Improving Diagnosis of Tuberculosis in HIV Infected Children in Asia (Cambodia, Vietnam)and Africa (Burkina Faso, Cameroon)

Study Overview
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Brief Summary
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Childhood tuberculosis (TB) accounts for 11% of the total 9 million annual TB cases and the difficulty of its diagnosis is increased in case of HIV infection in children. The aim of this study is to improve TB diagnosis in HIV-infected children by developing a new diagnostic algorithm incorporating new tools available such as: interferon gamma release assays (IGRAs), as alternative to the tuberculin skin test alternative specimen collection methods such as string test (or Enterotest (R)), nasopharyngeal aspirates and stools samples, as alternatives to gastric aspirate the Xpert MTB/RIF assay

Official Title
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Improving Diagnosis of Tuberculosis in HIV Infected Children in Asia (Cambodia, Vietnam) and Africa (Burkina Faso, Cameroon) ANRS 12229 PAANTHER 01 (Pediatric Asian African Network for Tuberculosis and HIV Research)

Conditions
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HIV, Tuberculosis, Pediatrics

Intervention / Treatment
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* Other: Development of a diagnosis algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: children aged from 0 to 13 years confirmed HIV infection suspicion of tuberculosis informed consent signed by at least one parent or guardian on ARVs or not Exclusion Criteria: history of anti TB treatment started in the past 2 years on going tuberculosis treatment Suspicion of exclusive extra-thoracic tuberculosis

Ages Eligible for Study
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Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Development of a diagnosis algorithm|At entry in the study, HIV infected children with suspected tuberculosis will undergo a complete evaluation including: interview on anamnesis clinical examination evaluation of HIV infection stage hematology and biochemistry tests CD4 count HIV viral load IGRA chest radiograph Abdominal ultrasonograph to detect abdominal lymphadenopathy Tuberculin skin test gastric aspirates, sputum and string tests according to the age of children nasopharyngeal aspirate stool sample lymph node fine needle aspirate or other specimen collection if applicable Diagnosis and treatment of all participating children will be done according to national guidelines. The children will be followed-up for 6 months until the end of their anti-TB treatment. For the analysis of data and the validation of the algorithm, children will be randomized into 2 groups. Data from Group I will be used to develop the algorithm; data from Group II will be used to validate it.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tuberculosis diagnostic algorithm | Development of an effective diagnostic algorithm for pediatric tuberculosis after evaluating the following diagnostic tests and sampling methods: Clinical examination Chest X-rays Abdominal ultrasound IGRAs Xpert MTB/RIF Gastric aspirate String test Nasopharyngeal aspirate Stools sample Sputum samples | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the QuantiFERON(R)-TB Gold In-Tube | Evaluation of the sensitivity, specificity, positive and negative predictive values of an in-vitro Interferon Gamma Release (IGRAs) : the QuantiFERON(R)-TB Gold iIn-Tube, for the diagnosis of TB in HIV infected children | 6 months | 
| Comparison of two in-vitro IGRAs | Comparison of the performances of two in-vitro IGRAs: the QauntiFERON(R)-TB Gold In-Tube and the T.SPOT-TB(R), for the diagnosis of tuberculosis in a sub-group of HIV infected children. | 6 months | 
| Percentage of TB diagnosis sampling procedures actually performed | To assess the feasibility of the following TB sampling procedures: the string test the nasopharyngeal aspirate stool sample | 6 months | 
| Evaluation of the morbidity (IRIS, drug toxicity and other opportunistic infections) and mortality in TB-HIV co-infected children |  | at 6 month of TB treatment | 
| Specificity and sensibility of TB diagnosis sampling procedures compared to TB diagnosis gold standard (sputum or gastric aspirate culture) | To assess the performance of the following TB sampling procedures: the string test the nasopharyngeal aspirate stools sample | 6 months | 
| Evaluation of the Xpert MTB/RIF assay | Evaluate the sensitivity, specificity, positive and negative predictive values of the Xpert MTB/RIF assay | 6 months | 
| Comparison of the Xpert MTB/RIF test to the gold standard (culture of gastric aspirates or sputum) |  | 6 months | 
| Comparison of the performance Xpert MTB/RIF assay on sampling methods other than the reference method (gastric aspirate and sputum) | Evaluation of the Xpert MTB/RIF assay on the following sampling methods: String test Nasopharyngeal aspirates Stool samples | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Asia, Tuberculosis, Diagnosis, Pediatrics, Africa