The Scope and Impact of Treatment of Latent Tuberculosis Infection in the United States and Canada

Isoniazid (INH) has been the mainstay of treatment of latent tuberculosis infection for almost 50 years. The currently recommended preferred regimen is 9 months daily self-administered INH (9H); this has efficacy of more than 90% if completed properly. Unfortunately, INH is associated with serious adverse events, including hepatotoxicity. Although risk factors for this complication are well established, allowing for better selection of candidates for therapy, this complication still occurs, and is occasionally fatal. Hence close follow up of patients is necessary, increasing the cost and complexity of treatment. This problem, plus the lengthy duration, results in poor acceptance by patients and providers, and poor adherence by patients. As a result, many preventable cases of tuberculosis continue to occur, and the public health impact of latent tuberculosis infection treatment is suboptimal. These problems have spurred interest in finding shorter, safer and cheaper alternative regimens, with similar efficacy. Of the many regimens that have been examined, 2 months of rifampin and pyrazinamide has excellent efficacy-in experimental studies in mice and randomized trials, largely in HIV-infected persons. However, while the safety of 2 months of rifampin and pyrazinamide appears acceptable in HIV-infected persons and children, in non-HIV-infected adults this regimen is associated with an unacceptably high rate of severe liver toxicity. Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials. However, completion of therapy and toxicity has been the same as with INH-possibly because two drugs are taken rather than one.The fourth commonly studied regimen is 4 months rifampin. This has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity. However, only one trial has evaluated efficacy and effectiveness of mono-rifampin therapy. In this trial, 3 months rifampin had somewhat better efficacy than either 3 months of isoniazid and rifampin (3HR) or 6 months isoniazid. Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self-administered), while the second, which is nearing completion, compares daily self-administered 9H with 3 months directly observed once weekly INH combined with rifapentine. The results of these two trials will likely shape future recommendations substantially.r esp_1751 603..622

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“…In the USA, for example, it is estimated that of the 300 000-400 000 persons who start LTBI treatment each year, more than 90% take INH. 48,54 …”

Section: Isoniazid For Latent Tuberculosis Infection Treatmentmentioning

confidence: 99%

Treatment of latent tuberculosis infection: An update

2010

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“…Treatment for this symptomless condition is lengthy (usually 6-12 months) and often not finished by those who initiate it. In [38], the authors use estimates of 30-64% and 69-93% for the percentages of treatments that are completed and the efficacy of treatment when completed, respectively. This gives a net efficacy for treatment of LTBI (including adherence and effectiveness) of about 20-60%.…”

Section: How Much Better Would One Vaccination Policy Be?mentioning

confidence: 99%

Could changes in national tuberculosis vaccination policies be ill-informed ?

Gerberry

Milner

2012

Math. Model. Nat. Phenom.

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Abstract. National policies regarding the BCG vaccine for tuberculosis vary greatly throughout the international community and several countries are currently considering discontinuing universal vaccination. Detractors of BCG point to its uncertain effectiveness and its interference with the detection and treatment of latent tuberculosis infection (LTBI).In order to quantify the trade-off between vaccination and treatment of LTBI, a mathematical model was designed and calibrated to data from Brazil, Ghana, Germany, India, Mexico, Romania, the United Kingdom and the United States. Country-specific thresholds for when LTBI treatment outperforms mass vaccination were found and the consequences of policy changes were estimated.Our results suggest that vaccination outperforms LTBI treatment in all settings but with greatly reduced efficiency in low incidence countries. While national policy statements emphasize BCG's interference with LTBI detection, we find that reinfection should be more determinant of a country's proper policy choice.

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“…prescribed and a course of treatment completed, rates of reactivation TB among persons with a positive tuberculin skin test (TST) may have been reduced (19).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Revisiting Rates of Reactivation Tuberculosis

Horsburgh¹,

O’Donnell²,

Chamblee³

et al. 2010

Am J Respir Crit Care Med

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131

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Rationale: Reactivation tuberculosis (TB) occurs as a result of reactivation of latent TB infection (LTBI), and was reported to occur in the United States at a rate of 0.10 to 0.16 cases per 100 person-years in the 1950s; it has not been measured since. Objectives: To calculate the rate of reactivation TB in a U.S. community. Methods: A population-based tuberculin skin test survey for LTBI was performed in western Palm Beach County, Florida, from 1998 to 2000 along with a cluster analysis of TB case isolates in the same area from 1997 to 2001. Reactivation (unclustered) TB was presumed to have arisen from the population with LTBI. Measurements and Main Results: The rate of reactivation TB among persons with LTBI without HIV infection was 0.040 cases per 100 person-years (95% confidence interval ½CI, 0.024-0.067) using the n method and 0.058 cases per 100 person-years (95% CI, 0.038-0.089) using the n-1 method. HIV infection was the strongest risk factor for reactivation (rate ratio ½RR, 57; 95% CI, 27-120; P , 0.001). Among persons without HIV infection, reactivation was increased among those older than 50 years (RR, 3.8; 95% CI, 1.3-11) and among those born in the United States (RR, 3.2; 95% CI, 1.1-9.3). Conclusions: Rates of reactivation TB in this area have declined substantially since the 1950s. The greatest part of this decline may be attributed to the disappearance of old, healed TB in the population. If similar declines are seen in other areas of the United States, the cost-effectiveness of screening and treatment of LTBI may be substantially less than previously estimated.

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The Scope and Impact of Treatment of Latent Tuberculosis Infection in the United States and Canada

Abstract: LTBI treatment is initiated among a substantial number of persons in the United States and Canada, primarily in the public sector. Treatment of LTBI can significantly decrease the tuberculosis burden.

Cited by 101 publications

References 5 publications

Treatment of latent tuberculosis infection: An update

Treatment of latent tuberculosis infection: An update

Could changes in national tuberculosis vaccination policies be ill-informed ?

Revisiting Rates of Reactivation Tuberculosis

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