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Journal of Clinical Microbiology, July 2001, p. 2736-2737, Vol. 39, No. 7
Department of
Microbiology2 and Department of
Infectious Diseases,3 Carlos III Hospital, and
Department of Parasitology, National Center for
Microbiology,1 Carlos III National Institute of
Health, Madrid, Spain
Received 11 January 2001/Returned for modification 28 March
2001/Accepted 2 May 2001
The rise of imported malaria cases and the high fatality rate in
Europe make the search for new and easy diagnostic methods necessary.
Rapid diagnosis tests (RDTs) are, in part, developed to cover the lack
of diagnosis experience. Unfortunately, our data suggest that the
accuracy of RDTs is insufficient and could increase the number of
incorrect malaria diagnoses.
In recent years, countries in which
malaria is not endemic have reported high and increasing numbers of
imported malaria cases, with fatalities
up from 3.8 to 20% (2).
Preventing fatal outcomes in malaria cases requires early recognition
of infection, accurate laboratory diagnosis, and prompt therapy
(2). Unfortunately, health-care personnel in countries
where malaria is not endemic frequently lack experience in the
microscopic diagnosis of malaria. In Italy, 80% of cases had less than
a 1-week elapse between the onset of malaria symptoms and the
microscopic diagnosis, but the average diagnosis took 8.5 days and the
range was 1 to 28 days (3). This fact makes the search for
new and easy diagnostic methods necessary. Rapid diagnosis tests (RDTs)
for malaria might offer a valid alternative to microscopy
(5).
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.7.2736-2737.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Limited Level of Accuracy Provided by Available
Rapid Diagnosis Tests for Malaria Enhances the Need for PCR-Based
Reference Laboratories
ABSTRACT
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TABLE 1.
False positives and false negatives of three RDTs
compared to microscopy analysis confirmed by PCR for the detection
of Plasmodium spp.
We studied 206 pre- and posttreatment samples from 169 patients in 1998 and 1999 by microscopic diagnosis and seminested multiplex PCR (4). These samples were also tested using three commercial RDT kits; 189 samples from 149 patients were tested with the ParaSight-F Kit (Becton Dickinson), 197 samples from 126 patients were tested with the OptiMal Kit (Flow Incorporated), and 54 samples from 41 patients were tested with the ICT Pf/Pv kit (Amrad). All patients (with ages of 16 months to 72 years) presented a history of fever and travel in the previous year to an area of malaria endemicity.
RDTs were performed according to the manufacturers' instructions. All
microscopy-positive samples were confirmed by PCR (4). Furthermore, PCR detected 6 samples with mixed infections (4 Plasmodium falciparum plus P. malariae and 2 P. falciparum plus P. ovale) from samples that
were characterized as P. falciparum-only by microscopy and
24 more positive samples (12 P. falciparum, 4 P. ovale, 6 P. malariae, and 2 P. vivax). The
three RDT methods showed a high rate of false positives and false
negatives (Table 1). Moreover, 29.2% of positive non- P. falciparum samples rendered a positive P. falciparum
result when the ParaSight-F test was used, which suggests a high number
of cross-reactions, as this test according to the manufacturer detects
only P. falciparum infections. In the same way, according to
the manufacturers, the OptiMal and ICT Pf/Pv kits are able
to detect P. falciparum specifically and the other
Plasmodium spp. unspecifically. Our data, however, show that
these two diagnostic methods missed, respectively, 62.5 and 83.3% of
Plasmodium infections other than P. falciparum
(Table 1). Also, a lack of sensitivity was detected at low levels of parasitemia (under 100 parasites/µl of blood). The comparison of the
sensitivity and specificity of the RDTs versus microscopy or PCR (Table
2) indicated that the detection rate was
low except for P. falciparum. After antimalaria treatment,
approximately 55% of treated patients remained positive (>10 days on
average for ParaSight-F and >17 days for OptiMal), while microscopy
and PCR tests were negative.
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The data presented here indicate that the accuracy of the three examined RDTs was insufficient and could lead to the incorrect diagnosis of malaria. The increasing use of RDTs in Spanish hospitals and the comparative results of sensitivity and specificity of RDTs versus PCR diagnosis indicate an essential need to enhance the role of reference laboratories with PCR-based diagnostic capabilities. Our data suggest that RDTs could help the initial assessment of malaria in returned travellers (1) and migrants, but this and other reported studies indicate the need to develop more specialized laboratories with available confirmatory diagnostic techniques (PCR). The main difficulty still encountered by the use of RDTs is the correct identification of Plasmodium species. False-positive results derived from patients with immunological disorders and/or rheumatoid factor have been partially corrected by the latest versions of kits targeting the HR-II protein of P. falciparum. However, the occurrence of false positives due to antigen persistence is still a serious constraint to the assessment of treatment failure (Table 1). Low sensitivity is apparent for patients with low parasite numbers and is commonly encountered for patients with low immunity or nonimmune patients treated with antimalarial chemoprophylaxis. The RDTs were, in part, developed to cover the lack of experience in microscopic malaria diagnosis, but unfortunately our data suggest that in the current stage these methods could increase the number of incorrect diagnoses. RDTs could play and will play in the future an important role in malaria diagnosis. However, for the present they should be used with great caution and should not replace conventional microscopy or PCR.
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FOOTNOTES |
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* Corresponding author. Mailing address: Servicio de Parasitología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain. Phone: 91 509 79 01. Fax: 91 509 79 66. E-mail: abenito{at}isciii.es.
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Journal of Clinical Microbiology, July 2001, p. 2736-2737, Vol. 39, No. 7
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.7.2736-2737.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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