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)

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)

Institut Pasteur, Cambodia, National Pediatric Hospital, Cambodia, Angkor Hospital for Children, Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam, Pediatric Hospital Nhi Dong 1, Ho Chi Minh City, Vietnam, Number 2 Children's Hospital, Ho Chi Minh City, Hôpital Necker-Enfants Malades, Paris, France, Groupe Hospitalier Pitie-Salpetriere, CHRU Arnaud de Villeveuve, Montpellier, France, IRD, Yaounde, Cameroon, Fondation Chantal Biya,Yaounde, Cameroon, CHU Sourô Sanou, Bobo Dioulasso, Burkina Faso, Centre Muraz, Centre Pasteur du Cameroun, Centre Hospitalier D'essos

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

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.

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

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

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.

To assess the feasibility of the following TB sampling procedures: the string test the nasopharyngeal aspirate stool sample

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

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

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

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

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

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.