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

ANRS, Emerging Infectious Diseases441 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

441

Conditions

HIV Tuberculosis Pediatrics

Interventions

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.

Eligibility

Sex: ALLMax age: 13 Years

Medical Language ↔ Plain English

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

Locations (8)

CHU Sourô Sanou

Bobo-Dioulasso, Burkina Faso

National Pediatric Hospital

Phnom Penh, Cambodia

Angkor Hospital for Children

Siem Reap, Cambodia

Centre Hospitalier d'Essos

Yaoundé, Cameroon

Centre Mère Enfant Chantal Biya

Yaoundé, Cameroon

Pediatric Hospital Nhi Dong 1

Ho Chi Minh City, Vietnam

Pediatric Hospital Nhi Dong 2

Ho Chi Minh City, Vietnam

Pham Ngoc Thach Hospital

Ho Chi Minh City, Vietnam

Outcomes

Primary Outcomes

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

Time frame: 3 years

Secondary Outcomes

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

Time frame: 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.

Time frame: 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

Time frame: 6 months

Evaluation of the morbidity (IRIS, drug toxicity and other opportunistic infections) and mortality in TB-HIV co-infected children

Time frame: 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

Time frame: 6 months

Evaluation of the Xpert MTB/RIF assay

Evaluate the sensitivity, specificity, positive and negative predictive values of the Xpert MTB/RIF assay

Time frame: 6 months

Comparison of the Xpert MTB/RIF test to the gold standard (culture of gastric aspirates or sputum)

Time frame: 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

Time frame: 6 months