Erik writes:

Hi there TWiP Advisors,

After hearing this week’s case of the week I can really only think of one thing that could be the causative agent of the woman’s symptoms. Ordinarily I would try to provide other possible infections that might explain the symptoms, but when I hear the words “sticky, foul-smelling loose stool” I can think of no other parasitic infection than Giardia lamblia. Giardia has a global distribution, including Thailand and Cambodia. We generally think of Giardiasis occurring as the result of drinking contaminated water while out in the wilderness hiking or camping. However, this doesn’t seem to have been the case with the woman who visited Thailand as she reports drinking bottled water. But Giardia can also be contracted by consuming food items that have been in contact with contaminated water. For example, a salad that was rinsed with water containing the parasite. Giardia infection is often treated with metronidazole (Flagyl) or tinidazole.

Regards,

Erik

Blair writes:

Dear Vincent, Dickson and Daniel,

I believe that this 61 year old lady is suffering from giardiasis (secondary to the parasite giardia lamblia). She has steatorrhoea and is bloated and gassy due to fat malabsorption in her small intestine where the parasite likes to reside.

It is notoriously tricky to confirm the diagnosis. Identifying the cysts or trophozoites in stool can be hard as shedding is irregular, and often requires several stool specimens taken on different days to increase the diagnostic yield.

As patients are usually being managed in the community it is laborious to get them to come back to submit stools specimens for analysis day after day, so at our centre we do a PCR test to increase sensitivity if microscopy is negative.

The other way to make the diagnosis is by getting a duodenal aspirate or biopsy, although these are invasive tests and hence generally reserved for specific situations.

We have a low threshold for empirical treatment with tinadazole 2g single dose if the history seems classical as in this case, but it is always nice to confirm the diagnosis! An alternative would be metronidazole – it is important to remember to let the patient know to avoid alcohol for a few days with either treatment…

It can and is sexually transmitted via the faeco-oral route…hence important to consider/ ask about sexual practices…I’ll leave it at that…

I first got in to listening to your parasitic podcasts when studying for the diploma in tropical medicine and hygiene a couple of years ago, and continue to enjoy them just as much today – keep up the good work!

Best wishes,

Blair Merrick

Adam writes:

Dear Vincent, Dickson and Daniel!

My guess for the case in TWiP 166 is Giardia (something I personally have had on a few occasions when travelling in Nepal). Diagnose is by microscopy or PCR of the feces. Treatment is tinidazol or metronidazol.

Best regards,

Adam Oscarson, Halmstad, Sweden

Nathan writes:

Hello TWiP Experts,

I teach a junior level parasitology course at UMass Dartmouth in the Medical Lab Science Program. This year, we adopted PD #6 as our textbook. The students were very happy to see that there is a free e-book version available.

The 25 students in the course listened to the case study this week and wanted to give it a shot. (We have covered everything except for trematodes and cestodes so far).

Based upon the symptoms, the students think this case is consistent with a Giardia duodenalis infection.

The patient reported foul smelling, sticky diarrhea (as opposed to the good smelling diarrhea), with flatulence, pain and bloating. This information is very consistent with the clinical disease description of Giardia duodenalsis on page 15 of PD 6. “The acute diarrhea of giardiasis is classically  described as foul-smelling with flatulence, nausea, weight loss and abdominal  cramps with bloating… Untreated, this type of diarrhea may last weeks or months”

She likely became infected when consuming food or drink contaminated with the infectious cysts.

The organism can be diagnosed via direct microscopy. The students reported that this organism is often difficult to find microscopically because fecal smears can be “messy”. NAATs and ELISA are alternative testing options.

If this patient is in fact infected with Giardia, the treatment is metronidazole for one week.

Thanks again for producing this podcast and inspiring the next generation of parasitologists. If we win the book, please re-spin as we are happy with the digital version.

Kevin writes:

Diarrhea Word of the Day (related to our case in the most tangential way possible):

lientery: A form of diarrhea, in which the food passes through the bowels partially or wholly undigested; an instance or kind of this. A lexicon of diarrhea terms appears in the endnotes.

THE CASE:

Diarrhea in a 61 y/o female traveler to Thailand and Cambodia. Our patient has diarrhea that has persisted for several weeks since returning to the US. Her stool is described as bulky, sticky and foul. The work ‘bulky’ is one that I have heard for years in reference to stool (where it is invariably associated with the malabsorption syndrome). After considering this case I realized that the precise definition of ‘bulky’ in reference to stool completely eluded me. I was reminded of the Karl Kraus quotation: “The closer the look one takes at a word, the greater the distance from which it looks back.” I usually considered bulky to mean big and chunky (bodybuilders were ‘bulked up’, a large book was ‘bulky’.) I always associated bulky with something solid, which gives rise to the rub- how can diarrhea (a liquid or semi-solid) be bulky ? To clarify this matter the Oxford English Dictionary assisted: the definition of bulky, (among others) was voluminous. Stool morphology is characterized in the Bristol Stool Chart (see REF in endnotes) where the term bulky is unmentioned, but their spectrum of stool character ranges from nuts to gravy (forgive my food metaphors). Finally, on a practical level, I suspect that if you asked someone if they were having bulky stools you would at best receive a puzzled expression and at worst a ‘clip in the earhole.’

The many varieties of traveler’s diarrhea, their relative etiologies, incidences and geographies are referenced below. Of course bacteria and viruses form the bulk of the cases. Relevant to us are protozoa and helminths. Traveler’s diarrhea survey studies and our patient’s clinical presentation with bloating and malabsorption-type diarrhea strongly suggests giardiasis. Other considerations are Cryptosporidium (immunocompromised at higher risk, diarrhea described as watery in PD6), , Cyclospora cayetanensis , Entamoeba, microsporidia (closely related to fungi but behave like intestinal protozoa…primarily a disease of the immunosuppressed) and Cystoisospora belli (immunocompromised, can manifest a malabsorption syndrome). Helminths such as strongyloides, ascaris, hookworm and trichuris should be kept in mind but our patient’s clinical presentation is not consistent with worms. Co-infection with multiple parasites must always be kept in mind, as studies and surveys provide ample evidence for this.

Diagnosis of giardiasis traditionally was with microscopic examination of fresh stool, and occasionally microscopy of duodenal aspirates. In the 80s an awkward intestinal sampling technique was used, formally named the Entero-test, informally called ‘the string test’, which PD6 charitably eulogizes with the entry “now relegated to a place in history.” Individual PCR testing is available but even this modern technique is being replaced by a variety of nucleic acid tests such as the LuminexTAG GI pathogen panel which tests 19 enteric pathogens including 3 protozoa. The BioFire Film Array GI panel has 22 targets and a potential one hour turnaround time. Other gene array panels are the TaqMan Array card and the Seegene Allplex GI panel. These tests have very impressive sensitivities, specificities and turnaround times (between one and four hours). Multiple internet sources list a price of about $150 for one GI panel. This price quote requires further research however, as it sounds too good to be true.

Treatment is succinctly outlined in PD6, with initial treatment being metronidazole or tinidazole. Refractory disease, resistant organisms and recurrent disease are fully discussed in that text. Recurrence or persistence of symptoms post-treatment should always raise the possibility of post-infectious irritable bowel syndrome. Patient should be offered HIV testing if it has never been done. Her overall prognosis should be excellent. Who knows where she picked up the offender, but as an old parasitology professor used to intone, quoting (perhaps apocryphally) the famous Rockefeller Institute parasitologist Norman R Stoll: “The path from the anus to the mouth is all too short.”

Thanking the TWiP panel for their time, dedication, humor &tc.

References, Endnotes, and a Terminal Curiosity

Hippocrates weighs in on diarrhea (Of the Epidemics Section II, part 1.):

During summer and autumn there were dysenteric affections, attacks of tenesmus and lientery, bilious diarrhoea, with thin, copious, undigested, and acrid dejections, and sometimes with watery stools; many had copious defluxions, with pain, of a bilious, watery, slimy, purulent nature, attended with strangury, not connected with disease of the kidneys, but one complaint succeeding the other; vomitings of bile, phlegm, and undigested food, sweats, in all cases a reduncance of humors.

https://www.continence.org.au/pages/bristol-stool-chart.html (Bristol Stool Chart.)—bulky not mentioned

A morphological classification of 7 types of stool.

Karl Krause original quote: Je näher man ein Wort ansieht, desto ferner sieht es zurück

Travelers’ Diarrhea in Thailand: A Quantitative Analysis Using TaqMan® Array Card. Lertsethtakarn P et al. Clin Infect Dis. 2018 Jun 18;67(1):120-127.

US military population. They give the figure of 6-16% of travelers who return from Thailand have experienced diarrhea. Commercial Enzyme-Linked Immunosorbent Assays (ELISA) kits were used to detect parasites (Cryptosporidium, Entamoeba histolytica, and Giardia) (TECHLAB®, Blacksburg, VA, USA)

TaqMan® Array Card nucleic acid extracted from ‘the sample’ was loaded into the TAC…(Taq Man Array Card)– it tests for the following: 12 different bacteria, two fungi [Encephalitozoon intestinalis and Enterocytozoon bieneusi]; five nematodes [Ancylostoma duodenale, Ascaris lumbricoides, Necator americanus, Strongyloides stercoralis, and Trichuris trichuria]; five protozoan parasites [Cryptosporidium, Cyclospora cayetanensis, E. histolytica, Giardia lamblia, and Cystoisospora belli];, and five viruses [adenovirus, astrovirus, norovirus GI/GII, rotavirus, and sapovirus].

Results in 154 cases: 31% Campylobacter. 1.3% cryptosporidium, 1.3% cyclospora, 0.7% Giardia, 0% E. histolytica.

Epidemiology of travelers’ diarrhea in Thailand. Chongsuvivatwong V, J Travel Med. 2009 May-Jun;16(3):179-85.

Based on 22,401 completed questionnaires, the attack rate for TD was highest among residents from Australia or New Zealand (16%), while those from the United States and Europe had attack rates of 7% to 8%. Independent risk factors for the development of TD were eating outside the hotel and eating meat. In contrast, a history of drinking tap water and consuming ice cream were protective. I

…..56 subjects studied for etiology, Aeromonas spp were found in 8 subjects (14%), enterotoxigenic Escherichia coli (ETEC) or Vibrio spp each was found in 7 (13%) with O1 V. cholera (cholera) seen in one, mixed pathogens were found in 3 (5%), with no pathogen being detected in 33 (59%).

Traveler’s Diarrhea: A Clinical Review, Robert Steffen, MD, et al. JAMA January 6, 2015 Volume 313, Number 1

The incidence of traveler’s diarrhea during a 2-week trip remains 10% to 40%,…a third of physician visits by returned travelers is for a compliant of diarrhea. Author’s definition: The disease is present if travelers develop at their destination 3 or more unformed stools per 24 hours plus at least 1 additional symptom, such as abdominal cramps, tenesmus, nausea, vomiting, fever, or fecal urgency

…South Asia and West/Central Africa remain the destinations with the highest risk of traveler’s diarrhea (where, what is ‘South Asia’=The World Factbook, based on geo-politics, people, and economy defines South Asia as comprising Afghanistan, Bangladesh, Bhutan, British Indian Ocean Territory, India, Maldives, Nepal, Pakistan, and Sri Lanka….) RISK of t.diarrhea has been decreasing in SE Asia…

Long-term complications of traveler’s diarrhea can occur:postinfectious irritable bowel syndrome (PI-IBS) after traveler’s diarrhea may occur in 3%to 17%of patients….The most important causes of traveler’s diarrhea occurring in developing regions, in decreasing order, are ETEC (heat-labile and heat stable toxin producing), enteroaggregative E coli, diffusely adherent Ecoli, noroviruses, rotavirus, Salmonella species, Campylobacter jejuni, Shigella species, Aeromonas species, Plesiomonas shigelloides, enterotoxigenic Bacteroides fragilis, and Vibrio species; the parasites Giardia duodenalis, Cryptosporidium species, Entamoeba histolytica, and Microsporidium species show regional importance.

Traveler’s Diarrhea Complicated by Persistent or Refractory Diarrhea Persistent diarrhea is present when diarrhea lasts for longer than 14 days; it occurs in approximately 2% of traveler’s diarrhea cases. Refractory diarrhea is diagnosed when traveler’s diarrhea fails to respond to antimicrobial therapy or recurs after an apparent clinical response.When this occurs, antibiotic-resistant bacteria and protozoan parasites, usually Giardia or Cryptosporidium, should be suspected. A stool sample should be collected and processed for Salmonella, Shigella, and Campylobacter. Protozoal pathogens should be evaluated by microscopy or enzyme immunoassay.Screening of asymptomatic returned travelers for intestinal parasites has a low yield unless they are at risk of schistosomiasis following freshwater exposure in Africa.

Traveler’s Diarrhea in Foreign Travelers in Southeast Asia: A Cross-Sectional Survey Study in Bangkok, Thailand, Chatporn Kittitrakul et al, Am J Trop Med Hyg. 2015 Sep 2; 93(3): 485–490.

Simply a survey. No information on etiology. Some clinical information. Airport 7,963 questionnaires….The attack rate of traveler’s diarrhea was 16.1%, with an incidence rate of 32.05 per 100 person months. Diarrhea attack rate varied according to patient nationality….highest in Oceanians and lowest in East Asians

[definition of East Asian: Geographically and geopolitically, the region constitutes China, Hong Kong, Macau, Taiwan, Japan, Mongolia, North Korea, and South Korea. ] ….(only 5.7% of the sample here was from North America)…Among travelers who only visiting Thailand, the attack rate of travelers’ diarrhea among the group was 10.9% (657/6,025)

Etiology of Travellers’ Diarrhea, Z.D. Jiang, Journal of Travel Medicine, 2017, Vol 24, Suppl 1, S13–S16

A literature review of 11 travelers diarrhea etiology studies conducted between 2010-2016 (total patients=4,838). Most studies determined etiology via multiplex PCR.

Using conventional PCR as a reference method, BioFire FilmArray GI panel yielded sensitivity and specificity of 100% for Giardia and Cryptosporidium. BD Max EPP had sensitivity of 93% for Cryptosporidium, 99% for Giardia, 100% for Entamoeba histolytica. PCR methods may be the optimal means of diagnosing protozoal enteric parasites included in the assays where published specificities were 100%……Lumniex xTAG GPP panel.6 This improved the diagnosis of TD significantly. The equipment is expensive in the range of $60 000 and the kits that run the broad range of pathogens in a single assay cost $750.

Cyclospora cayetanensis infections among diarrheal outpatients in Shanghai: aretrospective case study, Jiang, Y., Yuan, Z., Zang, G. et al. Front. Med. (2018) 12: 98.

A 2013 case series where 291 outpatient stool specimens from diarrhea patients were examined for Cyclospora with light microscopy and PCR. Microscopy yielded no cyclospora cases. PCR was positive for five cases (1.7%)

Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis, Sarah N. Buss, J Clin Microbiol 53:915–925 OPEN ACCESS

Prospectively collected stool specimens (n 1,556) were evaluated using the BioFire FilmArray GI Panel and

tested with conventional stool culture and molecular methods for comparison. The FilmArray GI Panel sensitivity was 100% for 12/22 targets and>94.5% for an additional 7/22 targets. For the remaining three targets, sensitivity could not be calculated due to the low prevalences in this study. The FilmArray GI Panel specificity was>97.1% for all panel targets. The FilmArray GI Panel provides a comprehensive, rapid, and streamlined alternative to conventional methods for the etiologic diagnosis of infectious gastroenteritis in the laboratory setting. The potential advantages include improved performance parameters, a more extensive menu of pathogens, and a turnaround time of as short as 1 h.

Case Report: Cyclospora cayetanensis: This Emerging Protozoan Pathogen in Mexico, Jose T. Sanchez-Vega, Am. J. Trop. Med. Hyg., 90(2), 2014, pp. 351–353 OPEN ACCESS

Cyclospora cayetanensis: a description of clinical aspects of an outbreak in Quebec, .F. Milord, Canada, Epidemiol. Infect. (2012), 140, 626–632 OPEN ACCESS

www.cdc.gov/parasites/cyclosporiasis/health_professionals/index.html

Cyclospora link

SOME TERMINAL CURIOSITIES

In re ‘bulky’ —-From the Oxford English Dictionary

1879   W. E. Gladstone Gleanings Past Years II. v. 213   This is a large, but not a bulky, Biography. For the word bulky insinuates the idea of size in excess of pith and meaning.

In the course of reading background material for our case I came across this sentence: “He had a history of periumbilical colic-like abdominal pain, push, tenesmus, meteorism, audible borborygmi, semi-liquid to pasty feces, and 5–8 explosive bowel movements a day.” Since some of these terms might be obscure to some listeners I have constructed a crude

Lexicon Diarrhoeae:

LOOSE: I hear this often, ‘loose stools’. I have never seen a proper definition of this. The OED in one definition lists ‘unrestrained’, which seems apt. The usual implication is that loose stools are unformed or liquid. I judge this term to be overly vague.

PUSH: (see above quote). I’ve never heard this and I suspect it is a translation problem by a non-native English speaker. OED lists one definition as ‘impulse, urge’.

EXPLOSIVE: as in ‘explosive diarrhea; difficult to get a technical definition. A less than peer reviewed source (Medical News Today) states: “Explosive, or severe, diarrhea causes a person to pass liquid or loose stool more frequently and forcefully than regular diarrhea” I recommend the urbandictionary.com definition which is enlightening and frightening. A classic disease association that reflexively uses the term explosive: Clostridium perfringens Type A enterotoxin diarrhea. We seem to be relying here on the “I know it when I see it” school of terminological precision. Most of the entries I viewed surround the term with qualifiers such as ‘large volume’, ‘urgent’, ‘pressure’, ‘velocity’, and ‘uncontrollable’. I think that the term ‘severe’ or ‘very severe’ would suffice for most uses and probably be less alarming to patients and their families.

METEORISM: “Inflation of the abdomen by gas within the intestinal loops we call meteorism.” Alois Pick, Clinical Symptomatology 1911. (ancient Greek, meteorismus- a lifting up, a swelling). For your patients, clarify the term by explaining that it is synonymous with tympanites. Maybe people will think you are smarter if you use obscure Hellenisms.

BORBORYGMI: “The term borborygmi is applied to the sound produced by displacement of gases contained within the abdomen.” August Chomel, Elements of General Pathology, 1848, or more prosaically from theGlossographia Anglicana Nova 1719 :a rumbling Noise in the Guts.

TORMINA: A golden oldie. Acute griping or wringing pains in the bowels; gripes.

TENESMUS: Chomel (1848) again: “In certain diseases of the rectum, defecation is exceedingly painful. To this pain is sometimes added a constant and ineffectual desire to go to stool together with a burning and smarting sensation about the anus; this constitutes tenesmus or epreintes (desidendi conatus), a symptom peculiar to dysentery. Tenesmus is sometimes followed by no excretion, sometimes a small quantity of bloody mucus is squeezed out with violent efforts.

LIENTERY: (See case intro above). quote from OED RE: lientery 1663   Robert Boyle Some considerations touching the usefulnesse of experimental naturall philosophy: propos’d in familiar discourses to a friend, by way of invitation to the study of it · 1663. ii. ii. 38   The slimy excretions voided in the lyantery.

Amichay writes:

Dear Tremendous Trio,

Though with way less confidence than last time, I think I have another guess for the mystery case.

The GI symptoms can indicate anything from virus to worms, but long symptomatic period suggests constant reinfection together with the antibacterial failed treatment a parasitic worm seems more plausible. The fact that the patient claims to avoid raw food and local water suggest infection route other than oral. Combined with the patient travel history my guess is Strongyloides stercoralis.

Also, I think prof. Despommier already mentioned that he and his wife had it once in previous episodes….

The larvae can be identified in stool sample, and as for treatment, PD 6th edition suggests albendazole and ivermectin.

Thank you for another interesting episode,

Alexander writes:

Hi all,

It’s been a long time since submitting a guess for a case. I’ve been busy with trying to get used to the change of life in university from college.

I think that the woman who was traveling to Thailand and Cambodia, might have giardiasis, from Giardia lamblia. The symptoms seem to line up with abdominal pain, flatulence, and loose and foul smelling stools. According to Dr. Google, symptoms tend to appear a few weeks after exposure. As she drank bottled water, I am going to assume that the exposure most likely came from the food that she ate. Was she the only one of the party that became ill, if so she might be immunocompromised or hopefully just really unlucky. PD 6th edition states that microscopy is still the definitive diagnosis, but ELISAs and NAATs are available depending on a lab’s resources. If it is G. Lamblia, PD 6th edition says that the nitroimidazoles are used to treat it, I’ll leave it to the professionals to know which one is the best.

I have gotten lucky before and got the hardcover of PD 6th edition however I wanted to see if my old college might want it, but being 100 miles away from there and only returning home on the holidays hasn’t allowed me to bring it over. So while I would like a copy for myself, please remove me from the drawings so that other people may have a greater chance.

Thank you,

Alexander Islas

Caitlin writes:

Dear Upper Class TWiPs,

The lady with sticky, foul-smelling diarrhea, abdominal cramps, and bloating appears to have a textbook case of giardiasis, caused by Giardia lamblia. All of the symptoms seem to fit, along with the timeline. This beastie is transmitted fecal-orally through contaminated water. Although the patient was careful to avoid potential sources of contamination, Giardia gets everywhere in endemic areas.

Other possibilities include:

She might have one of the many species of Cryptosporidium, but if she is not immunocompromised – not necessarily a valid assumption – the the diarrhea should have been fairly short-lived.

Cystoisospora is capable of causing prolonged diarrhea and most of the other symptoms. However, C. belli is unlikely to make a previously healthy patient so ill; it is mainly a serious disease in AIDS patients. It was noted that she is not sexually active – she may have been earlier, or might have become infected with HIV some other way, but it’s highly improbable that this wouldn’t have been detected earlier.

Cyclospora cayetanensis can cause diarrhea lasting 2-3 weeks and most of the other symptoms, but we’re at least on the upper end of that with “several weeks.” What’s more, it causes watery diarrhea, so it fits neither the symptoms nor the timeline.

Strongyloides can produce diarrhea lasting up to six weeks, in about 25% of symptomatic patients, with various other GI symptoms; but again, the diarrhea is supposed to alternate with constipation, and there would be other symptoms as well.

Capillaria philippinensis produces protracted diarrhea and malabsorption of fats which suggests it could result in the greasy/sticky stools in this case. But in addition to being not quite the right part of Asia, is caught by eating raw/undercooked seafood, which the patient avoided.

The infection is not 100% certain to be Giardia, but given that it is absurdly common, and causes noticeably sticky, oily, foul-smelling diarrhea (steatorrhea), it is by far the likeliest in this case. It can be detected by examining the stool for trophozoites or cysts, or, if we’re going to be more modern, antibody tests. The patient should be treated with metronidazole or tinidazole.

If we win the book, please donate it to a university – perhaps the maths department would appreciate it.

This letter is a tale of two continents, brought to you by Carrie, from Newcastle-upon-Tyne, England, and Caitlin, of Seattle.

5-Lauren writes:

Hello, TWIP

In response to the recent consult from gastroenterologist. regarding 61yr old woman on trip to Thailand, Cambodia for a few weeks.

Here is my differential; Entamoeba histolytica, Cryptosporidium parvum and Giardia lamblia. These are my usual suspects for diarrhea. Cryptosporidium parvum is notably watery and quite profuse. E. Histo When its clinical usually exhibits with a fever as well as heme-positive stool. Giardia checks a lot of the box’s diarrhea, bloated, gaseous, loose stools, sticky and foul smelling. Plus, active stage in the small intestine which so happens to be in the lower left side at the abdominal. So, I’ll have to go with my “gut feeling”, sorry couldn’t help it.

I suggest to you, diagnosis of Giardiasis from the protozoa Giardia lamblia. Here are some potential ways to confirm diagnosis; Stool ova and Parasites test; Antigen capture-ELISA from stool sample ,maybe not if she is immuno compromised Since it would not be affective; or Nucleic acid amplification tests (NAATs).

Treatment: Giardia usually clears up on its own in a couple of weeks, but in some individuals it may persist. If their immune system isn’t up to snuff or has difficulty dealing with Giardin. Preferred drug options are Metronidazole 250mg PO TID x 7 days or Tinidazole 2 grams PO x 1. Alternative drugs, Paromomycin, Furazolidone, Quinacrine and Albendazole. These also would be effective against other protozoans.  It may be one of those “newfangled” resistant variety of Giardia “…but with a different class of antimicrobial therapy or a longer course of the oral agent. in some refractory cases combination antimicrobial therapy may be necessary.”, (From the parasites without borders video on Giardia.) Azithromycin may not have been effective because it is used for bacterial infections? i.e. Vibrio cholerae, dysentery… yet, I also saw toxo in that list, which is a protozoan so…?

Sorry for the brevity of my email and the tardiness of my last. Thank you for everybody’s time and effort on TWIP.

P.s. For us non-Med students, what is the symptomatology in the quadrantal description called? The organ involvement based off the area of discomfort? It would be beneficial to know what that Is called in diagnosing. So, I can know what organs are being affected. Thanks.

Trudy writes:

Dear TWiPers,

I believe the 61-year-old woman is infected with Giardia lamblia. This parasite is acquired through the fecal-oral route, most often by drinking contaminated water. It is my understanding that she only drank bottled water during her travels, but have any of you seen Slumdog Millionaire? There’s a scene at the beginning where retailers of bottled water are refilling and resealing used bottles with tap water. This is in India, but I think it’s safe to assume that it would happen in other third world countries as well. Diagnosis would require analysis of a stool specimen by microscopy, ELISA techniques, or nucleic acid amplification. For treatment, the patient would be given a nitroimidazole, metronidazole, or tinidazole.

I already own a signed copy of Parasitic Diseases, so no need to enter me in the drawing. Thank you! However, I still need to come back to the TWiV studio so Dickson can sign my copy of West Nile Story. Hopefully soon!

Thanks again and Best Regards,

Trudy.

Charlotte writes:

Remote location

Dear Twipsters,

Thank you for keeping me entertained whilst on my sick bed … 4 months later still recovering from a prolapsed disc L5 and separated from reaching my scientific dreams (PhD and beyond), but you’ve raised a smile from me.

Charlotte

London, UK

Kevin writes:

Dear Twip professors

Not sure why my submission did not get received, but I’m sending it along so that perhaps it can be put into the show notes. Check out my elephantiasis anecdote under “A terminal curiousity”

K

TWiP 165 notes—Case read on TWiP 165 for discussion on TWiP 166

01/28/19

Kevin Carney

An adolescent male from eastern Uganda presents to Dr Griffin’s clinic with a painless scrotal mass. This approximately 6 centimeter swelling transilluminates when a light is placed behind the mass.

I begin with a quote from the English surgeon Percivall Pott (1714-1788), who many will remember elucidated the nature of “the soot ulcer”, scrotal carcinoma of chimney sweeps, one of the first occupational illnesses to be clearly described. Pott also described tuberculosis spondylitis and developed many surgical techniques, among those being correction of hydrocele: “An hydrocele is so irksome a disease to the indigent and laborious, furnishes even the easy and opulent with such disagreeable ideas and apprehensions, and is to all who are afflicted with it so troublesome and inconvenient, that every rational attempt toward relieving mankind form such an evil, will, I make no doubt, be favourably received.”

The difficulty in this case is not so much making the diagnosis, but rather grasping the enormity and complexity of the overall problem. The WHO estimates that almost 40 million persons are afflicted with some manifestation of lymphatic filariasis, with at least 25 million men suffering with hydrocele and 15 million persons with some degree of lymphedema. The offending agent in this case, and the culprit in over 80% of global parasitic lymphedema morbidity is Wuchereria bancrofti. In order not to fall into the habit of “System 1 thinking” however, a modest differential should be constructed. Other causes of scrotal swelling to consider: tuberculosis, cancer and indirect inguinal hernia. The fact that the mass transilluminates and the presence of many similar cases in the region makes W. bancrofti infection the overwhelming favorite. Chukwudi (2011) supports the use of transillumination as the sole diagnostic test in typical cases, and recommends forgoing the expensive and often unavailable scrotal ultrasound. Other diagnostic modalities: peripheral blood smear for microfilaria as well as field-ready immunologic tests such as immunochromatographic cards. In summary, typical presentation, regional prevalence and absence of other complications makes the use of “clinical diagnosis” -i.e. using you mind and hands – sufficient for definitive diagnosis in our case. Treatment of this condition poses some dilemmas. Conventional antihelminthic treatment (diethylcarbamazine) is a fairly poor macrofilaricidal agent and may even worsen the lymphatic pathology. Newer antibiotic approaches using doxycycline are being used with published data describing improvement in hydrocele pathology and progression. Doxycycline targets the endosymbiont Wolbachia which is believed to be crucial in the immunopathogenesis of lymphatic filariasis and hydrocele, via a variety of mechanisms involving VGEF, TNF, interleukins etc. Surgical management (using conventional surgery or sclerotherapy) is undertaken in selected cases but is often unavailable. Below references discuss patient selection etc for surgery. In addition to pharmacologic and surgical management, treatment must also include simple modalities such as scrupulous hygiene of the involved genitalia, since concomitant bacterial and fungal infection as well as generalized skin inflammation and fibrosis can contribute to the progression of the disease. It must be emphasized that tropical hydrocele is a cause of considerable psychological, social, sexual, and employment disability and mitigation of these factors must be included in the care of the patient. Further reading and background information is included in the endnotes, as well as near irrelevancies such as podoconiosis and a further examination of disease metaphors, this time of a zoological nature…(see culinary metaphors digression- the anchovy sauce affair in TWiP 159 case notes-Toddy Tappers). Speaking of medical terminology, please do not overlook the rather non-technical definition of ‘giant hydrocele’ in the Akpo reference below.

Thanks for your ongoing stimuli, which has revived my cortex after the polar vortex.

END NOTES AND A TERMINAL CURIOSITY

General Filariasis/ W bancrofti:

TWiP 25: Wuchereria bancrofti April 27, 2011, http://www.microbe.tv/twip/25-wuchereria-bancrofti/

A 2015 eight minute video from the BBC world service on lymphatic filariasis in India, primarily focussed on the mass drug administration program and its “operational challenges” : https://www.bbc.co.uk/sounds/play/p02jcqnp

This brief video is well worth viewing.

Manual of Tropical Medicine, (1242 pages) Sir Aldo Castellani, Albert John Chambers, William Wood & Company, 1910. Massive treatise available free via books.google.com. Interesting chapter on the filariases. Nice companion to PD6. No messy immunology or cellular biology.

Current Epidemiological Assessment of Bancroftian Filariasis in Tanga Region, Northeastern Tanzania

Happyness J. Mshana et al, J Trop Med. 2016; 2016: 7408187. OPEN ACCESS

Even after mass drug administration begun in 2000 for filiariasis in Tanzania, n=472, 5% had circulating filarial antigen, prevalence of hydrocele was 73%, lymphedema=16%  Our findings demonstrate a considerable reduction in filarial infection.

Guideline: Alternative mass drug administration regimens to eliminate lymphatic filariasis. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.

quote from Pfarr: Mass drug administration (MDA) programs aim to interrupt mosquito vector transmission and eventually eradicate the disease. However, MDA does not help those who suffer from lymphedema or hydrocele, estimated to affect 12% and 25 % of infected individuals.

Filariasis and lymphoedema, Pfarr KM et al, Parasite Immunol. 2009 Nov;31(11):664-72. doi: 10.1111/j.1365-3024.2009.01133.x. OPEN ACCESS

Abstract: Among the causes of lymphoedema (LE), secondary LE due to filariasis is the most prevalent. It affects only a minority of the 120 million people infected with the causative organisms of lymphatic filariasis (LF), Wuchereria bancrofti and Brugia malayi/timori, but is clustered in families, indicating a genetic basis for development of this pathology…. Importantly, as for the aberrant lymph vessel development, innate immune responses that are triggered by the filarial antigen ultimately result in the activation of vascular endothelial growth factors (VEGF), thus promoting lymph vessel hyperplasia as a first step to lymphoedema development. Wolbachia endosymbionts are major inducers of these responses in vitro, and their depletion by doxycycline in LF patients reduces plasma VEGF and soluble VEGF-receptor-3 levels to those seen in endemic normals preceding pathology improvement. The search for the immunogenetic basis for LE could lead to the identification of risk factors and thus, to prevention; and has so far led to the identification of single-nucleotide polymorphisms (SNP) with potential functional relevance to VEGF, cytokine and toll-like receptor (TLR) genes. Hydrocele, a pathology with some similarity to LE in which both lymph vessel dilation and lymph extravasation are shared sequelae, has been found to be strongly associated with a VEGF-A SNP known for upregulation of this (lymph-)angiogenesis factor.

Wolbachia filarial interactions, Mark J. Taylor et al, Cellular Microbiology (2013) 15(4), 520–526

OPEN ACCESS

A very technical, cell biology oriented review. Taylor is funded by the Bill & Melinda Gates Foundation. The website of the anti-wolbachia consortium: https://awol.lstmed.ac.uk/

I find it extraordinary that a parasite is dependent on an obligate intracellular bacterium for development, oogenesis, embryogenesis, larval development and establishment, and as “an essential partner to key biological processes in the life of the nematode.”

Chronic clinical manifestations related to Wuchereria bancrofti infection in a highly endemic area in Kenya

S.M. Njenga et al, Transactions of the Royal Society of Tropical Medicine and Hygiene (2007) 101, 439—444

Malindi district, Kenya. Of 186 males aged 15 years and above examined, 64 individuals (34.4%) had hydrocele, and the prevalence of the manifestation in those above 40 years old was 55.3%. The prevalence of leg lymphoedema in persons aged 15 years and above was 8.5%, with a higher rate in males (12.6%) than in females (5.7%). The overall prevalence of inguinal adenopathy was 8.6%, and males had a significantly higher (12.9%) prevalence of adenopathy than females (5.1%) (P < 0.001)……Hydrocele was the most common chronic clinical manifestation of lymphatic filariasis observed in the present study….This observation is consistent with reports from most studies in sub-Saharan Africa.

Excellent public health advertisement/ consciousness raising mass media piece:

Two minute public health video from the Sabin Vaccine Institute and Richard Hatzfeld directed to affected communities in India to assist with raising awareness and enhancing mass drug administration adherence. Quite a touching advertisement.

https://www.campaignindia.in/video/taking-giant-steps-to-end-filaria-with-awareness-campaign/421987

EXCELLENT fact sheet on lymphatic filariasis from the WHO:

https://www.who.int/en/news-room/fact-sheets/detail/lymphatic-filariasis

https://www.who.int/neglected_diseases/news/WHO_recommends_triple_medicine_therapy_for_LF_elimination/en/

Hydrocele:

Scrotal anatomy and the formation of hydrocele.

The testes are “suspended” in a potential cavity (the cavum vaginale) that is defined by two serous layers of the tunica vaginalis (the outer lamina parietalis and the inner lamina visceralis). It is this space that becomes distended by fluid that defines the clinical entity of hydrocele. ….blockage of lymphatic flow and chronic inflammation is believed to result in fluid secretion by the tunica layers with resultant swelling (hydrocele)

There is even an analog of hydrocele in women, Hydrocele of the Canal of Nuck (usually a congenital defect)

The Chirurgical Works of Percivall Pott FRS Vol III, 1779 (Free download at google.books.com)

Link below contains a very thorough review of filarial hydrocele, fairly nontechnical. Good illustrations.:

https://emedicine.medscape.com/article/438525-overview#a10

Reduction in levels of plasma vascular endothelial growth factor-A and improvement in hydrocele patients by targeting endosymbiotic Wolbachia sp. in Wuchereria bancrofti with doxycycline, Debrah AY, et al. Am J Trop Med Hyg 2009; 80: 956–963.

Discusses the effect of doxycycline on hydrocele…some emerging evidence for genetic / familial susceptibility to hydrocele development….people with SNPs that are associated with upregulated VEGF-A

WHO: The global baseline estimate of persons affected by lymphatic filariasis is 25 million men with hydrocele and over 15 million people with lymphoedema. At least 36 million persons remain with these chronic disease manifestations [https://www.who.int/lymphatic_filariasis/resources/9789241550161/en/]

Filarial hydrocele: a neglected condition of a neglected tropical disease, Kenneth Bentum Otabil, Seth Boateng Tenkorang, J Infect Dev Ctries 2015; 9(5):456 – 462 OPEN ACCESS.

A concise 7 page review. Filarial hydrocele is the MOST COMMON clinical manifestation of lymphatic filariasis.

Longstanding hydrocele in adult Black Africans: Is preoperative scrotal ultrasound justified?

Chukwudi O. Okorie, Nigerian Medical Journal. 2011 Jul-Sep; 52(3): 173–176.

Scrotal ultrasound is unnecessary in most cases. Transillumination is recommended. This study was a series of 102 patients, 97% were simple hydrocele, 3% had loculated hydrocele. hydrocele is more common on the right ( findings in 102 patients: left: 23 patients, right: 39, bilateral: 40.

An historical perspective:

HYDROCELE AMONGST THE LANGO OF UGANDA. WILLIAM P. KELLY, F.R.C.S.I., D.P.H.,

MEDICAL OFFICER (TEMPORARY), UGANDA MEDICAL SERVICE. The British Medical Journal, April 26, 1924

a description of a surgical technique to ameliorate this condition…interestingly, no mention of filiariasis is mentioned in the article. “THE natives of Lango (Uganda) do not appear to be possessed of any surgical skill whatever, and so pathological conditions amongst them tend to become very gross indeed. Hydroceles and, as a consequence, haematoceles are very common; some of these tumours grow to enormous proportions, often reaching nearly to the knee, causing great disability. The scrotal tissues are, as a rule, greatly thickened; and the disappearance.”

A Comparative Study of Sclerotherapy With Phenol Versus Surgical Treatment For Hydrocoele, Labib M A et al, East and Central African Journal of Surgery, Vol. 9, No. 2, Dec, 2004, pp. 25-27

Prospective trial of 80 consecutive hydrocele patients. The authors conclude: “Sclerotherapy for hydrocoele using phenol is as efficient as hydrocelectomy for cure. The risk of complications arising from phenol sclerotherapy is slight, while it allows the patient to return to normal activity on the same day, so sclerotherapy may be the option of choice for hydrocoele.”

Giant hydrocele – an epitome of neglect Emmanuel E Akpo, Afr Health Sci. 2005 Dec; 5(4): 343–344.

OPEN ACCESS. A case series. Akpo provides his own unique definition of giant hydrocele which for “clinical purposes, (is) a hydrocele equal to or bigger than the patient’s head.” Case 1, a 50 y/o man with bilateral scrotal enlargement to the knees and a ‘buried phallus’ had, upon surgery, 4 litres of fluid drained. Article contains some alarming photographs of the patient’s initial presentation.

Classifying Hydroceles of the Pelvis and Groin: An Overview of Etiology, Secondary Complications, Evaluation, and Management, Dagur G.Curr Urol. 2017 Apr;10(1):1-14

OPEN ACCESS. A massive review of ‘all things hydrocele’ …Fantastic diagrams of the many varieties of hydrocele. Did you know that there was a female variant of hydrocele?–you can read about the “Hydrocele of the canal of Nuck, also known as female hydrocele or cyst of the canal of nuck, affects infant females and results in painless or possibility painful inguinal swelling. It is an uncommon disease caused by the failure of the processus vaginalis to close during embryological development which can lead to inguinal hernia and hydrocele.”  Management options discuss aspiration and sclerotherapy versus hydrocelectomy.

PODOCONIOSIS:

I was fascinated to learn about this condition, which is new to me. Wikipedia’s definition: “Podoconiosis, also known as nonfilarial elephantiasis, is a disease of the lymphatic vessels of the lower extremities that is caused by chronic exposure to irritant soils.” The condition is found in highland tropical Africa, northwest India and Central America. It is mentioned since it is peripherally related to our case in the context of lymphedema. Podoconiosis is seen in Uganda, although at low levels. It typically causes leg lymphedema and does not usually involve the scrotum or result in hydrocele. As if poverty, neglect and an array of insect vectors and parasitic worms were not enough, even the soil beneath the feet becomes a threat to health.

How Soil Scientists Help Combat Podoconiosis, A Neglected Tropical Disease, Benjamin Jelle Visser, Int J Environ Res Public Health. 2014 May; 11(5): 5133–5136. OPEN ACCESS

Global epidemiology of podoconiosis: A systematic review, Kebede Deribe, et al, PLoS Negl Trop Dis. 2018 Mar; 12(3) OPEN ACCESS

Non-filarial elephantiasis in the Mt. Elgon area (Kapchorwa District) of Uganda. Onapa AW, et al, Acta Trop. 2001 Feb 23;78(2):171-6.

Abstract

Elephantiasis was observed in all age groups from 10 years and above. The overall prevalence was 4.5%, and the prevalence among individuals aged >/=20 years was 8.2%. Males and females were equally affected. However, there were only few cases of hydrocele (overall prevalence in males of 1.0%) and blood examinations were negative for W. bancrofti circulating antigens and microfilariae.\In view of the low hydrocele to elephantiasis ratio, the absence of filarial infection in humans and mosquitoes, the high altitude (1500-2200 m above sea level) and the volcanic soil type, it is concluded that elephantiasis seen in this area is not of filarial origin but most likely is due to podoconiosis (endemic non-filarial elephantiasis).

A Terminal Curiosity:

Several years ago I visited a bedbound woman who weighed well over 500 pounds. In addition to the burdens of obesity she was afflicted with massive bilateral lymphedema of the legs. This American woman had never travelled outside of the US. She had a condition known as Elephantiasis nostras verrucosa. This entity is reviewed by Castellani- a famous tropical medicine researcher who authored the 1913 ‘Note on Copra Itch’ (referenced in TWiP 157). This is the only time I had encountered anything like the appalling photographs seen in tropical medicine textbooks.

During our visit I mentioned that her condition was known as elephantiasis nostras. The patient immediately became very distressed by the association of her lamentable state with elephants. It took my best medical casuistry to backpedal out of this morass and the whole episode taught me the profound subjectivity and emotional content of medical language as interpreted by patients.

The WHO published guidelines concerning the naming of diseases in 2015. (see refs below). The press predictably branded the WHO initiative as a species of political correctness and reported the story in a slightly snide or frivolous way. As the above anecdote shows, a name can have profound emotional impact. Naming diseases after geographic locations can even have economic consequences.

This topic stimulated me to recall the many medical terms that are named after animals, many of which would probably be very distressing to patients. Fortunately many of these terms are being replaced by more accurate descriptors.

List of zoological medical metaphors:

rodent ulcer basal cell carcinoma is a bit more neutral

maus kopf used to describe facial appearance in scleroderma

pigbel pidgen-english term for post-starvation gastroenteritis

lupus pernio lupus- the wolf, purportedly used to describe skin that appears ravaged as if chewed by a wolf

swine flu

bird flu

icthyosis who wants to be compared to a fish?

moth-eaten alopecia

monkey pox

mad-cow

leonine facies a classic term in lepromatous leprosy, Paget’s disease of bone and diffuse cutaneous leishmaniasis

buffalo hump just what your Cushingoid patients want to hear- additionally, if they hear cushingoid they probably think they are being compared with a cushion

butterfly rash not too bad as these things go

simian crease monkey analogies are to be universally avoided.

raccoon sign

phocomelia

bulimia

eqinovarus deformity

elephant-man syndrome

spider angioma

(for completness let us mention anatomic terms with animal associations: hippocampus, pes anserinus, vermiform appendix)

References to accompany ‘A Terminal Curiosity’:

Elephantiasis Nostras Verrucosa, Krisanne Sisto et al, Am J Clin Dermatol 2008; 9 (3): 141-146

Castellani A. Researches on elephantiasis nostras and elephantiasis tropica with regard to their initial stage of recurring lymphangitis (lymphangitis recurrens elephantogenica). J Trop Med Hyg 1969 Apr; 72 (89): 89-96

WHO issues best practices for naming new human infectious diseases

https://www.who.int/mediacentre/news/notes/2015/naming-new-diseases/en/

WHO best practices for naming of new human infectious diseases

https://www.who.int/topics/infectious_diseases/naming-new-diseases/en/

https://apps.who.int/iris/bitstream/handle/10665/163636/WHO_HSE_FOS_15.1_eng.pdf;jsessionid=D39A60A9106CFB22897DEBB6D98D8ADC?sequence=1

Don’t Name New Human Infectious Diseases After Animals Or Places, Says WHO: Here’s Why

https://www.techtimes.com/articles/51994/20150511/dont-name-new-human-infectious-diseases-after-animals-or-places-says-who-heres-why.htm

Animals Eponyms in Dermatology, Nidhi Jindal, Indian J Dermatol. 2014 Nov-Dec; 59(6): 631. OPEN ACCESS

Favorite Animal Names in Dermatology, Walter H. C. Burgdorf, et al, JAMA Dermatology August 2013 Volume 149, Number 8

The term “elephantiasis” is more than 2000 years old and is mentioned by Celsus in his work De Medicina (Book III: 25). The term is derived from the Greek word for elephant, “elephas.”

The menagerie of neurology, Animal signs and the refinement of clinical acumen, Shin C. Beh et al, Neurol Clin Pract. 2014;4(3):e1-e9.