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isoniazid preventive therapy

Lisa Frigati, Moherdran Archary, Helena Rabie, Martina Penazzato, Nathan Ford
Early mortality and morbidity remain high in children initiating antiretroviral therapy (ART), especially in sub-Saharan Africa. Many children still present with advanced human immunodeficiency virus (HIV) disease. Tuberculosis, pneumonia, and severe bacterial infections are the main causes of hospital admission in HIV-infected children. In contrast to adults with advanced HIV disease, cryptococcal disease is not common in childhood, although there is a peak in infancy and adolescence. Interventions such as TB screening in symptomatic children, and isoniazid and cotrimoxazole prophylaxis should be implemented...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jody Boffa, Maria Mayan, Sithembile Ndlovu, Tsholofelo Mhlaba, Tyler Williamson, Reginald Sauve, Dina Fisher
INTRODUCTION: In response to revisions in global and national policy in 2011, six-month isoniazid preventive therapy (IPT) became freely available as a preventive measure for people living with HIV in the uMgungundlovu District of KwaZulu-Natal province, South Africa. Given a difference in uptake and completion by sex, we sought to explore the reasons why Zulu women were more likely to accept and complete IPT compared to men in an effort to inform future implementation. METHODS: Utilising a community-based participatory research approach and ethnographic methods, we undertook 17 individual and group interviews, and met regularly with grassroots community advisory teams in three Zulu communities located in uMgungundlovu District between March 2012-December 2016...
2018: PloS One
Henrik Cordes, Christoph Thiel, Vanessa Baier, Lars M Blank, Lars Kuepfer
Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism...
2018: NPJ Systems Biology and Applications
Liesl Page-Shipp, James J Lewis, Kavindhran Velen, Sedikanelo Senoge, Elizabeth Zishiri, Flora Popane, Violet N Chihota, Dave Clark, Gavin J Churchyard, Salome Charalambous
BACKGROUND: In South Africa, TB household contact tracing provides an opportunity for increased TB and HIV case finding. We aimed to determine the effect of two new potential interventions for TB contact tracing programmes: Point of Care CD4 (PoC CD4) on HIV linkage to care and household Isoniazid Preventive Therapy (IPT) provision on uptake and retention of IPT. METHODS: A pragmatic, three-arm, cluster-randomized trial was undertaken. TB Household contacts were randomised to 3 arms: 1) Standard of Care TB and HIV testing (SOC); 2) SOC with POC CD4 for those testing HIV positive; 3) SOC with POC CD4 and IPT for eligible household members...
2018: PloS One
Xiaoguang Wu, Yu Pang, Yanhua Song, Wenzhu Dong, Tingting Zhang, Shuan Wen, Hairong Huang, Mengqiu Gao
In this study, we identified a multidrug-resistant tuberculosis (MDR-TB) outbreak in a high school in northern China. The aim of this work was to describe TB transmission, drug resistance and treatment outcomes for this patient cluster. In January 2017, pulmonary TB was identified in a 17-year-old boy in northern China. Subsequently, a total of 11 TB cases were identified during 6-month follow-up of attendees of the same school. Of five students with latent TB infection (LTBI) receiving isoniazid preventive therapy (IPT), two pulmonary TB cases (40...
February 28, 2018: Epidemiology and Infection
Florian M Marx, Reza Yaesoubi, Nicolas A Menzies, Joshua A Salomon, Alyssa Bilinski, Nulda Beyers, Ted Cohen
BACKGROUND: In high-incidence settings, recurrent disease among previously treated individuals contributes substantially to the burden of incident and prevalent tuberculosis. The extent to which interventions targeted to this high-risk group can improve tuberculosis control has not been established. We aimed to project the population-level effect of control interventions targeted to individuals with a history of previous tuberculosis treatment in a high-incidence setting. METHODS: We developed a transmission-dynamic model of tuberculosis and HIV in a high-incidence setting with a population of roughly 40 000 people in suburban Cape Town, South Africa...
February 19, 2018: Lancet Global Health
D Thindwa, P MacPherson, A T Choko, M Khundi, R Sambakunsi, L G Ngwira, T Kalua, E L Webb, E L Corbett
SETTING: Despite worldwide scale-up of human immunodeficiency virus (HIV) care services, relatively few countries have implemented isoniazid preventive therapy (IPT). Among other programmatic concerns, IPT completion tends to be low, especially when not fully integrated into HIV care clinics. OBJECTIVE: To estimate non-completion of 6-month IPT and its predictors among HIV-positive adults aged 16 years. DESIGN: A prospective cohort study nested within a cluster-randomised trial of TB prevention was conducted between February 2012 and June 2014...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
Lisa M Cranmer, Heather R Draper, Anna M Mandalakas, Soyeon Kim, George McSherry, Emma Krezinski, Joan Coetzee, Charles Mitchell, Sharon Nachman, Mercia van der Linde, Mark F Cotton, Anneke C Hesseling
Young HIV-exposed children are at high risk for TB infection. We performed QuantiFERON®-TB Gold (QFT) among HIV-exposed children in South Africa at enrolment and one year follow-up. The incidence of TB infection was high for HIV+ (11 cases/100 child-years) and HIV-exposed uninfected (HEU) children (15 cases/100 child-years). QFT may identify HIV-exposed children at risk for TB disease progression.
February 16, 2018: Pediatric Infectious Disease Journal
Leonardo Martinez, David M le Roux, Whitney Barnett, Attie Stadler, Mark P Nicol, Heather J Zar
Background: Tuberculosis is a leading cause of global childhood mortality. However, the epidemiology and burden of tuberculosis in infancy is not well understood. We aimed to investigate tuberculin skin test conversion and tuberculosis in the Drakenstein Child Health study, a South African birth cohort in a community in which tuberculosis incidence is hyperendemic. Methods: In this prospective birth cohort study, we enrolled pregnant women older than 18 years who were between 20 and 28 weeks' gestation and who were attending antenatal care in a peri-urban, impoverished South African setting...
January 2018: Lancet Child & Adolescent Health
McNeil Ngongondo, Sachiko Miyahara, Michael D Hughes, Xin Sun, Gregory P Bisson, Amita Gupta, Johnstone Kumwenda, Jeffrey A Lavenberg, Thiago Silva Torres, Mulinda Nyirenda, Katende Kenneth Kidonge, Mina C Hosseinpour
BACKGROUND: Hepatotoxicity associated with isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) has not been well studied in severely immunosuppressed people with HIV. Our objective was to determine risk factors for hepatotoxicity in severely immunosuppressed individuals taking IPT and ART. SETTING: Multi-center study in resource limited settings with high burden of tuberculosis. METHODS: We conducted a secondary analysis of data from one randomized arm of the REMEMBER trial...
February 5, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Adrienne E Shapiro, Alastair van Heerden, Torin T Schaafsma, James P Hughes, Jared M Baeten, Heidi van Rooyen, Elioda Tumwesigye, Connie L Celum, Ruanne V Barnabas
INTRODUCTION: Tuberculosis (TB) is the leading cause of HIV-associated mortality in Africa. As HIV testing, linkage to care and antiretroviral treatment initiation intensify to meet UNAIDS targets, it is not known what effect these efforts will have on TB detection and prevention. We aimed to characterize the TB care cascade of screening, diagnostic testing, treatment and provision of isoniazid preventive therapy (IPT) in a study of community-based HIV screening and linkage to care and determine whether symptom screening results affected progress along the cascade...
January 2018: Journal of the International AIDS Society
Andrea T Cruz, Jeffrey R Starke
BACKGROUND: The traditional treatment of tuberculosis (TB) infection (9 months of daily isoniazid [9H]) is safe but completion rates of <50% are reported. Shorter regimens (3 months of once-weekly isoniazid and rifapentine [3HP] or 4 months of daily rifampin [4R]) are associated with improved adherence in adults. METHODS: This was a retrospective cohort study (2014-2017) of children (0-18 years old) seen at a children's TB clinic in a low-incidence nation. We compared the frequency of completion and adverse events (AEs) in children receiving 3HP, 4R, and 9H; the latter 2 regimens could be administered by families (termed self-administered therapy [SAT]) or as directly observed preventive therapy (DOPT); 3HP was always administered under DOPT...
January 23, 2018: Pediatrics
R Moh, A Badjé, J-B N'takpé, G M Kouamé, D Gabillard, T Ouassa, E Ouattara, J Le Carrou, F Bohoussou, E Messou, S Eholié, X Anglaret, C Danel
SETTING: TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
Jaya Ranjalkar, Sumith K Mathew, Valsan Philip Verghese, Anuradha Bose, Winsley Rose, Dulari Gupta, Denise H Fleming, Binu Susan Mathew
BACKGROUND: Sub-optimal plasma drug concentrations of Anti-Tubercular Therapy (ATT) could lead to delayed response and emergence of acquired drug-resistance. OBJECTIVES: To determine and compare the plasma concentrations of isoniazid and rifampicin in children treated for tuberculosis (TB) on daily or intermittent ATT regimen. To study the effect of the exposure of isoniazid and rifampicin on clinical outcome at the end of therapy. METHODS: Forty-one children aged 2 to 16 years, initiated on either daily or three-times a week (intermittent) ATT regimen were recruited into the study...
December 11, 2017: International Journal of Antimicrobial Agents
J Morgan Freiman, Karen R Jacobson, Winnie R Muyindike, C Robert Horsburgh, Jerrold J Ellner, Judith A Hahn, Benjamin P Linas
BACKGROUND: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV), and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in three high TB/HIV burden countries. METHODS: We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda...
December 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
A Carmone, C A Rodriguez, T D Frank, M Kiromat, P W Bongi, R G Kuno, T Palou, M F Franke
Setting: Tuberculosis (TB) is the leading cause of death among people living with the human immunodeficiency virus (PLHIV) in Papua New Guinea. Despite a policy for isoniazid preventive therapy (IPT) among PLHIV, implementation has been slow. Objective: We prospectively evaluated a standardized guided screening process, including TB diagnostic support, to increase IPT initiation in adult PLHIV on antiretro-viral treatment. Design: The guided process included a paper-based IPT screening tool that prompted review of patient history and TB symptoms and sputum analysis by smear microscopy and Xpert® MTB/RIF...
September 21, 2017: Public Health Action
Adriana Campa, Marianna K Baum, Hermann Bussmann, Sabrina Sales Martinez, Mansour Farahani, Erik van Widenfelt, Sikhulile Moyo, Joseph Makhema, Max Essex, Richard Marlink
Background: Coinfection with active tuberculosis (TB) is one of the leading causes of death in people living with HIV (PLWH) in Africa. This investigation explores the role of micronutrient supplementation in preventing active TB in PLWH. Methods: A randomized trial of nutritional supplementation was conducted among antiretroviral- naïve (without previous antiretroviral treatment [ART]) HIV-infected people in Botswana between 2004 and 2009. The study had a factorial design with four arms: the selenium (Se) alone arm, the multivitamins (MVT) alone arm that contained vitamin B complex and vitamins C and E, the combined Se+MVT group and the placebo group...
2017: Nutrition and Dietary Supplements
Yael Hirsch-Moverman, Andrea A Howard, Koen Frederix, Limakatso Lebelo, Anneke Hesseling, Sharon Nachman, Joanne E Mantell, Tsepang Lekhela, Llang Bridget Maama, Wafaa M El-Sadr
BACKGROUND: Effective, evidence-based interventions to prevent childhood tuberculosis (TB) in high TB/HIV-burden, resource-limited settings are urgently needed. There is limited implementation of evidence-based contact management strategies, including isoniazid preventive therapy (IPT), for child contacts of TB cases in Lesotho. METHODS/DESIGN: This mixed-methods implementation science study utilizes a two-arm cluster-randomized trial design with randomization at the health facility level...
November 21, 2017: Trials
Robert Belknap, David Holland, Pei-Jean Feng, Joan-Pau Millet, Joan A Caylà, Neil A Martinson, Alicia Wright, Michael P Chen, Ruth N Moro, Nigel A Scott, Bert Arevalo, José M Miró, Margarita E Villarino, Marc Weiner, Andrey S Borisov
Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin...
November 21, 2017: Annals of Internal Medicine
Erica L Stockbridge, Thaddeus L Miller, Erin K Carlson, Christine Ho
CONTEXT: Targeted identification and treatment of people with latent tuberculosis infection (LTBI) are key components of the US tuberculosis elimination strategy. Because of recent policy changes, some LTBI treatment may shift from public health departments to the private sector. OBJECTIVES: To (1) develop methodology to estimate initiation and completion of treatment with isoniazid for LTBI using claims data, and (2) estimate treatment completion rates for isoniazid regimens from commercial insurance claims...
October 27, 2017: Journal of Public Health Management and Practice: JPHMP
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