Annette writes:

Hi twip team

I think the two women have lymphatic filariasis caused by wuchereria bancrofti.

Sadly yet another disease which could be eliminated or at least controlled by annual mass treatment according to the CDC website.

It is 20 C ,sunny in Braunschweig, Germany. 

Thanks for all your work, it is very much appreciated. 

Cheers, Annette

Kimona writes:

TWIP #205

Hello again Dear TWiP team! I am submitting this response from a sunny and beautiful Uppsala, Sweden, where it is currently a brisk 3 degrees celcius (at 5am!). We flew in yesterday to celebrate my son’s high school graduation and I am hoping to submit my thoughts on case #205 before it is too late…..

At the top of my list of parasites re: the two ladies w/ lower extremity (LE) edema, is the lymphatic filaria, Wuchereria, and most likely W. bancrofti, as they reside in Ghana.

But first, consideration of a broader differential of these women’s LE edema:

Chronic venous insufficiency or stasis disease: they are both multiparous (lots of pregnancies!) which can contribute to LE edema

heart failure (due to a myriad of -viral, -parasitic, and -congestive causes)

renal or liver disease: causing hypoalbuminemia and edema due to 3rd spacing  

bacterial infections: unlikely in these chronic cases and would usually manifest as a unilateral edema/cellulitis

There were no clues to suggest that these women had specific renal or hepatic disease, such as hematuria/proteinuria or jaundice. Nor was there mention of any fever or redness of the LEs to suggest a bacterial cellulitis.

On the premise that any cause of heart failure can cause LE edema, then any parasitic disease that can cause a cardiac conduction system abnormality, arrhythmia, myocarditis, or pericarditis – could be responsible. This includes parasites such as T. cruzi causing Chagas disease, but distribution is in the Americas. T. gambiense and rhodesiense are more endemic to Ghana but I do not believe is as frequent a cause of heart failure.  Toxoplasma gondii, Taeniae solium, Trichonella spiralis, Entamaeba histolytica, and Echinococcus granulosum all have a worldwide distribution and can affect the heart in various ways. But most heart failure will manifest with an equal bilateral LE edema. These ladies were both described as having one leg worse than the other. I suspect that the women of the village spend much of their time down by the mosquito laden lagoon, washing clothes, etc., and thus are subject to frequent bitings. And I am venturing a guess that some men of the village may also be experiencing scrotal swelling.

Wuchereria bancrofti – is a thread-like nematode. It enters the human host when it’s vector, the culicine and anopheline mosquitoes, deposit L3 larvae on the skin next to their bite. These migrate through the subcutaneous tissues to the lymphatic vessels where they rest near draining lymph nodes and develop into mature adults. After mating, they can shed >10,000 microfilariae/day and live for many years. Living worms are believed to suppress the host’s immune response, whereas dead (calcified) worms trigger lymphocytic infiltration and blockage of lymphatics. When this happens in a large enough number of lymphatics within an extremity, it can lead to poor lymphatic drainage and ensuing edema which over time progresses to elephantiasis. In males the scrotum is often affected in the form of hydrocele.

Wolbachia is a bacterial symbiont that is also harboured by adult worms and plays a role in its pathogenesis.

Diagnosis: can be made by identifying microfilariae in blood (preferably using a nocturnal draw), Knott’s test, ELISA, serology IgG, or by ultrasound of spermatic cord (in men, of course) looking for “filarial dance sign”.

Treatment: DEC has both macro- and microfilaricidal properties and single dose treatments which are repeated every 6-12 months, are listed as effective. Co-infection with the microfilarial nematode, Loa Loa, can trigger severe adverse events and neurological manifestation with treatment, so care should be taken to screen for this. Doxycycline for 4-6 weeks is also mentioned, presumably to kill off the Wolbachia symbiont. Ivermectin and albendazole are also listed but will only kill the microfilarial forms.

Hoping my slightly hasty thoughts above aren’t too off. Looking forward to yet another case to plunge into……..Kimona

Andrew writes:

Kia ora from Pongaroa,

The last episodes case takes me back to TWiP 165 where Daniel gave us the symptoms and said this will be hard to guess and I thought of Elephantiasis and thought about sending in my first case guess but did not feel capable. I was so angry with myself for my lack of self confidence I have hardly missed a guess since. 

So I am going back to pre-Covid times and say that this is a case of lymphatic filariasis. 

This case is very therapeutic for me. I have exorcised a ghost. 

Now I am off to watch Puscast #2.

Andrew

Eyal writes:

G’Day from Sydney Australia, where we are in the middle of Autumn, the trees are changing and the weather is lovely.

I hope all of you are well, and especially a quick recovery to Prof. Despommier.

As to the case of the 2 women with life long swelling of the legs and groin area. My guess is Elephantiasis or Lymphedema, probably caused by the Wuchereria bancrofti parasite. 

It is amazing to think how much is dependent on different plumbing systems working correctly and what happens when there are blockages. It’s also a shame that when I was taught about the circulatory system in highschool, the lymphatic system was hardly mentioned.

It is so much fun learning about different ailments through your monthly case studies.

Thank you so much!

Eyal

Alice writes:

Dear TWIP,

I’m writing this from sunny Cambridge (UK), where it’s currently around 20 degrees. A weekend of initially sunny weather means everyone has got their barbeques out only for there to then be (at least what felt like) torrential rain yesterday afternoon- typical! I work as a scientist for a UKHSA microbiology laboratory. Being located in the UK means we receive relatively few parasites, although we do occasionally have patients who have returned from other countries with parasites or other diseases not endemic to the UK- we were even in the news recently with the first Lassa fever cases in the UK for over a decade. 

https://www.bbc.co.uk/news/uk-england-beds-bucks-herts-60335313

We also recently received an earthworm- perhaps more people should be listening to your podcast to prevent panic over non-existent parasites!

I believe the two Ghanaian patients are suffering from lymphatic filariasis. It can be caused by three species of nematode- Wuchereria bancrofti, Brugia malayi and Brugia timori, which are transmitted by various different species of mosquito. The literature seems to suggest that B. malayi and B. timori are not endemic to Africa, so it is likely in this village the cases are caused by Wuchereria bancrofti, transmitted by either Anopheles gambiae or Anopheles funestus. 

Diagnosis in patients with active disease is done by making a thick smear with blood taken at night (due to the nocturnal periodicity of the parasite), staining with Giesma or H&E and identification of the microfilariae under the microscope. Serological testing (looking for elevated IgG4 can also be carried out, although I guess would be less practical in resource limited settings. It is not unlikely that the two patients in the case study would have negative lab test results as lymphodema is a symptom of chronic infection, and does not require microfilariae to be present.

Most people infected with Wuchereria never develop symptoms, but being bitten multiple times over a long period increases the risk of developing lymphodema. In these patients, the adult nematodes block/damage lymph vessels, causing the severe swelling of limbs described. In males, it can also cause the same swelling of the scrotum. In addition to fluid, the lymphatic system also transports immune cells, so the damage can also lead to impaired immune function in the same areas, which is presumably what caused the ulcer in the second patient as the body was unable to adequately respond to some sort of bacterial infection.

In terms of treatment, diethylcarbamazine kills the microfilariae and some of the adult worms, although it can worsen onchocerciasis so in patients suffering from both diseases ivermectin is the recommended treatment. These are the drugs that the village members should have been receiving and which would have prevented symptomatic disease, but they are not recommended in people with lymphedema as these patients often do not have active disease. For the two Ghanaian women, (at least in an ideal world), WHO recommends ‘simple measures of hygiene, skin care, exercises, and elevation of affected limbs’. Antibiotics (the exact combination depending on the bacteria present in the wound) should be used to treat the ulcer in the second patient.

Lymphatic filariasis should be a preventable disease with a combination of vector control and mass drug administration (of ivermectin in Ghana as onchocerciasis is endemic). These cases highlight one of the many barriers to eliminating these diseases in practice.

Apologies for the slightly waffle-y answer, I tried to keep it reasonably short, and thank you for another fascinating case!

Best wishes,

Alice

Benjamin writes:

I think that the two women are suffering from lymphatic filariasis. It may have progressed to elephantiasis. 

Source: https://www.cdc.gov/parasites/lymphaticfilariasis/gen_info/faqs.html 

-Ben

Benjamin D. Sumner

PhD

Cardé Laboratory

Department of Entomology

University of California

Riverside, CA

Alex writes:

Dear Professors,

The women with the chronic lower extremity edema and related complications probably suffer from lymphatic filariasis, which is caused by filarial nematodes, which are transmitted by mosquitoes. The adult worms live and reproduce in lymph nodes of the body and evade the immune system until they die. As per Prof. Despommier: “When they die, they calcify.”, leading to obstruction of lymphatic drainage and chronic edema of the extremity, unflatteringly termed “elephantiasis”.

The most likely culprit here is Wuchereria bancrofti, which is the most common cause of lymphatic filariasis worldwide. The other filarias, Brugia malayi and timori, are not endemic to Ghana.

Loa loa can also cause lymphedema in some cases, but has been eradicated in Ghana and is therefore unlikely to cause such a high prevalence of disease in the village. Non-filarial elephantiasis, known as “podoconiosis”, is another possible differential, but is again not described in Ghana. It is possibly caused by antigens in soil and an immune predisposition of the exposed individual.

The more pronounced edema of the left foot is not uncommon; this is also commonly seen in congestive heart failure and other causes of fluid retention, as the left iliac vein has to cross over the right iliac artery to drain into the inferior vena cava, creating a narrowing in the lumen. This might contribute here, although n=2 is not an impressive sample size.

All the best and take care,

Alexander from Vienna, Austria

Now finally an ID resident

Gina writes:

Dear Vincent and the TWiPs, 😊👍

72 degrees Fahrenheit, and partly cloudy with a 10% chance of meatballs. 🍝

It sounds like lymphatic filariasis to me. The mosquitoes 🦟🦟🦟🦟🦟🦟 were the first clue for me. The thirsty nuisances are necessary for part of the parasite’s life cycle, if I remember correctly. The parasites  cause swelling in the legs and in men can cause swelling in the genitals. They can also cause the ulceration complained of by one of the patients. It is usually treated with albendazole and our versatile hero, ivermectin, I believe.  😉    This treatment kills the immature parasites and gives the adult worms time to die off, if my memory serves.  The use of mosquito 🦟 nets are also encouraged, as in malarious regions. 

Best wishes to you all, and thank you,

Gina 🐐

8 Anthony writes:

The woman have lymphatic filariasis transmitted by a mosquito vector.

A 2019 Ghana news Site states

Fight against elephantiasis almost won in Ghana

https://www.graphic.com.gh/news/general-news/fight-against-elephantiasis-almost-won-in-ghana.html

Anthony

Carol writes:

Hello everyone! The parasite causing the problem in case 205 is Wuchereria bancrofti, a blood microfilaria. As soon as Dr. Griffin mentioned mosquitos, swollen legs with thickening skin, and that it is a common issue in the village, I knew it had to be the disease lymphatic filariasis, also known commonly as elephantiasis. I remember learning about this in my clinicals and the pictures of the people with enlarged body parts have always stuck in my head. Then when Dr. Despommier almost mentioned an “unmentionable” problem with the men…I thought, YIKES. I definitely have this identification nailed down. By the way, if someone doesn’t say it before me, THAT problem is hydrocele, or swelling of the scrotum.  Those pesky microfilaria love to damage the lymphatic system so that the fluid doesn’t drain as it should. This results in the lymphedema noted in the cases of the two women. I’d love to see other lab test results on these patients, like a complete blood count (CBC). Eosinophils, which can be prevalent in parasitic disease, are so beautiful to look at under the microscope! Thanks for giving me an easy time on this one and I hope to win the book this time. Keep the interesting cases coming!

Carol Church, MT(ASCP)SM

Paddy writes:

Hi all.

Nice easy one this week. Guessing without research that it was a case of elephantiasis caused by the parasite Wucheria bancrofti. A terrible affliction and hopefully treated successfully.

Regards Paddy.

Sara writes:

Dear TWIP Experts, 

Hello from a pleasant 62 F (17 C) evening in Philadelphia. 

This month’s case involves two women who reside in a village in Western Ghana where there is a large lagoon and plenty of mosquitos. The 80-year-old woman is suffering with chronic left lower extremity hardened swelling with thickened skin and areas of hypopigmentation and scarring.  The 50-year-old woman initially experienced bilaterally lower extremity swelling, but over time her left lower extremity became chronically swollen, indurated, and disfigured and is now complicated by a non-healing ulcer on her left lower limb. They report that many of their family and community members in this village have had similar problems.

These women have chronic left lower extremity lymphedema most likely secondary to Wuchereria bancrofti filarial worms transmitted by anopheles mosquitos. Wuchereria worms climb along the lymphatics and damage the lymph system leading to chronic manifestations as were seen in these two patients in as many as 1/3rd of cases. Inguinal and intrascrotal lymph node damage can also lead to a hydrocele in patients who have scrota/testes.  I believe the preferred and only host for Wuchereria bancrofti is humans (c.f., Brugia which is mostly in Asia and will infect non-human animals as well as humans) and so a mass drug campaign can be especially effective in eradicating the disease in an area where it is endemic, as the 50-year-old patient pointed out. I would treat both women (and ideally the entire village) with diethylcarbamazine. However, they are also in a region where loa loa is endemic, and giving patients with loiasis diethylcarbamazine can lead to the dreaded, life-threatening Mazzotti reaction that has been mentioned before on this podcast. For that reason, I’d want people to have a thorough eye exam prior to administering DEC. Ideally, the village would receive a mass drug administration campaign on a yearly basis to protect everyone from suffering from these recurrent infections. 

On a separate note, damaging the lymphatics predisposes patients to recurrent bacterial infections and poor wound healing, which I suspect is the case for the 50-year-old patient. After the worms are eradicated, treating any bacterial infections appropriately and wearing compression stockings and protective footware would be important to prevent recurrent infections. 

I don’t believe it will be possible to reverse either of these women’s chronic lymphedema even after eradicating the worms — is that correct? 

Thank you for another fascinating case!! 

Gratefully, 

Sara

Elise writes:

Dear TWiP Collective, 
How are you? The weather here in Lower Manhattan  is a murky 66 degrees F, as the week recovers from a bizarre jolt of 90-plus degree weather this weekend.

I am back with a diagnostic guess after a hiatus during which I was ridiculously dissipated. 
I suspect the two Ghanian women are both suffering from lymphatic filariasis. The nematodes that are responsible for these infections are common all across Africa, with patients presenting these infections in different ways (including ocular inflammation, dermatitis, and other lymphatic illnesses). 

These two women live in a village with a large lagoon nearby, and the standing water offers an ideal habitat for the mosquitoes that carry the set of nematodes that are responsible for the infection (some common ones are W. Bancrofi,  Brugia malayi, and B. Timori). I suspect that it is very possible for both women to have been repeatedly infected over a period of many years (especially since the older patient says she’s had discomfort and swelling most of her life). I know that treatment, once the infection has become so pronounced, is difficult. (This presentation is also called Elephantiasis, though I was wondering if that name is a catchall that describes other infections with similar presentations as well.)  The fact that the women are so often barefoot leaves them susceptible to earth borne parasites, but the mosquitoes seem to be the most likely culprit for infection. 

Treatment includes anti parasitic medication to kill the nematodes (such as ivermectin or albendazole) in conjunction with a program of cleaning, elevating, and exercising or otherwise manipulating the effected tissue to promote blood and fluid circulation. 
I wonder if the fact that these symptoms are more common in the women of the village comes from the fact that the women are pregnant so often. I know that during pregnancy, the immune system is somewhat suppressed, so is there a chance they are more susceptible during those times? Alternatively, do the women spend more time in activities close to the water (especially in the early evening) where the mosquitoes are most likely to congregate? 

Thank you so much for everything you do. 

Many best wishes,
Elise (in Lower Manhattan)