Improving Diagnosis Of Tropical Diseases (Part 1)

THE FIRST STEP in treating a disease is diagnosing it. For tropical diseases in developing countries, such diagnoses aren't as easy as they should be. Many of these countries lack the trained personnel or reliable infrastructure to support complicated analyses. Simplified methods and equipment could improve such diagnoses. A symposium at Pittcon, held last month in Chicago, focused on efforts to develop better, cheaper methods for diagnosing tropical diseases. The American Chemical Society's Division of Analytical Chemistry organized and sponsored the symposium.
Courtesy of Helen Lee
Donor testing Diagnostic testing of blood donors in Ghana takes place outside the laboratory.
Helen Lee of the department of hematology at the University of Cambridge presented surprising statistics about the availability of basic supplies and infrastructure in developing countries. In a survey of African facilities, a small yet significant fraction lacked even the most basic resources, such as a reliable source of electricity and tap water (17% and 7%, respectively), she said. The availability of other supplies was worse, and 40% of facilities do not have incinerators to deal with medical waste.
Beyond the availability of basic resources, cost is a big issue in developing countries. For example, Lee said, the blood banks in Kumasi, Ghana, have a total annual budget of approximately $70,000, with 15% allocated to testing and 17% to consumables. In light of such meager funds, Bernhard Weigl, the group leader for the diagnostics development team at the Seattle-based nonprofit organization Program for Appropriate Technology in Health (PATH), said that his organization's goal is to lower the cost of each infectious disease test to no more than $1.50.
Infectious disease testing is important not only for diagnosing and treating patients but also for ensuring the safety of the emergency blood supply. African hospitals and clinics can't rely on a large volunteer donor pool like that available in many developed countries, Lee said. Approximately half of the donors are older family members with a higher prevalence of transfusion-transmitted viruses. In a study of more than 1,000 blood donors at a hospital in Ghana, nearly 20% were infected with one or more of HIV, hepatitis B, and hepatitis C, Lee said. Such findings demonstrate the magnitude of the challenge, because among developing nations "Ghana is a well-managed country with good infrastructure," she said.
The testing is often carried out under less than ideal circumstances. Lee described open-air pre-donation testing of volunteer blood donors recruited by FM radio in Kumasi. Access to refrigeration is often limited, so assays and reagents in tropical climates must be able to withstand temperatures that can soar past 35 oC (95 oF).
Given such challenges, scientists must make sure they are developing diagnostic tests that health care providers in developing countries want and need and, most important, can actually use. "The last thing" Western scientists "want to do is build something and find that no one wants to use it," said Paul Yager, a professor of bioengineering at the University of Washington, Seattle. For his projects, his team has done an initial assessment of the needs in India, their first target country. They are working on similar assessments in Brazil and sub-Saharan Africa.
For example, Yager said, tests need to be fast enough for patients to receive treatment. If the analysis takes too much time, patients might leave without appropriate treatment. Each sample test should ideally be completed in 15 minutes, he noted.
Diagnosis of tropical infectious diseases generally involves two types of assays. Nucleic acid analyses measure the presence of the pathogen's genetic material—either DNA or RNA—in the patient; immunoassays measure the patient's antibody response to the pathogen. Which assay provides better diagnosis depends on the stage of the infection. At early stages, nucleic acid analysis is better, but at later stages, the immunoassay is preferable. Because health care workers don't know at what stage of infection they are testing, they ideally will do both assays.
Nucleic acid testing involves three unavoidable steps, Lee said: sample preparation, amplification, and detection. Of those three, sample prep is always the one that will "stump" practitioners, she said. "There's no sense in using a simple back end if you don't have a simple front end," she said.