Journal of Clinical Microbiology, August 1999, p. 2412-2417, Vol. 37, No. 8
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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
Emiliana
Tjitra,1,2
Sri
Suprianto,3
Mary
Dyer,2
Bart J.
Currie,2 and
Nicholas
M.
Anstey2,*
Communicable Diseases Research Centre,
National Institute of Health Research and
Development,1 and Directorate General of
Communicable Disease Control and Environmental
Health,3 Jakarta, Indonesia, and
Tropical Medicine and International Health Unit, Menzies School
of Health Research, Darwin, Northern Territory,
Australia2
Received 30 November 1998/Returned for modification 22 January
1999/Accepted 29 April 1999
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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/µl but only 29% with parasitemias of <500/µl. 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.
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INTRODUCTION |
Microscopy of Giemsa-stained thick
and thin films by a skilled microscopist has remained the standard
laboratory method for the diagnosis of malaria both in regions where
malaria is endemic and in regions where malaria is nonendemic. In
eastern Indonesia, as in many other regions where malaria is endemic,
there are problems with microscopic diagnosis, particularly at the
periphery of the health care system. These include lack of skilled
microscopists, limited supply and maintenance of microscopes and
reagents, delays in results, and inadequate quality control. Moreover,
ready access to these microscopy services is limited for the vast
majority of symptomatic, malaria-exposed residents. For these reasons, the Indonesian Malaria Control Operational Policy still recommends early diagnosis and prompt treatment on the basis of a clinical diagnosis of malaria (10). Because of the nonspecific nature of the symptoms and signs of malaria, this results in considerable mistreatment, both overtreatment with antimalarial agents and undertreatment of those with nonmalarial illnesses. The World Health
Organization has recently reiterated "the urgent need for simple and
cost-effective diagnostic tests for malaria to overcome the
deficiencies of [both] light microscopy" and clinical diagnosis (43).
In recent years, multiple studies in areas of both endemicity and
nonendemicity have found that rapid dipstick antigen capture tests for
the circulating Plasmodium falciparum-specific antigen HRP2
have excellent sensitivity and specificity for the diagnosis of
P. falciparum malaria, generally at least as good as
microscopy of a thick and thin film by a skilled microscopist (1,
4-6, 9, 11, 13, 15-17, 19, 23, 28-32, 35, 36, 39-42). The two
commercially available methods of HRP2 antigen detection, ParaSight-F
(1, 4-6, 9, 13, 17, 22, 29-31, 35, 39, 42) and the
P. falciparum immunochromatographic test (ICT Malaria Pf)
(16, 19, 40, 41) have comparable performances (19, 28,
41), but a major limitation has been their inability to detect
malaria caused by other species, particularly Plasmodium vivax. In areas such as eastern Indonesia where both P. falciparum and P. vivax occur (33, 34),
rapid antigen detection tests need to be able to detect both species.
We therefore evaluated the new combined P. falciparum-P.
vivax immunochromatographic test (ICT Malaria P.f/P.v. [ICT
P.f/P.v]) for the detection of malaria. ICT P.f/P.v is based on
detection of the P. falciparum-specific HRP2 antigen and a
panmalarial antigen, and microscopy is used as the "gold standard."
The test kit is identical to the P. falciparum-specific
HRP-2 test described previously (15), but a second
monoclonal antibody directed against a panmalarial antigen is added.
This antigen is expressed by blood stages of P. falciparum
and P. vivax, and probably also by Plasmodium
ovale, but no data on antigen expression by Plasmodium
malariae are yet available (14).
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MATERIALS AND METHODS |
Study site.
The study was performed from February to May
1998 in Radamata Primary Health Centre, Laratama subdistrict, West
Sumba, East Nusa Tenggara Province, Indonesia, a subdistrict with a
Plasmodium infection rate in children 0 to 9 years of age of
5.1% (37). The study was approved by the Ethics Committee
of the National Institute of Health Research and Development,
Indonesian Ministry of Health, Jakarta, Indonesia, and by the Joint
Institutional Ethics Committee of Menzies School of Health Research and
Royal Darwin Hospital, Darwin, Northern Territory, Australia.
Patients.
A total of 560 symptomatic adults and children
attending the primary health care center were enrolled in the study.
Only those who had a presumptive diagnosis of clinical malaria were
eligible for the study. A diagnosis of clinical malaria was based on
fever or history of fever in the last 48 h and no other evident
cause of fever. In routine clinical practice in this setting, all of these people would have been treated empirically with antimalarial drugs. As such, all patients were treated with a standard regimen of
chloroquine with or without primaquine according to the malaria treatment protocols of the Indonesian Ministry of Health
(10).
Microscopy and immunochromatographic testing.
Thick and thin
films were prepared directly from fingerprick blood samples, and
immunochromatographic testing was performed directly with the
fingerprick blood samples. Thick and thin films were stained with 10%
Giemsa solution and examined at ×1,000 by an expert microscopist
(S.S.) with 24 years of experience. The microscopist was unaware of the
patient's diagnosis or immunochromatographic test result. The parasite
density was counted per 200 leukocytes and was then expressed as the
number of trophozoites per microliter by assuming a leukocyte count of
8,000/µl. The initial thick film was considered negative if no
parasites were seen in at least 100 high-power fields.
After a period of training, the immunochromatographic test with 15 µl
of fingerprick capillary blood was performed by clinic health workers
according to the manufacturer's instructions, and the results were
read by the study physician (E.T.), who was blinded to the microscopy
results. The MLO2 ICT P.f/P.v test card (AMRAD-ICT, Sydney, Australia)
was used. Batch 100088 was used for the first 393 tests, and batch
041388 was used for the remaining 167 tests. The test was considered
valid if the control line was visible and positive if the HRP2 and/or
panmalarial antigen lines were visible. An immunochromatographic test
diagnosis of P. vivax malaria was made if only the
panmalarial antigen line was visible. A diagnosis of P. falciparum malaria was made if the HRP2 line was visible, with or
without the panmalarial antigen line. Coinfection with both P. falciparum and P. vivax cannot be distinguished from
infection with P. falciparum alone: the test interpretation
when two lines are visible is P. falciparum malaria. Line
intensity was graded into four categories: absent, faint (just
visible), intermediate, or greater than or equal to that of the control.
All slides with discordant results and 20% of slides with concordant
results were cross-checked by an expert microscopist (M.D.) in Darwin
with over 20 years of experience. The microscopist was blinded to the
patient's diagnosis and to previous microscopy and
immunochromatographic test results. A thick film was considered negative on cross-checking only if at least 200 high-power fields were negative.
Data analysis.
Epi-Info version 6 (7) was used to
calculate test performance and acceptability evaluation indices, with
microscopy used as the gold standard. Performance indices were
calculated for each of the following microscopic diagnoses: malaria as
a whole (diagnosis of either species), P. falciparum malaria
(including mixed infection), and P. vivax malaria. The
variables measured were the number of true positives (TP), number of
true negatives (TN), number of false positives (FP), and number of
false negatives (FN). Sensitivity was calculated as TP/(TP + FN),
specificity was calculated as TN/(TN + FP), the positive
predictive value (PPV) was calculated as TP/(TP + FP), and the
negative predictive value (NPV) was calculated as TN/(FN + TN).
Sensitivity and specificity were used to calculate the likelihood
ratios for a positive test result [sensitivity/(1 
specificity)] and a negative test result [(1 sensitivity)/specificity] (18). The likelihood ratios were
used to determine posttest probabilities by using Fagan's nomogram
(12). Test accuracy, the proportion of all tests that gave a
correct result, was defined as (TP + TN)/number of all tests.
Reliability was expressed as the J index (TP × TN FP × FN)/(TP + FN)(TN + FP) (26).
In the analysis for malaria as a whole, results were considered false
positive if microscopy detected P. falciparum and the immunochromatographic test detected P. vivax, and vice
versa. Because mixed infections are read as P. falciparum
alone, when analyzing test performance for the detection of P. vivax, mixed infections detected by microscopy were considered
true negative if immunochromatographic testing detected P. falciparum and true positive if immunochromatographic testing
detected P. vivax. HRP2 is thought to be present in immature
(but not mature) gametocytes (4, 43), which may result in an
immunological true-positive antigen-detection test result. However, in
clinical evaluations of the ParaSight-F test, mature gametocytemia
alone has not been associated with an excess of positive test results
(4, 22, 43). Because sexual stages do not cause disease,
samples that were HRP2 or panmalarial antigen positive by
immunochromatographic tests but that were asexual parasite negative and
gametocyte positive on microscopy were considered false positive
(43).
The Kruskal-Wallis test was used to examine the overall relationship
between parasite density on microscopy and immunochromatographic test
line intensity categorized as described above. Stepwise two-sample t tests with log-transformed data were then used to test the
significance of differences in mean parasitemia between each category
of line intensity. Following Bonferroni adjustment for multiple
comparisons, a P value of 0.017 was considered significant.
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RESULTS |
Of the 560 patients who met the case definition for clinical
malaria, 289 (51.6%) were males and 271 (48.4%) were females. The age
range was 0 to 80 years, with 50.7% children (age, <13 years) and
49.3% adults (age, 
13 years). Almost all were Sumbanese (98.2%).
Two hundred ninety-four (52.5%) of the 560 people with a presumptive
clinical diagnosis of malaria were found to have parasitemia (with or
without sexual forms); 279 (49.8%) had asexual-stage parasitemia (with
or without sexual forms), and 15 (2.7%) had P. falciparum
gametocytes only. Of the 279 people with asexual-stage parasitemia, 230 (82.4%) were infected with P. falciparum as detected by
microscopy, 32 (11.5%) were infected with P. vivax, and 17 (6.1%) were infected with both P. falciparum and P. vivax.
The results of parasite detection by microscopy and
immunochromatographic testing are compared in Table
1. The test was sensitive (95.5%) and
specific (89.8%) for the diagnosis of falciparum malaria, with a PPV
and an NPV of 88.1 and 96.2%, respectively (Table
2). The corresponding sensitivity and
specificity for the diagnosis of vivax malaria were 75 and 94.8%,
respectively, with an NPV of 98.2% and a PPV of 50%. Other evaluation
indices are given in Table 2. Test sensitivity for the detection of
P. vivax increased with increasing density of parasitemia
(Fig. 1): sensitivity for the detection
of P. vivax was 96% with parasitemias of 500/µl but
only 29% with parasitemias of <500/µl. The mean P. vivax
parasitemia (excluding mixed infections) was 7,157/µl, with 22% (7 of 32) of the study subjects having parasitemias below 500/µl.
Infections in 6 of the 32 subjects with P. vivax infection
were not detected by the panmalarial antigen, 5 subjects had low
parasite densities (
280/µl), and 1 subject had a parasite density
of 4,880/µl. Both test antibodies were very sensitive for the
detection of P. falciparum antigens: 97% (223 of 230) for
HRP2 and 96.1% (221 of 230) for the panmalarial antigen. Of the seven
subjects with P. falciparum infection not detected by HRP2
(3%), not all had low parasitemias: four had parasite densities of
between 120 and 1,000/µl, but the three others had densities of
between 2,200 and 4,080/µl.
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TABLE 1.
Comparison of ICT P.f/P.v and microscopic examination for
malaria for 560 patients with a presumptive clinical diagnosis
of malaria
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TABLE 2.
Performance characteristics of ICT P.f/P.v relative to
those of microscopy for 560 patients with a presumptive clinical
diagnosis of malaria
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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.
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In febrile Sumbanese subjects in Radamata Health Centre the pretest
probabilities of falciparum and vivax malaria on the basis of a
clinical diagnosis were 44 and 5.7%, respectively. By using the
calculated likelihood ratios presented in Table 2 (12), a
positive ICT P.f/P.v result for each species gave posttest
probabilities for falciparum and vivax malaria of 88 and 44%,
respectively. A negative test gave posttest probabilities of 2.7 and
1.3%, respectively.
Panmalarial antigen line intensity was associated with parasitemia
density for both species (Fig. 2a)
(P < 0.0000001 and P < 0.0002 for
P. falciparum and P. vivax, respectively, by the Kruskal-Wallis test). The differences in mean parasitemia between absent and faint, faint and intermediate, and intermediate and greater
than or equal to that for control panmalarial antigen line intensities
were more significant for P. falciparum (P = 0.06, P < 0.001, and P = 0.0024,
respectively) than for P. vivax (P = 0.38, P = 0.014, and P = 0.17, respectively). HRP2 line
intensity was also associated with P. falciparum parasitemia
density (Fig. 2b) (by Kruskal-Wallis testing, P = 0.000005); however, the differences in mean parasitemias between
absent and faint, faint and intermediate, and intermediate and greater
than or equal to that for control HRP2 line intensities were less than
those for the panmalarial antigen and were not significant
(P = 0.38, P = 0.07, and P = 0.038, respectively).
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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).
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One-third (11 of 32) of subjects false positive for falciparum malaria
were infected with gametocytes, as detected by microscopy. Of those
with no asexual parasites on microscopy but an ICT P.f/P.v result
indicating the presence of P. falciparum or P. vivax, approximately half (14 of 30 who were false positive for
P. falciparum and 11 of 22 who were false positive for
P. vivax) had had chloroquine treatment in the preceding 4 weeks. For microscopy-negative subjects, those with a history of
chloroquine treatment in the preceding 4 weeks were twice as likely to
be false positive for HRP2 (11.1%) as those without recent treatment
(5.4%) (P = 0.17 by 
2 analysis) and
twice as likely to be false positive for the panmalarial antigen (20.7 versus 10.8%) (P = 0.03). False-positive test results for panmalarial antigen were equally distributed in both batches of the
MLO2 tests used, and the line intensity was faint for almost all (92%)
samples that tested false positive. In contrast, the line intensities
for only 53% of samples with false-positive HRP2 test results were
faint, with 47% being of intermediate intensity or greater. Of the 15 subjects in whom only P. falciparum gametocytes were found
by microscopy, 73.3% were positive for HRP2 (with 73% of these having
a line intensity of intermediate or above), and 80% were positive for
the panmalarial antigen (with 75% of these having a line intensity of
intermediate or above).
The addition of the panmalarial antibody to the HRP2 antibody used in
current antigen detection tests resulted in a significant reduction in
undertreatment at the expense of a modest increase in overtreatment.
Plasmodium infections in 41 (14.7%) of the 279 microscopy-positive patients with malaria were not detected by the HRP2
antibody. With the addition of the panmalarial antibody to the test
kit, infections in only 10 (3.6%) of these microscopy-positive patients were not detected by the combined ICT P.f/P.v. Of the 266 subjects who were microscopy negative for both asexual and sexual
parasites, 19 (7.1%) were false positive by HRP2 testing, and this
number increased to 41 (15.4%) with the addition of the panmalarial antibody.
| |
DISCUSSION |
Because the monoclonal antibody to HRP2 used in ICT P.f/P.v is
identical to that used in the ICT Malaria Pf, it is not surprising that
the 96% sensitivity and 90% specificity for the detection of P. falciparum that we found using the combined ICT P.f/P.v were
comparable to the high sensitivities (range, 92 to 100%) and
specificities (range, 84 to 99%) previously reported for ICT Malaria
Pf (11, 15, 16, 19, 23, 28, 32, 36, 40, 41). The sensitivity
of ICT P.f/P.v was better than that previously reported for HRP2
antigen detection tests in Indonesia (13, 35). For the
detection of P. falciparum, the sensitivity and specificity
of ICT P.f/P.v (current study), ICT Malaria Pf (11, 15, 16, 19,
23, 28, 32, 36, 40, 41), and ParaSight-F (1, 4-6, 9, 13,
17, 22, 29-31, 39, 42) for HRP2 are, overall, at least equal to
those of microscopy performed in a well-organized malaria diagnostic
laboratory and much better than those routinely achieved by microscopy
in remote primary health centers (43).
In contrast to the excellent sensitivity for the detection of P. falciparum, the overall sensitivity of ICT P.f/P.v for the detection of P. vivax was less than the desirable level.
Although sensitivity was 96% with parasitemias of >500/µl,
sensitivity was only 29% when parasitemias were below this level.
Because of the relatively few symptomatic patients with vivax malaria and low parasitemias, it was not possible to define the detection threshold with certainty. The utility of the current test for the
diagnosis of vivax malaria will depend on the clinical immunity and
pyrogenic threshold in the target population. Pyrogenic threshold, which is the density of plasmodia required to invoke a febrile reaction
in a given individual (20), is, on average, lower for vivax
malaria than for falciparum malaria (20) and is lower in
nonimmune subjects than in those with previous exposure (20, 21). For one large series of nonimmune subjects, the mean
pyrogenic threshold during initial infection with vivax malaria was
<500 parasites/µl (with over 70% of subjects developing fever when densities were <100/µl) (20), suggesting that with its
current level of sensitivity, ICT P.f/P.v would miss a significant
proportion of symptomatic nonimmune patients with vivax malaria. In
populations in whom malaria is endemic, the pyrogenic threshold for
vivax malaria is usually higher (20, 21), and in areas of
endemicity, the current ICT P.f/P.v may detect vivax malaria in a
greater proportion of semiimmune patients who show symptoms of vivax
malaria. In our study area, which is hypoendemic for malaria, 78% (25 of 32) of patients with symptoms of vivax parasitemia had parasitemias above 500/µl (mean, 7,157/µl), and parasitemia was detected in 96%
of these patients by the immunochromatographic test. As in previous
studies with HRP2 (28, 43), occasional false-negative results for HRP2 and panmalarial antigens were found with high falciparum and vivax parasitemias, but the cause for this is not known
(43).
The posttest probabilities of detection of vivax and falciparum malaria
were such that in febrile Sumbanese, treatment decisions could reliably
be made on the basis of the test results. Despite the less than
desirable sensitivity of ICT P.f/P.v for the detection of P. vivax, the addition of the antibody to the panmalarial antigen to
the monoclonal antibody to the HRP2 antigen significantly improved the
probability of diagnosis of malaria in the study area. Compared to
diagnosis and treatment decisions based on results of the test with
HRP2 alone and despite the relatively low frequency of vivax malaria in
Radamata, use of ICT P.f/P.v would significantly reduce the rate of
undertreatment (from 14.7 to 3.6%) of microscopy-positive patients at
the expense of only a modest increase (7.1 to 15.4%) in the rate of
overtreatment of microscopy-negative patients. This increase is modest
when one considers that 225 (84.6%) of these 266 microscopy-negative
patients would in almost all instances be saved unnecessary
antimalarial therapy. Moreover, they would also be more likely to be
offered appropriate alternative treatment for their underlying
nonmalarial illnesses.
It is possible that the true specificity of ICT P.f/P.v for the
detection of P. falciparum is higher than that found by
using microscopy as the gold standard. Specificity may have increased had PCR been used as the gold standard for the detection of parasitemia below the detection limit of microscopy. However, the higher rates of
both recent treatment and gametocytemia that we found in those subjects
with false-positive test results are consistent, with persistent
posttreatment antigenemia (43) and gametocytemia (38) being additional likely explanations for false-positive test results. While mature gametocytes do not appear to cause false-positive results by ParaSight-F with HRP2 (4, 22, 43), our longitudinal evaluations of ICT P.f/P.v with symptomatic Sumbanese with microscopy-confirmed malaria have shown that false-positive results by tests with HRP2 and panmalarial antigen 1 week after treatment are significantly associated with the presence of
gametocytemia (38). Rheumatoid factor has been found to
cross-react with the ParaSight-F immunoglobulin G (IgG) monoclonal
antibody to HRP2, causing false-positive results by this test (3,
24). However, rheumatoid factor only rarely cross-reacts or
causes false-positive results with the IgM monoclonal antibody to HRP2
used in ICT Malaria Pf and ICT P.f/P.v (2, 25) and is thus
very unlikely to be a cause of the false-positive results in tests with
HRP2 in this study.
Over half of the positive results by ICT P.f/P.v for the detection of
P. vivax were false positive, with the PPV of the test for
P. falciparum (88.1%) being much greater than that for
P. vivax (50%). Because of the low sensitivity of the
test for the panmalarial antigen with P. vivax parasitemias
of below 500/µl, vivax parasitemia below the detection limits of
microscopy is very unlikely to explain false-positive results of tests
with the panmalarial antigen. Although antibodies to both HRP2 and panmalarial antigens have high sensitivities for the detection of
P. falciparum, it is possible that parasites in
patients with P. falciparum parasitemia below the
detection limit for microscopy could in some cases bind to the
monoclonal antibody to the panmalarial antigen but not to the
antibody to HRP2 and could give a false-positive reading for
P. vivax. Alternative explanations are persisting posttreatment panmalarial antigenemia or nonspecific binding to the
panmalarial antibody. Although the monoclonal antibody to the
panmalarial antigen is IgG, cross-reactivity with rheumatoid factor
does not appear to occur (14) and is thus unlikely to explain the false-positive results for vivax malaria.
Line intensities for the HRP2 antigen and particularly the panmalarial
antigen were associated with parasite density. Semiquantitative assessment of these antigens in plasma may prove to be useful for the
rapid prediction of parasite biomass in and prognosis for patients with
severe malaria (8).
An alternative rapid dipstick method (OptiMAL) for the diagnosis of
both P. falciparum and P. vivax malaria has also
recently been introduced. This test uses a monoclonal antibody to the
intracellular antigen parasite lactate dehydrogenase (pLDH). Like ICT
P.f/P.v, this test also differentiates species by the use of a P. falciparum-specific antibody and a genus-specific antibody.
Initial results for symptomatic Honduran patients have shown
sensitivities of 88 and 94% and specificities of 100 and 99%
for the diagnosis of falciparum and vivax malaria, respectively
(27). Comparative studies will be required to assess the
relative utility of the available combined antigen detection tests in
areas of endemicity. However, current prices of all antigen detection
tests, including ICT P.f/P.v (presently US$1.20 per test for >10,000
tests), are too high to enable widespread use in developing countries.
Despite their advantages over microscopy and clinical diagnosis, the
cost of all rapid antigen detection tests must be reduced if these
tests are to ever become affordable in most areas where malaria is endemic.
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ACKNOWLEDGMENTS |
We thank Mary Garcia of AMRAD-ICT for providing ICT P.f/P.v; Umar
Fahmi, Sumarjati Arjoso, Harijani Marwoto, Thomas Suroso, and Ferdinand
Laihad, Ministry of Health, Jakarta, Indonesia, for support; Wang
Zhiqiang, James McBroom, Peter Morris, and Jeni Wie for statistical and
computing advice; Susan Hutton and Elizabeth Stubbs for logistic help;
and Bambang Purnomo, Agus Berek, Frankie Hartanto, Sunarno, Frans
Pello, Markus, Wayan, Yulius Weng, and staff, Regional, Provincial,
District, and Subdistrict Health Offices, West Sumba, East Nusa
Tenggara, Indonesia, for support and technical assistance.
Financial support for the study was received from Northern Territory
Government 50th Anniversary of Indonesian Independence Malaria-Tuberculosis Research Fellowships. ICT P.f/P.v kits and some
logistical costs were supported by AMRAD-ICT, Sydney, New South Wales, Australia.
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FOOTNOTES |
*
Corresponding author. Mailing address: Tropical
Medicine and International Health Unit, Menzies School of Health
Research, P.O. Box 41096, Casuarina, Darwin, Northern Territory, 0811 Australia. Phone: 61-8-8922 8932. Fax: 61-8-8927 5187. E-mail:
anstey{at}menzies.su.edu.au.
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Journal of Clinical Microbiology, August 1999, p. 2412-2417, Vol. 37, No. 8
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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Abstract
Introduction
