Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. Am J Respir Crit Care Med 161:S221‐S247, 2000). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States. The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta‐analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (eg with low‐quality evidence). These updated 2020 LTBI treatment guidelines include the NTCA‐ and CDC‐recommended treatment regimens that comprise three preferred rifamycin‐based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug‐resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al Treatment of drug‐resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93‐e142). The three rifamycin‐based preferred regimens are 3 months of once‐weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin‐based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin‐based regimens. In summary, sh...

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. Am J Respir Crit Care Med 161:S221-S247, 2000). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States. The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (eg with low-quality evidence). These updated 2020 LTBI treatment guidelines include the NTCA-and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019

Our results indicate that in a community that has implemented the essential elements of TB control, TB from ongoing transmission of M tuberculosis will continue to develop unless patients are diagnosed earlier and contacts are more completely identified. JAMA. 2000.

To determine whether chronic hypoxemia secondary to an intracardiac right-to-left shunt alters regulation of the myocardial 63-adrenergic receptor/adenylate cyclase system, we produced chronic hypoxemia in nine newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 wk. Eight lambs served as normoxemic controls. 13-receptor density (B.) and ligand affinity (KD) were determined with the radioligand '2"5iiodocyanopindolol and adenylate cyclase activity determined during stimulation with isoproterenol, sodium fluoride (NaF), and forskolin. During chronic hypoxemia, B.. decreased 45% (hypoxemic, 180.6±31.5 vs. control, 330.5±60.1 fmol/mg) in the left ventricle (exposed to hypoxemia alone) but was unchanged in the right ventricle (exposed to hypoxemia and pressure overload). KD was not different from control in either ventricle. Left ventricular isoproterenolstimulated adenylate cyclase activity was decreased by 39% (30.0±4.3% increase vs. 44.1±9.5% increase) whereas right ventricular adenylate cyclase activity was unchanged. Stimulation of adenylate cyclase with NaF or forskolin was not different from control in either ventricle. Circulating epinephrine was increased fourfold whereas circulating and myocardial norepinephrine were unchanged. These data demonstrate a downregulation of the left ventricular ,6-adrenergic receptor/adenylate cyclase system during chronic hypoxernia secondary to an intracardiac right-to-left shunt. (J. Clin. Invest. 1990. 85:68-74.) cyanotic heart disease -hypoxemia* myocardial fl-adrenergic receptor regulation

The propensity of Mycobacterium tuberculosis genotypes to spread across geographic boundaries was investigated by comparing the IS6110 and polymorphic GC-rich sequence patterns of M. The modern age of transportation has brought unprecedented rated countries and spread of multidrug-resistant organisms between distant domestic sites have been demonstrated, spread movement of large numbers of people across geographic boundaries, heightening concerns about the global disseminaof M. tuberculosis between geographically proximate regions has not been systematically examined [3, 5]. tion of infectious pathogens. This increasing mobility of human populations has resulted in instances of widespread disseminaAdvances in M. tuberculosis genotyping techniques have made it possible to determine the genetic relatedness of individtion of a number of pathogens, including serogroup A Neisseria meningitidis, Vibrio cholerae O1, and Mycobacterium tubercuual isolates and to study the geographic spread of specific genotypes [3 -5, 8 -11]. In this report, we describe a study in losis [1 -5].The dissemination of M. tuberculosis is of particular concern which IS6110 genotyping was used to investigate the occurrence of tuberculosis caused by the same genotype of M. tubergiven its airborne mode of transmission, the virulence of the organism, and the significant morbidity and costs associated culosis in geographically distinct but proximate areas, San Francisco and the East Bay. These areas are separated by San with tuberculosis. Furthermore, disparities in the prevalence of tuberculosis infection and disease, the frequency of drug Francisco Bay, but an estimated 371,403 individual trips are made daily across the bay by either bridge or rail [12,13]. resistance, and the effectiveness of tuberculosis control practices between different communities may favor the dissemination of M. tuberculosis from higher to lower prevalence areas [6,7]. The propensity of M. tuberculosis to spread between Materials and Methods communities, therefore, has important public health implica- losis registries. Isolates were genotyped using standard IS6110-The study protocol was reviewed and approved by the UCSF Committee based methods; the San Francisco and the East Bay isolates were on Human Research prior to initiation of the study.Grant support: NIH (AI-34238) and CDC (U52-CCU 900454).