Dear TWiP superheroes
This time I hope to redeem myself by not mentioning any diseases named after Nazis!
It sounds like the 28-year old man from Thailand with periodic high fever and chills has malaria, although he has an atypical pattern of fever. The clinical and lab findings (hepatosplenomegaly, jaundice, low platelets, anemia, infected red cells) all support this diagnosis.
The severity of his illness is consistent with Plasmodium falciparum… but the blood film appears to show P. malariae, with ‘band form’ trophozoites in normal-sized red cells. P. malariae causes a milder, chronic illness.
So… the probable diagnosis in this case is P. knowlesi (‘monkey malaria’) a zoonotic infection found in the jungles of SE Asia. It is morphologically similar to P. malariae on microscopy. P. knowlesi has a shorter life cycle and can cause daily spikes of fever and a rapid increase in parasite count. PCR confirms the diagnosis.
As he has >2% parasitemia, hypotension and renal failure, the treatment of choice would be intravenous artesunate or quinine if this is not available.
What was the outcome?
best wishes, Dan
My guess for the case of the Thai logger is P. knowlesi because of the geographic location, presumed proximity to monkeys, band forms and high parasitemia. The organomegaly suggests chronic malaria, so I wonder if he has more than one parasite or “ticks and fleas,” as they say.
I believe the young man in Bangkok has contracted a case of malaria, particularly malaria spurned by the species Plasmodium vivax. P. vivax is particularly dominant in areas of Asia such as Myanmar and Thailand. This also happens to be the particular species that causes splenomegaly, and has been found to rupture from erythrocytes within 48 hours of merozoite invasion, which may fit the man’s 2-day onset of chills. According to the 6th Edition of Parasitic Diseases, P. vivax infection typically causes around 2% infection in RBCs, but in this particular case, the man may have a higher parasite load due to the development of hepatosplenomegaly and the high number of mosquitos bites garnered while sleeping outside. The man’s other symptoms (jaundice, dark urine, difficulty breathing) are indicative of other malarial infections, so it is possible that since there is a higher RBC infection rate and multiple band forms present, he may have another species of malaria infecting him, particularly P. malariae (which causes “big spleen disease” in tropical regions.) Treatment includes antimalarials such as chloroquine, mefloquine, or artemisinin-based treatment.
Once again, thank you for the informative podcasts.
Good evening TWIP trio from cold, dark, foggy London, UK.
I last sent in an answer to a case study a couple of months ago while completing the Diploma in Tropical Medicine and Hygiene. I found your podcasts to be an invaluable source of information, and enjoyment, while studying parasitology for my exams, and having finished the course, I am trying my best not to let the knowledge I’ve gained slip. With that in mind, here is my answer for the most recent case – the gentleman from Thailand with fever and a high parasitaemia with band-forms visible on the film.
When Dr Griffin first mentioned band-forms, my immediate thought went to Plasmodium malariae, the trophozoite of which classically assumes a band-form shape within infected red blood cells. However, there were a couple of features of the case that challenged this diagnosis.
Firstly, the high parasite count in this patient is not something you would typically expect with P. malariae, which preferentially infects older (hence smaller) RBCs and wouldn’t typically cause a parasitaemia greater than a few percent.
Secondly, the daily (or quotidien) nature of the fever, while being perhaps a slightly soft sign, again is not typical of P. malariae, in which fevers classically occur every 72 hours. I’m sure you guys have discussed the ridiculous naming system for fever frequency with malaria before – a fever occurring every 3 days is called quartern!
Thirdly, you had an interesting discussion about this patients job, which would put him outside during the day in forested areas. Interestingly, I believe anopheles mosquitos in this part of the world are often day-biting, perhaps mitigating any effect of the patient not sleeping under a net. More importantly, his work might bring him to the vicinity of macaques in the forest. These happen to be the reservoir host for Plamsodium knowlesii, which is my guess for the case study.
This zoonotic parastic infection is associated with morphology similar to P. malariae but causes daily fevers and can have very high levels of parasitaemia, which in turn can make people very sick. It is also geographically limited to South-east Asia, in particular Malaysia and Borneo, but I assume it has made it as far as Thailand.
Treatment would be as per other severe malarial infections, with IV Artesunate and supportive care until the patient has improved, and then oral Artemisinin combination therapy to complete treatment.
He could also probably do with some advice to wear long-sleeved clothing when working outside – perhaps someone could come up with insecticide-treated shirts and trousers for these guys to wear???
Anyway, I hope the patient recovered well and I look forward to hearing the outcome in the next podcast.
Happy new year to all of you, and please keep up the great work.
This is Neeraj from gloomy, murky and insanely wet Bay Area in California. Don’t get me wrong, I am totally in for all the rain we are getting to help us make the deficit for the looming drought, but there’s just something about grey skies. I just HATE them.
Apart from this, I am glad that TwiP released a podcast early in the year and based on Dr Griffin’s presentation of the symptoms for the latest case for the male at the Burma Thai border, I would like to suggest that the man is suffering from malaria. All the physiological symptoms (like shaking chills and no diarrhea) along with the low glucose and RBC infections (a whopping 5-10%), point towards an advanced infection of malaria. I think the prescribed course of medication would be artemisinin coupled with antibiotics?
On a different note, I was recently reading about toxoplasma and while browsing the website for journal cell, I came across an interesting paper (please find attached). In this manuscript, The authors describe an intrinsically disordered protein (IDP) namely GRA24 and show how it activates a canonical MAP kinase pathway to maintain infectivity. Personally, I have always loved working with proteins as I think there is something very definitive about the in vitro experiments one can do with purified components. Obviously it’s a reductionist point of view (like most science), but it can give one the kind of insights that can be fascinating (at least that’s the way I feel). For example, this paper has a figure showing the structure of a complex between the IDP and p38 MAPK, solved using SAXS. (Dr Racaniello I was listening to the recent episode on TWiM about the bacterial calliper protein so thought you might be interested in seeing the diverse roles SAXS technique can serve. Although I still think the resolution on the order of Angstrom scale presented in that manuscript was a stretch).
In any case, thanks as always for a wonderful podcast. It’s always a pleasure and a great learning experience to listen to the esteemed group of TWiPologists, both conducting and listening to the podcasts. I can’t remember a single episode from which I never learnt plentiful. Please keep the ball rolling and here’s to an infectiously rewarding 2017 of scientific discoveries.
Neeraj Kapoor, Ph.D.
South San Francisco
As always, here is another very interesting case.
The clinical picture is that of a young patient with a fever and dark urine. This last suggests coluria, being hyperbilirubinemia one possible cause. In the clinical practice, among the long list of possible infectious causes of fever in tropical countries one must always consider typhoid fever and blood cultures should be taken. The symptoms, the hyperbilirubinemia and the fact that our patient had frequent contacts with animals also suggest leptospirosis, which is highly prevalent in tropical countries. And of course, highly endemic in SE Asian countries, dengue fever is always something to think of.
Said that, and assuming this is a case of HUMAN infection (not penguins this time!), the case strongly points to human malaria. The band forms are typical from both Plasmodium malariae and Plasmodium knowlesi. The first one is rare even in endemic countries. The second is recognized today as an emerging infection and in endemic countries, such as Malaysia may be the most frequently diagnosed species. Microscopy cannot really tell the difference between both species, so PCR test is mandatory. P.knowlesi causes higher levels of parasitemia, and the prognosis is a bit poorer than that of P.malariae. This species is a zoonosis, and different monkey species are considered the natural hosts. Deforestation is leading to an increase in the incidence, since it brings human beings, monkeys and anopheline mosquitos into close contact. So, in the former scenario the parasite follows a cycle monkey-mosquito-monkey, but in the new one, the cycles has changed to a monkey-mosquito-human or simply human-mosquito-human as is the case for the other four human species. Our patient works in the timber industry, making the contact with the parasite much more likely. Otherwise, one cannot rule out a mixed infection by different Plasmodium species, and again PCR could help in the diagnosis.
So, my best guess this is a case of a P.knowlesi infection or a mixed infection involving in any case P.knowlesi.
P.S. It seems to me very interesting to add that P.knowlesi is not a new discovered species. In fact, it was once used by Dr. Julius Wagner Jauregg as a treatment for patients with neurosyphilis with some success. The idea was to generate fever, as Treponema pallidum is a thermolabile microorganism. The parasite was transmitted intravenously from one patient to the next. In fact, we could see Dr Wagner as A VECTOR, a “human anopheline”. Unluckily, after some passages between patients, the resultant strain gained in virulence, complications began to occur, and the treatment had to be stopped. For theses achievements, in 1927, Dr. Julius Wagner Jauregg received for this work the Nobel Prize in Medicine, being actually the first psychiatrist to win the Nobel Prize.
Thank you very much. I anxiously wait for the next episode.
My guess as to the diagnosis of our Thai patient would be malaria. There aren’t many things that infect RBCs and since babesia is limited to the US, I believe that malaria is a safe bet. Plasmodium falciparum is the most common species to cause infection in Thailand and there is a good amount of resistance found within the country. This combined with the fact that 5-10% of RBCs are infected cause me to worry greatly for our patient. On Uptodate, there is a criteria for diagnosing someone with severe malaria. In our patient; if the glucose is less than 40 mg/dl, parasitemia > 10%, H&H < 7g/dl/20% respectively, or any episode of major bleeding would be enough to categorize this as severe. It is a good thing he was able to get to a hospital as soon as he did. I would start artesunate treatment as soon as possible, along with IV fluids with glucose. Depending on how bad his anemia is, I would consider packed RBC transfusion. I hope that this patient was able to get better.
Hofstra Northwell SOM
Class of 2018
Ryan and Perrin write:
We’re two students writing in for the first time from Ontario, where we’re currently experiencing mild January temperatures in the 2 degree-C range. We’ve been listening for a while and thought it was about time to take a crack at a case.
In regards to the case discussed in episode 124: Given geographical location, quotidian fever, spleen and liver involvement, as well as the risk factor of sleeping outdoors at night, we guess that the patient is suffering from Malaria. Based on the information, we think P. falciparum is the most likely culprit, although 5-10% infected RBCs seems high, this could be explained by increased exposure to hungry mosquitos or perhaps an immunocompromised status. Given his age and ongoing residence in this area, we would expect a higher degree of immunity, and so suspect an underlying condition. P. vivax also seems a potential organism, however has lower prevalence in this area, and additionally only infects reticulocytes and so rarely would reach this level of parasitemia. We expect to see infected erythrocytes of normal size. We suspect that this is a new infection, not a recrudescence (as which could be seen with vivax).
We suggest treatment with Atovaquone-proguanil or doxycycline
Looking forward to seeing if we are correct in our first TWiP diagnosis.
Ryan and Perryn
I am a longing term listener of TWiX, started with TWiV and then found TWiP.
It is a warm 33°C here in Muang (city) Ubon Ratchathani, Thailand. Where I am a temporary government employee at the Office of Disease Prevention and Control.
Shoutout to my professors: Dr. Gerald Esch and Dr. Raymond Kuhn at Wake Forest and Dr. Mario Grijalva at Ohio University/Pontifica Universidad Catholica de Ecuador. They are all wonderful educators that have surely changed many lives for the better.
Ok down to business.
My first guess ever.
For a Pt. presenting with raised rash that some might describe as serpiginous, has spent time in Western Dominican Republic, and walked around without shoes I would guess CLM. After ruling out S. stercoralis, due to lack of pain in lungs and/or belly. Not sure if it is A. braziliense, A. caninum, or another species.
Either way Tx. Outside US: 10% thiabendazole cream twice daily for 14 days. Inside US or if widespread lessons: oral Ivermectin (0.2 mg/kg single dose), albendazole (400mg daily for 7 days), or mebendazole (100-200mg daily for 5 days).
Thank you all for this wonderful gift and Happy New Year to you and yours.
Wake Forest University 2015
Religious Studies Minor
Dear Doktor Doktor Doktors,
In TWIP #124 (28:00) you commented on the price disparity of Albendazole between the US and the DR. While Dr. Griffin pointed to the freedom of the US capitalist market and the need for balance between profits and public health, other comments mentioned the expense of development and clinical trial failures. TWIP is so wonderfully authoritative that I worry about these off-expertise comments on the beliefs of your listeners.
Research & clinical trial costs are often used to justify high pricing. A cursory review of pharmaceutical company income statements show that R&D is around half of marketing expenses. As one example, Pfizer’s 2015 income statement shows Selling, Informational and Administrative (SIA) expenses to be 30% of sales while R&D is only 15.7% while still making an impressive 14% after tax profit. www.pfizer.com/system/files/presentation/2015_Pfizer_Financial_Report.pdf (average manufacturing sector profits are 5%) Even if the marketing portion of SIA is half the total, R&D is not the necessary reason for high prices.
Many may discount this calculation so to Dr. Griffin’s point, I would direct your listeners to an alternative R&D funding system proposed by Bucknell economist, Dean Baker He proposes federal funding and patent ownership allowing free market competition for drug manufacture and pricing. He points out that patents are a means of taxing the public to support research and innovation (www.deanbaker.net/books/rigged.htm). (Another example: According to the Kaiser Family Foundation, administrative costs in Medicare are only about 2 percent of operating expenditures. Defenders of the insurance industry estimate administrative costs as 17 percent of revenue. http://justcareusa.org/medicare-is-more-efficient-than-private-insurance).
As always, thanks for taking the time to provide the greatest public education shows ever. The world needs your format and style to be more infectious and spread to all areas of science.
Hi Vincent, Dickson and Daniel,
Good to find you back in my inbox so quickly into the New Year (And to see that your stable at Microbe.tv has enlarged too!). And a belated Happy 1000000th to Vincent too!
Your brief mention of parasites that ‘hoarders’ might get from an excess of pets, reminded me that I saw this piece on raccoon ascaris in Promed Mail the other day.
Looks to be a particularly nasty one to catch when it does get into humans. Your further mention of someone checking the parks for parasites from dogs and cats, made me think that in NY they might be finding the raccoon parasites too, and that people ought to be made aware of the risks of encouraging them to become too domesticated.
All the best,
Where it seems to have warmed up after a few sub zero days, and I can now hear myself think above the central heating pump!
Massive poo writes:
i have no formal scientific or medical training, but have managed a home lab for some years studying micro organisms along the following lines:
i have fungus in the bathroom
fungus in my bed
fungus in the kitchen
and fungus on my head
i got a parasite for christmas
and keep it quite well fed
it rides around inside my brain
on a neurotoxic sled
i think it makes me rhyme all day
but perhaps now it is died
(are parasites all criminals?
..they spend a lot of time inside!
err, well on with next weeks case study
as a lay person, i think dr griffins case next week will have the red herring of a do-gooder that doesn’t wear shoes,
but in this case the victim will be attacked by a face eating spider, or to use the latin name, faccio spidercium.
the life cycle of the face eating spider begins and ends with a mature female laden with eggs, who hides under peoples beds at night and giggles
until it can hear the sound of snoring, this triggers the spider to climb onto the bed and jump on the victims face and squirt the eggs into the rosy part of the cheek.
this serves two functions of masking any rash or soreness, and the closeness of blood vessels to the surface of the skin and injection site affords an easy meal for the hatching larvae
the circadium rhythms of the host (usual a mature male of advancing years, say dixon) trigger the larvae to errupt through the skin and crawl to the nearest ear duct or nasal canal where they proceed to masquerade as nose hairs and ear hairs, and feast on bogies and ear wax, the female young do this until pregnant and then scarper under the bed again to repeat the process
i hope that it is not too dispiriting to find a lay person and virtual novice can solve these problems without any research,
but as darwin once said “if you need to study, you’re doing it wrong”
best wishes and kind regards for all your fun and capers
i suppose you have added to the sum of human knowledge in a right prodigious way too, many congrats
Hosts with the mosts
Sorry that this is a question from the beginning of the show buuuuut. Just started listening at 119 and now working from the start to catch up.
It was mentioned that a team of explorers heading for the north pole by balloon went down and had to live on Polar Bear meat to survive. You mentioned that when the explorers bodies were found they were infested with Trichinella from eating polar bear meat. My question is, do fish carry Trichinella. My reasoning is that the mainstay of polar bears are seals and the main stay of seals is fish therefore the only (not quite but almost) source of Trichinella for the polar bears would be fish. Couldn’t find answer online but didn’t check very far.
Dave the sheep shearer in southern Alberta Canada where it is +2c and the chinook wind has died down
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