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Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: protocol for a prospective cohort study
  1. Sonja Y Hess1,
  2. Taryn J Smith1,
  3. Philip R Fischer2,
  4. Indi Trehan3,4,
  5. Laurent Hiffler5,
  6. Charles D Arnold1,
  7. Dalaphone Sitthideth6,
  8. Daniel J Tancredi7,
  9. Michael A Schick8,
  10. Jay Yeh9,
  11. Rebecca Stein-Wexler10,
  12. Christine N McBeth8,
  13. Xiuping Tan1,
  14. Kouyang Nhiacha11,
  15. Sengchanh Kounnavong6
  1. 1 Department of Nutrition, Institute for Global Nutrition, University of California Davis, Davis, California, USA
  2. 2 Pediatric and Adolescent Medicine, Mayo, Rochester, Minnesota, USA
  3. 3 Department of Pediatrics and Department of Global Health, University of Washington, Seattle, Washington, USA
  4. 4 Lao Friends Hospital for Children, Luang Prabang, Lao People’s Democratic Republic
  5. 5 Independent Pediatrician, Lagny sur Marne, France
  6. 6 Lao Tropical and Public Health Institute, Vientiane, Lao People’s Democratic Republic
  7. 7 Department of Pediatrics, University of California Davis Health System, Sacramento, California, USA
  8. 8 Emergency Medicine, University of California Davis Health System, Sacramento, California, USA
  9. 9 Department of Pediatrics, Division of Cardiology, University of California Davis Health System, Sacramento, California, USA
  10. 10 Department of Radiology, University of California Davis Health System, Sacramento, California, USA
  11. 11 Lao-Korea Children Hospital, Vientiane, Lao People’s Democratic Republic
  1. Correspondence to Dr Sonja Y Hess; syhess{at}


Introduction Diagnosis of infantile thiamine deficiency disorders (TDD) is challenging due to the non-specific, highly variable clinical presentation, often leading to misdiagnosis. Our primary objective is to develop a case definition for thiamine responsive disorders (TRD) to determine among hospitalised infants and young children, which clinical features and risk factors identify those who respond positively to thiamine administration.

Methods and analysis This prospective study will enrol 662 children (aged 21 days to <18 months) seeking treatment for TDD symptoms. Children will be treated with intravenous or intramuscular thiamine (100 mg daily for a minimum of 3 days) alongside other interventions deemed appropriate. Baseline assessments, prior to thiamine administration, include a physical examination, echocardiogram and venous blood draw for the determination of thiamine biomarkers. Follow-up assessments include physical examinations (after 4, 8, 12, 24, 36, 48 and 72 hours), echocardiogram (after 24 and 48 hours) and one cranial ultrasound. During the hospital stay, maternal blood and breast-milk samples and diet, health, anthropometric and socio-demographic information will be collected for mother–child pairs. Using these data, a panel of expert paediatricians will determine TRD status for use as the dependent variable in logistic regression models. Models identifying predictors of TRD will be developed and validated for various scenarios. Clinical prediction model performance will be quantified by empirical area under the receiver operating characteristic curve, using resampling cross validation. A frequency-matched community-based cohort of mother–child pairs (n=265) will serve as comparison group for evaluation of potential risk factors for TRD.

Ethics and dissemination Ethical approval has been obtained from The National Ethics Committee for Health Research, Ministry of Health, Lao PDR and the Institutional Review Board of the University of California Davis. The results will be disseminated via scientific articles, presentations and workshops with representatives of the Ministry of Health.

Trial registration number NCT03626337.

  • nutrition & dietetics
  • echocardiography
  • neuroradiology
  • paediatrics

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  • Twitter @DrTarynSmith, @IndiTrehan

  • Contributors SYH led the proposal writing. SYH and TJS developed all data collection tools and standard operational procedure manuals. PRF, IT and LH developed the thiamine treatment and physical examination protocols. MAS, JY, RS-W and CNM developed different aspects of the sonography protocols. MAS, CNM and KN prepared the sonography training plan. CDA and DJT developed the statistical analyses plan. XT programmed all data collection tools and developed the data management protocol together with CDA. SK, DS, TJS and SYH planned local study implementation. The manuscript was drafted by SYH, TJS and CDA. All coauthors reviewed the manuscript critically and approved the final content.

  • Funding This work is supported by the Bill & Melinda Gates Foundation (grant number OPP1182864). Dr Kenneth Brown provided technical support in the design of this study, when working for the Bill & Melinda Gates Foundation. The funding source will not have any role during its execution, analyses, interpretation of the data or decision to submit results.

  • Competing interests SYH has completed a consultancy for the Bill & Melinda Gates Foundation and her spouse previously worked for the Bill & Melinda Gates Foundation.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was reviewed and approved by a steering committee at the Ministry of Health and the Ministry of Foreign Affairs in Lao PDR. The study and consenting procedures were approved by the National Ethics Committee for Health Research, Ministry of Health, Lao PDR (ref. 11/2019) and the Institutional Review Board of the UC Davis (ref. 1329444). The trial is registered at (NCT03626337).

  • Provenance and peer review Not commissioned; peer reviewed for ethical and funding approval prior to submission.

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