Case guesses:
Lisset writes:
Dear TWiP professors,
I am going to jump straight to Case Study number 165. I think this young man has a filarial parasite that is causing the swollen scrotum. Filarial parasites are nematodes that cause lymphatic filariasis in humans. There are three species of this nematode, the most characteristic one being Wuchereria bancrofti which infects only humans, and Brugia malayi which can also infect feline and monkeys. Highlights of the life cycle include:
- Worms live in the lymphatics of the lower and upper extremities and male genitalia.
- Females release L1 larvae, instead of eggs, which are encased in a sheath.
- Microfilariae migrate from the lymphatic circulation into the blood at night when they can be ingested by a mosquito to continue their life cycle. W. bancrofti is transmitted by a wide variety of mosquito genera and species.
- After being deposited in the skin after the mosquito bite, the immature worms migrate to the lymphatic vessels and rest near the draining lymph nodes.
The characteristic inflammation of the extremities, or male genitalia in this case, is due to the dead or dying adult worms that trigger inflammatory reactions that result in alterations to the walls of the lymphatic vessels. Lymphedema is caused by occluded lymph channels by calcified worms. These individual remain largely asymptomatic otherwise. Also interesting to notice, the male scrotum is frequently affected and may become as gigantic as 10 Kg. For treatment, it is recommended to look for co-infection with Loa Loa due to risk of severe adverse events.
I based all my facts on the fantastic “Parasitic Diseases” sixth edition book which I am trying to get a signed copy of this time. I also wanted to use this time to congratulate you all for the great Podcast that you make every week or so for us. Thank you for your time and devotion to parasites. Lastly, I wanted to say that I found your Podcast thanks to one of my Eukaryotic Microbes professor from the University of Michigan – Ann Arbor who probably will never know how hard I fell in love with parasites after his class. Thank you to all science professors out there whose dedication to their job has great impact in our lives and never take credit for it.
Saludos from Ann Arbor, Michigan currently expecting a really bad winter storm this week,
Lisset Sánchez
University of Michigan, 2019
Sophia writes:
Dear Professors
greetings from Greece
My diagnosis for this case is Lymphatic filariasis caused by W. bancrofti.
This conclusion was made after searching in your book and reading that ” Lymphatic filariasis should be suspected in an individual who resides in an endemic region, is beyond the first decade of life, and has lymphedema in the extremities or genitalia.”
Now I am hoping that this young man did receive the medication and doses needed to get rid of this infection. However, I do a question: so how does this NGO work towards prevention of disease? I think it would be more efficient if the patients, besides their medication, were given insecticides, bed nets etc, anything needed to make sure they don’t get reinfected. Along those lines, you mention in your book that there a goal to eliminate LF by the year 2020 (p. 267). Ok, so it’s 2019 now. we have one year left. How does this NGO, or the ministry of Health in Uganda work towards this goal? Does the NGO collect and send epidemiological data to the Ministry for example? Does someone else do that? I can’t see any progress in elimination otherwise. I’d be interested to hear your thoughts
On another note, my email for ep 163 got lost in the queue and I did have a question about that case as well. My question was : how did the man with suspected leishmaniasis decide to come see you and didn’t proceed with the surgical intervention? Was he afraid of surgery? What would happen if he did go to the surgery instead? My point here being that timing and choosing the right doctor can make all the difference in one’s prognosis.
Anyway, I don’t want to write too much and take up radio space time
Thank you for doing this.
all the best
Iosif writes:
Dear Twip Team,
I believe the patient has an infection involving Wuchereria bancrofti that is leading to lymphedema of his scrotum; although this seems localized to the epididymis from your description. I don’t know if the infection can be limited to the lymph nodes draining that area although I don’t see why not. While I was in Kisoro we did have a few cases of elephantiasis, but they were always patient’s who had traveled from northern Uganda and none were local.
Sincerely,
Iosif Davidov
P.S. I am currently in the combined EM/IM program at North Shore/LIJ.
Leah writes:
Dear TWiPsters,
Hello! Long time listener, and I’ve finally managed to submit my guess in time (I hope)! I strongly suspect that the patient described is suffering from lymphatic filariasis. This came to mind as soon as the presence of individuals with swollen legs in the area was mentioned. However, to confirm my suspicion I consulted my .PDF copy of Parasitic Diseases. Consistent with the symptoms described, the adult worms live in lymphatics, including those of male genitalia, and transillumination of suspected swellings has been described as a diagnostic technique by WHO1. There have been three different nematodes identified which may cause this disease – Wuchereria bancrofti, Brugia malayi, and Brugia timori. >90% of cases can be attributed to Wuchereria bancrofti, which is known to occur in Africa, making that the prime suspect. B. malayi and B. timori occur in South East Asia and the Indonesian islands, respectively, making them extremely geographically unlikely to be the causative agent. Thus, W. bancrofti is my diagnosis. There are rapid serological IgG tests available for the worms which cause lymphatic filariasis available, which could be used to confirm the diagnosis. The patient, as long as he is not co-infected with Loa loa, should be treated with diethylcarbamazine(DEC), though all individuals in the area would ideally be screened and treated (including the asymptomatic ones) . Ultrasound could be used to track the status of the infection non-invasively during/after treatment!
I’m in my fourth year of a PhD in Immunology at the University of Calgary. My project focuses on Immunoparasitology – specifically the mechanisms of protective immunity involved in naturally acquired immunity to Leishmania major. Admittedly, my project focuses more on the immunology than the parasitology side of things, so I love listening to your podcast to keep my parasitology skills fresh! While I enjoy academia, I am also very interested in science communication, and I always appreciate and admire the clarity with which you explain complicated concepts – definitely something I try to emulate in my outreach activities!
Thank you very much for your time, while I find the digital copy of Parasitic Diseases extremely useful, I would love to be entered into the draw for the physical text book! Apologies for the essay of an email.
Leah Hohman
- WHO (2002). “Surgical approaches to the urogenital manifestations of Lymphatic Filariasis.” WHO/CDS/CPE/CEE/2002.33
Ivan writes:
Dear TWIP illuminators!
First about the case…
According to everything stated, a young teenager from Uganda is suffering from lymphatic filariasis, everything fits nicely. Even the WHO report of ongoing filariasis in Uganda! I especially like the way Daniel described that this lesion glowed. This clearly indicates, together with the fact that this is a non-tender swelling, that the content of it is edema fluid accumulating due to obstructed lymphatic drainage. A balloon full of plain water would make the exact same effect 🙂
Regarding the etiology, I think we could not be 100% without additional tests, but it is one of the following, in decreasing order of probability: the unpronounceable Wuchereria bancrofti, Brugia malayi, or Brugia timori.
I remember in one of the early episodes Vincent and Dick discussed this topic. I think Dick than mentioned that Brugia malayi in primates is the only animal model for this disease. However, during my studies for ECVP (European College of Veterinary Pathology) board exam, I found that the notorious Wuchereria bancrofti can actually be studied in Silvered Leaf monkey. Not probably a very significant fact, but still.
Here are the references:
https://www.askjpc.org/vspo/show_page.php?id=c1RVT3JOZmZ3em82UG92cCtXR3ExZz09 – link to a case of Edesonfilaria malayensis in a cynomolgus monkey on the Veterinary systemic pathology online (great site for any vet. pathologist); look in “comparative pathology” section
Therapy for this young Ugandan… Sure. But I’ll just leave the therapy part to Kevin and all the other correspondents and of course our Doc in charge.
And now few words regarding the Daniels kind proposition to ask Parasites Without Borders for Parasitic diseases 6th ed. I will try a bit more to win it by a bit of luck on the show. And I don’t mind waiting as long as it is signed! In case I really get tired of writing guesses then I’ll shoot an Email to PWB. Either way, I promise never to use it as Daniel used “Robbins Pathology” on his road trip!!!
Fortune favors the brave, or at least the persistent 🙂
Keep up the great show!
PS. I know this is the wrong podcast, but big, no, no, not big, an enormous applause for the selection of topics for the TWIV 532
(ASF and Peste de Petit Ruminants)!!
All the best,
Ivan from Zagreb, Croatia, EU
Bening writes:
Greetings TWiP professors,
It is a freezing 24F here in Atlanta after a much anticipated snow storm that turned out to be just rain. I hope you are all keeping warm and safe in the north with the arctic weather this week. A busy work schedule has kept me from writing in time on the last few cases, but I hope to write more often now.
My guess for this weeks case of the young boy with swelling of the scrotum is lymphatic filariasis caused by Wuchereria bancrofti. The differential here would be fairly limited(to my knowledge) and include Brugia malayi, Brugia timori, and Wuchereria bancrofti. Both Brugia species can cause lymphatic filariasis in humans, but neither is found in Africa. Unless the boy has had recent travel to Southeast Asia, India, or Indonesia, I would comfortably rule these out. Wuchereria is transmitted commonly by the anopheles mosquito in rural Africa and is likely the source of the other family members’ swollen limbs as well. Given the nocturnal cycle of Wuchereria, I would take a blood smear sample during the night time hours and confirm the presence of microfilariae in the blood. Given that he is not co-infected with Loa loa, treatment with diethylcarbamazine in combination with a cycle of doxycycline should reduce the parasitic load, though additional treatments may be required for curative elimination.
This case seemed fairly straight forward, but I would love if Daniel could shed some light on the results of the transillumination test, pun fully intended. Were you able to visualize worms using this method? I have already won a book, so please take me out of the running this time around. Thanks again for all that you do and keep the entertaining podcasts coming!
Best wishes,
Bening Hellriegel
Microbiology Technician II
CryoLife, Inc
Kennesaw, GA 30144
p.s. Vincent mentioned in this episode that he was out of autographed books. I was the lucky winner of a book back in November and wanted to check if it had been sent, or if you were already out of autographed copies by then. I am anxiously awaiting the addition to my collection!
Shelby writes:
Hello Docs,
I would like submit my guess for the case dealing with the young boy in Uganda with the large swollen scrotum. Dr. Griffin’s question about other individuals in the area having swollen legs leads me to believe that the boy has a hydrocele caused by filarial worms (probably Wuchereria bancrofti) obstructing inguinal lymphatic vessels.
To test this you may want to perform a peripheral blood smear looking for juvenile worms or an x-ray to look for the calcified remains of previous generations.
As far as treatment dr. Google says diethylcarbamazine and ivermectin will kill the microfilariae and adults and should be administered semiannually. The use of bed nets is recommended as well to prevent the transmission of the little wigglers by their mosquito vectors. Another paper (included below) suggests an anti-wolbachia regimen that seems to be very effective not only in treating lymphatic filariasis but also river blindness. Knock out the endosymbionts and the worms soon follow.
Thank you for all the podcasts. They make the drive between Nashville and MTSU far more entertaining.
Sincerely,
Shelby David Lowrie
Adam writes:
Hi!
My guess for the case in TWiP 165 is lymphatic filariasis, caused by
Wuchereria bancofti.
Best regards,
Adam Oscarson,
Halmstad, Sweden
Karen writes:
Dear TWIP trio,
I love your podcast! I recently listened to episodes (approximately) 55 through 65 during a roundtrip drive to University of California–Davis for a conference of the Pacific Southwest Center of Excellence in Vector-Borne Diseases. Researchers who study mosquitoes, ticks, and vector-borne diseases shared their findings with public health personnel and each other. The center is funded by the CDC and also awards several grants for one-year studies.
It sounds like the patient in episode 165 is suffering from lymphatic filariasis, which is called hydrocele when present in the scrotum. A filarial worm, that is vectored from person to person by mosquito bites, causes lymph fluid to accumulate in the scrotum. Wuchereria bancrofti (has Vincent mastered its pronunciation yet? ) is the species of filarial worm in Africa, vectored by nocturnal mosquitoes, with no reservoir hosts. Surgery such as described by this 2010 paper https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879368/ would be an effective treatment. Yearly doses of ivermectin or albendazole could be given to the population in the endemic area to interrupt transmission with the goal of eliminating the worm from the region.
Thanks for all the brain candy,
Karen
Vector control technician
Santa Barbara, CA
Sara writes:
Dearest Podfessors!
I write to you with a case guess and my sincerest apologies to Dr Griffin! I was horrified to hear in the last episode (TWiP 165) that Dr Griffin had tried to contact the Glasgow ScienceGrrls on his recent visit to Glasgow and Scotland and heard nothing back! We would obviously have loved a special guest at one of our meetings, I can’t tell you how sad I am to have missed it. I no longer have access to the email as I have been in self-imposed exile in New Zealand and Australia for the past few months (don’t feel bad for me, it’s pretty great down here) but I’m still active on the blog and Twitter. I hope Dr Griffin enjoyed his trip anyway, and indeed it sounds like he did. I always love hearing a bit about my old stomping grounds – I used to work at the Centre for Virus Research that Dr Racaniello mentions visiting and I studied Parasitology for 5 years at the University of Glasgow. Despite the terrible weather (I don’t know how many types of rain you all have encountered on your Scotland travels but I am convinced there are more than four!) I loved living in Glasgow and Scotland. I even like haggis! Hopefully I’ll be back sometime and overlap with a return visit, I’m sure you’d be welcome back Dr Griffin!
Now for my guess: the case of the Ugandan teenage boy with a swollen scrotum immediately screamed lymphatic filariasis to me, especially as Dr Griffin added that other people in the community had swollen legs. Lymphatic filariasis (LF) is a helminthic infection spread by culicine or anopheline mosquitoes (my favourite little beasties to work on) from human to human. Microfilaria circulate in the blood at night and get picked up for transmission, but normally dwell in lymphatic vessels (hence LF). With repeated infections the vessels can get blocked, preventing drainage of lymph and causing swelling, normally in the lower extremities and male genitalia. This clinical presentation combined with changes in the feel and appearance of the skin is normally referred to as elephantiasis. The most likely culprit in this scenario is Wuchereria bancrofti as the species of Brugia that could cause LF aren’t a great geographical fit. I’m not familiar with the techniques available for diagnosis where Dr Griffin was based in Uganda, but methods include microscopic identification of larvae in the blood (preferably drawn at night), ELISAs, PCR and ultrasound. As for treatment, it’s first (according to PD6) important to establish that the patient does not suffer from a co-infection with Loa loa as the treatment can have a negative effect in such a case. If co-infection is ruled out treatment options include diethylcarbamazine (DEC if Dickson is forced to read this already extended email), ivermectin and albendazole. Repeated treatment is needed as drugs are only partially effective against the adult stage. As for the state of the boy’s scrotum, this can be addressed with surgery if needed. It’s also important to check for secondary bacterial and fungal infections and treat them. Incidentally antibiotic treatment could also have an effect on the worms as they depend on their endosymbiont Wolbachia (my favourite intracellular beastie to work on). Of course the easiest way to deal with the disease would be not getting in the first place, and to this end WHO recommends mass administration of combination therapies at regular intervals and vector control strategies such as insecticides (for those non-crafty beasties with no developed resistance) and bed nets (for the night-biters) to reduce transmission.
Crossing my fingers for a book and forever looking forward to the next episode!
Cheers,
Sara the exiled ScienceGrrl
P.S. I know there’s no listener survey for TWiP but I’ve done the others. I used to listen at work and found it difficult to remember after finishing pipetting but luckily now I mainly listen when doing yoga and am only to eager to interrupt my exercise for such important things. Some might say too eager given the amount of cinnamon buns we Swedes eat…
Suellen writes:
When I heard the case study from this past week’s episode, I immediately thought of elephantiasis, so I went to Parasitic Diseases 6th Edition and started there.
After reading up on Lymphatic filariasis, I am pretty certain this is what our patient has. FL is spread by mosquitoes, who deposit the nematode Wuchereria bancrofti on the skin of victims. W. bancrofti enters through the bite wound, and makes its way to the lymphatic tissue, where the parasites will mature. Later, they will enter the bloodstream, but it is their activity in the lymph nodes that causes the swelling known as elephantiasis.
I hope I got it right! I already have a book, so feel free to pass on me for the giveaway. Thanks so much for this great podcast — I can’t believe how much I know now about parasites!
Suellen
Roswell, GA
where we are enjoying a 65 degree day today, after suffering below-freezing temps for the past 3 days.
Ken writes:
Greetings to the purveyors of parasitic knowledge.
Thank you so much for this podcast and Parasitic Diseases 6th edition (PDF version, would love a “hard” copy)! Vincent and Dixon may remember me from TWiV 195 (They did it in the hot tub). I have been listening to TWiP for a while but this is my first case guess. This seems to be a case of lymphatic filarasis, given the numerous hints given by Dr. Griffin and subsequent checks online and the definitive source, PD 6, probably caused by an infection by Wuchereria bancrofti. According to PD6, the best treatment for W.bancroftiis diethylcarbamazine, but only in the absence of a Loa loa infection. However, Loa loa does not seem to be endemic in Uganda, but diagnosis could be a challenge given the facilities at the clinic. Fortunately, I am not a physician and never have claimed to be one, so will leave treatment to the experts.
In case you were wondering why I am a “crossover” from TWiV, my lab has recently started working on improving diagnosis of soil-transmitted helminths (long story that I will spare you), and TWiP has helped immensely with my extremely steep learning curve. Thank you so much! When we get something published I will send it your way and, if you find it interesting enough, maybe we can have a TWiP followup to a TWiV.
Thanks again!
Cheers,
-Ken
Carol writes:
Greetings Esteemed Hosts,
I have been too slow to send in an email for the past few… months, but always enjoy listening to each episode. Sometimes it’s with a mixture of delight and dismay because my guess would have been right for the case study, and sometimes with a mixture of relief and dismay because my guess would have been wrong (and luckily no one heard it). Hopefully, this week I will just experience delight because my guess is right and in time!
I suspect the Ugandan young man has lymphatic filariasis presenting as a hydrocele, most likely due to Wuchereria bancrofti. The CDC says treatment for patients with hydrocele is surgery, though diethylcarbamazine or ivermectin, may also be prescribed to kill any microfilariae circulating in the blood stream. DEC can apparently be given either as a single dose or as a 12-day regimen with equally efficacy, which strikes me as odd. Why would someone choose 12 days if 1 day is as effective?
I won’t go into detailed differential, lifecycle, risk factor, prevention discussions here, as no doubt someone else will do so much more thoroughly and succinctly that I could. Thanks again for producing a suite of great podcasts. Whenever a TWIx podcast lands in my feed it moves straight to “listen next”.
Carol
Victoria, BC, Canada
Amichay writes:
Dear TWiP trio,
I’ve been listening for TWiV for a while, following my MSc Advisor’s (Dr. Oren Kobiler of Tel-Aviv University) recommendation, with great joy.
When I started my PhD six months ago I moved from viruses to cellular pathogens and I decided it was a good trigger to start listening to TWiP as well. I got hooked. Fast.
After bingeing the TWip archive during my daily commute, episode 165 was the first I’ve heard in close proximity to its release.
This is particularly exciting for me because I have a guess for the mystery case!
The first thing that came to my mind when the enlarged scrotum was mentioned was Wuchereria bancrofti, this initial thought was strengthen with the mention of the relative with swollen leg.
Though also causing Lymphatic filariasis, Brugia malayi and Brugia timori can be dismissed since they are found in south-east Asia (and to my understanding does not commonly lead to hydrocele).
Definite diagnosis can be made with looking at blood smears (preferably taken during the night-time)or specific Immunoassay. Since this patient is male, we might try and look for “dancing worms” using ultrasound.
I’m not a clinician but I assume that Albendazole might help with treatment? Probably draining of the hydrocele is also in order….
Thank you for your great (and entertaining) work!
Looking forward for more episode,
Amichay (ch like in Loch) Afriat
———————
Amichay Afriat
Shalev Itzkovitz lab
Weizmann Institute of Science
Department of Molecular Cell Biology
Rehovot, Israel
Carrie writes:
Dear CenTWiPetal Force,
Some people have swollen legs, and some people have swollen genitals. This instantly put me (Carrie) in mind of a high school biology lesson. My teacher mentioned it – well, he referred to it by the common term of elephantiasis. I remember that he claimed that people trying to treat and control this condition in impoverished areas ran into difficulties, because, so he said, people with swollen legs were happy to have their condition treated, but young men with greatly enlarged scrotums believed it to be not a disease at all but a sign of virility and were reluctant to be cured of it.
… I was told a lot of things in high school. Some of them may even have been true.
But, wild anecdotes aside, both of us are fairly sure of our diagnosis on this occasion.
Lymphatic filariasis occurs when filarial worms block the lymph ducts, blocking the flow of lymph and causing fluid retention and excessive cell growth, both of which cause swelling.
The swelling is most commonly seen in the legs or, in the case of young men, the scrotum. Which is exactly what we see here. In the case of this patient, the fact that the swelling glows when a light is shone through it suggests there is no solid mass or defined structure to it, but rather that it is a hydrocele, or accumulation of fluid. Which is exactly what we expect from lymphatic filariasis.
Wuchereria bancrofti, of course, is by far the most common cause of filariasis worldwide, and the two Brugia species are both restricted to specific regions in Asia, and unlikely to be behind these cases in Uganda. W. bancrofti is spread by mosquitoes, which the patient was exposed to virtually all the time.
However, we mustn’t jump to conclusions. Could this be anything else?
There aren’t any other obvious parasitic causes of scrotal swelling – even if we don’t assume this patient’s problem is connected to his sister-in-law’s leg.
A hydrocele can also be caused by an injury, or by STDs, but of course, this had to be the one time Vincent didn’t ask whether the patient is sexually active. Yet another possibility is an inguinal hernia. However, all of those things would probably cause tenderness, and this mass is non-tender. And, of course there are regular cysts, and tumours both benign and malignant. Even ordinary ingrown hairs can sometimes cause quite spectacular swellings – Caitlin’s husband had one that required surgical removal, though fortunately it was elsewhere on the body. However we would not expect the finding of glowing on trans-illumination with most of these things. We also wouldn’t expect it to be happening to lots of people in the area.
So we are confident in our diagnosis. But still, it would be advisable to confirm it.
The evildoers – or at least their children, since it is the adult worms that cause the main symptoms – can be spotted wiggling around the bloodstream at night. They should show up under a microscope in a thick blood smear – provided the blood sample is taken while they are active. During the day they will retreat to the capillaries of the lungs, which could result in a negative test. You could also do an antibody test, but it’s probably unavailable in this setting.
He should be treated with albendazole and ivermectin, which should prevent it from getting worse. Additionally, dosing with doxycycline should kill the symbiotic Wolbachia, sterilizing the adult worms and also causing early death. However, as it is mostly dead or dying worms that cause blockages and swelling, and the dead worms may become calcified and remain long-term, the damage done can only be repaired surgically. In this, the young man is lucky, though he may not feel that way – the swelling in the scrotum can be removed, but a swollen limb is hard to treat.
You may well have spotted them, but if not, we found a couple of interesting recent papers:
Here (https://www.sciencedirect.com/science/article/pii/S0944711318305336) is a trial of Artemisia as a possible treatment for schistosomiasis. The interesting thing is that the trial was of an infusion of the plant, not of artemisinin, and that it appeared to outperform the current standard treatment.
The second (http://stm.sciencemag.org/content/11/473/eaau3174) is about quinine’s mode of action – or at least one of its actions – which may have been discovered at long last.
Those two papers were brought to our attention by the excellent blog In the Pipeline (https://blogs.sciencemag.org/pipeline/). If you don’t read it, you should. Call that our pick of the week!
This letter is the product of your favourite transatlantic team: Carrie, from Newcastle-upon-Tyne, England, and Caitlin, living in exile in Seattle.
P.S. A cantrip is either a minor magical spell, or a piece of devious trickery.
Connor writes:
Hello Doctors,
My gut leads me to think it’s bancroftian filariasis due to the classic hydrocele
, the region, and local specificity of persons with lymphadenopathy and elephantiasis. The younger age did seem a bit odd without continued high transmission levels and repeat biting leading to high microfilaeremia.
But in this case the hoof beats lead me to think Wuchereria bancrofti as that accounts for the vast majority of reported filariasis cases.
Fingers still crossed for that illustrious signed PD6.
Connor E. Dunn
Tulane University School of Public Health and Tropical Medicine
MPH Tropical Medicine candidate
Wake Forest University 2015
Sneha writes:
Dear TWiP team,
I’m Sneha from Chennai, India. I recently completed my undergrad in Biotechnology and am hopefully waiting for positive responses from grad school applications. While I listen to TWiV and TWiM, this TWiP was my first episode and now I’m wondering why I didn’t follow it more regularly. All your podcasts give me something new to think about and this one was no exception.
As for the case diagnosis, when I heard ‘swollen leg’, I thought elephantiasis. I knew it can be caused by parasitic worms and is transmitted by mosquitoes, but that was the extent of my knowledge. So, I did some internet sleuthing and here’s what I found:
Three different parasitic worms can cause lymphatic filariasis: Wuchereria bancrofti, Brugia malayi, and Brugia timori. Wuchereria bancrofti is the most common (causes 90% of all cases) and is also the worm that is endemic to regions in Africa, including Uganda. Approximately 30% of people infected will develop lymphedema and/or hydrocele (scrotal swelling). Many infected during childhood can develop symptoms after years of infection.
The disease is transmitted by mosquitoes. Adult worms residing in the lymphatic vessels of infected humans produce microfilariae (immature larvae) by the millions, which circulate in the blood waiting to be picked up by mosquitoes. The larvae mature in the mosquitoes and when the mosquito bites an uninfected individual, the mature larvae travel to the lymphatic vessels where they grow into adult worms.
Diagnosis usually involves detection of microfilariae in blood smears collected at night, because that is when the microfilariae are active in the blood, or serologic detection of antifilarial Ig4. Lab tests are usually negative for people with lymphedema though, because the infection is no longer active. I am not sure if that is the case with hydrocele too.
Treatment involves anti-helminthic drugs —in African counties, this is usually a combination of albendazole with ivermectin or a combination of albendazole with diethylcarbamazine —to get rid of the microfilariae. The drugs don’t have much effect on adult worms.
There is a Global Programme to Eliminate Lymphatic Filariasis: annual mass drug administration (MDA) of anti-helminthic drugs to entire communities where the disease is endemic. Where does Uganda stand in this? It turns out the status of MDA in Uganda is ongoing. The programme has been implemented regularly since 2010 and from 2013, there has been a decrease in the population of people requiring preventive chemotherapy every year. As of 2017, geographical coverage is 100% (out of the 9 districts that require preventive chemotherapy, all 9 have implemented MDA). 66% of the population requiring preventive chemotherapy are getting treatment and a little more than half of the districts are getting effective (>65%) coverage. Check out this interactive graph that depicts the status of MDA in counties and how it has changed over the years: http://apps.who.int/neglected_diseases/ntddata/lf/lf.html
So to put everything together, I think the teenager has lymphatic filariasis caused by Wuchereria bancrofti (might or might not be an active infection). The symptom of scrotal swelling, his brother’s wife having swollen legs, and Uganda being endemic to the disease all fit with this. He probably must have been infected as a child. Considering there seem to be other people from his area suffering from the same symptoms, perhaps annual MDA is not implemented in that area while it has been in Bududa for several years; which might be why the nurse said that diagnoses like this was rare and also why it was a problem in the past.
The transillumination baffled me though, but a quick google search told me it’s a way to identify if a scrotal mass is solid or not. If you can transilluminate, it is probably fluid filled, which is the case with a filarial hydrocele; if not, it might be a solid mass.
References:
https://www.who.int/lymphatic_filariasis/en/
https://www.cdc.gov/parasites/lymphaticfilariasis/
http://apps.who.int/neglected_diseases/ntddata/lf/lf.html
http://www.meddean.luc.edu/lumen/MedEd/urology/hydrchx2.HTM
I have never tried solving a case diagnosis before and I had quite some fun trying to figure this out. Hope the teenagers are fine now.
Warm regards,
Sneha Sundar
Mike writes:
Dear Professors:
Greetings from Upstate New York, Rochester to be specific. Right now it is 33 degrees Fahrenheit, with a weather advisory for freezing rain.
I believe the young man in the case study presents with a hydrocele of the left testicle, brought about by lymphatic obstruction due to lymphatic filariasis, probably caused by Wuchereria bancrofti. This organism causes the syndrome known as elephantiasis, which the patient has said has occurred in several relatives. I have not been able to find out what size testicles elephants have, as the websites returned from a Google search do not seem to me to be scientific.
Hydroceles “transilluminate”, meaning they glow when a light is shined through the scrotum from behind. This is because they are filled with fluid, this case due to obstruction of the local lymphatic circulation, and so transmit some of the light.
Asymptomatic hydroceles do not require treatment, although surgery can be performed successfully. Treatment of the filariasis is recommended, however, as it can potentially avoid more extensive lymphatic damage. The usual treatment is with diethylcarbamazine (DEC), although prior treatment with ivermectin may be necessary, as coinfection with onchocerciasis is a contraindication for use of DEC.
I join with the other listeners in saying how much I hope you continue your podcast indefinitely, and I consider you all heroes for sharing your knowledge and expertise with the world.
Regards,
Dr. Mike Martin
Rochester, NY
Volker writes:
[pronounce my name Folka and let it rhyme with polka, then you should be close :-)]
Dear Podfessors,
Easy case I hope. Lymphatic filariasis, also known as elephantiasis. Three types of worms are known to cause the disease: Wuchereria bancrofti, Brugia malayi, and Brugia timori, with Wuchereria bancrofti being the most common. Treat with
Albendazole with ivermectin or diethylcarbamazine.
Volker (LTLFTW, mathematician who got distracted from his childhood idea to become a scientist and ended up in finance)
Blair writes:
Dear Vincent, Dickson and Daniel,
Hopefully I’ve managed to get my answer in this time!
I believe that this young chap has a hydrocele secondary to Bancroftian filariasis. His brother’s wife is also afflicted by the same parasite, except that she has developed elephantiasis as a complication of it. These are the typical presentations of this condition seen in males and females respectively.
It is a disorder of lymphatic drainage caused by the adult worms of the parasite Wuchereria Bancrofti. They impair lymph drainage resulting in the accumulation of fluid in the tissues. The adults can live for a number of years, and produce millions of microfilariae which they release into the bloodstream. These can be taken up by mosquitos and subsequently transmitted to new hosts, allowing the life cycle to continue.
Mass drug administration strategies in endemic areas (e.g. with DEC or ivermectin) have helped to dramatically decrease disease transmission. These predominantly work by reducing the microfilarial burden in the bloodstream, so that mosquitos are unable to pick them up and transmit to a new host. This must be repeated at regular intervals, as the drugs have minimal effect on the adult worms.
Despite the success of MDA, there is still a significant morbidity burden associated with the established lymphatic damage. This is not be corrected by antifilarial treatment, and may require surgical intervention if available, or good skin care to prevent damage and the development of complications such as soft tissue infections.
Really enjoy listening to your podcasts – please keep up the good work!
Best wishes,
Blair Merrick
Registrar in Infectious Diseases and General Medicine, London
Jessica writes:
Dear esteemed TWiP Team,
I am a long-time listener as well as parasite and neglected tropical disease enthusiast. This is my first time making a case attempt as I am often an episode behind in my listening, so hopefully my guess isn’t too late! This case particularly piqued my interest as I remember seeing similar presentations during my service as a Peace Corps Volunteer in Madagascar.
The nontender lesion in the young man’s scrotum sounds like hydrocele, most likely caused by a chronic filarial infection by Wuchereria bancrofti. The man is from a region of northeastern Uganda in a community where other young men are affected by similar lesions, suggesting an infectious or toxic etiology. Hydroceles are a common manifestation of chronic infection with this parasite, and there are also members of this man’s community with large, swollen legs – another hallmark of chronic W. bancrofti infection. Therefore, I would put lymphatic filariases at the top of my differential list.
On the African continent, W. bancrofti is transmitted by culicine and anopheline mosquitoes at the L3 stage. The larvae make their way via lymphatic vessels to the area of the local draining lymph nodes, where they develop into adults and eventually mate and release microfilariae into circulation. Repeated and long-standing infection (as experienced by those who live in endemic areas) can lead to more chronic pathology including lymphangitis with subsequent elephantiasis, characterized by firm swelling of the lower extremities. In this young man’s case, the presence of adult worms in the scrotal lymphatic vessels caused fluid accumulation in tissues of the scrotal sac, leading to hydrocele formation.
Definitive diagnosis can be obtained by peripheral blood sample collection, preferably late at night due to the periodicity of the parasites, followed by microscopic identification microfilariae. Serum antigen tests that can be performed on blood samples collected regardless of time of day are also available.
Treatment with DEC +/- doxycycline may be indicated in this patient provided he is not concurrently infected with Loa loa. Repeated treatments every 6-12 months may be required to fully clear the adult worms from the body.
Many thanks for the podcast and all the great work that you do. You have provided me with hours of entertainment at the microscope as I comb for parasites in chimpanzee feces.
Jess
__________
Jess Carag, MS
DVM Candidate | Class of 2020
University of Wisconsin-Madison
School of Veterinary Medicine
Benjamin writes:
Hi TWiPpostrongylus!
Long time listener, first time caller. I’m a PhD student at the University of Adelaide, Australia, where it is currently 28°C, although we hit our all time record temperature of 48°C a bit over a week ago! I was introduced to TWiV recently, which was the first podcast I’d ever listened to, before discovering the rest of the TWiX series. A couple months later and I’ve listened to almost all of the TWiP episodes and can’t imagine the prospect of doing my parasite culture without learning about the wild world of infectious diseases at the same time. Thank you for the wonderful podcasts and the reassurance that my utter fascination with parasites doesn’t make me crazy 🙂
My case guess for this week is lymphatic filariasis, caused by Wuchereria bancrofti. I believe lymphatic filariasis is still endemic in parts of Uganda and this fits with other people in his area having similar symptoms (ie. swelling of leg). I’m not sure what the ability to be transilluminated/glowing means but assume this would be part of a differential where a solid mass (non-illuminable) was causing the obstruction; like a tumour. Diagnosis could be confirmed by seeing microfilariae in the blood, although these usually circulate at night-time (depending on location) and so blood would likely need to be drawn at night. Antigen, PCR and serological tests all exist for W. bancrofti but I’m not sure how common they are for routine diagnosis. Treatment would be with DEC and doxycycline, I don’t think DEC and Loa Loa would be an issue as the WHO only reports loiasis on the DRC border and at very low levels.
Keep up the wonderful edutainment,
Regards,
Ben
PS. I think this would be a great paper for you to look at on TWiP (https://www.biorxiv.org/content/10.1101/508481v1.full). There has been growing evidence for some time that there is a significantly under appreciated burden of P. vivax in West Africa, even in Duffy negative individuals. Presumably this under appreciation is compounded by the fact that if you’re not looking/testing for P. vivax you won’t find it. This paper provides a mechanism for how P. vivax might be infecting these people!
—
Ben Liffner
PhD Candidate – Malaria Biology Lab (Wilson Lab)
Research Centre for Infectious Diseases
School of Biological Sciences
The University of Adelaide
Erin-Claire writes:
Dear TWiP Professors,
I have been a listener for a couple of months now, I like to listen when I’m doing my repetitive lab tasks or waiting for the bus which is consistently late. I am a biomedical sciences undergrad at the University of Manchester, UK (currently on a placement at Witten/Herdecke University in Germany) and I recently got the opportunity to take a module on parasitology. I loved it more than anything in my education so far and it has made me certain that this is something I want to pursue for a career.
I consider myself a bit of a novice when it comes to parasites, but every episode I have kicked myself for not being brave enough to send a guess as they have all been diseases I’ve learned about so far.
As soon as I heard of the patient’s swollen scrotum, I had a pretty good idea of what the culprit is likely to be, but I thought I would do a bit of Ctrl+F-ing of the Parasitic Diseases textbook before I committed to writing out my guess. The description of the swelling sounds very much like a hydrocele caused by the blockage of the inguinal lymph nodes, which is a common symptom of an infection with one of the filarial nematodes. The information of the swollen legs in the area gives us another symptom of the infection, elephantiasis. This infection is caused by 3 nematode parasites. As 2 of them (Brugia malayi and Brugia timori) are transmitted by mosquitoes only found in Asia, this leaves us with the final answer of Wuchereria bancrofti.
The infection is acquired when a mosquito, likely the Anopheles mosquito in Africa, deposits the larvae into the skin of the host and they travel to the lymphatic system where they can mature into adults. The blockage is caused by the accumulation of dead adult worms, which prevent the draining of lymph fluid and we start to see the swelling symptoms.
While the patient wasn’t in pain at that time, he probably would have liked to get the problem resolved before it swells to the enormous sizes that were shown to me in my lecture slides. Diagnosis can be done by looking for microfilariae under the microscope from blood samples which were taken at night, as the microfilariae exit circulation during the day when the host is active. A more sensitive diagnosis would be to look for circulating W. bancrofti antigens.
Assuming the patient isn’t also infected with Loa Loa or Onchocerca, they can be given diethylcarbamazine which can kill the adults and the microfilariae. Doxycycline can also be given to increase the efficacy of the treatment. The hydrocele itself can be directly treated by having the fluid drained and corrected with surgery to prevent it from forming again.
I look forward to the next episode coming out very soon and I hope that this wasn’t sent too late.
Best wishes to you all,
Erin
P.S. I would love to be entered to win a signed copy of your textbook. As a student, I don’t have any new textbooks. They’re all second-hand and covered in questionable drawings and messages.
Tatiana writes:
Dear TWiP Trio,
Undergrad Zoologist at Swansea University here, south Wales, UK! Two weeks ago I was in Borneo where the weather was consistently 35oC and 100% humidity; Swansea is more like 3.5oC (not sure what that is in Fahrenheit, I’ll leave that to you guys). I took a Parasitology module last year, then discovered TWiP while so filled with fever during this summer that I ended up sleeping on the kitchen floor to try and cool down. Speaking of Borneo – most of us who went there to do three weeks of field work in the rainforest and coral reefs had taken the Parasitology module, but most people had consequently forgotten most of what we learnt. They were not best pleased with my helpful facts about the various deadly parasites we could catch which I remembered from my TWiP listening habit. I listen to a lot of other podcasts, but none of them are quite as informative as TWiP, and it has accompanied many long train journeys.
When I saw the title of TWiP 163: Trout and Parasites, I was extremely excited, as my undergrad dissertation is on the behavioural changes in Salmo trutta by the parasitic larvae (glochidia) of the freshwater pearl mussel, Margaritifera margaritifera. I am taking the data previously published by my supervisor (Thomas et al., 2013*) and re-analysing it using new statistical techniques to try to quantify how different factors, such as time since infection, infection load, and sex affect the boldness of the fish. Many studies have indicated previously that the glochidia do not actually cause any significant physiological harm to the host in natural infection loads, and studies which do find that the parasite causes harm have used experimental parasitic loads far, far above what is found in nature. One study by Ziuganov (2005) even indicated that the presence of glochidia could delay the senescence process of S. salar, Atlantic salmon, and prolong their lifespan 5-6 times – though when I mentioned this in my first draft, Dr. Thomas highlighted it then commented underneath:
“Ziuganov says a lot of things…. 😉“
Based on the casual, sassy comment, including four ellipses and winky-face with a nose, I assume that there is some large issue with Ziuganov’s findings which I have thus far failed to identify and write about. The comment did rather spook me. It was the nose on the winky-face which did it.
At another point in the same draft, Dr. Thomas highlighted a fact I had cited him as writing about in his paper, and claimed that it was not true. It was very tempting to simply send him a screenshot of where he said it six years ago, perhaps accompanied by a photo of me raising my eyebrows questioningly, however I refrained for the time being. He is an amazing marine parasitologist whom I admire greatly and was very glad to have as my supervisor (and whom I sincerely hope does not listen to TWiP), but these two comments together on my draft did take some energy to deal with.
It’s due in twelve days, so I should probably be writing that rather than this, but I consider this to at least be a productive form of procrastination. The results I’ve found are exciting and interesting, however I shouldn’t really share them on an international podcast before I hand it in at the very least, I imagine. Maybe I can send you guys a copy of the finished thing once it’s been marked? That’s probably legal. I’ll ask Dr. Thomas. Gosh, I really do hope he doesn’t listen to this podcast. Awkward.
Anyway, the other reason I’m writing in – the case guess for the most recent episode. Quite often I have a vague idea based on what we studied last year and my memory of previous TWiP cases, which sometimes even prove to be right, but never sure enough to write in before. However, I am really keen to win a signed copy of Parasitic Diseases, so I decided to throw the hat in this time (as an excuse to talk about my trout-parasite-behaviour dissertation, of course). As soon as I heard Dr. Griffin mention the genital swelling, I had an idea of what to search for. His hint about the swollen legs of other people in the same area as the boy had come from made my mind up further. A quick Google to check, and I am almostcertain about my guess. I will be very embarrassed if it is wrong, especially after talking so excitedly about my dissertation for so long.
I would like to hazard that the boy is suffering from lymphatic filariasis, caused by filarial worms in the lymphatic system. Many times this presents asymptomatically, and many other people in his area may be infected who are not even aware. When it does present, it does so most often as a leg swelling, and sometimes as a swelling of the breast or genitalia. The mention of the swelling being non-tender could be a reference to elephantiasis, which is a condition that comes with the filariasis where the skin becomes hard and insensitive. I hope that the other details mentioned, such as transillumination, are not relevant in disproving this theory and indicating that a different parasite is to blame. Diagnosis should be done by blood test (at night, when the worms are most active, if memory serves me correctly), and I believe one of the treatments is chemotherapy.
I really hope that this diagnosis is correct and that the weather where you guys are is more pleasant than here. Oh, and that my story about my dissertation (and the fact that I discovered TWiP while fevered and laying on a cold kitchen floor) brought some amusement to you and/or the other listeners. I look forward to hearing the next episode and many more after it.
Best wishes,
Tatiana
Swansea, UK
* Thomas, GR; Taylor, J; de Leaniz, CG. (2013) Does the parasitic freshwater pearl mussel M. margaritifera harm its host? Hydrobiologia. DOI 10.1007/s10750-013-1515-8
Till writes:
Dear Daniel, Dick, & Vince,
This weeks case guess is once again an easy guess for the regular listener. The filarial parasite wucheria bancrofti is the perpetrator in this case, causing the described hydrocele as well as the elephantiasis of the brothers wife. The vector for these parasites are several species of mosquitoes and the disease can be found in south America, subsahara Africa as well as south and southeast Asia.
One question on this topic: is the filarial dance sign (FDS) regularly used in establishing the diagnosis of LF? Although I have never diagnosed a patient with LF myself it seems the FDS is quite an easy to recognize diagnostic sign if you know how to perform a sonography. However, I have read some papers (1) that claim FDS to be not specific but could also be the result of clumps of protein and/or sperm cells sticking together. However, reading the article, I thought the two would have to be quite easily distinguished. The clumps mentioned above are 2-3mm at max and are immobile, while the LF adults are worms that are (for the females) ~3mm in diameter and can reach several cm in length and that show a certain erratic pattern of movement (2).
Could you tell us your esteemed opinions about this?
Thanks and all the best,
Till.
(1) J Ultrasound Med. 2011 Aug;30(8):1145-50. The “filarial dance” is not characteristic of filariasis: observations of “dancing megasperm” on high-resolution sonography in patients from nonendemic areas mimicking the filarial dance and a proposed mechanism for this phenomenon. Adejolu M1, Sidhu PS. https://www.ncbi.nlm.nih.gov/pubmed/21795491
(2) https://www.youtube.com/watch?v=ER1BFx4_qGc
Pete writes:
Dear Hosts,
I only have a couple minutes, so I am going to wing this without checking references. I say filariasis commonly called elephantiasis, caused by (dead?) micro filaria blocking lymphatic channels, causing a fluid build up that results in swelling. I think the only effective way to reduce the swelling is microsurgery to clear the channels?
If I’m correct, credit to TWIP, because, while I have always had an odd fascination with parasites, my background is aerospace engineering and IT, and I believe what I know of filariasis is from Dickson’s descriptions in early TWIP episodes.
Thanks for the show, and Daniel has been a great addition, and I really like the new direction the show took after he joined.
Aloha,
Pete
Chris writes:
Dear Twipsters,
We reached an unbelievable 80F yesterday in Athens, GA. I’m not even sure I remember what winter is supposed to be.
This week’s case, however, makes a lot more sense. Considering the patient’s symptoms and background, I would be amazed if this was anything other than an infection with Wuchereria bancofti presenting with hydrocele. It’s interesting to note that hydrocele is only seen with infection by Wuchereria, not any of the Brugia species. So even if the case occurred in southeast Asia, the symptoms would still be diagnostic. If confirmation is required, a modified Knott test can be performed to concentrate microfilariae in day blood. Serological tests exist, but might not be available in this setting.
Treatment with DEC will clear any circulating microfilariae and may reduce adult worm burden, with the caveat that co-infection with O. volvulus or Loa loa can produce serious adverse reactions. Doxycycline can also be prescribed, which acts against the Wolbachia in the worms.The recommended treatment for hydrocele is surgery, and this is at least described as a relatively simple drainage procedure.
I’m interested to hear any anecdotes the Twip trio have on this parasite. It might be very odd in some circles to have a “favorite parasite”, but Wuchereria (and the filarial worms in general) have long been mine, both for the intriguing life cycle and the complex relationship they have with their host.
Best,
Chris
Delbert writes:
Hello TWIP-sters,
My guess for the case from TWIP 165 is lymphatic filariasis or elephantiasis. The scrotum development was a hint leading me to this diagnosis, and the information about people with large swollen legs clinched the diagnosis for me.
This infection in this young man is probably caused by Wuchereria bancrofti which is transmitted by a mosquito. The distribution depends on the distribution of the vector and is commonly found in areas with warm temperature, standing water and humidity. The pathogenesis of the disease is multi-phase. Phase I is asymptomatic and is characterized by tolerance and hyporesponsiveness. After a period of several years, tolerance is broken and an inflammatory reaction can be seen. This is phase II (inflammatory/acute phase) and is characterized by a response to adult worms, lymphatic inflammation, swollen areas (usually in the lower body) and the occasional abscess around dead worms. Frequent symptoms are: lymphadenitis, lymphangitis, orchitis, and presence of hydroceles. Phase III is the obstructive phase where lymph varices occur and lymph return is obstructed causing dilation of lymphatic ducts. Chyluria (lymph in urine) can occur. In some cases elephantiasis develops causing chronic lymphedema. Most common site in males in the scrotum and the most common site in females is legs and arms. The elephantoid organs are mostly fibrous connective tissue, granulomatous tissue, and fat. Diagnosis: presence of J3 in thick smears of blood (drawn at night) and calcified worms on X-rays. Treatment: surgery, DEC (diethylcarbamazine), and pressure bandages may decrease edema.
Note: Brugia malayi can also cause elephantiasis – however, its distribution is in Asia and it is unlikely that the Ugandan boy travelled to Asia.
I would love a signed copy of the book and hope to win!
Delbert (Dr. A)
from The Bio Busters podcast.