Olivier Marcy1, Mathurin Tejiokem2, Philippe Msellati3, Khanh Truong Huu4, Viet Do Chau5, Duong Tran Ngoc6, Boubacar Nacro7, Francis Ateba-Ndongo8, Suzie Tetang-Ndiang9, Vibol Ung10, Bunnet Dim11, Leakhena Neou12, Laureline Berteloot13, Laurence Borand11, Christophe Delacourt14, Stéphane Blanche15. 1. Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia; Bordeaux Population Health Centre U1219, Université de Bordeaux, Bordeaux, France. Electronic address: olivier.marcy@u-bordeaux.fr. 2. Service d'Epidémiologie et de Santé Publique, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur, Yaounde, Cameroon. 3. UMI 233-U1175 TransVIHMI, Institut de Recherche pour le Développement, Université de Montpellier, Montpellier, France. 4. Infectious Disease Department, Pediatric Hospital Nhi Dong 1, Ho Chi Minh City, Vietnam. 5. Infectious Disease Department, Pediatric Hospital Nhi Dong 2, Ho Chi Minh City, Vietnam. 6. Pediatric Department, Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam. 7. Service de Pédiatrie, Centre Hospitalier Universitaire Souro Sanou, Bobo Dioulasso, Burkina Faso. 8. Centre Mère et Enfant de la Fondation Chantal Biya, Yaounde, Cameroon. 9. Service de Pédiatrie, Centre Hospitalier d'Essos, Yaounde, Cameroon. 10. Tuberculosis/HIV Department, National Pediatric Hospital, Phnom Penh, Cambodia; Planning and Research Department, University of Health Sciences, Phnom Penh, Cambodia. 11. Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. 12. Neonatal Unit, Angkor Hospital for Children, Siem Reap, Cambodia. 13. Pediatric Radiology Department, Hôpital Necker Enfants Malades, AP-HP, Paris, France. 14. Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Necker Enfants Malades, AP-HP, Paris, France. 15. Unité d'Immunologie Hématologie Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
Abstract
BACKGROUND: Tuberculosis is a major cause of morbidity and mortality in HIV-infected children, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infected children presenting with suspected tuberculosis. METHODS: In this observational cohort study, HIV-infected children aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811. FINDINGS: 266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p<0·0001 for both). In a multivariate analysis, ART started during the first month of follow-up (hazard ratio 0·08; 95% CI 0·01-0·67), confirmed tuberculosis (6·33; 2·15-18·64), young age (5·90; 2·02-17·19), CD4 less than 10% (2·63; 1·25-5·53), miliary features (4·08; 1·56-10·66), and elevated serum transaminases (4·40; 1·82-10·65) were all independently associated with mortality. INTERPRETATION: In our cohort, mortality was high in the first 6 months after suspicion of tuberculosis in ART-naive children. ART should be started early, particularly in children with factors associated with high mortality. Documented or empirical tuberculosis treatment decision should be accelerated to reduce mortality and allow early ART initiation. FUNDING: ANRS and Fondation Total.
BACKGROUND:Tuberculosis is a major cause of morbidity and mortality in HIV-infectedchildren, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infectedchildren presenting with suspected tuberculosis. METHODS: In this observational cohort study, HIV-infectedchildren aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811. FINDINGS: 266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p<0·0001 for both). In a multivariate analysis, ART started during the first month of follow-up (hazard ratio 0·08; 95% CI 0·01-0·67), confirmed tuberculosis (6·33; 2·15-18·64), young age (5·90; 2·02-17·19), CD4 less than 10% (2·63; 1·25-5·53), miliary features (4·08; 1·56-10·66), and elevated serum transaminases (4·40; 1·82-10·65) were all independently associated with mortality. INTERPRETATION: In our cohort, mortality was high in the first 6 months after suspicion of tuberculosis in ART-naive children. ART should be started early, particularly in children with factors associated with high mortality. Documented or empirical tuberculosis treatment decision should be accelerated to reduce mortality and allow early ART initiation. FUNDING: ANRS and Fondation Total.
Authors: Anthony Enimil; Sampson Antwi; Hongmei Yang; Albert Dompreh; Wael A Alghamdi; Fizza S Gillani; Antoinette Orstin; Dennis Bosomtwe; Theresa Opoku; Jennifer Norman; Lubbe Wiesner; Taimour Langaee; Charles A Peloquin; Michael H Court; David J Greenblatt; Awewura Kwara Journal: Antimicrob Agents Chemother Date: 2019-09-23 Impact factor: 5.191
Authors: Alexander W Kay; Tara Ness; Sabine E Verkuijl; Kerri Viney; Annemieke Brands; Tiziana Masini; Lucia González Fernández; Michael Eisenhut; Anne K Detjen; Anna M Mandalakas; Karen R Steingart; Yemisi Takwoingi Journal: Cochrane Database Syst Rev Date: 2022-09-06
Authors: Alexander W Kay; Lucia González Fernández; Yemisi Takwoingi; Michael Eisenhut; Anne K Detjen; Karen R Steingart; Anna M Mandalakas Journal: Cochrane Database Syst Rev Date: 2020-08-27