Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR

Thiamine Deficiency

A hospital- and community-based study in Luang Prabang, Lao PDR, which will include a group of hospitalized children 21 days to \<18 months of age who are diagnosed with symptoms compatible with thiamine deficiency disorder (TDD). Based on the infants' response to thiamine administration, children will be defined as either thiamine responsive disorder (TRD) cases or non-responders. A community-based comparison group of infants in the same age range will be included in the study to serve as a control group for identification of potential risk factors.

The study's primary objective is the development of a case definition for TRD among infants and young children with symptoms consistent with TDD, with the case definition being based on those clinical symptoms and other predictors that we find are better able to distinguish those who respond positively to thiamine administration from those who do not respond. As diagnostic tools available to treating physicians may differ by setting, we will repeat analyses after excluding from the set of candidate predictors those that are derived from assessments only available in higher-resource settings, such as laboratory biomarkers and ultrasonography. A secondary objective is to fill the knowledge gap surrounding biomarkers of thiamine status in at-risk populations. Biomarker cut-offs for TRD will be developed in the hospital cohort and distributions will be characterised in both the hospital and community cohorts. The performance of our proposed cut-off will be compared to the performance of existing literature cut-offs. Additionally, all identified predictors and biomarker cut-offs will be compared across the community cohort, non-TRD hospital cohort, and TRD hospital cohort to assess the prevalence of risk factors among apparently healthy infants and young children and assess the usefulness of the TRD case definition in various settings. Infants and children in the target age range, who are seeking care at the collaborating hospital, will be screened by study staff to determine the presence of any of the inclusion criteria. The list of inclusion criteria has been developed based on a broad range of TDD-compatible symptoms to reduce the risk of potentially missing children who would respond clinically to thiamine administration to correct the deficiency. If a child is in the target age range (21 days to \<18 months) meets any one of the inclusion criteria, parental consent will be obtained and children will be referred to a study physician for a detailed physical exam. An echocardiogram and cranial ultrasound will be performed to explore the complete range of TDD complications. A venous blood sample will be obtained by venipuncture for assessment of indicators of thiamine status. The data collection will follow a structured timeline after the first thiamine dose has been administered. In particular, the thiamine administration will be defined as hour zero, and the above described physical exam will be repeated 4, 8, 12, 24, 36, 48, and 72 hours after the initial thiamine administration Blood samples will be analyzed for whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac), inflammation and cardiac biomarkers and for a complete blood count (CBC). The purpose of determining these indicators is to better describe the TRD cases and explore differences between TRD cases, non-TRD children and children in the community, with the ultimate goal that these indicators may be useful for screening in the future. Moreover, to determine the association between TRD and maternal thiamine status as a potential risk factor, investigators will collect a blood sample from infants's mothers to assess maternal thiamine status, and among breast feeding mothers a breastmilk sample for assessment of thiamine concentration.

Laos