Joshua writes:
Dear Doctors Despommier, Griffin, Naula and Racaniello,
It was a delight for me to win the prize in Episode 211, on my very first attempt (despite over-diagnosing the patient), and this spurs me on to continue learning about parasitology. I must mention one small point that came up in your congratulatory discussion when my name was drawn – Hobart is in southern Tasmania; I lived there while at University, but I don’t live there now; I live in the principal city of northern Tasmania, Launceston (pronounced “LON-ses-ten”, never “LAWN-ses-ten”). Please don’t get that wrong, it is a notorious shibboleth, as bad as mispronouncing Edinburgh or Dunedin (Dun-EE-den).
While on the subject of pronunciation, why does the esteemed Dr Griffin say “centimetres” (or I guess he would write “centimeters”) with an initial short “o” sound rather than a short “e”? Never before have I heard it said that way. But don’t worry, one great charm of your podcast is the selection of American accents! Many of my ancestors came from Scotland back in colonial times, so I love to hear a Glaswegian too.
This case was quite puzzling to me at first, despite a strong suspicion as to the likely diagnosis. At the outset, mention of a large painless skin lesion immediately suggested cutaneous leishmaniasis. However, the mention of three lesions seemed unusual, though Parasitic Diseases, 7th edition, notes that there may occasionally be more than one lesion. The fact that the lesions were itchy, and that the skin was not at all red around them, seemed a little unexpected, but, to quote the aforementioned tome, “the lesion[s]… may vary in size and shape, sometimes confounding even the most experienced clinician.” (ibid., p. 32.)
According to a 2013 paper by Paz et al. in the American Journal of Tropical Medicine and Hygiene (Volume 8, Issue 3, pages 583 to 585), Leishmania major is the only species of Leishmania known to cause leishmaniasis in Mali. As with all species of this genus in the Old World, it is transmitted by Phlebotomine sand flies; their contaminated bite infects the hapless human host, in whom the infectious protozoa multiply, and when subsequent sand flies come in for a blood meal, they become reinfected, thus completing the lifecycle.
The biopsy revealed the presence of many plasma cells and neutrophils, as expected in a Leishmania infection, but did not reveal any infectious organisms. However, your admirable textbook notes that “Histopathological examination of biopsy tissue… requires recognition of the characteristic amastigote tissue form of the parasite with the nucleus and kinetoplast (the dot and dash).” (Parasitic Diseases, 7th edition, p. 33.) Perhaps the laboratory technician was not looking out for this particular infection, nor familiar with its tell-tale features.
Parasitic Diseases therefore suggests that the test to apply is a NAAT (Nucleic Acid Amplification Test), which is more sensitive and should reveal presence of the Leishmania parasite and confirm which species it is. Other tests would take several days to complete, whether culture of specimens, or the Leishmaniasis skin test used in certain parts of the world (parts not further specified in the aforementioned book), which requires intradermal injection of killed promastigotes.
A remaining mystery concerns the nature of the exogenous material present in the biopsy, which was described as not obviously part of an insect or arthropod, nor as typical of a splinter. This last phrase, referring to the foreign body as not typical of a splinter, suggests that it could be some form of woody plant material. I therefore surmise that the patient may have had resort to a traditional remedy for skin lesions in the form of a poultice that could contain ligneous fragments, perhaps mashed and boiled, which could have adhered to the wound and become intermixed with the scab and scar tissue forming.
An internet search for traditional remedies used in Mali turned up a 2012 paper detailing Malian government-sponsored research and development of such preparations. (Willcox, et al., “Improved Traditional Medicines in Mali”, Journal of Alternative and Complementary Medicine, Volume 18, Issue 3, pages 212-220 – I cannot forbear to note that the first name of the first-listed author is Merlin, but let us prescind from any value judgements based on this and the title of the journal.) This reveals that a decoction of the bark, roots, or branches with leaves of a West African shrub, Psorospermum guineense, is commonly used in Mali to treat a wide range of skin conditions; according to the article, an extract of its bark has been shown to act against the intracellular forms of L. major, though I would wish to see confirmation of that result.
As the afflicted gentleman dwelt with his extended family while visiting his homeland, some of his relatives could have prepared and administered such a folk medicine to him there, or even sent him some of the plant material for him to prepare and apply to his developing lesions after his return to the United States. There is an ointment called “Psorospermine”, produced in Mali from this plant, which his relatives could have purchased and supplied to him – depending on its consistency, this may contain xyloid particles which could stick to the lesion and be found in a biopsy.
Whatever of the putative healing properties of such customary remedies, Parasitic Diseases notes that, in most cases, this unpleasant and unsightly condition will eventually resolve, albeit with significant scarring. There are a number of treatment options, including cryotherapy with liquid nitrogen (a treatment I once received for plantar warts as a child). Paromomycin could also be applied to the lesions.
At least, Old World infections with Leishmania do not have the possibility of developing into mucocutaneous leishmaniasis, as can happen in the Americas, with potentially awful and horrifyingly disfiguring results, as shown in a very upsetting photograph in Parasitic Diseases – my heart goes out to the person pictured, and I hope that they received all the care and plastic surgery they deserved to ameliorate their suffering, just as I hope the patient concerned in this case makes a full recovery soon.
Yours sincerely,
Joshua
2 Jillian writes:
Good evening from chilly Ottawa, Canada!
It’s a lovely clear evening and we’re finally coming down into seasonal temperatures, so we’re sitting at ~-4C, which google tells me is about 24.8F.
In terms of the gentleman’s diagnosis, I have to admit that I found this one rather tricky, as I’m unfamiliar with a lot of the medical terminology that was used to describe the patient’s complaint. All that being said, epidermal issues in isolated locations immediately make me think of insect bites, especially with a reported lack of risky behaviours, like injection drug and local swim hole usage.
Looking at what vectors / diseases are of note in the region – both Leishmaniasis and Onchocerciasis can present as cutaneous lesions. However, you are unlikely to be bitten by a only a few black flies, whereas sand flies do tend towards more singular bites. Also – if we take the individual at face value about their travel history– then it becomes even more unlikely for it to be Onchocerciasis as the blackfly vector is restricted to areas near fast flowing water (like rivers and streams).
By process of elimination then, I’m landing on Leishmaniasis, specifically Cutaneous Leishmaniasis (CL), caused by the bite (rather bites) of sandflies infected with Leishmania protozoa (likely L. major which is predominant in Mali (https://www.researchgate.net/publication/234156838_Leishmania_major_the_Predominant_Leishmania_Species_Responsible_for_Cutaneous_Leishmaniasis_in_Mali ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127506/ ). This is supported by the growth the lesions over time (https://rarediseases.org/rare-diseases/leishmaniasis/ ), which is characteristic, but also due to the lack of other defining features – leishmaniasis lesions seem to have extremely varied presentations. They also tend towards delayed onset and non-healing, which also aligns with the individual’s report. Another point in favour, is that the tests described were inconclusive. Although there appear several ways to positively identify Leishmania infection, those were not reported. I suspect that a Leishmanin skin test, Giemsa stained sample or PCR was used for a positive identification. Treatment for localized CL includes periodic intralesional injections every four weeks (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325692/ ) or taking a “wait and see” approach as they will typically resolve on their own given time.
What I haven’t been able to resolve though is the description of the lesions as itchy! None of the articles I’ve read indicates that itchiness is typical of these lesions, so it’s rather throwing me for a loop! I have found an article that indicates that it can be slightly itchy in areas where clothing is rubbing against the lesions (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325692/ ), but itchiness is far more aligned with Onchoceriasis, which is why I’ll keep it as my differential. I also found a report of co-infection of L. major and fungal spp., which I have since lost, that produced additional symptoms – but this was only reported in a HIV+ immunocompromised individual.
I’m very, very curious to see what other diagnoses come up for this one! Thank you all so much for your hard work and happy holidays for all the TWiPers.
Don’t forget to leave out your drenches for Rudolph’s Cephenemyia! (https://www.wired.com/2015/12/reindeer-bot-flies-are-not-as-cute-as-they-sound/ )
Jillian
Christopher writes:
This was a doozy! I am lucky this case was presented on a podcast about parasites because I would have been going down random differential diagnosis rabbit holes. At the top of my list is the parasitic flea, Tunga Penetrans. This flea has an interesting life cycle. When a female flea becomes pregnant, she seeks out a host. She then burrows into the skin of the host, leaving only her posterior end exposed to the environment. She lives on the host for about 2 to 3 weeks before she dies. During this period, she is releasing eggs into the environment, where the larvae will grow into full-fledged fleas.
The patient suffering from a dermatological complaint could have had Tungiasis, but this is not a slam-dunk presentation. For one, the lesions were on the thighs, and because this flea cannot jump very high, we would have expected them to be on the feet. However he did stay in a household with dozens of people, so he might have had to sleep on the floor, where the fleas would have had access to all of him.
Further, it has been a month since the symptoms presented, so the fleas would probably be dead and out by the time he saw a doctor, but as I once heard eloquently stated: “Open sores are open doors”. He probably has a secondary infection that is recruiting inflammatory infiltrate seen on the histological sample to the lesion. As for the exogenous material, he might have been poking at his lesion with something and part of it broke off in there.
This is all hand-waving on my end, and to be honest, the fact that additional testing lead to the diagnosis gives me pause. My pediatrics shelf exam is in a couple of days, so unfortunately I have limited time to peruse the literature.
Keep these coming! Thank you for all you do.
Cheers!
—
Christopher Hernandez
David Geffen School of Medicine, MSII
MPH 2020
Infectious Diseases and Vaccinology
University of California, Berkeley
Ben writes:
Leishmaniasis
Kimona writes:
Dear TWiP Team,
I’m sorry that my entry last month regarding the scabies infested hemodialysis man was submitted a bit tardy. I like how you announced when the next TWiP will go parasitic – this is very helpful for planning purposes. Here in Vermont it is now (-)6 degrees Celsius with a light snow-covering.
Dr. Daniel described a verrucous-type lesion with yellow crusting in this man from Mali. My first thought went to a bad case of impetigo (caused by Group A Strep) that was unresponsive to treatment; perhaps the same thought his PCP initially had.
But we need a parasitic culprit. I found quite a few parasitic infections associated with nodular or papular, itchy lesions (like ‘swimmers itch’ of Schistosomiasis – but our man denied swimming in any lakes). In only one did I find a description of multiple verrucous-like lesions, and it was in a case of atypical Cutaneous Leishmaniasis (CL) in a young Brazilian man. So, this will be my best guess.
Leishmania is a protozoan obligate intracellular parasite mainly of macrophages, transmitted from animal (often rodent or dog reservoir) to humans by several species of sandflies. In Mali, which would be Old World Leishmaniasis, the disease is primarily caused by L. tropica and L. major, transmitted by the Phlebotomus sand-fly. The promastigotes enter the subcutaneous tissue and are taken up by dendritic cells and macrophages. They are transformed into the amastigote stage and begin to replicate locally at the bite site. An erythematous lesion at the site of a sandfly bite evolves over weeks to months from a papule to a nodule, possibly ulcerating centrally and developing a brownish crust. Multiple primary lesions can be seen, especially in patients infected with L. major, resulting from the probing of sandflies as they try to get blood meals. But I also read that there can be secondary lesions arising along the line of lymphatic drainage of the initial lesion.
I did find a description of sub-types caused by L. Major reported in Mali, either “wet-type” or “dry-type”, differing in their incubation period and time to healing. It’s clinical presentations are known to mimick and mislead, masquerading as tumours, psoriasis, lupus, mycobacterial and fungal infections, etc. I’m not sure if our patient would fall more into the ‘wet-type’? But perhaps these lesions can take on a verrucous appearance.
Diagnosis can be made by dermal scraping smear from margin of a lesion, culture, incisional biopsy, and PCR (which has the added benefit of genotyping and species identification).
Treatment is dependent on species and severity of lesion and its location. Spontaneous healing will occur in the majority of CL cases, but our patient’s case may not fall into that category. He also sounded rather frustrated at the lack of progress with his current care, so I imagine he will be returning to Mali soon unless he is offered a highly effective remedy. Topical cryotherapy would be simple and without systemic effects but perhaps not satisfying enough. Systemic pentavalent antimonials, amphotericin, miltefosine, pentamidine and azole drugs, are all listed as preferred if there is risk for mucosal or systemic spread by the infecting species. Perhaps our patient received liposomal amphotericin, although it has significant side effects, or miltefosine, which is orally available and with lesser adverse effects?
So, this is where my guessing stops. I am in the midst of a busy work week and want to submit my response on time this month. Thank you all for another intriguing case!
Kimona
Michelle and Alexander from the First Vienna Parasitology Passion Club write
Dear Leish-maniacs,
We respond to the case of a young man who is complaining of several chronic, painless skin ulcers after travel to Mali. Antibiotics did not result in improvement and a biopsy of the lesion was not diagnostic.
The differential for chronic wounds on the lower extremities is broad; it is narrowed significantly by the occurrence of concomitant, similar lesions on other parts of the body, by the absence of pain and the absence of edema.
While there is some leprosy in West Africa, the incubation period is in the order of years, not weeks. Other mycobacterial infections like Buruli ulcers have a distinct morphology and also take longer to develop. Yaws usually presents with a nodular lesion and surrounding daughter lesions before progressing to a systemic phase within the timeframe given in the case. Sporotrichosis usually spreads along the paths of lymphatic drainage and does not disseminate as in the way described. Histoplasmosis, especially african histoplasmosis, might fit the case, but would probably be identifiable on biopsy.
By virtue of this being a podcast about eukaryotic parasites, the most likely diagnosis seems to be cutaneous leishmaniasis, caused by L. major, L. tropica or L. aethiopica.
Leishmaniasis is a parasitic disease transmitted by the bites of phlebotomine sandflies. Female sandflies transmit the parasite by biting their victims and injecting the infectious stage (promastigotes) into the skin of their victims. These then proceed to develop into amastigotes, the parasite’s tissue stage. Whether the infection becomes symptomatic and whether patients develop cutaneous or visceral leishmaniasis depends on the host, the parasite species, and other variables.
To diagnose cutaneous leishmaniasis, biopsy is recommended as the method of choice. Tissue should be extracted from the edges of the sores in order to identify the characteristic kinetoplast. The chance of detecting active leishmania is the highest within the edges of the wound, whilst the center usually becomes necrotic and does not contain diagnostic material. In the presented case, the tissue sample was taken from the center of the wound – a classic pitfall when diagnosing this disease. Other methods of detection include PCR plus sequencing to adequately identify the species and Leishmanin-Skin-Test (also known as Montenegro-Test).
There is limited evidence regarding the treatment of cutaneous leishmaniasis. Depending on the species, there are several substances that can be used for treatment, although most patients make a full recovery without medical intervention.
Thank you for this great case. All the best,
Michelle and Alexander from the First Vienna Parasitology Passion Club
Martha writes:
Dear TWiPsters,
Seasonal greeting to all. Although I missed responding to the last case, I do listen to every episode and I must say it was nice to hear that I (and all the other usual responders) had been missed.
Regarding the patient with a 10cm lesion that is not painful, began as small as a pimple and has not responded to treatment thus far. An extensive history is given, but I note the omission of description of the water supply of the family residence. What was used for drinking and washing the raw fruit and vegetables? Also, is there a fast flowing river in the area? We are told that none in the family has the condition. Did any of them ever have a similar condition? Perhaps this is why the person thinks he will get an accurate diagnosis in Mali.
The question boils down to: What eukaryotic parasite is present in Mali and causes a large, non-painful skin lesion and no other symptoms of note?
Running down the list:
Trypanosoma brucei gambiense can produce a painless chancre at the site of the tsetse fly bite. However, no other symptoms are mentioned, no fever, malaise, or joint pain. In the time described I would expect chancre from tsetse fly bite would have healed.
Dracunculus medinensis could have been acquired if the drinking water contained infected copepods. Although the Guinea worm does cause an ulcerated lesion, this is painful unlike the lesion described on the patient. Also the time elapsed does not seem in keeping with the one year from ingestion to eruption for D.medinensis.
Onchocerca volvulus produces skin changes that are unlike those described in the current case. (also no mention of the fast flowing river)
Cutaneous Leishmaniasis caused by members of the genus Leishmania fits the description of the appearance and progression of the lesion. The intracellular amastigotes are only in the skin cells at the edge of the crater which may explain the non-diagnostic biopsy. From consulting google I learned that L. major is present in Mali. From consulting the big red book I learned that Nucleic Acid Amplification Testing is diagnostic and that there are both topical and systemic treatments.
So, that is my answer: cutaneous Leishmaniasis caused by Leishmania major.
Best wishes to you all
Martha
Jason writes:
Greetings TWiP hosts!
It is a chilly morning in Seattle, Washington. The mercury lies at -1 degrees Celsius, and a fine dusting of snow is upon the ground. Harbor seals have flocked onto floating docks, and I can’t help but wonder if any of these pudgy pinnipeds are harboring – pun intended – adult Pseudoterranova decipiens nematodes, but that is a discussion for another time.
In TWiP #211’s Case of the Bamako Blackhead, our young male patient from Mali presents with slowly evolving cutaneous lesions that began as a small itchy pimple on his anterior left thigh that subsequently increased in size into a painless 10cm annular lesion. This initial lesion has been joined by two others of 2-3 cm in size, located on his right flank and right posterior thigh. The lesions are yellow, crusty, and verrucous in appearance. In addition, they are heaped up along the edges, and the edges do not appear to be undermined. The lesion distribution does not follow either a centripetal or centrifugal pattern, and their locations would suggest they are the result of an arthropod bite.
This patient’s clinical presentation, coupled with travel, environmental, dietary, and animal exposures are consistent with cutaneous infection with the protozoan parasite Leishmania major. This species of leishmaniasis is the most prevalent in Mali, and its arthropod vector is the bite of an infected female sandfly of the Phlebotomus genus – most likely Phlebotomus papatasi in this region. Leishmania major is described in the Hunter’s Tropical Medicine 9th edition text as “a zoonotic infection of desert rodents with humans infected as incidental hosts.” Leishmaniasis found east of the Atlantic Ocean is known as Old World leishmaniasis and is normally transmitted by Phlebotomus genus sandflies, while leishmaniasis found in the Americas is termed New World leishmaniasis as is normally transmitted via Lutzomyia genus sandflies.
A brief perusal of the literature on the signs and symptoms of cutaneous leishmaniasis supports this non-laboratory diagnosis, though I found only one mention of pruritus – contained within a 2022 article in The American Journal of Clinical Dermatology by de Vries and Schallig.
Medical practitioners may employ any of the following three tests for laboratory confirmation of cutaneous leishmaniasis: 1) microscopic detection of amastigote-stage parasites in smears taken from both the center and the edges of lesions, 2) detection of promastigote-stage parasites from lesion cultures (Novy-MacNeal-Nicolle medium is typically used), and 3) PCR testing.1
Treatment options for cutaneous leishmaniasis are highly varied, and include watch-and-wait, parenteral therapy, and local therapy. The watch-and-wait approach is generally reserved for cases in which the lesions are small, not located in cosmetically-important areas of the body, and do not carry risk of disease progression to mucocutaneous leishmaniasis. Parenteral treatment can be used in severe cases of cutaneous leishmaniasis, mucocutaneous leishmaniasis, and visceral leishmaniasis. Local therapy is the usual approach to Old World cutaneous leishmaniasis, and includes heat, cryotherapy, topical paromomycin, intralesional injections of pentavalent antimonial drugs, or laser treatment.2
Worm regards,
Jason
1 2020. Cheesbrough M. Tropical Medicine Point-of-Care Testing.
2 2016. Aronson N et al. Diagnosis and Treatment of Leishmaniasis: CPGs by the IDSA and ASTMH.
The University of Central Lancashire Parasitology Club writes:
Dear esteemed Professors,
Festive greeting from the University of Central Lancashire Parasitology Club.
We were a little late submitting for the previous case but were happy to hear that scabies was the cause for the ageing Asian dialysis patient with multiple comorbidities admitted to the Acronym City Hospital (ACH).
The man from Mali with the painless itchy lesions on the thighs might be suffering from cutaneous leishmaniasis. Leishmania major is prevalent in Mali and transmitted by sandfly bites. Paz et al., (2011) described the lesions as painless and erythematous growing larger and darker with a crust after several weeks. Microscopy of skin scrapings has been the traditional method for diagnosis and more recently real-time PCR amplification tests have been developed (Paz et al., 2013).
This is a rather hasty response as I listened to the end of the podcast this morning (22nd December) and heard that this was the deadline date!
From all of us at the University of Central Lancashire, we wish the TWIP team a wonderful Christmas and look forward to a Happy New Year with plenty of challenging and fascinating cases to stimulate our discussions.
David on behalf of:
The Parasitology Club of the University of Central Lancashire.
PS: We are eagerly awaiting the arrival of a copy of PD7 that was delayed during COVID and hope that Santa has this on his sleigh for us this yuletide.
References:
CDC-Centers for Disease Control (2020). CDC – Leishmaniasis
Paz C, Doumbia S, Keita S, Sethi A. Cutaneous leishmaniasis in Mali. Dermatol Clin. 2011;29(1):75-78. doi:10.1016/j.det.2010.08.013
Paz C, Samake S, Anderson JM, et al. Leishmania major, the predominant Leishmania species responsible for cutaneous leishmaniasis in Mali. Am J Trop Med Hyg. 2013;88(3):583-585. doi:10.4269/ajtmh.12-0434
Dr David Wareing
Senior Lecturer in Medical Microbiology
Course Leader for B.Sc. Microbiology
University of Central Lancashire