Case guesses:
Anna writes:
Hello, TWiPsters!
First, thank you for your excellent work on this podcast. I am a virologist-in-training, currently a graduate student in the laboratory of Dave O’Connor at UW-Madison, but I love all things related to the study of infectious diseases and have really enjoyed getting regular exposure through you all to the world of parasitology. So, thank you very much!
There has been one consistent issue with the show, though, that has really been quite disheartening. All the “heroes of parasitology” are men. And, additionally, I’m pretty sure they’re all white men. I really cannot emphasize enough how discouraging it is, as a female trainee in science, to consistently hear only males praised as heroes of an entire field (with, of course, the wonderful exception of Miriam Rothschild sent in by a listener a while ago). It is really hard to believe you belong in a field if you are never presented with a role model who is anything like you (and the same is true for people of color in STEM). I also found it hard to believe there could be no great women in the whole history of parasitology, though, so I went searching for some. And I found them!
Dr. Eloise B. Cram (https://en.wikipedia.org/wiki/Eloise_Blaine_Cram), the first woman president of the American Society of Parasitologists and a leader in the study of schistosomiasis, would make an excellent hero.
Another hero is Ann Bishop (https://en.wikipedia.org/wiki/Ann_Bishop_(biologist)), who is best known for her comprehensive study of Plasmodium. Ms. Bishop (who was apparently never officially awarded a doctorate, despite having completed one, because Cambridge did not award doctorates to women at the time she completed hers) also discovered several new parasitic species, was one of the first female fellows of the Royal Society, and founded the British Society for Parasitology.
A third hero is Dr. Susan Lim (https://en.wikipedia.org/wiki/Susan_Lim_(parasitologist)), a Malaysian parasitologist who specialized in the study of the class of parasitic flatworms the Monogenea. Four species of monogeneans and one monogenean genus have been named for Dr. Lim in honor of her pioneering work on these organisms.
There are quite a few other brilliant and influential female parasitologists I’ve found over the past day of searching.
I’ve combined all the short biographies of Dr. Cram that I could find online and have attached that document; feel free to use it or adapt it if you’d like. I can work on writing up the others I mentioned and the others I’ve found, too, and I’ll keep looking for more.
I figured I’d take a shot at the case while I’m at it. The young man with fever, pain in the right upper quadrant of the abdomen, and a single fluid-filled lesion in the liver is most likely suffering extraintestinal amoebiasis due to infection with Entamoeba histolytica. The severe right upper quadrant pain, along with an enlarged liver and a fluid-filled cavity on ultrasound, indicate an amoebic liver abscess, and the aspirated fluid would likely be of the brown “anchovy paste” variety. The pleural effusion is likely due to perforation by the abscess of the diaphragm. The intercostal tenderness is characteristic of extraintestinal amoebiasis. Severe infections can result in eosinopenia, as seen in this patient. The elevated white count with a left shift, the fever, and the general body aches are also all signs of a severe and systemic infection. The elevated alk. phos. is a sign of liver damage from the abscess. Diagnosis would be done by serological testing and imaging, like the ultrasound visualization in this case, and the appearance of the aspirated fluid would help confirm the diagnosis. Metronidazole is the drug of choice for both intestinal and extraintestinal E. histolytica disease, and alternative medications include nitazoxinide and ornidazole. The patient likely acquired this infection from a less-than-clean water supply.
The differential for this man includes a hydatid cyst in the liver due to Echinococcus granulosus, which would also result in a fluid-filled hepatic lesion and liver enlargement, though the rest of his symptoms fit better with E. histolytica. An enlarged liver and a pleural effusion could also indicate metastatic cancer, though a fluid-filled liver cavity which can be aspirated makes this less likely. A cystic lesion in the liver could also be a hemangioma or a hamartoma, but neither of these fit with the rest of the clinical picture. Credit for the above information goes to my med school classes taught by the wonderful Dr. Laura Knoll, to Sketchy Microbe (an online memory aid device used by medical students to learn their microbes), and to Parasitic Diseases 6th edition. If my diagnosis is wrong, credit for that can only be given to me.
The weather in Madison is a surprising 73 degrees Fahrenheit, with intermittent showers and sunshine. Thanks again for the wonderful podcast!
Anna
Eric writes:
Hi TWIP team!
I’ve been a lurker for over a year now, enjoying listening to cases but never have had time to write in….until now!
Here are my thoughts for the case of the gentleman in his 20s in India:
At first when you mentioned the date palm liquor, my mind went immediately to Nipah…then I remembered this was TWIP not TWIV (but was reminded of the new cases in India from the recent TWIV 504), and oh also the clinical signs don’t fit at all. Damn Type 1 Reasoning!
Once I got over that red-herring though….my top ddx is entamoeba histolytica creating a liver abscess. Based on PD6, there are a few pieces of evidence that fit with our patient: most common extraintestinal site is the liver, creating solitary fluid-filled abscess, then the lungs (the two locations affected in our patient). Nearly half of patients w amoebic liver abscess have no hx of amoebic colitis (nor did our patient), and few patients have peripheral eosinophilia and may even become eosinopenic (I suspect related to inflammation from the abscess, which would be consistent with our patient’s elevated white count and left shift), plus the “intercostal sign” of tenderness on palpation btwn the ribs.
Thanks for a great show!
Peter writes:
A cháirde (ah khawr-djeh) TWIP,
It has been some time since I emailed a case study answer as the TCD parasitology group have been traveling, writing up, setting up new experiments etc. Although it was still not possible for us to meet up for this week’s case study, I will brave it alone. I did want to thank Vincent for tweeting when the podcast was recorded, it was very useful at the time. I believe the patient has a hydatid cyst caused by the parasite Echinococcus granulosus. The aspiration of the cyst made me consider that perhaps the cyst was not of parasitic origin. As is described in PD 6th edition ruptured cyst contents can seed the area, and invade new tissues to produce second-generation hydatid cysts. However, later in the section it states that Puncture, Aspiration, Injection, Re-aspiration (PAIR) can work well with adjuvant anthelminthic chemotherapy started one month prior to performing this procedure. The hydatid liver cysts I am more familiar with are Hydatigera taeniaeformis cysts on woodmice livers. As I’ve only ever seen it on dead mice PAIR is not used, but I do find opening the deceptively small cyst and slowly drawing the long larvae from it, a great way to engage/gross out the public in outreach activities. I did this recently at the Probe, Research Uncovered night at TCD along with some other members of the TCD parasitology team. We wrote about it in a recent blog post that can be read here if interested.
I also wanted to write as it was mentioned on TWIV that Dickson it finding it hard to find female parasitology heroines. I found that surprising as I have always been lucky to work with and be mentored by inspirational female parasitologists. I would suggest Eloise B Cram (https://www.nal.usda.gov/exhibits/speccoll/exhibits/show/parasitic-diseases-with-econom/item/8196) . I spoke to lab mate Maureen Williams about this too and she pointed me towards a great twitter account, women in parasitology and the sad fact that there are only eight women parasitologists on Wikipedia. On that note it would be great to see some female authors on the next edition of Parasitic Diseases.
Finally I know you have moved on from parasitic poetry but my favourite is this short poem by William C Campbell.
Onchocerca
I don’t need your goddam eye!
All I need is a bit of skin
big enough for me to scatter
a few larvae in,
just enough to make it probable
that there’ll be a pick-up
and delivery.
Don’t look at me that way –
I don’t need your goddam eye.
Slán (slawn),
Peter Stuart,
@TCDParasitology
Sophia writes:
Dear Professors
I will keep this short as I think you’ll get loads of answers to this.
I think the patient is suffering from Chagas disease (only because you spent so much time talking about this on previous episodes I think I got it now!)
treatment: according to your book there are 2 drugs: nifurtimox and benznidazole. However, you do say that once heart involvement begins it might be too late (so then, what? I am assuming you did treat the patient)
diagnosis: observation of parasites through Giemsa staining and PCR.
I think your book is great–congratulations and thank you for making it available for free.
I also have a question: how does this disease affect the patient’s everyday life? in terms of physical activity? (what if they go jogging for example)
I’ve been listening since 2011 and still enjoying.
greetings from Greece
John writes:
Hello from the ever changing weather of Flagstaff, Arizona!
It definitely sounds like this poor gentleman has been infected with Trypanosoma cruzi, better known as Chagas’ Disease. With him being from Brazil as a farmer it would make sense that he would come in contact with the reduviid bugs that can carry this disease.
With the severity of the damage to the heart it sounds like this infection could be the chronic form of Chagas’, as the acute version typically infects younger children and even then do not show nearly as much heart damage. Blood testing may find some trypomastigotes, but if it is the chronic version a follow up using xenodiagnosis could be beneficial in identifying the specimen, if time allowed. I did also see that PCR nowadays could be a viable means to help confirm the diagnosis, and would definitely “bug” the gentleman less.
As for treatment, the drug Benznidazole has been known to have success in combating Chagas’. However, I am not entirely sure if that can help the chronic version entirely, considering it is definitely more intracellular than the acute version. The only treatment I have found through my readings is a heart transplant, but then again my parasitology book from college is older and google scholar has failed me in this arena.
I truly hope that he was able to have a less invasive means of treatment.
And of course, thank you for your amazing podcast.
Suellen writes:
Hey TWIP Trippers! I am calling you that because you kept me company today on my drive to Conyers, Georgia, from my home in Roswell. I’m here this weekend for a big horse show at the Georgia International Horse Park. Having TWIP on in the car made me feel like I was on a road trip with my three favourite docs — Vincent, Dickson, and Daniel. Instead of playing “Spot the License Plate,” though, we played “Spot the Parasite!” Great fun traveling with you all.
By the way, I received my copy of PD6 a few weeks ago, and am so proud to be an owner of an autographed copy! But I still find I use the PDF more, since it’s more easily searchable.
For this episode’s case, I used my search capabilities, but already thought I knew what our patient from Brazil has: I am guessing Chagas Disease, caused by the protozoa Trypanosoma cruzi. I remember hearing on a previous TWIP or two that T. cruzi is a leading cause of cardiomyopathy, and that it is common in Brazil and Argentina. PD6 supported my initial diagnosis, even echoing Daniel’s diagnostics with ” Right bundle branch block is typically the earliest disturbance evident on ECG.”
Now, for how we would confirm the diagnosis — well, here I have to rely on PD6, because of course I’m not a physician. The book says that for chronic, later-stage Chagas, which this patient has, confirmation is made based on detection of serum IgC. PD6 goes on to say, “Since no currently available tests for Chagas serology have the required specificity, a diagnosis is based on two positive diagnostic serology tests.” It also says that the parasites can be identified microscopically.
Unfortunately, once the cardiomyopathy has set in, there is not much that can be done to “cure” the disease. PD6 mentions nifurtimox and benznidazole, but does note that both can have very serious side effects. I would be interested to hear what this patient’s prognosis is, and whether there are any better treatments available.
Adil writes:
Dear Doctors,
I know I have been writing a lot lately but this is the one meant to be read. First I wanted to offer one theory for how the dogs are getting Dracunculiasis. One prevailing theory has to do with the potential of various fish species to serve as paratenic hosts for Dracunculus. This is why the Carter Center’s control program emphasizes techniques such as thorough cooking, burial of fish entrails and preventing entrails consumptions by dogs. With regards to finding out dogs were an alternative host to humans that was I think a major disappointment to everyone who rightly lauded the eradication efforts success in reducing case numbers to the extent it did and who had hoped President Carter’s stated goal of outliving the worm would have already come to pass or would do so soon.
Regarding the diagnosis of the latest case it sounds to me like Chagas. The patient is Brazilian and as you have noted in the past this condition is inextricably linked with that nation to the extent it is commemorated on a stamp. Switching from my medical historian’s reasoning to my more clinical one the patient has cardiomegaly and right bundle branch block known sequella of Chagas. You had asked for differential and treatment as well. Differential would include chronic hypertension which may result in hypertrophy, rheumatic heart disease and myocarditis. As for treatment if it is chagas the Mayo Clinic treatment guidelines state that ” benznidazole and nifurtimox may be of benefit”. After the parasite is killed the cardiac and other symptoms can be dealt with. The former may be treated with medications, a pace maker as the patient has already received or even a potential transplant. For the digestive symptoms diet modification may be necessary and medications including corticosteroids may be utilized. A severe case may require surgery.
Thank you once again for the book. In light of the win future submissions at least for now will be for learning and pride alone.
Carrie writes:
Dear TWiP Advisors,
The Brazilian gentleman has a fairly clear-cut case of Chagas disease, caused by the American trypanosome T. cruzi (not to be confused with the American tetrapod Ted Cruz).
The combination of South America, heart problems, and parasites immediately brings this beastie to mind, and the specific symptoms, notably the observation of right bundle branch block on the EKG, are consistent with chronic Chagas disease. (The initial acute phase may well have passed unremarked, as the symptoms are often mild and non-specific, and are followed by an asymptomatic period.)
The diagnosis could be confirmed by serology testing (a first positive test should be repeated due to the test’s lack of specificity.)
Unfortunately, treatment is more difficult than diagnosis. While benznidazole and nifurtimox are most commonly used, they are of limited value after years of chronic disease, and will not reverse the damage to his heart. Since these drugs have many side-effects, it would be better not to prescribe them if they would not help. Rather, the immediate focus of treatment should be managing the symptoms.
The heart is fairly important, so managing his condition is critical. One possibility is amiodarone or dronedarone, which are antiarrhythmic drugs that, conveniently, are also effective anti-T. Cruzi agents. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817734/). This can be used in combination with an implantable cardioverter defibrillator. Clinical data for the effectiveness of amiodarone alone is not available yet, but it seems that it might be the best option in this case.
Some Chagas patients eventually require a heart transplant. That would probably be jumping the gun for now, but might lie in this patient’s future.
Our conclusion is that Chagas disease really sucks, and neither of us is going to South America, ever. If we should win the textbook, please donate it to a worthy cause, or an unworthy one if you prefer. Caitlin would like a shot at the poetry book, though.
This was another transatlantic cooperative effort between Carrie, in Newcastle upon Tyne, England, and Caitlin, in Waterloo, Ontario, Canada.
P.S. No offence to Mr Cruz. We just can’t unsee it (and now neither can you.)
P.P.S. We almost forgot: Rrrrrreduviido!
Chris writes:
Dear TWIPsters,
The symptoms described quickly bring to mind chronic Chagas disease. Circulating trypomastigotes are only seen in the acute phase, so serological testing is recommended for diagnosis of older infections. A number of other parasitic infections show heart involvement and are nicely reviewed (1), but none fit the particular symptomology as well as American trypanosomiasis.
Transmission is of course through the excreta of reduviid bugs, either introduced into the bite wound or a sensitive area like the eye. I had always been told these bugs favor dwellings with cracked or wooden walls, so they’re unlikely to be seen in more modern houses.
The only drugs available for treatment are benznidazole and nifurtimox. Side effects are common with both drugs and are more pronounced in older patients. Therefore, the decision to treat needs to be weighed against likely adverse reactions, and anti-parasitic treatment may not be recommended at all. The lesson here seems to be that early recognition of infection is critical, but with so many infections being initially asymptomatic, how reliable is this? It’s astounding how a bug bite can irrevocably change someone’s life.
(1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863361/
On a side note, two episodes ago you mentioned the phone-based diagnostic tool, the LoaScope. The procedure involves taking up a blood sample with a capillary slide, which sits flat beneath the phone’s camera and the device’s microscope lens and is advanced by a servo, taking readings from multiple fields. We’ve been working with a modification of this tool for the quantification of heartworm microfilariae, lovingly dubbed the DiroScope, a short demo of which you can see here (2).
(2) https://youtu.be/4OMThVWvFRI
All the best,
Chris
Athens, GA
Emily writes:
Hello TWiP Team,
I would like to hazard a guess for the case study presented in TWiP 160, the man from Brazil with cardiac pathology. I have been a long-term, if intermittent, TWiP listener before having to stop listening to podcasts for a while during veterinary school, an internship, and an internal medicine residency. I recently started listening to TWiP again while working on DNA extractions for my PhD investigating control options for bovine leukemia virus in dairy cattle in North America. It has been a welcome distraction during pipette-intense but intellect-optional labwork.
Based on my almost total lack of human medicine experience – but with the great help of the electronic copy of Parasitic Diseases 6th ed and Dr. Google – my top differential for this patient would be chronic infection with Trypanosoma cruzi, commonly known as American trypanosomiasis or Chagas Disease. This parasite is common in the man’s native Brazil, where he likely became infected prior to immigration to the USA. As it is the leading worldwide cause of cardiomyopathy (an interesting counterpoint to the developing world’s overabundance of lifestyle and diet-related cardiovascular disease) and as this is a parasitic diseases podcast, it would also outrank other differentials related to genetic or toxic causes of cardiomyopathy.
As an internist, however, my differential list would not be complete unless I listed a few “zebra” parasitic causes that also affect the heart, courtesy of a nice review paper I have attached below: Trypanosoma brucei rhodesiense and gambiense, Toxoplasma gondii, Taenia solium, and Trichinella spiralis. (Sidenote: in veterinary medicine we also use the phrase “if you hear hoofbeats, it’s likely horses and not zebras” but in my clinical experience zebras aren’t always all that rare – they aren’t unicorns, after all.)
I hope I am on the right track, with my limited knowledge of human diseases; I actually faintly remember learning about Chagas Disease in veterinary school in one of our public health lectures about zoonoses and One Health but luckily live too far north to encounter the vector. Dogs can apparently suffer from T. cruzi infections, but as I have specialized in large animal internal medicine (horses and cows mostly, but also sheep/goats/alpacas/llamas) this disease hasn’t been on my radar recently. I did include a case report below about Chagas Disease in a horse in Texas, however, if any of the listeners are interested in a veterinary viewpoint on this disease.
Thanks again for entertaining my guess – and for producing an entertaining and educational podcast series. Although it would be great to have a hard copy of the book, if I was to win the random number draw I would prefer the book go to someone who would get more use out of it than a veterinary epidemiologist/large animal internist.
Sincerely,
Emily
Kevin writes:
40 y/o Brazilian farmer with multiple heart problems, visiting family in the US. Though the case report states that the patient does not have overt congestive heart failure (CHF) symptoms, his history of a dilated heart on echocardiography and being a recipient of an automatic implanted cardioverter-defibrillator (AICD) strongly suggests that he has ‘compensated’ CHF, basically pump failure that is not causing symptoms. For the less clinically inclined, CHF is a collection of symptoms due to a damaged heart’s inability to supply enough blood to keep up with physiologic demands. Typical symptoms of pump inadequacy are swelling of the legs, shortness of breath (due to ‘wet’ lungs=pulmonary congestion), fatigue, weakness, and fast heart rate. CHF has many causes which for our purposes can be divided into infectious and non-infectious.
Common causes of non-infectious CHF: ischemic, familial, alcohol/toxic, familial, post-partum, idiopathic and many others.
Infectious causes of CHF to consider: viral (HIV, rubella, EBV, echovirus, poliovirus, coxsackie, etc). Protozoa: toxoplasma myocarditis, rare cases of malarial myocarditis, cardiac involvement with Trypanosoma rhodesiense infection. Uncommon metazoan parasitic invasion of the heart includes echinococcus, trichinosis, entamoeba histolytica, and cysticercosis. Note also that schistosomiasis can cause pulmonary hypertension and enlargement of the right side of the heart. Even the lowly strongyloides has played a bit role (see ref). Satterthwaite’s 1913 cardiology text describes invasion of the heart by Pentastoma denticulatum (as well as throwing in syphilis, TB, blasto- and actinomycetes). Most of the foregoing are bagatelles compared to our patient’s affliction.
Our 40 year old farmer is no doubt one of the WHOs 2016 estimated 8 million worldwide patients who are infected with Trypanosoma cruzi. He is also one of the 20 to 30% of chronically infected people who go on to develop Chagas cardiomyopathy (CCM). It usually takes decades of latent infection with T. cruzi before heart involvement is apparent. The scale of this disease is large and now internationally distributed due to emigration and travel. CCM is often overlooked, especially in non-endemic areas. The main manifestations are heart failure, arrhythmia, heart block and thromboembolism (e.g. stroke, TIA, systemic and pulmonary embolus). Right bundle branch block is characteristic. Grossly the heart becomes dilated, fibrotic and thinned with the development of apical aneurysms. Prognosis is guarded with annual mortality estimated at 4% and five and ten year all-cause mortality of 35 and 60% respectively. Pathogenesis is debated but generally agreed to center on these processes: direct parasite damage, and immune mediated neurogenic and microvascular damage. Diagnosis is via immunologic assay, using ELISA and other confirmatory immunologic tests such as the Wiener recombinant ELISA, immunofluorescent assay, indirect hemagglutinin, Western blotting and PCR. Different clinical groups use a variety of diagnostic algorithms (outlined in below references).
Treatment of CCM is a dilemma since ‘cure’ rates decline with duration of infection and the benefits of therapy are unclear. Additionally, laboratory confirmation/ seroreversion can take years to occur. The drug of choice for Chagas disease in general is benznidazole. A second line drug is nifurtimox. Pharmacologic therapy in Chagas disease must be tailored to the stage of disease (acute, indeterminate, chronic) and the organ involved. Treatment in our patient first requires clinical staging. At least 5 clinical staging systems are used to classify patients (see REF). Our patient meets the inclusion criteria for the largest CCM therapy trial to date, the BENEFIT trial, a prospective randomized double-blind trial of benznidazole (published in 2015). Approximately 2,800 patients were followed for over 5 years. Though benznidazole decreased PCR positivity, unfortunately the clinical endpoints (noted in REFs) in treated vs untreated patients were not significantly different.
Anti-trypanosomal treatment may likely have little benefit for our patient. What other treatments may be offered? Medical therapy can include enalapril, carvedilol and spironolactone all of which have shown some benefit (trials nicely summarized by Bocchi et al). Thrombosis within an apical aneurysm usually necessitates long-term anticoagulation, traditionally with warfarin (unsure of the status of newer anticoagulants for this indication.) Cardiac resynchronization therapy has been attempted, but reliable trial data is not available. Amiodarone has been used in arrhythmia management but there are some troubling data suggesting increased mortality. A curious coincidence: some amiodarone derivatives have anti-trypanosomal activity (see ref). Our patient has an implanted defibrillator, though randomized trial data supporting an unequivocal mortality benefit are lacking. As disease progresses, LV assist device and heart transplant become possibilities, though limited in low resource countries. This case highlights the limits and relative crudity of current medical understanding of the pathogenesis and treatment of chronic Chagas cardiomyopathy. In addition to screening and public health preventive measures, advances in basic parasite-host/organ biology and understanding of the immunology of this disorder will be needed in order to improve treatment of this disease.
Thanking the professors of parasites for their insights.
REFERENCES AND NOTES
Treatment of Chagas Disease in the United States, Sheba Meymandi MD et.al. Curr Treat Options Infect Dis (2018) 10:373–388
Diagnosis and management of Chagas disease and cardiomyopathy Nat. Rev. Cardiol. 9, 576–589 (2012); Ribeiro, A. L. et al. published online 31 July 2012; doi:10.1038/nrcardio.2012.109
Chagas heart disease: A contemporary review, Alejandro Velasco, MD,et al, J. Nucl. Cardiol. (2018). https://doi.org/10.1007/s12350-018-1361-1
Anti-trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure, Pinto-Martinez A, et al, Exp Parasitol. 2018;189:8-15.
Cardiac surgery for Chagas disease, Michael Magarakis MD, et.al. J Card Surg. 2018;1–6.
Tropical diseases of the myocardium: a review, International Journal of General Medicine, 2017:10 101–111, Zoe C Groom, et. al.
Open Access. Very good general review. Absurd error on Table 2, p. 109 which enters “African trypanosomiasis” as Chagas disease.
Chronic Chagas Heart Disease Management From Etiology to Cardiomyopathy Treatment, Edimar Alcides Bocchi, MD, PHD,et al, Journal of the American College of Cardiology VOL.70 , NO.12 , 2017
Strongyloides hyper-infection: a case for awareness. Potter A Ann Trop Med Parasitol. 2003 Dec;97(8):855-60. “The patient, who survived, appears to represent the first reported case of S. stercoralis hyper-infection with suspected myocarditis.” When doesn’t strongyloides stick its head into affairs….?
Parasitic Diseases of the Heart ,Frontiers in Bioscience 9, 706-723, January 1, 2004, Louis V. Kirchhoff, Louis M. Weiss, Murray Wittner, and Herbert B. Tanowitz
This article is a réchauffé of Tanowitz’s 1992 article (which is much more comprehensive)
Parasitic diseases of the heart II: Toxoplasmosis and other protozoan and helminthic diseases Herbert B.Tanowitz MD, et al, Cardiovascular Pathology Volume 1, Issue 2, April–June 1992, Pages 97-106
Kean B.H. & R.C. Breslau: Parasites of the Human Heart. New York, Grune and Stratton (1964) $7.44 on Amazon Books (10/17/2018—only two copies remain !! this is NOT a romance novel)
Diseases of the Heart and Blood Vessels, Thomas Edward Satterthwaite, Lemoke and Buechner, 1913
Chapter XVIII: Cardiac Parasites free book downloadable at:
What Do We Know about Chagas Disease in the United States? Susan P. Montgomery et al,Am. J. Trop. Med. Hyg., 95(6), 2016, pp. 1225–1227 open access. “Fewer than 30 cases of locally acquired infection have been documented in the United States, although a sylvatic transmission cycle has been known to exist in this country for at least a century.”
Proceedings of joint event on 7th Edition of International Conference on Pain Management & 7th Edition of International Conference on Internal Medicine & Patient Care 2018: International Journal of Anesthesiology & Pain Medicine : Volume 4, EuroScicon EuroScicon, Mar 20, 2018 – Medical – 86 pages, Cardiac Manifestations of Parasitic Infections, Raghavendra, Rao, et. al.
Classification for Chagas cardiomyopathy: http://medicalcriteria.com/web/carchagas/
Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy, Carlos A. Morillo, M.D et.al, N Engl J Med 2015; 373:1295-1306
Primary clinical endpoints: death, resuscitated cardiac arrest, pacemaker or AICD implant, sustained ventricular tachycardia, cardiac transplant, new congestive heart failure, stroke-TIA-systemic or pulmonary thromboembolism.
From the Discussion section of the article: “Benznidazole did not significantly reduce the rate of the primary clinical outcome, despite reductions in the parasite detection in serum samples.”
Comment on the dilemma’s of treatment: “The role of treatment in patients with chronic Chagas’ disease and the effect of such treatment on the progression of the disease are unclear, since data have been reported only from observational and small, randomized studies.”
Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas’ cardiomyopathy: The BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT), Jose Antonio Marin-Neto, MD,Am Heart J 2008;156:37-43.
Open Access. This is the initial pre-study launch paper describing the rational, participant eligibility, end-points, etc.
Cardiac tamponade in a child with ascariasis, Georgios S. Papadopoulos , Cardiology in the Young, Volume 10, Issue 5 September 2000 , pp. 539-541:
Till writes:
Dear TWiP-Professors,
I have been listening to your podcast for some months now and have been wanting submit a case guess for some time, so I am happy to finally find the time to do so. I really appreciate the thoughtful and empathetic approach to patients, their class/social situation and also gender you convey in your podcast.
I work as an junior doctor/MD in the university clinic in Hamburg, Germany where I’m in training for internal medicine and infectious disease. We have the Bernhard-Nocht institute for tropical medicine here in Hamburg and I was fortunate enough to spend some time doing full-time research in the wonderful labgroup of Prof. Addo, an emerging disease specialist. After finishing my research stipend I am currently back in the clinical practice and work in the outpatient department for tropical medicine where we see mostly sick returning travelers and also do pre-travel consultations and vaccinations. I actually found out about the podcast from a student who did part of his internship with us and to whom I am very grateful for pointing me towards the wonderful hours of entertaining education that is TWiP.
As for my case guess for TWip 160, this one is, like Daniel Griffin said in the last show, pretty straight forward. The 40 yo farmer from Brazil with dilated cardiomyopathy is most likely suffering from the cardiac manifestation of the Chagas Disease or american trypanosomiasis, also called Chagas heart disease (CHD). This anthropozoonosis is caused by the protozoon Trypanosoma cruzi and transmitted by the so called kissing bug, a family of distinctively shaped insects that mostly feed on vertebrates blood and apparently likes to sting near the mouth (hence the name). As I’m sure you’ll explain later, the bug does not transmit the trypanosomes directly during the sting but rather defecates next to the bite wound, where the feces containing the parasites can be easily rubbed into the wound or any mucous membranes like that of the eye (classic Romaña’s sign, apparently only found in <5% of cases). Other modes of transmission include oral transmission (the infamous crushed sugar cane drinks on the beaches of brazil), vertical transmission (congenital/mother-to-child) and rarely blood transfusion or organ transplantation.
The acute phase of the infection is characterized by unspecific symptoms like fever, chills, lymphadenopathy, tachycardia and hepatosplenomegaly. Interestingly, about half of the patients already show some ECG-alteration at this stage. the acute stage ist seldom diagnosed and symptoms usually resolve after 2 – 4 weeks. Only 20 – 23% of patients continue to the chronic stage which may present years and decades after the acute phase. Cardiac (CHD) and intestinal manifestations (mega-esophagus, mega-colon) can be distinguished, and it is interesting to observe that in some latin american countries only a certain form of these manifestations occur. In Columbia, CHD seem to be the most prevalent form, while in Brazil both forms can be found. Maybe you could shed some light on the reasons for that.
The damage caused by the infection is twofold, a direct damage by the trypanosomes as well as indirect damage by autoimmune reaction. However, as in so many infectious diseases, it seems to be unclear why certain patients develop severe disease while others never develop any symptoms. Mostly during the acute phase of the disease, the parasympathetic nervous system is damaged. In the heart, this leads to an over-dominance of the sympathetic nervous system, ECG-abnormalities like the right bundle branch block described and subsequent dilatative heart failure, also called dilated cardiomyopathy (DCM). Aneurysm in the tip of the heart and subsequent formation of intramural thrombosis are also common. The prognosis of DCM in general is poor with a 10yr survival rate of ~10% although this depends on the severity of the disease.
Now for the additional questions asked by Dr. Griffin.
1) my differential for this would include other causes for DCM:
- hereditary (family history?)
- a previous myocardial infarction (patients history?)
- a long lasting history of hypertension and/or tachycardia (patients history?)
- toxic agents (Alcohol, chemotherapy) (patients history?)
- other infectious agents: viral (coxsacke B virus, enterovirus) or bacterial (tuberculosis) (could be diagnosed by PCR (viruses) or sputum/Chest X-ray (Tbc))
- endocrinological diseases like hyperthyroidism (TSH, fT3, fT4)
2) how to confirm the diagnosis?
in the acute phase the trypanosomes can be observed in a blood smear. Since the parasites apparently have a similar density as leucocytes it is also possible to do a density gradient centrifugation and find enriched parasites in the “buffy coat” between the plasma and the erythrocytes. In the chronic stages, serology (ELISA or immunoflourescence) can be performed as well as a PCR. Only of historical interest and hopefully of no clinical value is the method of Xenodiagnosis by letting uninfected kissing bugs feed on the patient and examining the bugs feces after 1, 2 and 3 months for trypanosomes.
3) How to treat? The antiparasitic drugs of choice are benznidazole (1st line) or nifurtimox as a second line therapy. The CDC recommends 5–7 mg/kg per day orally in 2 divided doses for 60 days for benznidazole and 8–10 mg/kg per day orally in 3 or 4 divided doses for 90 days for nifurtimox. However, in the chronic infection, like in our patient, it is not so clear whether or not anti parasitic treatment is beneficial. I would probably treat with a course of benznidazole if the patient was PCR positive.
Apart from the anti parasitic treatment, supportive treatment of the DCM should be performed, but I’m afraid the patient has already received the most potent medical (amiodarone) and interventional (implanted defibrillator) treatment available. As for amiodarone, that stuff is pretty horrible with tons of side-effects, so if at all possible physicians tend to avoid it. It ist, however, one of the few drugs that will significantly reduce mortality from heart arrythmia. The only curative treatment for DCM is heart transplantation.
The cardiac thrombus should probably be treated with anti-coagulation to prevent thrombo-embolism which could lead to strokes.
In handling the patient I would try to convey the severity of the disease (as mentioned above, the mortality is higher than that of many forms of cancers), stress the importance of regular cardiological follow up and convey that this not due to a personal error in behavior as Chagas is still endemic in the poorer population of southern Brazil (and was much more prevalent in the past).
If I should win, I don’t think I need a copy of red mother so maybe you could send it to someone else, but I would love to receive a signed copy of PD6. Thank you all for this most entertaining and educative podcast, you really made me start on the path to becoming a parasite-nerd, a path I will hope to progress upon for months and years to come.
All the best, Till.
Andrew writes:
Hello TWiP Trio,
I have just come back from a week-long training for Clinical Parasitology at the CDC in Atlanta… so hopefully it was worth the trip and I get this correct!!
My differential for the case of the Brazilian farmer with heart complications would be: Trypanosomiasis, Malaria, Filariasis, and Schistosomiasis. Not a very long differential, because these symptoms are so unique.
To keep this email shorter, I will dive right into my guess. I believe the Brazilian farmer in TWiP 160 has Chaga’s Disease that he most likely acquired as a child. Chaga’s is caused by Trypanosoma cruzi. T. cruzi is endemic to South America- it is thought that around 8 million people in S. America are infected and most don’t even know it.
A lot of people think Trypanosoma cruzi infects it’s host when the insect bites its victim, but that is incorrect. When a triatomine insect takes a blood meal, it defecates on the skin. The Trypanosoma organisms are in the insect’s feces. When a person scratches the bitten area, they effectively push the feces into the opening (or maybe another open wound close by or the eyes or mouth). This is how the organism enters the bloodstream. The insect usually will bite in the facial region because it is nocturnal and can only fly as high as about waist-level, so when you’re sleeping and your face is exposed, it is the perfect target.
Acute symptoms are not very common, but if they do show, they are usually very mild such as headache and swelling of the site of infection. The acute stage resolves spontaneously for most patients even after about a month or two even if not treated. About 60-70% of these patients will not develop clinically apparent diseases- they remain infected for life, but asymptomatic and otherwise healthy. Roughly 30-40% of patient’s develop the chronic cardiac and/or digestive form of Chaga’s- usually 10-30 years after initial infection, seemingly out of “nowhere”.
The cardiac form can cause cardiomegaly, heart failure and altered heart rate. The digestive form can cause megacolon and constipation. Both forms can be deadly.
Suggested treatment for Chaga’s is benznidazole however it must be obtained through the CDC as it is not available through US pharmacies. Other treatment for this man may include heart surgery or heart transplant if damage to the heart is severe enough.
Thank you for your great podcast, I love tuning in!
Erik writes:
Hi there TWiParoonies,
I feel reasonably confident in my guess for this week’s case. The description that Dr. Griffin gave was as close a description of Chagas cardiomyopathy as I’ve ever heard! The patient being a farmer from Brazil would also be consistent with that diagnosis as Chagas disease is quite an issue there. I tried to think of other possible diagnoses but, short of a non-parasitic etiology, I can’t think of any other parasites prevalent in Brazil that cause cardiomyopathy.
The best way to diagnose chronic Chagas disease is by looking for T. cruzi-specific antibodies in the patient’s serum.
This is quite a sad diagnosis because Chagas cardiomyopathy, from what I’ve read, is quite deadly since it’s a progressive disease. The exact cause of the pathology is not fully understood, but it’s thought to be either immune-mediated, or caused by the persistence of the parasite in the heart tissue.
For treatment, benznidazole is frequently given although there is no evidence that it provides any benefit in cases of Chagas cardiomyopathy. Treatment for the cardiac pathology, according to the European Society of Cardiology, is “angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) and adrenergic beta-blockers (BB) to reduce mortality and diuretics and/or digoxin to reduce morbidity.” In cases of particularly bad cardiomyopathy, sometimes a heart transplant is the only option.
This is quite an unfortunate diagnosis and I hope I’m wrong and that your patient is doing well.
Best regards,
Erik
David writes:
Dear parasitism panelists,
I finally manage to write in again after logging for a very long time.
My guess is that the Brazilian man with the heart problems has a chronic form of Chagas disease. This was my first intuition when I heard the case. I am unlikely to forget the consequences of Chagas, because when I started listening to TWIP some 5 years ago I remembered an episode of a swollen eye after a bug bite some years earlier – and in a prolonged state of anxiety I eventually made it to the red cross in the capital of Managua, where my blood tested negative.
Chagas obviously exists in Brazil, and the ekg with right bundle branch block of the heart seems to confirm this hypothesis.
I consulted the pdf of parasitic diseases, and I believe it may be a match. While thrombosis and aneurysms also appear as a consequence of Angiostrongylus Costaricensis, I think this would look very different, with a much more acute manifestation, and also there would be fever and possibly encephalitis, so this seems unlikely – although I have no medical background to sustain this gut feeling.
Confirmation with IgG would ensure the diagnosis is correct I suspect.
So, I would go with Chagas. If that is the case, I would recommend psychological counseling. Although Shakespeare refers to death by exclaiming “’tis a consummation devoutly to be wished!“, being confronted with our mortality will never come easy, especially with a sly killer as Chagas where it might take another decade or another hour. Maybe one might live life more to the fullest, but that is a meager silver lining.
Writing from a rather chilly Jinotepe where the rainy season is slowly coming to an end, I send you,
Best wishes,
David
Chris writes:
Hello Professors,
It is a chilly 47 F here in Stonybrook New York. for this weeks case study I Believe that the patient is suffering from Chagas disease, a protozoan parasite infection that is known to cause heart problems and mega colon. This parasite is common south America, can be found all the way up to Texas and is transmitted by the bugs from the family Reduviidae commonly called the Kissing bugs. I would go into more detail but I am writing this in between classes and don’t have the time to look up how to treat this unfortunately. If i win I would very much like a copy of red mother!
I also had a question about dracunculus and its ability to utilize dogs as a reservoir host. The three of you discussed how the parasite can infect and survive in dogs and cats but I question whether or not these animals can serve as an effective host. Although they can infect and survive in dogs, is it reliable enough to sustain a population of these parasites? First off I wonder if dogs are a significant enough host to sustain this parasite and if they are how come it didn’t come to our attention long ago, specially because this parasite has been known about since biblical times. Secondly, even if dogs could serve as a significant host, we have effectively reduced the populations of this parasite to near extinction levels, could it even rebound? I know in many diseases that once it hits a certain threshold the disease is effectively extinct, such as malaria in America where although we have the occasional person infected with malaria in New York city as well as the vectors, one person (or even tens of people) is not enough for the parasite to to transmit and sustain a life cycle. Could this be the case with the dogs and cats acting as a reservoir, where they can sustain the parasite but not effectively to save the parasite from extinction. Regardless I found the paper very interesting, and I am glad you all discussed it, I am just curious about the disease ecology aspects of it.
Also If you remember I wrote you all about a month ago about having Rich Ostfeild on for a tick episode. Well about 3 days after I sent that email I attended a fascinating lecture from Dr. Maria Diuk-Wasser a tick specialist that is at Columbia, and being that she is at your university I thought I would let you all know that she has some very cool work Ideas about the Dilution hypothesis and that she would make a great guest for the show.
Lastly I thought I would like to ask if any of you will be attending the New York Area Meeting for Parasitology this December 3rd . There is no registration fee, there is both a oral and poster presentation and its super close. I just found out about this the other day so I figured I would pass the knowledge onto you all. Here is the link to register if any of you are interested in attending https://sites.google.com/view/nycparasitology3/home. Hope to see you there, and hopefully I can get Dickson to sign my copy of people parasites and plow shares!
Warm regards,
Chris
Kevin C writes:
Hello TWiPsters!
I have been hesitant to email with my personal diagnosis for this podcast’s case studies, but considering that my last diagnosis was correct I think now is the time to start. Even though I may not be as prolific with my diagnoses as the other Kevin that regularly emails with every episode, I am confident with what is wrong with the patient from Brazil.
Considering this man emigrated to the US after having worked as a farmer in Brazil, the EKG results showing heart dilation with apical aneurysm is key in determining that this patient has been infect by none other than Trypanosoma cruzi which causes Chagas Disease or otherwise known as American trypanosomiasis. Since there are two phases of infection-both acute and chronic- there is a divergence in treatment for this patient. With acute phases typically resulting from the infection of young children and with the symptoms for such infection being the mild enlargement of the liver and swollen glands, I feel that the patient should be considered to have chronic Chagas Disease. Further blood tests can be done to ensure of this diagnosis. If these results appear to be true than a simple implementation of anti-parasitic medication will not be enough to rid the patient of the T. cruzi and would only slow parasitic progression. Instead if the patient wish to truly remove the parasite, a heart transplant would be necessary considering that he has already had a defibrillator implanted in his current heart.
Thank you so much for these wonderful podcasts to help those of us trying to stay current on the forever changing field of hard biological based science. I have been listening to all of the TWiX podcasts at the behest of my boyfriend and have been hooked! I also have been recommending all of these fine podcasts to all of my coworkers almost daily. You even heard from one of them in the last episode, John the man that proclaimed to love parasites! We even have a friendly competition to see who will receive a signed copy of the textbook first. Keep up all of the hard work that these podcasts require and happy to see what you have in store for us listeners next!
From a rainy day in Flagstaff Arizona with a temp of 10 degrees C,
Kevin C
Connor writes:
Hello Doctors,
I got to catch up on the TWIPs I missed on a 19hr drive so I’m hopefully in time for the Chagas case.
As I’m a wee bit busy with projects and preparations for the annual ASTMH meetings I shan’t be doing a proper Ddx.
Case: the man from South America (Brazil) with a profession in agriculture (risk factor) and cardiovascular manifestations I assume he has chronic Chagas’ disease due to T. cruzi infection earlier in his life as cardiomegaly doesn’t often set in for a few decades. Tx would be with benznidazole and nifurtimox but must contact CDC for approval due to nifurtimox not being FDA approved. Tx will not cute current symptoms but will/should slow or halt further disease progression.
I hope I am in the running for both PD6 and the poem book in this round. Especially because I am about to schedule a test to see if I have Chagas from my work in Ecuador a few years back.
PS: I was very pleased to hear the cases with entomological ethology as I loved my medical entomology class with Dr. Dawn Wesson.
As always thank you all for all you do for education, the advancement of the field, and society sensu lato.
Karen writes:
I think the patient in episode 160 has the chronic form of Chagas’ disease/Trypanosoma cruzi/American trypanosomiasis. If I were a doctor and if for some reason I didn’t know the patient was an immigrant from South America, I’m not sure if I would think to suspect this, but diagnosis can be made by testing the serum for IgG. Xenodiagnosis, allowing an uninfected bug to blood feed and testing the bug, is another option. Nifurtimox or benznidazole could be used to treat, but a heart transplant may be the best bet. Hopefully a better treatment is developed soon.
Karen
Santa Barbara, CA
Bening writes:
Greetings TWiPsters!
I hope I am not too late to write in on the Brazilian man’s case. It is a rainy 60 degrees F in Atlanta today. I was recently recommended TWiM by a colleague as a study aide for my upcoming ASCP microbiology certification exam. It is excellent! I then discovered TWiP, and now have a hard time peeling myself away from it. Parasitism is true hobby of mine and have enjoyed every episode thus far. As for the most recent case, the man from Brazil with cardiac symptoms, my best answer (guess) is Trypanosoma cruzi. I do not have a copy of Parasitic Diseases vol 6 (hint hint), but I do have Google, my old parasitology textbook from undergrad, and a curious mind. After realizing the amount of parasites known to have cardiac involvement, I decided to narrow down the search by specifically finding cases involving apical aneurysms as this seemed an unusual symptom. Sure enough, there are multiple case studies involving post mortem findings of apical aneurysms in Chagas disease cases, which sets this infection apart from other parasitic organisms having cardiac involvement. In addition to the aneurysm, the man’s travel from Brazil would also implicate Trypanosoma cruzi. Given that he is 40 and has had ongoing cardiac problems, he is likely in the chronic phase of the infection. In questioning the patient, I would ask if he sustained any facial insect bites in his recent time in Brazil, or noticed any facial swelling that may have mistaken for a mosquito bite. Trypanosoma Cruzi is transmitted via the triatomine bug and the insects are active at night so the patient may not have noticed the bite. Given the chronic symptoms, the patient is likely beyond effective treatment. There are options to treat symptoms and slow progression, such as the pacemaker to help his heart or surgical involvement for the aneurysm. I am not a medical student, nor did I have as much time as I would have liked to research this case, but enjoyed the process and look forward to the next case. I am also interested in the fate of the patient, if Daniel has time to explain the case conclusion.
Sincerely,
Bening
p.s. pronounced ben-ing