CHILD (Child Health and Infection With Low Density) Malaria

Proportion of routine Hb measurements that are low (<11 g/dL) or moderate-severe low (<8 g/dL)

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 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 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 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.

Vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence.

Number of fever episodes (reported fever in the past 48hrs and/or axillary temperature of ≥37.5°C) per person time

Number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time

New episodes of positive malaria test (with fever or other clinical symptoms) per person time

Proportion of fever episodes that lead to clinical failure, defined as persistent or worsening symptoms assessed 7 and 28 days after initial evaluation.

Proportion of routine samples with parasites detected by microscopy or quantitative polymerase chain reaction (qPCR).

Number of antibiotic regimens prescribed per person time

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.

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.

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.

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.

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.

The number of days of school absenteeism for any reason including illness.

School performance will be defined as the incidence of school advancement to the next grade.

Estimated long-term income loss due to impaired early childhood development

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.

Estimated costs of testing and treatment for caregiver-reported number of sick visits.

Cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.)

Proportion of sick visits with elevated elevated C-reactive pep-tide (CRP)

Percentage of patients with antimalarial antibodies

Percentage of patients with elevated cytokines

Percentage of patients with vaccine antibodies

Percentage of patients with common pathogen antibodies

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 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 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.