Dear The Three Twipeteers,
For this case my main diagnosis is: Plasmodium vivax. Malaria can cause a tertian fever (fever every other day) as the hypnozoites in the liver release more schizonts and merozoites. I am unaware of any single infection that can last 16 years; after some research I was able to find someone who seems to have had a plasmodium malariae infection for more than 40 years, but she was mostly asymptomatic during that period. I am assuming that the man is being reinfected by mosquitos every so often (especially if other people in the village are being infected) and that is what is leading to the extended course. Liver failure, splenomegaly, and anemia would result from chronic infection. The darkened skin may just be his manifestation of jaundice since it would not take on the classical yellow skin in a darker skinned person.
Babesiosis: It is less likely since I don’t believe it is endemic to India. It can cause hepatomegaly, splenomegaly, jaundice, etc.; however, I am unaware of anyone carrying it for more than a year. Furthermore, it is unlikely to be severe unless there is a predisposing factor such as a previous splenectomy or immunodeficiency.
Erlichiosis and Anaplasmosis: Same as Babesia in that I don’t believe it is endemic to India, and I am unaware of any case lasting so long.
The next step I would take is to look at a blood smear. All of these would be diagnosable by directly seeing the parasites. Treatment for Babesia and the other tick-borne parasites would be with Doxycyline. If it is malaria, then the use of primaquine is necessary to clear out the liver hypnozoites.
Leptospirosis: Can be obtained by coming into contact of the infected animals urine. Can lead to liver failure and undulating fever (although I don’t believe it is tertian), but not the splenomegaly. It absolutely would not last for 16 years.
Adult Onset Still’s Disease: The fever is classically daily or even twice daily (quotidian or double quotidian.) There is hepatomegaly in a minority of patients, but most do have splenomegaly. There is also a maculopapular rash; which once again would have a variable presentation depending on our patient’s skin color. There is an elevation of liver enzymes. Overall, this fits quite well with the vignette. The problems are that the patient would be suffering from many more problems (kidney damage, TTP, etc.) than this and especially if it has been going on for 16 years.
Hemochromatosis: Admittedly, this was my immediate thought as you were going through the vignette and mentioned liver failure with darkening of the skin. Unfortunately, it shouldn’t cause fevers on its own.
Diagnosis unrelated stuff:
Arsenic poisoning. I have heard that arsenic poisoning can cause a patient to have garlic breath. Is it really noticeable? I always thought of myself as a curious person, but actually testing this one out is crossing a line.
Eosinophilic granulomatosis: Thank you for the correction. I usually have to remind myself of the change between Wegener’s to Granulomatosis with polyangiitis.
Longest fast ever: The longest confirmed record for a fast is 382 days. It was a 27 year old man and you can find the paper here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2495396/pdf/postmedj00315-0056.pdf. He was given water and vitamins so he was relatively ok. The paper claims that there were no ill effects to the patient in the long term; however, I find that really hard to believe given the permanent changes that occur in children’s GI tracts when they are marasmic. Overall, I would not recommend this as a diet for weight loss or to remove worms.
Thank you again for all your hard work!
Hofstra Northwell SOM Medical Student
Class of 2018
Jere Miah writes:
Dr. Wink writes:
Dear TWIP Professors,
Great episode. As they say on Monday night TV, 107 was your “Best dance yet!”
My guess for the chronically ill man from Assam is tertian malaria due to P. vivax.
Dear TWIP Trifecta,
I hope this finds you all well and Dr. Griffin, I hope very much that your mother has recovered, without mystery, from whatever undermined her evening at the opera.
After a wave of super cold days, it is now just chilly in lower Manhattan, 49 degrees F (9.4 C), but it is sunny.
I am very sorry to have missed responding to TWIP 106 (although I really don’t think I would have gotten a correct diagnosis). I seem to be in a very hectic moment. Having said that, I recently had a somewhat embarrassing moment, parasite-wise. At the gym, a woman I know slightly was on the phone discussing what was clearly a parasitic infection in her child and I think my head swiveled around a little too fast. I was very sympathetic to her plight, and told her that I happen to be very interested in parasitic diseases and that I was exactly the person she could talk to about this without fear of me getting squicked-out. She seemed relieved, but I suspect she now thinks I am a bit peculiar. (I think I provided a service, because it can be difficult for parents to find non-squeamish ears to talk to about these things.)
I do have a guess diagnosis for TWIP 107. I think the farmer in Assam may have been suffering (for a very long time) from Kala-Azar, or Visceral Leishmaniasis. It is caused by protozoa that spread to a human host through sandfly bites. Unfortunately, this is not an uncommon disease in India (though it shows up as well in parts of Africa and South America and I did find an interesting case study of a Sicilian patient who was initially misdiagnosed as having Cirrhosis of the liver). Visceral Leishmaniasis is fascinating in its progress because it can be almost symptomless for a long long time, or it can kill a patient within a couple of years. Its symptoms are consistent with the patient’s: enlarged spleen and liver, recurring fevers, loss of appetite and weight and, most curiously, skin on the face, hands, feet and abdomen can become darker. This change in skin color is the source of the Indian name “Kala-Azar” which means “black fever”.
There are lots of other diseases that could participate in a differential diagnosis. Cirrhosis, as I mentioned, is a possible suspect as is malaria.
Visceral Leishmaniasis is treatable, but I do wonder, after 16 years of having to put up with countless protozoa, if the patient’s liver and spleen can recover entirely. Apparently treatment is not easy and requires a long course of medication that can be difficult to acquire and maintain in rural areas, which makes me worry about the patient even more. Please let us know what his prognosis is.
As always, thank you so much and I wish you all the best.
Dear TWiP Trio,
The 45 year old gentleman from Assam seems to have contracted a classic textbook case of malaria – particularly Plasmodium falciparum. The man’s recurrent fever (36-48 hours) is symbolic of malaria infection, and the hepatosplenomegaly described may be a cause of his abdominal pain. Hepatosplenomegaly and jaundice in the man’s eyes and skin are all telltale signs of the sporozoites and merozoites in the liver, and there has been documentation of elevated bilirubin levels due to the infection – the breakdown of hemoglobin that the parasites incur. The high elevation of liver enzymes is also a sign of disease progression.
I am glad to announce to the TWiP Team that I have been accepted by the Cummings School of Veterinary Medicine at Tufts a PhD candidate in the Molecular Helminthology lab, where I will be studying the tegumental proteins and host-parasite interactions of schistosomes! I am very excited, and I am sure TWiP will come in handy during the process.
twip 107: a man from Assam.
After a home run with the twip102 Indian woman from Calcutta case, I am compelled to expose my ignorance again.
It seems that this 45 year gentlemen got a bad case of Kala-Azar, also known as black sickness, black (or dumdum) fever, or visceral leishmaniasis. In fact the local names of the disease tell his story in clear and unambiguous terms. The viceral form of the disease caused by Leishmania donovani affects spleen and liver and is life threatening. It must be his healthy lifestyle that kept him alive for 16 years.
Treatment option for visceral leishmaniasis are not straightforward, issues with toxicity, efficacy, and cost. Liposomal Amphotericin B (expensive) and short course Miltefosine and or Paromomycin sulfate is an option. Pentavalent antimonials would not be my first choice. Of course it is always possible that I am completely wrong on all counts.
Not a big fan of the weather discussions but a huge fan of the TWIP geniuses.
Ruben Abagyan, Ph.D.
University of California, San Diego
Skaggs School of Pharmacy & Pharmaceutical Sciences
San Diego Supercomputer Center
La Jolla, CA
I’ve been hooked on all the TWiX podcasts for a while and a really enjoy learning about these fields in medicine/biology. I went to school for chemistry but now regret not spending more time on biology or biochemistry. That’s ok, though! TWiX to the rescue!
This is the first time I’ve tried to figure out a case study. At first I thought it was a slam dunk with one google search – the 2-day periodic fever was most striking to me and seemed to be most associated with malaria, particularly P. vivax or P. ovale. I then tried to find common parasites to the Assam region and ruled out several, leaving echinococcus type tapeworm, malaria, and leishmania. Great, malaria is still on the list!
I was very focused on this fever, and malaria explained that and also the enlarged spleen and liver. I couldn’t really find other case studies of such a long-term infection, but I thought maybe there was some kind of immunity involved that kept the disease somewhat in check (i.e., the patient was able to survive for so long). I was about to call it a day, but didn’t like that I couldn’t find the darkening skin as a symptom of malaria on any article or website.
So, I went further down the rabbit hole. I kept the echinococcus tapeworm on the list because it could have a years-long incubation and cause jaundice. However, there were too many symptoms not accounted for to consider this further. Then I read about leishmaniasis and came across why it’s sometimes called “black fever” – there is the skin darkening! Also, the liver and spleen are specifically listed as becoming enlarged with viceral leishmaniasis. Periodic fever, check. This disease is often mistaken for malaria as well! Uh-oh, now I don’t know what to pick. Leishmaniasis seems to be very deadly if untreated, and this man has been sick for 16 years already.
After much internal debate, and finding one case study of a Nepalese man infected with both malaria and leishmaniasis (http://www.e-jmii.com/article/S1684-1182(11)00015-6/abstract?cc=y=), my guess is the patient has had malaria and more recently leishmaniasis.
I feel pretty good about my first try at this. I’m looking forward to the next podcast so I can learn about which details I overlooked that would have made a difference in my analysis!
All the best,
Chris from Massachusetts
In regards to the Swiss surfer it sounds like she has a case of thelaziasis from Thelazia callipaeda?
Also, wanted to thank you all for putting this podcast to together. I truly enjoy listening to it.
Dr. Christopher Martin, Emergency Medicine, Syracuse, NY
An interesting side note… While reading the “Lost City of Z” by David Grann, a book about the expeditions of Percy Fawcett in the Amazon…descriptions are given on how the indigenous tribes would remove maggots with sound: “[The Echojas] would make a curious whistling noise with their tongues, and at once the grub’s head would issue from blowhole…Then the Indian would give the sore a quick squeeze, and the invader would eject.” p. 134
Have any of you ever heard of such tricks? Thought it was an interesting tale of perhaps a lost art of native medicine, sharply contrasting our Western knowledge.
I think these moving objects could be maggots (first stage, because of the small size). This is going with insect exposure (flies).
The moving objects are the maggots of the (specific necrobiotes and specific sarcobiotes flies)
If these objects are seen under the microscope, you will find an anterior tapering end with black spine or hooklet, a posterior thicker end and a segmented body. Of course these small objects if left to grow will reach one or more centimeter in length.
Also this type of infection never affects the blood picture.
Eye wash with antiseptic eyedrops will be good. Eye ointment can block the respiration of these maggots and let them come out of the eye.
Professor of Medical Parasitology
Faculty of Medicine, Cairo University
Dear Vincent, Daniel, and Dickson
As a regular listener of TWIV, TWIM, and of course TWIP, I was delighted to see the latest podcast profile our paper on tuft cells, taste, and parasite immunity. In fact after we published this paper, I mentioned to a colleague that it would be cool to end up on TWIP. I can tell you that we are pursing several of the questions brought up by the three of you, including identifying the potential parasite agonist(s) that stimulate taste receptors in tuft cells. Thank you for a really nice discussion. I was especially gratified to hear such kind words from an esteemed parasitologist like Dickson.
Keep up the good work. These podcasts are a wonderful asset to microbiology.