Serology: Clear Answers

The Centers for Disease Control and Prevention (CDC), in its MMWR, has just released a summary of a study of HIV algorithms.        The CDC analysis finds that a testing process used in four areas identified a substantial number of acute, or very early, infections that would have been missed using the currently-recommended process. In light of recent advances in HIV testing technology, CDC evaluated a testing process that incorporates cutting-edge tests to better identify acute HIV and additional follow-up tests for conflicting results to minimize misdiagnosis. Among people newly diagnosed with HIV infection using this algorithm, 32% were detected in the acute phase of infection in a Phoenix emergency department screening program and 9% were in the acute phase in an ongoing testing study in New York City, North Carolina, and San Francisco. Following the currently-recommended process, these infections may have been misreported as negative. Early HIV diagnosis, particularly for those in the highly-infectious acute phase of HIV infection, is a critical step toward stopping HIV transmission and starting life-saving treatment and care. CDC will consider these findings as it continues the process of evaluating and refining testing recommendations. In the meantime, researchers call on clinicians to remain vigilant for acute infection and to perform additional, follow-up testing for HIV for patients with conflicting test results. Click here to read the CDC’s summary.

Development focuses on creating testing options that are faster, better, and easier

BY RENEE DIIULIO

       With well-established technologies, traditional clinical serology laboratories see consolidation of menus for improved efficiencies and new test options that are transforming virology screening.
       To the uninitiated, the bright red-colored portion of blood would seem to be its most important component. But as laboratory technologists are well aware, it’s the clear serum left behind when whole blood is centrifuged that often holds the answers clinicians seek.
       Is a patient pregnant? Test for the presence of the hormone human chorionic gonadotropin (HCG) in the blood serum. Wondering about kidney health? Determine overall protein presence, in the blood serum. The liver? Look at related enzymes—in the blood serum. Diagnosing an infection—are there antibodies in the blood serum?
       The right test can help clinicians determine diagnoses and, in some instances, appropriate treatment paths. But what is the right test? For each clinical laboratory, the answer is different, based on their patient populations, physician customers, and available resources. And over time (although sometimes, it happens seemingly overnight), the answer changes with the introduction of a new diagnostic, new procedure, or new medication.
       Today’s clinical serology laboratories (those typically running antigen and antibody tests) are constantly adapting to incorporate these advances into their programs, balancing their ability to bring on new options against an ever-tightening pool of resources as they evolve.
       Many technologies in the laboratory (eg, ELISAs, IFAs, etc) are well established, with automation having already been introduced. Progress in recent years has occurred with a slow but steady climb, and development now is currently focused on creating testing options that are faster, better, and easier. Part of that strategy involves developing a leaner workflow by consolidating test menus on integrated platforms. But much of what enables labs to provide faster and better testing comes in the form of new assays, especially in the evolving realm of virology screening.
       “Serological tests are playing an increasingly important role in screening and diagnosis, and we’ve seen them transition from immunology and other specialty laboratories to the mainstream testing line, typically an integrated chemistry and immunoassay system,” says Jan DeVazier, marketing manager for Women’s Health, Roche Diagnostics Corp, Indianapolis.
       As part of the mainline, much (or at least some) of the process is automated, bringing the benefits of greater accuracy, faster turnarounds, less hands-on time, and improved economics.
       Various factors play into which tests are moved to the mainline, but efficiency is often a significant driver. High-volume tests, as well as those commonly ordered in conjunction with other routine tests, are more likely to find themselves heading toward the line. Consolidation is key. “The trend in laboratories is to get as many tests on that line as possible to reduce any inefficiencies in the lab,” DeVazier says.
As a result, manufacturers’ serology menus are continuously expanding the serology assay menus on their integrated analyzer platforms. New tests offer improved specificity and sensitivity, while new test combinations create time and cost savings.
       While menu consolidation and new assays are improving efficiency and test quality for the main analyzer line, rapid tests are also getting rapidly accepted inside and outside the lab. “These technologies are important when it comes to improving access to testing in clinical and nonclinical settings, and in some areas—such as HIV testing—they’ve also found their place in screening algorithms,” De Vazier says.

“Serological tests are playing an increasingly important role in screening and diagnosis, and we’ve seen them transition from immunology and other specialty laboratories to the mainstream testing line, typically an integrated chemistry and immunoassay system.”—Jan DeVazier, marketing manager for Women’s Health, Roche Diagnostics Corp

Ahead of the Algorithm
       The new HIV screening algorithm proposed by the Association of Public Health Laboratories (APHL) and the Centers for Disease Control and Prevention (CDC) may not quite be official yet, but health care organizations are already implementing the recommendations. Because the HIV screening algorithm has not been updated since 1989, many institutions had already upgraded their diagnostic technologies to third- and fourth-generation technologies, but some were still using traditional techniques, such as Western blot, for confirmation—per CDC guidelines.      
       The Multispot HIV-1/HIV-2 Rapid Test by Bio-Rad Laboratories differentiates between HIV-1 and HIV-2 The new path replaces Western blot with a rapid test that is more sensitive than the older method. The Multispot HIV-1/HIV-2 Rapid Test by Bio-Rad Laboratories, Hercules, Calif, differentiates between HIV-1 and HIV-2 and is, thus far, the only rapid test approved for this use by the FDA. Facilities performing the test in-house can realize savings in time and money with the switch from an involved Western blot to a moderately complex rapid test; those sending it out can bring it back in for cost savings and shorter turnarounds.
       The serology lab at Strong Memorial University of Rochester Medical Center (URMC), Rochester, NY, announced in late April that it would transition to the new algorithms in May. Incorporating the suggested pathway, the facility’s serology lab will process screening samples on its Abbott ARCHITECT instrument using the company’s fourth-generation assay (the Abbott HIV Ab/AG Combo Assay). The test detects both HIV-1 and HIV-2 antibodies as well as the p24 antigen, which significantly closes the window period for infected individuals (and therefore allows earlier awareness and treatment).
       “This new algorithm is an important step forward in the laboratory diagnosis of HIV infection—an area that continues to pose challenges,” says Marilyn A Menegus, PhD, D(ABMM), F(AAM), professor of microbiology and immunology, Clinical Microbiology Laboratories, URMC. “While we still have a way to go, overall I am very pleased with the reduced turnaround time and more definitive approach of this next-generation HIV screening assay.”
       Results will be confirmed using Bio-Rad’s Multispot test in-house, meaning these specimens need no longer be sent to a reference lab. Discordant specimens will, however, be sent off-site for the diagnostic nucleic acid amplification testing (NAAT) recommended by the new algorithm.
       By implementing the change now, URMC’s goal is to not only prepare for when the guidelines become official, but also to improve care now. The new algorithm and suggested technologies mean facilities now have the potential to obtain a specimen, screen it, and confirm the diagnosis within the same day, providing tremendous benefit to clinicians and patients.
       “These are very exciting times for HIV diagnostic testing,” says Ginger Weeden, (MLS)ASCP^cm, US marketing manager, Bio-Rad Laboratories. “With the advent of fourth-generation HIV screening by Bio-Rad and Abbott, plus added flexibility in the algorithm for supplemental testing such as the Multispot Rapid test, the laboratory wins with ease of use and faster turnaround times. The clinicians win with more complete information in a shorter period of time, and the patient wins by being linked with care more quickly to improve the outcome. Finally, public health wins because we are reducing the spread of the virus and decreasing the risk of HIV/AIDS in our communities.”

“This new algorithm is an important step forward in the laboratory diagnosis of HIV infection—an area that continues to pose challenges. While we still have a way to go, overall I am very pleased with the reduced turnaround time and more definitive approach of this next generation HIV screening assay.”—Marilyn A Menegus, PhD, D(ABMM), F(AAM), professor of microbiology and immunology, Clinical Microbiology Laboratories, University of Rochester Medical Center

Spreading Hepatitis
       New recommendations have also come out recently regarding hepatitis C virus (HCV) that have similar aims of increasing awareness and improving outcomes. In August of last year, the CDC augmented its recommendations for screening and testing for HCV in response to concerns regarding incidence and care.
       According to the agency, many of the 2.7 to 3.9 million people living with HCV do not know they are infected and are therefore not receiving care and treatment. A large portion of these unaware individuals have been identified as falling within a certain age cohort: those born between 1945 and 1965. The CDC estimates that although this population comprises only an approximate 27% of the population, it accounts for roughly three-fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and is at the greatest risk for hepatocellular carcinoma and other HCV-related liver disease.
       New therapies have become available that can halt disease progression and provide a virologic cure for many patients, helping to reduce the statistics cited above—if the patient seeks treatment. Screening is therefore an important step in care. To reduce the number of patients unaware of their status, the CDC has recommended that all people in this age group undergo one-time testing for HCV without prior ascertainment for risk.
       This, naturally, means more tests. Hepatitis testing, in general, is fairly common, and many manufacturers offer analyzers for either diagnostic or monitoring purposes. (HCV viral load monitoring is typically done via qualitative PCR-based tests on molecular lab analyzers, some of which offer automated processing.) Automated results can be produced for the alphabet of hepatitis conditions seen today (eg, hepatitis A, hepatitis B, hepatitis C, viral hepatitis), saving laboratories technologist time and creating greater efficiency.
       Roche, for example, has been expanding hepatitis and other infectious disease test capabilities for its cobas modular systems and other serum work area platforms for some time. In recent years, hepatitis menu extensions have included tests for Anti-HBs, anti-HCV, hepatitis B surface antigen, and Anti-HBc IgM.
       “We are moving toward putting hepatitis on all of our systems, and are looking at the addition of more ToRCH assays as well,” DeVazier says. (ToRCH assays produce results for Toxoplasma gondii (toxoplasmosis), rubella (German measles), cytomegalovirus (CMV), and herpes simplex virus (HSV).) The company recently launched Herpes Simplex Virus 1 and 2 assays, and has other tests in development that fit into its ToRCH panel.

Faster, Better, Easier
       Performance is key to any test released today. Laboratories must keep a constant eye on the clock. Staffs are shrinking while volumes grow, and any technology that offers walkaway time is in demand. Systems that can further reduce redundancy and consolidate effort add even more value.
       “As laboratories are increasingly faced with staff shortages, they are looking for more automated solutions to help their staff be more productive. The ability to consolidate and integrate as much testing as possible onto a single analyzer or line helps laboratories increase efficiency and maximize their resources,” DeVazier says.
       It’s much faster and easier to put one tube on an instrument and walk away than it is to draw multiple tubes, split them into aliquots, send them to different departments, run the tests, and collect the results in pieces.
       In fact, some laboratories today don’t need equipment so much as assistance with retooling their workflow. “Labs that are used to manual sample preparation and dedicated analyzers can often find significant efficiency gains and economic benefits simply by automating several of these steps and consolidating different tests onto a single platform. Not only can those process changes give them more consistent turnaround times, they can free up their staff to focus on more important value-added tasks,” DeVazier says.
       As labs performing serology-based testing reap the benefits of faster, better, and easier assays and leaner workflow options, they also gain the potential to provide enhanced value to clinicians, especially as the rapidly developing segment of virology screening moves into the mainstream. The right test can provide the right answers for clinicians as well as create efficiencies in the lab for busy personnel. It may require the simple addition of an assay to the line or it may require the creation of a line, but with the variety of instruments and the broadening of menus, manufacturers are providing the tools to allow laboratories to adapt to changing conditions—clearly.

Renee Diiulio is a contributing writer for CLP. For more information, contact Editor Judy O’Rourke, at [email protected].