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

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)

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 Overview

• Status: Completed
• Conditions: HIV; Tuberculosis; Pediatrics
• Intervention / Treatment: Other: Development of a diagnosis algorithm

• Study Type: Interventional
• Enrollment (Actual): 441
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Burkina Faso
  • Bobo Dioulasso, Burkina Faso
    • CHU Souro Sanou
• Cambodia
  • Phnom Penh, Cambodia
    • National Pediatric Hospital
  • Siem Reap, Cambodia
    • Angkor Hospital for Children
• Cameroon
  • Yaounde, Cameroon
    • Centre Hospitalier d'Essos
  • Yaounde, Cameroon
    • Centre Mère Enfant Chantal Biya
• Vietnam
  • Ho Chi Minh City, Vietnam
    • Pediatric Hospital Nhi Dong 1
  • Ho Chi Minh City, Vietnam
    • Pediatric Hospital Nhi Dong 2
  • Ho chi Minh ville, Vietnam
    • Pham Ngoc Thach Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Groupe Hospitalier Pitie-Salpetriere; Centre Muraz; Children's Hospital Number 2, Ho Chi Minh City, Vietnam; Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam; Institut Pasteur, Cambodia; Centre Pasteur du Cameroun; National Pediatric Hospital, Cambodia; Angkor Hospital for Children; Pediatric Hospital Nhi Dong 1, Ho Chi Minh City, Vietnam; Hôpital Necker-Enfants Malades, Paris, France; CHRU Arnaud de Villeveuve, Montpellier, France; IRD, Yaounde, Cameroon; Fondation Chantal Biya,Yaounde, Cameroon; CHU Sourô Sanou, Bobo Dioulasso, Burkina Faso; Centre Hospitalier D'essos
• Investigators: Study Chair: Olivier Marcy, MD, Institut Pasteur in Cambodia, Phnom Penh, Cambodia; Study Chair: Vibol Ung, MD, National Pediatric Hospital, Phnom Penh, Cambodia

Publications and helpful links

General Publications

• Marcy O, Borand L, Ung V, Msellati P, Tejiokem M, Huu KT, Do Chau V, Ngoc Tran D, Ateba-Ndongo F, Tetang-Ndiang S, Nacro B, Sanogo B, Neou L, Goyet S, Dim B, Pean P, Quillet C, Fournier I, Berteloot L, Carcelain G, Godreuil S, Blanche S, Delacourt C; ANRS 12229 PAANTHER 01 STUDY GROUP. A Treatment-Decision Score for HIV-Infected Children With Suspected Tuberculosis. Pediatrics. 2019 Sep;144(3):e20182065. doi: 10.1542/peds.2018-2065.
• Borand L, de Lauzanne A, Nguyen NL, Cheng S, Pham TH, Eyangoh S, Ouedraogo AS, Ung V, Msellati P, Tejiokem M, Nacro B, Inghammar M, Dim B, Delacourt C, Godreuil S, Blanche S, Marcy O; Pediatric Asian African Network for Tuberculosis and HIV Research (PAANTHER) Study Group. Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus-infected Children With Suspected Tuberculosis. Clin Infect Dis. 2019 May 2;68(10):1750-1753. doi: 10.1093/cid/ciy897.
• Marcy O, Tejiokem M, Msellati P, Truong Huu K, Do Chau V, Tran Ngoc D, Nacro B, Ateba-Ndongo F, Tetang-Ndiang S, Ung V, Dim B, Neou L, Berteloot L, Borand L, Delacourt C, Blanche S; ANRS 12229 PAANTHER 01 Study Group. Mortality and its determinants in antiretroviral treatment-naive HIV-infected children with suspected tuberculosis: an observational cohort study. Lancet HIV. 2018 Feb;5(2):e87-e95. doi: 10.1016/S2352-3018(17)30206-0. Epub 2017 Nov 23.
• Marcy O, Ung V, Goyet S, Borand L, Msellati P, Tejiokem M, Nguyen Thi NL, Nacro B, Cheng S, Eyangoh S, Pham TH, Ouedraogo AS, Tarantola A, Godreuil S, Blanche S, Delacourt C. Performance of Xpert MTB/RIF and Alternative Specimen Collection Methods for the Diagnosis of Tuberculosis in HIV-Infected Children. Clin Infect Dis. 2016 May 1;62(9):1161-1168. doi: 10.1093/cid/ciw036. Epub 2016 Feb 7.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 4, 2011
• First Submitted That Met QC Criteria: April 7, 2011
• First Posted (Estimate): April 8, 2011

Study Record Updates

• Last Update Posted (Estimate): August 5, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: HIV; Pediatrics; Diagnosis; Tuberculosis; Africa; Asia
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: ANRS12229 PAANTHER 01