The impact of point-of-care testing on the diagnosis of infectious diseases

The impact of point-of-care testing on the diagnosis of infectious diseases – Lab Management

Robin G. Weiner

Rapid or point-of-care testing (POCT) in the identification and management of infectious diseases is a hot topic worldwide. Medical, political, media and lay people are paying close attention to POCT technology developments in both conventional and highly novel contexts. Not since smallpox, polio and tuberculosis were daily risks in the developed world, have infectious diseases been as high on the list of public health priorities as they are today.

From the advent of HIV/AIDS in 1981 to the emergence in the new millennium of potent influenza strains and fears about “weaponizing” a multitude of organisms, it has become increasingly obvious that successfully identifying and conquering the “old” infectious diseases has not put an end to easily transmissible and lethal diseases. In the United States alone, a nearly century-long decline in deaths from infectious diseases has been reversed; deaths rose 58% between 1980 and 1992 (see graph). The pathogens involved run the gamut from routine but bothersome, to highly lethal. They cause widespread suffering and death; cost governments, insurers and individuals billions of dollars in direct medical costs; disrupt commerce, tourism and other economic activities; and threaten the stability and growth of less-developed countries. More often than not, there are effective therapies for these diseases–effective, that is, if clinicians could diagnosis symptomatic patients rapidly and accurately. Recent experience with Severe Acute Respiratory Syndrome (SARS) also is a reminder that, even when available therapy is less than optimal, the ability to identify contagious individuals and enforce a quarantine saves lives.

What impact do POCT technologies have on managing infectious disease? There are two distinct viewpoints. The first is that of the clinician who wants to be able to provide better patient care in routine practice situations. The second is that of clinicians, public health officials and others who work with both real and anticipated scenarios–like SARS, monkeypox, West Nile virus, or weaponized influenza–that are clearly being encountered more often. Both of these stakeholder groups benefit from access to POCT technology currently in world markets, creating enormous pressure on innovators to develop rapid diagnostics where none currently exist.

POCT: improving patient outcomes

As the number of rapid tests has increased, so has the number of situations in which use of these tests can make a real difference in infectious disease management. A few examples:

* Group B Streptococcus (GBS), the most common cause of life-threatening infections in newborns, can be transmitted from an infected mother to an infant during delivery. One in every 20 newborns with GBS dies. Babies that survive, particularly those who have meningitis, may have long-term problems, such as hearing or vision loss or learning disabilities. While GBS can be diagnosed and treated in pregnant women, many women in the United States and elsewhere still have no prenatal care and arrive at the hospital for delivery with GBS infections. Rapid GBS testing (15 minutes from test to result) in the delivery room allows physicians to identify infected women and push IV antibiotics before delivery that may prevent GBS transmission as the baby moves through the birth canal.

* HIV testing. Results from conventional HIV antibody screen tests are generally not available for one to two weeks. POC tests for HIV infection, on the other hand, allow the diagnosis to be made in 10 minutes, while the individual is still present. This turnaround time can be critical. According to the Centers for Disease Control and Prevention (CDC), up to 25% of HIV-positive persons and 33% of HIV-negative persons testing at publicly funded clinics do not return for their test results and do not receive counseling about medical treatment or the need for behavioral change. Use of a POCT with immediate results substantially increases the number of people who know their HIV status and receive information about next steps. (1)

* Respiratory Syncytial Virus. RSV is a highly contagious, acute, viral infection of the respiratory tract that can become a problem when it is severe or leads to complications. Babies–especially those born prematurely–immunocompromised individuals, and older adults are at increased risk of complications. RSV is the leading cause of hospitalization of children during the first year of life. Infection involving the lower respiratory tract carries an associated mortality rate of 0.5%, especially in premature infants or infants and children with underlying lung disease. Because RSV’s flu-like symptoms are also typical of many other diseases, quick and accurate diagnosis is important to determining optimal treatment. Rapid immunoassays using highly sensitive monoclonal antibodies specific for RSV antigens can be run in a physician’s office, an emergency department or clinic in 15 minutes.

* Influenza and the new importance of “flu-like” symptoms. Most people who get the flu recover completely in one to two weeks, but some develop serious and potentially life-threatening medical complications, such as pneumonia. According to the CDC, 36,000 people die and approximately 100,000 people are hospitalized each year from influenza in the United States alone. Rapid flu tests are fast and accurate ways to test for influenza, particularly in anticipation of new strains developing–or being developed as an instrument of bioterror. Use of rapid flu tests prevents unnecessary use of costly therapeutics and slows the rate at which essential antibiotics become ineffective. Recent concerns about inappropriate antibiotic prescribing have led many in the medical leadership to make this a priority message for clinicians. For example, an American College of Physicians website (www.doctorsforadults.com) highlights the fact that one in six adult visits to physicians are for sore throats and that when a physician uses a rapid test (with a throat swab), the 75% inappropriate antibiotic prescription rate for adults’ sore throats is greatly reduced. (2)

Managing “the new normal” in infectious disease

The importance of rapid POCT in emerging infectious disease was reinforced by the recent outbreak of several new and potentially lethal pathogens, including SARS and West Nile virus. The quick spread of SARS from Asia to North America demonstrated how critical speedy diagnosis and treatment decisions are to disease containment efforts. Dr. Julie Gerberding, CDC director, and other public health officials worldwide, emphasize the importance of being prepared to move quickly to counter the rapid spread of previously unknown infectious agents or weaponized known agents. In her June 2003 keynote address to the AMA House of Delegates, Dr. Gerberding was blunt: “The new normal is emerging infectious diseases, and emerging infectious diseases that are almost instantaneously a global concern because of the speed with which people, animals and products move around the world.” (3) In the United States, both the private sector and public health agencies have echoed and responded to the CDC’s concerns. The U.S. Food and Drug Administration (FDA) has ramped up its approval process for novel, rapid diagnostics as illustrated by its clearance of a rapid assay for West Nile virus in time for this summer’s mosquito season. (4)

The FDA and CDC are also working with private organizations on development of a rapid test for SARS. The FDA has approved dozens of tests for use in diagnosing different types of acute respiratory syndromes that may have symptoms similar to SARS, which helps in the differential diagnosis of patients at the grassroots level. (5) Indeed, the CDC’s International SARS Case Report form (Version 3-27-03) specifically asks under “Diagnostic evaluation” about test results for “rapid influenza test” and “Respiratory Syncytial Virus.”

Another facet of the new normal is bioterrorism–the need to be able to diagnose rapidly and in large populations a host of pathogens (e.g., smallpox, anthrax, plague or weaponized influenza). Researchers in Texas recently noted that during the last century, a series of flu epidemics had killed millions of people all over the world as the virus naturally mutated. They added that sequencing of the genome of the virus from the 1918 flu pandemic is nearly complete, making it possible for bioterrorists to create and deploy a lethal influenza virus. “Recently, the possibility of synthesizing an infectious agent solely by following instructions from a written sequence has moved from theory to practice.” (6)

HIV and hepatitis testing are also becoming the new normal in many parts of the world. In Africa and Asia where these infections are growing exponentially and there is substantially less medical infrastructure than in the United States and Europe, expanded access to rapid testing is vitally important. For example, the government of Nepal recently bought rapid HIV and hepatitis test kits for use in a government surveillance program in rural areas. The Red Cross in Nepal may also use these tests in its blood bank screening program. (7) Only fast and relatively inexpensive test kits that can be used anywhere are viable in these settings.

Conclusion

The public is demanding and industry is working hard to develop the rapid, reliable point-of-care testing technology needed worldwide in these extraordinary times. The goal is to make these test systems so stable, so simple and so accurate that anyone, who needs to, can read the directions and get reliable test results within minutes. POCT for infectious disease is everywhere: hospital emergency rooms, physician offices, community health centers, corporate medical centers, prisons, home care settings, schools and health outreach programs, such as STD or HIV clinics. In infectious disease management, POCT technology is well positioned to become the most accessible diagnostic testing in the 21st century.

References

(1.) Update: HIV counseling and testing using rapid tests–United States, 1995. MMWR 1998;47(11);211-15.

(2.) Antibiotics overused in treating sore throats. American College of Physicians. www.doctorsforadults.com. Accessed July 16, 2003.

(3.) Elliott, VS. Cold-and-flu seasonal spread suggests new burst of SARS. American Medical News 2003 July 7:1-2.

(4.) FDA clears first test for West Nile Virus. U.S. Food and Drug Administration Press Release, July 9, 2003. http://www.fda.gov/bbs/topics/NEWS/2003/NEW00920.html. Accessed July 16, 2003.

(5.) U.S. Food and Drug Administration SARS Home Page. http://www.fda.gov/oc/ opacom/hottopics/sars/. Accessed July 16, 2003.

(6.) Madjid M, Lillibridge S, Mirhaji P, Casscells W. Influenza as a bioweapon. J R Sec Med. 2003 Jul;96(7):345-46.

(7). World Diagnostics opens point of care testing in Nepal; Red Cross Nepal to evaluate WDI rapid HIV and hepatitis tests for use in blood screening program. Business Wire August 13, 2002. http://www.aegis.com/news/bw/2002/BW020806.html. Accessed July 17, 2003.

Robin G. Weiner is vice president of Clinical and Regulatory Affairs, Quidel Corp., San Diego, and Julia K. Tyler, an independent medical writer in Albuquerque.

COPYRIGHT 2003 Nelson Publishing

COPYRIGHT 2003 Gale Group