Trial Outcomes & Findings for A Surveillance Study of Diseases Specified as Adverse Events of Special Interest, of Other Adverse Events Leading to Hospitalisation or Death, and of Meningitis in Children in Africa Prior to Implementation of the RTS,S/AS01E Candidate Vaccine (NCT NCT02374450)

NCT ID: NCT02374450

Last Updated: 2024-09-19

Results Overview

AESI were a predefined list of adverse events historically associated with vaccines other than RTS,S/AS01E or potentially associated with RTS,S/AS01E. This was because the RTS,S/AS01E vaccine contained new components not present in widely used vaccines at the time.

• Recruitment status: COMPLETED
• Target enrollment: 36366 participants
• Primary outcome timeframe: During the entire study period (From Month 0 up to Month 79)
• Results posted on: 2024-09-19

Participant Flow

The first participant was enrolled on 05 October 2015 in Burkina Faso site (which have early terminated the study and participants were not analysed), on 26 January 2016 in KE_Kombewa, on 07 February 2016 in GH_Kintampo and on 27 May 2017 in GH_Navrongo. Therefore, 26 January 2016 was considered the start date for the analysis.

Out of the 36366 participants initially enrolled in the study, 12939 participants from the Burkina Faso site were excluded from the According-To-Protocol (ATP) cohort. Therefore, 23427 participants formed the ATP cohort in Ghana and Kenya.

Participant milestones

Measure	Active Surveillance 6-12 Weeks Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Overall Study STARTED	9032	9694	4701
Overall Study COMPLETED	8060	8534	4218
Overall Study NOT COMPLETED	972	1160	483

Reasons for withdrawal

Measure	Active Surveillance 6-12 Weeks Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Overall Study Protocol Violation	0	1	0
Overall Study Withdrawal by Subject	91	110	4
Overall Study Lost to Follow-up	168	194	138
Overall Study Death	173	185	81
Overall Study Migrated from the study area	538	648	181
Overall Study Enrollment in NCT03855995 study	0	1	0
Overall Study Vaccination with RTS,S/AS01E vaccine	2	0	0
Overall Study Other	0	21	79

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.	Total n=23427 Participants Total of all reporting groups
Age, Continuous	1.646 MONTHS STANDARD_DEVIATION 0.2895 • n=9032 Participants	7.130 MONTHS STANDARD_DEVIATION 5.1777 • n=9694 Participants	20.860 MONTHS STANDARD_DEVIATION 15.4136 • n=4701 Participants	7.771 MONTHS STANDARD_DEVIATION 10.3828 • n=23427 Participants
Sex: Female, Male Female	4476 Participants n=9032 Participants	4754 Participants n=9694 Participants	2089 Participants n=4701 Participants	11319 Participants n=23427 Participants
Sex: Female, Male Male	4556 Participants n=9032 Participants	4940 Participants n=9694 Participants	2612 Participants n=4701 Participants	12108 Participants n=23427 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the According-To-Protocol (ATP) cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

AESI were a predefined list of adverse events historically associated with vaccines other than RTS,S/AS01E or potentially associated with RTS,S/AS01E. This was because the RTS,S/AS01E vaccine contained new components not present in widely used vaccines at the time.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With at Least One Adverse Events of Specific Interest (AESI) From Month 0 to Month 79	12 Participants	11 Participants	16 Participants

PRIMARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

AEs assessed in children <5 years old, included in active or enhanced hospitalization surveillance, prior to implementation of RTS,S/AS01E.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With at Least One Adverse Event (AE) Leading to Hospitalization or Death From Month 0 to Month 79	1703 Participants	1763 Participants	4465 Participants

PRIMARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

Aetiology-confirmed meningitis was defined by the presence of symptoms and/or signs of meningitis and the identification of any known aetiologic agent (bacterial or not) in the Cerebrospinal Fluid (CSF).

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With at Least One Aetiology Confirmed Meningitis From Month 0 to Month 79	1 Participants	1 Participants	11 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

Final classification refers to the definitive categorization of meningitis cases after further investigation, typically involving additional laboratory testing and review by an external panel of experts. The criteria for final classification included:

Aetiology-Confirmed Meningitis, which was defined if any known aetiologic agent (bacterial or not) was identified in the CSF sample.

Probable Meningitis, which was defined if no aetiologic agent was identified in the CSF, but abnormalities were detected, or if there was a positive blood culture indicating bacterial infection.

Clinically Suspected Meningitis, which was defined if all laboratory results were normal after second line laboratory testing, or if no CSF sample was available but no alternative diagnosis was found based on clinical symptoms and signs.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With at Least One Confirmed Meningitis Case From Month 0 to Month 79 (Final Classification) Aetiology-confirmed and/or probable meningitis	2 Participants	2 Participants	15 Participants
Number of Participants With at Least One Confirmed Meningitis Case From Month 0 to Month 79 (Final Classification) Probable meningitis	1 Participants	1 Participants	4 Participants
Number of Participants With at Least One Confirmed Meningitis Case From Month 0 to Month 79 (Final Classification) Aetiology-confirmed, probable and/or clinically suspected meningitis	3 Participants	7 Participants	24 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

First Line Laboratory refers to the initial laboratory testing conducted on cerebrospinal fluid (CSF) samples taken from patients suspected of having meningitis. The purpose of first line laboratory testing was to identify any bacterial agents present in the CSF or detect abnormalities that may indicate meningitis. The criteria for classifying cases at this stage included:

Bacterial Confirmed Meningitis which was defined if a bacterial agent was identified in the CSF sample.

Probable Meningitis which was defined if no bacterial agent was identified, but abnormalities were detected in the CSF or if there was a positive blood culture indicating bacterial infection.

Clinically Suspected Meningitis which was defined if no bacterial agent was identified and all laboratory results were normal at the first line level, or if no CSF sample was available but no alternative diagnosis was found based on clinical symptoms and signs.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With at Least One Confirmed Meningitis Case Identified at Site Level From Month 0 to Month 79 (First Line Laboratory) Bacterial confirmed meningitis	0 Participants	1 Participants	3 Participants
Number of Participants With at Least One Confirmed Meningitis Case Identified at Site Level From Month 0 to Month 79 (First Line Laboratory) Probable meningitis	5 Participants	5 Participants	23 Participants
Number of Participants With at Least One Confirmed Meningitis Case Identified at Site Level From Month 0 to Month 79 (First Line Laboratory) Clinically suspected meningitis	4 Participants	8 Participants	13 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was planned to perform on ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with enrollment procedures defined in protocol, and had no elimination criteria during study. As per analysis plan, Poisson regression models for analyzing potential risk factors for AESI, aetiology-confirmed meningitis, cerebral malaria, and death were only planned if there were at least 10 cases. Since the case count was below 10, no analysis was conducted.

As per Statistical analysis plan, Univariate and multivariate Poisson regression models for analysis of potential risk factors for AESI, aetiology-confirmed meningitis and cerebral malaria were only planned to be conducted if there were a minimum of 10 cases.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With Risk Factors for AESI, Meningitis and Malaria Among Hospitalized Participants	NA Participants As per Statistical analysis plan, Univariate and multivariate Poisson regression models for analysis of potential risk factors for AESI, aetiology-confirmed meningitis, cerebral malaria and death were only planned to be conducted if there were a minimum of 10 cases. Since the number of cases were less than 10, analysis was not performed.	NA Participants As per Statistical analysis plan, Univariate and multivariate Poisson regression models for analysis of potential risk factors for AESI, aetiology-confirmed meningitis, cerebral malaria and death were only planned to be conducted if there were a minimum of 10 cases. Since the number of cases were less than 10, analysis was not performed.	NA Participants As per Statistical analysis plan, Univariate and multivariate Poisson regression models for analysis of potential risk factors for AESI, aetiology-confirmed meningitis, cerebral malaria and death were only planned to be conducted if there were a minimum of 10 cases. Since the number of cases were less than 10, analysis was not performed.

SECONDARY outcome

Timeframe: Day 31 to approximately Month 13 (Within an at-risk period of 12 months after virtual secondary schedule)

Population: The analysis was performed only on the participants from the Active surveillance 6-12 weeks and Active surveillance 5-17 months groups, as only they received a secondary dose of DTP/HepB/Hib administered at Day 31. The participants belonged to the ATP cohort, met all eligibility criteria, complied with the enrollment procedures defined in the protocol and had no elimination criteria during the study.

Incidence rate was calculated by dividing the number of participants reporting at least one event over the follow-up period by the total person-time. Analysis of this outcome measure were reported only for the Active surveillance 6-12 weeks and Active surveillance 5-17 months groups, as the participants in the Enhanced hospitalization surveillance group were not administered with the DTP/HepB/Hib vaccine.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=8871 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9339 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Incidence Rates of Death After the Virtual Secondary Schedule (Secondary Dose of DTP/HepB/Hib Administered at Day 31) for the Active Surveillance 6-12 Weeks and Active Surveillance 5-17 Weeks Groups	677.42 events per 100,000 person-years Interval 560.72 to 811.25	642.97 events per 100,000 person-years Interval 531.3 to 771.18	—

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

Hospitalized cases attributed to an AESI, other AE, meningitis, or malaria were assessed in children <5 years old, included in active or enhanced hospitalization surveillance, prior to implementation of RTS,S/AS01E.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants Hospitalized With Causes (Including Those Attributed to an AESI, Other AE, Meningitis, or Malaria) From Month 0 to Month 79 Hospitalization - AESI	12 Participants	11 Participants	16 Participants
Number of Participants Hospitalized With Causes (Including Those Attributed to an AESI, Other AE, Meningitis, or Malaria) From Month 0 to Month 79 Hospitalization - Other AE	1703 Participants	1763 Participants	4465 Participants
Number of Participants Hospitalized With Causes (Including Those Attributed to an AESI, Other AE, Meningitis, or Malaria) From Month 0 to Month 79 Hospitalization - Meningitis	3 Participants	7 Participants	24 Participants
Number of Participants Hospitalized With Causes (Including Those Attributed to an AESI, Other AE, Meningitis, or Malaria) From Month 0 to Month 79 Hospitalization - Malaria	1013 Participants	1224 Participants	2458 Participants
Number of Participants Hospitalized With Causes (Including Those Attributed to an AESI, Other AE, Meningitis, or Malaria) From Month 0 to Month 79 Hospitalization - P. falciparum	1007 Participants	1218 Participants	2068 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

Mortality events were assessed in children <5 years old, included in active or enhanced hospitalization surveillance, prior to implementation of RTS,S/AS01E.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants Reported Deaths From Month 0 to Month 79	173 Participants	183 Participants	80 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

Any malaria includes uncomplicated and severe cases, including cerebral malaria. Uncomplicated is defined as: Plasmodium parasitaemia greater than (>) 0 detected by microscopy and/or RDT, fever (temperature ≥ 37.5°C) and no signs of severity or evidence (clinical or laboratory) of vital organ dysfunction. Severe is defined as: P. falciparum parasitaemia > 0 detected by microscopy and/or RDT and one or more of the following: impaired consciousness, prostration, multiple convulsions, acidosis, hypoglycaemia, severe malarial anaemia, renal impairment, jaundice, pulmonary oedema, significant bleeding, shock, hyperparasitaemia. Cerebral malaria is defined as severe P. falciparum malaria with impaired consciousness.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With Malaria Cases Reported Using Rapid Diagnostic Test (RDT) and/or Microscopy From Month 0 to Month 79 Cerebral Malaria cases	8 Participants	9 Participants	20 Participants
Number of Participants With Malaria Cases Reported Using Rapid Diagnostic Test (RDT) and/or Microscopy From Month 0 to Month 79 Any Malaria	5072 Participants	5714 Participants	2458 Participants
Number of Participants With Malaria Cases Reported Using Rapid Diagnostic Test (RDT) and/or Microscopy From Month 0 to Month 79 Severe Malaria	202 Participants	247 Participants	550 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

Cases of anaemia were defined as follow: All anaemia: haemoglobin lower than 11grams per deciliter (g/dL). Severe anaemia: haemoglobin lower than 7g/dL .

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With All Anaemia and Severe Anaemia Cases Among Hospitalized Children From Month 0 to Month 79 All anaemia	1132 Participants	1215 Participants	2783 Participants
Number of Participants With All Anaemia and Severe Anaemia Cases Among Hospitalized Children From Month 0 to Month 79 Severe anaemia	254 Participants	338 Participants	758 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

The hospitalization cases were assessed in children <5 years old, included in active surveillance, prior to implementation of RTS,S/AS01E. Hospitalisation for malaria (including P. falciparum) was defined as a hospitalized participants with malaria (including P. falciparum malaria) and for whom malaria is the primary cause of hospitalization.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants With All Cause Hospitalizations and Hospitalizations Attributed to Malaria (Including P. Falciparum) From Month 0 to Month 79 Hospitalisation - All causes	1788 Participants	1907 Participants	4701 Participants
Number of Participants With All Cause Hospitalizations and Hospitalizations Attributed to Malaria (Including P. Falciparum) From Month 0 to Month 79 Hospitalisation - P. falciparum	1007 Participants	1218 Participants	2441 Participants

SECONDARY outcome

Timeframe: During the entire study period (From Month 0 up to Month 79)

Population: The analysis was performed on the ATP cohort, which included all evaluable participants who met all eligibility criteria, complied with the enrollment procedures defined in the protocol, and had no elimination criteria during the study.

All cause mortality and death attributed to malaria are summarized by overall and gender.

Outcome measures

Measure	Active Surveillance 6-12 Weeks n=9032 Participants Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.	Active Surveillance 5-17 Months n=9694 Participants Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.	Enhanced Hospitalization Surveillance n=4701 Participants All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.
Number of Participants Reported All-cause Mortality and Deaths Attributed to Malaria (Overall and by Gender) From Month 0 to Month 79 Death- All cause(Male)	81 Participants	105 Participants	49 Participants
Number of Participants Reported All-cause Mortality and Deaths Attributed to Malaria (Overall and by Gender) From Month 0 to Month 79 Death- All cause(Female)	92 Participants	78 Participants	31 Participants
Number of Participants Reported All-cause Mortality and Deaths Attributed to Malaria (Overall and by Gender) From Month 0 to Month 79 Death(Overall)	173 Participants	183 Participants	80 Participants
Number of Participants Reported All-cause Mortality and Deaths Attributed to Malaria (Overall and by Gender) From Month 0 to Month 79 Death - Malaria(Male)	18 Participants	34 Participants	0 Participants
Number of Participants Reported All-cause Mortality and Deaths Attributed to Malaria (Overall and by Gender) From Month 0 to Month 79 Death - Malaria(Female)	24 Participants	21 Participants	1 Participants
Number of Participants Reported All-cause Mortality and Deaths Attributed to Malaria (Overall and by Gender) From Month 0 to Month 79 Death - Malaria(Overall)	42 Participants	55 Participants	1 Participants

Adverse Events

Active Surveillance 6-12 Weeks

Serious events: 0 serious events

Other events: 0 other events

Deaths: 173 deaths

Active Surveillance 5-17 Months

Serious events: 0 serious events

Other events: 0 other events

Deaths: 183 deaths

Enhanced Hospitalization Surveillance

Serious events: 0 serious events

Other events: 0 other events

Deaths: 80 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinic.
• Publication restrictions are in place

Restriction type: OTHER