Malaria, Malaria,Falciparum
Conditions
Keywords
malaria, child health, chronic infection, subclinical infection, patent infection, subpatent infection, active case detection, passive case detection, fever case management
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
Interventions
OTHERActive case detection using molecular testing (ACDm)
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.
OTHERPassive case detection using molecular testing (PCDm)
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.
Sponsors
University of California, San Francisco
National Institute of Allergy and Infectious Diseases (NIAID)
Ifakara Health Institute
Swiss Tropical & Public Health Institute
Stanford University
Chan Zuckerberg Biohub
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
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.
Intervention model description
Individual randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
6 Months to 10 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of all-cause sick visits | 24-30 months from enrollment | Number of sick visits to health facility per person time, excluding planned admissions for medical care, elective surgery, and trauma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Socioeconomic costs to family | 24-30 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 | 24-30 months from enrollment | Estimated costs of testing and treatment for caregiver-reported number of sick visits. |
| Prevalence of anemia | 24-30 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 | 24-30 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 | 24-30 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 | 24-30 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 | 24-30 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 | 24-30 months from enrollment | Vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence. |
| All-cause fever episodes | 24-30 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 | 24-30 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 | 24-30 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 | 24-30 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 | 24-30 months from enrollment | Proportion of routine samples with parasites detected by microscopy or quantitative polymerase chain reaction (qPCR). |
| Incidence in antibiotics prescribed | 24-30 months from enrollment | 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) | 24-30 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) | 24-30 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 | 24-30 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 | 24-30 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) | 24-30 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 | 24-30 months from enrollment | The number of days of school absenteeism for any reason including illness. |
| School performance | 24-30 months from enrollment | School performance will be defined as the incidence of school advancement to the next grade. |
| Cost effectiveness | 24-30 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.) |
| Prevalence of systemic inflammation | 24-30 months from enrollment | Proportion of sick visits with elevated elevated C-reactive pep-tide (CRP) |
| Proportion with antimalarial antibodies against P.falciparum | 24-30 months from enrollment | Percentage of patients with antimalarial antibodies |
| Proportion with biomarkers of inflammation | 24-30 months from enrollment | Percentage of patients with elevated cytokines |
| Proportion with general antibody responses to vaccines | 24-30 months from enrollment | Percentage of patients with vaccine antibodies |
| Proportion with general antibody responses to common pathogens | 24-30 months from enrollment | Percentage of patients with common pathogen antibodies |
| Incidence of adverse events (AEs) | 24-30 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 | 24-30 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. |
| Socioeconomic costs to participant | 24-30 months from enrollment | Estimated long-term income loss due to impaired early childhood development |
| Incidence of stunting | 24-30 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. |
Countries
Tanzania
Contacts
PRINCIPAL_INVESTIGATORMichelle Hsiang, MD, MSc
University of California, San Francisco
PRINCIPAL_INVESTIGATORAlly Olotu, MD, PhD
Ifakara Health Institute
Outcome results
None listed