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Sunday, December 2, 2012

Rapid Diagnostic Tests, Types, Strength and Weakness Applications



Rapid diagnostic tests (RDTs) are diagnostic assays designed for use at the point-of-care (POC), and can be adapted for use in low-resource settings. An RDT is low-cost, simple to operate and read, sensitive, specific, stable at high temperatures, and works in a short period of time. RDTs are already in use for several neglected diseases.

Overview

Rapid diagnostic tests (RDTs) are a type of point-of-care diagnostic, meaning that these assays are intended to provide diagnostic results conveniently and immediately to the patient while still at the health facility, screening site, or other health care provider. Receiving diagnosis at the point of care reduces the need for multiple visits to receive diagnostic results, thus improving specificity of diagnosis and the the chances the patient will receive treatment, reducing dependence on presumptive treatment, and reducing the risk that the patient will get sicker before a correct diagnosis is made. Rapid tests are used in a variety of point-of care-settings—from homes to primary care clinics or emergency rooms -- and many require little to no laboratory equipment or medical training.


Rapid Diagnostic Test


RDTs are particularly important in low-resource settings, where:

Harsh environmental conditions combined with limited access to electricity and refrigeration preclude the use of sensitive equipment
Technology, equipment, and training required for more complicated laboratory tests are lacking
Many patients cannot travel easily to the clinic to follow-up on results that take a long time

RDTs can be especially useful with patient samples that can be collected by minimally trained health personal, such as community health workers.1 Body fluids that can be collected non-invasively, such as nasal swabs, urine, saliva, and tears, are preferred as these are most amenable to collection with only minimal training. However, capillary blood collection techniques, such as those used for malaria RDTs, demonstrate that innovation in sample collection can be used to improve the utility of RDTs in low resource settings.

Rather than one specific type of technology, rapid diagnostic tests can be built in a variety of platforms, each with their own benefits and limitations. The vast majority of RDTs in use today for neglected diseases are based on immunoassay technology due to its relative simplicity. These tests generally involve the interaction of a fixed reagent of either target antigen or antibody that is linked to some type of visible detector, that then reacts with a patient sample. Other types of technologies, such as nucleic-acid amplification, may be too expensive and require too much advanced technology to be applicable as a point of care test.

Rapid diagnostic tests have particular value as epidemiological tools, in addition to use as diagnostics. They enable a rapid screening of a potentially affected population, and can be used, as is the case with lymphatic filariasis, as a test of cure to determine when a mass drug administration has been successful. RDTs are less necessary for diseases that are generally accurately diagnosed syndromically, but could prevent over-prescription of antibiotics if used to differentially diagnose fever or diarrhea, respectively.

Common RDT Platforms

There are several different platforms commonly used to build rapid diagnostic tests. The relative utility of common RDT platforms is summarized below.

Lateral flow tests are the simplest type of RDT, requiring only very minimal familiarity with the test and no equipment to perform, since all of the reactants and detectors are included in the test strip. In a lateral flow test, the sample is placed into a sample well and migrates across the zone where the antigen or antibody is immobilized. The results are read after a certain amount of time has passed. Another type of RDT, a flow-through test, obtains results even faster than lateral flow tests, but requires an added wash and buffer step, which can limit its portability and stability.

Rapid Test: Lateral Flow

An agglutination test works very simply by observation of the binding of carrier particles and target analytes into visible clumps, seen either through a microscope or with the naked eye. However, if the binding of the particles is weak, the results of the test can be inconclusive.



Dipstick format RDTs (with binding sites to test for multiple antigens) work by placing the dipstick in a sample. The dipstick is then washed and incubated to prevent non-specific analyte binding. These additional steps can limit their usability in low-resource point of care settings.

Microfluidics, or “labs on a chip” are an emerging area of rapid diagnostic development. Using electrochemical sensors, these tests would include all detectors and reactants in a single portable cassette. For more information, see the Diagnostics Innovation Map Report. The limitations and advantages of each of these test types is summarized in the table below. For more information about the mechanisms of these tests, see PATH’s RDT Info website.


Microfluidics - Rapid Diagnostic Test


Strengths and Weaknesses of RDTs and Common RDT Platforms
The general strengths of RDTs include their ease of use, minimum training requirements, rapid results, and limited need for instrumentation/infrastructure. The general weaknesses of RDTs including their subjective interpretation of readout, low throughput, often limited sensitivity relative to laboratory or reference tests, and need for quality control mechanisms.

RDTs as Non-Neglected Tropical Disease Diagnostics
Rapid diagnostic tests are commercially available for detection of multiple non-neglected diseases and conditions, including pregnancy, blood sugar in diabetic patients, and strep throat. The simplicity of these assays often allows them to be used at home or by minimally trained health care works in both the developed and developing worlds. In the United States, the use of rapid diagnostic tests by doctors is limited as current Medicaid/Medicare reimbursement schemes favor the use the centralized laboratories for diagnosis.

RDTs as Neglected Tropical Disease Diagnostics
One of the particular problems facing the production and implementation of RDTs in low-resource settings is the lack of an evaluative process to determine their real efficacy in the field. For example, the WHO recently issued a policy statement to recommend that rapid serological tests for TB not be useddue to a lack of sensitivity and specificity.4 WHO-TDR and FIND now have lot-testing programs for RDTs for neglected diseases, such as malaria and HIV, to improve standards and recommendations for use of RDTs in the field.

In order to address the ongoing challenge of quality assurance for rapid test, the WHO now independently evaluates RDTs for several diseases, including HIV and malaria, in order to evaluate them for pre-qualification. As with pre-qualification for drugs or vaccines, this designation is the WHO’s method of validating the quality of specific diagnostic assays and manufacturers for those in countries without rigorous and stringent diagnostic approval processes.

References

P. van Lode (2005). “Point-of-care immunotesting: Approaching the analytical performance of central laboratory methods”. Clinical Biochemistry 38.
Mabey et al. (2004). “Diagnostics for the Developing World.” Nature Reviews Microbiology (2)
PATH. RDT Info.
WHO News Release (2011). “WHO warns against the use of inaccurate blood tests for active tuberculosis”.
WHO. Malaria Rapid Diagnostic Tests.
FIND. Malaria RDT Product Testing.
WHO. HIV Diagnostic Test Kit.

Source:
http://www.bvgh.org/Biopharmaceutical-Solutions/Global-Health-Primer/Targets

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