Back to resultsCHILD (Child Health and Infection With Low Density) Malaria
Primary Purpose
Malaria,Falciparum, Malaria
Status
Recruiting
Phase
Not Applicable
Locations
Tanzania
Study Type
Interventional
Intervention
Active case detection using molecular testing (ACDm)
Passive case detection using molecular testing (PCDm)
Control (standard of care)
Sponsored by
About this trial
This is an interventional prevention trial for Malaria,Falciparum focused on measuring malaria, child health, chronic infection, subclinical infection, patent infection, subpatent infection, active case detection, passive case detection, fever case management
Eligibility Criteria
Inclusion Criteria:
- 6 months to 10 years of age
- Residence in the study area
- Agree to come to study clinic for any illness
- Agree to avoid medications outside the study
Exclusion Criteria:
- Another child from household already randomly selected for recruitment
- Not able or refusal to provide informed consent
- Need for emergency intervention
- Antimalarial use within the last 28 days
- Known history of chronic illness including diabetes mellitus, cancer, or stage 3 or 4 HIV/AIDS (per WHO criteria)
- Contraindications to artemether-lumefantrine (AL) including history of allergic reaction, weight under 5 kg
- Participation in another active/ongoing intervention trial
Sites / Locations
- Kiwangwa and Fukayosi clinicsRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Active Case Detection using molecular testing (ACDm)
Passive Case Detection using molecular testing (PCDm)
Standard passive case detection (PCD)
Arm Description
Per standard of care, children will receive passive case detection (PCD) using rapid diagnostic test (RDT) if they present with fever. Children will receive malaria active case detection (ACD) using RDT and qPCR (quantitative polymerase chain reaction) three times yearly with treatment using artemether-lumefantrine (AL) if RDT or qPCR positive.
Children who present with fever will receive PCD using RDT and qPCR with treatment using AL if RDT or qPCR positive. Per standard of care, children will not receive malaria ACD.
Per standard of care, children will receive PCD using RDT. Per standard of care, children will not receive malaria ACD.
Outcomes
Primary Outcome Measures
Incidence of all-cause sick visits
Number of sick visits to health facility per person time, excluding planned admissions for medical care, elective surgery, and trauma.
Secondary Outcome Measures
Prevalence of anemia
Proportion of routine Hb measurements that are low (<11 g/dL) or moderate-severe low (<8 g/dL)
Prevalence of underweight status
Prevalence of underweight status will be defined as the percentage of participants with low weight for age z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.
Prevalence of stunting
Prevalence of stunting will be defined as the percentage of participants with low height for age z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.
Prevalence of wasting
Prevalence of wasting will be defined as the percentage of participants with low weight for height z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.
Prevalence of malnutrition
Prevalence of malnutrition will be defined as the percentage of participants with a z-score of -3 to -2 indicating moderate malnutrition or a z-score of less than -3 indicating severe malnutrition in any of the following: weight for age, height for age, or weight for height.
Prevalence of vomiting following administration of study drugs
Vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence.
All-cause fever episodes
Number of documented fever episodes (axillary temperature of ≥37.5°C) per person time and number of fever episodes (documented and reported) per person time
Incidence of clinical symptoms
Number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time
Incidence of clinical malaria
New episodes of positive malaria test (with fever or other clinical symptoms) per person time
Proportion of fever episodes with clinical failure
Proportion of fever episodes that lead to clinical failure, defined as persistent or worsening symptoms assessed 7 and 28 days after initial evaluation.
Prevalence of parasitemia
Proportion of routine samples with parasites detected by microscopy or quantitative polymerase chain reaction (qPCR).
Incidence in antibiotics prescribed
Number of antibiotic regimens prescribed per person time
Cognitive ability among children 0-3.4 years of age on the Global Scales of Early Development (GSED)
GSED is a validated instrument that measures population-level early childhood development. The tool measures children's early skills and behaviors in four primary domains: motor, cognitive, language, and social-emotional development.Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Cognitive ability among children 3.5-5 years of age on the International Development and Early Learning Assessment (IDELA)
The IDELA is a validated, global tool that uses direct child assessment to measure early learning and development across 4 core domains (Emergent Literacy, Emergent Numeracy, Motor, Social-emotional). Scores range from 0-100% as a percentage of correct tasks averaged across the 4 domains. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Cognitive ability among children 6-12 years of age on the East Africa Neurodevelopment Assessment Tool
The East African Neurodevelopment Assessment Tool is a locally adapted modification of the Kaufman Brief Intelligence Test 2nd Ed. The test assesses 3 core metrics including general intelligence, executive function, literacy skills - in addition to behavioral and emotional development. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Sustained attention among children 5-8 years of age on the Pencil Tapping Test
The pencil tapping test is one of the tasks in the Preschool Self-Regulation Assessment (PSRA) and is used to assess inhibitory control in younger children. The child and an assessor have pencils, and child is instructed to tap one/two times(s) depending on what assessor does, with the number of correct responses scored. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Sustained attention among children 9-12 years of age on the Code Transmission Test, a local adaptation of the Test of Everyday Attention for Children(TEA-Ch)
Code transmission test is a sub-test of Test of Everyday Attention for Children (TEA-Ch) used for assessment of sustained attention in children. In the test, the child must remember spoken digits, and remember the digit that comes before sequence of numbers. Child is scored on completed and correct answers. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Incidence of school absenteeism
The number of days of school absenteeism for any reason including illness.
School performance
School performance will be defined as the incidence of school advancement to the next grade.
Socioeconomic costs to participant
Estimated long-term income loss due to impaired early childhood development
Socioeconomic costs to family
Total caregiver-reported costs of sick visits and transport to sick visits plus estimated loss of income from number of days of caregiver work absenteeism.
Socioeconomic costs to health system
Estimated costs of testing and treatment for caregiver-reported number of sick visits.
Cost effectiveness
Cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.)
Prevalence of systemic inflammation
Proportion of sick visits with elevated elevated C-reactive pep-tide (CRP)
Proportion with antimalarial antibodies against P.falciparum
Percentage of patients with antimalarial antibodies
Proportion with biomarkers of inflammation
Percentage of patients with elevated cytokines
Proportion with general antibody responses to vaccines
Percentage of patients with vaccine antibodies
Proportion with general antibody responses to common pathogens
Percentage of patients with common pathogen antibodies
Incidence of adverse events (AEs)
Number of AEs per person time. AEs will be considered as any grade 3-4 AE or serious adverse event (SAE); individual AEs; or AEs related to study drugs.
Incidence of wasting
Incidence proportion of wasting will be defined for each age range of measurement. It is defined as the proportion of children not wasted at the start of the period who became wasted during the age period (the proportion of children who had the onset of new episodes during the period). Incident wasting episodes are defined as a change in weight-for-length z-scores from above -2 Z in the prior measurement to below -2 Z in the current measurement. We will define incident severe wasting analogously using a -3 Z cutoff. We will assume a 60-day washout period before a new wasting episode could occur.
Incidence of stunting
Incidence proportion of stunting will be defined for each age range of measurement. It is defined as the proportion of children not stunted at the start of the period who became stunted during the age period. Incident stunting episodes will be defined as a change in length-for-age z-scores from above -2 Z in the prior measurement to below -2 Z in the current measurement. We will define incident severe stunting analogously using a -3 Z cutoff.
Full Information
NCT ID
NCT05567016
First Posted
September 30, 2022
Last Updated
September 15, 2023
Sponsor
University of California, San Francisco
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Ifakara Health Institute, Swiss Tropical & Public Health Institute, Stanford University, Chan Zuckerberg Biohub
1. Study Identification
Unique Protocol Identification Number
NCT05567016
Brief Title
CHILD (Child Health and Infection With Low Density) Malaria
Official Title
Child Health and Infection With Low Density (CHILD) Malaria, a Randomized Controlled Trial to Assess the Long-term Health and Socioeconomic Impact of Interventions Targeting Low-density Malaria Infection (LMI) Among Children in Tanzania
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 18, 2023 (Actual)
Primary Completion Date
October 1, 2025 (Anticipated)
Study Completion Date
April 14, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Ifakara Health Institute, Swiss Tropical & Public Health Institute, Stanford University, Chan Zuckerberg Biohub
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This trial will assess the long-term health and socioeconomic impact of interventions targeting low-density malaria infection (LMI) among children in Tanzania
Detailed Description
This is a 3-arm open-label randomized control trial of 600 children aged 6 months to 10 years in Tanzania, where transmission is low and a high proportion of infections are low-density. Standard of care based on passive case detection (PCD) using rapid diagnostic test (control arm) will be compared to two different approaches to detect and treat P. falciparum LMI: active case detection using molecular testing (ACDm) and PCD using molecular testing (PCDm). Aims are:
To assess the impact of standard PCD plus ACDm vs standard PCD on long-term child health
To assess the impact of PCDm vs standard PCD on long-term child health
To evaluate the cost-effectiveness of ACDm and PCDm
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria,Falciparum, Malaria
Keywords
malaria, child health, chronic infection, subclinical infection, patent infection, subpatent infection, active case detection, passive case detection, fever case management
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Individual randomized controlled trial
Masking
None (Open Label)
Masking Description
This will be an open label randomized controlled trial. Participants and personnel administering the intervention will be unblinded. Assessment of the primary outcome will be unblinded. Assessment of several secondary outcomes will be blinded as feasible.
Allocation
Randomized
Enrollment
600 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Case Detection using molecular testing (ACDm)
Arm Type
Experimental
Arm Description
Per standard of care, children will receive passive case detection (PCD) using rapid diagnostic test (RDT) if they present with fever.
Children will receive malaria active case detection (ACD) using RDT and qPCR (quantitative polymerase chain reaction) three times yearly with treatment using artemether-lumefantrine (AL) if RDT or qPCR positive.
Arm Title
Passive Case Detection using molecular testing (PCDm)
Arm Type
Experimental
Arm Description
Children who present with fever will receive PCD using RDT and qPCR with treatment using AL if RDT or qPCR positive.
Per standard of care, children will not receive malaria ACD.
Arm Title
Standard passive case detection (PCD)
Arm Type
Active Comparator
Arm Description
Per standard of care, children will receive PCD using RDT.
Per standard of care, children will not receive malaria ACD.
Intervention Type
Other
Intervention Name(s)
Active case detection using molecular testing (ACDm)
Intervention Description
In the ACDm arm, children will receive ACD using RDT and qPCR 3x yearly with treatment using artemether-lumefantrine (AL) if RDT or qPCR positive. With fevers, participants will receive standard PCD using RDT.
Intervention Type
Other
Intervention Name(s)
Passive case detection using molecular testing (PCDm)
Intervention Description
With fevers, participants will receive PCDm, in which qPCR will be done in RDT negatives with treatment using AL if positive.
Intervention Type
Other
Intervention Name(s)
Control (standard of care)
Intervention Description
With fevers, participants will receive standard PCD using RDT with treatment using AL if positive.
Primary Outcome Measure Information:
Title
Incidence of all-cause sick visits
Description
Number of sick visits to health facility per person time, excluding planned admissions for medical care, elective surgery, and trauma.
Time Frame
24 months from enrollment
Secondary Outcome Measure Information:
Title
Prevalence of anemia
Description
Proportion of routine Hb measurements that are low (<11 g/dL) or moderate-severe low (<8 g/dL)
Time Frame
24 months from enrollment
Title
Prevalence of underweight status
Description
Prevalence of underweight status will be defined as the percentage of participants with low weight for age z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.
Time Frame
24 months from enrollment
Title
Prevalence of stunting
Description
Prevalence of stunting will be defined as the percentage of participants with low height for age z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.
Time Frame
24 months from enrollment
Title
Prevalence of wasting
Description
Prevalence of wasting will be defined as the percentage of participants with low weight for height z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.
Time Frame
24 months from enrollment
Title
Prevalence of malnutrition
Description
Prevalence of malnutrition will be defined as the percentage of participants with a z-score of -3 to -2 indicating moderate malnutrition or a z-score of less than -3 indicating severe malnutrition in any of the following: weight for age, height for age, or weight for height.
Time Frame
24 months from enrollment
Title
Prevalence of vomiting following administration of study drugs
Description
Vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence.
Time Frame
24 months from enrollment
Title
All-cause fever episodes
Description
Number of documented fever episodes (axillary temperature of ≥37.5°C) per person time and number of fever episodes (documented and reported) per person time
Time Frame
24 months from enrollment
Title
Incidence of clinical symptoms
Description
Number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time
Time Frame
24 months from enrollment
Title
Incidence of clinical malaria
Description
New episodes of positive malaria test (with fever or other clinical symptoms) per person time
Time Frame
24 months from enrollment
Title
Proportion of fever episodes with clinical failure
Description
Proportion of fever episodes that lead to clinical failure, defined as persistent or worsening symptoms assessed 7 and 28 days after initial evaluation.
Time Frame
24 months from enrollment
Title
Prevalence of parasitemia
Description
Proportion of routine samples with parasites detected by microscopy or quantitative polymerase chain reaction (qPCR).
Time Frame
24 months from enrollment
Title
Incidence in antibiotics prescribed
Description
Number of antibiotic regimens prescribed per person time
Time Frame
24 months from enrollment
Title
Cognitive ability among children 0-3.4 years of age on the Global Scales of Early Development (GSED)
Description
GSED is a validated instrument that measures population-level early childhood development. The tool measures children's early skills and behaviors in four primary domains: motor, cognitive, language, and social-emotional development.Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Time Frame
24 months from enrollment
Title
Cognitive ability among children 3.5-5 years of age on the International Development and Early Learning Assessment (IDELA)
Description
The IDELA is a validated, global tool that uses direct child assessment to measure early learning and development across 4 core domains (Emergent Literacy, Emergent Numeracy, Motor, Social-emotional). Scores range from 0-100% as a percentage of correct tasks averaged across the 4 domains. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Time Frame
24 months from enrollment
Title
Cognitive ability among children 6-12 years of age on the East Africa Neurodevelopment Assessment Tool
Description
The East African Neurodevelopment Assessment Tool is a locally adapted modification of the Kaufman Brief Intelligence Test 2nd Ed. The test assesses 3 core metrics including general intelligence, executive function, literacy skills - in addition to behavioral and emotional development. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Time Frame
24 months from enrollment
Title
Sustained attention among children 5-8 years of age on the Pencil Tapping Test
Description
The pencil tapping test is one of the tasks in the Preschool Self-Regulation Assessment (PSRA) and is used to assess inhibitory control in younger children. The child and an assessor have pencils, and child is instructed to tap one/two times(s) depending on what assessor does, with the number of correct responses scored. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Time Frame
24 months from enrollment
Title
Sustained attention among children 9-12 years of age on the Code Transmission Test, a local adaptation of the Test of Everyday Attention for Children(TEA-Ch)
Description
Code transmission test is a sub-test of Test of Everyday Attention for Children (TEA-Ch) used for assessment of sustained attention in children. In the test, the child must remember spoken digits, and remember the digit that comes before sequence of numbers. Child is scored on completed and correct answers. Measures will be normalized within our sample to mean 0 and standard deviation 1, with higher scores indicating better test performance.
Time Frame
24 months from enrollment
Title
Incidence of school absenteeism
Description
The number of days of school absenteeism for any reason including illness.
Time Frame
24 months from enrollment
Title
School performance
Description
School performance will be defined as the incidence of school advancement to the next grade.
Time Frame
24 months from enrollment
Title
Socioeconomic costs to participant
Description
Estimated long-term income loss due to impaired early childhood development
Time Frame
24 months from enrollment
Title
Socioeconomic costs to family
Description
Total caregiver-reported costs of sick visits and transport to sick visits plus estimated loss of income from number of days of caregiver work absenteeism.
Time Frame
24 months from enrollment
Title
Socioeconomic costs to health system
Description
Estimated costs of testing and treatment for caregiver-reported number of sick visits.
Time Frame
24 months from enrollment
Title
Cost effectiveness
Description
Cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.)
Time Frame
24 months from enrollment
Title
Prevalence of systemic inflammation
Description
Proportion of sick visits with elevated elevated C-reactive pep-tide (CRP)
Time Frame
24 months from enrollment
Title
Proportion with antimalarial antibodies against P.falciparum
Description
Percentage of patients with antimalarial antibodies
Time Frame
24 months from enrollment
Title
Proportion with biomarkers of inflammation
Description
Percentage of patients with elevated cytokines
Time Frame
24 months from enrollment
Title
Proportion with general antibody responses to vaccines
Description
Percentage of patients with vaccine antibodies
Time Frame
24 months from enrollment
Title
Proportion with general antibody responses to common pathogens
Description
Percentage of patients with common pathogen antibodies
Time Frame
24 months from enrollment
Title
Incidence of adverse events (AEs)
Description
Number of AEs per person time. AEs will be considered as any grade 3-4 AE or serious adverse event (SAE); individual AEs; or AEs related to study drugs.
Time Frame
24 months from enrollment
Title
Incidence of wasting
Description
Incidence proportion of wasting will be defined for each age range of measurement. It is defined as the proportion of children not wasted at the start of the period who became wasted during the age period (the proportion of children who had the onset of new episodes during the period). Incident wasting episodes are defined as a change in weight-for-length z-scores from above -2 Z in the prior measurement to below -2 Z in the current measurement. We will define incident severe wasting analogously using a -3 Z cutoff. We will assume a 60-day washout period before a new wasting episode could occur.
Time Frame
24 months from enrollment
Title
Incidence of stunting
Description
Incidence proportion of stunting will be defined for each age range of measurement. It is defined as the proportion of children not stunted at the start of the period who became stunted during the age period. Incident stunting episodes will be defined as a change in length-for-age z-scores from above -2 Z in the prior measurement to below -2 Z in the current measurement. We will define incident severe stunting analogously using a -3 Z cutoff.
Time Frame
24 months from enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
6 months to 10 years of age of age at enrollment
Primary residence in the study area during the study period
Agree to come to study clinic for any illness
Agree to avoid medications outside the study, even herbal medication
Exclusion Criteria:
Another child from household already randomly selected for recruitment
Not able or does not provide informed consent
Need for emergency intervention
Known history of chronic illness requiring regular specialty care including diabetes mellitus, cancer, or Stage 3 or 4 HIV/AIDS
Contraindications to artemether-lumefantrine (AL) including history of allergic reaction, weight under 5 kg
Participation in another active/ongoing intervention trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pamela Gangar, MD
Phone
415-476-2300
Email
pamela.gangar@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Michelle Hsiang, MD, MSc
Phone
415-476-2300
Email
michelle.hsiang@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michelle Hsiang, MD, MSc
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ally Olotu, MD, PhD
Organizational Affiliation
Ifakara Health Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kiwangwa and Fukayosi clinics
City
Bagamoyo
Country
Tanzania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ally Olotu, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
CHILD (Child Health and Infection With Low Density) Malaria
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