Alan writes:


Babesiosis (speciation to be determined ie B.microti vs B Duncani)

Alan MacDonald MD

Andrew writes:

Kia ora koutou from Pongaroa, New Zealand,  [kee oo-ra cow-tow (rhymes), Pong-ah-roh-ah]

I am a long time listener to TWIP and the rest of the twixiverse. However, this is my first contact. I am a computer programmer by profession but have always been turned on by science and voraciously devour podcasts, audio-books and videos on many subjects – including Vincent’s virology lectures and Dixon and Daniel’s video series. 

Winter is turning into spring here and the temperature is 11°C and cloudy.

My medically untrained diagnosis is Babesiosis. 

My first web searches turned up lots of possibilities including malaria but an article on dog parasites caught my eye and I fell down a rabbit-hole or a mouse-hole would be more accurate a white-footed mouse hole.

So I listed some facts about the disease and checked them off against the information provided by Daniel:


Fever – tick

Hemolytic anemia – tick

Loss of appetite – tick

Dry cough – tick

Liver affected – tick


Vector, a black-legged tick, is endemic in Rhode Island – tick


Can be identified under a microscope, due to characteristic “Maltese cross formations”, so the 90 minute time frame works.  Also Dixon mentioned a microscope.

Usually a self-limiting disease it can be more severe, even deadly, in the immunocompromised. A 70 year old with diabetes might well have trouble clearing the infection.

The disease is common, if under-reported, in the Northeastern US so Daniel would not be overthinking things if this were the case. 

I will wait with anticipation to see if I am right – if not, I have enjoyed learning about Babesia Starcovivi and how can one not love an organism that is also called Nuttallia.

Nā mihi,


Cameron writes:

Hello TWIP experts,

First time writer here, it is a cool 78 degrees near Kansas City, Missouri and is quite literally the calm before the storm as we brace for incoming weather.

I’m going to go with my gut instinct here and guess the patient has presented with babesiosis. Babesia microti is an intracellular parasite, being an Apicomplexan it is of the same family as Plasmodium, which would explain the similar symptoms. Babesiosis often spread by ticks of the Ixodes family, or possibly even our new friend, the longhorned tick. This would explain the elevated bilirubin, burst cells (assuming I heard that correctly) and elevated reticulocytes as Babesia has a tendency to lyse its generous hosts. The patients age and location are both risk factors for infection. I suppose you could have ran an ELISA test to determine the infection, however you could just as easily run an eyeball test and look for two ring trophs within the red blood cells of the patient or the four-pointed merozoite. Treat with chloroquine and azithromycin, or clindamycin and quinine if he’s really sick. 

Even if I’m wrong, I enjoy any opportunity to talk about this fascinating organism, it is a current favorite of mine due to the vast similarities to malaria. I had a fun time presenting a paper on the disease and its effects to a poor, unprepared English major for proofreading before handing it in for my parasitology class.

As an aside, I’m currently wrapping up my last year as an undergrad and am getting ready to enter into a medical lab sciences program in the next year, and hope to find myself working even closer to infectious diseases in the future. I love all of the ASM shows, although I find myself partial to this show and TWIV, and Immune is becoming a quick favorite as well.



P.S. If you have any extra books laying around, I believe my school’s biology department could provide a good home for it.

Cecelia writes:

Dear Doctors,

  The case study you presented reminded me of the case from Episode 156 from August 2018.  Your patient had become infected with Babesia on a camping trip. Since the patient in the current case study had been hiking in Rhode Island I thought he might have unknowingly been bitten by Ixodes scapularis, and become infected.

  I did a Google search of the incidence of Babesia in Rhode Island and according to their state health department, there were 161 cases in 2017 with the majority occurring between June and August. Since the gentleman’s hiking trip was in June this would also point to Babesiosis.

  Since Babesia causes red blood cell destruction, the patient’s anemia could be caused by Babesia.  The elevated liver enzymes and 102 F fever are also symptoms according to PD7.

   The most likely species causing the patient’s illness would probably be Babesia microta. Since there are over 100 species of Babesia, it could be another as well.

  Babesiosis is classified by the CDC as an emerging infection due to its increased incidence.

  The patient could also have co-infection with Lyme Disease or Ehrlichia, 

since they share a common vector. Since this is a parasitology podcast, Babesia is the most likely cause.

  Thank you very much for sharing your knowledge through the podcast as well as the fantastic resources made available to your listeners! I hope I got the right answer to the case study!



Saint Petersburg, Florida 

Courtney writes:

Dear Doctors, 

Hello from Omaha, Nebraska. It is currently 32 degrees celsius and the sun is shining. 

I am submitting my guess for episode 175: Babesiosis. 

Babesiosis was my  original starting point (hiking in the woods = ticks. Ticks=disease). At first I wasn’t completely sold on Babesiosis as the description in Parasitic disease didn’t include anything about losing consciousness and our patient didn’t immediately scream “immunocompromised” (at least to us non medical folks).  Turning to the tables in PD where it lists signs/ symptoms and the associated diseases, I began comparing between Fever/Chills & Malaise. I read through several other diseases: T. cruzi, Toxoplasmosis,  Lymphatic filariasis, and Balantidiasis. Nothing really fit. Either the location was wrong or the patient was missing a few symptoms. 

So, I googled ” parasitic disease losing consciousness,  malaise, and fever”.. And lo and behold: Babesiosis. Even though it turned up a second time, I still wasn’t completely sold on it.. So I read the CDC’s information about it ( Alas!  There is says the elderly are susceptible to it. This still didn’t solve my issue of him losing consciousness.. Until I noticed anaemia and blood pressure mentioned. Low blood/unstable blood pressure can cause loss of consciousness.

At this point I decided to listen to the part in the podcast where ya’ll talk about the new case.. And anaemia popped up along with low platelet counts, other signs of Babesiosis.  

Therefore, Babesiosis. 

Thanks for the amazing work, 

Kevin writes:

TWiP 175 is reminiscent of TWiP 156, a case presented almost exactly one year ago. In that case a Nepalese woman tangled with the exotic diseases of Long Island. Now we see a 70 year old East Indian man with fevers and various hematologic abnormalities. He has the suspicious history of bushwacking in Rhode Island. This puts me in mind of a now archaic (circa 40s and 50s) joke in Chicago that went: 

Q: “Where ya going on vacation?”

A: “The Islands.”

Q: “Hawaii?”

A: “No. Stoney Island, Blue Island, Rock Island.” (Interpretation: three very unglamorous Chicago-area locations)

I suppose that our TWiP 175 patient might reply “Long Island, Coney Island and Rhode Island.”

The solution of TWiP depends on some refreshingly low tech aspects. In our world of cell sorters, nucleic acid manipulations and the whole schmear of automated methods it is nice to hear terminology that describes humble blood smear findings. The entire concept of smear transcends the idea of low tech and even sounds a bit degraded, almost disgusting. I recall the term ‘fecal smear’ being regularly used in parasitology, though it does not appear in PD7. It still makes an appearance in PubMed as a MeSH heading/search term. 

Unstained red cells were described by Swammerdam, Malpighi and Leeuwenhoek in the mid 1600s, but it was not until 1877 that Paul Ehrlich used stains to differentiate blood cells. Polychromasia is a pretty but misleading word that describes the delicate greyish-blue coloration of Romanosky or May-Grünwald Giemsa stained RBCs (in distinction to their normal pinkish coloration.) The word polychromasia misleads because the cells so described are more monochromatic than polychromatic.) Our patient’s polychromasia most likely reflects the high percentage of reticulocytes identified in the automated cell count. The anisocytosis refers to RBCs displaying a variation in size which probably reflects the immature cells (which are larger than mature RBCs) entering the circulation. 

Our patient’s elevated bilirubin, anemia, mildly elevated liver enzymes all point to a hemolytic anemia. 

When energetic I try to construct a differential diagnosis of at least three alternatives. This arbitrary construct may owe something to numerology, remnants of Trinitarian theology, and just plain cussedness. Anyway, it signifies an attempt to forestall ‘premature closure.’ Despite this good intention I will discuss only two alternative diagnoses.

DX 1: Our patient has been to India within the past 1-3 years. It is possible that his fever, low platelets and hemolytic anemia is relapsed malaria due to Plasmodium vivax, which is widespread in India. PD7 states that latent malaria (hypnozoites in the liver which emerge and cause acute malaria infection) can relapse up to five years after initial infection and the Australian Public Health Network cites a figure of 8 to 9 years. Dr. Griffith mentioned that the diagnosis was available within ninety minutes. Such a quick turnaround time is possible using either a rapid diagnostic test (RDT) which detects malaria antigens, or an examination of thick and thin blood smears (films) by an experienced technologist, physician, etc. 

DX 2: Our patient’s rural idyll, his hike in Rhode Island 4 to 8 weeks ago, may have resulted in an Ixodes scapularis bite with transmission of Babesia microti organisms.  The CDC states that the incubation period for Babesiosis is 1-4 weeks. In 2017 there were 161 reported cases of babesiosis in Rhode Island, with most cases composed of males in the 70-79 y/o age group; (compare this with 138 babesia cases in 2017 Suffolk County Long Island). The ninety minute turnaround time could be achieved by the inspection of at least 300 high power fields using 100x oil immersion light microscopy. Serologic or nucleic acid based testing would take longer. CDC recommended treatment: atovaquone plus azithromycin. The combination of clindamycin and quinine is also an option. 

I will submit that our peripatetic patient has contracted babesiosis in the pedestrian fleshpots of Rhode Island. He is admonished to practice ‘safe walking’ in future, using insect repellents and providently tucking his trousers into his stockings. 

Thanks for a great show.


Malaria references:

Howes RE, Battle KE, Mendis KN, et al. Global Epidemiology of Plasmodium vivax. Am J Trop Med Hyg. 2016;95(6 Suppl):15–34.

Cases from just three countries—India, Pakistan, and Indonesia—together represented > 80% of cases globally.

P vivax relapse malaria can occur ‘up to 5 years after the initial infection’ per PD7….re-emergence of erythrocytic form of malaria from hypnozoites in the liver

Chu CS, White NJ. Management of relapsing Plasmodium vivax malaria. Expert Rev Anti Infect Ther. 2016;14(10):885–900. OPEN ACCESS

high transmission of P vivax occurs in parts of India….Manson provided proof in 1901 when relapse was documented 9 months after mosquito induced P. vivax malaria in a human volunteer (his son!) living in a non-endemic setting [9].=9. Manson PT. Experimental malaria: recurrence after nine months. Br Med J. 1901;2(2115):77. long-latency v short-latency vivax ?varies between geographic region and vivax strain—17. White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011;10(1):297. •• This paper describes the different relapse patterns and provides an explanation for the periodicity of P. vivax relapse. {paper summary by Chu et al, authors of the review}……….In endemic settings, recrudescence, reinfection, and relapse (collectively known as recurrence) cannot be distinguished reliably because relapses in endemic areas…..are commonly caused by heterologous genotypes…In contrast in areas where relapse is less frequent (i.e. India ~20%, South America ~30%) vivax malaria is reported more in older age groups

Recrudescence, Reinfection, or Relapse? A More Rigorous Framework to Assess Chloroquine Efficacy for Plasmodium vivax Malaria. , Popovici J Infect Dis. 2019 Jan 7;219(2):315-322

Various types of RDTs on the market

Malaria RDTs detect specific antigens (proteins) produced by malaria parasites that are present in the blood of infected individuals. Some RDTs detect a single species (either P. falciparum or P. vivax), some detect multiple species (P. falciparum, P. vivax, P. malariae and P. ovale) and some further distinguish between P. falciparum and non-P. falciparum infection, or between specific species. Blood for the test is commonly obtained from a finger-prick and results are available within 15–30 minutes. Though there are variations among the more than 200 malaria RDT products on the market, the principles of the tests are similar. 

Babesia references:

Current advances in detection and treatment of babesiosis, Mosqueda J,et al. Curr Med Chem. 2012;19(10):1504–1518.

Microscopy detection methods are still the cheapest and fastest methods used to identify Babesia parasites although their sensitivity and specificity are limited

Lab diagnosis from the CDC—Babesia

If the diagnosis of babesiosis is being considered, manual (non-automated) review of blood smears should be requested explicitly. In symptomatic patients with acute infection, Babesia parasites typically can be detected by light-microscopic examination of blood smears, although multiple smears may need to be examined. Sometimes it can be difficult to distinguish between Babesia and Plasmodium (especially P. falciparum) parasites and even between parasites and artifacts (such as stain or platelet debris). Consider having a reference laboratory confirm the diagnosis—by blood-smear examination and, if indicated, by other means, such as molecular and/or serologic methods tailored to the setting/species.

Babesia diagnosis

Human babesiosis, an emerging tick-borne disease in the People’s Republic of China Xia Zhou et al, Parasites & Vectors, volume 7, Article number: 509 (2014)

Due to the low level parasitemia of babesiosis in the early course of illness, it has been suggested that at least 300 microscopical fields should be reviewed before considering a blood smear free of Babesia…Major problems associated with diagnosing Babesia spp. infections in humans include the general lack of clinical awareness of babesiosis in the medical community, the non-specific clinical manifestations, and the absence of simple and effective rapid diagnostic test (RDT). Convenient, well-evaluated diagnostic tools such as serological tests or molecular biological assays designed for rapid and reliable detection of such pathogens are not yet readily available to most routine diagnostic laboratories [4]. Additionally, conventional laboratory test-results in clinical cases of human babesiosis may be non-specific, such as high levels of transaminases, alkaline phosphatases, unconjugated bilirubin, and lactic dehydrogenase in addition to normochromia, normocytic anaemia, and thrombocytopenia. Occasionally, leucopenia may also be present, probably owing to a tumour necrosis factor (TNF)-mediated immune response similar to that seen in severe cases of malaria.

Akel T, Mobarakai N. Hematologic manifestations of babesiosis. Ann Clin Microbiol Antimicrob. 2017;16(1):6. Published 2017 Feb 15. doi:10.1186/s12941-017-0179-z

Blood Smear References:

Detection of Intracellular Parasites by Use of the CellaVision DM96 Analyzer during Routine Screening of Peripheral Blood Smears, Lori D. Racsa, January 2015, Volume 53:Number 1, Journal of Clinical Microbiology

“A total of 281 slides were analyzed, consisting of 130 slides positive for Plasmodium or Babesia species and 151 negative controls. Slides were blinded, randomized, and analyzed by CellaVision and microscopy for red cell morphology scans. The technologists were blinded to prior identification results. The parasite detection rate was 73% (95/130) for CellaVision and 81% (105/130) for microscopy for positive samples…

The percentage of positive specimens detectable by CellaVision (73%) approaches results for microscopy on routine scan of peripheral blood smears for red blood cell morphology.” Authors summary: “This study demonstrates that CellaVision has the potential to detect intracellular parasites in routine screening of blood smears for RBC morphology. In addition, the software is a valuable resource for storing images to be used for educational purposes, including training technologists in the detection of intracellular parasites.”

The above study by Racasa et al is a feasibility study of automated parasite scanning. It is important to note that this technology is not approved for such use. This lab (U Texas SW Med Ctr/Parkland) does a manual (human) slide screen for RBC morphology on every CBC ordered in the ER…this involves examination of at least 10 microscope fields at low power (time estimate=60 seconds). In contrast, a formal malaria screen involves the preparation of 2 thick and 2 thin smear slides, examination at oil immersion 100x power, 300 fields 

Gulati G, Song J, Florea AD, Gong J. Purpose and criteria for blood smear scan, blood smear examination, and blood smear review. Ann Lab Med. 2013;33(1):1–7. 

This is a good, clearly written explanation of what goes on in the hematology lab regarding manual blood smear examination. 

“Currently avail­able automated hematology analyzers do not generate any re­portable information about the presence of many of the red cell abnormalities (elliptocytes/ovalocytes, target cells, sickle cells, acanthocytes, echinocytes, SC crystalloids, stomatocytes, tear drop cells, rouleaux, Howell Jolly bodies, Pappenheimer bodies, basophilic stippling, intraerythrocytic organisms, etc), white cell abnormalities (Auer rods, toxic granulation, toxic vacuolization, Dohle bodies, hypogranular/agranular granulocytes intraleuko­cytic organisms, etc), and platelet abnormalities (platelet satellit­osis, abnormal granulation, and hypogranulation/agranulation bizarre platelets). “

A blood smear review —BSR may be requested by the clinician or initiated by the lab­oratory staff …many reasons to order a BSR, one of which is suspicion of parasitic infection

Contributor’s comment: It was very difficult for me to find a good, solid history of the blood smear.

A Short History of Histopathology Technique, Michael Titford, The Journal of Histotechnology I Vol. 29, No. 2 1 June 2006….very little except for mentions of staining advances (Giemsa, Romanovsky)

History of Microtechnique by B. Bracegirdle (unable to access). Who is named ‘Bracegirdle??”….it was the name of a Hobbit family

The Human Red Blood Cell, Cleveland Clinic Journal of Medicine, 1941, Russell Haden..April;8(2):111-134

Unstained red cells were described by Swammerdam, Malpighi and Leeuwenhoek in the mid 1600s, but it was not until 1877 that Paul Ehrlich used stains to differentiate blood cells. 

Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease 

Cleveland Clinic Journal of Medicine. 2008 July;75 [7]:521-530 

Adewoyin AS, Nwogoh B. Peripheral blood film – a review. Ann Ib Postgrad Med. 2014;12(2):71–79. 

Informative and refreshingly direct review of this deceptively simple technique. From the University of Benin Teaching Hospital in Nigeria. 


Smear, Schmear….

Now Shmear This, ON LANGUAGE, The Jewish Daily Forward by Philologos | Fri. Feb 10, 2006

TWiP is schoolin’ me in the 3 Re’s- recrudescence, relapse and recurrence:


“Recrudescence” is the term for recurrence of infection with all malaria species including P. falciparum, P. malariae and P. knowlesi, which lack hypnozoites. This occurs when the infection (unless a new infection) has persisted in the blood at undetectable levels and then becomes detectable again. P. malariae can persist as a low-level, normally asymptomatic erythrocytic, infection in humans for up to 40 or 50 years.

The Popovici reference (2019) defines recrudescence as “real treatment failure.”

2. relapse:

Reactivation of dormant parasites from the liver. (Popovici).

3. reinfection: 

A new infection due to a new infectious mosquito bite.

Joel writes:

Hello!  I haven’t made a guess on a diagnosis since TWiP 99 so I thought I’d give it another go.  I’m not very well versed with parasites other than what I’ve learned on the podcast so it took me a while to get to a point where I’m confident enough to try to make a guess.  I love the challenge that you pose with each of these and I had fun digging through the internet to put the clues together.  

Initially, I thought the signs of anemia sounded like malaria, but you mentioned that he hadn’t left the country in a couple years so I figured that wasn’t it.  I then chased a few ideas that eventually led to dead ends with various worms and flukes. But finally, I came across something I was not aware of that causes hemolytic anemia as well as some flu-like symptoms, is endemic to the northeastern US, and the key for me was that it is spread by tick bites.  This clicked for me since your patient had been hiking in Rhode Island shortly before having symptoms. So my diagnosis is that he was infected by Babesia microti. From my research, it seems that the primary method of diagnosis is by simply viewing the parasites in the blood cells from the blood smear so I’m not completely sure what additional test would be ordered to confirm.  I see that PCR is used, but as was discussed, that would be difficult to get done in 90 minutes. Perhaps an antibody detection assay that would be able to get a quick confirmation. That’s my best guess anyway. As for the treatment, I found 2 main options that appear to be relatively equal in efficacy. First is a combination of atovaquone and azithromycin, and the other is a combination of clindamycin and quinine.  Both treatments are given for about a week or two.  

Thank you so much for doing this podcast! I really enjoy learning about a subject that doesn’t get the attention it probably deserves.  And even if I’m wrong, it’s still a fun exercise and I always learn something new, which is more important anyway. I’ll try not to wait so long this time before sending in another diagnosis.  Have a great day!

Jim writes:

Dear Twippers of the Bite Parasitic:

My guess is the 70 year old gentleman was bitten by an infected tick while hiking in Rhode Island and has come down with a serious case of Babesiosis.

Thanks to a quick diagnosis and intervention by Dr. Griffin, followed by a course of select antibiotics, he should recover well provided he still has his spleen.  Let us all hope for a speedy recovery in any event. 

I listen to TWIP frequently but this is my first time guessing. 

Great podcast as always.

Take care,

Jim in Vancouver

Peter writes:

A cháirde TWIP,

Just a quick guess as I have recently started a new lecturing position in the Institute of Technology Tralee so I am busy preparing lectures and brushing up on my veterinary anatomy. Although I miss my colleagues in Trinity College Dublin, I am delighted to have gotten a position not so far away and to keep collaborating with them. Also looking forward to studying parasitology in the waters and the wilds of Kerry (Southern Ireland). I was also able to keep my practical parasitology teaching position with the Royal College of Surgeons Ireland (RCSI) and as a result of that I am now sending this email from RCSI Bahrain. I was lucky enough to have breakfast with Prof. Samuel McConkey (Head of the Department of International Health and Tropical Medicine at the RCSI) this morning and like any self-respecting parasitologist, we soon got to talking about animals trying to eat us from the inside. I brought up this month’s case study and Prof. McConkey suggested I consider Babesiosis. Looking into Rhode Island prevalence I see a seroprevalence of 20-25% so although I do not have time to read deeper, I am happy to put my money on that. Prof. McConkey also spoke of the importance of a differential in successfully treating a patient and what else you might consider for this patient. Based on that discussion I would include Strongyloides and P.vivax.

I have already won a book, if not sent already I would be grateful if the delivery address be changed to that below.


Peter Stuart

Biological & Pharmaceutical Sciences

Institute of Technology Tralee South Campus

Dana writes:

Hello TWiP professors, 

We believe the most likely diagnosis to be babesiosis because of the patient’s history of a hiking trip 1-2 months prior, high fever, hemolytic anemia, thrombocytopenia, and elevated liver enzymes. A treatment option would be atovaquone with clindamycin.


WesternU Global Health Track Students: Steven, Alex, Vickie, Irene, Chris, and Dana

Peter writes:

Good day dear Drs of TWIP

Judging from the website I might be just in time with this guess. Unfortunately (?) exciting developments in the world of genomic epidemiology have kept me away from Parasitic Diseases 7th Edition and thus a chance to hazard a guess for most of this month. Hopefully this email manages to sneak in before episode 176 is released.

The 70 year old presenting with fever and cough might be suffering from babesiosis, caused by the tick-borne parasites of the genus Babesia. In the North-East USA the pathogen of interest is often B. microti, spread by the deer tick Ixodes scapularis. This disease is associated with anisocytosis, increased reticulocyte percentage (a symptom of hemolytic anemia), thrombocytopenia (low platelet count) and elevated bilirubin. It is known to be more severe in the elderly due to their weaker immune symptoms. Cough is not a common symptom but can be present in some cases. The history of hiking could suggest exposure to the ticks that carry this parasite, but time to onset is typically weeks, not months. The 90 minute test that Dr Griffin reports could be an antibody test; these are available for detecting B. microti. Treatment for severe illness is, according to PD 7, intravenous clindamycin combined with oral quinine or IV quinidine.

Another possibilities is malaria, specifically that caused by the parasite Plasmodium vivax. He has a background in India, one of the parts of the world where P. vivax is prevalent (a recent map is in Gething et al 2012, presumably P. vivax was more prevalent in India in the past) and P. vivax malaria can recur many years after initial infection. The elevated bilirubin also suggests malaria but the increased percentage of reticulocytes suggests to me that this is *not* malaria, since P. vivax destroys these young red blood cells, however Singh et al report a case of Plasmodium vivax infection with autoimmune hemolytic anaemia that had elevated reticulocyte count (Singh et al 2012) Again the 90 minute test could have been an antibody based rapid diagnostic test of which there are several for malaria.

I tend to think the babesiosis diagnosis is more likely than malaria though.


Gething et al  ‘A Long Neglected World Malaria Map: Plasmodium vivax Endemicity in 2010’  PLOS Neglected Tropical Diseases 2012

Singh et al ‘A case of Plasmodium vivax malaria associated with severe autoimmune hemolytic anaemia’ Annals of Tropical Medicine and Public Health 2012;year=2012;volume=5;issue=2;spage=133;epage=136;aulast=Singh


from Cape Town

Caitlin writes:

Dear Parasitriarchs,

Forgive me, fathers, for I have sinned. It has been five months (!) since I last wrote in to TWiP, and since then, I confess that I have been cheating on you with other podcasts. But is it really infidelity if they’re also on

When I first listened to this case, my mind immediately went to relapsing malaria. Although he had not visited India for two or three years, that is well within the window of time for hypnozoites to wake up. However, I would also expect for there to be relapses every few months if that were that case. Furthermore, PD6 tells me that Plasmodium vivax typically infects a relatively low proportion of erythrocytes, and usually has only one or so per cell. Thus, I looked further. 

The extensive f*&kery that showed up in the blood smear made me think of the spleen, and the hiking trip in Rhode Island made me think of ticks. I would hazard that this gentleman has babesiosis. He fits the typical profile given of a high fever, loss of appetite, generally feeling like crap, and, given that he is more or less immunocompetent, improvement within a reasonable period of time. I note that infection of the erythrocytes can reach a whopping 80%, which is frankly quite rude, even by the standards of parasites. It is also fairly easy to diagnose – with PCR, or by looking for the Maltese Cross on a thin blood smear. I’m hoping for PCR, since even I know how to do that. Treatment is either a combination of atovaquone and azithromycin, or clindamycin and quinine, which has the advantage of also working if my initial guess was correct after all. So, without access to Daniel’s test, I’ll cover my butt and pick that one for my imaginary patient.

Caitlin, in Seattle, where it’s supposedly 14 degrees Celsius, but I don’t believe them.

Philip writes:

Dear Esteemed TWIP Team,

You had an interesting case study for TWIP 175.

I’m going to guess that Dr. Griffin ordered a parasite blood smear, and the patient was found to have babesiosis.

I don’t think this was a malaria relapse case, only because I have had friends who were born in India and endured malaria, and they seemed keenly aware when they had it again. Also, the fever history described for the patient did not seem to fit malaria. 

The 1-2 month interval between the patient’s tick exposure in Rhode Island, and the onset of symptoms is very interesting. Back in the late 1990s I worked with the New York State Department of Health and reviewed dozens of babesiosis cases on Long Island. It was difficult to judge when onset of symptoms occurred following a tick bite since so many of the cases were continually exposed to deer ticks. The literature generally considered babesiosis onset to occur 1-3 weeks after a tick bite, and a number of cases I reviewed had tick bites in that time frame. However, epidemiologically we found babesiosis onsets peaked from mid-July through mid-August, lagging a good month behind the deer tick nymph season and Lyme disease rash diagnosis peak.  We suspected median incubation could be longer than typically stated. A 2011 Annals of Internal Medicine review of transfusion associated babesiosis cases (where the Babesia exposure timing is pinpointed) found the median interval from transfusion to symptom onset was 37 days.1  Perhaps tick transmitted Babesia infections fall along those lines too.  In any case, Dr. Griffin’s patient demonstrates how more distant exposures need to be considered.

I would also recommend Dr. Griffin and other clinicians consider babesiosis for any febrile patient with deer tick exposure in a babesiosis transmission area who also has: hemolytic anemia, low platelets, and high monocytes. I worked at a hospital on eastern Long Island that used those three hematological criteria to trigger a reflex parasite smear. We found dozens of babesiosis cases that way. The reflex likely sped up administration of appropriate therapy, and curbed unnecessary antibiotic administration. Just something to consider.

I enjoy the TWIP podcasts immensely, and I am astounded you all find the time to do them.

Be great.

– Philip

Long Island, NY

1.  Herwaldt B, et al. Transfusion-Associated Babesiosis in the United States:

A Description of Cases. Ann Intern Med. 2011;155:509-519.

Kim writes:

Dear TWIPsters I have only recently been introduced to your dynamic and totally absorbing podcasts. I am a travel health nurse living in Torquy, England. Mother of 5 now grown up children with a fascination for all things parasitic. I have a degree in medical microbiology and recently completed a diploma in tropical nursing at Liverpool school of tropical medicine. I am new to parasitology but will make an educated guess at this week’s remote location gentleman. To be honest I have found this one a bit tricky so possibly not a good case to start with!!! But here it goes! Looks like this chap has contracted the disease Babesiosis. My reasoning is as follows:

Babeosis is a disease caused by the invasion of the red blood cells by the protozoa of the genus Babesia resulting in an febrile haemolytic anaemia. In America most human cases of babesiosis are due to Babesia microti. These parasites are spread by the tick Ixodes scapularis (black legged ticks or deer ticks). It seems to me that this gentleman has picked up a tick bite when trekking previously. Malaria is unlikely as he hasn’t returned to India for 2-3 years. Blood film indicates a haemolytic anaemia with other examinations unremarkable. Most cases of babesosis are contracted in the United States and Europe. Haemolytic manifestations of the disease are common namely pancytopenia, splenic rupture , DIC or even HLH. In this case the gentleman has evidence of haemolytic anemia in the blood film with acute onset fever. Typically liver enzymes are only mildly raised. 

Tickborne transmission is typically in certain regions of the US namely Northeast and upper Midwest hence Rhode Island where this gentleman has previously been hiking is endemic for these insects. Daniel asked for one test which was conclusive for his diagnosis of this condition. I believe he asked for a blood film to be done specifically looking for the intracellular parasites in the red blood cells. Typically seen on the film within the red blood cells is a structure called a “Maltese cross”-four merozoites budding asexually but remaining attached.

Treatment is with atovoquone plus azithromycin or clindamycin plus quinine. Atovoquone-750mg B.D plus azithromycin day 1-500-1000mg orally with 250-1000mg on subsequent days. Clindamycin 600mg T.D.S or 300-600mg IV Q.D.S plus quinine 650mg orally T.D.S.

Sorry if this is wrong but have really enjoyed researching it. Can’t wait to hear your next podcast!!!

Best wishes from Torquay, Devon England!

David writes:

Dear Esteemed Professors,

I have been an avid follower of the TWIP podcast for a couple of years now and I want to thank you for such an entertaining and educational show.

I love the rapport between the three of you and in particular I love the cases that Daniel brings to test our knowledge.

I worked for the Public Health Laboratory Service in the UK for 22 years and a large part of that time was spent working in the enteric diseases laboratory. As part of the daily routine in our enteric laboratory we would pour over stool samples looking for intestinal parasites.  Our laboratory is in the beautiful North West of England, quite close to the Lake District and we are well served with clean water and functional sewage services so we found mainly Giardia and Cryptosporidium and very little more exotic than that.  We were always excited to receive external quality control samples for faecal parasitology and competed to find a wider range of more unusual parasites.

I had a second career in biotech working for a succession of incrementally larger US biotech companies in business management but now I have started my third career and taken a wonderful job at my alma mater, The University of Central Lancashire, teaching our undergraduates the wonders of medical microbiology.  

Stimulated by your wonderful podcasts I have started a parasitology club and we will tackle the fascinating challenges set by Daniel as a group activity.

 This is my first crack at winning a signed copy of your wonderful book or at least chipping my opinion in to the case for TWIP 175.

The haematological profile suggests a haemolytic anaemia, supported by the raised reticulocyte count, red cell hypochromia and microcytosis.  I believe the low haemoglobin levels and general anaemia may have induced the collapse. With the patient being of south Asian origin and having been a relatively frequent visitor to the region I immediately concluded that this was obviously a kind of malaria, which may have reactivated due to failing immunocompetence due to age. I found in PD7 that malaria species other than P.falciparum may produce hypnozoites which can lie dormant in the liver for up to five years, so I clung to the malaria diagnosis for a little longer.  Many of the clinical signs, high fever, thrombocytopaenia, anaemia, and altered liver function could fit with this diagnosis.  

Somehow I was uneasy about the conclusion and distracted by Daniel’s comments that he was not overthinking the diagnosis and that a single test was all that was needed to confirm the diagnosis in around 90 minutes.   I hunted PD7 for more options and came across the section on babesiosis. This was a parasite that I had not encountered in my laboratory days, as it is normally the domain of a haematologist rather than a poo-ologist.   A biblical light shone on the page and a choir harmonised in the background… The clinical signs for the case were consistent with babesiosis and data from the CDC confirmed that the geographical distribution was consistent with the gentleman living in the north east of North America.  His recent hiking trip to Rhode Island could have exposed him to being bitten by the black deer tick, Ixodes scapularis that can transmit Babesia microti.  Data from CDC shows that Rhode Island has the highest incidence of babesiosis in North America with 16.3 cases per 100,000 population and the gentleman was living in New York, which is in the top 5 with 2.4 cases per 100,000. 

So I am saying a prayer and making the sign of a Maltese cross and putting my a hard earned British Pound on babesiosis as the diagnosis for this pyrexial and anaemic Indian gentleman.

The single laboratory test that Daniel will have ordered would have been a Giemsa or Wright stain on a thick and thin peripheral blood film.  The haematologist would have been looking for characteristic ring forms in single, pair, or the characteristic tetrad ‘Maltese cross’ formation.

Treatment for the infection as recommended by CDC is Atovaquone with either Azithromycin or Clindamycin and Quinine. 

The first meeting of our parasitology club will consider this case and the new challenge coming in TWIP 176.

Thank you again for your fantastic podcast.

David Wareing

University of Central Lancashire

Lisset writes:

Dear TWiP professors, 

Greetings from sunny Florida! I am hoping this email still makes it on time for this month’s case study. I really want that signed copy of your Parasitic Diseases book. Last time, I did not win so I am going to keep trying! I could just buy it, but this way is so much more entertaining. 

I am going to keep it short so here is my guess for this case: Babesiosis. The main clues that got me to this parasite were (1) hiking trip in North America not long ago, (2) main symptom was fever and anemia, and  (3) patient had relative good health but included in high risk group due to diabetes and age. Also the fact that Daniel said to keep it simple. Since the last paper was on Malaria, when I listened to the presentation of the case study my mind went straight to Babesia. By the location, it is most probably B. microti. I remember my professor stressed a lot the differences and similarities between these two protozoans. 

My last guess is that the “quick” test was an antibody testing to find specifically B. microti. Am I close?

Thank you so much for your amazing podcast and keep up the good work! 

Best regards, 

Lisset Sánchez (she/her/hers)

University of Michigan, Class of 2019

Bachelor of Science in Microbiology