This trial will assess the long-term health and socioeconomic impact of interventions targeting low-density malaria infection (LMI) among children in Tanzania
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
600
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.
With fevers, participants will receive PCDm, in which qPCR will be done in RDT negatives with treatment using AL if positive.
With fevers, participants will receive standard PCD using RDT with treatment using AL if positive.
Kiwangwa and Fukayosi clinics
Bagamoyo, Tanzania
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.
Time frame: 24-30 months from enrollment
Prevalence of anemia
Proportion of routine Hb measurements that are low (\<11 g/dL) or moderate-severe low (\<8 g/dL)
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
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Time frame: 24-30 months from enrollment
Prevalence of vomiting following administration of study drugs
Vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence.
Time frame: 24-30 months from enrollment
All-cause fever episodes
Number of fever episodes (reported fever in the past 48hrs and/or axillary temperature of ≥37.5°C) per person time
Time frame: 24-30 months from enrollment
Incidence of clinical symptoms
Number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time
Time frame: 24-30 months from enrollment
Incidence of clinical malaria
New episodes of positive malaria test (with fever or other clinical symptoms) per person time
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
Prevalence of parasitemia
Proportion of routine samples with parasites detected by microscopy or quantitative polymerase chain reaction (qPCR).
Time frame: 24-30 months from enrollment
Incidence in antibiotics prescribed
Number of antibiotic regimens prescribed per person time
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
Incidence of school absenteeism
The number of days of school absenteeism for any reason including illness.
Time frame: 24-30 months from enrollment
School performance
School performance will be defined as the incidence of school advancement to the next grade.
Time frame: 24-30 months from enrollment
Socioeconomic costs to participant
Estimated long-term income loss due to impaired early childhood development
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
Socioeconomic costs to health system
Estimated costs of testing and treatment for caregiver-reported number of sick visits.
Time frame: 24-30 months from enrollment
Cost effectiveness
Cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.)
Time frame: 24-30 months from enrollment
Prevalence of systemic inflammation
Proportion of sick visits with elevated elevated C-reactive pep-tide (CRP)
Time frame: 24-30 months from enrollment
Proportion with antimalarial antibodies against P.falciparum
Percentage of patients with antimalarial antibodies
Time frame: 24-30 months from enrollment
Proportion with biomarkers of inflammation
Percentage of patients with elevated cytokines
Time frame: 24-30 months from enrollment
Proportion with general antibody responses to vaccines
Percentage of patients with vaccine antibodies
Time frame: 24-30 months from enrollment
Proportion with general antibody responses to common pathogens
Percentage of patients with common pathogen antibodies
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment
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.
Time frame: 24-30 months from enrollment