Trajectories and Mechanisms of Recovery From Malaria: An Observational Study

Study Overview
=================
Brief Summary
-----------------
This observational research study aims to answer the question: 'Which aspects of human biology play an important role in recovery from symptomatic malaria?' In particular, the researchers aim to identify human genes for which the level of gene activity reflects the patient's overall rate of recovery. The researchers believe this approach may reveal new targets for adjunctive therapies. The researchers aim to recruit 240 people, of all ages, who have been diagnosed with symptomatic malaria at selected hospitals in London. Blood samples, urine samples, and clinical information will be collected over the 14 days following malaria diagnosis.

Official Title
-----------------
Search for Correlates of Recovery in the Patient Transcriptome (SCRIPT) (Malaria) Study

Conditions
-----------------
Malaria

Intervention / Treatment
-----------------
* Other: Symptomatic malaria


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of any age with symptomatic malaria confirmed by asexual stage parasitaemia (of any Plasmodium species) on blood film. Exclusion Criteria: Patients with asymptomatic malaria; Patients with congenital malaria; Patients with Plasmodium gametocytaemia only; Patients with known HIV; Patients who have received antimalarial treatment for symptomatic malaria in the 28 days prior to hospital presentation; Patients who explicitly deny consent.

Ages Eligible for Study
-----------------
Minimum Age: 8 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Symptomatic malaria|This observational study will be recruiting patients who have symptomatic malaria (confirmed by presence of asexual stage parasitaemia of any Plasmodium species on blood film)|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genes for which expression (level of gene activity) correlates with a 'composite recovery score' | The 'composite recovery score' will be calculated by principal component analysis of rates of recovery for individual markers of tissue, organ, or organ system dysfunction, and extraction of the value of the first principal component for each participant. Genes for which expression correlates with the 'composite recovery score' will be identified by whole blood transcriptome analysis. | Each study participant will be assessed over the 14 days following malaria diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genes for which expression (level of gene activity) correlates with rate of recovery for individual markers of tissue, organ, or organ system dysfunction | Genes for which expression correlates with the individual markers of tissue, organ, or organ system dysfunction will be identified by whole blood transcriptome analysis. | Each study participant will be assessed over the 14 days following malaria diagnosis | 
| Rate of recovery for individual markers of tissue, organ, or organ system dysfunction | Rates of recovery will be calculated for individual markers of tissue, organ, or organ system dysfunction | Each study participant will be assessed over the 14 days following malaria diagnosis | 
| Sequences of clinical events predictive of recovery, as determined by Bayesian inference of dynamic pathways using the HyperTraPS statistical platform | Hypercubic transition path sampling (HyperTraPS) will be used to characterise patterns of recovery and identify predictors of fast vs slow recovery | Each study participant will be assessed over the 14 days following malaria diagnosis | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Malaria, Recovery, Transcriptomics