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Abstract Background In Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private sector. Methods Between October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB Program (NTP) in Ha Noi, Hai Phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate regression. Results The pre-treatment median monthly household income was significantly higher in the private sector versus NTP cohort (USD 868 vs USD 578; P = 0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313; P = 0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTP participants (USD 754 vs USD 164; P

Abstract Objective: The objective of this study was to determine factors associated with testing positive for SARS-CoV-2 among healthcare personnel. Secondary objectives were to assess representativeness of recruited participants and the effectiveness of a multiple-contact protocol for recruiting healthcare personnel in this COVID-19 study. Design: Survey study, conducted as part of an observational test-negative study of COVID-19 vaccine effectiveness. Setting: University of Utah Health system, including both inpatient and outpatient facilities. Participants: Clinical and non-clinical healthcare personnel at University of Utah Health. 1456 were contacted and 503 (34.5%) completed the survey. Cases were all eligible employees testing positive for COVID-19, with 3:1 randomly selected, matched controls (test negative) selected weekly. Methods: Online survey. Results: Significant differences in the demographics of participants and the source population were observed; e.g., nursing staff comprised 31.6% of participants but only 23.3% of the source population. The multiple-contact recruitment protocol increased participation by ten percentage points and ensured equal representation of controls. Potential exposure to illness outside of work was strongly predictive of testing positive for SARS-CoV-2 (OR = 3.74; 95% CI: 2.29, 6.11) whereas potential exposure at work was protective against testing positive (OR: 0.51, 95% CI: 0.29, 0.88). Conclusions: Carefully designed recruitment protocols increase participation and representation of controls, but bias in participant demographics still exists. The negative association between potential workplace exposure and positive test suggests testing bias in the test-negative design. Healthcare personnel’s potential exposures to COVID-19 outside of the workplace are important predictors of SARS-CoV-2 seropositivity.

Abstract Background The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. Methods We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. Results There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. Conclusion Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Objectives: We assessed whether combining (pooling) four individual's samples and testing with Xpert Ultra has the same accuracy as testing samples individually as a more efficient testing method. Methods: We conducted a cross-sectional study of individuals with presumptive tuberculosis attending primary health care or general hospital facilities in Alagoas, Brazil. The sputum samples of four consecutive individuals were pooled and the pool and individual samples were tested with Xpert Ultra. The agreement of the tests was compared using kappa statistics. We estimated the sensitivity and specificity of pooling using the individual test as the reference standard and potential cartridge savings. Results: A total of 396 participants were tested. A total of 95 (24.0%) individual samples were Mycobacterium tuberculosis (MTB)-positive, 300 (75.8%) “MTB not detected”, including 20 “MTB trace”, and one reported an error. A total of 99 pools of four samples were tested, of which 62 (62.6%) had MTB detected and 37 (37.4%) MTB not detected, including six (6.1%) with MTB trace. The agreement between individual and pooled testing was 96.0%. Pooling had a sensitivity of 95.0% (95% confidence interval 86.9-99%), specificity of 97.1% (95% confidence interval 85.1-99.9%), and kappa of 0.913. The method saved 12.4% of cartridge costs. Conclusion: The pooled testing of specimens had a high level of agreement with individual testing. The pooling of samples for testing improves the efficiency of testing, potentially enabling the screening and testing of larger numbers of individuals more cost-effectively.

Background: Diagnosis and management of suspected urinary tract infection (UTI) in outpatient settings has been shown to be suboptimal. We previously developed a set of stewardship metrics for UTIs based on electronic health record (EHR) data (Antimicrobial Stewardship & Healthcare Epidemiology 2022;2 suppl 1:S5–S6. doi:10.1017/ash.2022). A tier-based approach was used to more fully capture antibiotic use associated with genitourinary (GU) symptoms and diagnoses. Herein we report a preliminary analysis of validity and reliability of these metrics based on chart abstraction. Methods: The study cohort consisted of patients who visited Veterans Affairs emergency departments or primary care clinics between 2015 and 2022 and who had a GU diagnosis based on International Classification of Disease, Tenth Revision (ICD-10) codes, divided into 3 categories: tier 1 (antibiotics always indicated), tier 2 (antibiotics sometimes indicated), and tier 3 (antibiotics not indicated). Visits related to urological procedures, nontarget settings, or concomitant non-GU infections were excluded. Cases were randomly sampled for manual review from within 8 strata based on tier, use of antibiotics, and visit type. An infectious disease physician and pharmacist abstracted charts using a standardized data-collection instrument. Clinical judgments regarding diagnosis and treatment were recorded on a Likert scale without knowledge of how the patient was managed. The intraclass correlation coefficient (ICC) was used to estimate interrater reliability. Results: To date, 148 cases have been reviewed (50 by both reviewers). Mean (SD) age was 67.5 (15.3) years and 12.2% were female. In a majority of tier 1 and 2 visits in which antibiotics were given, the reviewers found evidence for GU infection (69.7%) and favored prescribing of antibiotics (60.6%) (Table). In contrast, most patients in the tier 3 category who received antibiotics were judged to have noninfectious conditions (eg, benign prostatic hypertrophy) and to not require antibiotics. In the subset of records examined by both reviewers, the interrater reliability of judgments of whether antibiotics were warranted was good (ICC = .704). Conclusions: This preliminary validation provides support for a tier-based approach for stewardship metrics for GU conditions that relies upon electronic data to identify patients for whom antibiotics are generally not indicated.

Background: Tracking antibiotic use is a core element of antimicrobial stewardship. We developed a set of metrics based on electronic health record data to support an outpatient stewardship initiative to improve management of urinary tract infections (UTIs) in Veterans’ Affairs (VA) emergency departments (EDs) and primary care clinics. Because UTI diagnostic codes only capture a portion of genitourinary (GU)-related antibiotic use, a tier-based approach was used to evaluate practices. Methods: Metrics were developed to target practices related to antibiotic prescribing and diagnostic testing (Table 1). GU conditions were divided into 3 categories: tier 1, conditions for which antibiotics are usually or always indicated; tier 2, conditions for which antibiotics are sometimes indicated; and tier 3, conditions for which antibiotics are rarely or never indicated (eg, benign prostatic hypertrophy with symptoms). Patients with visits related to urological procedures, nontarget providers, and concomitant non-GU infections were excluded. Descriptive analyses included calculation of the correlation matrix for the 7 metrics and the construction of box plots to display interfacility variability. Results: Metrics were calculated quarterly for 18 VA medical centers, including affiliated clinics, in a western VA network, from July 2018 to June 2020 (Table 1). Tier 3 GU conditions accounted for 1,276 of 11,840 (11%) of GU-related antibiotic use. Metrics 1 and 6b were strongly correlated with each other and were also positively correlated with metrics 2 and 5 (coefficients > 0.5) (Fig. 1). Substantial interfacility variation was observed (Fig. 2). Conclusions: Stewardship metrics for suspected or documented UTIs can identify opportunities for practice improvement. Broadly capturing GU conditions in addition to UTIs may enhance utility for performance feedback. Antibiotic prescribing for tier 3 GU conditions is analogous to unnecessary antibiotic use for acute, uncomplicated bronchitis and upper respiratory tract infections.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%–98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%–100% specificity and 27%–31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

Cryptococcus neoformans: (H99W) was serially passaged in the invertebrate wax moth Galleria mellonella fifteen times to study how fungal virulence evolves under selection and whether those adaptations affect virulence. The G. mellonella passaged strain (P15) and the pre-passage H99W strains were used to infect three different host models of C. neoformans: C. elegans, G. mellonella, and Balb/c mice. While there was no difference in survival in the invertebrate models, P15 killed mice faster than H99W through both intratracheal and intravenous routes of infection and mice infected intravenously with P15 showed higher fungal burden in the brain. Characterization of the major virulence factors of C. neoformans found that P15 had increased capsule size, GXM release, and melanization. Whole genome sequencing of P15 and H99W revealed two mutations in P15, an insertion in the promoter region of NADH dehydrogenase (CNAG_09000) and an insertion in the LMP1 gene (CNAG_06765). Both ATP production and metabolic rate were higher in P15 compared to H99W. Quantitative RT-PCR suggested that the increased ATP was due to increased RNA levels of NADH dehydrogenase. Thus, adaptation to growth in hemocytes resulted in increased production of ATP, increased metabolic rate, and increased virulence in mice. This was likely due to differential expression of virulence factors, which skewed the host immune response to a less efficient Th2 response, with higher levels of IL-4, IL-10, and TNF-α in the brain. Overall, serial passage experiments have increased our understanding of how this yeast evolves under innate immune selection pressure.

Setting: The introduction of Xpert MTB/RIF (Xpert) and renewed interest in chest x-ray (CXR) for tuberculosis testing has provided additional choices to the smear-based diagnostic algorithms used by TB programs previously. More programmatic data is needed to better understand the implications of possible approaches. Objective: We sought to evaluate how different testing algorithms using microscopy, Xpert and CXR impacted the number of people detected with TB in a district hospital in Nepal. Design: Consecutively recruited patients with TB-related symptoms were offered smear microscopy, CXR and Xpert. We tested six hypothetical algorithms and compared yield, bacteriologically positive (Bac+) cases missed, and tests conducted. Results: Among 929 patients, Bac+ prevalence was 17.3% (n = 161). Smear microscopy detected 121 (75.2% of Bac+). Depending on the radiologists’ interpretation of CXR, Xpert testing could be reduced by (31%–60%). Smear microscopy reduced Xpert cartridge need slightly, but increased the overall diagnostic tests performed. Conclusion: Xpert detected a large proportion of Bac+ TB cases missed by microscopy. CXR was useful in greatly reducing the number of diagnostic tests needed even among presumptive TB patients. Loose CXR readings should be used to identify more people for TB testing. More analysis of costs and standardized CXR reading should be considered. Keywords: Diagnostic algorithms Chest X-ray, Xpert MTB/RIF, Case detection, Tuberculosis

Background: Cambodia has one of the highest tuberculosis (TB) prevalence rates in the world. People aged 55 years and over account for an estimated 50% of the country's TB burden, yet this group has a low notification rate owing to specific barriers in accessing health services. One-off active case finding (ACF) days with mobile GeneXpert and X-ray systems were organized at 75 government health facilities in four operational districts. Symptomatic community members with an abnormal chest X-ray were tested using the Xpert MTB/RIF assay. People with TB were then treated at health facilities after screening services moved onto the next site. Methods: De-identified project data were analysed to produce descriptive statistics about the people tested on Xpert and those diagnosed with TB. A linear regression was fit through the 12 quarters of National TB Program (NTP) TB case notification data immediately prior to ACF. The regression was used to calculate trend-expected notifications during and after the ACF quarters. Notifications from the ACF quarters were then compared to actual notifications from the previous year and to the trend-expected notifications during the ACF quarter by age group and type of TB. Finally, NTP TB treatment outcomes for the patients started on treatment during the ACF quarter were compared to those from a year prior. Results: 2068 individuals submitted sputum for Xpert MTB/RIF testing, resulting in the identification of 319 (15.4%) bacteriologically-positive TB patients and an additional 574 people who were clinically diagnosed with TB. In the ACF quarters, new bacteriologically-positive notifications increased +119.2% for all ages and +262.7% for people aged 55 and over compared with trend-expected notifications. Treatment initiation figures remained above trend-expected notifications for three full quarters after ACF. The treatment success rate across all operational districts was significantly higher for patients detected in the ACF quarters (88.8% vs 94.5%, p = 0.012). Conclusion: A series of roving, one-off ACF days at government health facilities were able to increase TB diagnosis, treatment initiation and treatment outcomes in a key population with high TB prevalence. Targeted ACF interventions such as this could be used to reduce a backlog of untreated, prevalent TB. Keywords: Tuberculosis, Active case finding, Elderly, Chest X-ray, Xpert, GeneXpert

Background: Better screening and testing approaches are needed to improve TB case finding, particularly in health facilities where many people with TB seek care but are not diagnosed using the existing approaches. Objective: We aimed to evaluate the performance of various TB screening and testing approaches among hospital outpatients in a setting with a high prevalence of HIV/TB. Methods: We screened outpatients at a large hospital in Cameroon using both chest X-ray and a symptom questionnaire including current cough, fever, night sweats and/or weight loss. Participants with a positive screen were tested for TB using smear microscopy, the Xpert MTB/RIF assay, and culture. Results: Among 2051 people screened, 1137 (55%) reported one or more TB symptom and 389 (19%) had an abnormal chest X-ray. In total, 1255 people (61%) had a positive screen and 31 of those screened (1.5%) had bacteriologically confirmed TB. To detect TB, screening with cough >2 weeks had a sensitivity of 61% (95% CI, 44–78%). Screening for a combination of cough >2 -weeks and/or abnormal chest X-ray had a sensitivity of 81% (95% CI, 67–95%) and specificity of 71% (95% CI, 69–73%), while screening for a combination of cough >2 weeks or any of 2 or more symptoms had a similar performance. Smear microscopy and Xpert MTB/RIF detected 32% (10/31) and 55% (17/31), respectively, of people who had bacteriologically-confirmed TB. Conclusions: Screening hospital outpatients for cough >2 weeks or for at least 2 of current cough, fever, night sweats or weight loss is a feasible strategy that had a high relative yield to detect bacteriologically-confirmed TB in this population. Clinical diagnosis of TB is still an important need, even where Xpert MTB/RIF testing is available. Keywords: Tuberculosis, HIV/AIDS, Case detection, Molecular diagnostics, Chest X-ray