Case guesses:

Evan writes:

Hello Drs. Racaniello, Despommier, and Griffin,

I write to posit my guess at episode 174’s mystery case. Based upon the patient’s location and symptoms, as well as that of the other children in the refugee camp, I would suspect the patient has visceral leishmaniasis. The recurring fever initially made me think of malaria, but the cycle in this case is far shorter and antimalarial drugs failed to relieve symptoms. However, the enlarged liver and spleen could be indicative of a Leishmania infection. The location is endemic for Leishmania and an open-air camp would give the sandfly vector ample access to unfortunate people. Amphotericin is an effective drug against leishmaniasis and proved to work in the case of these children.

First time writing in and hope I’m not proven too wrong!

I just began my MD-PhD program at the University of Virginia and hope to further explore infectious diseases. Thank you for the amazing and informative podcasts. 



Caleb writes:

Greetings Drs. Racaniello, Desponommier, and Griffin:

My case guess for the 12 yo male living in a refugee camp after fleeing Sudan, is visceral leishmaniasis, also known as kala-azar or Black fever. As a medical and veterinary entomologist, I appreciate cases that involve insects as vectors of the parasites. When Dr. Griffin stated the history of recurrent fevers, my initial response was malaria, but after hearing that the antimalarials failed, and the keywords of ” enlarged liver and enlarged palpable spleen” or hepatosplenomegaly, leishmaniasis became the only parasitic option in my mind. Only with a quick google search of IV amphotericin and leishmaniasis, which turned up “Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL),” my diagnosis was confirmed. I appreciate all the hard work you all put into each episode and the entertainment you provide! 

Caleb Hubbard  

Ph.D. Candidate: Medical and Veterinary Entomology

University of California, Riverside

Daniel writes:

Honored professors,  The temperature is 75 degrees F and mostly sunny in Goshen, Indiana (the land of milk and honey).  I am a long time listener and first time writer. Thanks for your outstanding podcast and ongoing educational efforts.  My guess for case from episode #174 is visceral leishmaniasis. I have inserted a somewhat old abstract related to the Sudan and visceral leishmaniasis.  I do think the empiric trial of anti-malarial therapy made sense. Unfortunately patients around the world don’t have the advanced diagnostic tests that we have in the United States so I am glad the subsequent empiric amphotericin therapy was successful.  I may have missed it from an earlier podcast but I would be very interested in how Dr. Griffin balances his clinical, academic work and world travel. Dan

Trans R Soc Trop Med Hyg. 2001 Apr;95 Suppl 1:S27-58.

Leishmaniasis in Sudan. Visceral leishmaniasis.

Peter writes:

Dear Drs TWIP

Long time listener, first time guesser. Also long time bioinformatician, somewhat newer pathogen hunter.

I suspect that the boy whose disease was described in TWIP 174 is suffering from visceral leishmaniasis (VL). From the description in Parasitic Diseases, 7th Edition, enlarged spleen and liver (hepatosplenomegaly) is a symptom of this disease. However, PD 7 goes on to state that “Onset of disease is accompanied by high  fever, which may be irregular, often giving rise to a characteristic double daily spike”, whereas the patient reported a fever every second day. I will rely on the description of fever as “irregular” though to explain this discrepancy. Finally Dr Griffin mentioned that treatment with amphotericin appeared to relieve the symptoms. Again looking at PD 7, amphotericin is only mentioned in the treatment of VL and (without much success) in the treatment of N. fowleri infection, but since this case has none of the CNS symptoms of N. fowleri I remained persuaded that this is a case of visceral leishmaniasis. 

In addition Zijlstra and El-Hassan [1] report that “[f]rom the early 1900s, visceral leishmaniasis (VL; kala-azar) has been among the most important health problems in Sudan, particularly in the main endemic area in the eastern and central regions”, and the very regions the authors name have been sites of conflict in Sudan and thus a likely origin for this unfortunate boy.

Besides references (more commonly to the cutaneous form) to leishmaniasis on TWIP, I am can credit my knowledge of leishmaniasis to conversations with   in Nairobi, Kenya. You can read more about their excellent work in building endogenous (East African) capacity in managing Neglected Tropical Diseases in [2].  

Three diseases listed in PD 7 are also associated with splenomegaly, and I list them here as an attempt at differential diagnosis. This differential is complicated by the widespread prevalence of fever-causing parasitic diseases in the region. 

1. Malaria – but it was reported that anti-malarials were administered with no effect. P. malariae, which is associated with splenomegaly has, however, been found with antimalarial drug resistance [3] so this lack of response is not necessarily definitive.

2. Acute stage of African Trypanosomiasis – but no joint pain was reported

3. Visceral Larva Miigrans – but no lower respiratory symptoms reported

4. Schistosomiasis – but no diarrhea reported

5. Non-parasitic diseases: syphilis (but antibiotics had no effect and it also seems unusual for a 12 year old boy) and hepatitis C but low prevalence in Sudan [4] and no muscle pain reported.

I both work and am a student at the South African National Bioinformatics Institute in Cape Town, South Africa. The weather today is cold (14 C – about 57 F) and somewhat cloudy but with no rain.


[1] E.E. Zijlstra, A.M. El-Hassan, Leishmaniasis in Sudan. 3. Visceral leishmaniasis, Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 95, Issue Supplement_1, April 2001, Pages S27–S58,

[2] Masiga DK, Igweta L, Saini R, Ochieng’-Odero JP, Borgemeister C (2014) Building Endogenous Capacity for the Management of Neglected Tropical Diseases in Africa: The Pioneering Role of ICIPE. PLoS Negl Trop Dis 8(5): e2687.

[3] Antony HA, Parija SC. Antimalarial drug resistance: An overview. Trop Parasitol. 2016;6(1):30–41. doi:10.4103/2229-5070.175081

[4] Mudawi HM. Epidemiology of viral hepatitis in Sudan. Clin Exp Gastroenterol. 2008;1:9–13.

Adam writes:

Good morning Twip’ers! 

I have recently discovered this fantastic podcast and I thoroughly enjoy the case studies. This is the first time that I have been able to write in my case diagnosis prior to the next TWIP episode. I have recently started my Internal Medicine residency with a goal to continue on to an Infectious Disease fellowship in the future. Needless to say, your podcast has helped fill the doldrums of residency while simultaneously filling my need for interesting infectious disease cases, so please keep up the great work!

The case of the 12 y.o. Sudan boy with fever and hepatosplenomegaly is a curious one, but I think I have the correct diagnosis. In short we have a boy with chronic, undulating fevers, chronic abdominal pain, hepatosplenomegaly, and improvement in symptoms with treatment of amphotericin. Initially my thought process was that common things are common. Undulating fevers in a patient in Africa is malaria until proven otherwise in my opinion. Yet in this case there was no improvement with anti-malarials. My next thought was that this could be a presentation of Human African Trypanosomiasis (HAT) also known as African Sleeping Sickness. Patients will often present with undulating fevers, can have hepatosplenomegaly along with some associated abdominal pain early in the infection. With a long incubation period, this could account for the chronicity in the 12 y.o. boy. The issue with this diagnosis is that the boy had no neurologic symptoms, and the treatment for HAT is suramin in an acute infection and melarsoprol in more severe infections with neurologic involvement, which our patient did not receive. 

This then brought me to what I believe to be the diagnosis: Visceral Leishmaniasis. My only hesitation is that just a few TWIPs ago, the case study was of cutaneous leishmaniasis. But if the boot fits, then wear it in order to avoid sand fly bites. Visceral Leishmaniasis is spread by the sand fly as was explained in the previous TWIPs. Two species exist that cause visceral leishmaniasis: L. Donovoni and L. Infantum.  In our patient’s case, I believe him to be infected with the Donovoni species given his location, however from my reading the species does not necessarily need to be distinguished. In any case, visceral leishmaniasis often presents with fever (sometimes undulating), hepatosplenomegaly, and pancytopenia due to bone marrow involvement. I can only speculate that the boys abdominal pain is due to his now enlarged spleen and perhaps liver. One pathomnemonic phrase or sign seen with visceral leishmaniasis is kala-azar and is why it can sometimes be called “black fever.” This of course is referring to the darkening of the skin of those infected. However, this is really only seen in South Asia and is only present about 20% of the time. Definitive diagnosis of the disease is done via bone marrow aspirate showing amastigotes. Treatment of course would include amphotericin but could also include stibogluconate sodium. 

Thank you again for the great podcast and I look forward to hearing the resolution of this case on the next episode. 

Adam Ladzinski, D.O. PGY-I

Kalamazoo, MI


1. Famularo, Giuseppe,M.D., PhD., Mancini S, M.D. Visceral leishmaniasis. Mayo Clin Proc. 2016;91(9):1322-1323. doi:

2. Agrawal, S., Rai, M., and Sundar, S. (2005). Management of visceral leishmaniasis: Indian perspective. J. Postgrad. Med. 51(Suppl. 1), S53–S57.

Lauren writes:

Hello, Daniel, Dickson, and Vincent.

Case Study for TWiP 174 for the patient a 12-year-old refugee with a history of fevers every other day, for many months. Utilizing the free PDF of parasitic diseases 7th edition I started to look up what was effective. Using control F to search for Amphotericin, the results were 26 hits, but 5 species, yet two phylum protozoa and amoeba. With this short list I went to Parasites Without Borders web page to watch Parasitic diseases lectures on Protozoan parasites. Once there I watched lectures on the 5 species of parasites.

Differential; Balamuthia mandrillaris, Naegleria fowleri, Malaria,  cutaneous and visceral leishmaniasis. PD7 posted that both Balamuthia mandrillaris, Naegleria fowleri Could be found in the perfunctorily named Protozoans of Minor Medical Importance,(can you guys explain the reason for the naming of “minor medical importance”, is this do to the low Incidents of disease/number of cases?), corresponding to PWB lectures 18#. Both B. mandrillaris and N. fowleri we’re not consistent with our patient symptoms, because he lacks CNS involvement, or the pathogen is not found in the region. For malaria I did not disregard due to the possibility for resistance to anti-malarial medication. Listening to TWIP in the past cutaneous and Muco-cutaneous Leishmaniasis has been frequent for case studies and cutaneous even easier to diagnose. The key to identifying cutaneous Leishmaniasis are the three nons; nontender, non-undermined nonhealing ulcer.  But what of old world Visceral leishmaniasis? I remembered seeing pictures of splenomegaly. I knew the correlation of liver damage and fevers. So I’m glad I checked leishmaniasis out anyway. the case study example for PWB was extraordinarily similar two our case study of the 12-year-old South Sudanese refugee.

Diagnosis; Visceral leishmaniasis by an old World leishmania donovani. Consistent with splenomegaly and hepatomegaly, Chronic fevers occurring every other day, 80% mortality if untreated, and found in Sedan and Southern Sudan. To confirm if there were resources, aspirating the spleen (not recommended, Needlessly dangerous),  flow cytometry of bone marrow anagen tests, and the preferred method of rK39 dipstick, normally widely available and not as invasive. 

Treatment; Continue treatment of and as much comfort as can be provided in this severely underserved setting for recuperation.  lookout for Post-Kala-azar Dermal Leishmaniasis within 6 months? Not sure of correlation with age of the patient, or of the disease.  

Prevention will be difficult; I am not just talking about stopping sand flys from spreading leishmaniasis, nor obtaining necessities for this refugee camp, but the cause of the long-term instability of the region. What one needs for prevention is the prevention of patients being bitten from sand flys and subsequently others from being bitten by sandflies, protective clothing, bed netting, personal and area insecticide, avoiding areas and times of day that the sand flies are active. It’s hard to stay indoors when there’s no doors to stay in. it’s hard to get protective covering when there’s no protection. Uncertainty is  what you need to prevent. South Sudan has been both blessed and cursed with rich geologic resources. The following is sloppily paraphrased from Human Rights Watch on South Sudan; Improvements; In July the UN imposed an arms embargo. leaders are subject to individual sanctions. The bad; Leaders on all sides are operating with Impunity. Warring parties continue to restrict access for the UN and humanitarian groups. The government has become increasingly intolerant and repressive. civilians have been killed, often because of their ethnicity or perceived political alliances. civilian infrastructure has been looted and destroyed.(HRW)

Regrettable yet understandable, when you consider the vast reserves of petroleum and valuable metal ores South Sudan has.  South Sudan needs to diversify their economy anyway that the citizens would be more valuable as the workforce, then the commercial value of petroleum and ore. Something better paying and economically secure than traditional agriculture; and may be some kind of global futures market that would benefit from successful healthcare and disease prevention in South Sudan. 

Thank you, Vincent, Daniel, and Dickson, sincerely.


Lauren Hall

P.S. Disclaimer; I am not trying to be offensive to Sudanese or south Sudanese peoples but trying to offer some alternative ideas.

Octavio writes:

Esteemed Professors,

As Professor Griffin was telling the tale of the 12 year old boy, I instantly remembered some papers from the Médicins sans Frontiéres, the Human Rights Watch and the UN Office for Humanitarian Affairs I read some years ago, telling the tragic story of the Nuar, Leek and Dinka people of South Sudan, in the area around the River of the Gazelles (Bahr al Gazal) and the White Nile, during the early 1980s, describing a grim circus of violence, displacement,  famine, disease and death.

There were several articles on the newspapers during those years, up to the early 90s where stories such as those of the villages where half to five quarters of the population died, made the short term impact that happens whenever such a story of chronic emergency gets to us.

All over the Continent the story never changes much: In this area of the Unity Province (a very ironic name indeed), the tribal rivalries served as a good way to fuel territorial claims in this resource-rich land; cattle raisers were deprived of their animals, homes were burned, people murdered and survivors moved to different areas, in search for food and places to hide from raids. Frequently bushland areas of Acacia and Balanites trees, where some foraging could yet be done.

As people moved from the Jikany area, south of the El Ghazal River, towards north and east, during the early to mid 1980s, they carried the same disease the 12 year-old boy of the case had. It is estimated that more than 100.000 people had died from it since 1984. The spread of the pathogen causing it results from the dissemination of the vector insect due to the expansion of the Acacia forests caused by reduced cattle grazing; the introduction of the parasite by military, militia and a myriad of more or less organized armed groups moving between Ethiopia and Sudan in the mid 1980s and; Also a very important factor was the high susceptibility to the infection caused by mass starvation, nonexistence of health care facilities, and the attacks on the ones installed by humanitarian services.

It’s a story that could illustrate John of Patmo’s Apocalypse, where the four horsemen (war, pestilence, famine, and death) seem to ride in circles in this land for almost 40 years now. It’s easy to see in Google Earth, even today, the scars caused by artillery shelling in vast areas of those provinces (just look for a settlement as Leer or Bentiu and zoom in. One will see the land peppered by thousands of impact craters).

The disease is kala-azar or visceral Leishmaniasis, caused by several strains of Leishmania donovani. The transmission is by Phlebotomus orientalis. Many patients develop Post Kala Azar Dermal Leishmaniasis.

The search for a vaccine carries on, and have evolved from whole irradiated live parasites, to the use of antigens as LEISH-F, in the form of DNA vaccines or microbial vectors.

Unfortunately the progress has been slow and the very important adjuvant factor of  peace and stability in the area has also been an objective difficult to reach.

I hope the boy got well and was, at the end, a good story in the middle of all this decade-lasting tragedy.

Thank you very much for your remarkable work spreading the word of Science.

Gratefully yours,



(Veterinarian @ BI Animal Health)

Erin writes:

Hi TWIP team!

I wanted to write in with a comment on this week’s episode (174 – fat cat) and a case guess, while I’m at it. 

I really appreciated the great discussion on toxo and cats – as a veterinarian, something I deal with a lot. You’d mentioned wondering whether cats experience the same problems in pregnancy as humans do when infected with toxo…while the research on this is slim, there is at least some evidence that yes, new toxo infection while pregnant is bad for cats and their fetal kittens. I attached a good recent review that goes over some of this evidence, and their summary is: “kittens born to queens infected with T. gondii during gestation can become infected transplacentally or via suckling; in general, clinical illness is common and severity varies with the stage of gestation at the time of infection.” So I guess cats shouldn’t clean the litter box either 😉

Also in relation to the cat/toxo discussion, just to speak for the cats: cats infected by toxo CAN become seriously ill from their toxo. While often initial infection leads to nothing but mild GI signs, and as you mentioned cats that harbor latent infections can become clinically ill if their immune systems are compromised. But, there are also reports of normal healthy cats developing systemic manifestations of toxoplasmosis – whether disease manifestation in these cases is related to toxo strain, coinfection, infective dose, etc, seems to be still unknown. I can attest to this with some cases I’ve seen myself, though, of otherwise healthy cats developing serious pulmonary, neurologic, or ocular disease from toxoplasma infection.

Finally, switching gears – my case guess: I think in this case the doctor who prescribed the amphotericin b as a treatment trial for this boy was suspecting visceral leishmaniasis. Based on PD7, typical symptoms of VL include intermittent fevers and hepatosplenomegaly, and according to the WHO, VL is endemic in that area of E. Africa. Amphotericin (liposomal) is the treatment of choice for VL in India, so if available in the resource-limited setting described would be a good option for a treatment trial.

Thanks for a great show (and sorry for the long email)!

Kevin writes:

12 year old Sudanese boy living in a refugee camp due to the displacements of civil war. The patient has fevers every other day, chronic abdominal pain and hepatosplenomegaly on exam. Failed empiric antimalarial and empiric antibiotic treatment. Empiric parenteral amphotericin resulted in symptom resolution.

Multiple risk factors and clinical clues coalesce here to lead to a diagnosis. Patient age (child), geographic location, gender, socioeconomic status (poverty stricken refugee), presumed poor nutrition as well as fevers and hepatosplenomegaly beat a path directly to a presumptive diagnosis of visceral leishmaniasis. Of course other common diseases in the region must be considered, such as malaria, tuberculosis, schistosomiasis. Intercurrent illnesses such as dysentery and pneumonia must also be borne in mind. The fact that amphotericin resulted in a rapid resolution of symptoms is another strong indicator that our patient had kala-azar. 

A tidy clinical definition of kala-azar is given in the 7th edition of Manson’s Tropical Diseases (1923): “An infective disease characterized by chronicity, irregular fever, enlargement of the spleen and often of the liver, the presence in these and other organs of Leishmania donovani, emaciation, anaemia, leukopenia, and relative increase of large mononuclear leukocytes, frequently a peculiar hyperpigmentation of the skin, and a high mortality.”

This case is refreshing due to being stripped down to its clinical essentials, where we are bereft of the glories of technology and must fall back on our now oft derided sensory and intellectual skills. I am compelled to quote another golden-oldie (to wit Castellani & Chambers 3rd edition Manual of Tropical Diseases (1920):

“A systematic clinical examination of every patient is most essential. It is the sum total of the various symptoms, none alone pathognomonic, which establishes the diagnosis in conjunction with which the results from the laboratory must be considered. A Practitioner who is unable to come to some sort of a diagnosis without the aid of a laboratory should, in our opinion, utilize his earliest spare moments in a course of post-graduate instruction with regard to clinical methods.” 

The history of kala-azar is quite interesting and colorful and has been beautifully reviewed by Steverding in 2017. A few tit-bits can be found in my end notes.

Diagnosis and treatment of kala-azar is well described in PD6. In brief, though the gold standard of diagnosis is demonstration of amastigotes in infected tissue, DNA and immunological methods have largely replaced histopathology. Treatment is critical, since mortality rates can be as high as 95-100% in untreated disease. There are multiple treatment strategies, and, according to the WHO: “The treatment of leishmaniasis depends on several factors including type of disease, concomitant pathologies, parasite species and geographic location.” WHO Technical Report 949 states that the pentavalent antimonials have been standard first line therapy for seventy years. Though resistance has been noted in some areas, the WHO 949 states that cure rates of 93% have been demonstrated with antimonials. The Federal Ministry of Health for the Republic of Sudan’s 2014 report states that first line treatment is a combination of sodium stibogluconate and paromomycin. Liposomal amphotericin is listed as a second line treatment. 

Out of respect for the listener’s patience, I have buried my obsessive digressions in the end notes. Suffice to say that my superannuation slapped me in the face when I began to fiddle about with the term ‘reticuloendothelial system.’ Then there is my obligatory sniffing around the etymology of kala-azar (with all due respect to PD6’s well crafted explanation), and lastly, I wanted to explore Dr Griffiths intriguing comment during TWiP 173 referring to a form of echinococcosis with malignant characteristics. 

Thanking the TWiP professors; you are not twipping a dead horse. Carry on.


The History of Leishmaniasis, Dietmar Steverding, Parasites & Vectors, volume 10, Article number: 82 (2017)

Manson’s Tropical Diseases, A Manual of the Diseases of Warm Climates, Manson-Bahr, Philip H, 7th edition London: Cassell & Company 1923 Free download at GoogleBooks

Manual of Tropical Medicine , Sir Aldo Castellani, Albert John Chalmers, W. Wood, 1920.

Free download on GoogleBooks, Check out Part II, Section B, Chapter XI: Arrow poisons.

Manual for the diagnosis and treatment of leishmaniasis, Republic of Sudan, Federal Ministry of Health, Neglected Tropical Disease Division (NTDs) October 2014

WHO Technical Report series #949, Control of the Leishmaniases 2010. An open access comprehensive 200 page monograph.

Anorectal tumor as a debut form of visceral leishmaniasis, JoséPintor-Tortolero, et al Surgery 0 0 0 (2018) 1–2  Bizzare case of a 77 y/o man with proctalgia and anal suppuration. Another candidate for the monniker ‘The Great Imitator?”

From the Reticuloendothelial to Mononuclear Phagocyte System – The Unaccounted Years, Simon Yona and Simon Gordon, Frontiers in Immunology 6:328. 2015  The authors wittily describe their review as a ‘phagocyte retropective.’


Kala-azar etymology, from Assamese: black disease (according to OED). Castellani’s text notes that Ross states that the correct name is kala-jwar (black or mortal sickness). Though the OED quotation suggests that the name derives from the associated hyperpigmentation of the skin, it seems possible that the word ‘black’ might be metaphorical rather than descriptive (of skin changes.) Other names for the disease: dum-dum fever, Sahib’s disease, cachectic fever, tropical splenomegaly, non-malarial remittant fever, Sirkari disease)

NOTE: Dum Dum -a town near Calcutta, really a military cantonment/arsenal/military camp during the Raj. 

According to Steverding (2017): “The naming of the disease as kala-azar refers to the greyish discolouration of the skin of light coloured people in the course of the infection.”

Quote from the OED entry on kala-azar:

1883   J. J. Clarke in Ann. Sanitary Rep. Assam 1882 36   As far back as 1869, the attention of administrative officers in Assam became directed to a peculiar disorder (called ‘Kala Azar’, the ‘Black Disease’, from the singular bronzing of the skin so often observed with it), the ravages of which decimated..numerous villages in the district of the Gáro Hills.


I was shocked to learn that the biology of visceral leishmania transmission (by phlebotomine sandflies) was not delineated until 1941. 

from Wikipedia:

“The actual mode of transmission through the bite of the sand fly was finally demonstrated by the British-Israeli parasitologist Saul Adler (1895–1966) in 1941 when he successfully infected five volunteers with sand flies experimentally infected with L. tropica in the laboratory. One year later, it was also conclusively proven that sand flies are the vector of kala-azar.”


Kala-azar was at one time considered to be largely an infection of the RES. This case resurrected a term that I haven’t seen used in a long time, and one that I never completely understood. Hence these quasi-relevant musings:

The quantitative word search engine, the Google Ngram Viewer ( shows the declining fortunes of the term RES. It peaked in 1973 and I never noticed. I always thought of the RES as a mysterious grouping of organs (liver, spleen, lymph nodes and bone marrow) united in the jobs of immunity and general debris ‘clean-up.’ The term reticuloendothelial system was coined by Karl Aschoff in 1924 to describe a widespread group of phagocytic cells that were capable of taking up vital dyes. As Yona and Gordon note: “…reticulo refers to the propensity of these large phagocytic cells to form a network or a reticulum by cytoplasmic extensions; endothelial refers to their proximity to the vascular endothelium, from which they were sometimes believed to arise, these cells formed Aschoff ’s unified system throughout the organism. The capture and clearance of unwanted particulate material from blood were considered to be the major function of the RES.”

The literature on this topic quickly becomes specialized. The main point I come away with is that the term RES has been largely replaced by the term ‘mononuclear phagocyte system’, though there are numerous technical quibbles on this point. 


In my TWiP 167 reply I noted two parasitological martrys: Prowazek and Schaudinn. Apropos of our Sudan location in TWiP 174, I call your attention to another casualty of tropical research:

Alexander Mactier Pirrie FRAI (1882–13 November 1907) was an early 20th century Scottish anthropologist, studied anthropology at the University of Edinburgh graduating with a BSc in 1904. He then took a further postgraduate medical degree graduating MB ChB in 1906. He was created a Fellow of the Royal Anthropological Institute. 

In 1906 he went to the Sudan with the Wellcome Research Institute to work in their laboratory in Khartoum. In 1907 he went on an expedition to Shilluk territory in the south. He took many photographs of the Nuba people in Renk. However, within a month he had contracted Kala-azar fever and he returned to Khartoum and ultimately died in Edinburgh in 1907. 


(image in the public domain, from Castellani & Chambers ,Manual of Tropical Medicine 1920)


In the two classic tropical medicine textbooks I reference above, fever figures prominently in the tables of contents. Old medical articles and texts almost always contain abundant fever graphs. I recall fever charts being a staple of old cartoons, where a doctor (invariably wearing a head-mirror) holds a clip-board with a fever chart. Note the Wikipedia entry for ‘head mirror’: “Because they were once in common use, notably by general practitioners and otorhinolaryngologists, head mirrors are often a stereotypical part of a physician’s uniform by costumers and prop men e.g. in comic routines.” 

Below is a more or less random list of some fever terms I came across while researching this episode.

undulant fever–a kind of sine wave pattern..brucellosis

rat-bite fever

japanese river fever

relapsing fever borrelia

blackwater fever

phlebotomus fever

quotidian every 24 hours (daily- e.g. P knowlesi, adult Still disease)

double quotidian

tertian 48 hour periodicity (vivax, ovale)

malignant tertian (P falciparum)

quartan 72 hour periodicity (P malariae)

hectic fever: “A fever with accessions at noon and evening generally with night sweats and later lateritious 

urine. {Lateritious=brick-red in color} (The Philadelphia Medical Dictionary, John RedmanCoxe, 1808)

erratic fever

remittant fever: temp goes up and down but never touches the baseline normal

intermittent fever: temp oscillates between fever and normal

continuous fever

drug fever

neutropenic fever

NOTE: periodicity of fever is an unreliable guide to malaria diagnosis

1865 medical dictionary A Dictionary of Medical Science–Robley Dunglison– lists scores of fever entities such as febris hepatica, febris anomala, febris amatoria, febris continua putrida icterodes Caroliniensis {a subset of the febris flava americana}

Hippocrates Aphorism 30: Those intermitting fevers are hard to be determined, when the paroxysm returns the next day at the same hour, at which it left the patient the day before. 


This TWiP case location moves me to recommend a fantastic and heartbreaking documentary that is about a solo American physician working in the remote and war ravaged Nuba region of the Sudan. Measles, malaria, and many other scenarios not unfamiliar to listeners to the TWiX family of podcasts.

The Heart of Nuba 2016 ‧ Documentary ‧ 1h 25m….American doctor Tom Catena dedicates his life to treating patients in the Nuba Mountains of war-torn Sudan. Can watch for $2.99 on Amazon. Also available on Hulu


I was stimulated by Dr Griffith’s comment on a TWiP letter mentioning echinococcus infection in Canada (from a July 25, 2019 NEJM correspondence). He alluded to cancer like behavior of some echinococcus infections. I briefly discuss 2 cases below that reprise the parasite/cancer matrix. 

The November 5, 2015 NEJM has an arresting leader ” Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms.” WOW. Tapeworms don’t get cancer (at least until this paper was published.) 

The article’s summary concludes, “Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.” This is the strange case of a 41 y/o Colombian man with HIV in whom small invasive malignant appearing cells of ‘non-human origin’ were found. PCR targeting eukaryotic cells identified Hymenolepis nana. The host–parasite interaction that we report should stimulate deeper exploration of the relationships between infection and cancer.” There are some very intriguing references with this article, ranging from neoplasms in coelenterates, flatworm cancer and canine transmissible cancers (dirty dirty libidinous dogs.)

The echinococcus case referenced involved a 61 y/o Swiss woman with a typical liver hydatid with associated bilateral calcific pulmonary nodules. Clinically she appeared to have an advanced malignancy. She was treated with albendazole but ultimately died of complications due to her advanced echinococcus infection. The authors are concerned that alveolar echinococcosis is increasing in incidence in Europe and Switzerland. 

Disseminated alveolar echinococcosis resembling metastatic malignancy: a case report, Caire Nail L et al, J Med Case Rep. 2017 Apr 18;11(1):113. doi: 10.1186/s13256-017-1279-2. OPEN ACCESS 

Malignant Transformation of Hymenolepis nana in a Human Host, Atis Muehlenbachs, et al, NEJM November 5, 2015, 373:1845-1852

Denise writes:

Hi all,

I hope this finds you well.  I’m a long term listener from an at the moment gloriously rainy Blighty, and wish to hazard my first semi-educated guess in the case from episode 174.  Based on the enlarged organs, fever and response to amphotericin, I would suspect visceral leishmaniasis (probably L. infantum based on the location.)  

While I understand that further diagnostic tests could not be performed on this patient, would it have been possible to conduct an autopsy on one of the other children who had sadly already perished?  From PD7 it appears that the parasites can be seen microscopically in biopsied material. I suspect that if not there were very good reasons, but as a lowly biomed undergrad it is currently beyond my ken.

Thank you all for producing such a fantastic show, TWiP always makes it to the front of my podcast queue (although the rest of the TWiX universe is never far behind!)

Take care,


Daniel writes:

Ciao successful hosts,

I’m a long-time listener and first-time tackler of a case study.

I’ll jump right in and say the prolonged fever indicates the child was infected some months ago and the chronic abdominal pain is likely caused by enlarged liver and spleen. 

The ineffectiveness of antibiotics and antimalarials rule out their respective target pathogens, and given the location, I think the culprit is Leishmania donovani or L.  infantum causing  Kala-azar (visceral leishmaniasis VS). 

The parasite and sandfly vector are both endemic to Sudan and referencing Parasitic Diseases (7th ed.) Kala-Azar has a 3-6 month incubation time which fits with the child’s bouts of irregular fever. Visceral leishmaniasis also explains the hepatosplenomegaly and as the disease is common in children it may explain the recent deaths of the other children with similar symptoms. 

Also, amphotericin is used to treat Leishmania and explains the boy’s recovery after treatment. 

This is actually the first time I decided I would do a little research and attempt to answer a case here on TWIP and I had a lot of fun in the process. In fact, I stumbled upon a fascinating case study in the Saudi Medical Journal were “an 8-year-old Yemeni boy…presented with prolonged fever, hepatosplenomegaly, and diarrhoea…after performing a blood film a full therapeutic course of antimalarial and schistosoma [drugs] was administered but the boys fever, weight loss, and increased hepatosplenomegaly continued. Bone marrow aspiration was carried out also revealed Leishman-Donovan bodies (amastigote form)! This 8-year boy was concurrently suffering from leishmaniasis, malaria, and schistosomiasis! Fortunately, he survived. I was complaining about having to run a few gels over the weekend but after reading that I’ll do it with a smile!

(doi: 10.15537/smj.2015.4.10757)

I really appreciate your podcasts, it’s such a pleasure to listen to you all so I was very happy to join the Patreon group, I’m only in the buck a month club but after my PhD, I’ll hopefully be able to up that to a few bucks at least. I feel pretty bad because I’ve been listening to TWIP since we covered Plasmodium in my undergrad zoology course in 2009 or 2010…  I think, is TWIP really running so long?

Anyway, you’re worth more than a dollar a month but I’m a perpetual student it’ll have to do for now.

I look forward to hearing the reality of the case study and taking part again.

Sorry for the long email,

All the best from very hot and humid Padova, Italy, 

Ben writes:

Dear members of a TWiPartite complex,

I believe the boy had visceral leishmaniasis, most likely caused by Leishmania donovani. This diagnosis fits well with the symptoms, and additionally amphotericin B works well against leishmaniasis without as many side effects as some of the other antimonial leishmania drugs. Visceral leishmaniasis also fits well with the child’s location, according to the WHO more than 95% of visceral leishmaniasis cases occur in only 10 countries; and Sudan is one of these 10. Sadly, many of the countries that have >95% of visceral leishmaniasis cases have large and growing refugee populations and large numbers of internally displaced people so it seems likely that the incidence of leishmania will grow amongst the some of the world’s most vulnerable people in years to come. Furthermore, it is predicted that climate change will significantly enhance the spread of Phlebotomine sandflies in the future and so leishmaniasis may be an emerging public health care issues in regions where it isn’t currently. It seems to me that the influence of climate change on the distribution of disease vectors is something that doesn’t receive the media coverage it deserves.

In the previous episode Vincent said that I had not previously won a book, but I did on episode 170, so I’m glad the random number generator didn’t pick me last time! 

I’ll re-attach my details to this email in-case they’ve gotten lost somewhere 🙂

It’s a balmy 7 degrees Celsius in Adelaide today and we’ve just had a weekend of wild weather; but you can never keep the sunshine away from South Australia for long 🙂

Thank you all for parasitising my headphones on the daily commute.



Ben Liffner

PhD Candidate – Malaria Biology Lab (Wilson Lab)

Research Centre for Infectious Diseases

School of Biological Sciences

The University of Adelaide

Mike writes:

My Dear Professors:

Regarding the boy in the vignette with prolonged fever, hepatosplenomegaly, and abdominal pain, I would like to guess visceral leishmaniasis, also known as kala-azar. Given the setting of a refugee camp in the Sudan, a prolonged course, and several other refugees who succumbed from a similar illness, it is my first and only guess. VL ranks second only to malaria in mortality, and is prevalent in eastern Africa. It has a high fatality rate without treatment (over 90%). Although we are generally taught to make the diagnosis before starting treatment, the doctors caring for this young fellow had few resources other than their experience. Having failed to respond to antimalarials, which could also present similarly, their next choice would be to treat for the next most likely fatal illness. Had they access to a laboratory, they would most likely have noted anemia, thrombocytopenia, leukocytosis (all nonspecific findings) and visualized the amastigote on blood smear. More advanced diagnostic techniques such as culture or molecular detection of parasite DNA would have helped. 

In general, response to treatment is not a diagnostic test, as amphotericin is used to treat a variety of fungal infections which can also cause fever of unknown origin, hepatosplenomegaly, and abdominal pain. However, there would unlikely be so many others dying of fungal infection all at the same time. 

I would also like to commend you on the excellent podcast. I enjoy them all, but I especially enjoyed this episode, from the case to the fascinating paper on toxoplasmosis. 


Joyrell writes:

Hello hosts,

   This is my first time trying a diagnosis and I am looking forward to hearing it read on the podcast. As Daniel was recounting the medical history, my knee jerk response was malaria. All the symptoms fit and the Sudan area is at risk. Then he mentioned that anti-malarial medication did not work. So much for the easy guess. While it is possible that the patient was unfortunate enough to have a resistant strain, the clue that he showed improvement when treated with amphotericin suggests another diagnosis. As I am unfamiliar with the drug, I looked it up. Typically used as an anti fungal, it can also be used to treat leishmaniasis. According to the World Health Organisation (WHO), in 2017 a large percentage of new cases of visceral leishmaniasis occurred in 10 counties. one of which is Sudan. The symptoms of visceral leishmaniasis include irregular fever, enlargement of the spleen and liver. Also, the symptoms have been going on for a while and this was mentioned as an important clue in the visceral leishmaniasis video from the Parasitic Diseases Lecture series (Video #8). These clues lead me to the diagnosis of visceral leishmaniasis.  The improvement the patient showed after treatment is likely the only proof of diagnosis given the limited resources of the refugee camp. Case studies like this makes me appreciate the health care system that I usually take for granted. As a Canadian, I am fortunate to have access to diagnostic tests and a wide variety of treatments that so many do not.


Rhonda writes:

Hello TWIP,

I would like to throw in my guess for Case 174. I think the most likely diagnosis is visceral leishmaniasis. The patient comes from an endemic area and presents with symptoms suggestive of visceral leishmaniasis including tachycardia, hepatomegaly, and splenomegaly. Neither broad-spectrum antibiotics or antimalarials improved the patient’s condition however the child improves while taking amphotericin. I would love to win the signed copy of your book!



Christine writes:

Good Day Gents!!

I am a super huge fan of your podcast, I listen to you guys while I work, cook dinner, clean house and pretty much every opportunity I get…except for at dinner time because my boyfriend has forbidden it lol! 

The chemistry between the 3 of you guys is great and makes for a very entertaining show every time. Never a dull moment! I love the way Vincent picks on Dickson, I get a good laugh out of it. I have a similar relationship with my best friend. I also love hearing Daniel’s stories about sailing and hearing about your very smart kids. Barnaby is a fantastic name, love it! 

I work as a receptionist for an oilfield company but have a wild love for all things parasites. I also love TWIV and TWIM but I wanted to finish all the episodes of TWIP before diving head first into the other podcasts. Almost there, I have about 20 to go before I’m all caught up and waiting each month for the next episode. I had to listen to 174 though because I want to take a shot at the diagnosis and hopefully win an autographed copy of the book! 

I live in Edmonton Alberta Canada. We’ve had pretty much a rainy season instead of summer this year. Today is a cool and cloudy day at 11° Celsius with a mild wind and so far no rain yet! 

I had to do a bit of research in order to come to my conclusion and I’m 95% sure that I have it right. I am going to go with Visceral Leishmaniasis. According to WHO in 2017 95% of all new cases of this parasite have occurred in 10 countries,  Sudan being one of them. The parasite is transmitted by the female phlebotomine sand fly who feeds on blood to produce eggs. Poor diet results in a full blown infection and the symptoms are enlargement of the liver and spleen, anemia, irregular bouts of fever, irregular heartbeat, and weight loss. Left untreated this infection sadly results in death.

Liposomal Amphotericin B has been used increasingly to treat this parasitic infection and is the treatment of choice for immunocompetent patients in the Mediterranean region. A total dose of 20 mg/kg is effective in these immunocompetent patients. 

Phew!! I hope I am right after all that lol. Tried to keep it short but it didn’t workout that way. 

I am happy to hear that the young man began to recover after receiving his treatment and they can prevent future deaths now that they know what the illness is and how to treat it.


Live long and prosper!

Your BIGGEST Canadian fan,



PS if I do by some chance win the book which I doubt I will because I never win , I would love it if all 3 of you signed it for me because I love you all equally

Alex writes:

Hello TWiP Gang,

This is my first time writing in and I hope I am not too late in replying to this case. I can’t believe it took me this long to find this podcast! I have been an avid parasite ‘lover’ since I was little. I guess I have had my head in books a little too much and haven’t been surfing the web enough. 

For this case I would say this young boy has visceral leishmaniasis (aka kala-azar) caused by a species of the leishmania parasite transmitted from a member of the sandfly family. The two main things that led me to this diagnosis were his enlarged liver and spleen and the improvement of his condition after an intravenous amphotericin treatment. I knew that amphotericin is generally used as an antifungal medication, but the boy’s lungs were clear. I did not know that amphotericin is also used as an antiprotozoal medication, now I know! Visceral leishmaniasis (VL) shares many symptoms with malaria and is often misdiagnosed as malaria which explains why they treated him with antimalarials to no effect. 

It is unfortunate that the camp has limited resources I would recommend an HIV test since HIV/VL co infected individuals have a great likelihood of presenting VL symptoms (VL is often asymptomatic, in Sudan ratio of asymptomatic incidence to active VL is 11:1 – Reference: Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelaert M. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol. 2007 Nov;5(11):873-82). and a greater likelihood of treatment failure and relapse. The CDC reports ( that a HIV positive individual has a 100-2330 times greater likelihood of getting VL – and once the are infected the likelihood of being symptomatic and having treatment failure is higher. If the child continues to improve after his treatment I would hypothesize that he is not HIV positive, the reappearance of his symptoms would be cause for concern it is very difficult to treat VL successful in immunocompromised HIV positive individuals especially with refugee camp resources.

I did not intend to end on such a sullen note… but alas that is all my brain has conjured up for now.

Thanks for the great case, can’t wait for the next episode!

All the best,


Wink writes:

Do you know what this is? Passed a segmented, moving worm of about 40 cm. Nicaragua mission 5 years ago. No self-prepared farm-fresh food. No seizures. Mild eosinophilia. Dr. Wink Weinberg 

Anthony writes:

T. gondii and the house cat

In addition to the hygiene you mentioned (that I’d think to be routine for all), those with a particular concern should have the cat tested for infection,  No active infection in the cat means maintaining vigilance, but no need for an immediate alarm.

Most house cats now probably only know mice from their ancestral dreams and so can’t catch toxoplasmosis by consuming infected prey.  Sad to relate though is the formal and informal practice of feeding felines raw food:

Home mixes will mean a cat harboring T. gondii.   For this and other parasites and microbial pathogens there is the interesting use of High Pressure Processing — cold pasteurization.  Done correctly, this method has been observed to render both oocysts and bradyzoites non infectious.

Whether the commercial products indeed are processed correctly would be something interesting to test.

BTW, as a digression, I find it curious — considering the public health importance — that it’s not known for certain how livestock become infected.  I’m told that piles of feed can be contaminated with cat feces. Why doesn’t someone check to see if this actually is the source? If it is, why aren’t handling methods put in place to eliminate that?  

Christine writes:

Good day!! 

Its me again lol I just got to TWIP 172, listening right now and you just read my first email from a couple months ago. I just want to say I love you too Daniel!! As Vincent assumed I had not reached the episodes where you became a part of the show. Once you started reading my email I realized I repeated myself a bit in my diagnosis email. 


Hope you’re all having a great day, I just wanted to make sure Daniel felt the love too