Evaluation of the DPP II Assay in Laos

Study Overview
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Brief Summary
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Fever is the most frequent symptom in patients seeking care globally. Several causative agents of febrile illness have been described with a high prevalence in South East Asia. They include malaria, dengue, Rickettsia, Leptospira and Burkholderia species. Since their introduction in the market, rapid diagnostic tests for malaria have driven patient management and care. Malaria negative cases are commonly treated with antibiotics without confirmation of bacteraemia. This can be explained by conventional laboratory diagnostic tests such as blood culture that usually require a skilled staff and appropriate facilities. Several Rapid Diagnostic tests (RDTs) are currently in the market but only limited data on their performance are available, rendering them unsuitable to replace laboratory conventional tests. In addition, RDTs have been developed for single disease diagnosis and remain costly for Low and Middle Income Countries (LMIC). Chembio, in collaboration with FIND (Foundation for Innovative New Diagnostics) and MORU (Mahidol Oxford Tropical Medicine Research Unit), has developed a multiplex lateral flow immunoassay (DPP® Fever Panel II Assay) that is able to detect serum immunoglobulin M (IgM) and specific microbial antigen of the most common agents of Acute Febrile Illness (AFI) in Asia. The assay comes with a reader that provides results interpretation to the operator. So far, DPP II assay performance has been estimated using a limited number of retrospective serum samples. More data are required to assess the performance of the assay using prospective serum samples. In addition, only limited data are available regarding the performance of the assay using blood samples. FIND will conduct a clinical trial to estimate the clinical performance of the assay in comparison to reference tests, using blood and serum samples and in intended settings of use.

Official Title
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Performance Assessment of the DPP Fever Panel II Assay for Detection of Infectious Causes of Acute Febrile Illness in Laos

Conditions
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Acute Febrile Illness

Intervention / Treatment
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* Diagnostic Test: DPP Fever Panel II assay and DPP Micro Readers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants > 12 years old enrolled in the Prospective study of the causes of fever amongst patients admitted to Mahosot Hospital, Vientiane, Lao PDR (UI-2 study). Fever (≥ 37.5 °C) Illness duration < 14 days Willingness to provide blood samples by venepuncture Exclusion Criteria: Absence of consent (and assent for children) to participate to the Prospective study of the causes of fever amongst patients admitted to Mahosot Hospital, Vientiane, Lao PDR (UI-2 study). Non-infectious known or suspected cause of fever No left over blood sample or insufficient volume of left over sample

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AFI patients<br>Blood will be collected from patients presenting with an undifferentiated fever. Samples will be tested with: the Malaria Ag Pf/Pan test SD Bioline the SD Bioline Dengue Duo IgM/IgG/NS1 the DPP Zika Chikungunya Dengue test from Chembio the DPP Fever Panel II assay the Leptospira IgM ELISA test from Serion an in-house ELISA tests for scrub and murine typhus IgM blood culture for detection of Burkholderia pseudomallei | Diagnostic Test: DPP Fever Panel II assay and DPP Micro Readers<br>* Detection of common causes of acute febrile illnesses in Asia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of samples with concordant results for marker detection in paired whole blood and serum samples for each reader | The percentage of samples with concordant results using two types of assay readers will be calculated for each marker and each specimen type (blood and serum) | 5 months | 
| Optimal reader cut-offs for serum samples and for blood samples to obtain the overall highest diagnostic accuracy per sample type | The reader cut-offs (numerical values) that give the highest specificity and specificity will calculated for each marker and reader | 5 months | 
| Percentage of more targeted treatments that would have been prescribed if the DPP II assay test was used in routine in comparison to actual prescribed treatments and to treatment that would have been prescribed based on comparator tests | In comparison to reference tests and routine tests, the impact of the DPP Fever Panel II assay on antibiotic prescriptions will be modeled | 5 months | 
| Cost impact of more targeted treatments that would have been prescribed if the DPP II assay test was used in routine in comparison to actual prescribed treatments and to treatment that would have been prescribed based on comparator tests | In comparison to reference tests and routine tests, the impact of the DPP Fever Panel II assay on health costs will be modeled. | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimates of sensitivity and specificity of the DPP assay for detection of fever causative agents using venous blood samples, in comparison to reference tests |  | 5 months | 
| Estimates of sensitivity and specificity of the DPP assay for detection of fever causative agents using serum samples, in comparison to reference tests. |  | 5 months | 
| Estimates of operational characteristics, including invalid and indeterminate rates | The % of invalid results and indeterminate rates will be calculated. | 5 months | 
| Estimates of ease-of-use will be captured through user-appraisal questionnaire. | Answers to each question will be graded either positive, neutral or negative. The % and absolute numbers of positive, neutral and negative answers will be reported in tables and charts. | 5 months |