Rapid tests for malaria

Diagnostic overview

Introduction

Malaria diagnosis, particularly in remote areas lacking laboratory support, frequently relies on the patient’s symptoms. The first symptoms of malaria (fever, chills, sweats, headaches, muscle pains, nausea, and vomiting) are not specific to malaria. While clinical diagnosis is inexpensive and can be effective, clinicians often misdiagnose malarial infection. Misdiagnosis often leads to the unnecessary prescription of malaria medications which are becoming increasingly expensive as drug resistance grows globally and new medicines are required for effective treatment. Thus, increasing the accuracy of malaria diagnosis is becoming more important and will continue to be so in the future.

Laboratory assays

Microscopy

Microscopy is the most popular method of detecting malaria infection and is usually available in better-equipped clinics. This technique can confirm clinical diagnoses and provide important treatment information by identifying which of the multiple parasite species are in circulation and which drug treatment to initiate. After the initial expense of procuring a microscope, microscopy is relatively inexpensive (US$0.25 to US$0.50 per slide) and is a standard technique used for diagnosing other diseases (such as tuberculosis). Many factors affect the quality of microscopic diagnosis of malaria. The experience and training of the microscopist along with the quality of the slide preparation, staining, and reading are paramount to accurate diagnosis. Other important factors include the quality of the equipment, availability of electricity, and necessary reagents.

Nucleic acid amplification tests

Several nucleic acid amplification technologies (NAATs) now exist to detect parasite DNA circulating in the bloodstream and they are very sensitive. NAATs such as PCR are currently not widely available in malaria endemic areas because they require expensive reagents and equipment as well as specialized training. Interpreting NAAT results can be challenging due to the fact that parasite DNA can remain in the bloodstream long after the infection is cleared. Thus, differentiating an active infection from a recently cleared infection is difficult.

Due to the many challenges in diagnosis of malaria by microscopy and/or NAATs, these methods are often not amenable to many settings and other solutions are required.

Rapid diagnostic tests

Rapid diagnostic tests (RDTs) for malaria offer the potential to extend accurate malaria diagnosis to areas when microscopy services are not available such as in remote locations or after regular laboratory hours. Rapid malaria diagnostic tests have been developed in the lateral flow format. These tests use finger-stick or venous blood, take only 10 to 15 minutes, and do not require a laboratory. Even non-clinical staff can easily learn to perform the test and interpret the results.

Malaria RDTs rely on the detection of parasite specific antigens (proteins) circulating in the bloodstream. The most common antigens for RDTs are P. Falciparum histidine-rich Protein-2(pfHRP2) and Plasmodium spp. lactose dehydrogenase (pLDH). Tests based on the pfHRP2 antigen are specific to P. falciparum, the most dangerous species of malaria, and are more readily available and less expensive. Tests based on pLDH come in two varieties:  pan-malarial tests which detect all malaria species, or species specific tests that detect malaria species other than P. falciparum. Pan-malarial tests are also available which detect the Aldolase antigen.

Some malaria treatment programs require testing of patients after treatment to confirm that parasites have been cleared. RDTs based on pfHRP2 are not suitable for this purpose as the pfHRP2 antigen remains in the bloodstream long after parasite clearance. RDTs based on pLDH are suitable for treatment monitoring.

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