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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 in which the size distributions of putative TB transmission clusters were enumerated. We fitted cluster-size–distribution data to a negative binomial branching process model to jointly infer the transmission parameters [Formula: see text] (the reproduction number) and the dispersion parameter, [Formula: see text] , which quantifies the propensity of superspreading in a population (generally, lower values of [Formula: see text] ([Formula: see text]) suggest increased heterogeneity). Of 4,796 citations identified in our initial search, 9 studies from 8 global settings met the inclusion criteria (n = 5 studies of all TB; n = 4 studies of drug-resistant TB). Estimated [Formula: see text] values (range, 0.10–0.73) were below 1.0, consistent with declining epidemics in the included settings; estimated [Formula: see text] values were well below 1.0 (range, 0.02–0.48), indicating the presence of substantial individual-level heterogeneity in transmission across all settings. We estimated that a minority of cases (range, 2%–31%) drive the majority (80%) of ongoing TB transmission at the population level. Identifying sources of heterogeneity and accounting for them in TB control may have a considerable impact on mitigating TB transmission.

US long-term care facilities (LTCFs) have experienced a disproportionate burden of COVID-19 morbidity and mortality.We examined SARS-CoV-2 transmission among residents and staff in 60 LTCFs in Fulton County, Georgia, from March 2020 to September 2021. Using the Wallinga-Teunis method to estimate the time-varying reproduction number, R(t), and linear-mixed regression models, we examined associations between case characteristics and R(t).Case counts, outbreak size and duration, and R(t) declined rapidly and remained low after vaccines were first distributed to LTCFs in December 2020, despite increases in community incidence in summer 2021. Staff cases were more infectious than resident cases (average individual reproduction number, R i = 0.6 [95% confidence intervals [CI] = 0.4, 0.7] and 0.1 [95% CI = 0.1, 0.2], respectively). Unvaccinated resident cases were more infectious than vaccinated resident cases (R i = 0.5 [95% CI = 0.4, 0.6] and 0.2 [95% CI = 0.0, 0.8], respectively), but estimates were imprecise.COVID-19 vaccines slowed transmission and contributed to reduced caseload in LTCFs. However, due to data limitations, we were unable to determine whether breakthrough vaccinated cases were less infectious than unvaccinated cases. Staff cases were six times more infectious than resident cases, consistent with the hypothesis that staff were the primary drivers of SARS-CoV-2 transmission in LTCFs.

OBJECTIVE In cross-sectional U.S. studies, patients with diabetes had twice the prevalence of latent tuberculosis infection (LTBI) compared with those without diabetes. However, whether LTBI contributes to diabetes risk is unknown. We used longitudinal data to determine if LTBI is associated with increased diabetes incidence. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study among U.S. Veterans receiving care in the Veterans Health Administration from 2000 to 2015. Eligibility included all patients without preexisting diabetes who received a tuberculin skin test (TST) or interferon-γ release assay (IGRA). We excluded patients with a history of active TB and those diagnosed with diabetes before or within 2 years after LTBI testing. Patients were followed until diabetes diagnosis, death, or 2015. LTBI was defined as TST or IGRA positive. Incident diabetes was defined by use of ICD-9 codes in combination with a diabetes drug prescription. RESULTS Among 574,113 eligible patients, 5.3% received both TST/IGRA, 79.1% received TST only, and 15.6% received IGRA only. Overall, 6.6% had LTBI, and there were 2,535,149 person-years (PY) of follow-up after LTBI testing (median 3.2 years). The diabetes incidence rate (per 100,000 PY) was greater in patients with LTBI compared with those without (1,012 vs. 744; hazard ratio [HR] 1.4 [95% CI 1.3–1.4]). Increased diabetes incidence persisted after adjustment for covariates (adjusted HR [aHR] 1.2 [95% CI 1.2–1.3]) compared with those without LTBI. Among patients with LTBI, diabetes incidence was similar in those treated for LTBI compared with those who were not treated (aHR 1.0 [95% CI 0.9–1.1]). CONCLUSIONS Comprehensive longitudinal data indicate that LTBI is associated with increased diabetes incidence. These results have implications for people with LTBI, ∼25% of the global population.

BackgroundThree months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP.MethodsWe analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated.ResultsAmong 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19–3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19–3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15–4.42).ConclusionsAlthough most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve.

Background Clinical pediatric tuberculosis (TB) diagnosis may lead to overdiagnosis particularly among children with human immunodeficiency virus (CHIV). We assessed the performance of monocyte-lymphocyte ratio (MLR) as a diagnostic biomarker and constructed a clinical prediction score to improve specificity of TB diagnosis in CHIV with limited access to microbiologic testing. Methods We pooled data from cohorts of children aged ≤13 years from Vietnam, Cameroon, and South Africa to validate the use of MLR ≥0.378, previously found as a TB diagnostic marker among CHIV. Using multivariable logistic regression, we created an internally validated prediction score for diagnosis of TB disease in CHIV. Results The combined cohort had 601 children (median age, 1.9 [interquartile range, 0.9–5.3] years); 300 (50%) children were male, and 283 (47%) had HIV. Elevated MLR ≥0.378 had sensitivity of 36% (95% confidence interval [CI], 23%–51%) and specificity of 79% (95% CI, 71%–86%) among CHIV in the validation cohort. A model using MLR ≥0.28, age ≥4 years, tuberculin skin testing ≥5 mm, TB contact history, fever >2 weeks, and chest radiograph suggestive of TB predicted active TB disease in CHIV with an area under the receiver operating characteristic curve of 0.85. A prediction score of ≥5 points had a sensitivity of 94% and specificity of 48% to identify confirmed TB, and a sensitivity of 82% and specificity of 48% to identify confirmed and unconfirmed TB groups combined. Conclusions Our score has comparable sensitivity and specificity to algorithms including microbiological testing and should enable clinicians to rapidly initiate TB treatment among CHIV when microbiological testing is unavailable.

BackgroundThe Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to evaluate loss to follow-up (LTFU) from the hepatitis C care cascade among persons diagnosed with active tuberculosis (TB) disease.MethodsUsing national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015, to September 30, 2020. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes.ResultsAmong 11,985 patients with active TB, 9,065 (76%) were tested for HCV antibodies, and 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 20% of patients with a positive antibody test not undergoing viremia testing, and 43% of patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last three years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019.ConclusionsLTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes. Existing large-scale programs for both TB and hepatitis C in Georgia create a unique opportunity for such integration to contribute to hepatitis C elimination efforts.

Few reports have described how university programs have controlled COVID-19 outbreaks. Emory University established a case investigation and contact tracing program in June 2020 to identify and mitigate transmission of SARS-CoV-2 in the Emory community. In February 2021, this program identified a surge in COVID-19 cases. In this case study, we present details of outbreak investigation, construction of transmission networks to assess clustering and identify groups for targeted testing, and program quality metrics demonstrating the efficiency of case investigation and contact tracing, which helped bring the surge under control. During February 10–March 5, 2021, Emory University identified 265 COVID-19 cases confirmed by nucleic acid testing in saliva or nasopharyngeal samples. Most students with COVID-19 were undergraduates (95%) and were affiliated with Greek life organizations (70%); 41% lived on campus. Network analysis identified 1 epidemiologically linked cluster of 198 people. Nearly all students diagnosed with COVID-19 (96%) were interviewed the same day as their positive test result. Of 340 close contacts, 90% were traced and 89% were tested. The median time from contact interview to first test was 2 days (interquartile range, 0-6 days); 43% received a positive test result during their quarantine. The surge was considered under control within 17 days, after which new cases were no longer epidemiologically linked. Early detection through systematic testing protocols and rapid and near-complete contact tracing, paired with isolation and quarantine measures, helped to contain the surge. Our approach emphasizes the importance of early preparation of adequate outbreak response infrastructure and staff to implement interventions appropriately and consistently during a pandemic.

Background Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB. Methods We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015–September 2020) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian national programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. A Cox proportional hazards model was used to calculate adjusted hazard ratios (aHRs). Results A total of 1 828 808 adults were included (median follow-up time: 26 months; IQR: 13–39 months). Active TB was diagnosed in 3163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1–18 months). The incidence rate per 100 000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9; 95% CI: 2.4–3.4) and treated (aHR = 1.6; 95% CI: 1.4–2.0) HCV infections were associated with a higher hazard of active TB, compared with HCV-negative persons. Conclusions Adults with HCV infection, particularly untreated individuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high-TB-burden areas.

Fluoroquinolone-based preventive therapy reduced risk for tuberculosis disease by 65%., In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.

Background Black, Hispanic, and Indigenous persons in the United States have an increased risk of SARS-CoV-2 infection and death from COVID-19, due to persistent social inequities. However, the magnitude of the disparity is unclear because race/ethnicity information is often missing in surveillance data. Methods We quantified the burden of SARS-CoV-2 notification, hospitalization, and case fatality rates in an urban county by racial/ethnic group using combined race/ethnicity imputation and quantitative bias analysis for misclassification. Results The ratio of the absolute racial/ethnic disparity in notification rates after bias adjustment, compared with the complete case analysis, increased 1.3-fold for persons classified Black and 1.6-fold for those classified Hispanic, in reference to classified White persons. Conclusions These results highlight that complete case analyses may underestimate absolute disparities in notification rates. Complete reporting of race/ethnicity information is necessary for health equity. When data are missing, quantitative bias analysis methods may improve estimates of racial/ethnic disparities in the COVID-19 burden.

HIV infection is a significant risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to M. tuberculosis have not been fully defined. Evaluation of M. tuberculosis–specific CD4 T cells is commonly based on IFN-γ production, yet increasing evidence indicates the immune response to M. tuberculosis is heterogeneous and encompasses IFN-γ–independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human M. tuberculosis–specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI. PBMCs from HIV-infected and HIV-uninfected adults in Kenya were stimulated with CFP-10 and ESAT-6 peptides and evaluated by flow cytometry for upregulation of the activation markers CD25, OX40, CD69, and CD40L. Although M. tuberculosis–specific IFN-γ and IL-2 production was dampened in HIV-infected individuals, M. tuberculosis–specific CD25+OX40+ and CD69+CD40L+ CD4 T cells were detectable in the AIM assay in both HIV-uninfected and HIV-infected individuals with LTBI. Importantly, the frequency of M. tuberculosis–specific AIM+ CD4 T cells was not directly impacted by HIV viral load or CD4 count, thus demonstrating the feasibility of AIM assays for analysis of M. tuberculosis–specific CD4 T cells across a spectrum of HIV infection states. These data indicate that AIM assays enable identification of M. tuberculosis–specific CD4 T cells in a cytokine-independent manner in HIV-uninfected and HIV-infected individuals with LTBI in a high-tuberculosis burden setting, thus facilitating studies to define novel T cell correlates of protection to M. tuberculosis and elucidate mechanisms of HIV-associated dysregulation of antimycobacterial immunity.

Long-term care facility (LTCF) residents are at particularly high risk for morbidity and mortality associated with infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), given their age and high prevalence of chronic medical conditions, combined with functional impairment that often requires frequent, close contact with health care providers, who might inadvertently spread the virus to residents (1,2). During March-May 2020 in Fulton County, Georgia, >50% of COVID-19-associated deaths occurred among LTCF residents, although these persons represented

Introduction Diabetes might confer a modestly increased risk of latent tuberculosis infection, which without treatment can progress to active tuberculosis disease. Three recent analyses of the National Health and Nutrition Examination Survey found a positive association between diabetes and a positive test for Mycobacterium tuberculosis infection. This study examines whether prevalence of a positive test still varies by diabetes status after stratifying by race/ethnicity. Methods This cross-sectional analysis used the public-use National Health and Nutrition Examination Survey 2011–2012 data sets and was conducted in 2018–2019. Interview and examination results for 5,560 adult participants yielded estimates for 219 million U.S. adults in the 4 largest race/ethnicity groups. The weighted prevalence of positive tuberculin skin test or interferon-gamma release assay by diabetes status was ascertained in each group. Results Among white and black adults, diabetes was associated with no difference in positive skin test prevalence and little difference in positive interferon-gamma release assay prevalence. The positive assay prevalence difference was +14.5% (95% CI=2.3%, 26.7%) among Hispanic and +9.9% (95% CI=1.2%, 18.6%) among Asian adults, when comparing those with diabetes with those with neither diabetes nor prediabetes. Based on assay results, 23.6% (95% CI=14.0%, 36.9%) of Hispanic and 27.2% (95% CI=19.6%, 36.5%) of Asian adults with diabetes also had latent tuberculosis infection. Conclusions Hispanic and Asian subpopulation results drove much of the previously reported positive association between diabetes and a positive test for M. tuberculosis infection. Hispanic and Asian adults with diabetes might particularly benefit from screening and treatment for latent tuberculosis infection.

BACKGROUND: A single 2-year National Health and Nutrition Examination Survey (NHANES) cycle is designed to provide accurate and stable estimates of conditions with prevalence of at least 10%. Recent NHANES-based estimates of a tuberculin skin test ≥10 mm in the noninstitutionalized U.S. civilian population are at most 6.3%. METHODS: NHANES included a tuberculin skin test in 1971–1972, 1999–2000, and 2011–2012. We examined the robustness of NHANES-based estimates of the U.S. population prevalence of a skin test ≥10 mm with a bias analysis that considered the influence of non-U.S. birth distributions and within-household skin test results, reclassified borderline-positive results, and adjusted for tuberculin skin test item nonresponse. RESULTS: The weighted non-U.S. birth distribution among NHANES participants was similar to that in the overall U.S. population; further adjustment was unnecessary. We found no evidence of bias due to sampling multiple participants per household. Prevalence estimates changed 0.3% with reclassification of borderline-positive tuberculin skin test results and 0.2%–0.3% with adjustment for item nonresponse. CONCLUSIONS: For estimating the national prevalence of a tuberculin skin test ≥10 mm during these three survey cycles, a conventional NHANES analysis using the standard participant weights and masked design parameters that are provided in the public-use datasets appears robust.

A once-weekly oral dose of isoniazid and rifapentine for 3 months (3HP) is recommended by the CDC for treatment of latent tuberculosis infection (LTBI). The aim of this study is to assess 3HP-mediated clearance of M. tuberculosis bacteria in macaques with asymptomatic LTBI. Twelve Indian-origin rhesus macaques were infected with a low dose (~10 CFU) of M. tuberculosis CDC1551 via aerosol. Six animals were treated with 3HP and 6 were left untreated. The animals were imaged via PET/CT at frequent intervals. Upon treatment completion, all animals except 1 were coinfected with SIV to assess reactivation of LTBI to active tuberculosis (ATB). Four of 6 treated macaques showed no evidence of persistent bacilli or extrapulmonary spread until the study end point. PET/CT demonstrated the presence of significantly more granulomas in untreated animals relative to the treated group. The untreated animals harbored persistent bacilli and demonstrated tuberculosis (TB) reactivation following SIV coinfection, while none of the treated animals reactivated to ATB. 3HP treatment effectively reduced persistent infection with M. tuberculosis and prevented reactivation of TB in latently infected macaques.

Background The M2 metabolite of bedaquiline causes QT-interval prolongation, making electrocardiogram (ECG) monitoring of patients receiving bedaquiline for drug-resistant tuberculosis necessary. The objective of this study was to determine the relationship between M2 exposure and Fridericia-corrected QT (QTcF)-interval prolongation and to explore suitable ECG monitoring strategies for 6-month bedaquiline treatment. Methods Data from the PROBeX study, a prospective observational cohort study, were used to characterize the relationship between M2 exposure and QTcF. Established nonlinear mixed-effects models were fitted to pharmacokinetic and ECG data. In a virtual patient population, QTcF values were simulated for scenarios with and without concomitant clofazimine. ECG monitoring strategies to identify patients who need to interrupt treatment (QTcF > 500 ms) were explored. Results One hundred seventy patients were included, providing 1131 bedaquiline/M2 plasma concentrations and 1702 QTcF measurements; 2.1% of virtual patients receiving concomitant clofazimine had QTcF > 500 ms at any point during treatment (0.7% without concomitant clofazimine). With monthly monitoring, almost all patients with QTcF > 500 ms were identified by week 12; after week 12, patients were predominantly falsely identified as QTcF > 500 ms due to stochastic measurement error. Following a strategy with monitoring before treatment and at weeks 2, 4, 8, and 12 in simulations with concomitant clofazimine, 93.8% of all patients who should interrupt treatment were identified, and 26.4% of all interruptions were unnecessary (92.1% and 32.2%, respectively, without concomitant clofazimine). Conclusions Our simulations enable an informed decision for a suitable ECG monitoring strategy by weighing the risk of missing patients with QTcF > 500 ms and that of interrupting bedaquiline treatment unnecessarily. We propose ECG monitoring before treatment and at weeks 2, 4, 8, and 12 after starting bedaquiline treatment.

It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure toIn this cross-sectional study, we performed interferon-γ release assays, TB symptom screening, and point-of-care glycolated hemoglobin (HbA1c) testing among HHCs of active TB cases. Diabetes status was classified into diabetes (HbA1c ≥6.5% or self-reported diagnosis), prediabetes (5.7%-6.4%), and euglycemia (≤5.6%). Multivariable logistic regression was used to determine the association of diabetes with LTBI.Among 597 study participants, 123 (21%) had dysglycemia including diabetes (n = 31) or prediabetes (n = 92); 423 (71%) participants were diagnosed with LTBI. Twelve of 31 (39%) HHCs with diabetes were previously undiagnosed with diabetes. The prevalence of LTBI among HHCs with diabetes, prediabetes, and euglycemia was 87% (27/31), 73% (67/92), and 69% (329/474), respectively. In multivariable analysis adjusted for age, sex, and HIV status, the odds of LTBI among HHCs with diabetes were 2.33 (95% confidence interval [CI], .76-7.08) times the odds of LTBI without diabetes. When assessing interaction with age, the association of diabetes and LTBI was robust among participants aged ≥40 years (adjusted odds ratio [aOR], 3.68 [95% CI, .77-17.6]) but not those40 years (aOR, 1.15 [95% CI, .22-6.1]).HHCs with diabetes may be more likely to have LTBI than those with euglycemia. Further investigations are needed to assess mechanisms by which diabetes may increase risk of LTBI after

Households are important for SARS-CoV-2 transmission due to high intensity exposure in enclosed spaces over prolonged durations. We quantified and characterized household clustering of COVID-19 cases in Fulton County, Georgia.We used surveillance data to identify all confirmed COVID-19 cases in Fulton County. Household clustered cases were defined as cases with matching residential address. We described the proportion of COVID-19 cases that were clustered, stratified by age over time and explore trends in age of first diagnosed case within households and subsequent household cases.Between June 1, 2020 and October 31, 2021, 31,449(37%) of 106,233 cases were clustered in households. Children were the most likely to be in household clusters than any other age group. Initially, children were rarely (∼ 10%) the first cases diagnosed in the household but increased to almost 1 of 3 in later periods.One-third of COVID-19 cases in Fulton County were part of a household cluster. Increasingly children were the first diagnosed case, coinciding with temporal trends in vaccine roll-out among the elderly and the return to in-person schooling in Fall 2021. Limitations include restrictions to cases with a valid address and unit number and that the first diagnosed case may not be the infection source for the household.

BackgroundHouseholds are important for SARS-CoV-2 transmission due to high intensity exposure in enclosed living spaces over prolonged durations. Using contact tracing, the secondary attack rate in households is estimated at 18-20%, yet no studies have examined COVID-19 clustering within households to inform testing and prevention strategies. We sought to quantify and characterize household clustering of COVID-19 cases in Fulton County, Georgia and further explore age-specific patterns in household clusters.MethodsWe used state surveillance data to identify all PCR- or antigen-confirmed cases of COVID-19 in Fulton County, Georgia. Household clustered cases were defined as cases with matching residential address with positive sample collection dates within 28 days of one another. We described proportion of COVID-19 cases that were clustered, stratified by age and over time and explored trends in age of first diagnosed case within clusters and age patterns between first diagnosed case and subsequent household cases.ResultsBetween 6/1/20–10/31/21, there were 106,233 COVID-19 cases with available address reported in Fulton County. Of these, 31,449 (37%) were from 12,955 household clusters. Children were more likely to be in household clusters than any other age group and children increasingly accounted for the first diagnosed household case, rising from 11% in February 2021 to a high of 31% in August 2021. Bubble plot density of age of first diagnosed case and subsequent household cases mirror age-specific patterns in household social mixing.DiscussionOne-third of COVID-19 cases in Fulton County were part of a household cluster. High proportion of children in household clusters reflects higher probability of living in larger homes with caregivers or other children. Increasing probability of children as the first diagnosed case coincide with temporal trends in vaccine roll-out among the elderly in March 2021 and the return to in-person schooling for the Fall 2021 semester. While vaccination remains the most effective intervention at reducing household clustering, other household-level interventions should also be emphasized such as timely testing for household members to prevent ongoing transmission.

Background We examined differences in mortality among coronavirus disease 2019 (COVID-19) cases in the first, second, and third waves of the COVID-19 pandemic. Methods A retrospective cohort study of COVID-19 cases in Fulton County, Georgia, USA, reported to a public health surveillance from March 2020 through February 2021. We estimated case-fatality rates (CFR) by wave and used Cox proportional hazards random-effects models in each wave, with random effects at individual and long-term-care-facility level, to determine risk factors associated with rates of mortality. Results Of 75 289 confirmed cases, 4490 (6%) were diagnosed in wave 1 (CFR 31 deaths/100 000 person days [pd]), 24 293 (32%) in wave 2 (CFR 7 deaths/100 000 pd), and 46 506 (62%) in wave 3 (CFR 9 deaths/100 000 pd). Compared with females, males were more likely to die in each wave: wave 1 (adjusted hazard ratio [aHR], 1.5; 95% confidence interval [CI], 1.2–1.8), wave 2 (aHR 1.5, 95% CI, 1.2–1.8), and wave 3 (aHR 1.7, 95% CI, 1.5–2.0). Compared with non-Hispanic whites, non-Hispanic blacks were more likely to die in each wave: wave 1 (aHR, 1.4; 95% CI, 1.1–1.8), wave 2 (aHR, 1.5; 95% CI, 1.2–1.9), and wave 3 (aHR, 1.7; 95% CI, 1.4–2.0). Cases with any disability, chronic renal disease, and cardiovascular disease were more likely to die in each wave compared with those without these comorbidities. Conclusions Our study found gender and racial/ethnic disparities in COVID-19 mortality and certain comorbidities associated with COVID-19 mortality. These factors have persisted throughout the COVID-19 pandemic waves, despite improvements in diagnosis and treatment.

BACKGROUND: Recent evidence suggests transmission of Mycobacterium tuberculosis (Mtb) may be characterized by extreme individual heterogeneity in secondary cases (i.e., few cases account for the majority of transmission). Such heterogeneity implies outbreaks are rarer but more extensive and has profound implications in infectious disease control. However, discrete person-to-person transmission events in tuberculosis (TB) are often unobserved, precluding our ability to directly quantify individual heterogeneity in TB epidemiology. METHODS: We used a modified negative binomial branching process model to quantify the extent of individual heterogeneity using only observed transmission cluster size distribution data (i.e., the simple sum of all cases in a transmission chain) without knowledge of individual-level transmission events. The negative binomial parameter k quantifies the extent of individual heterogeneity (generally, k < 1 indicates extensive heterogeneity, and as k → ∞ transmission becomes more homogenous). We validated the robustness of the inference procedure considering common limitations affecting cluster size data. Finally, we demonstrate the epidemiologic utility of this method by applying it to aggregate US molecular surveillance data from the US Centers for Disease Control and Prevention. RESULTS: The cluster-based method reliably inferred k using TB transmission cluster data despite a high degree of bias introduced into the model. We found that the TB transmission in the United States was characterized by a high propensity for extensive outbreaks ([Formula: see text]; 95% confidence interval = 0.09, 0.10). CONCLUSIONS: The proposed method can accurately quantify critical parameters that govern TB transmission using simple, more easily obtainable cluster data to improve our understanding of TB epidemiology.

The World Health Organization (WHO) recommends tuberculosis (TB) diagnostic evaluation for children with HIV (CHIV) who have history of TB contact, poor weight gain, cough, or fever. These screening criteria were developed based on studies of symptomatic CHIV with incomplete microbiologic confirmation. We performed routine TB microbiologic evaluation of hospitalized CHIV with and without symptoms to develop a data-driven TB symptom screen.Among hospitalized antiretroviral therapy-naive Kenyan CHIV enrolled in the Pediatric Urgent Start of Highly Active Antiretroviral Therapy (PUSH) trial, we performed Xpert MTB/RIF and mycobacterial culture of respiratory and stool specimens independent of TB symptoms. We evaluated performance of WHO and other published pediatric TB screening criteria and derived optimized criteria using a combination of symptoms.Of 168 CHIV who underwent TB microbiologic evaluation, 13 (8%) had confirmed TB. WHO TB symptom screening had 100% sensitivity and 4% specificity to detect confirmed TB. Published TB screening criteria that relied on prolonged symptoms missed cases of confirmed TB (sensitivity 85%-92%). An optimized symptom screen including weight loss, cough, anorexia, or TB contact had 100% sensitivity and improved specificity (31%) compared with the WHO pediatric TB symptom screen.The WHO TB symptom screen was highly sensitive but resulted in a high proportion of hospitalized CHIV who would require TB diagnostic evaluation. Other published TB screening criteria missed CHIV with confirmed TB. Our optimized screening tool increased specificity while preserving sensitivity. Future multicenter studies are needed to improve TB screening tools for CHIV in both inpatient and outpatient settings.

BackgroundReliable detection of SARS-CoV-2 infection is essential for diagnosis and treatment of disease as well as infection control and prevention during the ongoing COVID-19 pandemic. Existing nucleic acid tests do not reliably distinguish acute from resolved infection, as residual RNA is frequently detected in the absence of replication-competent virus. We hypothesized that viral nucleocapsid in serum or plasma may be a specific biomarker of acute infection that could enhance isolation and treatment strategies at an individualized level.MethodsSamples were obtained from a retrospective serological survey using a convenience sampling method from adult inpatient and outpatient encounters from January through March 2021. Samples were categorized along a timeline of infection (e.g. acute, late presenting, convalescent) based on timing of available SARS-CoV-2 testing and symptomatology. Nucleocapsid was quantified by digital immunoassay on the Quanterix HD-X platform.ResultsIn a large sample of 1860 specimens from 1607 patients, the highest level and frequency of antigenemia were observed in samples obtained during acute SARS-CoV-2 infection. Levels of antigenemia were highest in samples from seronegative individuals and in those with more severe disease. Using ROC analysis, we found that antigenemia exhibited up to 85.8% sensitivity and 98.6% specificity as a biomarker for acute COVID-19.ConclusionsNucleocapsid antigenemia is a sensitive and specific biomarker for acute SARS-CoV-2 infection and may aid in individualized assessment of SARS-CoV-2 infection resolution or persistence, although interpretation is limited by absence of a diagnostic gold standard for active infection.

Background Plasma bedaquiline clearance is reportedly more rapid with African ancestry. Our objective was to determine whether genetic polymorphisms explained between-individual variability in plasma clearance of bedaquiline, its M2 metabolite, and clofazimine in a cohort of patients treated for drug-resistant tuberculosis in South Africa. Methods Plasma clearance was estimated with nonlinear mixed-effects modeling. Associations between pharmacogenetic polymorphisms, genome-wide polymorphisms, and variability in clearance were examined using linear regression models. Results Of 195 cohort participants, 140 were evaluable for genetic associations. Among 21 polymorphisms selected based on prior genome-wide significant associations with any drug, rs776746 (CYP3A5∗3) was associated with slower clearance of bedaquiline (P = .0017) but not M2 (P = .25). CYP3A5∗3 heterozygosity and homozygosity were associated with 15% and 30% slower bedaquiline clearance, respectively. The lowest P value for clofazimine clearance was with VKORC1 rs9923231 (P = .13). In genome-wide analyses, the lowest P values for clearance of bedaquiline and clofazimine were with RFX4 rs76345012 (P = 6.4 × 10−7) and CNTN5 rs75285763 (P = 2.9 × 10−8), respectively. Conclusions Among South Africans treated for drug-resistant tuberculosis, CYP3A5∗3 was associated with slower bedaquiline clearance. Different CYP3A5∗3 frequencies among populations may help explain the more rapid bedaquiline clearance reported in Africans. Associations with RFX4 and CNTN5 are likely by chance alone.

We describe severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG seroprevalence and antigenemia among patients at a medical center in January–March 2021 using residual clinical blood samples. The overall seroprevalences were 17% by infection and 16% by vaccination. Spent or residual samples are a feasible alternative for rapidly estimating seroprevalence or monitoring trends in infection and vaccination.

Linezolid is widely used for drug-resistant tuberculosis (DR-TB) but has a narrow therapeutic index. To inform dose optimization, we aimed to characterize the population pharmacokinetics of linezolid in South African participants with DR-TB and explore the effect of covariates, including HIV coinfection, on drug exposure. Data were obtained from pharmacokinetic substudies in a randomized controlled trial and an observational cohort study, both of which enrolled adults with drug-resistant pulmonary tuberculosis. Participants underwent intensive and sparse plasma sampling. We analyzed linezolid concentration data using nonlinear mixed-effects modeling and performed simulations to estimate attainment of putative efficacy and toxicity targets. A total of 124 participants provided 444 plasma samples; 116 were on the standard daily dose of 600 mg, while 19 had dose reduction to 300 mg due to adverse events. Sixty-one participants were female, 71 were HIV-positive, and their median weight was 56 kg (interquartile range [IQR], 50 to 63). In the final model, typical values for clearance and central volume were 3.57 liters/h and 40.2 liters, respectively. HIV coinfection had no significant effect on linezolid exposure. Simulations showed that 600-mg dosing achieved the efficacy target (area under the concentration-time curve for the free, unbound fraction of the drug [[Formula: see text] at a MIC level of 0.5 mg/liter) with 96% probability but had 56% probability of exceeding safety target ([Formula: see text]. The 300-mg dose did not achieve adequate efficacy exposures. Our model characterized population pharmacokinetics of linezolid in South African patients with DR-TB and supports the 600-mg daily dose with safety monitoring.

Background Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescribers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. Patients and methods We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifampicin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. Results One hundred and fifty-one participants, 63% HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI 0.02–0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin >2 g/dL. Trough linezolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemoglobin and treatment-emergent anaemia (adjusted OR 2.9; 95% CI 1.3–6.8). SNPs 2706A > G and 3010G > A in mitochondrial DNA were not associated with linezolid toxicity. Conclusions Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.

ObjectiveTo describe case rates, testing rates, and percent positivity of coronavirus disease 2019 (COVID-19) among children aged 0-18 years by school-age grouping.DesignWe abstracted data from Georgia’s State Electronic Notifiable Disease Surveillance System on all 10,437 laboratory-confirmed COVID-19 cases among children aged 0-18 years during March 30, 2020 to June 6, 2021. We examined case rates, testing rates, and percent positivity by school-aged groupings, namely: preschool (0-4 years), elementary school (5-10 years), middle school (11-13 years), and high school (14-18 years) and compared these data among school aged children to those in the adult population (19 years and older).SettingFulton County, Georgia.Main outcome measuresCOVID-19 case rates, testing rates, and percent positivity.ResultsOver time, the proportion of pediatric cases rose substantially from 1.1% (April 2020) to 21.6% (April 2021) of all cases in the county. Age-specific case rates and test rates were consistently highest among high-school aged children. Test positivity was similar across school-age groups, with periods of higher positivity among high-school aged children.ConclusionsLow COVID-19 testing rates among children, especially early in the pandemic, likely underestimate the true burden of disease in this age group. Despite children having lower measured incidence of COVID-19, we found when broader community incidence increased, incidence also increased among all pediatric age groups. As the COVID-19 pandemic continues to evolve, it remains critical to continue learning about the incidence and transmissibility of COVID-19 in children.

ObjectiveTo describe case rates, testing rates and percent positivity of COVID-19 among children aged 0–18 years by school-age grouping.DesignWe abstracted data from Georgia’s State Electronic Notifiable Disease Surveillance System on all 10 437 laboratory-confirmed COVID-19 cases among children aged 0–18 years during 30 March 2020 to 6 June 2021. We examined case rates, testing rates and percent positivity by school-aged groupings, namely: preschool (0–4 years), elementary school (5–10 years), middle school (11–13 years), and high school (14–18 years) and compared these data among school-aged children with those in the adult population (19 years and older).SettingFulton County, Georgia.Main outcome measuresCOVID-19 case rates, testing rates and percent positivity.ResultsOver time, the proportion of paediatric cases rose substantially from 1.1% (April 2020) to 21.6% (April 2021) of all cases in the county. Age-specific case rates and test rates were consistently highest among high-school aged children. Test positivity was similar across school-age groups, with periods of higher positivity among high-school aged children.ConclusionsLow COVID-19 testing rates among children, especially early in the pandemic, likely underestimated the true burden of disease in this age group. Despite children having lower measured incidence of COVID-19, we found when broader community incidence increased, incidence also increased among all paediatric age groups. As the COVID-19 pandemic continues to evolve, it remains critical to continue learning about the incidence and transmissibility of COVID-19 in children.

Background Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. Methods We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) >500 ms or an absolute change from baseline (ΔQTcF) >60 ms. Results We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF >500 ms and 19 experienced a ΔQTcF >60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir. Conclusions Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients., Severe prolongation of the QT interval corrected by the Fridericia method (QTcF) was uncommon among participants treated for multidrug-resistant or extensively drug-resistant tuberculosis with a regimen containing both bedaquiline and clofazimine. Outcomes were favorable in this setting with high human immunodeficiency virus prevalence. Participants receiving concurrent lopinavir-ritonavir did not experience further QTcF prolongation.

Contains fulltext : 244688.pdf (Publisher’s version ) (Open Access) Bedaquiline is recommended for the treatment of all patients with rifampin-resistant tuberculosis (RR-TB). Bedaquiline accumulates within cells, but its intracellular pharmacokinetics have not been characterized, which may have implications for dose optimization. We developed a novel assay using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure the intracellular concentrations of bedaquiline and its primary metabolite M2 in patients with RR-TB in South Africa. Twenty-one participants were enrolled and underwent sparse sampling of plasma and peripheral blood mononuclear cells (PBMCs) at months 1, 2, and 6 of treatment and at 3 and 6 months after bedaquiline treatment completion. Intensive sampling was performed at month 2. We used noncompartmental analysis to describe plasma and intracellular exposures and a population pharmacokinetic model to explore the relationship between plasma and intracellular pharmacokinetics and the effects of key covariates. Bedaquiline concentrations from month 1 to month 6 of treatment ranged from 94.7 to 2,540 ng/ml in plasma and 16.2 to 5,478 ng/ml in PBMCs, and concentrations of M2 over the 6-month treatment period ranged from 34.3 to 496 ng/ml in plasma and 109.2 to 16,764 ng/ml in PBMCs. Plasma concentrations of bedaquiline were higher than those of M2, but intracellular concentrations of M2 were considerably higher than those of bedaquiline. In the pharmacokinetic modeling, we estimated a linear increase in the intracellular-plasma accumulation ratio for bedaquiline and M2, reaching maximum effect after 2 months of treatment. The typical intracellular-plasma ratios 1 and 2 months after start of treatment were 0.61 (95% confidence interval [CI]: 0.42 to 0.92) and 1.10 (95% CI: 0.74 to 1.63) for bedaquiline and 12.4 (95% CI: 8.8 to 17.8) and 22.2 (95% CI: 15.6 to 32.3) for M2. The intracellular-plasma ratios for both bedaquiline and M2 were decreased by 54% (95% CI: 24 to 72%) in HIV-positive patients compared to HIV-negative patients. Bedaquiline and M2 were detectable in PBMCs 6 months after treatment discontinuation. M2 accumulated at higher concentrations intracellularly than bedaquiline, supporting in vitro evidence that M2 is the main inducer of phospholipidosis.

Background: We present data on risk factors for severe outcomes among patients with coronavirus disease 2019 (COVID-19) in the southeast United States (U.S.). Objective: To determine risk factors associated with hospitalization, intensive care unit (ICU) admission, and mortality among patients with confirmed COVID-19. Design: A retrospective cohort study. Setting: Fulton County in Atlanta Metropolitan Area, Georgia, U.S. Patients: Community-based individuals of all ages that tested positive for SARS-CoV-2. Measurements: Demographic characteristics, comorbid conditions, hospitalization, ICU admission, death (all-cause mortality), and severe COVID-19 disease, defined as a composite measure of hospitalization and death. Results: Between March 2 and May 31, 2020, we included 4322 individuals with various COVID-19 outcomes. In a multivariable logistic regression random-effects model, patients in age groups ≥45 years compared to those Conclusions: Multiple risk factors for hospitalization, ICU admission, and death were observed in this cohort from an urban setting in the southeast U.S. Improved screening and early, intensive treatment for persons with identified risk factors is urgently needed to reduce COVID-19 related morbidity and mortality.

Schistosoma mansoni (SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM. Relative to the wealth of information regarding the immune response to SM eggs, little is known about the immune response to the adult worm. In addition, while a great deal of research has uncovered mechanisms by which co-infection with helminths modulates immunity to other pathogens, there is a paucity of data on the effect of pathogens on immunity to helminths. As such, we sought to characterize the breadth of the T cell response to SM and determine whether co-infection with Mycobacterium tuberculosis (Mtb) modifies SM-specific T cell responses in a cohort of HIV-uninfected adults in Kisumu, Kenya. SM-infected individuals were categorized into three groups by Mtb infection status: active TB (TB), Interferon-γ Release Assay positive (IGRA+), and Interferon-γ Release Assay negative (IGRA-). U.S. adults that were seronegative for SM antibodies served as naïve controls. We utilized flow cytometry to characterize the T cell repertoire to SM egg and worm antigens. We found that T cells had significantly higher proliferation and cytokine production in response to worm antigen than to egg antigen. The T cell response to SM was dominated by γδ T cells that produced TNFα and IFNγ. Furthermore, we found that in individuals infected with Mtb, γδ T cells proliferated less in response to SM worm antigens and had higher IL-4 production compared to naïve controls. Together these data demonstrate that γδ T cells respond robustly to SM worm antigens and that Mtb infection modifies the γδ T cell response to SM., Author summary Schistosomiasis, a disease caused by parasitic helminths including Schistosoma mansoni (SM), affects hundreds of millions of people globally. SM undergoes a complex life cycle within humans resulting in adult worm pairs that release eggs into the circulatory system. The human immune response to SM, especially to adult worms, is not well characterized. In addition, the impact of co-infections, which are common in SM endemic regions, on the immune response to SM is unknown. In this study, we first sought to characterize the T cell response to different stages of the SM life cycle. We next evaluated whether T cell responses to SM were altered in the setting of co-infection with Mycobacterium tuberculosis, the bacteria that causes tuberculosis. We determined that human T cell responses to SM adult worm antigen are more robust than to SM egg antigen. This response is dominated by a non-classical T cell subset of γδ T cells producing IFNγ and TNFα. Lastly, we found that the ability of γδ T cells to proliferate in response to SM worm was lower in individuals with tuberculosis compared to naïve controls. This study provides novel insights into the immune response to SM and how tuberculosis may impair SM immunity.

Black, Hispanic, and Indigenous persons in the United States have an increased risk of SARS-CoV-2 infection and death from COVID-19, due to persistent social inequities. The magnitude of the disparity is unclear, however, because race/ethnicity information is often missing in surveillance data. In this study, we quantified the burden of SARS-CoV-2 infection, hospitalization, and case fatality rates in an urban county by racial/ethnic group using combined race/ethnicity imputation and quantitative bias-adjustment for misclassification. After bias-adjustment, the magnitude of the absolute racial/ethnic disparity, measured as the difference in infection rates between classified Black and Hispanic persons compared to classified White persons, increased 1.3-fold and 1.6-fold respectively. These results highlight that complete case analyses may underestimate absolute disparities in infection rates. Collecting race/ethnicity information at time of testing is optimal. However, when data are missing, combined imputation and bias-adjustment improves estimates of the racial/ethnic disparities in the COVID-19 burden.

BACKGROUND Helminth infections can modulate immunity to Mycobacterium tuberculosis (Mtb). However, the effect of helminths, including Schistosoma mansoni (SM), on Mtb infection outcomes is less clear. Furthermore, HIV is a known risk factor for tuberculosis (TB) disease and has been implicated in SM pathogenesis. Therefore, it is important to evaluate whether HIV modifies the association between SM and Mtb infection. SETTING HIV-infected and HIV-uninfected adults were enrolled in Kisumu County, Kenya, between 2014 and 2017 and categorized into 3 groups based on Mtb infection status: Mtb-uninfected healthy controls, latent TB infection (LTBI), and active TB disease. Participants were subsequently evaluated for infection with SM. METHODS We used targeted minimum loss estimation and super learning to estimate a covariate-adjusted association between SM and Mtb infection outcomes, defined as the probability of being Mtb-uninfected healthy controls, LTBI, or TB. HIV status was evaluated as an effect modifier of this association. RESULTS SM was not associated with differences in baseline demographic or clinical features of participants in this study, nor with additional parasitic infections. Covariate-adjusted analyses indicated that infection with SM was associated with a 4% higher estimated proportion of active TB cases in HIV-uninfected individuals and a 14% higher estimated proportion of active TB cases in HIV-infected individuals. There were no differences in estimated proportions of LTBI cases. CONCLUSIONS We provide evidence that SM infection is associated with a higher probability of active TB disease, particularly in HIV-infected individuals.

Mass screening for SARS-CoV-2 infection in long-term care facilities revealed significantly higher prevalence of infection in facilities that screened in response to a known infection compared to those that screened as a prevention measure. “Response” facilities had a SARS-CoV-2 prevalence of 28.9% while “preventive” facilities’ prevalence was 1.6% (p