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.

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.

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.

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.