Cost-effectiveness of mask mandates on subways to prevent SARS-CoV-2 transmission in the United States.

BACKGROUND: Community-based mask wearing has been shown to reduce the transmission of SARS-CoV-2. However, few studies have conducted an economic evaluation of mask mandates, specifically in public transportation settings. This study evaluated the cost-effectiveness of implementing mask mandates for subway passengers in the United States by evaluating its potential to reduce COVID-19 transmission during subway travel. MATERIALS AND METHODS: We assessed the health impacts and costs of subway mask mandates compared to mask recommendations based on the number of infections that would occur during subway travel in the U.S. Using a combined box and Wells-Riley infection model, we estimated monthly infections, hospitalizations, and deaths averted under a mask mandate scenario as compared to a mask recommendation scenario. The analysis included costs of implementing mask mandates and COVID-19 treatment from a limited societal perspective. The cost-effectiveness (net cost per averted death) of mandates was estimated for three different periods based on dominant SARS-CoV-2 variants: Alpha, Beta, and Gamma (November 2020 to February 2021); Delta (July to October 2021); and early Omicron (January to March 2022). RESULTS: Compared with mask recommendations only, mask mandates were cost-effective across all periods, with costs per averted death less than a threshold of $11.4 million (ranging from cost-saving to $3 million per averted death). Additionally, mask mandates were more cost-effective during the early Omicron period than the other two periods and were cost saving in January 2022. Our findings showed that mandates remained cost-effective when accounting for uncertainties in input parameters (e.g., even if mandates only resulted in small increases in mask usage by subway ridership). CONCLUSIONS: The findings highlight the economic value of mask mandates on subways, particularly during high virus transmissibility periods, during the COVID-19 pandemic. This study may inform stakeholders on mask mandate decisions during future outbreaks of novel viral respiratory diseases.

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.

Ethical issues in expanding latent TB management in high burden countries.

Global efforts are being made to eliminate tuberculosis (TB) as a public health problem by 2030. These efforts are being thwarted by the challenge of effective management to minimise the progression of latent TB infection (LTBI) to TB, thereby interrupting the chain of transmission. Approximately 5%-10% LTBI cases eventually develop TB in their lifetime with the risk being higher in children, people living with HIV/AIDS (PLHIV), undernourished people, and patients with diabetes, chronic kidney disease, silicosis, and other comorbid conditions. Apart from operational barriers, complex ethical issues govern decision-making processes in either retaining current LTBI management practices or advocating implementation of the latest World Health Organization guidelines, which suggest extending treatment to vulnerable groups who have a higher risk of progression to TB. Newer LTBI treatment regimens have a diminished risk of toxicity that allays threats to patient safety. Public health justification for treating LTBI can also override patient autonomy, but the lack of a patient-centred approach is associated with poor adherence and treatment outcomes. Cost-effectiveness studies need to evaluate the gains and losses accruing from funding treatment of LTBI versus similar costs in nutritional interventions for managing undernutrition. Similarly, the impact of diverting resources available for management of the existing active TB control programmes to expanding LTBI treatment also needs to be assessed. In conclusion, a comprehensive LTBI treatment strategy built on the basis of high-quality evidence is the best way forward for resolving the ethical considerations at the heart of LTBI management in the developing world. Keywords: Tuberculosis; India; Latent TB; Medical ethics.

Rifampin-resistant Tuberculosis in the United States, 1998-2014.

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.

Bedaquiline for the Treatment of Multidrug-resistant Tuberculosis in the United States.

BACKGROUND: In 2012, the Food and Drug Administration approved use of bedaquiline fumarate as part of combination therapy for multidrug-resistant tuberculosis (MDR TB). We describe treatment outcomes, safety, and tolerability of bedaquiline in our case series. METHODS: Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through 4 TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events. RESULTS: Of 14 patients, 7 (50%) had MDR, 4 (29%) had pre-extensively drug-resistant (XDR), and 3 (21%) had XDR TB. All had pulmonary TB, 5 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear positive. One patient (7%) had HIV coinfection, 5 (36%) had diabetes mellitus, and 5/14 (36%) had previous treatment TB. All patients were non-US-born and 5/14 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26-116); 5 after starting bedaquiline. Twelve (86%) completed treatment and 1 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. Common adverse events were peripheral neuropathy 7/14 (50%), not customarily associated with bedaquiline use, and QTc prolongation 6/14 (43%). CONCLUSIONS: Of 14 patients, 1 (7%) had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series (7%) support use of bedaquiline for the treatment of MDR/XDR TB.

Tuberculosis Regional Training and Medical Consultation Centers in the United States: Characteristics, outcomes, and quality of medical consultations, June 1, 2010 - May 31, 2014.

BACKGROUND: Tuberculosis (TB) Regional Training and Medical Consultation Centers (RTMCCs) were established in 2005 for TB medical consultation, training and education in the United States. A medical consultation database (MCD) captured all consultations provided by RTMCCs; we report on those provided from June 1, 2010 to May 31, 2014. METHODS: All MCD consultations during 2010-2014 were categorized into: provider type, setting, consultation topic, and patient age. We analyzed data frequencies and performed subgroup analyses by RTMCC, by TB incidence for the geographical area, and by year of consultation. End-user satisfaction was assessed by a 2016 telephone evaluation of RTMCC services. RESULTS: A total of 11,074 consultations were delivered, with 10,754 (97.1%) in the U.S. and its current or former territories. Of these, 6018 (56%) were for high, 2443 (22.7%) for medium, and 2293 (21.3%) for low TB incidence settings. Most were for adults (81.3%) and answered within 24 h (96.2%). Nearly 2/3 consultations originated from health departments; providers included mostly physicians (44.3%) or nurses (37.6%). Common consult categories included TB disease (47.7%), case management (29.8%), latent TB infection (19.3%), diagnosis (16.1%), pharmacology (14.7%) and adverse side effects (14.3%). Among adverse side effects, hepatotoxicity was most common (39.6%). Volume and nature of consult requests remained relatively stable over the four-year period. Feedback from a 2016 CDC evaluation indicated overall satisfaction with RTMCC medical consultation services. CONCLUSION: RTMCCS were an important source of TB medical consultation over the time-frame of this assessment and provided quality expert consultation within 24 h. RMTCCs represent a reservoir of TB subject-matter expertise in the United States.

Treatment of Drug-Resistant Tuberculosis.

The treatment of drug-resistant tuberculosis (TB) is complicated and has evolved significantly in the past decade with the advent of rapid molecular tests and updated evidence-based guidelines of the World Health Organization and other organizations. The latest recommendations incorporate the use of new drugs and regimens that maximize efficacy and minimize toxicity to improve treatment outcomes for the patients. This article provides an overview of the latest published strategies for clinical and programmatic management of drug-resistant TB.

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.

Background: 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.Methods: 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.Results: 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.Conclusions: 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.

Tuberculosis in the United States: Medical Consultation Services Provided by 5 Tuberculosis Regional Training and Medical Consultation Centers, 2013-2017.

With only 9105 new US tuberculosis (TB) cases reported in 2017, expert consultation is essential for TB care. Data were captured 2013-2017 from consultations by 5 CDC-funded centers, now the TB Centers of Excellence (COEs). 14 586 consultations were provided to TB providers, most related to TB disease and treatment regimens.

The end TB strategy for India.

India has made great progress towards TB prevention and control with the adoption of the National Strategic Plan 2017-2025 with significantly greater allocated resources and high level political commitment. Aligning with the global End TB Strategy, India has announced the target of ending TB by 2025, five years ahead of the rest of the world. The End TB strategy is comprised of a multi-pronged approach incorporating patient-centered care and prevention, bold policies and supportive systems, and intensified research and innovation. In the past decade, India has made great strides towards ending TB, but the challenges, especially in a high burden setting, are great, and achieving our ambitious targets and goals will require partnering with all stakeholders including civil society and the community.

Higher Rates of Tuberculosis Among Class B1 Filipino Immigrants to Hawaii Compared to Nationwide, 2010-2014.

BACKGROUND: Immigrants to the United States from countries with a high burden of tuberculosis (TB) who have abnormal chest radiographs but negative sputum cultures during pre-immigration screening (TB Class B1) have a high risk of being diagnosed with TB disease within 1 year of arrival. METHODS: Using 2010-2014 national surveillance data, we compared proportions of Class B1 Filipino immigrants who received a diagnosis of TB disease within 1 year of arrival to Hawaii to proportions in other U.S. states (not including Hawaii) using chi-squared tests. RESULTS: In Hawaii, 40/1190 (3.4%) of Class B1 Filipino immigrants to Hawaii received a diagnosis of TB disease within 1 year of arrival compared with 220/16,035 (1.4%) nationwide (P < .01). CONCLUSIONS: During 2010-2014, the percentage of recent Class B1 Filipino immigrants in Hawaii with TB disease diagnosed within 1 year of arrival was over twice that as nationwide.

Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India.

The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection.

Pediatric tuberculosis consultations across 5 CDC regional tuberculosis training and medical consultation Centers.

BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) funds five Regional Tuberculosis Training and Medical Consultation Centers (RTMCCs) that provide training and consultation for tuberculosis (TB) control and management. RTMCC utilization for assistance with diagnosis and management of TB in children has not been described. We analyzed pediatric TB consultations performed across all RTMCCs in terms of question type, provider type, and setting. METHODS: The CDC medical consultation database was queried for consultations regarding patients ≤ 18 years provided between 1/1/13-4/22/15 by all RTMCCs (Curry International TB Center, Heartland National TB Center, Mayo Clinic Center for TB, New Jersey Medical School Global TB Institute, Southeastern National TB Center). Each query was categorized into multiple subject areas based on provider type, setting, consultation topic, and patient age. RESULTS: The 5 RTMCCs received 1164 pediatric consultation requests, representing approximately 20% of all consultations performed by the centers during the study period. Providers requesting consults were primarily physicians (46.3%) or nurses (45.0%). The majority of pediatric consult requests were from state and local public health departments (679, 58.3%) followed by hospital providers (199, 17.1%); fewer requests came from clinicians in private practice (84, 7.2%) or academic institutions (40, 3.4%). Consults addressed 14 different topics, most commonly management of children with TB disease (19.1%), latent TB infection (LTBI) (18.2%), diagnosis or laboratory testing (18.7%), and pharmacology (9.2%). DISCUSSION: Pediatric consultations accounted for approximately 20% of all consultations performed by RTMCCs during the study period. RTMCCs were utilized primarily by public health departments regarding management of TB disease, LTBI, and diagnosis or laboratory testing. The relative underutilization of the RTMCCs by clinicians in non-public health settings, who often manage children with TB exposure or infection, warrants further study. As US TB case rates decline and providers become less experienced with childhood TB, medical consultation support may become increasingly important.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection.

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis.

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.

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

BACKGROUND: In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies. METHODS: Blood samples were collected at 0 (RMI only), 1, 2 and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and maximal drug concentration (Cmax) of levofloxacin, elimination half-life and area under the curve from 0 to 24 hours (AUC0-24 hours × µg/mL) were correlated to determine the optimal dosage and to examine associations. Population pharmacokinetics and target attainment were modeled. With results from the Federated States of Micronesia, dosages were increased in RMI toward the target Cmax for Mycobacterium tuberculosis, 8-12 µg/mL. RESULTS: Cmax correlated linearly with per-weight dosage. Neither Cmax nor half-life was associated with gender, age, body mass index, concurrent medications or predose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ≥8 µg/mL was observed, and modeling corroborated a high target attainment across the ratio of the area under the free concentration versus time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values. CONCLUSIONS: Levofloxacin dosage should be 15-20 mg/kg for Cmax ≥8 µg/mL and a high target attainment across fAUCss,0-24/MIC values in children ≥2 years of age.