By Nicholas Borgert

 Infectious diseases drew substantial attention and investment from the diagnostic testing industry during the past year. While some argue that predicted outbreaks of Lyme disease and West Nile virus were overstated, other threats to public health continued, including SARS, bird flu, and mad cow disease. Old pathogens are becoming more drug resistant; potent new strains are surfacing.

Chembio Diagnostics
Chembio Diagnostics’ revenues increased nearly 22% for the 3 months ending June 2004, driven primarily by a technology transfer agreement and HIV test sales to a Brazilian group. Strong HIV test sales were offset by lower sales of Chembio pregnancy-test kits.

Company President Lawrence Siebert says overseas markets offer prime opportunities to boost sales of Chembio’s rapid HIV tests. A case in point is the recent Chembio transfer agreement with Bio-Manguinhos. An affiliate of the Brazilian Ministry of Health, Bio-Manguinhos is a division of the Oswaldo Cruz Institute and the largest manufacturer of vaccines in Brazil. This collaboration will enhance distribution of a Brazilian-made rapid HIV test to serve that country’s population.

“We believe the main market for rapid HIV tests is currently in the developing world,” Siebert says. “Our strategy has been to establish scalability of the product, obtain more field data, and then secure funding for the US submission process. We believe that receiving FDA approval will facilitate international as well as US marketing of our products.”

As it approaches its 20th year in business, the Medford, NY-based company continues to expand sales of its the Sure Check™ HIV and HIV Stat-Pak. “We are currently not aware of any other company that offers multiple formats of rapid HIV tests,” Siebert says. “The Sure Check HIV test is user-friendly because it eliminates the need for a separate step for sample transfer when used with finger stick whole blood. The advantages of the other rapid test, the HIV Stat-Pak, is its flexibility: it uses the same procedure for whole blood, serum and plasma.”

While the Sure Check HIV and HIV Stat-Pak strip tests are widely used around the world, the products are not yet approved for use in the United States by the Food and Drug Administration (FDA). Clinical trials on the two HIV rapid tests were expected to wrap up this fall after Chembio won an FDA Investigational Device Exemption (IDE). The company plans to use the trials to support a premarketing approval application to the FDA.

Also, Chembio is working on a rapid test for detection of antibodies to active pulmonary tuberculosis in nonhuman primate whole blood samples. It also produced the only FDA-cleared rapid Lyme disease test.

“We have focused our expertise on developing tests for HIV and tuberculosis as well as contract development and manufacturing opportunities for dental disease and BSE [mad cow disease],” Siebert says. “However, we are always looking for other collaborations that can combine our development and manufacturing capabilities with good reagents, technologies, or distribution.”

Atlas Public Health
Calabasas, Calif-based Atlas Public Health is the newest division of Atlas Development Corp. “The division is focused on developing comprehensive networks for the tracking, reporting, and investigation of infectious disease incidents,” says Bob Gregory, the division’s managing director. His group’s core product is a case management system that is part of the Atlas Public Health Information Network (PHIN) Suite™.

The PHIN Suite began with discussions Atlas held in 1998 with Los Angeles County public health officials. The county was seeking a new system capable of tracking information received via paper and telephone-based communications and creating electronic reports on infectious diseases gathered through field offices and networked to a central location. The electronic reports could then be used to maintain and improve field investigations of incidents.

“The September 11, 2001 terrorist attacks drove home the need for a tracking system that could enhance public health’s response, not only to potential bioterrorism attacks but also to infectious diseases, such as SARS, West Nile virus, and emerging flu strains,” Gregory says.

Experience in clinical connectivity solutions made Atlas a logical choice for the comprehensive new monitoring network, according to Gregory. “We understood the form, the standards, and the fact that much of the incident information used by public health officials comes from laboratory test results,” Gregory says. “Public health officials recognized it was critical to obtain information quickly and efficiently so they could act decisively.”

A growing list of providers has joined Kaiser Permanente in the Los Angeles County reporting network. In fact, Kaiser now generates about 40% of all the infectious-disease incidents electronically reported to county health officials. San Diego and Monterey counties have adopted the Atlas PHIN system as well, Gregory says. The company is now rolling out the suite nationwide.

“Soon, Atlas will be handling about 65% of all the incident reports of infectious diseases within the state of California,” Gregory says. “Such electronic tracking could reduce a typical infectious disease incident investigation from 3 to 4 weeks to as little as 7 days. The PHIN Suite enables a public health department to create new disease categories and develop a work flow—including forms, sample requirements, and required field responses—on the fly.” Gregory says the tracking system reflects his company’s recognition that post-9/11, public health officials are on the front line of first responders regarding bioterrorism and infectious diseases.

To complement the PHIN Suite, Atlas is also introducing a Public Health Information Link (PHIL) system that enhances the interfacing of data among labs and health departments. PHIL takes data in any form from any source, sifts through it, identifies information of interest, and reformats and recodes the data for reporting to public health officials. In another project, Atlas is helping a California State University campus install a version of its system that will enhance internal tracking and trending of postoperative, staph, and other infections at its affiliated medical center.

Chemicon International
Since its acquisition by Serologicals Inc 18 months ago, Chemicon is taking advantage of a new synergy that recently welcomed Upstate, another leading supplier to life-science researchers.

Chemicon offers nearly 7,000 proprietary products, including antibodies, proteins, assays, and custom services. The company has evolved into a medium-sized and well-funded company that invests heavily in research and the development of innovative products, says Marketing Director John Ambroziak.

Key growth areas include signaling, neuroscience, stem-cell biology, drug discovery, and infectious-disease antibody and reagent products. Serologicals revenues from Chemicon’s three units will total more than $200 million for this fiscal year.

“We’re a company focused on innovation, a company that values research and is working aggressively to predict as well as meet evolving customer needs,” Ambroziak says. “On an annual basis, Chemicon is growing in the mid-20th percentile—ahead of many others in the industry.”

Among proprietary areas Chemicon is exploring are two ultrasensitive detection methods that use living organisms from the oceans. The company is harvesting recombinant aequorin, a 22,000-molecular weight photoprotein obtained from the jellyfish Aequorea victoria. The photoprotein emits a flash of blue light when exposed to calcium ions. Its direct and ultrasensitive signal can be measured using a luminometer. When fused with other proteins—including antibodies, streptavidin, and small molecules called biotin—the conjugate functions as a detection label in bioluminescence-based assays (BIA). The technology is protected by a number of US and related foreign patents.

In addition, Chemicon is using a bioluminescent molecule called Renilla luciferase obtained from the sea pansy. This material, when supplemented by a substrate ceolenterazine, produces a long-lasting “glow” that facilitates BIAs when conjugated with other proteins.

Among the company’s hottest products is a proprietary formulation for embryonic stem cell hosting. Called ESGRO®, the cell culture reagent assists in maintaining and expanding murine embryonic stem (ES) cells without the need to add feeder layers. Such feeder layers have traditionally been required as a source of in vitro factors to help prevent ES cell differentiation.

Infectious-disease reporting is big business at TheraDoc, the Utah-based medical informatics supplier. “We have signed more new business, both contract and dollar volume, in the first 6 months of 2004 than we did in all of 2003,” says Richard Livingston, TheraDoc executive vice president. In addition to contracts with several universities, the company won approval to sell into the Veterans Administration, with the first implementation at the Salt Lake City Veteran’s Hospital.

The Antibiotic Assistant, its flagship product, has been available since 2001. “Clinicians throughout the hospital benefit from being connected in real-time to patient data and evidence-based medical knowledge through TheraDoc’s technology,” Livingston says. “In particular, it helps clinicians to address key industry issues.”

Infection management has surfaced as an urgent patient safety and public health challenge. CDC stats indicate about 2.1 million patients each year—6% of all admissions—will contract a hospital-acquired infection. More than 70% of bacteria that cause hospital-onset infections are resistant to at least one of the drugs most commonly used to treat them.

TheraDoc provides technology and expertise to link growing volumes of data hospitals collect electronically on their patients and the wealth of evidence-based medical knowledge electronically cataloged by the medical publishers, Livingston says. An infrastructure feature called Power to Reason interprets records, alerts clinicians, and recommends patient-specific treatment options. “Each of our products is based on current medical guidelines and evidence, within the context of the patient’s condition, at the time of care,” Livingston says.

Diagnostic Products Corp
For publicly traded Diagnostic Products Corp (DPC), which has been supplying immunodiagnostic systems and reagents since 1971, the past year has been exceptional. The company moved into its new Los Angeles headquarters, and in the first half of this year, sales increased more than 18% from the same period a year earlier. For all of 2004, the company expects double-digit growth. At the core of DPC’s success is its established IMMULITE® line of products. IMMULITE-related products accounted for more than $9 of every $10 the company generated in the first half of 2004. DPC recently saw its base of IMMULITE systems surpass 10,000 units.

IMMULITE® 1000 has a menu of nearly 100 assays, including turbo assays that provide test results in about 15 minutes. For its IMMULITE 2000 platform, the company offers 78 tests in the United States; 71 tests are available for introduction on the new IMMULITE 2500; with more awaiting FDA authorizations. The 2000 unit is designed to consolidate workstations and boost productivity.

A Conversation With Ernest T Takafuji of NIAID

Ernest T. Takafuji, MD, MPH, serves as assistant director for biodefense research at the National Institute of Allergy & Infectious Diseases (NIAID). The Project BioShield Act of 2004 charges NIAID with expediting peer review of grants, contracts, and cooperative agreements to perform, administer, and support research and development of countermeasures to treat, identify, and prevent harm from any biological, chemical, radiological, or nuclear agent that may cause a public health emergency affecting national security or adverse health consequences.

Takafuji has said that influenza is likely one of the most serious biological warfare agents the nation faces. Influenza is far more contagious than smallpox; its rare and supervirulent strains would pose a challenge far exceeding anything the health system is presently capable of coping with.

Before accepting his current position, Takafuji served with distinction in the US Army. He was commander and director of Walter Reed Army Medical Institute of Research, and commander of the Army Medical Research Institute of Infectious Diseases. CLP recently interviewed Takafuji regarding infectious disease–related issues.

CLP: Do you see an overlap between government-funded biodefense efforts and ongoing development of rapid tests for common and treatable infectious diseases?

Takafuji: Let me emphasize that infectious diseases and immunity remain the primary focus of NIAID. Current research efforts that are aimed at expanding our scientific knowledge base and developing innovative interventions that will improve health have not been compromised by research over bioterrorism. What has really evolved is a recognition that bioterrorism, where malicious intent is implied, represents another subset of the global challenges that we face with infectious diseases.

When confronted with an unusual outbreak of illness, as we experienced with SARS and new strains of influenza, the initial approach has been and will continue to be:

  • Rapid identification and confirmation of the agent or agents
  • Characterization of the agent down to the molecular level
  • Comparing this new agent with other strains by accessing libraries of genomic and microbial information
  • Recognizing what is happening clinically from the standpoint of morbidity and mortality, which may provide us clues about pre-existing immunity and host immune defenses and the effectiveness of our current countermeasures
  • Identifying risk factors and modes of transmission
  • Arriving at additional possible therapeutic interventions

The ability to respond to an emerging event uses many of the same resources that we would use in a bioterrorist agent scenario. Therefore, I do not view biodefense research as an overlap issue, but an opportunity for the nation to increase its defenses against biological threats, in general. There are clear opportunities to develop synergy with our ongoing efforts with emerging and re-emerging infections.

CLP: Are the same companies that market and develop rapid tests for infectious diseases also seeking funding in the area of bioterrorism or is that an entirely separate market segment?

Takafuji: Industry, in general, is interested in addressing infectious diseases and biodefense, but companies decide on where to place their major strategic research investments, not the government. The biodefense arena has certainly generated a high level of interest, but that has also meant that it is a very competitive marketplace. In general, industry understands that there will always be a need for new and improved products. Technological innovations represent a large part of the industrial involvement with efforts directed at detection, diagnostics, therapeutics, or prevention.

CLP: Is NIAID taking a fast-track approach in administering the BioShield Act? What is different about the approval process compared to the approval process for traditional infectious disease reagents and instruments?

Takafuji: The BioShield Act of 2004 gives the Secretary of the Department of Health and Human Services authority to institute expedited peer review procedures for biodefense countermeasures. This is done in direct consultation with the director of the National Institutes of Health. NIAID recently instituted new biodefense research procedures, in accordance with the Act. Normal processes that once took 14 months have now been reduced to 6 months or less. The processes involve expedited clearance procedures for initiatives and a more simplified approach in announcement, submission, and review of grants and contracts dealing with biodefense. For example, specific requirements must be met before submission of applications, a process that eliminates unqualified organizations from even applying. Direct communication with interested applicants answers questions quickly and avoids delays. The review process is still necessary but every attempt is being made to expedite the review without compromising the quality of the review. Awards are also announced faster.

Nicholas Borgert is a contributing writer for Clinical Lab Products.