Background. Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because ...published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. Methods. We conducted a systematic review of studies published 1 January 1994–31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. Results. We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%–99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Conclusions. Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.
The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline ...on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.
Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.
New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.
We estimated direct costs of a 4-month or 6-month regimen for drug-susceptible pulmonary tuberculosis treatment in the United States. Costs were $23,000 per person treated. Actual treatment costs ...will vary depending on examination and medication charges, as well as expenses associated with directly observed therapy.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public ...health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Monoresistance to rifamycins necessitates longer and more toxic regimens for tuberculosis (TB). We examined characteristics and mortality associated with rifampin-monoresistant ...(RMR) TB in the United States.
Methods
We analyzed Mycobacterium tuberculosis culture-positive cases reported to the National TB Surveillance System (excluding California) between 1998 and 2014. We defined RMR TB found on initial drug susceptibility testing and possible acquired rifampin-resistant (ARR) TB. We assessed temporal trends in RMR TB. For both classifications of rifampin resistance, we calculated adjusted risk ratios (adjRRs) and 95% confidence intervals (CIs) for characteristics associated with mortality when compared with drug-susceptible TB in multivariable models using backward selection.
Results
Of 180 329 TB cases, 126 431 (70%) were eligible for analysis, with 359 (0.28%) of eligible cases reported as RMR. The percentage of RMR TB cases with HIV declined 4% annually between 1998 and 2014. Persons with HIV and prior TB were more likely to have RMR TB (adjRR, 25.9; 95% CI, 17.6–38.1), as were persons with HIV and no prior TB (adjRR, 3.1; 95% CI, 2.4–4.1) vs those without either characteristic, controlling for other statistically significant variables. RMR cases had greater mortality (adjRR, 1.4; 95% CI, 1.04–1.8), controlling for HIV and other variables. Persons with HIV had greater risk of ARR than persons without HIV (adjRR, 9.6; 95% CI, 6.9–13.3), and ARR was also associated with increased mortality, controlling for HIV and other variables.
Conclusions
All forms of rifampin resistance were positively associated with HIV infection and increased mortality.
We examined cases of rifampin-monoresistant and acquired rifampin-resistant tuberculosisin in the United States between 1998 and 2014. All forms of rifampin resistance were positively associated with human immunodeficiency virus infection, delayed culture conversion, and increased mortality.
To investigate treatment outcomes and associated characteristics of persons experiencing homelessness who received 12-weekly doses of directly observed isoniazid and rifapentine (3HP/DOT) treatment ...for latent TB infection (LTBI).
Among homeless persons treated with 3HP/DOT during July 2011 -June 2015 in 11 U.S. TB programs, we conducted descriptive analyses of observational data, and identified associations between sociodemographic factors and treatment outcomes. Qualitative interviews were conducted to understand programmatic experiences.
Of 393 persons experiencing homelessness (median age: 50 years; range: 13-74 years), 301 (76.6%) completed treatment, 55 (14.0%) were lost to follow-up, 18 (4.6%) stopped because of an adverse event (AE), and 19 (4.8%) stopped after relocations or refusing treatment. Eighty-one (20.6%) had at least one AE. Persons aged ≥65 were more likely to discontinue treatment than persons aged 31-44 years. Programs reported difficulty in following up with persons experiencing homelessness because of relocations, mistrust, and alcohol or drug use.
This study demonstrates the feasibility of administering the 3HP/DOT LTBI regimen to persons experiencing homelessness, a high-risk population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United ...States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity.
We created a mathematical model using all incident TB disease cases during 2013-2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals CI) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015.
We estimated that 2.7% (CI: 2.6%-2.8%) of the U.S. population, or 8.6 (CI: 8.3-8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%-1.1%) and among non-US-born persons was 13.9% (CI: 13.5%-14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45-64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%).
Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
We estimated long-term tuberculosis (TB) trends in the US population and assessed prospects for TB elimination. We used a detailed simulation model allowing for changes in TB transmission, ...immigration, and other TB risk determinants. Five hypothetical scenarios were evaluated from 2017 to 2100: 1) maintain current TB prevention and treatment activities (base case); 2) provision of latent TB infection testing and treatment for new legal immigrants; 3) increased uptake of latent TB infection screening and treatment among high-risk populations, including a 3-month isoniazid-rifapentine regimen; 4) improved TB case detection; and 5) improved TB treatment quality. Under the base case, we estimate that by 2050, TB incidence will decline to 14 cases per million, a 52% (95% posterior interval (PI): 35, 67) reduction from 2016, and 82% (95% posterior interval: 78, 86) of incident TB will be among persons born outside of the United States. Intensified TB control could reduce incidence by 77% (95% posterior interval: 66, 85) by 2050. We predict TB may be eliminated in US-born but not non–US-born persons by 2100. Results were sensitive to numbers of people entering the United States with latent or active TB, and were robust to alternative interpretations of epidemiologic evidence. TB elimination in the United States remains a distant goal; however, strengthening TB prevention and treatment could produce important health benefits.
As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per ...million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).
To estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.
We created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.
In the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to $48 billion. These had an incremental cost per QALY of $657,000 to $3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.
Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Older age is a risk factor for tuberculosis (TB) in low incidence settings. Using data from the US National TB Surveillance System and American Community Survey, we estimated ...trends and racial/ethnic differences in TB incidence among US-born cohorts aged ≥50 years.
Methods
In total, 42 000 TB cases among US-born persons ≥50 years were reported during 2001–2019. We used generalized additive regression models to decompose the effects of birth cohort and age on TB incidence rates, stratified by sex and race/ethnicity. Using genotype-based estimates of recent transmission (available 2011–2019), we implemented additional models to decompose incidence trends by estimated recent versus remote infection.
Results
Estimated incidence rates declined with age, for the overall cohort and most sex and race/ethnicity strata. Average annual percentage declines flattened for older individuals, from 8.80% (95% confidence interval CI 8.34–9.23) in 51-year-olds to 4.51% (95% CI 3.87–5.14) in 90-year-olds. Controlling for age, incidence rates were lower for more recent birth cohorts, dropping 8.79% (95% CI 6.13–11.26) on average between successive cohort years. Incidence rates were substantially higher for racial/ethnic minorities, and these inequalities persisted across all birth cohorts. Rates from recent infection declined at approximately 10% per year as individuals aged. Rates from remote infection declined more slowly with age, and this annual percentage decline approached zero for the oldest individuals.
Conclusions
TB rates were highest for racial/ethnic minorities and for the earliest birth cohorts and declined with age. For the oldest individuals, annual percentage declines were low, and most cases were attributed to remote infection.
Among US-born individuals aged 50 and over, estimated tuberculosis incidence rates are highest for racial/ethnic minorities and for the earliest birth cohorts. Within birth cohorts, incidence rates decline with age for almost all groups.
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