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Background Throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers (HCWs) have faced risk of infection from within the workplace via patients and staff as well as from the outside community, complicating our ability to resolve transmission chains in order to inform hospital infection control policy. Here we show how the incorporation of sequences from public genomic databases aided genomic surveillance early in the pandemic when circulating viral diversity was limited. Methods We sequenced a subset of discarded, diagnostic SARS-CoV-2 isolates between March and May 2020 from Boston Medical Center HCWs and combined this data set with publicly available sequences from the surrounding community deposited in GISAID with the goal of inferring specific transmission routes. Results Contextualizing our data with publicly available sequences reveals that 73% (95% confidence interval, 63%–84%) of coronavirus disease 2019 cases in HCWs are likely novel introductions rather than nosocomial spread. Conclusions We argue that introductions of SARS-CoV-2 into the hospital environment are frequent and that expanding public genomic surveillance can better aid infection control when determining routes of transmission.

BackgroundIn January 2022, US guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask-wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown.MethodsWe conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for reverse-transcription polymerase chain reaction (RT-PCR) testing and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4–6 compared with culture.ResultsAmong 92 SARS-CoV-2 RT-PCR–positive participants, all completed the initial vaccine series; 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset, with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For 14 substudy participants, sensitivity and specificity of day 4–6 RDT were 100% and 86%, respectively.ConclusionsThe majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though guidance to mask for days 6–10 is supported by our finding that 17% of participants remained culture-positive after isolation.

Background The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible in vaccinated and unvaccinated populations. The dynamics that govern its establishment and propensity toward fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. Here, we describe the dynamics of Omicron at 3 institutions of higher education (IHEs) in the greater Boston area. Methods We use diagnostic and variant-specifying molecular assays and epidemiological analytical approaches to describe the rapid dominance of Omicron following its introduction into 3 IHEs with asymptomatic surveillance programs. Results We show that the establishment of Omicron at IHEs precedes that of the state and region and that the time to fixation is shorter at IHEs (9.5–12.5 days) than in the state (14.8 days) or region. We show that the trajectory of Omicron fixation among university employees resembles that of students, with a 2- to 3-day delay. Finally, we compare cycle threshold values in Omicron vs Delta variant cases on college campuses and identify lower viral loads among college affiliates who harbor Omicron infections. Conclusions We document the rapid takeover of the Omicron variant at IHEs, reaching near-fixation within the span of 9.5–12.5 days despite lower viral loads, on average, than the previously dominant Delta variant. These findings highlight the transmissibility of Omicron, its propensity to rapidly dominate small populations, and the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

Multidrug-resistant tuberculosis (MDR-TB) has historically required longer treatment regimens that were associated with higher unfavorable outcomes and side effects rates compared with drug susceptible TB (DS-TB). During the last decade, several studies conducted mostly in high-incidence settings have shown that MDR-TB can be successfully treated using all-oral shorter regimens of 6- to 9-month duration. In this article, we review the evolution of MDR-TB treatment from the early long regimens with injectables agents (IAs), followed by the shorter regimens with IA, to the groundbreaking, all-oral, 6- to 9-month regimens. Finally, we propose a framework for implementation of the shorter all-oral regimens in the United States.

Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on individual institutions to establish sample repositories. As a safety-net hospital, Boston Medical Center (BMC) recognized the importance of creating a COVID-19 biorepository to both support critical science at BMC and ensure representation in research for its urban patient population, most of whom are from underserved communities. This article offers a realistic overview of the authors' experience in establishing this biorepository at the onset of the COVID-19 pandemic during the height of the first surge of cases in Boston, Massachusetts, with the hope that the challenges and solutions described are useful to other institutions. Going forward, funders, policymakers, and infectious disease and public health communities must support biorepository implementation as an essential element of future pandemic preparedness.

Background Omicron rapidly replaced delta as the predominant strain causing COVID-19 related illness in the United States (US) in December 2021, the same month the US CDC reduced the recommended isolation period from 10 to 5 days for asymptomatic individuals or those with resolving symptoms. New evidence suggests some asymptomatic individuals with omicron remain culture positive beyond 5 days from diagnosis. We sought to evaluate the performance of a SARS-CoV-2 antigen rapid diagnostic test (RDT) in predicting persistent potential for transmission at the end of a five-day isolation period among young, fully vaccinated individuals in a university community setting. Methods A subgroup of participants enrolled in a longitudinal COVID-19 cohort were asked to self-perform RDTs on days 4 to 6 from diagnostic test date in addition to a separate self-collected anterior nasal swab used for culture and RT-PCR, and a daily symptom screen (15 COVID-19 symptom questions on a 4-point scale). We calculated the daily and overall sensitivity and specificity of the RDTs in comparison to SARS-CoV-2 culture result. We also compared the N1 cycle threshold (CT) values and symptom score on each day of the study by RDT results. Results Of 23 participants, the mean age was 20 years, all had completed their primary COVID-19 vaccine series, and 13 (65.0%) had received a booster vaccine (Table 1). Compared to culture, sensitivity and specificity of the RDTs were 100% and 62% respectively (Table 2). Compared to participants with negative RDTs, median CT values were lower in those with positive RDTs on each day of the study (Figure 1). Participants who had positive RDTs on all three days had higher symptom scores (Figure 2) than those without. Conclusion RDTs have a high sensitivity in detecting culture positive SARS-CoV-2 on Days 4 to 6 from initial diagnostic test. However, the high false positive rate of 38% means that over a third of culture negative individuals will stay in isolation longer than necessary if RDTs are used in test to release from isolation protocols. Viral loads (CT values) and symptom scores were higher for participants with persistently positive RDT result. An approach that uses a combination of RDTs, CT values and symptom score may prove useful in guiding isolation duration. Disclosures Davidson H. Hamer, MD, Trinity Biotech: Advisor/Consultant Catherine M. Klapperich, Ph.D., BioSens8, LLC: Ownership Interest.

Background The coronavirus disease 2019 (COVID-19) pandemic disrupted access to and uptake of hepatitis C virus (HCV) care services in the United States. It is unknown how substantially the pandemic will impact long-term HCV-related outcomes. Methods We used a microsimulation to estimate the 10-year impact of COVID-19 disruptions in healthcare delivery on HCV outcomes including identified infections, linkage to care, treatment initiation and completion, cirrhosis, and liver-related death. We modeled hypothetical scenarios consisting of an 18-month pandemic-related disruption in HCV care starting in March 2020 followed by varying returns to pre-pandemic rates of screening, linkage, and treatment through March 2030 and compared them to a counterfactual scenario in which there was no COVID-19 pandemic or disruptions in care. We also performed alternate scenario analyses in which the pandemic disruption lasted for 12 and 24 months. Results Compared to the “no pandemic” scenario, in the scenario in which there is no return to pre-pandemic levels of HCV care delivery, we estimate 1060 fewer identified cases, 21 additional cases of cirrhosis, and 16 additional liver-related deaths per 100 000 people. Only 3% of identified cases initiate treatment and Conclusions A recommitment to the HCV epidemic in the United States that involves additional resources coupled with aggressive efforts to screen, link, and treat people with HCV is needed to overcome the COVID-19-related disruptions.

Author(s): Hahn, Judith A; Murnane, Pamela M; Vittinghoff, Eric; Muyindike, Winnie R; Emenyonu, Nneka I; Fatch, Robin; Chamie, Gabriel; Haberer, Jessica E; Francis, Joel M; Kapiga, Saidi; Jacobson, Karen; Myers, Bronwyn; Couture, Marie Claude; DiClemente, Ralph J; Brown, Jennifer L; So-Armah, Kaku; Sulkowski, Mark; Marcus, Gregory M; Woolf-King, Sarah; Cook, Robert L; Richards, Veronica L; Molina, Patricia; Ferguson, Tekeda; Welsh, David; Piano, Mariann R; Phillips, Shane A; Stewart, Scott; Afshar, Majid; Page, Kimberly; McGinnis, Kathleen; Fiellin, David A; Justice, Amy C; Bryant, Kendall; Saitz, Richard | Abstract: BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8nng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8nng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

In 2011, South Africa implemented a policy to decentralize treatment for rifampin-resistant tuberculosis (TB) to reduce durations of hospitalization and enable local treatment. We assessed policy implementation in Western Cape Province, where services expanded from 6 specialized TB hospitals to 406 facilities, by analyzing National Health Laboratory Service data on TB during 2012-2015. We calculated the percentage of patients who visited a TB hospital

BackgroundIn January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown.MethodsWe conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture.ResultsAmong 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively.ConclusionsThe majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation.Main PointBeyond day 5, 17% of our Delta and Omicron-infected cohort were culture positive. We saw no significant impact of booster vaccination on within-host Omicron viral dynamics. Additionally, we found that rapid antigen testing may provide reassurance of lack of infectiousness.

ObjectiveTo quantify the proportion of people living with HIV (PLWH) with other tuberculosis (TB) risk factors that completed the latent tuberculosis infection (LTBI) care cascade and describe factors associated with attrition. The care cascade was defined as follows: (1) receipt of an LTBI test and result, (2) initiation of LTBI treatment and (3) completion of LTBI treatment.DesignProspective cohort study.SettingReactivation of LTBI remains a large source of active TB disease in the USA. PLWH and those who use substances are at greater risk and are harder to engage and retain in care.ParticipantsParticipants enrolled in a Boston cohort of PLWH from 2012 to 2014.Primary and secondary outcome measuresOur primary outcome was the number and proportion of participants who completed each stage of the cascade and the factors associated with completing each stage. Our secondary outcomes were differences between participants tested with an interferon gamma release assay (IGRA) versus tuberculin skin test and differences between participants who tested positive versus negative for LTBI.ResultsOnly 189 of 219 (86.3%) participants completed testing. Five of the 11 with LTBI initiated and three completed treatment. Participants tested with an IGRA were more likely to complete testing (OR 3.87, 95% CI 1.05 to 14.30) while among participants successfully tested, being foreign-born was associated with a positive test result (OR 3.95; 95% CI 1.13 to 13.77).ConclusionsAlthough the majority completed LTBI testing, our findings warrant further investigation in a larger cohort to better understand factors that lead to suboptimal treatment initiation and completion in a low-burden country.

As of July 5, 2020, approximately 2.8 million coronavirus disease 2019 (COVID-19) cases and 130,000 COVID-19-associated deaths had been reported in the United States (1). Populations historically affected by health disparities, including certain racial and ethnic minority populations, have been disproportionally affected by and hospitalized with COVID-19 (2-4). Data also suggest a higher prevalence of infection with SARS-CoV-2, the virus that causes COVID-19, among persons experiencing homelessness (5). Safety-net hospitals,† such as Boston Medical Center (BMC), which provide health care to persons regardless of their insurance status or ability to pay, treat higher proportions of these populations and might experience challenges during the COVID-19 pandemic. This report describes the characteristics and clinical outcomes of adult patients with laboratory-confirmed COVID-19 treated at BMC during March 1-May 18, 2020. During this time, 2,729 patients with SARS-CoV-2 infection were treated at BMC and categorized into one of the following mutually exclusive clinical severity designations: exclusive outpatient management (1,543; 56.5%), non-intensive care unit (ICU) hospitalization (900; 33.0%), ICU hospitalization without invasive mechanical ventilation (69; 2.5%), ICU hospitalization with mechanical ventilation (119; 4.4%), and death (98; 3.6%). The cohort comprised 44.6% non-Hispanic black (black) patients and 30.1% Hispanic or Latino (Hispanic) patients. Persons experiencing homelessness accounted for 16.4% of patients. Most patients who died were aged ≥60 years (81.6%). Clinical severity differed by age, race/ethnicity, underlying medical conditions, and homelessness. A higher proportion of Hispanic patients were hospitalized (46.5%) than were black (39.5%) or non-Hispanic white (white) (34.4%) patients, a finding most pronounced among those aged

Background Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection. Methods Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication. Results We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells. Conclusions Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.

The Omicron variant of SARS-CoV-2 is highly transmissible in vaccinated and unvaccinated populations. The dynamics governing its establishment and propensity towards fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. In this work, we describe the dynamics of Omicron at three institutions of higher education (IHEs) in the greater Boston area.We use diagnostic and variant-specifying molecular assays and epidemiological analytical approaches to describe the rapid dominance of Omicron following its introduction to three IHEs with asymptomatic surveillance programs.We show that the establishment of Omicron at IHEs precedes that of the state and region, and that the time to fixation is shorter at IHEs (9.5-12.5 days) than in the state (14.8 days) or region. We show that the trajectory of Omicron fixation among university employees resembles that of students, with a 2-3 day delay. Finally, we compare cycle threshold (Ct) values in Omicron vs. Delta variant cases on college campuses, and identify lower viral loads among college affiliates harboring Omicron infections.We document the rapid takeover of the Omicron variant at IHEs, reaching near-fixation within the span of 9.5-12.5 days despite lower viral loads, on average, than the previously dominant Delta variant. These findings highlight the transmissibility of Omicron, its propensity to rapidly dominate small populations, and the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

BackgroundAccurate measurement of antibodies is a necessary tool for assessing exposure to SARS-CoV-2 and facilitating understanding of the role of antibodies in immunity. Most assays are qualitative in nature and employ a threshold to determine presence of antibodies. Semi-quantitative assays are now available. Here we evaluate the semi-quantitative SARS-CoV-2 IgG II (anti-spike (S)) assay. We aim to reassess the seroprevalence using anti-S assay and subsequently compare it to the previously measured IgG (anti-nucleoprotein (N)) in health care workers at an academic medical center in Boston.Methods1743 serum samples from HCWs at Boston Medical Center were analyzed for SARS-CoV-2 anti-S IgG and IgM using the Abbott SARS-CoV-2 IgG II and□Abbott AdviseDx□SARS-CoV-2 IgM assay, respectively. Precision, linearity, positive and negative concordance with prior RT-PCR test were evaluated for anti-S IgG. Seroprevalence and its association with demographics variables was also assessed.ResultsLinearity and precision results were clinically acceptable. The positive and negative concordance for anti-S IgG with RT-PCR was 88.2% (95% CI: 79.4% - 94.2%) and 97.43% (95% CI: 95.2% - 98.8%), respectively. Overall, 126 (7.2%) of 1,743 participants were positive by anti-S IgG. Among the 1302 participants with no prior RT-PCR, 40 (3.1%) were positive for anti-S IgG antibody. The original agreement in this population with the qualitative, anti-N IgG assay was 70.6%. Upon optimizing the threshold from 1.4 to 0.49 S/CO of the anti-N IgG assay, the positive agreement of the assay increases to 84.7%.ConclusionThe anti-S IgG assay demonstrated reproducible and reliable measurements. This study highlights the presence of asymptomatic transmission among individuals with no prior history of positive RT-PCR. It also highlights the need for optimizing thresholds of the qualitative SARS-CoV-2 IgG assay for better agreement between assays by the same vendor.

Unhealthy alcohol use is associated with increased progression to tuberculosis (TB) disease, but its effect on adherence to isoniazid (INH) preventive therapy is not known.This was a prospective study of persons with HIV with latent TB in southwestern Uganda reporting any current (previous 3 months) alcohol use or no alcohol consumption in the previous year (2:1 ratio). All received INH. We defined suboptimal adherence as90% of days with at least 1 Medication Event Monitoring System cap opening, over the previous 90 days. Alcohol use was categorized as follows: none: no self-report and phosphatidylethanol (PEth)8 ng/mL; moderate: Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) 1-2 (women) or 1-3 (men) and/or PEth 8 ≥ 50 ng/mL; and unhealthy: AUDIT-C ≥3 (women) or ≥4 (men) and/or PEth ≥50 ng/mL. We used generalized estimating equation logistic regression analyses to assess the association between the level of alcohol use and suboptimal INH adherence.Three hundred two persons were enrolled; 279 were on INH for 3 or more months. The prevalence of suboptimal INH adherence was 31.3% at 3 months and 43.9% at 6 months. The odds of suboptimal INH adherence were higher for unhealthy (adjusted odds ratio, 2.78; 95% confidence interval: 1.62 to 4.76) and moderate (adjusted odds ratio, 1.59; 95% confidence interval: 0.94 to 2.71) compared with no alcohol consumption.Suboptimal adherence to INH at 3 and 6 months was high among prospective study of persons with HIV and associated with unhealthy alcohol use. Adherence support and alcohol reduction strategies are needed for this group at high risk for active TB.

People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis (Mtb) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602. Date of Registration: 5 November 2019.

Background Coronavirus disease 2019 (COVID-19) vaccine trials and post-implementation data suggest that vaccination decreases infections. We examine vaccination’s impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case rates and viral diversity among health care workers (HCWs) during a high community prevalence period. Methods In this prospective cohort study, HCW received 2 doses of BNT162b2 or mRNA-1273. We included confirmed cases among HCWs from 9 December 2020 to 23 February 2021. Weekly SARS-CoV-2 rates per 100,000 person-days and by time from first injection (1–14 and ≥15 days) were compared with surrounding community rates. Viral genomes were sequenced. Results SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted rate ratios (95% confidence intervals) were 0.73 (.53–1.00) 1–14 days and 0.18 (.10–.32) ≥15 days from first dose. HCW ≥15 days from initial dose compared to 1-14 days were more often older (46 vs 38 years, P = .007), Latinx (10% vs 8%, P = .03), and asymptomatic (48% vs 11%, P = .0002). SARS-CoV-2 rates among HCWs fell below the surrounding community, an 18% vs 11% weekly decrease, respectively (P = .14). Comparison of 50 genomes from post–first dose cases did not indicate selection pressure toward known spike antibody escape mutations. Conclusions Our results indicate an early positive impact of vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

Setting Ethiopia has a high prevalence of tuberculosis (TB) and is one of the countries with the highest burden of multidrug-resistant TB (MDR-TB). Objective To understand the costs that patients incur in obtaining diagnosis and treatment for MDR-TB. Design In March 2013, interviews were conducted with 169 MDR-TB patients at three hospitals in Ethiopia to identify the cost to patients and the impact on employment and family income. Results The average MDR-TB patient incurred a total cost of US$1378, which represented 25 months of a mid-treatment household income of US$54. The impact on the patient's employment and on overall patient and family income was generally catastrophic: 74% of all respondents reported losing their jobs, 66% of patients lost household income, and household income was reduced by 38%. To help cover the costs, 38% of patients sold some type of property, while 7% leased out property and 41% took out loans, any of which could jeopardize their future financial situation even further. Conclusion Despite services being officially free of charge, most patients incurred catastrophic costs and suffered significant income loss as a result of obtaining diagnosis and treatment for MDR-TB.

Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes., In tuberculosis (TB) patients from post-conflict eastern Democratic Republic of the Congo, 11.1% had rifampicin-resistant TB, of whom 46.5% had no prior TB. Cures were achieved in 83% and 74% of patients on 9- and 20/24-month multidrug-resistant TB regimens, respectively.

Background: South Africa temporarily banned alcohol and tobacco sales for about 20 weeks during the COVID-19 lockdown. We described changes in alcohol and tobacco consumption after implementation of these restrictions among a small number of participants in a tuberculosis treatment cohort. Method: The timeline follow-back procedure and Fägerstrom test for nicotine dependence was used to collect monthly alcohol and tobacco use information. We report changes in heavy drinking days (HDD), average amount of absolute alcohol (AA) consumed per drinking day, and cigarettes smoked daily during the alcohol and tobacco ban compared to use prior to the ban. Results: Of the 61 participants for whom we have pre-ban and within-ban alcohol use information, 17 (27.9%) reported within-ban alcohol use. On average, participants reported one less HDD per fortnight (interquartile range (IQR): −4, 1), but their amount of AA consumed increased by 37.4 g per drinking occasion (IQR: −65.9 g, 71.0 g). Of 53 participants who reported pre-ban tobacco use, 17 (32.1%) stopped smoking during the ban. The number of participants smoking >10 cigarettes per day decreased from 8 to 1. Conclusions: From these observations, we hypothesize that policies restricting alcohol and tobacco availability seem to enable some individuals to reduce their consumption. However, these appear to have little effect on the volume of AA consumed among individuals with more harmful patterns of drinking in the absence of additional behavior change interventions.

Background Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude “regular and heavy alcohol drinkers” from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. Setting The Immune Suppression Syndrome Clinic of Mbarara, Uganda. Methods We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8–21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p Conclusions Pre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Healthcare workers (HCWs) are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes Coronavirus Disease (COVID-19). We aim to assess the seroprevalence of SARS-CoV-2 IgG among healthcare workers and compare risk-factors between seropositive and seronegative HCWs. In this observational study, serum samples were collected from HCWs between July 13th to 26th, 2020 at Boston Medical Center (BMC). Samples were subsequently tested for SARS-CoV-2 IgG antibody using the Abbott SARS-CoV-2 IgG assay. Participants also answered a questionnaire capturing data on demographics, history of COVID-19 symptoms, occupation, infection prevention and control measures. Overall, 95 of 1743 (5.5%) participants tested positive for SARS-CoV-2 IgG. Of these, 1.8% of the participants had mild or no COVID-19 symptoms and did not require a diagnostic test. Seropositivity was not associated with gender, occupation, hand hygiene and personal protective equipment (PPE) practices amongst HCWs. However, lack of physical distancing among health care workers in work areas and break room was associated with seropositivity (p = 0.05, p = 0.003, respectively). The majority of the HCWs are negative for SARS-CoV-2 IgG. This data highlights the need to promote infection prevention measures, and the importance of distance amongst co-workers to help mitigate infection rates.

BackgroundComorbid mental disorders in patients with tuberculosis (TB) may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes.MethodsWe searched eight databases for studies published from 1990-2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (OR) with 95% confidence intervals (CI).FindingsOf 7,687 studies identified, ten were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95% CI: 0.85-5.37), 1.90 (0.33-10.91), and 1.60 (0.81-3.02), respectively. High statistical heterogeneity was present.InterpretationOur review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.

BACKGROUND A major challenge for prospective, clinical tuberculosis (TB) research is accurately defining a metric for measuring medication adherence. OBJECTIVE We aimed to design a method to capture directly observed therapy (DOT) via mobile health carried out by community workers. The program was created specifically to measure TB medication adherence for a prospective TB cohort in Western Cape Province, South Africa. METHODS Community workers collect daily adherence data on mobile smartphones. Participant-level adherence, program-level adherence, and program function are systematically monitored to assess DOT program implementation. A data dashboard allows for regular visualization of indicators. Numerous design elements aim to prevent or limit data falsification and ensure study data integrity. RESULTS The cohort study is ongoing and data collection is in progress. Enrollment began on May 16, 2017, and as of January 12, 2021, a total of 236 participants were enrolled. Adherence data will be used to analyze the study’s primary aims and to investigate adherence as a primary outcome. CONCLUSIONS The DOT program includes a mobile health application for data collection as well as a monitoring framework and dashboard. This approach has potential to be adapted for other settings to improve the capture of medication adherence in clinical TB research. CLINICALTRIAL Clinicaltrials.gov NCT02840877; https://clinicaltrials.gov/ct2/show/NCT02840877

Background A major challenge for prospective, clinical tuberculosis (TB) research is accurately defining a metric for measuring medication adherence. Objective We aimed to design a method to capture directly observed therapy (DOT) via mobile health carried out by community workers. The program was created specifically to measure TB medication adherence for a prospective TB cohort in Western Cape Province, South Africa. Methods Community workers collect daily adherence data on mobile smartphones. Participant-level adherence, program-level adherence, and program function are systematically monitored to assess DOT program implementation. A data dashboard allows for regular visualization of indicators. Numerous design elements aim to prevent or limit data falsification and ensure study data integrity. Results The cohort study is ongoing and data collection is in progress. Enrollment began on May 16, 2017, and as of January 12, 2021, a total of 236 participants were enrolled. Adherence data will be used to analyze the study’s primary aims and to investigate adherence as a primary outcome. Conclusions The DOT program includes a mobile health application for data collection as well as a monitoring framework and dashboard. This approach has potential to be adapted for other settings to improve the capture of medication adherence in clinical TB research. Trial Registration Clinicaltrials.gov NCT02840877; https://clinicaltrials.gov/ct2/show/NCT02840877

Background Tuberculosis (TB) is the leading cause of death among people living with HIV (PLWH), and current evidence suggests that heavy alcohol users have an increased risk of developing TB disease compared to non-drinkers. Not known is whether the increased risk for TB disease among alcohol users may reflect higher rates of latent TB infection (LTBI) among this population. We assessed the latent TB infection prevalence based on tuberculin skin testing (TST) and examined association with current alcohol use among HIV-infected persons on antiretroviral therapy (ART) in south-western Uganda. Methods We included PLWH at the Mbarara Regional Hospital HIV clinic, who were either current alcohol consumers (prior 3 months) or past year abstainers (2:1 enrolment ratio). Participants were recruited for a study of isoniazid preventive therapy for LTBI. TST was performed using 5 tuberculin units of purified protein derivative. The primary outcome was a positive TST reading (≥5mm induration), reflecting LTBI. We used logistic regression analyses to assess the cross-sectional association between self-reported current alcohol use and a positive TST. Results Of the 295 of 312 (95%) who returned for TST reading, 63% were females and 63% were current alcohol drinkers. The TST positive prevalence was 27.5% (95% confidence interval [CI]: 22.6% - 32.9%). The odds of a positive TST for current alcohol users compared to abstainers was 0.76 (95% CI: 0.41, 1.41), controlling for gender, age, body mass index, history of smoking, and prior unhealthy alcohol use. Conclusions The prevalence of LTBI among PLWH on ART in south-western Uganda was moderate and LTBI poses a risk for future infectious TB. Although alcohol use is common, we did not detect an association between current drinking or prior unhealthy alcohol use and LTBI. Further studies to evaluate the association between LTBI and different levels of current drinking (heavy versus not) are needed.

We examined Massachusetts tuberculosis surveillance data from to 2009 to 2018. Of 1533 culture-confirmed cases, 190 (12.4%) demonstrated resistance to isoniazid including 32 (2.1%) with rifampin resistance. In multivariable analysis, isoniazid resistance increased significantly over time (per-year odds ratio = 1.07, 95% confidence interval = 1.01–1.13, P = .018) and was associated with younger age, foreign birth, and prior tuberculosis treatment.

Rapid screening for tuberculosis (TB) disease at intake into immigrant detention facilities allows for early detection and treatment. Detention facilities with United States Immigration and Customs Enforcement (ICE) Health Service Corps (IHSC) medical staffing utilize chest radiography and symptom screening as the primary screening for pulmonary TB (PTB) disease. This analysis describes the demographic, clinical, and microbiological characteristics of individuals identified with TB disease at these facilities.We conducted a retrospective analysis to describe the population of immigrant detainees identified via chest radiography with PTB disease between 1 January 2014 and 31 December 2016 at facilities with IHSC medical staffing. We collected demographic variables, clinical presentation, diagnostic testing results, and microbiological findings. We generated descriptive statistics and examined univariate and multivariate associations between the variables collected and symptomatic status.We identified 327 patients with confirmed PTB disease (incidence rate, 92.8 per 100 000); the majority of patients were asymptomatic (79.2%) at diagnosis. Adjusting for all other variables in the model, the presence of cavitary lesions, acid-fast bacillus smear positivity, and multilobar presentation were significantly associated with symptomatic status. Among all patients identified with TB disease who had a tuberculin skin test (TST) result recorded, 27.2% were both asymptomatic and TST negative, including those with smear-positive disease.Asymptomatic PTB disease is a significant clinical entity among immigrant detainees and placement in a congregate setting calls for aggressive screening to prevent transmission. Early identification, isolation, and treatment of TB disease benefit not only the health of the patient, but also the surrounding community.

Setting Alcohol use increases the risk of tuberculosis (TB) disease and is associated with worse outcomes. Objective To determine whether alcohol use affects TB severity at diagnosis in a high-burden setting. Design Participants were smear-positive people living with TB (PLWTB) in India. Disease severity was assessed as 1) high versus low smear grade, 2) time to positivity (TTP) on liquid culture, 3) chest radiograph cavitation, and 4) percent lung affected. Alcohol use and being at-risk for alcohol use disorders (AUD) were assessed using the AUDIT-C. Univariable and multivariable analyses were conducted. Results Of 1166 PLWTB, 691 (59.3%) were drinkers; of those, 518/691 (75.0%) were at-risk for AUD. Drinkers had more lung affected than non-drinkers (adjusted mean difference 10.8%, p Conclusions A large proportion of PLWTB were drinkers and were at-risk for AUD. Alcohol drinkers had more lung affected than non-drinkers. Studies are needed to explore mechanisms of this association.

BACKGROUND: Mycobacterium tuberculosis (TB) infection induces systemic inflammation that could impact HIV-1 persistence. SETTING: HIV-1–seropositive individuals either with or without pulmonary TB disease were recruited in Kampala, Uganda. METHODS: Plasma cytokines, HIV-1 DNA, and cell-associated (ca)-RNA were compared among those coinfected with TB (cases) to those without TB (controls). TB-coinfected cases and controls were compared at presentation (n = 15 and n = 16, respectively) and at around 6 months after HIV-1 treatment initiation among those who had achieved virologic suppression (n = 6 and n = 8, respectively). At follow-up, the TB-coinfected cases had also finished TB treatment. RESULTS: Before treatment, the TB-coinfected cases as compared to the controls had higher levels of soluble(s)-CD163 (P = 0.0002) and interleukin-6 (P = 0.006) but lower levels of macrophage chemoattractant protein-1 (P = 0.04). After treatment, the TB-coinfected cases as compared to controls still had higher plasma s-CD163 levels (P = 0007). Controls as compared to the coinfected cases had higher ca-RNA per DNA template both at baseline (P = 0.03) and at follow-up (P = 0.07). Levels of ca-RNA per DNA copy at follow-up showed a negative correlation with baseline plasma s-CD163 (P = 0.008) and interleukin-6 (P = 0.05) levels. CONCLUSIONS: TB disease is associated with inflammation and decreased HIV-1 RNA expression relative to the number of infected cells, both before and after viral suppression. Infections present before antiretroviral initiation impact HIV-1 latency.

Background. Xpert MTB/RIF (Xpert) detects rifampicin-resistant tuberculosis (RR-tuberculosis), enabling physicians to rapidly initiate a World Health Organization-recommended 5-drug regimen while awaiting second-line drug-susceptibility test (DST) results. We quantified the second-line DST results time and proportion of patients potentially placed on suboptimal therapy. Methods. We included RR-tuberculosis patients detected using Xpert at the South African National Health Laboratory Services (NHLS) of the Western Cape between November 2011 and June 2013 and at Eastern Cape, Free State, and Gauteng NHLS between November 2012 and December 2013. We calculated time from specimen collection to phenotypic second-line DST results. We identified isoniazid and ethionamide resistance mutations on line probe assay and performed pyrazinamide sequencing. Results. Among 1332 RR-tuberculosis patients, only 44.7% (596) had second-line DST for both fluoroquinolones and second-line injectable: 55.8% (466 of 835) in the Western Cape and 26.2% (130 of 497) in the other provinces. Patients with smear negative disease and age

Tuberculosis (TB) diagnosis and treatment requires patients to have multiple encounters with health care systems and the different stakeholders who play a role in curing them to coordinate their efforts. To optimize this process, high-quality, readily available data are required. Data systems to facilitate these linkages are a neglected priority which, if weak, fundamentally undermine TB control interventions.To describe lessons learnt from the use of programmatic data for TB patient care and research.We did a survey of researcher and clinical provider experiences with information systems and developed a tiered approach to addressing frequently reported barriers to high-quality care.Unreliable linkages, incomplete data, lack of a reliable unique patient identifier, and lack of data management expertise were the most important data-related barriers to high-quality patient care and research. We propose the creation of health service delivery environments that facilitate, prioritize, and evaluate high-quality data entry during patient or specimen registration.An integrated approach, focused on high-quality data, and centered on unique patient identification will form the foundation for linkages across health systems that reduce patient management errors, bolster surveillance, and enhance the quality of research based on programmatic data.Le diagnostic et le traitement de la tuberculose (TB) exigent des patients de multiples rencontres avec le système de santé et les différentes parties prenantes qui jouent un rôle dans leur guérison afin de coordonner leurs efforts. Pour que cela se passe au mieux, des données de grande qualité facilement disponibles sont requises. Les systèmes de données visant à faciliter ces liens sont une priorité négligée dont la faiblesse affaiblit intrinsèquement les interventions de lutte contre la TB.Décrire les leçons apprises à partir de l'utilisation des données de programme dans la prise en charge des patients atteints de TB et pour la recherche.Nous avons réalisé une enquête sur les expériences de chercheurs et de cliniciens relatives aux systèmes d'information et élaboré une approche progressive pour examiner les obstacles fréquemment rapportées à une prise en charge de bonne qualité.Des liens non fiables, des données incomplètes, l'absence d'un identifiant unique fiable pour chaque patient et le manque d'expertise en gestion des données ont été les obstacles les plus importants, en termes de données, à une bonne qualité de la prise en charge des patients et de la recherche. Nous proposons la création d'un environnement de prestation des soins de santé qui facilite, priorise et évalue la saisie de données de bonne qualité lors de l'enregistrement du patient ou d'un échantillon biologique.Une approche intégrée, concentrée sur des données de qualité élevée, centrée sur une identification unique de chaque patient, constituera la base des liens entre systèmes de santé qui réduisent les erreurs de prise en charge des patients, renforcent la surveillance et améliorent la qualité de la recherche basée sur les données du programme.El diagnóstico de la tuberculosis (TB) y su tratamiento exigen contactos múltiples de los pacientes con el sistema de atención de salud y los diferentes interesados directos que intervienen en su curación a fin de coordinar sus esfuerzos. Una coordinación óptima precisa la existencia de datos de gran calidad. El hecho de descuidar la prioridad de los sistemas de datos que facilitan estos vínculos, los debilitan y socava las intervenciones de control de la TB.Describir las enseñanzas extraídas de la utilización de los datos programáticos en la atención de los pacientes y la investigación en materia de TB.A partir de una encuesta sobre la experiencia de los investigadores y los proveedores de atención con los sistemas de información, se elaboró un método escalonado con el fin de abordar los obstáculos frecuentes referidos en la prestación de una atención de buena calidad.Los principales obstáculos relacionados con la buena calidad de la atención de salud y la investigación fueron los vínculos poco fiables, los datos incompletos, la falta de un número único seguro de identificación de los pacientes y la incompetencia en la gestión de los datos. Se propone la creación de entornos de prestación de servicios de salud que faciliten, den prioridad y evalúen el ingreso de datos de buena calidad en el momento del registro del paciente o de las muestras.Un enfoque integrado basado en la calidad de los datos, alrededor de un número de identificación único de los pacientes, constituirá el cimiento de vínculos entre sistemas de salud que promueven la disminución de los errores de manejo de los pacientes, el refuerzo de la vigilancia y la promoción de la calidad de la investigación basada en los datos programáticos.