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Background: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring., Methods: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring., Results: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months., Conclusions: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible., Competing Interests: Potential conflicts of interest. C. A. H. reports honoraria from the Infectious Diseases Society of America for an IDWeek 2022 presentation, travel support from the University of Employer, and Pfizer stock ownership. M. C. S. reports grants from the National Institute of Minority Health and Health Disparities (R21MD017943-01; Neighborhood transportation vulnerability and geographic patterns of diabetes-related limb loss) and the American Diabetes Association (Diabetic Ulcer Computational Sensing System), paid to the institution, and payment from the Society for Advancement in Wound Care for speaking at the 2023 spring meeting. D. A. reports a grant from the Centers for Disease Control and Prevention (CDC) as the primary investigator of TB Centers of Excellence, travel support from the CDC, and participation in the CDC's Tuberculosis Trials Consortium data and safety monitoring board. L. C. reports grants from USAID (federal award to institution for global research capacity building) and the California Department of Public Health (training award to institution for pandemic response); an unpaid position as president of the Executive Leadership Board for the North American Region Union Against Tuberculosis and Lung Diseases; and an unpaid position on the coordinating board of STOP TB USA. M. B. D reports institutional contracts with the CDC and Westat. A. V. E. reports travel support for meetings from the CDC. K. A. R. reports grants and travel support from the CDC’s Division of TB Elimination and a position as the liaison for the National Association of County and City Health Officials to the Advisory Committee for the Elimination of Tuberculosis. M. C. R. reports travel support for meeting from Association of Public Health Laboratories (APHL) and positions as chair of the APHL Infectious Diseases Committee and member of the APHL Tuberculosis Subcommittee and the College of American Pathologists Microbiology Committee. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anemia remains an important global health problem. Inexpensive, accurate, and noninvasive solutions are needed to monitor and evaluate anemia in resource-limited settings. We evaluated the performance of multiple point-of-care hemoglobin devices, including a novel noninvasive smartphone application tested on Apple® and Android® cell phones, Masimo Pronto®, and HemoCue® Hb-301 and Hb-801, against a gold-standard hematology analyzer (reference hemoglobin) using venous blood. We examined correlations between hemoglobin devices and reference hemoglobin, device accuracy (average bias, Bland-Altman plots, clinical performance) and classification bias (sensitivity, specificity) among 299 refugees (10mo-65y) in Atlanta, GA. Semi-structured interviews (n = 19) with participants and staff assessed usability and acceptability. Mean reference hemoglobin was 13.7 g/dL (SD:1.8) with 12.5% anemia. Noninvasive hemoglobin devices were not well correlated with reference hemoglobin (Apple® R2 = 0.08, Android® R2 = 0.11, Masimo Pronto® R2 = 0.29), but stronger correlations were reported with HemoCue® Hb-301 (R2 = 0.87) and Hb-801 (R2 = 0.88). Bias (SD) varied across each device: Apple®: -1.6 g/dL (2.0), Android®: -0.7 g/dL (2.0), Masimo Pronto®: -0.4 g/dL (1.6), HemoCue® Hb-301: +0.4 g/dL (0.7) and HemoCue® Hb-801: +0.2 g/dL (0.6). Clinically acceptable performance (within ± 1 g/dL of reference hemoglobin) was higher for the invasive devices (HemoCue® Hb-301: 90.3%; HemoCue® Hb-801: 93.4%) compared to noninvasive devices (Apple®: 31.5%; Android®: 34.6%; Masimo Pronto®: 49.5%). Sensitivity and specificity were 63.9% and 48.2% for Apple®, 36.1% and 67.6% for Android®, 45.7% and 85.3% for Masimo Pronto®, 54.3% and 97.6% for HemoCue® Hb-301, and 66.7% and 97.6% for HemoCue® Hb-801. Noninvasive devices were considered easy to use and were the preferred method by participants. Among the only studies to compare multiple point-of-care approaches to hemoglobin testing, the diagnostic ability of HemoCue® was comparable to reference hemoglobin, while noninvasive devices had high user acceptability but considerable biases. Improvements in noninvasive device performance and further testing in anemic populations are recommended before broader use., Competing Interests: The authors have declared that no competing interest exists.

The association between human immunodeficiency virus (HIV) infection and tuberculosis (TB) mortality has been studied extensively, but the impact of HIV on other clinically relevant aspects of TB care such as TB drug-related adverse events (AEs), hospital readmissions, and TB treatment duration is less well characterized. We describe the association of HIV infection with TB clinical complexities and outcomes in a high HIV prevalence cohort in the United States. This is a retrospective cohort study among patients treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital in Atlanta, GA. Univariate analysis was used to estimate association of HIV with TB treatment interruption due to AEs, hospital readmissions, and treatment duration. Final unfavorable TB treatment outcome was defined as death, loss to follow-up, or recurrent TB. Logistic regression modeling was used to estimate association of HIV with final unfavorable outcomes. Among 274 patients with TB, 96 (35%) had HIV coinfection. HIV-positive patients had more TB treatment interruptions due to AE (34% vs. 15%), were more likely to have a hospital readmission (50% vs. 21%), and received longer TB treatment (9.9 months vs. 8.8 months) compared to HIV-negative patients ( p  < .01 for all). HIV infection was not associated with final unfavorable outcomes in univariate [odds ratio (OR) = 1.86; confidence interval (95% CI) 0.99-3.49] or multivariate analysis (aOR = 1.13; 95% CI 0.52-2.39) ( p  ≥ .05 for both). While HIV infection was not associated with final unfavorable TB outcomes, TB/HIV coinfected patients had more complex treatment course underscoring the importance of maintaining resources and expertise to treat coinfected patients in our and similar settings.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis -specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 M. tuberculosis Ags. Using IFN-γ production as a readout of Ag specificity, the assay can be conducted using 50 μl of blood per test condition and can be expanded to accommodate additional Ags. We evaluated the intra- and interassay variability, and implemented testing of the assay in diverse cohorts of M. tuberculosis -unexposed healthy adults, foreign-born adults with latent M. tuberculosis infection residing in the United States, and tuberculosis household contacts with latent M. tuberculosis infection in a tuberculosis-endemic setting in Kenya. The M. tuberculosis -specific T cell response spectrum assay further enhances the immunological toolkit available for evaluating M. tuberculosis -specific T cell responses across different states of M. tuberculosis infection, and can be readily implemented in resource-limited settings. Moreover, application of the assay to longitudinal cohorts will facilitate evaluation of treatment- or vaccine-induced changes in the breadth and specificity of Ag-specific T cell responses, as well as identification of M. tuberculosis -specific T cell responses associated with M. tuberculosis infection outcomes., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Background: Antiretroviral therapy (ART) for persons with HIV infection prevents tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB treatment improves outcomes. We examined ART use, retention in care, and viral suppression (VS) before, during, and 3 years following TB treatment for an inner-city cohort in the United States., Methods: Retrospective cohort study among persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital., Results: Among 274 persons with culture-confirmed TB, 96 (35%) had HIV co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous diagnoses. Among those with known HIV prior to TB, the median time of known HIV was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only 32% of patients had continuous VS 3 years after completing TB treatment. There were 3 TB recurrences and 3 deaths post-TB treatment; none of these patients had retention or VS after TB treatment., Conclusions: Among persons with active TB co-infected with HIV, we found that the majority had known HIV and were not on ART prior to TB diagnosis, and retention in care and VS post-TB treatment were very low. Strengthening the HIV care continuum is needed to improve HIV outcomes and further reduce rates of active TB/HIV co-infection in our and similar settings.

Background: Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes., Methods: A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC., Results: Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis., Conclusions: There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This study determines the nutritional status among refugee children entering one of the largest resettlement counties in the United States and identifies differences between incoming populations. Medical records of all newly arriving pediatric refugees (0-18 years) entering DeKalb County, Georgia between October 2010 and July 2011 were reviewed. Refugee children were grouped as African, Bhutanese, or Burmese (resettling from either Thailand or Malaysia) for comparative analysis. Approximately one in five refugees were anemic or malnourished, while a quarter had stool parasites, and nearly half had dental caries. African refugees had the highest anemia but the lowest underweight prevalence (p < 0.05). Compared to Burmese resettling from Malaysia, Burmese children from Thailand had a higher prevalence of anemia, underweight, and stool parasites (p < 0.05). Clinicians should use CDC medical screening guidelines for newly arriving pediatric refugees, as well as ensure proper nutritional support and follow-up care.

Background: People who travel to areas with high rabies endemicity and have animal contact are at increased risk for rabies exposure. We examined characteristics of international travelers queried regarding rabies vaccination during pretravel consultations at Global TravEpiNet (GTEN) practices during 2009-2010., Material and Methods: We performed bivariate and multivariable analyses of data collected from 18 GTEN clinics. Travel destinations were classified by strength level of rabies vaccination recommendation., Results: Of 13,235 travelers, 226 (2%) reported previous rabies vaccination, and 406 (3%) received rabies vaccine at the consultation. Common travel purposes for these 406 travelers were leisure (26%), research/education (17%), and nonmedical service work (14%). Excluding the 226 who were previously vaccinated, 8070 (62%) of 13,009 travelers intended to visit one or more countries with a strong recommendation for rabies vaccination; 1675 (21%) of these 8070 intended to travel for 1 month or more. Among these 1675 travelers, 145 (9%) were vaccinated, 498 (30%) declined vaccination, 832 (50%) had itineraries that clinicians determined did not indicate vaccination, and 200 (12%) remained unvaccinated for other reasons. In both bivariate and multivariate analyses, travelers with trip durations >6 months versus 1-3 months (adjusted odds ratio [OR]=4.9 [95% confidence interval [CI] 2.1, 11.4]) and those traveling for "research/education" or to "provide medical care" (adjusted OR=5.1 [95% CI 1.9, 13.7] and 9.5 [95% CI 2.2, 40.8], respectively), compared with leisure travelers, were more likely to receive rabies vaccination., Conclusions: Few travelers at GTEN clinics received rabies vaccine, although many planned trips 1 month long or more to a strong-recommendation country. Clinicians often determined that vaccine was not indicated, and travelers often declined vaccine when it was offered. The decision to vaccinate should take into account the strength of the vaccine recommendation at the destination country, duration of stay, availability of postexposure prophylaxis, potential for exposure to animals, and likelihood of recurrent travel to high-risk destinations.

Background: Approximately 70,000 refugees are resettled to the United States each year. Providing vaccination to arriving refugees is important to both reduce the health-related barriers to successful resettlement, and protect the health of communities where refugees resettle. It is crucial to understand the process and resources expended at the state/local and federal government levels to provide vaccinations to refugees resettling to the United States., Objectives: We estimated costs associated with delivering vaccines to refugees at the Board of Health Refugee Services, DeKalb county, Georgia (DeKalb clinic)., Methods: Vaccination costs were estimated from two perspectives: the federal government and the DeKalb clinic. Data were collected at the DeKalb clinic regarding resources used for vaccination: staff numbers and roles; type and number of vaccine doses administered; and number of patients. Clinic costs included labor and facility-related overhead. The federal government incurred costs for vaccine purchases and reimbursements for vaccine administration., Results: The DeKalb clinic average cost to administer the first dose of vaccine was $12.70, which is lower than Georgia Medicaid reimbursement ($14.81), but higher than the State of Georgia Refugee Health Program reimbursement ($8.00). Federal government incurred per-dose costs for vaccine products and administrative reimbursement were $42.45 (adults) and $46.74 (children)., Conclusions: The total costs to the DeKalb clinic for administering vaccines to refugees are covered, but with little surplus. Because the DeKalb clinic 'breaks even,' it is likely they will continue to vaccinate refugees as recommended by the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background:  International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness., Methods:  We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011., Results:  The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≥1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines., Conclusions:  Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.

Hepatitis B virus infection (HBV) remains highly endemic in many parts of the world. Refugees resettling in their host countries may carry a significant burden of disease due to HBV and may require long-term medical care. A retrospective descriptive study was conducted to assess the epidemiology of HBV and entry into medical care in refugee communities resettled in the State of Georgia over a five-year period: 2003-2007. Among 6,347 refugees (89.7% of those resettled) screened for HBV infection, six hundred and eighty (10.7%) were found to be HBsAg seropositive. Those between the ages of 10-39 years of age contributed to the majority of cases; and most originated from Africa (71%). All HBsAg positive cases were adequately referred to a primary care physician for further management but there are no formal feedback mechanisms in place to learn if those who tested positive for HBsAg accessed the primary healthcare system. HBV infection is a frequent infection among refugees resettled in the US. but their entry into healthcare to treat those with chronic infection is often unknown. Further efforts are required to assure their entry into the healthcare system. Primary care physicians caring for refugee patients should think about verifying HBV-infection status as part of health maintenance protocols.

Vitamin D regulates calcium homeostasis in the body and may play a major role in regulating immune responses to tuberculosis (TB). Pilot studies suggest that vitamin D supplementation may improve outcomes in pulmonary TB (PTB), but clinical evidence using vitamin D in TB treatment is limited. We present a case of vitamin D deficiency in a woman with refractory drug-susceptible PTB. Antituberculous therapy and the correction of vitamin D deficiency resulted in clinical and microbiologic improvement at month 13 of her treatment. The basis for vitamin D/TB interactions and a brief literature review are discussed. Data from controlled trials are needed to evaluate the efficacy of vitamin D as adjunctive TB therapy.

A 27-year-old, previously healthy Somali refugee presented with infertility. Cultures of endometrial tissue were positive for fully susceptible tuberculosis and she was diagnosed with genital tuberculosis. After 12 months of antituberculosis therapy, she attempted to become pregnant; however, use of in vitro fertilization and surrogate carrier probably will be needed given the degree of scar tissue present before treatment. Due to the increasing numbers of US-resettled refugees, physicians should consider genital tuberculosis in any refugee woman presenting with infertility or amenorrhea.