The Effectiveness of a 9-Month Regimen of Isoniazid Alone versus 3- and 4-Month Regimens of Isoniazid plus Rifampin for Treatment of Latent Tuberculosis Infection in Children: Results of an 11-Year Randomized Study

Spyridis, Νikos; Spyridis, Panayotis; Gelesme, Anna; Sypsa, Vana; Valianatou, Mina; Metsou, Flora; Gourgiotis, D; Τσολιά, Μαρία

doi:10.1086/520983

Cited by 220 publications

(128 citation statements)

References 32 publications

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“…A combination of isoniazid and rifampicin for 3 months has been shown to be a promising alternative. It is effective, increases adherence and has been recommended in the UK [102,151,152].…”

Section: Sectionmentioning

confidence: 99%

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

Mack

Migliori

Sester

et al. 2009

European Respiratory Journal

509

446

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Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-c release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection.In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

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“…A combination of isoniazid and rifampicin for 3 months has been shown to be a promising alternative. It is effective, increases adherence and has been recommended in the UK [102,151,152].…”

Section: Sectionmentioning

confidence: 99%

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

Mack

Migliori

Sester

et al. 2009

European Respiratory Journal

509

446

View full text Add to dashboard Cite

show abstract

“…However, the combination regimen was associated with more discontinuations because of adverse effects 156. A few paediatric studies have shown that a 3‐month regimen of isoniazid and rifampicin treatment is safe and effective 157, 158. Therefore, we recommend that children with HIV infection who have been exposed to TB or have latent TB infection and who are not receiving ART can be treated with either 3 months of isoniazid and rifampicin or 6−9 months of isoniazid (according to local policy in HIV‐uninfected children); for those on ART, in view of drug interactions, the preferred preventive treatment is 6–9 months of isoniazid.…”

Section: Coinfectionsmentioning

confidence: 99%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

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The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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“…Rifampin (RIF) for 4 months is an alternative in the United States and Canada (1,4,11). In the United Kingdom, a 3-month regimen of RIF1INH is used with success (12,13). The combination of RIF1pyrazinamide (PZA) was first shown to have potent sterilizing activity in a model of LTBI using mice immunized with BCG (14).…”

mentioning

confidence: 99%

Short-Course Therapy with Daily Rifapentine in a Murine Model of Latent Tuberculosis Infection

Zhang¹,

Zhang²,

Rosenthal³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Regimens recommended to treat latent tuberculosis infection (LTBI) are 3 to 9 months long. A 2-month rifampin1 pyrazinamide regimen is no longer recommended. Shorter regimens are highly desirable. Because substituting rifapentine for rifampin in the standard regimen for active tuberculosis halves the treatment duration needed to prevent relapse in mice, we hypothesized daily rifapentine-based regimens could shorten LTBI treatment to 2 months or less. Objectives: To improve an existing model of LTBI chemotherapy and evaluate the efficacy of daily rifapentine-based regimens. Methods: Mice were immunized with a more immunogenic recombinant Bacille Calmette-Guérin strain (rBCG30) and received very lowdose aerosol infection with Mycobacterium tuberculosis to establish a stable lung bacterial burden below 10 4 CFU without drug treatment. Mice received a control (isoniazid alone, rifampin alone, rifampin1isoniazid, rifampin1pyrazinamide) or test (rifapentine alone, rifapentine1isoniazid, rifapentine1pyrazinamide, rifapentine1 isoniazid1pyrazinamide) regimen for 8 weeks. Rifamycin doses were 10 mg/kg/d, analogous to the same human doses. Outcomes were biweekly lung CFU counts and relapse after 4 to 8 weeks of treatment. Measurements and Main Results: M. tuberculosis CFU counts remained stable around 3.65 log 10 in immunized, untreated mice. Isoniazid or rifampin left all or most mice culture-positive at week 8. Rifampin1 isoniazid cured 0 and 53% of mice and rifampin1pyrazinamide cured 47 and 100% of mice in 4 and 8 weeks, respectively. Rifapentine-based regimens were more active than rifampin1isoniazid and indistinguishable from rifampin1pyrazinamide. Conclusions: In this improved murine model of LTBI chemotherapy with very low lung burden, existing regimens were well represented. Daily rifapentine-based regimens were at least as active as rifampin1pyrazinamide, suggesting they could effectively treat LTBI in 6 to 8 weeks.Keywords: BCG; mouse; isoniazid; rifampin; pyrazinamide Identification and treatment of latent tuberculosis infection (LTBI) is necessary to eliminate tuberculosis (TB) in lowincidence countries (1-4). This strategy may soon be applied more widely now that new diagnostic tests are available to discriminate LTBI from past vaccination with Bacille CalmetteGuérin (BCG) or exposure to nontuberculous mycobacteria (5). Preventive therapy is also effective, though vastly underutilized, in reducing TB risk among HIV-infected persons with LTBI in high-prevalence settings, including persons receiving concomitant highly active antiretroviral therapy (6-9).Current LTBI treatment guidelines generally consider isoniazid (INH) for 6 to 12 months to be the first-line regimen (1, 4, 10). Rifampin (RIF) for 4 months is an alternative in the United States and Canada (1, 4, 11). In the United Kingdom, a 3-month regimen of RIF1INH is used with success (12, 13). The combination of RIF1pyrazinamide (PZA) was first shown to have potent sterilizing activity in a model of LTBI using mice immunized with BCG (14). Aft...

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The Effectiveness of a 9-Month Regimen of Isoniazid Alone versus 3- and 4-Month Regimens of Isoniazid plus Rifampin for Treatment of Latent Tuberculosis Infection in Children: Results of an 11-Year Randomized Study

Cited by 220 publications

References 32 publications

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Short-Course Therapy with Daily Rifapentine in a Murine Model of Latent Tuberculosis Infection

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