Field and laboratory comparative evaluation of ten rapid malaria diagnostic tests

In non-endemic areas, the diagnosis of clinical malaria may be made on the basis of fever and a positive blood film. However, in areas of high endemicity, asymptomatic parasitaemia is very common: to assume that a child who presents with fever and parasitaemia is ill from malaria will result in overdiagnosis. In this article, Jo Schellenberg, Tom Smith, Pedro Alonso and Richard Hayes discuss the relationship between fever and parasite density in such areas, and show how the proportion of fevers due to malaria (the attributable fraction) can be estimated and used to evaluate case definitions for use in field trials.

Two field studies in Kenya and an experimental challenge study in the USA were done to assess the accuracy of a dipstick antigen-capture assay based on qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) in peripheral blood for diagnosis of P falciparum infection. In these studies, the assay was 96.5-100% sensitive for detection of greater than 60 P falciparum asexual parasites/microL blood, 70-81% sensitive for 11-60 parasites/microL blood, and 11-67% sensitive for 10 parasites or less/microL blood. Specificity was 95% (95% CI 85-105%; n = 20) among naive American volunteers, 98% (96-101%; n = 112) among volunteers exposed to the bite of P falciparum-infected mosquitoes, and 88% (84-92%; n = 285) among Kenyans living in an area with holoendemic malaria. Our results also indicated that PfHRP-2 antigen was not detectable in blood 6 days after initiation of curative chemotherapy, and suggest that such circulating antigens rarely lead to false-positive tests. The dipstick assay's sensitivity, specificity, simplicity, and speed may make it an important tool in the battle against malaria.

Malaria causes significant morbidity and mortality worldwide, including countries with mainly imported malaria. In developing nations, scarce resources lead to inadequate diagnostic procedures. In affluent countries, poor familiarity with malaria may cause clinical and laboratory misdiagnosis. Microscopy of Giemsa-stained thick and thin films remains the current standard for diagnosis. Although it has good sensitivity and allows species identification and parasite counts, it is time consuming, requires microscopical expertise and maintenance of equipment. Microscopy with fluorescent stains (QBC), dipstick antigen detection of HRP2 and pLDH (Parasight-F, ICT Malaria Pf, OptiMAL), polymerase chain reaction assays and some automated blood cell analysers offer new approaches and are reviewed here, with emphasis on clinical relevance and their potential to complement conventional microscopy, especially in countries with imported malaria.