Field evaluation of the ICT malaria P.f/P.v immunochromatographic test for detection of Plasmodium falciparum and Plasmodium vivax in patients with a presumptive clinical diagnosis of malaria in eastern Indonesia

Abstract

In areas such as eastern Indonesia where both Plasmodium falciparum and Plasmodium vivax occur, rapid antigen detection tests for malaria need to be able to detect both species. We evaluated the new combined P. falciparum-P. vivax immunochromatographic test (ICT Malaria P.f/P.v.) in Radamata Primary Health Centre, Sumba, Indonesia, from February to May 1998 with 560 symptomatic adults and children with a presumptive clinical diagnosis of malaria. Blinded microscopy was used as the "gold standard," with all discordant and 20% of concordant results cross-checked blindly. Only 50% of those with a presumptive clinical diagnosis of malaria were parasitemic. The ICT Malaria P.f/P.v immunochromatographic test was sensitive (95. 5%) and specific (89.8%) for the diagnosis of falciparum malaria, with a positive predictive value (PPV) and a negative predictive value (NPV) of 88.1 and 96.2%, respectively. HRP2 and panmalarial antigen line intensities were associated with parasitemia density for both species. Although the specificity and NPV for the diagnosis of vivax malaria were 94.8 and 98.2%, respectively, the overall sensitivity (75%) and PPV (50%) for the diagnosis of vivax malaria were less than the desirable levels. The sensitivity for the diagnosis of P. vivax malaria was 96% with parasitemias of >500/microl but only 29% with parasitemias of <500/microl. Nevertheless, compared with the test with HRP2 alone, use of the combined antigen detection test would reduce the rate of undertreatment from 14.7 to 3.6% for microscopy-positive patients, and this would be at the expense of only a modest increase in the rate of overtreatment of microscopy-negative patients from 7.1 to 15. 4%. Cost remains a major obstacle to widespread use in areas of endemicity.

FIG. 1

Sensitivity of antibodies to the HRP2 and panmalarial antigens at different parasite densities (excluding mixed infections). (a) Sensitivity of tests for HRP2 antigen for detection of P. falciparum. (b) Sensitivity of tests for panmalarial antigen for detection of both species. Dark shading, asexual-stage P. falciparum; pale shading, P. vivax. The numbers in each category for P. falciparum and P. vivax, respectively, are as follows: <50/μl, 3 and 5; 50 to 499/μl, 30 and 2; 500 to 4,999/μl, 86 and 14; >5,000/μl, 107 and 11.

FIG. 2

Box plots of asexual parasite density per microliter by line intensity of the panmalarial antigen (a) and the HRP2 antigen (b), excluding mixed infections. Boxes show the interquartile ranges. The bold horizontal lines indicate medians; vertical lines indicate 1.5 times the interquartile range (or the total range if this is less), with significant outliers indicated by stars. The width of the boxes is proportional to the numbers in each category. For analysis of panmalarial antigen line intensity (a), there were 9 (3.9%), 61 (26.5%), 53 (23.1%), and 107 (46.5%) patients in the line intensity categories of absent, faint, intermediate, and greater than or equal to that for the control, respectively, for P. falciparum (Pf) and 6 (18.8%), 6 (18.8%), 8 (25%), and 12 (37.5%) patients in the four categories, respectively, for P. vivax (Pv). Panmalarial antigen line intensity was associated with increasing parasite density for both P. falciparum (P < 0.0000001) and P. vivax (P = 0.0002). For analysis of HRP2 antigen line intensity (b), there were 7 (3%), 38 (16.5%), 33 (14.4%) and 152 (66.1%) patients in the line intensity categories of absent, faint, intermediate, and greater than or equal to that for the control, respectively, for P. falciparum. HRP2 antigen line intensity was associated with increasing P. falciparum parasite density (P = 0.000005).