Module 4: Screening and Diagnostics in Developing Countries

The Importance of Screening and Diagnostics in Public Health Surveillance

The success of surveillance systems depends on the accurate identification and diagnosis of health conditions; in order for a case to be counted by a surveillance system, it first must be diagnosed. Public health surveillance in developing countries could be dramatically improved with increased access to quality screening and diagnostic tests.(1) Outcomes resulting from these conditions would improve with earlier detection, especially for conditions that do not cause specific, recognizable symptoms. In developing countries where resources are limited, spending on diagnostics is often inadequate. The Global Burden of Disease Health Financing Collaborator Network gathered data from 2014, showing that in low income countries government spending as a percentage of total health spending was only 18%, an extremely low number when compared to the government spending on health in high income countries of 63.4%.(2)

Types of Tests and Their Application in Developing Countries

Microscopy is used to identify pathogens in samples taken from patients in the field. Though diagnosing with microscopy is effective, it is not always available in developing countries that lack access to a laboratory or an educated scientist—both of which are needed to identify pathogens with a microscope.(3)

Culture(when cells are grown in controlled conditions) is a common way that diagnosis occurs in the developed world. There is a variety of problems with culture in the developing world, however. One is that growing cells takes significant time, so test results can take weeks to return from the laboratory. This is not suitable for an environment in which people may be traveling long distances to health clinics and cannot afford a return trip to view the results of their tests.(4) Currently a Tuberculosis culture from patient specimens is a problem in the developing world because Tuberculosis is a very slow-growing bacterium. Culture also requires supplies of reagents, electricity, special transportation of samples from the field, and educated personnel.(5) These necessities for culture diagnostics are often unavailable in developing countries.

Antibody or Antigen detection tests are thought of as better suited for the conditions of the developing world than are culture tests. They only require simple equipment and do not need special transportation. They are also less expensive to make, and their results can be available in a matter of hours.(6)

Nucleic Acid Amplification Technology (NAAT) tests are highly sensitive and specific tests that facilitate cost effective public health interventions. They have a high potential for application in the developing world because they can generate a test result from urine and other specimens that can be gathered in minimally invasive ways.(7) However, NAAT tests need special equipment and educated personnel to conduct them, which are often unavailable in low-income countries.(8)

Point of care tests (POC) are thought of as the most applicable type of tests in developing countries. These tests usually work by detecting antibodies that fight particular pathogens. They are relatively inexpensive, but give fast results, and are easy to conduct.(9) The problem with POC tests in the developing world is that they are of varying reliability in the field, and also have not been developed and tested enough to be deemed cost effective for many major diseases. POC tests are currently available for some diseases, however, including malaria (pictured below), syphilis, and HIV.(10)  

[INSERT GRAPHIC]

The Need for the Development of New Tests

Research and development of new diagnostic tests for illnesses that disproportionately affect developing countries are highly dependent on donations from private sources (e.g. the Bill and Melinda Gates Foundation or pharmaceutical companies).(11) Major players need to be better educated on the importance of diagnostic tests in the global fight against disease. In some cases, new diagnostic test development may be more cost-effective than the development of new drugs.(12) Diseases need to be assessed to determine whether resource allocation to develop better diagnostic screening tests is appropriate.

The WHO has created a list of criteria by which diseases should be assessed in deciding if a new diagnostic test should be developed.(13) They are:

• Disease burden

• Probable effect of a new test on the disease burden

• Availability, cost, and consequences of treatment

  • Can you treat the illness presumptively or does the illness need to be diagnosed to treat successfully?

  • Is the available treatment for the disease safe and effective?

• Possibility of elimination or eradication

• Feasibility of new test development

  • Does the technology exist to build a new test?

New diagnostic tests should be developed with the challenges of a developing country in mind. The Sexually Transmitted Disease Diagnostics Initiative calls the ideal diagnostic test an ASSURED test.(14) ASSURED is an acronym that describes the most valuable diagnostic test characteristics:

• Affordable (the people affected by the disease can afford the test)

• Sensitive (few false negatives)

• Specific (few false positives)

• User-friendly (can be performed by people with minimal training)

• Rapid (quickly generates results) and Robust (doesn’t need to be refrigerated)

• Equipment-free (easily collected test specimen like urine, saliva)

• Delivered to those who need it (portable, acceptable to population)

Which Diseases Need New Diagnostics in Developing Countries

POC tests currently exist for a number of pathogens including Tuberculosis (TB), Influenza and other respiratory viruses, group A Streptococcus, Chlamydia, and Gonorrhea. As technology evolves, POC testing is moving toward predominantly antigen-based testing to nucleic acid amplification tests, as well as “panel” that can test for multiple pathogens at one time.(15)

The following are barriers that exist in developing countries to developing appropriate diagnostic tests:(16)

• Insufficient investment in diagnostic tests (can take two to ten million dollars and five to ten years to develop a new diagnostic test)(17)

• Regulatory standards are lacking in countries for diagnostic tests, particularly tests for uncommon diseases in industrialized countries, so tests with unacceptably low sensitivity and specificity levels are being used. This is concerning because it means that cases are not being correctly diagnosed, so treatments are inadequate. Unnecessary treatment of false positive cases could also contribute to anti-microbial resistance.

• Lack of measures for quality control of tests used in the field

• Variability of test results in the field due to inadequate testing of diagnostic test during development

• Lack of education of those disseminating the tests in the field. This contributes to incorrect performance of the test, and incorrect reading of the test’s results.

• Appropriate diagnostic tests may be available, but people lack access to these tests, or the health care system in general.

Footnotes

(1) Mabey, D., Peeling, R. , Ustianowski, A., & Perkins, M. D. (2004). Diagnostics for the Developing World. Nat. Rev. Microbiol. 2004 Mar; 2(3): 231-40.

(2) Dieleman, J. L., Campbell, M., Chapin, A., Eldrenkamp, E., Fan, V. Y., Haakenstad, A., ... & Reynolds, A. (2017). Future and potential spending on health 2015–40: development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries. The Lancet, 389(10083), 2005-2030.

(3) Mabey, D., Peeling, R. , Ustianowski, A., & Perkins, M. D. (2004). Diagnostics for the Developing World. Nat. Rev. Microbiol. 2004 Mar; 2(3): 231-40.

(4) Ibid.

(5) Ibid.

(6) Ibid.

(7) Ibid.

(8) Ibid.

(9) National Institute of Health. (2018) Point-of-Care Testing.https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=112.

(10) Mabey, D., Peeling, R. , Ustianowski, A., & Perkins, M. D. (2004). Diagnostics for the Developing World. Nat. Rev. Microbiol. 2004 Mar; 2(3): 231-40.

(11) Ibid.

(12) Ibid.

(13) Ibid.

(14) Peeling, R., Holmes, K., Mabey, D., & Ronald, A. (2006). Rapid tests for sexually transmitted infections (STIs): the way forward. Sexually transmitted infections, 82(suppl 5), v1-v6.

(15) Dolen, V., Bahk, K., Carroll, K. C., Klugman, K., Ledeboer, N. A., & Miller, M. B. (2017). Changing diagnostic paradigms for microbiology. https://www.ncbi.nlm.nih.gov/books/NBK447255/pdf/Bookshelf_NBK447255.pdf.

(16) Peeling, R. W., & Mabey, D. (2010). Point-of-care tests for diagnosing infections in the developing world. Clinical microbiology and infection, 16(8), 1062-1069.

(17) Ibid.

(18) Ibid.