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Ensuring quality and access for malaria diagnosis: how can it be achieved?

Key Points

  • Increasing use of higher cost antimalarial drugs necessitates a move to parasite-based diagnosis for malaria. This offers further benefits to management of non-malarial fevers through early exclusion of malaria.

  • Rapid diagnostic tests (RDTs) are the only practical method to provide parasite-based early diagnosis in remote and poorly resourced areas, where most malaria cases and malaria mortality occurs.

  • Widespread introduction of RDTs requires considerable planning, and often significant changes in the way malaria and non-malarial febrile infections are addressed at a community level, with an emphasis on developing capacity to manage multiple diseases rather than purely vertical programmes.

  • To be useful, malaria RDTs must be sensitive, simple to use and stable at ambient temperatures in the tropics. Published trials indicate that current products frequently do not achieve these standards, but limitations in trial design and reporting reduce the opportunity to identify faults requiring further development or changes in management practice.

  • There is an urgent need to demonstrate and publish data on the quality of the rapidly expanding RDT product range, and to address the limited capacity for internal quality control and product development of the manufacturing sector.

  • The development of a product testing and quality control network by the WHO and various partner institutions aims to demonstrate product capabilities to guide procurement and selection of products for field evaluations, and to develop the capacity to monitor RDT sensitivity after procurement and in the field.

  • Guidelines for field trials published with this review set minimum standards for field trials that, if followed, should allow more confidence in field trials results, identification of the reasons for RDT failure in trials, and comparison of performance between trials.

Abstract

The replacement of conventional antimalarial drugs with high-cost, artemisinin-based alternatives has created a gap in the successful management of malaria. This gap reflects an increased need for accurate disease diagnosis that cannot be met by traditional microscopy techniques. The recent introduction of rapid diagnostic tests (RDTs) has the potential to meet this need, but successful RDT implementation has been curtailed by poor product performance, inadequate methods to determine the quality of products and a lack of emphasis and capacity to deal with these issues. Economics and a desire for improved case management will result in the rapid growth of RDT use in the coming years. However, for their potential to be realized, it is crucial that high-quality RDT products that perform reliably and accurately under field conditions are made available. In achieving this goal, the shift from symptom-based diagnosis to parasite-based management of malaria can bring significant improvements to tropical fever management, rather than represent a further burden on poor, malaria-endemic populations and their overstretched health services.

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Figure 1: Stages of development of Plasmodium falciparum at which antigens detected by malaria rapid diagnostic tests are produced.
Figure 2: Global distribution of malaria.
Figure 3: Hypothetical comparison between case cost of malaria diagnosis by microscopy and rapid diagnostic tests (RDTs).
Figure 4: The effect of adding parasite-based diagnosis to malaria case management based on symptoms and signs.
Figure 5: Outline of requirements for an adequate national quality assurance system for malaria rapid diagnostic tests (RDTs).
Figure 6: Mode of action of antigen-detecting malaria rapid diagnostic tests (RDTs).

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Acknowledgements

The authors wish to thank L. Dini and R. Peeling for advice and for reviewing the manuscript.

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DATABASES

Entrez Genome Project

Plasmodium falciparum

Plasmodium vivax

FURTHER INFORMATION

AusAID

Centers for Disease Control and Prevention (CDC)

Global Fund to fight AIDS, Tuberculosis and Malaria

HIV: the 3 by 5 initiative

Integrated Management of Childhood Illness

Kenya Medical Research Institute (KEMRI)

Malaria rapid diagnostic tests

Rapid tests for malaria

Roll Back Malaria partnership

Stop TB

UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR)

Glossary

Lateral flow immunochromatographic assay

A device that produces a visible mark to signal the presence or absence of a protein antigen, based on the accumulation of dye-labelled antibodies to form a visible line after binding directly, or through a common antigen, to a fixed line of unlabelled antibody.

Artemisinin-based combination therapies (ACT)

Drug therapy for malaria consisting of a combination of an artemisinin derivative (derived from the plant Artemisia, also known by the Chinese name Qing Hao), and another drug with anti-plasmodial activity. ACT is rapidly replacing cheaper conventional medicines, to which parasite resistance is now widespread.

Positive predictive value

(PPV) The probability that a positive result accurately indicates the presence of infection.

Negative predictive value

(NPV) The probability that a negative result accurately indicates the absence of infection.

Arrhenius equation

The Arrhenius equation describes the relationship between temperature and the rate at which a reaction proceeds.

Heterophile antibodies

IgM antibodies that can reach high levels in serum after febrile illnesses (for example, infectious mononucleosis), and can bind nonspecifically to other proteins. They can cause false-positive reactions in immunochromatographic assays.

Giemsa-stained light microscopy

Detection of malaria parasites in blood by drying a thin blood film on a glass slide, fixing with methanol and staining with a mixture of aninline dyes, designed to highlight Plasmodium parasites when examined under a high-powered light microscope. Sometimes other aniline dye-based stains are used (for example, JSB or Field's stain).

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Bell, D., Wongsrichanalai, C. & Barnwell, J. Ensuring quality and access for malaria diagnosis: how can it be achieved?. Nat Rev Microbiol 4, 682–695 (2006). https://doi.org/10.1038/nrmicro1474

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