Sara writes:

Dear Drs Racaniello, Despommier, Griffin, and Naula, 

I’m listening on a sunny, humid, 78 F evening in Philadelphia. Thank you for another wonderful episode with a fascinating case!!!

I struggled with this case. This is a 31-year-old woman presenting with a fever and severe headache, one week after returning from an 11-day safari in Tanzania found to have an expanding, painless, purple lesion, with leukopenia, thrombocytopenia and mild bump in her liver enzymes. My mind first jumped to Rickettsia africae, which presents with an eschar and can cause fever and thrombocytopenia. Scrub typhus (another rickettsial species) would have presented similarly. 

However, following presumptive treatment for rickettsial disease, she did not do better, the lesion grew and she returned with cyclically recurring fevers lasting 3-days. This sounds like Borrelia recurrentis (a spirochete)– however she had PCR for Borrelia species sent that were negative.  

Thick and thin blood smears were negative for Plasmodium species and presumably Trypanosoma species though those were not mentioned.

 She seroconverted for Rickettsia antibodies but we weren’t given a four-fold rise in titers, and her fevers recurred after a course of doxycycline.  I don’t know what to make of those antibodies.

She could have been bitten by a sandfly and developed cutaneous leishmania; however, the isolated nature of the lesion that was not described as ulcerating banished Leishmania from my differential. 

Could her purple lesion have been a trypanosomal chancre from a Tetse fly bite, maybe it was missed because only one set of blood smears were obtained? (I remember Trypanosoma species with the mnemonic “Chagas Kisses Cruzi and Brucei Bites”, since Tsetse fly bites can transmit Trypanosoma brucei while kissing bug feces within a bite will transmit chagas disease. ) The problem with Trypanosoma for this patient is that I believe those chancres are painful and this patient did not have pain in the area. 

I’m thoroughly stumped. Against my better judgment, I’m guessing Trypanosoma brucei even though I really want this to be a case of relapsing fever from a Borrelia species.  

Anxiously awaiting a final diagnosis, 

Sara 

Sara Rendell, PhD
MD candidate 
Pronouns: She/Her/Hers 
Perelman School of Medicine 
and Department of Anthropology 
University of Pennsylvania 

Jody writes:

On Christina’s student’s case of the pyretic safari-goer with a lesion near her rear:

Although a quick trip through PD7 is not exactly a feast for the eyes, “lesion” is now officially my least favorite word to Command-F for within the PDF due to the associated photographs. 7 years of avid TWiP consumption have apparently not yet cured my squeamishness, and I admit I do much of my reading while holding a hand up to cover a photo or two. I absolutely love the complex life cycles and disease ecology (and I have tremendous compassion for the poor people suffering in these photos), but clearly a career in clinical parasitology is not in the cards for me. 

In her presentation of the case, Christina mentioned specifically that blood smears were taken when the patient did not have a fever, which led me down a surprisingly tough path with Dr. Google; I was sure I’d easily find plenty of papers discussing a specific pathogen or two that can only be diagnosed via blood smear when the patient is actively febrile. Sadly, no. I thought I might have stumbled upon it with the louse borne relapsing fever caused by Borrelia recurrentis, but I believe that the PCR tests would have picked this up. 

I think our patient may have had an unlucky encounter with a sandfly and the Leishmania donovani or L. infantum she was carrying. Kala-azar or Visceral Leishmaniasis is characterized by skin sores, a high intermittent fever, anemia, low blood counts, and hepatosplenomegaly, to name a few. As the venerable authors of PD7 state, “Diagnosing the disease can require a high index of suspicion as many presentations are similar to the other febrile diseases common in the areas where VL is endemic.” This is a tough one but I’m going with VL. 

I’ve already won a book (though I’m still eagerly awaiting its signing and shipment) so please don’t enter me into the guessers’ grab bag. 

Thanks!

Jody
Jody Rieck   //   L O S T    L A B O R A T O R Y   //   lostlaboratory.com

Daniel writes:

Greetings Twip team,

I have been recently listening to some of the first Twip episodes (even taking notes along the way) and now I guess you could say the power of Dickson flows through me. I think the answer you are looking for is tryptastic! More specifically east African trypanosomiasis caused by the parasite Trypanosoma brucei rhodesiense. Oh right, now I have to explain why I came to this conclusion. In east Africa, the Tsetse fly vector breeds in the open plains where many different mammals can act as reservoir hosts. Going on a safari would put this woman at risk of exposure, but if she stayed on more domesticated land she wouldn’t be at much risk because they eliminate Tsetse flies to protect precious cattle. About a week after being bitten, an ulcer called a shanker will form. This is the initial site of T. brucei replication but it does not stay there, it enters the circulatory system. Soon after lymph nodes on the back of the neck will begin to enlarge, known as winter bottoms. This sign could have been easily missed by the women as they are on the back of the neck and they also would have disappeared before her visit to the hospital. Her first bout of fever would have cleared 99% of the protozoan, which is why the blood smears were negative. Also, the biopsy of the shanker was taken too late as T. brucei has already left. The small percentage T. brucei that evaded the immune system will then replicate until another fever occurs. This variation in the T. brucei coat protein is remarkable. I wonder if it is due to proofreading mistakes or some random recombination in this gene. Anyways, these doctors were very unlucky with their blood smears. They should have taken a smear before the fever when the population was high. I now realize there are quite a few assumptions here.  How many assumptions are too many assumptions when making a diagnosis? My other guess would be visceral Leishmaniasis which can cause dromedary fevers. But a lesion at the bite would only occur if it was cutaneous Leishmaniasis. Unless you can develop visceral Leishmaniasis from cutaneous Leishmaniasis. Did the lesion disappear? If it did then it’s definitely not Leishmaniasis.

Cheers,

Daniel from Vancouver, Canada

Gabriel writes:

Hello from Baja California

It seems the 31 year old woman may have been bitten by a tick of the genus Amblyomma, infected with: Rickettsia, likely R. africae, making her eventually seropositive; and a secondary pathogen causing her to have relapsing fever, Borrelia would have fit the symptoms nicely, but was discarded. So, supposing that it is not a bacteria being this is TWiP, I suggest Babesia sp.

A intraerythrocytic protozoan parasite transmitted by ticks, causing from no symptoms to fever, headache, chills, anemia, fatigue, malaise, and a few others. Treated with: Atovaquone along with Azithromycin or, Clindamycin along with Quinine. I found none of these medications would have been used for her first identified Rickettsia infection where doxycycline, chloramphenicol,  or ciproflaxin were likely prescribed.

I’d expect the Babesia symptoms to be amplified by the coinfection, at least during the pre-treatment phase of the Rickettsia.  and remain unaffected by the Rickettsia treatment. At least the last fever must have been caused exclusively by this protozoan, supposing that the Rickettsia was solved by the medication.

The small purple lesion is mentioned for the tick bite area when Rickettsia is involved.

Thank You          Gabriel

Andrew writes:

Kia ora from Pongaroa,

No book won yet. Will I be the first Incubator winner? I like my books warm.

The weather here is fine and 16°C.

The woman who went on safari in Tanzania, I think, has trypoansomiasis or sleeping sickness. 

She seems to have antibodies for Ricksettsia but this is not This Week in Bacteria so that is a bit of a red herring. That said, a 2012 paper in Science Direct indicates that the Tsetse fly (Glossina morsitans) that transmits Trypanosoma may also harbour Rickettsia felis

https://www.sciencedirect.com/science/article/abs/pii/S0147957111001305

If my guess is right she has been infected with the subspecies Trypanosoma brucei rhodesiense  found in this region of Africa and will probably soon be developing the neurological symptoms. 

According to PD7 if the disease has not reached the CNS then the treatment of choice is Suramin. However, as this does not cross the blood-brain barrier melarsoprol is the only effective drug for treatment of T. b. Rhodesiense and comes with a risk of encephalopathy.

Nā,

Andrew

Martha writes:

Dear TWiP,

I am writing to you more promptly than is usual for me since I am flying off for a month’s vacation. Usually I like to ruminate on the problem for a while, but here is my quick analysis of the problem of the young woman returning from safari in Tanzania with a fever that recurs and a purple lesion on the upper thigh. No mention of swimming so eliminate those parasites acquired aquatically. No mention of paint-ball fights so I guess the purple lesion is from the bite of a vector. So focus on vector borne disease.

If I were the patient I would want to make sure this was not Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei rhodesiense, since this east African version of the disease can progress more quickly to neurologic involvement and death. Her clinical presentation and lab work are consistent with this, including the false positive for rickettsia. Although the bite of the tsetse fly is reportedly painful, some people take insect pests in stride and don’t complain much unless specifically asked.

I would suggest that you go ahead with treatment for HAT while continuing to test and observe.

Best wishes to you all,

Kevin writes:

Dear TWiP Doctors,

I am still dealing with some COVID-19-induced fatigue, but while I’m quarantined, I might as well throw in a guess for the Episode 198 case study. (My clinical course is relatively mild 🙂 )

I will wager leishmaniasis  I am doubtful but here is my reasoning: 

It sounded like the patient remembered some event related to lesions, perhaps the bite of a sandfly. The timecourse is perhaps on the quick side for development of a leishmania lesion (two weeks?) but plausible. A painless purple lesion fits cutaneous leishmaniasis, but those lesions typically result from multiple papules and I don’t know if that fits the “single, small lesion” description. If the lesion was not sampled properly, the histology may have missed the trypanosomes. The symptoms the patient experience line up somewhat with visceral leishmaniasis (bouts of fever and anemia). However, there was also little evidence of hepatic or splenic effects other than C reactive protein, which I’d expect from visceral leishmaniasis. I didn’t find a description of a Leishmania species that could cause a cutaneous lesion as well as these visceral symptoms, but it sounds plausible. Cutaneous Leishmania lesions can leave victims vulnerable to secondary bacterial infections, possibly explaining her becoming Rickettsia-positive. 

Thanks for keeping me edutained while I recover,

Kevin

The University of Central Lancashire Parasitology Club writes:

Dear TWIP Professors,

Hello again from the Parasitology Club at the University of Central Lancashire in the Autumnal Northwest of England. 

We were absolutely delighted to win a signed copy of PD7 for our response to the TWIP 197 case of cyclosporasis.

Dr Nualla’s new fascinating new case has some intriguing signs and symptoms for the patient, and it has also given us a real headache.

The periodic fever was immediately suggestive of malaria and advice on travel to Tanzania from the UK Government highlights malaria, dengue fever and cholera as the greatest risks (Gov.uk 2021). There were no details about taking anti-malarial prophylaxis but and we wondered if the patient may have had a low parasitaemia that evaded detection by thick and thin blood film.

The patient was treated for African tick bite fever caused by Rikettsia africae (Jensenius et al., 2003) and subsequently seroconverted to positive for Rikettsia antibodies, so it is plausible that the patient had an infection that was successfully treated and this may account for the eschar at the inoculation site, but was also suffering from an additional parasitic infection with Plasmodium falciparum.

A report from Jelinek et al.,(2002) described a cluster of cases of African sleeping sickness in travellers to Tanzanian national parks caused by the East African form Trypansoma brucei rhodesiense.  The diagnostic features included a trypanosome chancre at the tsetse fly bite site which seems to fit with the eroding lesion in this case and identification of trypanosomes in thick and thin blood films which were negative in this case.

So altogether we are unclear of the cause but will put our tanner (a Lancashire term for six pence in old money) on a dual infection with Rikettsia africae and Plasmodium falciparum.

Thank you as always for your wonderful podcasts and stimulating case studies.

We are waiting excitedly by the post-box to receive the signed copy of PD7.

David

On behalf of the University of Central Lancashire Parasitology Club

 References

Jelinek T, Bisoffi Z, Bonazzi L, et al. Cluster of African trypanosomiasis in travelers to Tanzanian national parks. Emerg Infect Dis. 2002;8(6):634-635. doi:10.3201/eid0806.010432

Jensenius M, Fournier PE, Kelly P, Myrvang B, Raoult D. African tick bite fever. Lancet Infect Dis. 2003 Sep;3(9):557-64. doi: 10.1016/s1473-3099(03)00739-4. PMID: 12954562.

https://www.gov.uk/foreign-travel-advice/tanzania/health

Katy-Jane writes:

Hi everyone,

16C and raining here in northcentral Wisconsin. Our fall colours peaked last weekend, and, wow, were they beautiful this year! The leaves are now falling, and it’s starting to look like October. 

I found this case rather tricky, but I’ve got the last two wrong, so I need to redeem myself. Actually, I probably need to win a book. Either way, I’ll keep trying!

My first thought was a soil-borne helminth, such as cutaneous larva migrans from a hookworm infection. However, those are very itchy, don’t produce fevers, and it’s rare to have systemic problems.

Next I thought of African Trypanosomiasis, or sleeping sickness. PD7 states that people infected with T. brucei rhodesiense get severe headaches and intermittent fevers (I was going with rhodesiense rather than gambiense due to Tanzania being the travel history). This infection also occurs in people who have travelled to game parks (e.g. for a safari). However, trypanosomes should show up on a blood smear, and the blood smear was negative.

Next up is cutaneous leishmaniasis. The symptoms don’t seem to fit, and the biopsy of the lesion would have shown parasites, which it didn’t. Also, how does rickettsia fit into this? Co-infection with African tick bite fever could be a possibility. But I think I can do better.

What about visceral leishmaniasis? That certainly induces intermittent bouts of fever but is usually accompanied by splenomegaly, and has an incubation period of several months, not 1 week as with our patient. Although not impossible, it is not common in Tanzania.

I’m clutching at straws here because of the mention of seroconversion to Rickettsia. Onchocerca volvulus is known for causing river blindness, but I remember from early TWiP episodes that the parasites can also house the rickettsia-like organisms Wolbachia. PD7 gives the distribution as western and central Africa…can Tanzania be counted as central Africa? According to the WHO website…maybe. However, in cases of onchodermatitis (the only type that might show a skin lesion), usually there are multiple lesions, and (according to PD7) if there are fewer than 5 lesions, most cases are asymptomatic.

Back to African Trypanosomiasis for further evaluation. PD7 states that fevers coincide with organisms entering the bloodstream, so if blood smears were only taken when she didn’t have fever, would they still show up on a blood smear? PD7 also states that thick blood smears miss a large percentage of infections. This seems like it fits the bill, but the seroconversion to Rickettsia was still tripping me up. I did a little more internet digging, fell down a few more rabbit holes, and then found what (I think) I needed. According to medicalecology.org, female tsetse flies carrying rickettsia-like organisms are 6 times more likely to be infected with trypanosomes than those without. Therefore, I think our unlucky traveller was bitten by a trypanosome-rickettsia infected tsetse fly and has the early stages of African Sleeping Sickness. If left untreated, this disease is fatal, so I hope her story has a happier ending.  

Thanks for making me think – if I’m wrong again, I still enjoyed the process!

Katy-Jane Shanak
Faculty in Veterinary Technology & Dairy Science
Northcentral Technical College
Wausau, WI