Typhoid fever diagnostics
Typhoid fever Typhoid fever, a bacterial disease caused by infection with Salmonella enterica serotype Typhi, is a major cause of morbidity and mortality in developing countries, with an estimated 21 million cases and 0.2 million death each year. Prompt diagnosis and treatment may prevent the development of severe sequellae. The clinical diagnosis of typhoid fever is difficult as symptoms and signs may resemble those of other major febrile illnesses. Isolation of the pathogen from blood or bone marrow is the most reliable means for the confirmation of the infection. However, culture facilities are rarely available in developing countries and patients are often reluctant to donate the large volume of blood required for culture. In absence of culture facilities the Widal test may be used for serological confirmation but the interpretation of the test results is cumbersome due to the presence of cross-reactive antibodies in the serum of patients and of low levels of specific antibodies during the acute phase of the disease.
Point-of-care diagnostics Most people at risk of attracting typhoid fever live in resource poor countries where diagnostic laboratories are rarely available. We have developed field tests for typhoid fever in several attractive assay formats that may be used without the need of specific training, expensive equipment, electricity and refrigeration, and that are both use and patient friendly. One of these assays, the Typhoid fever Dri Dot assay, is simple performed by spotting a drop of serum onto a white agglutination card containing a dot of dried activated latex particles, which then is suspended in the serum sample. The test result is obtained within 30 seconds. The dried latex particles are extremely stable and may be stored at 55 degrees centigrade for at least two years without effect on activity. The Typhoid IgM lateral flow assay is even more convenient to use is. This assay is simply performed by spotting a drop of whole blood obtained by finger prick onto the sample pad of a plastic assay device; after addition of some test fluid, the result is read after 10 minutes by visual inspection for staining in the assay window of the device.
Approach
Different assay formats including dipstick, lateral flow assay and latex agglutination using different antigens and probes are being investigated to develop a point-of-care test for the serodiagnosis of typhoid fever. The dipstick assay has proven to have a relatively high sensitivity and specificity when tested in different countries including Indonesia and Vietnam. In a study in Vietnam the test sensitivity at initial diagnosis was 77% and the specificity 95%. Currently evaluation studies of the lateral flow and latex agglutination assays are ongoing.
Focal points
- Development, evaluation and application of a point-of-care test for typhoid fever.
Publications
- Abdoel, T.H. - Laboratory evaluation of a simple and rapid latex agglutination assay for the serodiagnosis of typhoid fever.
- Pastoor, R. - Simple, rapid and affordable point of care test for the serodiagnosis of typhoid fever