Malaria antigen detection tests are a group
of commercially available tests that allow the rapid diagnosis of malaria
There are
currently over 20 such tests commercially available, but none of the rapid
tests are currently as sensitive as a thick blood film, nor as cheap. A major
drawback in the use of all current dipstick methods is that the result is
essentially qualitative. In many endemic areas of tropical Africa, however, the
quantitative assessment of parasitaemia is important, as a large percentage of
the population will test positive in any qualitative assay.
Antigen tests
look for one of four main markers:
pGluDH
The enzyme pGluDH does not occur in the host red cell and is therefore
specific to plasmodium sp.
GluDH activity in
P.vivax, P.ovale and P. malariae has never been tested, but given the
importance of GluDH as a branch point enzyme, it is assumed that every cell
must have a high concentration of GluDH.
Histidine Rich Protein II
The
histidine-rich protein II (HRP II) is a histidine - and alanine -rich,
water-soluble protein, which is localized in several cell compartments
including the parasite cytoplasm.
The antigen is
expressed only by P. falciparum trophozoites.
pLDH
P.falciparum
lactate dehydrogenase (pLDH) is a 33 kDa oxidoreductase It is the last enzyme
of the glycolytic pathway, essential for ATP generation and one of the most
abundant enzymes expressed by P.falciparum.
pLDH does not
persist in the blood but clears about the same time as the parasites following
successful treatment. The lack of antigen persistence after treatment makes the
pLDH test useful in predicting treatment failure.
In this respect,
pLDH is similar to pGluDH. LDH from P. vivax, P.malariae, and P.ovale exhibit
90-92% identity to pLDH from P.falciparum.
pAldo
Fructose-bisphosphate aldolase catalyzes a
key reaction in glycolysis and energy production and is produced by all four
species. The P.falciparum aldolase is a 41 kDa protein and has 61-68% sequence similarity
to known eukaryotic aldolases.
The presence of antibodies against p41 in
the sera of human adults partially immune to malaria suggest that p41 is
implicated in protective immune response against the parasite.
However
these techniques are not without drawbacks.
Cross-reactions
with autoantibodies:
Studies have
reported cross reactivity of the various RDTs with autoantibodies such as
rheumatoid factor, resulting in false positive tests for malaria. Studies in
patients with positive rheumatoid factor have shown that the false positive
reactions.
Sensitivity:
RDTs for the
diagnosis of P. falciparum malaria generally achieve a sensitivity of >90%
at densities above 100 parasites per µL blood and the sensitivity decreases markedly
below that level of parasite density.
Many studies have
achieved >95% sensitivity at parasitemia of ~500 parasites/µL, but this high
parasitemia is seen in only a minority of patients. For the diagnosis of P.
vivax malaria, many tests have a lower sensitivity compared to that for P.
falciparum malaria; however, the pLDH test has an equal or better sensitivity
for P. vivax malaria compared to P. falciparum malaria.
For the diagnosis
of P. malariae and P. ovale infections, the sensitivity is lower than that of
P. falciparum malaria at all levels of parasitemia on pLDH tests.
The sensitivity of the RDTs at low levels
of parasitemia and for non-immune populations remains a problem. Compared to
microscopy,many tests were found to be less sensitive in detecting asymptomatic
patients, particularly at low parasitemias.
Also, the RDTs
have been reported to give false negative results even at higher levels of
parasitemia. Therefore, in cases of suspected severe malaria or complex health
emergencies, a positive result may be confirmatory but a negative result may
not rule out malaria. A negative RDT result should always be confirmed by
microscopy.
