Identification based on the blood smear? How might this correlate with the rapid antigen test?
Wednesday, August 28, 2019
Case of the Week 558
This week's case presents a bit of a conundrum. The patient is a 50 year old woman with recent travel to Kenya. She presents with acute onset of fever and chills and was tested by a rapid malaria antigen test (P. falciparum and Pan-malaria antigens) and was negative. A follow-up Giemsa-stained thin blood smear from the same blood collection shows the following:
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Babesiosis ?
Huge parasitemia; I'll bet this is antigen excess / prozone phenomenon causing a false-negative.
This is probably a strain of P. falciparum that lacks the HRP-II antigen (i.e., the falciparum-specific antigen). Such strains have been documented in South America (Amazon?) and Africa (including Kenya).
falciparum malaria.
Negative RDT could be due to deletion of the hrp2 histidine-rich repeat region, reported in some African countries including Kenya, Eriteria and Tanzania and other countries in Latin America and Asia.
My personal experience...the RDTs are a helpful tool, but far from being perfect. In fact, I think in developed countries they can often have pretty low value outside of their TAT advantages.
Possibilities that come to my mind are:
Prozone
Poor kit performance (bad lot?)
I would not favour the HRP defieicent strains because the aldolase should still detect.
Marc
Marc made a good point regarding my comment; the pan-malarial antigen should still have been positive in an HRP-II deficient strain of Pf.
Bottom line, microscopy continues to be superior :-D
Well, it appears that there may be a post-zone phenomenon where there are too much antigen for antibody. Other than that, I tend to agree with Blaine and others.
There are no evidence indicating Babesiosis.
Florida Can
Could be Babesiosis!
Plasmodium falciparum
Could be babesiosis if the patient is immunocompromised or splenectomised. PCR or IFAT is advisable for confirmation.
I'd rule out the prozone affect, first.
BW in Vt
Morphologically and epidemiologically, this looks like Plasmoidum falciparum. I think the negative rapid malaria antigen test is most likely due to prozone effect due to the high parasitemia seen on the smear. If there was deletion or heterogeneity of the HRP2 protein, only the Plasmodium falciparum band would be negative, but the pan-malarial band should still be positive. Also, do we know if the Control line was positive? If not, this would mean the entire assay did not work at all!
Babesiosis, although less likely, should be kept in the differential and more information regarding the patient's medical history and exposure should be obtained.
Babesia. Multiply infected cells. Marginal forms. With this degree of malarial parasitemia I'd expect the patient to present with more than just "fever and chills".
The pictures shows only various appearances of the ring forms such as "headphones", "applique" forms, multiple rings in the same red cell. The infected red cells also are of various sizes from small to large, this indicates that there is no predilection for neither young nor older red blood cells. As such this favors a diagnosis of P. falciparum infection where all stages of red cells can be infected.
Unlike Babesiosis, we do not see any extra-erythrocytic parasites as seen in case 554.
Everything considered, I would favor a diagnosis of P. falciparum infection. As far as why the rapid tests were negative, I would consider the possibility of a post zone phenomenon and/or the explanations expressed by Blaine and others.
Florida Fan
P.f. is most likely but why hemozoin is not visualized in RBCs? P.f. rings are more delicate than in Babesiae invasion and if they are >24hrs they (P.f. rings) may get thicker but again: where is haemozoin?
I don't think this would be Babesiosis. The shapes would be more varied.We see only rings, which is more like Plasmodium. Also, such a high amount would mean the person is dying if it were Babesiosis. Babesiosis makes a person sick with a much lower amount of parasites.
There is hint of malarial pigment in the cytoplasm. I would rule out Babesia and suggest Pf. Ag could be negative with HRP2 negative strains and/or due to kit incompetence.
Plasmodium falciparum.
Very much a learner in malaria microscopy. We get alot of P. knowlesi ring forms here and not using RDT. Not sure about the Plasmodoum coverage/detection of the RDT. Just kicking up more sand everyone here.
I neglected to mention that you can test the antigen excess hypothesis by diluting the specimen 10x or 100x; if it turns positive, that strongly suggests prozoning.
It is definitly P falciparum, I would also go for prozoon effect, but as far as I know it is not known to appear w pLDH.
Agree
Morphology is with Pl. falciparum
Morphology with Pl.faciparum
False negative result of Pl. falcip. maybe due to operator error, poor product design or quality regarding sensitivity, specificity. Affinity or insufficient antibody quantity
The parasite may express low antigen level
Variation in the sequence of amino acid targeted by monoclonal antibody
A learner of Malaria Microscopy. Assuming that was a very high parasitemia slide that was disguised as false negative ( P. falciparun) on RDT isn't that a big issue in economically deprived settings with no facility for further investigations? What about blind administration of Antimalarials?
I think it is more likely P.falciparum, the RDT fails to identify which could be unvalid test card, prozone effect.
Other possibility is P. knowlesi infection which may cause negative on RDT however P. knowlesi so far is known endemic in Asia
Correct... Pl. Knowlesi should be kept in mind especially if blood film shows Pl. malariae species so differentiation will be impossible except by PCR also presence of history of traveling to endemic area will support diagnosis of Pl knowlesi
If prozone phenomenon suspected.. the line for Pldh should appear as it s panspecific
Pl knowlesi morphological similar to Pl malariae but present with severe rapid progressive manifestations with low parasitaemia
Agree with P. falciparum with false negative RDT result. Here´s a WHO paper on the subject:
https://apps.who.int/iris/bitstream/handle/10665/258972/WHO-HTM-GMP-2017.18-eng.pdf;jsessionid=43AF2EC1CA02E075B796FFF1759D4087?sequence=1
I agree with you. Plasmodium falciparum.
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