Travel Medicine and Infectious Disease (2003) 1, 119–122

www.elsevierhealth.com/journals/tmid

Sensitivity of P. vivax rapid antigen detection tests

and possible implications for self-diagnostic use
Martin P. Grobuscha,b,*, Thomas Hänscheidc, Klaus Göbelsa,
Hortense Slevogta, Thomas Zollera, Gertrud Röglera, Dieter Teichmanna

a
Department of Infectious Diseases, Charité, Humboldt University, Berlin, Germany
b
Department of Parasitology, Institute of Tropical Medicine, Eberhard Karls University, Wilhelmsstr.
27, D-72074 Tuebingen, Germany
c
Lab. Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Portugal

Received 11 February 2003; received in revised form 21 March 2003; accepted 24 March 2003

KEYWORDS
Malaria; Diagnosis; Self-
diagnosis; Rapid antigen
detection; P. vivax
Summary In a prospective study amongst febrile travellers returning from malaria-
endemic areas to Berlin, Germany, two rapid malarial antigen detection tests were
compared for the diagnosis of vivax malaria with routine microscopy. With ICT Malaria
P.f./P.v.w, 664 samples of 492 patients were examined. 17 patients had vivax malaria,
out of which 11 infections were missed (35.3% sensitivity). With OptiMalw, 659 samples
of 539 patients were examined. 22 patients had vivax malaria, and all infections were
identified correctly (100% sensitivity). Specificity was 100% with both tests. The ICT
Malaria P.f./P.v.w is advertised for layman use during travel, and the literature was
reviewed with respect to the question of suitability of these devices for self-testing. It
is concluded that with the ICT Malaria P.f./P.v.w, the detection of non-falciparum (i.e.
predominantly vivax) malaria is unreliable, and test interpretation for medically
untrained individuals particularly in distress might be too complicated even after
proper instruction.
Q 2003 Elsevier Ltd. All rights reserved.

Introduction parasite-specific lactate dehydrogenase with one

The second generation of rapid tests for malaria is
designed to detect antigens from Plasmodium
falciparum, P. vivax, and potentially P. ovale and
P. malariae. The OptiMalw assay (Flow, Portland,
Oregon, USA; marketed currently by
DiaMed, Cressier-sur-Morat, Switzerland) detects
*Corresponding author. Address: Department of Parasitology,
Institute of Tropical Medicine, Eberhard Karls University,
Wilhelmsstr. 27, D-72074 Tuebingen, Germany. Tel.: þ 49-
7071-298-0234; fax þ 49-7071-29-4684.
E-mail address: martin.grobusch@uni-tuebingen.de
monoclonal antibody specific for P. falciparum
(17E4), and the ICT Malaria P.f./P.v.w (ICT Diag-
nostics, Sydney, Australia; marketed currently
under various labels) detects P. falciparum-specific
histidine-rich protein 2. Both tests use panspecific
antigens. The OptiMalw uses parasite-specific lac-
tate dehydrogenase (19G7), and the ICT Malaria
P.f./P.v.w uses aldolase,1 also dubbed pan-malarial
antigen to detect P. vivax, P. ovale and P. malariae.
The performance of these tools for the detection of
non-falciparum malaria has been reported pre-
viously, mainly in populations in endemic areas.1
However, the recent trend to market tests for

1477-8939/03/$ - see front matter Q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S1477-8939(03)00037-1
120
self-diagnosis in travellers from non-endemic areas
and the possibility that ‘combination’ test kits
could be marketed for this purpose means that
sensitivity and specificity in this population need to
be determined. Over a period of three years, we
compared both test kits suitable for P. vivax
diagnosis with standard microscopy in travellers
returning from endemic areas who presented with
an acute febrile illness suggestive of malaria to the
Department of Infectious Diseases, Charité, Berlin,
Germany. Apart from sensitivity and specificity, the
controversial issue whether rapid malarial antigen
detection tests are useful for self-testing with
particular reference to the results is reviewed.
Materials and methods
Tests as described above were carried out on
admission to, or on outpatient presentation at the
Department of Infectious Diseases, Charité, Berlin,
Germany, and compared to standard expert
microscopy results of Giemsa-stained thick ($ 200
visual fields/slide) and thin films. Antigen detection
tests and microscopy were carried out indepen-
dently by different examiners that were blinded to
each other’s results.
Results
The main study results are given in Table 1. Parasite
densities were in the range of 0.01 – 3%. In those 11
cases not detected with ICT Malaria P.f./P.v.w,
parasitaemia ranged between 0.1 to 2.5% of
erythrocytes infected. With both tests, no false
positives (indicating P.f. monoinfections) occurred
(specificity 100%). In a subset of 202 patients, both
tests were performed in parallel. Out of those, 7
patients had P. vivax infections. In direct compari-
son, ICT Malaria P.f./P.v.w yielded 4 of 7 (57.1%)
positive results (OptiMalw 7 of 7, 100%).
Table 1 Synopsis of main results.
Test ntotal of n ptsa n micr.b
samples tested neg.
ICT Malaria P.f./P.v.w 664 492 336
OptiMalw 659 539 384
a
Patients.
b
Microscopically.
c
Rapid malarial antigen detection tests.
d
Sensitivity.
M.P. Grobusch et al.
Discussion
The sensitivity and specificity obtained in a large
cohort of returning travellers is in accordance with
findings described previously. For example, with
the ICT Malaria P.f./P.v.w, Huong et al.2 found a
sensitivity of 20% in 95 P. vivax cases in a cohort of
507 individuals in Vietnam, whereas Tjitra et al.3
found a 75% sensitivity in a comparable cohort from
Indonesia. With OptiMalw, sensitivities found for P.
vivax range between approximately 75% to well
over 95%.1,4 With both tests, specificities ranged
from 95 to 100%. Overall, it seems that OptiMalw
performs reproducibly more reliably than ICT
Malaria P.f./P.v.w for the detection of P. vivax,
i.e. parasite-specific lactate dehydrogenase
appears to be a better target for P. vivax antigen
detection than aldolase as used in combination with
histidine-rich protein 2. In comparison, histidine-
rich protein 2 detection appears to be overall
superior for P. falciparum detection; but in the
majority of studies from endemic and non-endemic
areas, the specificity ranged between 90 and 100%
for both antigens.5
There is a recent trend to market antigen
detection tests for self-diagnosis of malaria in
febrile travellers to remote areas who might be
unable to obtain medical attendance within a
reasonable period of time, to facilitate better
decision-making whether to start standby-emer-
gency malaria treatment or not. This marketing
strategy applies particularly to the ICT Malaria
P.f./P.v.w test format.
In an initial trial to determine whether
travellers can carry out successfully and interpret
rapid malarial antigen detection tests, 160 Swiss
travel clinic attendees were asked to test their
own blood and to interpret 5 pre-prepared test
strips of the ParaSight-Fw, the test prototype
based on histidine-rich protein 2 detection of P.
falciparum. 75% succeeded with self-testing after
oral instruction only, whereas 90% managed to
handle the test correctly after having received
n micr. non-vivax P. vivax Correct RDTc sens.d
pos. Pl. spp. for P. vivax (%)
156 139 17 6 35.3
155 133 22 22 100
Sensitivity of P. vivax rapid antigen detection tests and possible implications for self-diagnostic use
combined written and oral instructions.6 With
only 70.6% correct results, the interpretation of
pre-prepared tests was regarded as unsatisfying.
An accomplishing comparative study between
ParaSight-Fw and MalaQuickw (identical with ICT
Malaria P.f.w) 164 participants in total yielded no
significant difference regarding self-testing with
both systems.7 Regarding test interpretation of
pre-prepared tests, both test systems were
associated with unacceptably high levels of
false-negative interpretations. In an investigation
of 98 European tourists with febrile disease in
Kenya under field conditions, only 68% of patients
were able to complete the MalaQuickw correctly.
Most important, 10 of 11 patients with micro-
scopically confirmed falciparum malaria were
unable to self-diagnose their condition by rapid
testing. The authors concluded that a consider-
able proportion of patients might be too sick to
obtain a correct diagnosis and subsequently, to
start standby-emergency malaria treatment by
themselves.8 In contrast, in a prospective UK
study with 153 febrile returning travellers, only
14 (9%) failed to carry out a valid MalaQuickw
test on presentation, using an improved test
instruction leaflet based on feedback from earlier
test persons. Most importantly, all 22 patients
with microscopically confirmed falciparum
malaria successfully completed self-testing.9 The
authors argued that differences in the various
studies were possibly due to poor quality of the
instructions provided. They concluded that a
more user-friendly kit could possibly be
implemented correctly by travellers
without additional instruction and training. The
importance of a correct diagnosis of falciparum
malaria is under most circumstances of greater
immediate clinical relevance than that of the
other species, particularly in non-immune indi-
viduals, and these studies have been all carried
out with the simpler first generation of tests for
P. falciparum antigen detection. However, the
introduction of a P. vivax-reactive stripe probably
adds a new dimension of complexity to test
interpretation not only to laymen. For example,
the P. vivax-indicating portions of the test strips
detect, to a variable but poor extent P. ovale
and P. malariae as well, but cannot differentiate
between those three.10 Thus, a positive test
indicates not necessarily a P. vivax infection
but, more exactly, a non-falciparum parasitemia,
what might have implications for the choice of
treatment.
Currently, the ICT Malaria P.f./P.v.w cardboard
format is suitable principally for ‘outdoor’ use,
whereas the initial OptiMalw test strip format is
121
better adapted to laboratory use. However, that
might change with the cassette format intro-
duced recently, for which published sensitivity
data and handling experience is, to our knowl-
edge, not yet at hand.
Apart from technical problems directly inherent
to these tests and those related to their handling as
described above in detail, the most profound
problem with layman use of a test for malaria is
probably that it seeks to diagnose only one of many
possible causes of fever, and it would need a very
intelligent and well informed traveller to put the
information obtained from the test result in a useful
context.
In conclusion, rapid malarial antigen detection
tests are a useful adjuvant diagnostic tool provided
that their drawbacks are understood, and that
variations in their antigen detection capacity are
taken into account. With the ICT Malaria P.f./P.v.w,
the detection of non-falciparum (which is predomi-
nantly vivax) malaria is unreliable. Although simple
to carry out, test interpretation for medically
untrained individuals particularly if in distress
might be too complicated even after comprehensive
and thoughtful instruction.
Acknowledgements
We thank S. Schwenke and C. Acar, Department of
Infectious Diseases, Charité, Berlin, Germany, for
technical assistance.
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