Table 3.

Summary of procedures for cases in the enteropathy substudy

Assessment	Hospitalisation		Post discharge*
	Baseline†	Discharge‡	2 weeks	4 weeks	12 weeks	24 weeks	48 weeks
Caregiver informed consent to join observational cohort and enteropathy substudy	X
Summary checklist	X
Locator information§	X
Acute admission information	X
Baseline data	X
Daily clinical review¶	Daily during hospitalisation
Blood collection**	X	X			X	X	X
HIV testing††	X
CD4 count and viral load (HIV-infected children only)	X				X	X	X
Full blood count‡‡	X	X			X	X	X
Gastric aspirate§§	X
Stool collection¶¶	X	X			X	X	X
Lactulose-mannitol testing***	X	X			X		X
Anthropometry	X	X	X	X	X	X	X
Skinfold thickness†††		X	X	X	X	X	X
Body composition‡‡‡	X	X	X	X	X	X	X
Discharge data collection		X
Daily morbidity diary			Daily during follow-up period by caregivers
Follow-up clinic: history, examination, morbidity and mortality data			X		X	X	X

*Windows will be created around these post-discharge time points to maximise follow-up for caregivers who miss visits or are unavailable, as follows: 2 weeks (1–3 weeks); 4 weeks (3–5 weeks); 12 weeks (10–14 weeks); 24 weeks (20–28 weeks) and 48 weeks (44–52 weeks).

†Children will be enrolled within 24 hours of hospitalisation and will undergo baseline investigations within 72 hours of hospitalisation. This is to provide a window of opportunity to time collection of research specimens with clinical specimens, and to ensure that the child is clinically stable before undertaking research investigations.

‡The discharge procedures will be undertaken on the day of discharge or as close as possible to that date.

§Locator information will updated at subsequent visits if caregivers have moved or changed contact details.

¶Daily clinical review will be conducted every day between admission and discharge by the study clinician.

**During hospitalisation, 5.4 mL of blood (depending on child weight; amount will not exceed 2 mL/kg total over 2-week period) will be collected by a study nurse into a 2.7 mL endotoxin-free EDTA tube and a 2.7 mL PAXGene tube, for subsequent isolation of RNA and gene expression analysis. After discharge (weeks 12, 24 and 48), 5.4 mL of blood (depending on child weight; amount will not exceed 2 mL/kg total over 2-week period) will be collected by a study nurse into two 2.7 mL endotoxin-free EDTA tubes.

††HIV testing is conducted as part of routine clinical practice, but if it has not been undertaken, the study sample will be used to test for HIV (see section 9.4), as stated in the informed consent form, since HIV status is required to allocate children to study groups.

‡‡Full blood count results will be transcribed from clinical records; if not done by clinical teams, the EDTA sample will be used to measure FBC in clinical laboratories at each site.

§§A gastric juice sample will be collected at the same time as the blood draw by aspirating the nasogastric tube with a sterile feeding syringe, to test for gastric pH; sterile water or saline will then be instilled and a sample of gastric juice collected for storage for subsequent PCR and culture (section 7.5.2).

¶¶Stool collection will be undertaken at the same time as the blood draw.

***Lactulose-mannitol (LM) testing will be conducted, with collection of a baseline urine sample, followed by a 2-hour urine collection post-LM ingestion. This test will be deferred until children are judged to be clinically stable by the study physician during daily reviews. In general, this will be a child in the nutritional rehabilitation phase, who has no cardiorespiratory compromise.

†††Skinfold thickness (triceps, subscapular, supra-iliac) and mid-thigh circumference will be measured using Holtain callipers or tape measure.

‡‡‡Body composition will be assessed by bioimpedance vector analysis.