The Role of Point-of-Care Testing in Travel Medicine

Use and Regulation of Point-of-Care Tests in the United States

The regulation of laboratory testing in the United States is administered by the FDA and is based on complexity of performance, including specimen preparation. The complexity model assigns a category of moderate or high complexity category based on the guidelines in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). These moderate and highly complex tests are most often performed in a traditional laboratory setting. Some rapid tests (e.g., Remel XPECT Giardia/Cryptosporidium lateral flow assay) fall into the category of moderate complexity, meaning that they are subject to inspection and that technicians must perform proficiency testing and quality control and meet personnel requirements. POC tests in the moderate complexity category (e.g., blood gases, electrolytes) are often performed in a healthcare environment in which the laboratory supports these requirements. A third category, and the category most often associated with POC testing, is known as “waived tests.” Waived tests are defined as “simple laboratory examinations and procedures that have an insignificant risk of an erroneous result.” Clearly, this definition is problematic if applied to tests such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and others that can have significant consequences if results are erroneous. In addition, a single positive result for those tests that require confirmation (e.g., HIV) should never be provided to the patient without confirmation; therefore, personnel performing such POC tests much be trained and have appropriate oversight to prevent such occurrences. In 1988 when the CLIA regulations were written, there were only eight analytes; as of February 2016 there were currently more than 125 analytes and hundreds of test systems available.

Importantly, waived tests, even though they may be regarded as “simple,” require knowledge, competence, and an understanding of basic testing procedures. If reagents have expired or are used in either insufficient or excessive volume or the testing times are either prolonged or abbreviated, the results of testing may be difficult to interpret. For example, the interpretation of many tests is based on the accumulation of a specific color reaction after 1-2 minutes of reaction. If reaction times are not monitored closely and tests are allowed to sit for an extra 2-3 minutes or more, the extra time can greatly enhance the accumulation of color, resulting in false positive results.

In the United States it is important to distinguish which POC tests are in the moderate complexity or “waived” category, because that categorization determines the personnel, training, and quality assurance requirements for performing the test. A list of waived analytes is available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/analyteswaived.cfm and a list of waived test systems is available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/testswaived.cfm .

For travel clinics in the United States in which there is no laboratory oversight (e.g., no requirements for training, quality assurance, or proficiency testing), there are a limited number of tests in the waived category for infectious diseases. Tests cleared by the FDA as “waived tests” include those for HIV, HCV, influenza, respiratory syncytial virus, Epstein-Barr virus, Group A Streptococcus , adenovirus, Helicobacter pylori , trichomonas, and presence of Gram-negative bacteria in vaginal specimens (bacterial vaginitis).

An example of a rapid diagnostic test (RDT) that is considered a POC in international settings is the malaria antigen detection assay. While their use in malaria-endemic areas has proven a major step forward in providing rapid treatment, in the United States only one test system (BinaxNOW® Malaria) for malaria has been approved by the FDA. It is categorized as moderately complex and must meet the requirements listed above for performance of moderately complex testing.

Use and Regulation for Point-of-Care Tests in Resource-Limited Settings

Many of the countries that present the highest risk to international travelers lack regulatory standards regarding production or importation of test kits. A WHO report addressing regulation of in vitro diagnostics established that many POC tests sold in limited-resource countries perform poorly due to the lack of regulatory oversight or enforcement. Because many of these low-quality POC tests are inexpensive, countries where there are no quality standards often use cost as the single factor in the decision to purchase and use a test kit.

POC tests in resource-limited settings have been valuable in addressing the HIV epidemic, in providing rapid diagnosis of malaria infections, and, more recently, in transfusion medicine (rapid syphilis test). However, studies describing the value of these tests emphasize that the effectiveness of POC tests is dependent on test quality and conditions of use.

In international settings where there is no oversight of performance or of manufacturing of tests, there are insufficient data to determine common parameters such as sensitivity and specificity, and no studies in populations of intended use to provide data on predictive value. Therefore, test results from these settings should be viewed with caution and repeated if necessary.