Olivier Marcy1,2, Vibol Ung3,4, Sophie Goyet1, Laurence Borand1, Philippe Msellati5, Mathurin Tejiokem6, Ngoc Lan Nguyen Thi7, Boubacar Nacro8, Sokleaph Cheng9, Sara Eyangoh10, Thu Hang Pham7, Abdoul-Salam Ouedraogo8, Arnaud Tarantola1, Sylvain Godreuil11,12, Stéphane Blanche13, Christophe Delacourt14. 1. Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. 2. University of Bordeaux, Centre INSERM U1219, France. 3. TB/HIV Department, National Pediatric Hospital. 4. University of Health Sciences, Phnom Penh, Cambodia. 5. UMI 233- U1175 TransVIHMI, IRD, Université de Montpellier, France. 6. Service d'Epidémiologie et de Santé Publique, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur, Yaounde, Cameroon. 7. Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam. 8. Centre Hospitalier Universitaire Souro Sanou, Bobo Dioulasso, Burkina Faso. 9. Mycobacteriology Laboratory, Medical Laboratory Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. 10. Service de Mycobactériologie, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur, Yaounde, Cameroon. 11. Département de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Montpellier, Hôpital Arnaud de Villeneuve. 12. INSERM U1058, Montpellier. 13. Unité d'Immunologie Hématologie Rhumatologie Pédiatrique. 14. Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
Abstract
BACKGROUND: The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infected children is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infected children using Xpert MTB/RIF (Xpert). METHODS: HIV-infected children aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged <10 years and expectorated sputum samples were taken for children aged ≥10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged ≥4 years (alternative samples). All samples were tested with Xpert. The diagnostic accuracy of Xpert for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches. RESULTS: Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were ≥97.5%. Xpert combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively. CONCLUSIONS: The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infected children. CLINICAL TRIALS REGISTRATION: The ANRS (Agence Nationale de Recherche sur le Sida) 12229 PAANTHER (Pediatric Asian African Network for Tuberculosis and HIV Research) 01 study is registered at ClinicalTrials.gov (NCT01331811).
BACKGROUND: The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infectedchildren is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infectedchildren using Xpert MTB/RIF (Xpert). METHODS:HIV-infectedchildren aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged <10 years and expectorated sputum samples were taken for children aged ≥10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged ≥4 years (alternative samples). All samples were tested with Xpert. The diagnostic accuracy of Xpert for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches. RESULTS: Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were ≥97.5%. Xpert combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively. CONCLUSIONS: The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infectedchildren. CLINICAL TRIALS REGISTRATION: The ANRS (Agence Nationale de Recherche sur le Sida) 12229 PAANTHER (Pediatric Asian African Network for Tuberculosis and HIV Research) 01 study is registered at ClinicalTrials.gov (NCT01331811).
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