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Editorial

Assessing rapid diagnostic tests for malaria

Hasifa Bukirwa
Editorial Article

Malaria remains a major cause of illness and death in Africa and other endemic, and often resource-limited, settings.[1] Most cases of malaria are uncomplicated but can quickly turn into severe, often fatal, episodes in vulnerable individuals if not promptly diagnosed and effectively treated. Parasitological diagnosis of malaria has for a long time been based on microscopic detection of asexual malaria parasites on a blood smear from a person suspected to have malaria. But many areas lack laboratory support to provide malaria microscopy. Even where it is available, many factors affect the quality of microscopic diagnosis: the experience and training of the microscopist; the quality of the slide preparation, staining, and reading; the quality of the equipment; and the availability of electricity and reagents.[2] Malaria diagnosis is frequently based on non-specific symptoms, often resulting in misdiagnosis and unnecessary treatment with antimalarials.

Rapid, accurate, and accessible detection of malaria parasites has an important role in diagnosis and in promoting more rational use of increasingly costly drugs. Rapid diagnostic tests (RDTs) can potentially provide accurate diagnosis to all at-risk populations, reaching those unable to access good-quality microscopy services in endemic areas. RDTs work by detecting specific malaria antigens or enzymes.[3]

Abba and colleagues carried out a Cochrane Review of the diagnostic accuracy of RDTs for detecting clinical Plasmodium falciparum malaria in people living in malaria endemic areas who presented to outpatient healthcare facilities with symptoms of malaria.[4] They also sought to identify which types and brands of commercial RDTs best detected clinical P falciparum malaria. The review included 74 trials, with 111 test evaluations conducted in Africa, Asia, and South America. The authors have synthesised the results in a comprehensive but rather complex matrix of analyses comparing sensitivities and specificities in a sequence of hierarchical comparisons. The main comparison was by antibody type: histidine-rich protein 2 (HRP-2) versus plasmodium lactate dehydrogenase (pLDH). Other comparisons were by antigen type and commercial brands.

The review found no significant difference in sensitivity between type 1 and type 4 RDTs or between HRP-2 and pLDH tests, although type 1 RDTs tended to be more sensitive than type 4, and HRP-2 tests were generally more sensitive than pLDH tests. The review showed important differences in specificity, with type 4 performing significantly better than type 1 and pLDH showing superior specificity compared with HRP-2 tests. Within each RDT type, there were no important differences between the commercial brands.

These are important findings with practical implications for the choice of RDT in field conditions. The findings help to resolve the uncertainty about the performance of HRP-2 and pLDH RDTs in varying malaria epidemiology settings. Irrespective of malaria transmission setting, the sensitivities of the HRP-2 and pLDH tests were both over 90%. Specificity was variable, with lower specificity seen for HRP-2 RDT types in areas of high malaria transmission. This reduction was not significant in the analyses where studies were subdivided by endemicity. However, when studies were subdivided by continent, there was a statistically significant reduction in Africa, where most high malaria transmission occurs (making it a good a surrogate for high endemicity).[5] In Africa there is a high risk of re-infection soon after treatment, so the issue of persistent antigenaemia, and thus the difficulty of distinguishing a new malaria infection from other causes of fever, makes HRP-2 type RDTs less attractive. In such settings pLDH type RDTs may offer a better diagnostic choice due to their higher specificity. The high sensitivity of HRP-2 RDT types becomes very important in areas where malaria prevalence is less than 20% and where, therefore, the clinical suspicion index for malaria as a cause of observed symptoms is low. The low specificity is less critical an issue under such settings.[6]

The findings of this Cochrane Review support the recently updated World Health Organization (WHO) guidelines for malaria treatment. The guidelines recommend that in all settings clinical suspicion of malaria should be confirmed by parasitological diagnosis using microscopy or RDT.[7]

Concern remains about clinicians adhering to the negative results of any malaria diagnostic test. Clinicians, especially those in high malaria prevalence areas, often ignore negative results.[8] For RDTs to be useful in improving malaria case management clinicians have to learn to respect the negative results and to evaluate cases with such results more carefully for other possible causes of the malaria-like symptoms and only prescribing antimalarials when warranted.[9] National malaria control programmes and other responsible bodies must strictly enforce malaria treatment policies.

Related Cochrane Reviews