Ted Cohen

• MD MPH DPH
• Professor at Yale School of Public Health

Background Massive internal migration from rural to urban areas poses new challenges for tuberculosis control in China. We aimed to combine genomic, spatial, and epidemiological data to describe the dynamics of tuberculosis in an urban setting with large numbers of migrants. Methods We did a population-based study of culture-positive Mycobacterium...

Background: In high-incidence settings, recurrent disease among previously treated individuals contributes substantially to the burden of incident and prevalent tuberculosis. The extent to which interventions targeted to this high-risk group can improve tuberculosis control has not been established. We aimed to project the population-level effect...

Background The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with seve...

Background. We aimed to identify and determine the etiology of ‘hotspots’ of concentrated multi-drug resistant tuberculosis (MDR-TB) risk in Lima, Peru. Methods. From 2009-2012, we conducted a prospective cohort study among households of TB cases from 106 health center (HC) areas in Lima, Peru. All notified TB cases and their household contacts we...

Finding optimal dosing strategies for treating bacterial infections is extremely difficult, and improving therapy requires costly and time-intensive experiments. To date, an incomplete mechanistic understanding of drug effects has limited our ability to make accurate quantitative predictions of drug-mediated bacterial killing and impeded the ration...

Over the past three decades, molecular epidemiological studies have provided new opportunities to investigate the transmission dynamics of M. tuberculosis. In most studies, a sizable fraction of individuals with notified tuberculosis cannot be included, either because they do not have culture-positive disease (and thus do not have specimens availab...

Delays in identifying and treating individuals with infectious tuberculosis (TB) contribute to poor health outcomes and allow ongoing community transmission of M. tuberculosis (Mtb). Current recommendations for screening for tuberculosis specify community characteristics (e.g., areas with high local tuberculosis prevalence) that can be used to targ...

Background Tuberculosis (TB) notifications and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends. Methods We identified four mechanisms potentially contributing to observed TB trends during 2020–...

Rationale: Individuals surviving TB disease may experience chronic sequelae that reduce survival and quality-of-life. These post-TB sequalae are not generally considered in estimates of the health impact of TB disease. Objectives: To estimate the TB-attributable reductions in life expectancy and quality-adjusted life expectancy for individuals d...

Background: In the United States, older adults have elevated prevalence of latent tuberculosis infection (LTBI) and incidence of tuberculosis (TB). Objective: To estimate the health benefits and cost-effectiveness of LTBI testing and treatment among the Medicare-eligible population. Design: Model-based cost-effectiveness analysis. Data source...

Background Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed samp...

Background Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians’ decisions to initiate TB treatment when initial bacteriological test results are negative. Methods and findings...

SARS-CoV-2 infection rates displayed striking temporal and spatial variation during the emergence of new variants globally and within the United States. While spatiotemporal “waves” of infection have been observed, quantitative assessments of their spread remain limited. Here, we estimate and compare the speed and spatial extent of the first two ma...

Effectively responding to drug-resistant tuberculosis (TB) requires accurate and timely information on resistance levels and trends. In contexts where use of drug susceptibility testing has not been universal (i.e. not all patients are offered testing), surveillance for rifampicin-resistance—one of the core drugs in the TB treatment regimen—has rel...

Pathogen sequencing is an important tool for disease surveillance and demonstrated its high value during the COVID-19 pandemic. Viral sequencing during the pandemic allowed us to track disease spread, quickly identify new variants, and guide the development of vaccines. Tiled amplicon sequencing, in which a panel of primers is used for multiplex am...

Background: One barrier to intervening in the global tuberculosis (TB) pandemic is that it is unknown whether M. tuberculosis transmission largely occurs through repeated close exposures among few contacts or many shorter-term contacts. Identifying sources of transmission is particularly urgent in congregate settings with high incidence of infectio...

Graph structures are often used to visualize transmission networks generated using genomic epidemiological methods. However, tools to interactively visualize these graphs do not exist. A browser-based tool allowing users to load and interactively visualize transmission graphs was developed in JavaScript. Associated metadata can be loaded and used t...

Over the past three decades, molecular epidemiological studies have provided new opportunities to investigate the transmission dynamics of M. tuberculosis. In most studies, a sizable fraction of individuals with notified tuberculosis cannot be included, either because they do not have culture-positive disease (and thus do not have specimens availab...

Background: A substantial fraction of individuals initiating tuberculosis (TB) treatment do not successfully complete the regimen. Understanding variation in TB treatment outcomes could reveal opportunities to improve the effectiveness of TB treatment services. Methods: We extracted data on TB treatment outcomes, patient covariates, and location of...

Background: Even after successful treatment, tuberculosis (TB) survivors experience elevated morbidity and mortality. However, there is limited evidence on how these risks vary over time and according to individual characteristics. Methods: We conducted a retrospective cohort study of individuals diagnosed with TB in Brazil, using national TB notif...

UNSTRUCTURED During the COVID-19 pandemic a number of jurisdictions in the United States began to regularly report levels of SARS-CoV-2 in wastewater for use as a proxy for SARS-CoV-2 incidence. Despite the promise of this approach for improving situational awareness, the degree to which viral levels in wastewater track with other outcome data has...

Background Mycobacterium tuberculosis complex (MTBC) species evolve slowly, so isolates from individuals linked in transmission often have identical or nearly identical genomes, making it difficult to reconstruct transmission chains. Finding additional sources of shared MTBC variation could help overcome this problem. Previous studies have reported...

We conducted a matched retrospective cohort study comparing mortality among individuals receiving a false-positive tuberculosis (TB) diagnosis (n = 3701) to individuals correctly diagnosed with TB (n = 8595) in Brazil from 2007 to 2016. Over an average 5.4-year follow-up period, we estimated a mortality rate ratio of 1.95 (95% confidence interval,...

Background: Individuals surviving TB disease may experience chronic sequelae that reduce survival and quality-of-life. These post-TB sequalae are not generally considered in estimates of the health impact of TB disease. We estimated reductions in life expectancy and quality-adjusted life expectancy for individuals developing TB disease in the Unite...

Introduction Effective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the fifty United States (U.S.) and the District of Columbia from January 2020 through December 2023. Methods We updated a m...

During the COVID-19 pandemic a number of jurisdictions in the United States began to regularly report levels of SARS-CoV-2 in wastewater for use as a proxy for SARS-CoV-2 incidence. Despite the promise of this approach for improving situational awareness, the degree to which viral levels in wastewater track with other outcome data has varied, and b...

Background Tuberculosis (TB) cases and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends. Methods We identified four mechanisms potentially contributing to observed TB trends during 2020-2023: imm...

Background: Tuberculosis incidence is increasing in Latin America, where the incarcerated population has nearly quadrupled since 1990. We aimed to quantify the impact of historical and future incarceration policies on the tuberculosis epidemic, accounting for effects in and beyond prisons. Methods: In this modelling study, we calibrated dynamic co...

Introduction: Host-response-based transcriptional signatures (HrTS) have been developed to identify "incipient tuberculosis (TB)". No study has reported the cost-effectiveness of HrTS for post-arrival migrant screening programs in low-incidence countries. Objectives: To assess the potential health impact and cost-effectiveness of HrTS for post-arri...

Importance Despite significant progress made toward tuberculosis (TB) elimination, racial and ethnic disparities persist in TB incidence and case-fatality rates in the US. Objective To estimate the health outcomes and economic cost of TB disparities among US-born persons from 2023 to 2035. Design, Setting, and Participants Generalized additive re...

Background Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for indi...

Background: Untreated pulmonary tuberculosis (TB) causes ongoing lung damage, which may persist after treatment. Conventional approaches for assessing TB health effects may not fully capture these mechanisms. We evaluated how TB–associated lung damage and post–TB sequalae affect the lifetime health consequences of TB in high HIV prevalence settings...

New tuberculosis (TB) drugs with little existing antimicrobial resistance enable a pan-TB treatment regimen, intended for universal use without prior drug-susceptibility testing. However, widespread use of such a regimen could contribute to an increasing prevalence of antimicrobial resistance, potentially rendering the pan-TB regimen ineffective or...

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015–2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing...

Background For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. Methods Using a m...

Background A pan-tuberculosis regimen that could be initiated without knowledge of drug susceptibility has been proposed as an objective of tuberculosis regimen development. We modelled the health and economic benefits of such a regimen and analysed which of its features contribute most to impact and savings. Methods We constructed a mathematical...

Tuberculosis is a major infectious disease worldwide, but currently available diagnostics have suboptimal accuracy, particularly in patients unable to expectorate, and are often unavailable at the point-of-care in resource-limited settings. Test/treatment decision are, therefore, often made on clinical grounds. We hypothesized that contextual facto...

Effectively responding to drug-resistant tuberculosis (TB) requires accurate and timely information on resistance levels and trends. In contexts where use of drug susceptibility testing has not been universal, surveillance for rifampicin-resistance—one of the core drugs in the TB treatment regimen—has relied on resource-intensive and infrequent nat...

Background Isoniazid-resistant, rifampin-susceptible tuberculosis (Hr-TB) is associated with poor treatment outcomes and higher rates of acquisition of further drug resistance during treatment. Due to a lack of widespread diagnostics, Hr-TB is frequently undetected and its epidemiology is incompletely understood. Methods We studied the molecular e...

Infectious disease dynamics are driven by the complex interplay of epidemiological, ecological, and evolutionary processes. Accurately modeling these interactions is crucial for understanding pathogen spread and informing public health strategies. However, existing simulators often fail to capture the dynamic interplay between these processes, resu...

The COVID-19 pandemic is marked by the continuing emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which these lineages establish themselves in new geographical areas. In this study, we performed a discrete phylogeographic analysis on ∼19,000 SARS-CoV-2 sequences of Omicron BA.5 lineages between February and June 2...

Introduction Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. Methods We obtained data on individuals treated for TB between 2015 and 2018 f...

Background Delays in identifying and treating individuals with infectious tuberculosis (TB) contribute to poor health outcomes and allow ongoing community transmission of M. tuberculosis ( Mtb ). Current recommendations for screening for tuberculosis specify community characteristics (e.g., areas with high local tuberculosis prevalence) that can be...

Background Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- o...

Background: Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed sam...

Background Tuberculosis incidence is increasing in Latin America, where the incarcerated population has nearly quadrupled since 1990. The full impact of incarceration on the tuberculosis epidemic, accounting for effects beyond prisons, has never been quantified. Methods We calibrated dynamic compartmental transmission models to historical and conte...

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative diagnostic test result. Understanding factors associated with clinicians' decisions to initiate treatment for individuals with negative test results is critical for predicting the potential impact of new diagnos...

The projected trajectory of multidrug resistant tuberculosis (MDR-TB) epidemics depends on the reproductive fitness of circulating strains of MDR M. tuberculosis (Mtb). Previous efforts to characterize the fitness of MDR Mtb have found that Mtb strains of the Beijing sublineage (Lineage 2.2.1) may be more prone to develop resistance and retain fitn...

Background: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. Objective: To quantify trends in racial/ethnic disparities in TB incidence among...

Background Multidrug resistant tuberculosis (MDR-TB) represents a major public health concern in the Republic of Moldova, with an estimated 31% of new and 56% of previously treated TB cases having MDR disease in 2022. A recent genomic epidemiology study of incident TB occurring in 2018 and 2019 found that 92% of MDR-TB was the result of transmissio...

Background In Brazil, many individuals with tuberculosis (TB) do not receive appropriate care due to delayed or missed diagnosis, ineffective treatment regimens, or loss-to-follow-up. This study aimed to estimate the health losses and TB program costs attributable to each gap in the care cascade for TB disease in Brazil. Methods and findings We co...

Background: For low TB incidence settings, disease elimination is a long-term goal. We investigated pathways to TB pre-elimination and elimination (incidence <1.0 and <0.1 per 100,000, respectively) in the United States. Methods: Using a mathematical modelling framework, we simulated how U.S. TB incidence could be affected by changes in TB services...

The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, we used a multivariable linear mixed mode...

Introduction Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. Methods We obtained data on individuals treated for TB between 2015 and 2018 f...

Background Persistent racial and ethnic disparities in tuberculosis incidence exist in the USA, however, less is known about disparities along the tuberculosis continuum of care. This study aimed to describe how race and ethnicity are associated with tuberculosis diagnosis and treatment outcomes. Methods In this analysis of national surveillance d...

Background. Because M. tuberculosis evolves slowly, transmission clusters often contain multiple individuals with identical consensus genomes, making it difficult to reconstruct transmission chains. Finding additional sources of shared M. tuberculosis variation could help overcome this problem. Previous studies have reported M. tuberculosis diversi...

The projected trajectory of multidrug resistant tuberculosis (MDR-TB) epidemics depends on the reproductive fitness of circulating strains of MDR M. tuberculosis (Mtb). Previous efforts to characterize the fitness of MDR Mtb have found that Mtb strains of the Beijing sublineage (Lineage 2.2.1) may be more prone to develop resistance and retain fitn...

SARS-CoV-2 Omicron surged as a variant of concern (VOC) in late 2021. Subsequently, several distinct Omicron variants have appeared and overtaken each other. We combined variant frequencies from GISAID and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction...

Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempt...

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disabil...

Background In the United States, the tuberculosis (TB) disease burden and associated factors vary substantially across states. While public health agencies must choose how to deploy resources to combat TB and latent tuberculosis infection (LTBI), state-level modeling analyses to inform policy decisions have not been widely available. Methods We de...

Background Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-m...

Background: People who are incarcerated are at high risk of developing tuberculosis. We aimed to estimate the annual global, regional, and national incidence of tuberculosis among incarcerated populations from 2000 to 2019. Methods: We collected and aggregated data for tuberculosis incidence and prevalence estimates among incarcerated individual...

Background Epidemiological nowcasting traditionally relies on count surveillance data. The availability and quality of such data may vary over time, limiting their representation of true infections. Wastewater data correlates with traditional surveillance data and may provide additional value for nowcasting disease trends. Methods We obtained SARS...

Background: While a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021 - February 2022, the subsequent evolution of population immunity reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Methods: Using...

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential inte...

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performan...

Background: Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we co...

Understanding factors that contribute to the increased likelihood of pathogen transmission between two individuals is important for infection control. However, analyzing measures of pathogen relatedness to estimate these associations is complicated due to correlation arising from the presence of the same individual across multiple dyadic outcomes,...

Background In the United States, over 80% of tuberculosis (TB) disease cases are estimated to result from reactivation of latent TB infection (LTBI) acquired more than 2 years previously (“reactivation TB”). We estimated reactivation TB rates for the US population with LTBI, overall, by age, sex, race–ethnicity, and US-born status, and for selected...

Importance: While a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021-February 2022, the subsequent evolution of population immunity against SARS-CoV-2 Omicron variants reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections a...

Background Isoniazid preventive therapy (IPT) can prevent tuberculosis among people receiving antiretroviral therapy (ART). HIV programmes are now initiating patients on ART with higher average CD4 cell counts and lower tuberculosis risks under test-and-treat guidelines. We aimed to investigate how this change has affected the health impact and cos...

The degree to which individual heterogeneity in the production of secondary cases ("superspreading") affects tuberculosis (TB) transmission has not been systematically studied. We searched for population-based or surveillance studies in which whole genome sequencing was used to estimate TB transmission and the size distributions of putative TB tran...

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy (ART) have driven dynamic TB epidemics, complicating estimation of burden, trends, and potentia...

BACKGROUND Diagnosing drug resistance is critical for choosing effective TB treatment regimens. Next-generation sequencing (NGS) represents an alternative approach to conventional phenotypic drug susceptibility testing (pDST) for diagnosing TB drug resistance.METHODS We undertook a budget impact analysis estimating the costs of introduction and rou...

Reliable subnational estimates of TB incidence would allow national policy makers to focus disease control resources in areas of highest need. We developed an approach for generating small area estimates of TB incidence, and the fraction of individuals missed by routine case detection, based on available notification and mortality data. We demonstr...

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Diagnostic challenges in children include low bacterial burden, challenges around specimen collection, and limited access to diagnostic expertise. Algorithms that guide decisions to initiate tuberculosis treatment in res...

Reported COVID-19 cases and deaths provide a delayed and incomplete picture of SARS-CoV-2 infections in the United States (US). Accurate estimates of both the timing and magnitude of infections are needed to characterize viral transmission dynamics and better understand COVID-19 disease burden. We estimated time trends in SARS-CoV-2 transmission an...