Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR
Condition: Thiamine Deficiency
MeSH terms: Thiamine Deficiency; Beriberi
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Thiamine 100 MG/ML
Intervention type(s): Drug
Intervention description(s): 100 mg thiamine provided as intramuscular injection
Other intervention name(s): Standard of care
Intervention MeSH terms: Thiamine
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Hospitalized children:

        Infants and children in the target age range (21 days to <18 months), who are admitted to
        the participating hospitals, will be screened by hospital staff to determine the presence
        of at least one of the inclusion criteria

        Community-based cohort:

        A sex-, age- and regionally-similar comparison group will be enrolled based on the
        characteristics of the hospitalized group.

        Mothers of all participating infants will be invited to the study.
      
Biospecimen description: 
      Blood, plasma and erythrocyte samples will be collected among children. Blood, plasma,
      erythrocyte and breastmilk samples will be collected among their mothers.