Trends in HIV-2 Diagnoses and Use of the HIV-1/HIV-2 Differentiation Test - United States, 2010-2017.

Since 2014, the recommended laboratory testing algorithm for diagnosing human immunodeficiency virus (HIV) infection has included a supplemental HIV-1/HIV-2 differentiation test to confirm infection type on the basis of the presence of type-specific antibodies (1). Correctly identifying HIV-1 and HIV-2 infections is vital because their epidemiology and clinical management differ. To describe the percentage of diagnoses for which an HIV-1/HIV-2 differentiation test result was reported and to categorize HIV type based on laboratory test results, 2010-2017 data from CDC's National HIV Surveillance System (NHSS) were analyzed. During 2010-2017, a substantial increase in the number of HIV-1/HIV-2 differentiation test results were reported to NHSS, consistent with implementation of the HIV laboratory-based testing algorithm recommended in 2014. However, >99.9% of all HIV infections identified in the United States were categorized as HIV-1, and the number of HIV-2 diagnoses (mono-infection or dual-infection) remained extremely low (<0.03% of all HIV infections). In addition, the overall number of false positive HIV-2 test results produced by the HIV-1/HIV-2 differentiation increased. The diagnostic value of a confirmatory antibody differentiation test in a setting with sensitive and specific screening tests and few HIV-2 infections might be limited. Evaluation and consideration of other HIV tests approved by the Food and Drug Administration (FDA) that might increase efficiencies in the CDC and Association of Public Health Laboratories-recommended HIV testing algorithm are warranted.

Evaluation of disparity in care for perforated appendicitis in a universal healthcare system.

PURPOSE: Racial and socioeconomic disparities have been reported in the management of appendicitis. Perforated appendicitis (PA) is used as an index for barriers to care due to delays in treatment. This study evaluates the effect of racial and socioeconomic differences on the likelihood of PA in a universally insured national healthcare system. METHODS: A retrospective review of pediatric patients enrolled in TRICARE who underwent appendectomy during a 5-year period was performed. Logistic regression was used to examine the association between ethnicity, age, gender, parent, or guardian marital status and deployment status of the active duty parent, type of facility, and type of admission with the odds of perforated appendicitis. RESULTS: A total of 3124 children met inclusion criteria. One-third of children carried the diagnosis of PA. Increased odds of PA was associated with younger age of patient among children of military personnel with enlisted ranks and senior officer ranks. CONCLUSION: In a universal healthcare system, no disparities across race with regard to presentation of appendicitis were identified. Increased odds of perforated appendicitis were observed in younger patients, but this was demonstrated in families of both high and low socioeconomic status. Universal coverage does appear to eliminate some barriers to healthcare.

Enhancements to the National HIV Surveillance System, United States, 2013-2023.

HIV infection is monitored through the National HIV Surveillance System (NHSS) to help improve the health of people with HIV and reduce transmission. NHSS data are routinely used at federal, state, and local levels to monitor the distribution and transmission of HIV, plan and evaluate prevention and care programs, allocate resources, inform policy development, and identify and respond to rapid transmission in the United States. We describe the expanded use of HIV surveillance data since the 2013 NHSS status update, during which time the Centers for Disease Control and Prevention (CDC) coordinated to revise the HIV surveillance case definition to support the detection of early infection and reporting of laboratory data, expanded data collection to include information on sexual orientation and gender identity, enhanced data deduplication processes to improve quality, and expanded reporting to include social determinants of health and health equity measures. CDC maximized the effects of federal funding by integrating funding for HIV prevention and surveillance into a single program; the integration of program funding has expanded the use of HIV surveillance data and strengthened surveillance, resulting in enhanced cluster response capacity and intensified data-to-care activities to ensure sustained viral suppression. NHSS data serve as the primary source for monitoring HIV trends and progress toward achieving national initiatives, including the US Department of Health and Human Services' Ending the HIV Epidemic in the United States initiative, the White House's National HIV/AIDS Strategy (2022-2025), and Healthy People 2030. The NHSS will continue to modernize, adapt, and broaden its scope as the need for high-quality HIV surveillance data remains.

Time From HIV Infection to Diagnosis in the U.S., 2014-2018.

INTRODUCTION: Understanding the role of sociologic, structural, and biomedical factors that influence the length of time from HIV infection to diagnosis and reducing the time from infection to diagnosis are critical for achieving the goals of the Ending the HIV Epidemic initiative. In a retrospective analysis, the length of time from HIV infection to diagnosis and its association with individual- and facility-level attributes are determined. METHODS: Data reported by December 2019 to the U.S. National HIV Surveillance System for people with HIV diagnosed during 2014-2018 were analyzed during December 2020. A CD4 depletion model was used to estimate the time from HIV infection to diagnosis. RESULTS: During 2018, the median time from HIV infection to diagnosis was shorter for those infections diagnosed using the rapid testing algorithm (30.3 months, 95% CI=25.5, 34.5) than those diagnosed using the recommended (41.0 months, 95% CI=39.5, 42.0), traditional (37.0 months, 95% CI=29.5, 43.5), or other (35.5 months, 95% CI=32.5, 38.0) diagnostic testing algorithms. From 2014 to 2018, the time from HIV infection to diagnosis remained stable overall for all testing methods except for the traditional diagnostic testing algorithm. In multivariate analyses, those more likely to have HIV diagnosed closer to the time of infection were younger, were White, had transmission risk factors of injection drug use or heterosexual contact (for female individuals) or male-to-male sexual contact and injection drug use, or had HIV diagnosed at a correctional or screening facility (p<0.01). CONCLUSIONS: Providing access to expanded testing, including rapid testing in nonclinical settings, is likely to result in a decrease in the length of time a person is unaware of their HIV infection and thus reduce onward transmission of HIV infection.

Differences among diagnostic testing algorithms in the time from HIV diagnosis to care.

BACKGROUND: The association between the type of diagnostic testing algorithm for HIV infection and the time from diagnosis to care has not been fully evaluated. Here we extend an earlier analysis of this association by controlling for patient and diagnosing facility characteristics. STUDY DESIGN: Descriptive analysis of HIV infection diagnoses during 2016 reported to the National HIV Surveillance System through December 2017. Algorithm type: traditional = initial HIV antibody immunoassay followed by a Western blot or immunofluorescence antibody test; recommended = initial HIV antigen/antibody immunoassay followed by HIV-1/2 type-differentiating antibody test; rapid = two CLIA-waived rapid tests on the same date. RESULTS: In multivariate analyses controlling for patient and diagnosing facility characteristics, persons whose infection was diagnosed using the rapid algorithm were more likely to be linked to care within 30 days than those whose infection was diagnosed using the other testing algorithms (p < 0.01). The median time to link to care during a 30-day follow-up was 9.0 days (95% CI 8.0-12.0) after the rapid algorithm, 17.0 days (95% CI 17.0-18.0) after the recommended algorithm, and 23.0 days (95% CI 22.0-25.0) after the traditional algorithm. CONCLUSIONS: The time from HIV diagnosis to care varied with the type of testing algorithm. The median time to care was shortest for the rapid algorithm, longest for the traditional algorithm, and intermediate for the recommended algorithm. These results demonstrate the importance of choosing an algorithm with a short time between initial specimen collection and report of the final result to the patient.

Trends in testing algorithms used to diagnose HIV infection, 2011-2015, United States and 6 dependent areas.

BACKGROUND: In 2014 the Centers for Disease Control and Prevention (CDC) and the Association of Public Health Laboratories (APHL) issued updated laboratory testing recommendations for the diagnosis of HIV infection. OBJECTIVES: To examine trends in the use of HIV diagnostic testing algorithms, and determine whether the use of different algorithms is associated with selected patient characteristics and linkage to HIV medical care. STUDY DESIGN: Analysis of HIV infection diagnoses during 2011-2015 reported to the National HIV Surveillance System through December 2016. Algorithm classification: traditional = initial HIV antibody immunoassay followed by a Western blot or immunofluorescence antibody test; recommended = initial HIV antibody IA followed by HIV-1/2 type-differentiating antibody test; rapid = two CLIA-waived rapid tests on same date. RESULTS: During 2011-2015, the percentage of HIV diagnoses made using the traditional algorithm decreased from 84% to 16%, the percentage using the recommended algorithm increased from 0.1% to 64%, and the percentage using the rapid testing algorithm increased from 0.1% to 2%. The percentage of persons linked to care within 30 days after HIV diagnosis in 2015 was higher for diagnoses using the recommended algorithm (59%) than for diagnoses using the traditional algorithm (55%) (p < 0.05). CONCLUSIONS: During 2011-2015, the percentage of HIV diagnoses reported using the recommended and rapid testing algorithms increased while the use of the traditional algorithm decreased. In 2015, persons with HIV diagnosed using the recommended algorithm were more promptly linked to care than those with diagnosis using the traditional algorithm.

Rapid and sensitive detection of biological warfare agents using time-resolved fluorescence assays.

We have achieved sensitive, rapid and reproducible detection of three biological threat agents in a variety of biological and environmental matrices using the DELFIA time-resolved fluorometry (TRF) assay system (Perkin-Elmer Life Sciences, Akron, OH). Existing ELISA assays for the detection of Francisella tularensis, Clostridium botulinum A/B neurotoxin (BotNT A/B), and Staphylococcus aureus enterotoxin B (SEB) were converted to TRF assays. They use 100 microl of positive control or unknown per test well and require just over 2 h to run. Fluorescent signal read time is a fraction of a second per well. The assay format consists of a capture ELISA utilizing a biotinylated capture antibody, prebound to a streptavidin-coated 96-well plate and a lanthanide (Europium, Eu3+)-labeled detector antibody. The bound Eu-labeled detector antibody produces a fluorescent signal upon the addition of an enhancement solution. The signal results from the dissociation of the Europium from the antibody, creating a micelle, thus amplifying the signal nearly one million-fold. Sensitivities achieved by these assays were between 4 and 20 pg/ml in buffer. Additionally, we have tested this system in different matrices such as serum, urine, dirt, and sewage. Concentration curves generated from standard solutions produced a wide linear range making serial dilutions of unknown samples unnecessary. DELFIA TRF assays are significantly better in terms of sensitivity, linear range, and run time than standard capture ELISAs and should facilitate early detection of potential biological warfare agents in clinical and environmental samples.

Rapid diagnostic assays in the genomic biology era: detection and identification of infectious disease and biological weapon agents.

In this special section of BioTechniques, we examine the role of rapid molecular technologies in the detection and identification of agents of infectious disease (ID) and biological weapons (BWs). Besides the threat posed by the global proliferation of BW technologies, there are numerous emerging and reemerging ID agents with significant public health consequences. Further compounding this already complicated situation are the estimated 600 million international tourists annually, many with the potential to the spread disease globally in a matter of hours. While clinical laboratories have key roles in the detection and identification of potential ID/BW agents, most staff are unfamiliar with these agents because of their rarity and the often laborious conventional methodologies needed to identify them. To meet this challenge, a vast array of rapid assay strategies has been developed for use in clinical diagnostics and environmental detection. Technologies have been developed or adapted to the challenges posed by these agents, permitting detection and identification in several minutes to hours. In particular, the development of improved reagents and detection systems has led to dramatic improvements in the sensitivity and specificity of immunological and nucleic acid-based systems, allowing an ever-increasing range of analytes to be identified and quantitated. In the accompanying articles, we have brought together experts from the many overlapping aspects of this arena in order to present a comprehensive and critical analysis of these technologies.

Immunoassay of infectious agents.

Immunoassays have evolved for a broad range of applications since the pioneering work of Yalow and Berson who developed the first competitive radioimmunoassay (RIA) for human insulin in 1959. Immunoassay detection of specific antigens and host-produced antibodies directed against such antigens consitutes one of the most widely used and successful methods for diagnosing infectious diseases (IDs). The number and variety of new assay systems that are continually being developed reflect the increasing demand for immunoassays possessing greater sensitivity, speed, and ease of use. This trend has been driven, in part, by the need for improved immunodiagnostic systems to perform rapid testing and counter emerging IDs and biothreat (BT) agents. Another factor driving this trend is the need to integrate immunoassays with more sensitive nucleic acid-based methods for a comprehensive approach. Here we examine the development of immunoassays, some of the key formats used for the detection and identification of BT/ID agents, and the application of these technologies under different scenarios.

Detection of staphylococcal enterotoxin B (SEB) by enzyme-linked immunosorbent assay and by a rapid hand-held assay.

Staphylococcal enterotoxins are a frequent cause of food poisoning. Immunologically-based assays for the detection of staphylococcal enterotoxins are commercially available, but require at minimum of 3 hours. We used staphylococcal enterotoxin B to compare two commercially available assays with a newly developed rapid immunochromatographic-based hand-held assay. The detection limit of the commercially available assays accounted for 500 pg and 100 pg enterotoxin B/ml, respectively, whereas 50 pg enterotoxin B /ml were detected within 15 min using the hand-held assay. Enterotoxin B-spiked custard served as a model to detect staphylococcal enterotoxin in food. Depending on the extraction method applied, the detection limit was in the range of 500 pg to 2500 pg/g custard for the commercially available assays and 62.5 pg/g for the hand-held assay. We conclude that the hand-held assay is widely applicable because it is sensitive, specific with regard to the tested enterotoxins, and the results can be read with the naked eye.

Strengthening public health laboratory capacity in Thailand for International Health Regulations (IHR) (2005).

INTRODUCTION: Thailand conducted a national laboratory assessment of core capacities related to the International Health Regulations (IHR) (2005), and thereby established a baseline to measure future progress. The assessment was limited to public laboratories found within the Thai Bureau of Quality and Safety of Food, National Institute of Health and regional medical science centres. METHODS: The World Health Organization (WHO) laboratory assessment tool was adapted to Thailand through a participatory approach. This adapted version employed a specific scoring matrix and comprised 16 modules with a quantitative output. Two teams jointly performed the on-site assessments in December 2010 over a two-week period, in 17 public health laboratories in Thailand. The assessment focused on the capacity to identify and accurately detect pathogens mentioned in Annex 2 of the IHR (2005) in a timely manner, as well as other public health priority pathogens for Thailand. RESULTS: Performance of quality management, budget and finance, data management and communications was considered strong (>90%); premises quality, specimen collection, biosafety, public health functions, supplies management and equipment availability were judged as very good (>70% but ≤90%); while microbiological capacity, staffing, training and supervision, and information technology needed improvement (>60% but ≤70%). CONCLUSIONS: This assessment is a major step in Thailand towards development of an optimized and standardized national laboratory network for the detection and reporting of infectious disease that would be compliant with IHR (2005). The participatory strategy employed to adapt an international tool to the Thai context can also serve as a model for use by other countries in the Region. The participatory approach probably ensured better quality and ownership of the results, while providing critical information to help decision-makers determine where best to invest finite resources.