Two diseases, millions at risk
PATH and our partners addressed a critical gap in elimination programs—the need for new rapid diagnostic tests that could be used to guide decision-making for mass drug administration—for the neglected tropical diseases (NTDs) onchocerciasis (oncho) and lymphatic filariasis (LF). Our innovation was in response to the call for new diagnostics for surveillance to support elimination of oncho and LF by 2020 as part of the London Declaration on Neglected Tropical Diseases.
Onchocerciasis, commonly known as river blindness, is caused by a parasitic worm, Onchocerca volvulus, transmitted to humans through the bite of the blackfly. With chronic exposure, the disease causes permanent blindness. Oncho typically affects poor, rural communities near streams and rivers, which are blackfly breeding grounds. Worldwide, 169 million people are at risk of infection. In many regions, a combination of mass drug administration and blackfly control has decreased disease prevalence, paving the way for elimination.
Lymphatic filariasis, also known as elephantiasis, is a painful and profoundly disfiguring disease, transmitted by mosquitos carrying parasitic worms. Of the three species known to cause LF, Wuchereria bancrofti accounts for 90 percent of cases, including all on the African continent. Nearly 900 million people worldwide are at risk of infection. Global campaigns to eliminate LF have reduced the burden, with tens of millions treated for LF each year. Many countries are approaching or achieving elimination.
Shortcomings in traditional diagnostic methods
The traditional test for oncho surveillance is a procedure called skin snip microscopy. Results from this method have given NTD programs the information they need to significantly reduce disease prevalence in some areas. But skin snips are painful, which discourages community participation, and not sensitive enough to detect the very low levels of infection that become more common after years of mass drug administration (MDA).
The traditional method for surveillance of LF required health workers to draw blood from individuals at night, when the parasites are active in the bloodstream, which is inconvenient for communities and health workers. Furthermore, two newer tests for LF—the immunochromatographic test (ICT) and the Filariasis Test Strip—also have drawbacks: the ICT has been found to be less sensitive than ELISA in low-prevalence settings,[i] and both tests can cross-react with another filarial infection, Loa loa, causing false positives.[ii] Also, because antigen tests only detect active infection, they must be timed before MDA is administered, adding a level of complexity to elimination programs.
Three tests, including a two-in-one
To address these challenges, PATH and Standard Diagnostics (SD) (acquired in 2017 by Abbott), a global leader in rapid diagnostics, worked together to develop three highly sensitive, highly specific, serology-based lateral flow tests that check for exposure to oncho and LF by detecting antibodies. All three tests use just a single drop of blood from a finger prick, making them easier to perform and more acceptable to communities. The tests are designed for use in rural settings under harsh environments, and they provide results in just 30 minutes. Because they detect antibodies, these tests do not need to be timed with mass drug administration, and they can be conducted at any time of day.
This test detects exposure to O. volvulus by checking for IgG4 antibodies to the Ov16 antigen. It is fast, accurate, easy to use, and less painful for patients than the skin snip test.
Designed for use in regions where LF is endemic, this test detects antibodies to Wb123 for LF alone. The Wb123 does not cross-react with Loa loa infections.
Onchocerciasis and LF often strike the same geographic areas of Africa; combining surveillance for both diseases reduces expenses and maximizes efficiency for NTD programs. This “biplex” test simultaneously detects IgG4 antibodies to both the Ov16 antigen and the Wb123 antigen for W. bancrofti. The biplex test can also be used in areas where Loa loa is endemic.
With these tests, PATH and our partners transformed the way surveillance for oncho and LF could be conducted by making it easier to perform, and crucially, more acceptable for communities being tested. As of mid-2018, more than half a million of these diagnostic tests have been used in 18 countries worldwide.
“Visit www.alere.com for more information about these tests and to order.”
Collaboration was key
The development of these rapid tests was the result of extensive collaboration on a global scale. Dedicated researchers from the National Institutes of Health (NIH), NTD program implementers, and the private sector joined forces with PATH to innovate, solve challenges, and translate concepts into on-the-ground reality. The result was a game-changing suite of rapid tests that are now crucial tools in the push to eliminate these diseases.
Biological materials from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) were essential to the successful development of these tests. Thomas Nutman, MD, and his team at the NIAID provided essential early and ongoing support to the project, including characterized antigens to Ov16 and Wb123.
Using these antigens, PATH developed prototypes for all three tests, conducted extensive evaluation and validation in the lab and field, and guided the manufacturer, SD, through the process of technology transfer and commercialization.
Tools to support test users
PATH developed a suite of quality assurance (QA) and quality control (QC) materials to support use of the tests in the field. A QA program for diagnostics is designed to guarantee that the final diagnostic results reported by a laboratory or testing program are as accurate as possible. An important component of any QA program is QC to indicate whether the test run was valid and produced acceptable results. A robust QA program reinforces the validity of the test results, builds capacity to use tests for surveillance and research, and aligns with global guidance and best practices for post-market surveillance of new diagnostic tools.
To support successful implementation of the new SD tests, PATH developed a suite of QA and QC materials and panels with two critical components:
- Sample panels using recombinant monoclonal human IgG4 antibodies for Ov16 and Wb123 instead of patient samples. The recombinant antibodies are renewable and sustainable; they provide a consistent, inexhaustible supply of specimen, allowing for standardized testing.
- Print and digital training materials for operator training and proficiency, product evaluation, lot testing, and post-market surveillance.
These QA materials are available at no cost to programs using the oncho and LF diagnostics.
This work is supported by the Bill & Melinda Gates Foundation.
PATH extends our gratitude for collaboration on this work to Standard Diagnostics (acquired by Abbott in 2017); Dr. Thomas Nutman, National Institute of Allergy and Infectious Diseases at the National Institutes of Health; the US Centers for Disease Control and Prevention; and the Task Force for Global Health.
[i] Gounoue-Kamkumo R, Nana-Djeunga HC, Bopda J, Akame J, Tarini A, Kamgno J. Loss of sensitivity of immunochromatographic test (ICT) for lymphatic filariasis diagnosis in low prevalence settings: consequence in the monitoring and evaluation procedures. BMC Infectious Diseases. 2015;15:579. Available at https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-015-1317-x.
[ii] Steel C, Golden A, Kubofcik J, et al. Rapid Wuchereria bancrofti-specific antigen Wb123-based IgG4 immunoassays as tools for surveillance following mass drug administration programs on lymphatic filariasis. Clinical and Vaccine Immunology. 2013;20(8):1155–1161. Available at http://cvi.asm.org/content/20/8/1155.long.