The epidemiology of allergic bronchopulmonary aspergillosis (ABPA) in the United States is not well-described. To estimate national ABPA prevalence among patients with asthma or cystic fibrosis, characterize ABPA testing practices, and describe ABPA clinical features, treatment, and 6-month outcomes. We used the 2016-2022 Merative™ MarketScan® Commercial/Medicare and Multi-State Medicaid Databases to identify cohorts of patients with 1) asthma, 2) cystic fibrosis (CF), and 3) ABPA. We calculated ABPA prevalence per 10,000 patients with asthma or CF, assessed diagnostic testing for ABPA among patients with severe asthma, and described features of patients with ABPA using diagnosis and procedure codes. The overall ABPA prevalence among patients with asthma was 2.8/10,000 (Commercial/Medicare) and 1.0/10,000 (Medicaid). ABPA prevalence increased with asthma severity (Commercial/Medicare: mild 1.3, moderate 9.3, severe 70.6, Medicaid: mild 0.3, moderate 2.4, severe 32.4). Among patients with CF, ABPA prevalence was 183.7/10,000 (Commercial/Medicare) and 134.6/10,000 (Medicaid). Among patients with severe asthma, 10.3% (Commercial/Medicare) and 7.4% (Medicaid) received total immunoglobulin E testing, which is recommended for ABPA diagnosis. Among all patients with ABPA (Commercial/Medicare: n = 1,564, Medicaid: n = 410), ABPA treatments included inhaled corticosteroids (>70%), systemic corticosteroids (>62%), and antifungals (>18%). Patients with ABPA and Medicaid were more likely to experience hospitalization (45.1% vs. 22.5% of patients with Commercial/Medicare insurance) and respiratory failure (18.5% vs. 10.9%). This analysis provides initial estimates of national ABPA prevalence. Further studies could identify potential barriers to ABPA testing and investigate potential factors affecting payer-related differences in ABPA burden.

BACKGROUND: Measures of diagnostic test accuracy provide evidence of how well a test correctly identifies or rules-out disease. Commonly used diagnostic accuracy measures (DAMs) include sensitivity and specificity, predictive values, likelihood ratios, area under the receiver operator characteristic curve (AUROC), area under precision-recall curves (AUPRC), diagnostic effectiveness (accuracy), disease prevalence, and diagnostic odds ratio (DOR) etc. Most available analysis tools perform accuracy testing for a single diagnostic test using summarized data. We developed a SAS macro for evaluating multiple diagnostic tests using individual-level data that creates a 2 × 2 summary table, AUROC and AUPRC as part of output. METHODS: The SAS macro presented here is automated to reduce analysis time and transcription errors. It is simple to use as the user only needs to specify the input dataset, "standard" and "test" variables and threshold values. It creates a publication-quality output in Microsoft Word and Excel showing more than 15 different accuracy measures together with overlaid AUROC and AUPRC graphics to help the researcher in making decisions to adopt or reject diagnostic tests. Further, it provides for additional variance estimation methods other than the normal distribution approximation. RESULTS: We tested the macro for quality control purposes by reproducing results from published work on evaluation of multiple types of dried blood spots (DBS) as an alternative for human immunodeficiency virus (HIV) viral load (VL) monitoring in resource-limited settings compared to plasma, the gold-standard. Plasma viral load reagents are costly, and blood must be prepared in a reference laboratory setting by a qualified technician. On the other hand, DBS are easy to prepare without these restrictions. This study evaluated the suitability of DBS from venous, microcapillary and direct spotting DBS, hence multiple diagnostic tests which were compared to plasma specimen. We also used the macro to reproduce results of published work on evaluating performance of multiple classification machine learning algorithms for predicting coronary artery disease. CONCLUSION: The SAS macro presented here is a powerful analytic tool for analyzing data from multiple diagnostic tests. The SAS programmer can modify the source code to include other diagnostic measures and variance estimation methods. By automating analysis, the macro adds value by saving analysis time, reducing transcription errors, and producing publication-quality outputs.

INTRODUCTION: Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis. Pediatric data comparing the two IGRAs in the United States are very limited. We compared the performance of the two IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cut-off values. METHODS: Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON TB-Gold In-Tube (QFT-GIT) tests were identified from a U.S. multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. RESULTS: Among 3,793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, p < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cut-off of 0.35 IU/mL. CONCLUSIONS: In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cut-offs.

Currently there is no detailed, internationally agreed protocol defined to evaluate antimicrobial susceptibility testing (AST) for Legionella pneumophila (required to establish epidemiological cut-off value or "ECOFF" boundaries); therefore, antimicrobial resistance in these isolates cannot be defined. AST methods utilising media containing activated charcoal as an ingredient, to enable Legionella growth, are unreliable as noted in an internationally authored opinion paper and a new gold standard is required. Here we define a detailed protocol for broth microdilution (BMD) using defined cell culture collection-deposited control reference strains (Philadelphia-1 and Knoxville-1) as well as two accessible reference strains with moderately (lpeAB-carrying) and markedly (23S rRNA mutation-carrying) elevated azithromycin minimum inhibitory concentration (MIC). The defined protocol enables up to eight L. pneumophila strains to be set up on a single 96-well plate per antimicrobial tested. Initial ranges to routinely capture an MIC for these reference strains using clinically relevant antimicrobials azithromycin (0.01-0.25 mg/L), levofloxacin (0.008-0.03 mg/L), lefamulin (0.01-2 mg/L), rifampicin (0.0002-0.0008 mg/L) and doxycycline (0.25-16 mg/L) following incubation for 48 h at 37 °C in a shaking incubator have been empirically determined. Establishment of this internationally agreed protocol sets the scene for the next step: validation and comparison of antimicrobial ranges between international Legionella reference laboratories to establish putative resistance cut-off thresholds for these clinically relevant antimicrobials.

BACKGROUND: Serology for dengue viruses (DENV) and Zika virus (ZIKV) has been hindered by antibody cross-reactivity, which limits the utility of these tests for surveillance and assessment of sero-status. Our aim was to develop a multiplexed IgG-based assay with increased accuracy to assess the history of previous DENV and ZIKV infections. METHODS: We developed and assessed the analytical performance of a sample-sparing, multiplexed, microsphere-based serological assay using domain III of the envelope protein (EDIII) of DENV serotypes 1-4 and ZIKV, the most variable region between each virus. We used a reference panel of well-characterised serum samples from US-based travellers or residents of southeast Asia, central America, or Puerto Rico, who were naive or immune to either or both DENV and ZIKV, to develop an algorithm for detecting previous exposure to DENV and ZIKV and identify optimal positivity cutoffs to maximise assay performance. To independently confirm the performance of the assay and algorithm, we used a second test set of previously collected samples from healthy children (aged 9-16 years) living in Puerto Rico, whose DENV and ZIKV serostatus had been defined using the gold-standard virus neutralisation assay. We evaluated the performance of the multiplex assay compared with the gold-standard assay by estimating sensitivity and specificity for identification of past exposure to ZIKV and DENV. FINDINGS: The multiplexed EDIII assay showed reproducible results over different days and a linearity range from μg to pg levels for various EDIII antigens. Using a reference panel of serum samples from individuals who were DENV naive (n=136), DENV immune (n=38), ZIKV naive (n=67), and ZIKV immune (n=28), we optimised the assay and developed a testing algorithm that was 94·9% (95% CI 83·1-99·1) sensitive and 97·1% (92·7-98·9) specific for identifying previous exposure to DENV, and 100% (95% CI 88·0-100) sensitive and 97·0% (89·8-99·5) specific for identifying previous exposure to ZIKV. In an analysis with an independent test set of 389 samples, the assay and algorithm had 94·2% (89·9-97·1) sensitivity and 92·9% (87·3-96·5) specificity for DENV, and 94·1% (88·7-97·4) sensitivity and 95·0% (90·0-98·0) specificity for ZIKV. INTERPRETATION: The multiplexed EDIII serology assay can accurately identify the history of previous infection with either DENV or ZIKV. This high-throughput and sample-sparing assay is a promising new tool for supporting flavivirus surveillance, epidemiological and clinical studies, and serological testing for dengue vaccine eligibility. Further studies are needed to reduce the cost of the assay, eliminate high background in some samples, and to assess performance in DENV-endemic and ZIKV-endemic countries. FUNDING: US National Institutes of Health.

In the Global Polio Laboratory Network (GPLN), poliovirus (PV) screening results from acute flaccid paralysis (AFP) surveillance is based on virus isolation (VI) through cell culture, entailing long turnaround times and the amplification of live poliovirus. An alternative Direct Detection strategy (DD-ITD) for screening viral nucleic acid from stools, bypassing the need for virus culture, has been developed and extensively validated by GPLN partners. A multi-laboratory demonstration project was conceived to field-test the DD-ITD method by GPLN laboratories from the WHO African, Western Pacific, and Eastern Mediterranean regions, where wild serotype 1 or vaccine-derived polioviruses still circulate. Strategically selected laboratories were tasked to simultaneously process stool suspensions with the current gold-standard VI method and the new DD-ITD strategy. Results from 12 laboratories were compiled and analyzed to assess the quality of each RNA extraction and rRT-PCR run. Matched results for both methods of over 10,500 specimens showed an overall method agreement of 91%. All laboratories detected more PV presumptive positive samples with the DD-ITD strategy than with VI, but a large proportion of DD-ITD positive results (72%) were inconclusive or non-typeable, requiring confirmation through sequencing. A total of 298 (2.8%) samples were PV positive using both methods, 828 (7.9%) positive only for DD-ITD, and 62 (0.6%) positive only with VI. The DD-ITD overall performance, quality of results, and agreement between method results varied significantly across participating laboratories. DD-ITD implementation would entail building proficiency in advanced molecular laboratory techniques and data analysis, and increased demand for confirmatory sequencing. IMPORTANCE: Surveillance of acute flaccid paralysis (AFP) and sensitive poliovirus detection are key components of the WHO Global Polio Eradication Strategy. This work summarizes the results of a multi-laboratory evaluation designed to field-test the performance and applicability of a molecular Direct Detection strategy (DD-ITD) that does not require amplification of live poliovirus. AFP samples were processed in parallel with both the DD-ITD and the current gold-standard PV detection methodology, based on virus isolation (VI) through cell culture. All participating laboratories detected more PV presumptive positive samples using the DD-ITD strategy than with virus isolation methodology, although a higher proportion of DD-ITD results required confirmatory sequencing. Significant variability among laboratories was observed in the quality of the results and overall DD-ITD performance. Implementing DD-ITD would entail building proficiency in advanced molecular laboratory techniques and strengthening data analysis skills.

BACKGROUND: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown. METHODS: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife. RESULTS: Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g. , PFOA: 1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women. DISCUSSION: Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.

For this narrative review, we describe recent high-profile and severe outbreaks of emerging fungal infections, emphasizing lessons learned and opportunities to improve future prevention and response efforts. Several themes and challenges remain consistent across a diverse array of fungal outbreaks, including the multidisciplinary need for improved diagnostic testing to determine species and perform antifungal susceptibility testing, clinical awareness, and optimization of antifungal use. Recent outbreaks exemplify the growing promise of non-culture-based tools in identifying fungal outbreaks and improving responses, although access remains limited. Culture-based tools remain critical for performing antifungal-susceptibility to guide therapy.

Introduction: The avoidance of asthma triggers, like tobacco smoke, facilitates asthma management. Reliance upon caregiver report of their child’s environmental tobacco smoke (ETS) exposure may result in information bias and impaired asthma management. This analysis aimed to characterize the chronicity of ETS exposure, assess the validity of caregiver report of ETS exposure, and investigate the relationship between ETS exposure and asthma attack. Methods: A secondary data analysis was performed on data from a longitudinal study of 162 children aged 7–12 years with asthma living in federally subsidized housing in three US cities (Boston, Cincinnati, and New Orleans). Data were collected at three time points over 1 year. Results: Over 90% of children were exposed to ETS (≥0.25 ng/ml of urine cotinine (UC)). Exposure was consistent over 1 year. Questionnaire data had a sensitivity of 28–34% using UC ≥0.25 ng/ml as the gold standard. High ETS exposure (UC ≥ 30 ng/ml) was significantly associated with asthma attack (aOR 2.97, 0.93–9.52, p = 0.07). Lower levels (UC 0.25–30 ng/ml) were not statistically significant (aOR 1.76, 0.71– 4.38, p = 0.22). No association was found using caregiver-reported ETS exposure. Conclusion: Relying on questionnaire data to assess children’s exposure to tobacco smoke may lead to substantial information bias. For children with asthma, incorrect characterization may substantially impact asthma morbidity. © The Author(s), 2024.

The 37(th) International Conference on Antiviral Research (ICAR) was held in Gold Coast, Australia, May 20-24, 2024. ICAR 2024 featured over 75 presentations along with two poster sessions and special events, including those specifically tailored for trainees and early-career scientists. The meeting served as a platform for the exchange of cutting-edge research, with presentations and discussions covering novel antiviral compounds, vaccine development, clinical trials, and therapeutic advancements. A comprehensive array of topics in antiviral science was covered, from the latest breakthroughs in antiviral drug development to innovative strategies for combating emerging viral threats. The keynote presentations provided fascinating insight into two diverse areas fundamental to medical countermeasure development and use, including virus emergence at the human-animal interface and practical considerations for bringing antivirals to the clinic. Additional sessions addressed a variety of timely post-pandemic topics, such as the hunt for broad spectrum antivirals, combination therapy, pandemic preparedness, application of in silico tools and AI in drug discovery, the virosphere, and more. Here, we summarize all the presentations and special sessions of ICAR 2024 and introduce the 38(th) ICAR, which will be held in Las Vegas, USA, March 17-21, 2025.

During 2016-2022, Medicare part D beneficiaries filled 8,674,460 clotrimazole-betamethasone dipropionate prescriptions. Annual rates were stable (30.9 prescriptions/1,000 beneficiary-years in 2022, enough for one in every 33 beneficiaries). Diagnostic testing was infrequent, particularly among internal medicine, family medicine, and general practitioners, suggesting potential opportunities to improve diagnostic and prescribing practices.

BACKGROUND: Mumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known. METHODS: We conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB(®) Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease. RESULTS: Among 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT. CONCLUSION: A test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation.

INTRODUCTION: In 2021, among all age groups, falls ranked as the third leading cause of unintentional injury death in the USA. Unlike fatal data, which rely on death certificates as the gold standard, there is not a gold standard for non-fatal data. Non-fatal falls data are often based on insurance claims or administrative billing data. The purpose of our study is to compare three claims databases to estimate rates of unintentional fall-related hospitalisations in 2019, the most recent year of available data across the three sources. METHODS: Three databases were used to produce incidence rates of fall-related hospitalisations for the year 2019: (1) Merative MarketScan research databases, (2) Centers for Medicare and Medicaid Services (CMS) data and (3) Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample. Inpatient falls were identified using International Classification of Diseases, 10th Revision, Clinical Modification codes. Incidence rates per 100 000 people were then produced across all three datasets by payer type. Unadjusted incidence rate ratios were estimated with corresponding 95% CIs. RESULTS: There were wide disparities among fall rates between the three datasets by payer type. HCUP had the highest rate of falls among Medicare (1087.6 per 100 000) and commercial enrollees (74.7 per 100 000), while CMS had the highest rates of falls among Medicaid enrollees (148.0 per 100 000). CONCLUSIONS: This study shows wide variation in fall hospitalisation rates based on the claims data used to estimate rates. This study suggests that database selection is an important consideration when determining incidence of non-fatal falls.

BACKGROUND: The OraQuick In-Home HIV self-test represents a fast, inexpensive, and convenient method for users to assess their HIV status. If integrated thoughtfully into existing testing practices, accompanied by efficient pathways to formal diagnosis, self-testing could enhance both HIV awareness and reduce HIV incidence. However, currently available self-tests are less sensitive, particularly for recent infection, when compared to gold-standard laboratory tests. It is important to understand the impact if some portion of standard testing is replaced by self-tests. We used a compartmental model to evaluate the effects of self-testing in diverse scenarios among gay, bisexual and other men who have sex with men (MSM) in the United States for the period 2020-2030, and to understand which scenarios maximize the advantages of self-testing. METHODS: We introduced a novel 4-compartment model for HIV self-testing. We employed the model under different screening rates, self-test proportions, and delays to diagnosis for those identified through self-tests to determine the potential effects of self-testing on HIV incidence and awareness of status when applied to the US MSM population. We studied scenarios in which self-tests supplement laboratory-based tests, with no replacement, and scenarios in which some replacement occurs. We also examined how future improvements in self-test sensitivity may affect our results. RESULTS: When HIV self-tests are supplemental rather than substitutes for laboratory-based testing, self-testing can decrease HIV incidence among MSM in the US by up to 10 % and increase awareness of status among MSM from 85 % to 91 % over a 10-year period, provided linkage to care and formal diagnosis occur promptly following a positive self-test (90 days or less). As self-tests replace a higher percentage laboratory-based testing algorithms, increases in overall testing rates were necessary to ensure reductions in HIV incidence. However, such needed increases were relatively small (under 10 % for prompt engagement in care and moderate levels of replacement). Improvements in self-test sensitivity and/or decreases in the detection period may further reduce any necessary increases in overall testing by up to 40 %. CONCLUSIONS: If properly utilized, self-testing can provide significant long-term reductions to HIV incidence and improve awareness of HIV status. Ensuring that self-testing increases overall testing and that formal diagnosis and engagement in care occur promptly following a positive self-test are necessary to maximize the benefits of self-testing. Future improvements in self-test sensitivity and reductions in the detection period would further reduce HIV incidence and the potential risks associated with replacing laboratory tests with self-tests.

BACKGROUND: The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. METHODS: Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. RESULTS: CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2-2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7-3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1-15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2-4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2-6.5) among patients aged 20-49 years and 2.2 (95%CI:2.1-2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5-12.1), Hispanic/Latino (10.9, 95%CI:10.5-11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20-49 had the highest CVE prevalence ratios. CONCLUSIONS: These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.

In a commercial claims database analysis, <0.5% of patients with inflammatory bowel disease or rheumatoid arthritis developed an IFI within one year of initiating TNF-alpha therapy. Histoplasmosis was the most common IFI type. Overall IFI incidence varied based on region, underlying conditions, and use of certain immunosuppressive medications.

BACKGROUND: HIV testing remains an entry point into HIV care and treatment services. In 2007, Nigeria adopted and implemented a two-test rapid HIV testing algorithm of three HIV rapid test kits, following the sequence: Alere Determine (first test), Unigold(TM) (second test), and STAT-PAK(®) as the tie-breaker. Sub-analysis of the 2018 Nigeria HIV/AIDS Indicator and Impact Survey data showed significant discordance between the first and second tests, necessitating an evaluation of the algorithm. This manuscript highlights lessons learnt from that evaluation. INTERVENTION: A two-phased evaluation method was employed, including abstraction and analysis of retrospective HIV testing data from January 2017 to December 2019 from 24 selected sites supported by the United States President's Emergency Plan for AIDS Relief programme. A prospective evaluation of HIV testing was done among 2895 consecutively enrolled and consented adults, aged 15-64 years, accessing HIV testing services from three selected sites per state across the six geopolitical zones of Nigeria between July 2020 and September 2020. The prospective evaluation was performed both in the field and at the National Reference Laboratory under controlled laboratory conditions. Stakeholder engagements, strategic selection and training of study personnel, and integrated supportive supervision were employed to assure the quality of evaluation procedures and outcomes. LESSONS LEARNT: The algorithm showed higher sensitivity and specificity in the National Reference Laboratory compared with the field. The approaches to quality assurance were integral to the high-quality study outcomes. RECOMMENDATIONS: We recommend comparison of testing algorithms under evaluation against a gold standard. WHAT THIS STUDY ADDS: This study provides context-specific considerations in using World Health Organization recommendations to evaluate the Nigerian national HIV rapid testing algorithm.

Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.

INTRODUCTION: Due to their faithful recapitulation of human disease, nonhumanprimates (NHPs) are considered the gold standard for evaluating drugs against Ebolavirus and other filoviruses. The long-term goal is to reduce the reliance on NHPswith more ethical alternatives. In silico simulations and organoidmodels have the potential to revolutionize drug testing by providing accurate,human-based systems that mimic disease processes and drug responses without theethical concerns associated with animal testing. However, as these emergingtechnologies are still in their developmental infancy, NHP models are presentlyneeded for late-stage evaluation of filovirus vaccines and drugs, as theyprovide critical insights into the efficacy and safety of new medicalcountermeasures. AREAS COVERED: In this review, the authors introduce available NHP models andexamine the existing literature on drug discovery for all medically significantfiloviruses in corresponding models. EXPERT OPINION: A deliberate shift towards animal-free models is desired to alignwith the 3Rs of animal research. In the short term, the use of NHP models canbe refined and reduced by enhancing replicability and publishingnegative data. Replacement involves a gradual transition, beginning withthe selection and optimization of better small animal models; advancingorganoid systems, and using in silico models to accurately predictimmunological outcomes.

BACKGROUND: Pityriasis versicolor (PV), a cutaneous fungal infection, most commonly affects adolescents and young adults and is associated with hyperhidrosis and humid weather. Understanding other factors associated with PV might help improve diagnostic and treatment practices. OBJECTIVES: PV's associations with patient demographics, comorbidities and medication exposures were assessed using the All of Us Database, a large, diverse, national database from the United States. METHODS: A case-control study with multivariable analysis was performed. RESULTS: We identified 456 PV case-patients and 1368 control-patients. PV case-patients (vs. control-patients) were younger (median age [years] (standard deviation): 48.7 (15.4) vs. 61.9 (15.5); OR: 0.95, CI: 0.94-0.96) and more likely to be men versus women (42.8% vs. 33.9%, OR: 1.45, CI: 1.16-1.79) and Black (19.5% vs. 15.8%, OR: 1.35, 95% CI: 1.02-1.80) or Asian (4.6% vs. 2.7%, OR: 1.86, CI: 1.07-3.24) versus White. PV case-patients more frequently had acne (5.3% vs. ≤1.5%, OR: 5.37, CI: 2.76-10.48) and less frequently had type 2 diabetes mellitus (T2DM) (14.7% vs. 24.7%, OR: 0.52, CI: 0.39-0.70) and hypothyroidism (OR: 10.3% vs. 16.4%, OR: 0.59, CI: 0.42-0.82). In multivariable analysis, PV odds were significantly higher in those with acne and lower in those with T2DM, older age and female sex. CONCLUSIONS: Our results may be used as a basis for future studies evaluating whether acne treatment may decrease PV risk. Physicians could educate patients with acne about PV, including strategies to control modifiable PV risk factors, such as avoidance of hot and humid environments and avoidance of use of topical skin oils.

BACKGROUND: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico. METHODS: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS. RESULTS: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1-3)-β-d-glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis. CONCLUSION: Antifungal prophylaxis may be useful in preventing donor-derived infections in recipients of organs from donors that are found to have Fusarium meningitis.

Among 207 914 multimember households with a tinea case, a secondary case was diagnosed in another household member in 8.5%. Excluding same-day diagnoses (20%), the median time from index case to first secondary case was 138 days. To prevent household tinea transmission, appropriate treatment and strategies to reduce environmental contamination are needed.

Sudan is endemic for multiple neglected tropical diseases, including trachoma, onchocerciasis (OV), lymphatic filariasis (LF), and schistosomiasis (SCH). In 2019, dried blood spot samples were collected for a baseline trachoma serosurvey in three localities (El Seraif, Kotom, and Saraf Omrah) in North Darfur State. None were classified previously as OV- or LF-endemic, although low levels of SCH had been identified in all three. Approximately 30 households from 25 communities in each locality were selected by multistage cluster random sampling. Collections of DBSs were analyzed by multiplex bead assay for antibodies to multiple pathogens. This paper presents data on OV (Ov16), LF (Wb123, Bm14, Bm33), and SCH (soluble egg antigen [SEA], Sm25) antibodies among 8,322 individuals from 2,119 households. The survey-adjusted seroprevalence estimates for Ov16 were <0.3% in all localities. Lymphatic filariasis-antigen seroprevalences were discordant. Seroprevalence estimates ranged from 4.6-6.0% (Wb123), 0.99-1.4% (Bm14), and 29.2-33.3% (Bm33). Schistosomiasis seroprevalence estimates among school-aged children ranged from 2.7-8.0% (SEA) and 10.9-15.6% (Sm25). Ov16 seropositivity was low and supported the localities' classification as nonendemic. The results suggested LF exposure, but discordance between antigens, challenges defining seropositivity thresholds, and the absence of programmatic guidance based on antibody serology alone for Wuchereria bancrofti indicate a need for remapping surveys to confirm transmission. Schistosomiasis antibody levels were high enough to warrant further mapping to guide treatment decisions. The lack of gold standards limited interpretation of results, particularly for LF, but in resource-challenged areas, integrated serological surveillance offers the possibility of efficient monitoring of exposure to multiple diseases.

Malaria programs rely upon a variety of diagnostic assays, including rapid diagnostic tests (RDTs), microscopy, polymerase chain reaction (PCR), and bead-based immunoassays (BBA), to monitor malaria prevalence and support control and elimination efforts. Data comparing these assays are limited, especially from high-burden countries like the Democratic Republic of the Congo (DRC). Using cross-sectional and routine data, we compared diagnostic performance and Plasmodium falciparum prevalence estimates across health areas of varying transmission intensity to illustrate the relevance of assay performance to malaria control programs. Data and samples were collected between March-June 2018 during a cross-sectional household survey across three health areas with low, moderate, and high transmission intensities within Kinshasa Province, DRC. Samples from 1,431 participants were evaluated using RDT, microscopy, PCR, and BBA. P. falciparum parasite prevalence varied between diagnostic methods across all health areas, with the highest prevalence estimates observed in Bu (57.4-72.4% across assays), followed by Kimpoko (32.6-53.2%), and Voix du Peuple (3.1-8.4%). Using latent class analysis to compare these diagnostic methods against an "alloyed gold standard," the most sensitive diagnostic method was BBA in Bu (high prevalence) and Voix du Peuple (low prevalence), while PCR diagnosis was most sensitive in Kimpoko (moderate prevalence). RDTs were consistently the most specific diagnostic method in all health areas. Among 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection. Inherent differences in assay performance should be carefully considered when using community survey and surveillance data to guide policy decisions.

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.