CHILD (Child Health and Infection With Low Density) Malaria

Not Applicable

Active, not recruiting

• Conditions: Malaria,Falciparum; Malaria
• Interventions: Other: Active case detection using molecular testing (ACDm); Other: Control (standard of care); Other: Passive case detection using molecular testing (PCDm)

• Registration Number: NCT05567016
• Lead Sponsor: University of California, San Francisco

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:

1. To assess the impact of standard PCD plus ACDm vs standard PCD on long-term child health

2. To assess the impact of PCDm vs standard PCD on long-term child health

3. To evaluate the cost-effectiveness of ACDm and PCDm

Study Timeline

• Study First Submitted: 2022-09-30
• Study First Submitted QC: 2022-09-30
• Study First Posted: 2022-10-05
• Study Start: 2023-07-18
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-03
• Primary Completion: 2025-11-28
• Study Completion: 2025-11-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. 6 months to 10 years of age of age at enrollment
2. Primary residence in the study area during the study period
3. Agree to come to study clinic for any illness
4. Agree to avoid medications outside the study, even herbal medication

Exclusion Criteria

1. Another child from household already randomly selected for recruitment
2. Not able or does not provide informed consent
3. Need for emergency intervention
4. Known history of chronic illness requiring regular specialty care including diabetes mellitus, cancer, or Stage 3 or 4 HIV/AIDS
5. Contraindications to artemether-lumefantrine (AL) including history of allergic reaction, weight under 5 kg
6. Participation in another active/ongoing intervention trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Case Detection using molecular testing (ACDm)	Active case detection using molecular testing (ACDm)	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.
Standard passive case detection (PCD)	Control (standard of care)	Per standard of care, children will receive PCD using RDT. Per standard of care, children will not receive malaria ACD.
Passive Case Detection using molecular testing (PCDm)	Passive case detection using molecular testing (PCDm)	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.

Primary Outcome Measures

Name	Time	Method
Incidence of all-cause sick visits	24 months from enrollment	Number of sick visits to health facility per person time, excluding planned admissions for medical care, elective surgery, and trauma.

Secondary Outcome Measures

Name	Time	Method
Proportion with antimalarial antibodies against P.falciparum	24 months from enrollment	Percentage of patients with antimalarial antibodies
Proportion with biomarkers of inflammation	24 months from enrollment	Percentage of patients with elevated cytokines
Proportion with general antibody responses to vaccines	24 months from enrollment	Percentage of patients with vaccine antibodies
Proportion with general antibody responses to common pathogens	24 months from enrollment	Percentage of patients with common pathogen antibodies
Prevalence of anemia	24 months from enrollment	Proportion of routine Hb measurements that are low (\<11 g/dL) or moderate-severe low (\<8 g/dL)
Prevalence of underweight status	24 months from enrollment	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	24 months from enrollment	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	24 months from enrollment	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	24 months from enrollment	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	24 months from enrollment	Vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence.
All-cause fever episodes	24 months from enrollment	Number of fever episodes (reported fever in the past 48hrs and/or axillary temperature of ≥37.5°C) per person time
Incidence of clinical symptoms	24 months from enrollment	Number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time
Incidence of clinical malaria	24 months from enrollment	New episodes of positive malaria test (with fever or other clinical symptoms) per person time
Proportion of fever episodes with clinical failure	24 months from enrollment	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	24 months from enrollment	Proportion of routine samples with parasites detected by microscopy or quantitative polymerase chain reaction (qPCR).
Incidence in antibiotics prescribed	24 months from enrollment	Number of antibiotic regimens prescribed per person time
Prevalence of systemic inflammation	24 months from enrollment	Proportion of sick visits with elevated elevated C-reactive pep-tide (CRP)
Cognitive ability among children 0-3.4 years of age on the Global Scales of Early Development (GSED)	24 months from enrollment	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)	24 months from enrollment	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	24 months from enrollment	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	24 months from enrollment	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)	24 months from enrollment	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	24 months from enrollment	The number of days of school absenteeism for any reason including illness.
School performance	24 months from enrollment	School performance will be defined as the incidence of school advancement to the next grade.
Socioeconomic costs to participant	24 months from enrollment	Estimated long-term income loss due to impaired early childhood development
Socioeconomic costs to family	24 months from enrollment	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	24 months from enrollment	Estimated costs of testing and treatment for caregiver-reported number of sick visits.
Cost effectiveness	24 months from enrollment	Cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.)
Incidence of adverse events (AEs)	24 months from enrollment	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	24 months from enrollment	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	24 months from enrollment	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.

Trial Locations

Locations (1)

Kiwangwa and Fukayosi clinics; 🇹🇿 Bagamoyo, Tanzania