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:

Identification based on the blood smear? How might this correlate with the rapid antigen test?

Answer to Case 558

Answer to Parasite Case of the Week 558: Plasmodium falciparum malaria, >10% parasitemia. NEGATIVE rapid antigen.

So why is the rapid antigen test negative???

As noted by our readers, there are many possible reasons for a positive blood smear and negative rapid malaria antigen test (RDT). Here are our options, along with the reasons why each is or isn't a likely explanation in this case:

1. This is babesiosis, and not malaria. This is a very important consideration given the morphologic similarities between Babesia spp. and Plasmodium falciparum. However, the moprhologic features in this case are highly consistent with P. falciparum, including the presence of relatively-homogenous rings, without the size and shape pleomorphism usually seen with Babesia spp. There are also applique forms and headphone forms (arrows, below) which are characteristic, but not definitive, for P. falciparum infection. There may also be a hint of hemazoin (malaria pigment), but it is not obvious. Overall, we can rule out babesiosis based on the microscopic morphology.
   
2. The negative RDT is due to deletion of the P. falciparum histidine rich protein II repeat region in the parasite infecting this patient. This deletion has been reported in some African and South American countries, including Kenya where this patient had recently traveled. While this is a good thought, it would not explain why the pan-malaria antigen band (in this case, aldolase) is also absent, resulting in a completely negative RDT result. Thus, we can also exclude this as the reason for the negative RDT. 
3. This is the well-described prozone (or 'hook') phenomenon, where antigen excess (seen in cases like this with high parasitemia) binds to both the capture and detection antibodies and interferes with the formation of an antibody-antigen-antibody 'sandwich'. (You can refresh your memory on how a lateral flow immunoassay works by reading this fairly well-written Wikipedia article on malaria RDTs HERE). Prozone effect is well-described for malaria RDTs. You can read a nice study on how often this might occur HERE. In my mind, this is the most likely cause of the false negative result seen in this case.
4. The kit is faulty, or the test was not performed correctly. We unfortunately can't rule this out.

What additional testing would help us sort out the cause of the false negative RDT?

As some of you mentioned, confirmatory testing by another method would be useful to prove this was indeed malaria. Fortunately, we were able to perform PCR and it was strongly positive for P. falciparum, thus confirming our microscopic impression. To evaluate for possible RDT prozone phenomenon, we could also test serial dilutions of the fresh blood specimen to see if specimens with diluted antigen become positive. Repeat RDT testing would confirm that the test was performed correctly to begin with. Finally, we could easily confirm that the test kit isn't expired by checking the box that was used, and checking the storage conditions to ensure that they were appropriate for the test kits.

While we don't have a definitive answer for this case, I thought it was an excellent opportunity to discuss how the prozone phenomenon is a real risk in cases of high malaria parasitemia and may result in false negative results. This is one reason why malaria RDT results should always be followed gold standard blood film examination (or PCR). Also, we always need to remember that no lab test is perfect, and must always be interpreted in the context of the individual patient. 

Thank you all for the excellent comments and discussion on this case!

Case of the Week 557

This week's case was donated by Florida Fan and one of his coworkers who found this beauty in some fresh salmon:

Posterior end:

 Anterior end:

Identification?

Answer to Case 557

Answer to Parasite Case of the Week 557: As mentioned by Bernardino Rocha, this is either an L3 larva of the Anisakidae or Raphidascarididae - 2 families of nematodes that are commonly found in fish. I tend to agree with Blaine and Bernardino that this is most likely a Type I Anisakis or Pseudoterranova sp.; however, we would need to see its internal features to be sure (you can read the comments to learn how to clear the worm to visualize its internal structures). As Blaine mentioned, the presence of the mucron (the terminal spicule-like structure shown below) rules out Contracaecum spp. and Type II Anisakis. Other morphologic features that can be used to differentiate Anisakis, Pseudoterranova, and Contracaecum species are the features of the ventriculus, the number of intestinal cells in cross section, and the shape of the lateral chords (also seen in cross-section).

Blaine Mathison and Alex da Silva recently wrote an excellent chapter on Anisakiasis in Ortega's and Sterling's book entitled "Foodborne Parasites" (email Blaine if you want more information).

Thanks again to Florida Fan for donating this nice case of an anisakid nematode, with nice visualization of the anterior boring tooth and mucron. It serves as an excellent reminder to us all to cook your fish thoroughly before eating it! For the sushi lovers out there, you can kill all parasites in raw fish by freezing it for 7 days at -20C. Bon appetite!

Case of the Week 556

This week's case was donated by Dr. Neil Harris and Dr. Stacy Beal. The patient is an infant with a history of tracheobronchomalacia and "eosinophilia" on prior bronchoscopy. A routine complete blood count was negative without evidence of peripheral eosinophilia. The following structures were seen on a Giemsa-stained bronchoalveolar lavage specimen using the 100x objective. They have a diameter of 1-3 micrometers. Identification?

Answer to Case 556

Answer to the Parasite Case of the Week 556: Curschmann spirals

Curshmann spirals can be a very pretty, but sometimes confounding parasite mimic in sputum, BAL and bronchial lavage specimens. They are spiral-shaped plugs of mucus from obstructed bronchioles, and are seen in patients with asthma and other conditions affecting the airways (e.g. tracheobronchomalacia as seen in this case). Although they can take on a roundworm-like appearance, they can be differentiated by their lack of defined morphologic features such as a cuticle and internal structures. Here is a striking photo from a different case (Papanicolaou stain):

Case of the Week 555 - a Special Challenge!

Dear readers,
I am excited and humbled to be posting my 555th Parasite Case of the Week. I am continuously inspired by your comments, questions, and the rich discussion that occurs with each post. To mark this occasion, I'm asking you all to comment on ways that parasites relate to the number 5. I'll start you off with two that were previously suggested to me when I thought up this challenge:

1. Pentatrichomonas hominis is a nonpathogenic intestinal flagellate named for its 5 flagella (penta from the Greek pente, meaning five + trich, pertaining to hair [flagella]). By Dr. Neil Anderson
2. There are 5 lobes of the human lung, and all can be infected by Paragonimus species. By Brian Duresko

Feel free to be as creative as you'd like. 5-lined poems (e.g. limericks) are also accepted! I will post all of the responses next Friday, so you have all weekend and next week to think of ideas. Enjoy!

Answer to Case 555 - Parasites and the Number Five

Wow - we received so many excellent comments on how parasites and the number 5 go together! Here are many of them - in no particular order - for your viewing pleasure:

1. Pentatrichomonas hominis is a nonpathogenic intestinal flagellate named for its 5 flagella (penta from the Greek pente, meaning five + trich, pertaining to hair [flagella]). By Neil Anderson and Bernardino Rocha.
2. There are 5 lobes of the lung, and all can be infected by Paragonimus species. By Brian Duresko.
3. The are 5 Plasmodium species that are responsible for the bulk of malaria in humans: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi (the latter is a zoonotic parasite and important cause of malaria in regions of SE Asia). By Aimee Boerger, Nipunie Rajapakse, and LS.
4. Pentastomes have a name meaning "five openings". Although having a single mouth, there are 2 pairs of hollow fang-like hooks beside the mouth. These fangs can be retracted into slits giving the appearance of 5 mouths. By Old One.
5. Quintan fever, also known as trench fever, is due to infection with the bacterium Bartonella quintana, and is transmitted by the body louse, Pediculus humanus humanus. The infection is characterized by fevers that recur every five days; hence the name of the bacterium and the resultant disease. By Kristin Nagaro.
6. The gametocytes of Plasmodium vivax appear in the blood ~5 days after the liver stage, whereas it takes 10-12 days for P. falciparum to appear. Thus, P. vivax infection can be acquired by mosquitoes at the very first blood stage cycle, and this may confer a transmission advantage for P. vivax over P. falciparum. Plasmodium vivax has the most widespread distribution of the human malaria-causing Plasmodium spp., and the early gametocytemia will have important implications for malaria eradication. By BW in Vt.
7. Pentamidine is a drug used to treat some protozoal infections such as leishmaniasis and African trypanosomiasis. The first part of the drug's name comes from the pentane component which has 5 carbon atoms (C5H12). By Andy Norgan.
8. Human parasites can be divided into 5 major groups: protozoa, platyhelminthes, acanthocephala, nematoda, and arthropoda. By Bernardino Rocha.
9. The 5 main symptoms of giardiasis are diarrhea, abdominal pain, fatigue, weakness, weight loss. By bks. I use a similar one - the 5 "F's" of giardiasis: Foul-smelling Fatty Feces that Floats and Flatulence.
10. The US Centers for Disease Control and Prevention has targeted 5 neglected parasitic infections (Chagas disease, neurocysticercosis, toxocariasis, toxoplasmosis, and trichomoniasis) as priorities for public health action, based on the numbers of people infected, the severity of illnesses, or our ability to prevent and treat them. Anonymous.
11. Toxoplasmosis, a protozoal infection, in one of the ‘infamous 5’ TORCH infections that cause congenital abnormalities; the acronym stands for Toxoplasmosis, Other (syphilis, VZV, parvovirus b-19), Rubella, CMV, and Herpes simplex virus infections. By Vik Holenarasipur and Anonymous.
12. Human bot flies (and other insects) have 5 eyes - 2 are compound and 3 are simple. This paper wasp (below) is not a parasite, but was willing to pose for a photograph of its five eyes. By John Carlson (@JohnCarlsonMD).
    

There were also some wonderful stories and poems with 5 lines or words/line:

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From Blaine Mathison:

Many of the earth-based religions use the pentagram to represent the Five Elements: Spirit, Air, Water, Earth, and Fire. Many religious beliefs are grounded in scientific phenomena that were unknown at the time. What many people do not know, is the earth religions are rooted in Parasitology!

Spirit represents Loa loa and its microfilariae that circulate in the body. This belief is shared with Voodoo as the term 'loa' is a spirit in Voodoo religion.

Water represents Schistosoma, as water is natural reservoir for which the spirit enters the body.

Fire represents Trichomonas vaginalis, as people occupied by this spirit often have a burning sensation.

Earth represents Strongyloides stercoralis as they enter the body from the soil. Some liken Strongyloides to Mother Earth as she can create life in a host without a male counterpart.

Air represents Plasmodium, as it is carried by flying arthropods! And its erythrocytic cycle created periods of suffering and relief, as a reminder Life is a balance of Good and Evil.

If you have read this far, yes I am being silly and having fun, letting the creative juices overflow a bit :-D

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From Old One:

Now in Rochester’s sunny clime

Where I used to spend me time

A-servin’ the majestic Clinic Mayo

Of all that brilliant crew

The finest Doc I knew

Was Dr. Pritt, Diagnostic Mistro

It was Dr. Pritt, Pritt, Pritt

Most skillfull Parasite Gal, Dr.Pritt

Hi! Slippy Hitherao

Diagnosis please, Panee Lao

And be quick, about it. “Lickety split” Dr. Pritt

This noble Parasite Gal

Has a blog that’s really swell

Which has been followed round the globe for many years

She’s now at 555

And if I stay alive

I expect to see 666. Note to Satan, please stand clear

If I’m ever on campaign

Licking boots and water green

I will make tracts to Dr. Pritt at Mayo Clinic

She’s the one to check my blood and stool

Mama didn’t raise a fool

For I’ll surely have a case most parasitic

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Also from Old One:

Zen queries to Madam Ascaris

What is the sound of one hand clapping?

What does a three lip smile look like?

A happy worm is the ascarid

Swims in chyme and squirms like a squid

As happy as she is

She has but one regret

“How do you smile with three lips on the tip of ones head?”

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From Sir Galahad,

5 verses of J.Swift:

Big fleas...

Big fleas have little fleas

Upon their backs to bite' em

And little fleas have lesser fleas

And so, ad infinitum

(Filastrocca di Jonathan Swift

Disegno di Robert Hegner, 1938)