL = moderate anemia, Hb 8 to \<11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia).

Time frame: Day 1 (CSC1/day 1) - period 1

Population: Individual subject data from eligible clusters set defined as all infants and children (\>6 months and \<5 years) randomized for which CSC1 was conducted, data was available, and census data were obtained as per protocol.

Anemia status based on Community Screening Campaign 4 (CSC4/Day 1) in infants and children (\>6 months and \<5 years) was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) \<5 g/dL = severe anemia, Hb 5 to \<8 g/dL = moderate anemia, Hb 8 to \<11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia).

Time frame: Month 12 (CSC4/day 1) - period 1

Population: Individual subject data from eligible clusters set defined as all infants and children (\>6 months and \<5 years) randomized for which CSC4 was conducted, data was available, and census data was obtained as per protocol.

Data is presented per cluster. Comparison of hemoglobin level (g/dL) from Community Screening Campaign 1 (CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 in infants and children (\>6 months and \<5 years) by study arm was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant.

Time frame: Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1

Population: The number of units represents the number of clusters that include all infants and children (\>6 months and \<5 years) randomized participants for which CSCs 1 and 4 were conducted, data was available, and census data were obtained as per protocol.

Change in hemoglobin level (g/dL) from Community Screening Campaign 1 (CSC1)/Day 1 to CSC1/Day 28 in infants and children (\>6 Months and \<5 Years) for asymptomatic carriers at CSC1 was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) \<5 g/dL = severe anemia, Hb 5 to \<8 g/dL = moderate anemia, Hb 8 to \<11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia).

Time frame: Day 1 and day 28 - period 1

Population: Individual subject data from eligible clusters set defined as all infants and children (\>6 months and \<5 years) randomized for which CSC1 was conducted, data was available, and census data were obtained as per protocol.

Cumulative number of asymptomatic carriers having Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) from Week 1 to Week 50, was measured from group of participants diagnosed as asymptomatic carriers at Community Screening Campaign (CSC1)/Day1. Number of participants affected before and after diagnosed with ≥1 symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) (complicated and uncomplicated episodes combined). Number of SMRC5000s was detected by Rapid Diagnostic Test (RDT) using a blood sample from each participant and later confirmed to have a parasite density \> or = 5000/uL by microscopy. Week (1-2) indicates day1 to day14, week (3-4) indicates day 15 to day 28, week (5-6) indicates day 29 to day 42, etc. After first diagnosis of asymptomatic carriers at CSC1/Day1.

Time frame: Week 1 to Week 50

Population: Individual subject data from eligible randomized participants from Community Screening Campaign 1 (CSC1) for which data on Symptomatic malaria episode, RDT-confirmed (SMRCs) was collected and available form analysis and census data was obtained as per protocol.

Data is presented per cluster. Hemoglobin levels at Community Screening Campaign 1 and 4 (CSC1 and CSC4) on day 1 per age group (5-9 years, 10-14 years, and ≥15 years) in the intervention versus the control arm was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant.

Time frame: Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1

Population: The number of units represents the number of clusters that include all randomized participants (ages 5-9 years, 10-14 years, and ≥15 years) clusters for which CSC1 and CSC4 was conducted, data was available, and census data were obtained as per protocol.

Data is presented per cluster. Mean number of gametocyte carriers at Day 1 for Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) was measured using gametocyte assessments (prevalence and density) via microscopy. Mean measured in this analysis is the mean percent indicating the mean of percentages of cluster frequencies under the study arm for that particular category.

Time frame: 12 months - period 1

Population: Eligible clusters set consisted of all randomized participants for which CSCs 1, 2, 3 and 4 were conducted, data was available, and census data were obtained as per protocol.

Data is presented per cluster. Mean number of asymptomatic carriers from Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) was measured by confirmed positive microscopy for P. falciparum asexual forms in participants with absence of clinical signs and symptoms of malaria. Mean measured in this analysis is the mean percent indicting the mean of percentages of cluster frequencies under the study arm for that particular category.

Time frame: 12 months - period 1

Population: The number of units represents the number of clusters that include all randomized participants for which CSC 1, 2 3 and 4 was conducted, data was available, and census data were obtained as per protocol.

Data is presented per cluster. Microscopy confirmation of asymptomatic carriers of P. falciparum at Community Screening Campaign 4 (CSC4) was conducted at month 12. Blood films were histologically treated and examined microscopically. When it was ascertained that P. falciparum was present, a count of the asexual forms against leukocytes was made using a tally counter.

Time frame: Month 12 - period 1

Population: The number of units represents the number of clusters that include all randomized participants for which CSC4 was conducted, data was available, and census data was obtained as per protocol.

Data is presented per cluster. Microscopy confirmed gametocyte carriers at Community Screening Campaign 4(CSC4) were assessed via microscopy at month 12 of period 1. Blood films were histologically treated and examined microscopically.

Time frame: Month 12 - period 1

Population: The number of units represents the number of clusters that include all randomized participants for which CSC4 was conducted, data was available, and census data were obtained as per protocol.

Number of asymptomatic carriers diagnosed with 1 Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000), 2 SMRC5000, 3 SMRC5000 and \>3 SMRC5000 (complicated and uncomplicated episodes combined). Number of SMRC5000s is measured by Rapid diagnostic test (RDT) and later confirmed to have a parasite density ≥ 5000/uL by microscopy.

Time frame: 12 months - period 1

Population: Individual subject data from eligible clusters set defined as all participants randomized for which data on Symptomatic malaria episode, RDT-confirmed (SMRCs) was collected and census data was obtained as per protocol.

Individual data of number of asymptomatic carriers with increase in hemoglobin levels by at least 0.5 g/dL from Day 1 to Day 28 from Community Screening Campaign 1 (CSC1) infants and children (\>6 months and \<5 years). Hemoglobin levels were measured using the HemoCue® rapid test. This test was performed with a drop of blood collected from the fingertip at Day 1 and at Day 28.

Time frame: Day 1 to Day 28- period 1

Population: Individual subject data from eligible clusters set defined as all infants and children (\>6 months and \<5 years) randomized for which CSC1 was conducted, data was available, and census data was obtained as per protocol.

Data is presented per cluster. Cluster data of number of asymptomatic carriers with increase in hemoglobin levels by at least 0.5 g/dL from Day 1 to Day 28 of Community Screening Campaign 1 (CSC1) in infants and children (\>6 months and \<5 years) was measured by Hemoglobin levels based on microscopy reading. Mean and Standard Deviation (SD) percent were measured indicating the mean and SD of percentages of cluster frequencies under the study arm for that particular category.

Time frame: Day 1 to day 28 - period 1

Population: The number of units represents the number of clusters that include all infants and children (\>6 months and \<5 years) randomized for which CSC1 was conducted, data was available, and census data were obtained as per protocol.

Number of gametocyte carriers at Community Screening Campaign 4 (CSC4) was measured via microscopy and confirmed using Quantitative Reverse Transcription PCR (qRT-PCR) at day 1 of CSC4.

Time frame: Month 12 (CSC4/day 1) - period 1

Population: Individual subject data from eligible clusters set defined as all randomized participants for which CSC4 was conducted, data was available, and census data was obtained as per protocol.

Total number of participants (infants and children (\> 6 months and \< 5 years)) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed.

Time frame: 12 months - period 1

Population: Safety analyzable carriers set consisted of all infants and children (\> 6 months and \< 5 years)) from intervention clusters confirmed positive for P. falciparum asexual forms at any CSC or when migrating into the cluster, who in the absence of clinical signs and symptoms received at least one dose of COA566 for the diagnosed asymptomatic infection.

Total number of participants (all ages) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed.

Time frame: 12 months - period 1

Population: Safety analyzable asymptomatic carriers set consisted of all consenting inhabitants from intervention clusters confirmed positive by RDT for P. falciparum asexual forms at any CSC or when migrating into the cluster, in the absence of clinical signs and symptoms who received at least one dose of COA566 to treat the diagnosed asymptomatic infection.

Data is presented per cluster. Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) in asymptomatic carriers by study arm from all inhabitants diagnosed at any time for asymptomatic carriers. Number of SMRC5000s is measured by Rapid diagnostic test (RDT) and later confirmed to have a parasite density ≥ 5000/uL by microscopy.

Time frame: 12 months - period 1

Population: The number of units represents the number of clusters that include all participants randomized for which data on Symptomatic malaria episode, RDT-confirmed (SMRCs) were collected and census data were obtained as per protocol.

Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000s) per person-year in post Community Screening Campaign (CSC), by study arm (individual level data) was detected by Rapid Diagnostic Test (RDT) (using a blood sample from each participant) and later confirmed to have a parasite density ≥5000/uL by microscopy. Number of SMRC5000: sum of all SMRC5000 for all subjects in post CSC. Person-year observed: sum of duration (in days) in post CSC for all subjects present in study /365.25. Number of SMRC5000 per person-year = number of SMRC5000/person-year observed.

Time frame: 12 months - period 1

Population: Individual subject data from eligible clusters set defined as all randomized participants for which CSCs 1, 2, 3 and 4 were conducted, data was available, and census data were obtained as per protocol.

Percentage of participants with parasitological cure confirmed via microscopy at day 7 after treatment with COA566. This assessment was done on asymptomatic carriers from Community Screening Campaigns 1, 2 and 3 (CSC1, CSC2 and CSC3) from the intervention group only.

Time frame: Day 7 of CSC1, CSC2 and CSC3 - period 1

Population: Treated asymptomatic carriers from CSC1, CSC2 and CSC3 confirmed by microscopy and treated with study medication. Subjects are counted multiple times if diagnosed and treated more than once during the study. Subjects missing day 7 parasitemia data are excluded. Percentages are based on the number of subjects treated with any formulation.

Percentage of microscopy-confirmed gametocyte asymptomatic carriers treated with COA566 for asymptomatic carriers in Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3).

Time frame: Day 1, day 7 and day 28 - period 1

Population: Treated asymptomatic carriers from CSC1, CSC2 and CSC3 confirmed by microscopy and treated with study medication. Subjects are counted multiple times if diagnosed and treated more than once during the study. Subjects missing day 7 parasitemia data are excluded. Percentages are based on the number of subjects treated with any formulation.