Case guesses:

Chris writes:

Dear TWiPsters,

The season is finally changing in Athens, GA, where it’s a very tolerable 73°F (23°C), humidity 32%. I just listened to the latest TWIP and there’s no way I’m going to miss sending in a case diagnosis this time!

The presence of furuncles and serosanguineous fluid on the one-year-old patient, paired with her location in Kenya, make me think immediately of a fly infestation, particularly of the tumbu fly (Cordylobia anthropophaga).

The presence of a central punctum on the furuncle may be enough to suspect myiasis, after which, the larvae may be persuaded to emerge by cutting off their air supply. The larva’s posterior spiracles require access to outside air for respiration and can be covered with a layer of petroleum jelly to induce suffocation. I was unable to find reports on how long this process can take, so the disposition of the patient may be of special relevance. Once partially emerged, the larvae may be removed with forceps or simply squeezed out. Care should be taken not to rupture the larvae in situ, for all the ‘usual’ reasons. Secondary bacterial infection is uncommon, due to the antimicrobial products of the larva, but an antibiotic regimen is still recommended for safety.

At this point, definitive species identification can be made by examining the larva. The number and location of spines, as well as overall shape and size, can be diagnostic. Three Cordylobia species are known to infest humans: C. anthropophagia, C. rodhaini, and C. ruandae. The first is by far the most common and, considering geography, the most likely diagnosis. Removed larvae can also be allowed to develop and the species more easily determined by features of the adult fly. While potentially fascinating from an epidemiological perspective, all of this is likely of dubious interest to the patient and her mother.

Now, for the source of this infestation. If left unperturbed, at 8-12 days post-infection the larva will have matured to the prepupal stage. From there, it will drop free of the host and abscond into the soil to continue pupation until it emerges as an adult fly. Females live for about 2 weeks and lay their eggs (in batches of 100-300) in sandy soil, typically contaminated with feces or urine. However, if damp clothing is available (as in this case), the flies will readily lay their eggs on this. After a few days, the larvae hatch and penetrate intact skin while the clothing is being worn. Because of their thinner skin, children more commonly become hosts. Dogs serve as a reservoir for the fly, which are reported to be present around the home, and the patient’s mother may be advised to examine their pet for signs of infestation. Ironing clothes will kill eggs and may be used to prevent future infestation, but I know from personal experience how hard it is to keep up with ironing.

Very interesting case, and I look forward to your insight on it.

Stay fly,

Chris

Wink writes:

Dear TWIP Professors (a gender-neutral term!):

The poor child in your most recent case sounded, from my Western-hemisphere orientation, like the botfly. I didn’t think that species was in East Africa, so I turned to The textbook and read: “myiasis [caused by] Cordylobia anthropophaga, the tumbu fly, is a larval parasite of humans and other animals, especially rats, in Africa.” This made me concerned that the case history was implying that this infant was spending time near rats. [I guess it is important to be reminded often about the lifestyle of those less fortunate.] So, that is my guess, myiasis caused by tumbu fly larvae.

Wink Weinberg

Atlanta

John writes:

Hi Drs TWiP,

My guess for the case of the one-year-old girl with itchy upper-body lesions in TWiP 140 is onchocerciasis; more commonly known as African River Blindness (though it is not restricted to Africa, more on that later).

The disease is caused by the nematode worm Onchocerca volvulus and is spread by the black fly (Simulium). These flies rely on fast-moving rivers to breed, hence the common name of the disease. The range of the flies is several miles from its breeding grounds and in the past has meant that large regions around rivers were not inhabited. The disease is endemic across sub-Saharan Africa and parts of northern South America.

Humans are the definitive host. When a human is infected by larvae from a (female) black fly bite, the larvae migrate to the subcutaneous layers and mature in nodules which vary in size from barely discernable to 5cm in diameter. Maturation takes 6 to 18 months. When mature, the males and females mate and the females produce about 700 microfilariae per day for their 8-10 year lifespan. The microfilariae migrate throughout the skin and eyes. Subsequent bites from black flies pick up the microfilariae which mature into larvae in the flies and migrate to the proboscis of the fly to continue the cycle during the next blood-meal.

While alive, microfilariae are non-immunogenic. Interactions between antigens from dead or dying microfilariae, their endosymbiotic wolbachia and our immune system are though to cause the lesions that lead to the various symptoms  in the eyes (including, eventually, blindness which may take 20-30 years to develop). The antigens also cause an increase in neutrophils and eosinophils. The skin symptoms (severe itching, thickening, depigmentation) are mainly caused by antigens from the microfilariae alone.

The location of subcutaneous nodules on the body of the infected person depends on the biting pattern of the flies and the clothing styles of the inhabitants of the region. Typically, in Africa, the nodules are on the lower body while in South America the nodules tend to be on the upper body. The patient in this case is a one-year-old girl so styles of clothing for babies may account for the difference from the usual African pattern.

Diagnosis can be made by microscopic examination of a 2-5mm square bloodless skin-snip from a region thought to have a high level of microfilariae. Multiple snips should be examined to increase sensitivity.

Alternatively, the Mazzotti Test can be performed. From Parasitic Diseases 6ed:

The Mazzotti Test is a provocative challenge test using a 50 mg dose of diethylcarbamazine (DEC).  Within 3 hours after treatment, patients with O. volvulus infection will develop pruritus. In heavily infected patients, the Mazzotti reaction can be severe and may exacerbate the ocular pathology in a patient. As an alternative, some physicians perform a type of patch test by applying DEC to a small region in order to elicit a local Mazzotti-like reaction

Treatment is typically with ivermectin. Ivermectin binds to glutamate-gated chloride channels in the microfilariae resulting in paralysis and death of the parasite directly or by starvation. The adults in the nodules are unaffected and treatment must be repeated at 6-monthly intervals while the adults survive. The nodules containing the adults may be surgically removed.

The death of the microfilariae as a result of ivermectin treatment may trigger a severe immune response in the patient. This is particularly true in patients co-infected with Loa Loa. Patients at risk of co-infection should be checked.

It is worth noting that Merck, the manufacturers of ivermectin pledged in 1987 to donate the drug to anyone who needed it for as long as it was needed.

I think I’ve plagiarised, eh, referenced your book enough for one email,

Thanks to all for the continued spread of information and education,

Regards,

John in Limerick where the recent weather has included ex-hurricane Ophelia and Atlantic storm Brian.

Allan writes:

Dear TWIP Wataalamu,

Warm Kona greetings,

For anyone who has lived any time in rural Central or East Sub-Saharan Africa, the patient history described by Dr. Mumelo screams mango fly or tumbu fly, Cordylobia anthropophaga, particularly the described dirt floor, nearby dogs, and clothesline drying without ironing.

anthropophagi with it’s apt Greek name: human eater, causes cutaneous myiasis.

Each female mango or tumbu fly lays 100-300 eggs in contaminated soil or on damp clothing or bed linens often drying after a wash. Unless ironed, the eggs on the clothing or linen will hatch into larvae after 2–3 days and penetrate the skin. With larvae that hatch in soil, they can remain viable in the soil for 9-15 days and any disturbance of the soil causes them to wriggle to the surface to penetrate the skin of the host.

At the site of penetration, a red papule forms and slowly enlarges, first with only intermittent itching, but pain develops and increases in frequency and intensity as the lesion becomes a furuncle. The furuncle’s aperture opens, permitting fluids containing blood and waste products of the maggot to drain, as described in the patient history.

After 8-12 days the larvae has gone through three larval stages before it reaches the pre-pupal stage at which point It drops to the ground, buries itself, and pupates into an adult fly able to reproduce and begin the cycle again. Humans are in fact accidental hosts. Dogs are the most common domestic host and several species of wild rats are the preferred field hosts.

Treatment is usually simple. You cover the punctum or breathing hole with petroleum jelly to cut off the larva’s air supply, which forces it to the surface, where it can be captured with forceps. Sometimes the punctum needs to be enlarged a bit.   But the furuncles are painful so prevention is much preferred. Iron the cloths.

OK, due diligence…

Here are some other possible causes:

According to the inestimable Parasitic Diseases 6th Edition, Wohlfahrtia and Sarcophaga can also cause cutaneous myiasis in unbroken skin, but these flies don’t live in Africa. The Congo floor maggot, Auchmeromyia luteola could be the cause if the patient slept on the floor, but the patient history said they slept on beds, so this is unlikely. Chrysomyia, the Old World screwworm, as well as green or blue bottle flies (Lucilia or Calliphora) can cause myiasis, but these flies only lay eggs in wounds or mucus membranes and the lesions described were of unbroken intact skin.

So I’m sticking with the Mango or Tumbu fly, (Cordylobia anthropophaga) as the most likely cause.

Thanks for another great TWIP case study.

Allan Robbins

Kona, Hawaii

Ryan writes:

Hello Doctors,

The case presented in episode 140 sounds to be caused by myiasis-causing Dipteran fly larvae.  The description of a furuncular boil is characteristic of larvae that have taken residence under this poor girls skin, in the five locations described. I believe the girl acquired the infection from eggs deposited by the adult fly on her clothes while they were drying. It is also possible the girl was exposed to the eggs by fecally-contaminated ground caused by the dog(s).

The warmth of her body would excite the eggs to hatch and penetrate her skin.  The larvae are developing under her skin, hence the “central punctate” area to allow for waste discharge and gas exchange required by the parasite. A quick google search finds cases of these infections cause eosinophilia and enlarged lymph nodes, which fits this case well. Painful, itchy lesions are expected to worsen as the larvae grow, but eventually, the larvae would make it’s way out of the host, drop to the ground and continue it’s life cycle to become an adult fly.

Reading Parasitic Diseases 6th Edition, I believe the culprit to be the tumbu fly, Cordylobia anthropophaga due to the geographic location of the patient. This species appears to be the only cutaneous myiasis-causing larvae in the region. In the same region, Chrysomyia spp. infect wounds or mucous membranes which were not included in the presentation; Lucilia and Calliphora spp. prefer to feed on necrotic tissue. The Congo floor maggot, Auchmdfomyis luteola, does not seem a viable culprit because they do not penetrate tissues. Cuterebra spp. in the USA, or Dermatobia hominis in South/Central America may have caused similar lesions to the ones presented.

To treat this infection, petroleum jelly can be used to cover the lesion to starve the larva of oxygen, forcing it to the skin surface. The larva can then be surgically removed.

Thanks again for the work you put into this educational and entertaining podcast. I particularly enjoyed the Blastocystis paper discussed the last episode. A friend of mine was one of the unlucky few who appeared to harbor one of those pathogenic variants. As of August this year, he was told he is Blastocystis free.

All the best,

Ryan

Hannah writes:

Dear TWiP doctors,

As soon as you mentioned unironed clothes, I knew what it was: Cordylobia anthropophaga, the mango or tumbu fly. The mango fly (not to be confused with the mango-loving flies in a previous TWiP episode) is a common cause of myiasis in central and eastern Africa, including Kenya. The adult fly lays a large number of eggs in urine/faeces-contaminated sandy soil or, as likely happened in this case, on damp clothes or linens hanging to dry. There, the larvae hatch and wait for a host – a human, for example, who didn’t iron his or her clothing. It then burrows into the skin, and a furuncle forms around it, becoming more itchy and painful as the larva grows. Meanwhile, blood and larval waste products drain out of a hole. Eventually, the larva leaves the host, pupates in the soil, and develops into an adult fly. All of this can be avoided if you iron your clothes before putting them on.

The only reason I know anything about mango flies is this Washington Post article that I read last month. It’s about the parasitic horrors faced by wildlife biologists, and it features a few other TWiP favourites as well: https://www.washingtonpost.com/news/animalia/wp/2017/09/22/want-to-be-a-wildlife-biologist-beware-the-eyeball-leeches-and-chest-maggots/

I can’t think of any other East African arthropods that would present with similar symptoms. The closest would probably be the human botfly (Dermatobia hominis), but it’s not present in Africa – it’s native to Central and South America – and the description of the lesion doesn’t sound quite right. Tunga penetrans is present in Kenya, but they tend to end up embedded in feet or hands, whereas this child has lesions all over the body. As for non-arthropod parasites, the lesion is wrong for leishmaniasis (wrong shape, plus leishmaniasis lesions don’t move), and doesn’t match any worm that I know of either. If it weren’t for the changing shape and movement, my money would be on some routine bacterial infection.

All the best,

Hannah

Iosif writes:

Dear Triple Twip,

I’m not too sure of my diagnosis, but the differential that I am thinking of are mainly Trypanasoma brucei gambiensii or cutaneous leishmanisis. The child has occipital lymphadenopathy which could be Winterbottom’s sign which is associated with West African trypanosomiasis. There is usually just a single chancre at the area of the blackfly bite and it shouldn’t be changing in size or looking as if there is a worm underneath. There is usually also no eosinophilia noted with the infection.

In regards to cutaneous leishmanisis; the skin findings are also usually different. The initial lesion often swells, but then starts to ulcerate which was not mentioned within the case. There is also peripheral eosinophilia within the cutaneous lesion, but I don’t think there is usually significant increase in the serum eosinophil concentration.

The last diagnosis that I was entertaining was guinea worm due to the mention of worms moving within the skin lesions, but Kenya has not had guinea worm infections in many years and unless this case was sometime in the past it cannot fit. Furthermore, this is a 1 year old child; why would they be drinking water at this point in time? Lastly, it was mentioned that the family had access to clean water.

Overall, I am not sure of the diagnosis and am not confident in any of my thoughts. I am looking forward to the answer!

Sincerely,

Iosif Davidov

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

Class of 2018

Gavin writes:

Dear TWiP team,

I believe that the child in TWiP 140 is suffering from a case of myiasis caused the Tumbu or Mango fly (genus Cordylobia). This is consistent with the presentation of furuncles with a central punctum, the presence of serosanguinous fluid, eosinophilia, and geographic location. I’m running a little behind, so I didn’t have time to look up the difference between C. anthropophaga and C. rodhaini, but I feel that we can safely rule out D. hominis (bot fly) and Cuterebra which are more common in the Americas. Wohlfahrtia species are located around the Mediterranean basin, and can also be ruled out.

My differential includes insect bites, pyoderma, cysts, and tungiasis. Diagnosis can be made on clinical grounds or with the aid of ultrasound. Maggots can be expressed with a kitchen tool or encouraged to leave by smothering with paraffin.

Cheers,

Gavin

UCSF SOM

Class of 2021

email

Hannah writes:

Dear TWiP hosts (and associated parasites),

I just came across this blog post from an entomologist acquaintance of mine and thought it would be of interest. It chronicles the author’s experience with several human botflies, details their biology, and features some gorgeous photos of one of the larvae (even in situ!) as well as the adult fly that it developed into: http://gilwizen.com/botfly/

Keep up the good work!

Cheers,

Hannah

Anthony writes:

Terrie the earthworm takes a wrong turn at the tree stump

In TWiP 52

http://www.microbe.tv/twip/52-not-your-ordinary-unsegmented-roundworm/

there’s a bit of a discussion on how might earthworms happen to be cavorting underwater.  Earthworms that are washed into a pond, lake or river are most likely to be quickly consumed by fish, salamanders, frogs or turtles.  Earthworms won’t consume parasite larvae in the water.  Earthworms will drown.

I think that the reference’s mention of “aquatic oligochaetes”, meant just that and not an earthworm that made a wrong turn at the tree stump.

http://www.dfo-mpo.gc.ca/Library/33909.pdf

Tubifex

https://en.wikipedia.org/wiki/Tubifex

and blackworms

https://en.wikipedia.org/wiki/Lumbriculus_variegatus

are commonly used in aquaculture, tropical fish in particular.  It’s long been thought that fish catch disease from eating tubifex, including conditions related to parasites.  (Blackworms are considered cleaner; I don’t know if that belief is based on facts or faith.)

I wonder if aquatic oligochaetes transmit parasites or other diseases — in nature or under domestication — to economically important fish?

Robert J. Goldstein is a parasitologist and a prolific writer on exotic fish.

https://www.amazon.com/Robert-J.-Goldstein/e/B001IR1I2I/

This appears to be him on LinkedIn:

https://www.linkedin.com/in/robert-goldstein-03918117

I don’t recall reading any discussions by Dr. Goldstein on parasites of fish from tubifex or blackworms.

A friend is in communication with him and could provide contact information.

Thank you.

Tropical fish expert Marc Weiss tells me that Dr. Goldstein has “some obscure fish parasite named after him. “

BTW, on a separate note, I shuddered when Dr. Griffin conflated the founder of the field of Tropical Medicine with the American horror.  I must admit, though, that the mnemonic was remarkably effective.  Glancing at this Facebook post.

https://www.facebook.com/groups/292338824121330/permalink/1584598568228676/

I immediately recognizes S. mansoni after never having seen a picture, but only having heard Dr. Griffin’s description.

FWIW

John writes:

Hi Vincent,

Hope all is well. Thoughts go out to recent victims of the Mexican Earthquake and Hurricanes Harvey and Irma.

I thought the following might be interesting discussion for Twip.

GSK completed a clinical trial on Mosquirix in 2014 indicating a low efficacy, nevertheless an efficacy that would have a significant impact on Malarial disease in sub-Saharan Africa if vaccination was conducted en masse. The company is part of a multilateral partnership that includes funding from multiple sources including the Wellcome Trust and the Bill and Melinda Gates Foundation.

Please find link to paper below:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114488/

A recent study conducted by Professor Karen Day et al in Gabon has contributed to validation of the “Strain Theory”  developed by Professor Sunetra Gupta and Professor Day, surface antigen variation could threaten efficacy of a malarial vaccine.

Please find Fierce Pharma article below:

http://www.fiercepharma.com/vaccines/malaria-s-genetic-diversity-might-compromise-gsk-s-mosquirix

Please find PNAS publication below:

http://m.pnas.org/content/114/20/E4103.abstract

It would be interesting to hear what insights the TwiPanel could bring to the fore on challenges that face malarial vaccines.

Apologies if this has been covered in a previous episode, I haven’t caught up yet.

Thank you again for all you do!

Best Regards,

John B

Chris writes:

Dear TWIPpers,

Considering the persistent, asymptomatic nature of this case, several acute infections can be reasonably eliminated, and while a thorough differential is very much justified, I’m going to take a decidedly reckless stab at this one.

One possibility that remains is Strongyloides; eosinophilia is suggestive, and chronic infection is often asymptomatic. Diagnosis would be by observation of larvae in stool (VERY indicative), or by antigen blood test. A fecal exam may have the added benefit of turning up signs of other potential infections.

But from the information provided, a more likely suspect is Wuchereria bancrofti. This is a parasite present throughout the tropics and is responsible for the great majority of human lymphatic filariasis cases. It is the only species expected in Cameroon and Gabon, where our patient served, and her residence there may have been sufficiently long for the parasite to establish. Mosquitoes of the Anopheles and Culex genera seem to be the most common vectors in this region. Adult worms end up in the lymphatics, where they can survive for up to 10 years (according to one study). High eosinophilia is often present, and the infection (though characterized most famously by edema and hydrocele) is usually asymptomatic.

Microscopic diagnosis may be made by observation of microfilariae in the peripheral blood by way of thick smears, thin smears, or buffy coat films. However, circulating microfilariae are not always present, and the strain likely encountered in central Africa is nocturnally subperiodic, requiring a nighttime blood draw (this is a fascinating phenomenon in itself, and still poorly understood). If available, a Circulating Filarial Antigen test is more sensitive and convenient.

Treatment with DEC is recommended, in either a 1- or 12-day regimen of 6 mg/kg. However, DEC is not advised in areas coendemic with onchocerciasis (like Cameroon and Gabon), so for safety’s sake the patient might be tested for this infection as well.

I’ve only started listening recently and this certainly is one of the tougher cases, but I would feel remiss if I didn’t offer some input even if I did put all my eggs (or microfilariae) in one basket. I’m interested to hear other takes on it, and I’m sure there will be much more thorough and insightful tests recommended by the TWIP team and other listeners. Keep up the excellent work!

Your newly converted TWIPtophan,

Chris

Anthony writes:

TWiP 59 errors

Canaries do indeed come from the Canary Islands.  I understand that they continue to do so.  I’ve read that Canary breeders on the Iberian Peninsula mate wild birds with domestic stock to add variety to the song.

The birds are named after the islands, not the other way around.  The ever practical Romans were impressed by a large breed of dog bred there, not little singing birds.  They called the place the Dog Islands.  Canary is derived from Latin for dog as in cave canem. The 

Birds are not divided into passeriformes and waterfowl.  Eagles are not passeriformes.  (If I actually heard that.)

https://www.allaboutbirds.org/guide/browse_tax.aspx

On a separate, but related note — and this time it turns out to be a pun.  I’d have to look up the cite, but canary song is negatively affected by parasite infection.  That could mean that singing gives the hen a clear indication of the health of a potential mate.