12/10: Q: In reviewing the lifecycles of some of the parasites, I have come  across some minor differences between Schaecter and the CDC.  For example:1. Entamoeba histolytica- CDC notes excystation occurs in the small  intestine, but the text says excystation occurs in the stomach. 
    2. Giardia lamblia- similar disjunction between the CDC and Schaecter  information, regarding the excystation in small intestine or stomach,  respectively. 
    3. Ascaris- You mentioned in class that adult ascaris can live in the small intestine for weeks to months, Schaecter does not give a timeline, and the CDC says 1-2 years. 
    4. Cutaneous Larva migrans- the link to the CDC website for Cutaneous Larva Migrans goes to the site for Toxocara canis and T. cati and the description seems to fit more with visceral larva migrans as written in the notes.  Are these associated with a cutaneous form as well?
    I am not sure how important these differences are, or if it is relevant to the clinical approach we would take.

A: 1.,2.  The differences you noted are minor.  The main thing is that the cysts must pass through the stomach to be stimulated to excyst.  Whether they complete excystation in the stomach or small intestine is not important.   

3.  I was estimating the life span for Ascaris.  I knew it was a long time.  I'd definitely concede almost all facts on these things to CDC, so it likely is years. 

4.  The link from cutaneous larva migrans was wrong - it pointed to visceral larva migrans.  Thanks for pointing that out.  The correct link for cutaneous only goes to human hookworms and doesn't really show cutaneous larva migrans, so I'm just deleting the link.  I relabeled the link as visceral larva migrans.

12/7: In response to an appeal, I asked Dr. Antonelli about question 7 - the girl with acute otitis externa.  Although he agreed that the most correct answer was topical antibiotics, he said that cleaning alone should be given credit, so it has.  That affects about 27% of you.  I am still waiting on Dr. Islam's essay grades - sorry. 

The average on the MCQs is about 85.5%, which is not too different from previous exams.  It's the spread in the grades that is remarkable, and the challenge over the next 8 days is to help those who contributed to the lower portion of the spread increase their performance on the finals.

12/9: Q: I was trying to draw parallels between these parasites life cycles and was wondering what happens if you swallow an egg from a hookworm or strongyloides? Would you see a similar life cycle to that of ascaris which would include the egg hatching larva which would then penetrate the mucosa -> lung -> bronchial tree -> swallow then back to the small intestine as an adult form?

A: I am very (but not 100%) sure that ingesting eggs of hookworms or strongyloides will not work (from the worm’s point of view).  First, the eggs of the hookworm mature and develop in the soil.  They were not made to survive and be stimulated in the stomach like the Ascaris worms.  So I highly doubt that they would survive the gastric transit, and I doubt that the environmental conditions inside our body are appropriate for the maturation process (I would hope that our g.i. tract does not mimic the soil!).  Pretty much the same would be true for strongyloides.  Note that the strongyloides eggs usually mature into rhabditiform larvae insides the intestines before they pass out.  I suppose if you somehow ingested strongyloides eggs and they survived the stomach, they would mature to rhabditiform larvae in the gut and then pass out.  I suppose that there could be a small possibility that IF the eggs hatched to rhabditiform larvae and they matured to filariform larvae in the gut, the normal life cycle could be triggered.  BUT – let’s just assign this hole discussion to completely theoretical and focus on the real – at least for the exams!

12/8: Q:  I am confused about Trypanosoma cruzi's life cycle. In the book, it says the kissing bug releases trypomastigotes in the wound, then you rub these in and they convert to amastigotes that invade and replicate. Then it says that cells containing lots of amastigotes rupture and release trypomastigotes (pg.501). If your cells pump out trypomastigotes, then it seems like there is no need for the epimastigote stage within the kissing bug- if so, couldn't Chaga's disease be spread in areas that do not have the bug present? Also, is it the trypomastigote form that can be spread through blood transfusion and vertical transmission?

A: Check out the CDC life cycle page (http://www.dpd.cdc.gov/DPDx/HTML/TrypanosomiasisAmerican.htm).  It's great.  What you said is true, but there is one minor error in my notes and powerpoint.  The trypomastigotes infect cells and then transform into intracellular amastigotes (apparently the amistigotes are not infective).  I would not split the difference on an exam with that level of detail.  Before the cell ruptures, the amistigotes transform back to trypomastigotes, which then go on to infect other cells (or be picked up by reduviid bugs, or passed by blood transfusion).

Now, as to your other question.  The epimastigote stage is apparently an essential part of the life cycle within the reduviid bug.  So without that stage, the bugs could not transmit the disease.  Without the bugs transmitting the disease, it could not be passed from person to person.  This would be true for areas without the bugs – the disease could not be spread.  However, note that Dr. Archibald said that a high number of asymptomatic infected people are endangering the blood (and tissue?) supplies.  It is from trypomastigotes.  I do not know about vertical transmission occurring or not.  The trypomastigotes would have to be able to cross the placenta, and I don’t know if they can do that.

12/6: I noted (and I hope that you did, too) during Dr. Archibald’s lecture today he twice referred to the rhabditiform larvae of Strongyloides as being the tissue invasive form.  This is not correct.  For both exogenous infection from the soil and auto/hyper infection in the gut, it is filariform larvae that do the invading.  In the gut, it is the rare transformation that occurs from rhab-filari that causes a low grade autoinfection that keeps the patient infected for longer than the life span of an adult in the absence of reinfection from contaminated soil.  With hyperinfection, the rhabs in the gut convert to filiaris en masse causing a severe invasion through the intestines with hitch hiking bacteria (sepsis and peritonitis) and the worms going all through the body, as he graphically described in lecture.  Check out the CDC’s excellent web page on this for clarification: http://www.dpd.cdc.gov/DPDx/HTML/Strongyloidiasis.htm.

I know that Dr. Archibald went 100 mph and skipped over lots of stuff.  He and I are conferring on what is expected of you.  Don’t forget that there is the material from my lectures and self-teaching along with the BUGS cases for this final section.  He does favor having you be able to recognize some specific images associated with specific parasites, and I concur.  I can assure you that standardized exams, including the shelf next week, will have these images.  Your board review books should agree with us there.  We will be very specific in terms of which images/forms you need to recognize.

12/6: In response to an appeal, I looked into it, and the KOH test can be used for Trichomonas, so I accepted the whiff test as a correct answer for that question on the exam.  Apparently, Dr. Poff says this in his video, but he didn't include it on the handout, and I failed to take note while I was taking notes. 

For the vast majority of you who put that the KOH was inappropriate, you still get it correct (!), but do note this for the next time you are doing wet preps during a vaginal exam.

12/6: Immunology and Microbiology are on the same exam form for the Shelf exam.  However, the immunology is appended at the end as an additional 25 questions.   

We are NOT scoring the immunology for our course.  Therefore, you should not complete that portion of the exam.  Of course, you should look at it to get a good idea of what will be coming on the Step 1 exam. 

All of that being said, immunology and microbiology are obviously linked.  There are immunology questions within the microbiology section - mostly on what we have already taught you: what is the appropriate form of innate or adaptive immunity for specific or general infectious diseases, how innate and adaptive immune responses contribute to disease, how immunodeficiencies predispose to specific diseases, and how microbes evade immunity.  They seem to always slip one or two questions that in my opinion belong in the immunology section into the micro section - about T cell receptor or immunoglobulin gene rearrangements.  But it is not much, and I don't know if it's worth worrying about those. 

We have done an excellent job of preparing you for this exam and the Step 1.  Because we are normalizing the scores to fit the rest of the exams, very few of you will likely change your grades by more than a point or two.  Do look over a good board review book to get the flavor of the types of questions.  About 60% of the questions are clinical vignettes that expect you to determine the agent, and the question is a basic question about the agent (you will appreciate all of the pathogenesis that we have been teaching at that point in time!).  Of course, there is also diagnosis and treatment that I find to be about 40%.  Also, there are some things that make it into these standardized exams that we do not feel are appropriate to take up our time or your brain cells - lambda phage genetics, lac operon, reading restriction digests, experimental methods that I would ask our PhD students.  Even though we covered a HUGE number of viruses, bacteria, fungi, and parasites and assigned a significant number for self study, we did not cover all of them.  You will find some holes in the coverage in a good review book and decide if you want to try to learn those other agents on your own for this exam.  But please note this: 

I always do an analysis of the questions and your performance after the scores come in.  Of the 125 questions (I think) on the exam, we teach you directly the ability to answer about 90% of them outright.  Of the other 10%, we equip you to be able to make it a 50-50 on about 7% (no phoning a friend or polling the audience, please!), and the remaining 3% fall into what we would call the inappropriate class.  That means you should all have a 95% correct rate!

12/6:  I have input the CMC essay grades for all groups except Dr. Islam's.  So if you check your grade, the final score is there. 
     In response to a request from your class, I gave 0.5 points for "virus" for the most common cause of diarrhea.  I would advise that when there is a question that could be ambiguous, it is always better to provide the most specific answer.

12/5:  Here is the first official course correction for this last part of MMID.  It is very clear from authoritative sources that Candida albicans DOES make true hyphae (in addition to pseudohyphae) even during infection.  I must also state for the record that, although I will not ask this specific question on your exam, the terms hyphae or pseudohyphae WILL show up on exam questions (both ours and standardized) because understanding that hyphae are the invasive form of Candida expressed during infection at 37C is a very important part of diagnosis and understanding pathogenesis.  It is also important to note that this yeast-mycelial transition is different for Candida versus the other systemic fungi (Histo, Blasto, Coccidio).

12/4: Q:  During Dr Lewins lecture he mentioned that it was important for us to know what causes tinea and then he mentioned the three organisms that can be responsible for all types of tinea. Is that sufficient information or do you think it may be important to know which organisms cause which certain types of tinea, such as what causes tinea corporis?

A: If you know the three genera that collectively cause the various tineas (without specific associations), that's enough from our perspective.  I can't speak to the boards, though.  However, it's my feeling that trying to learn all of the species names with all of the various forms would take up a lot of brain space that might better be spent learning worm and protozoan life cycles!

12/4: Dear Class: 1.  I apparently misspoke in class.  The syllabus, which is the official document governing class this year, has our part of the final as 10%.  In the past it has been as low as 5%, but the 10% has been the case for several years.  I'm sure that no one was going to blow it off, but please note that the correction for the record. 

2.  Also, I see that you have "free IST" time next week at 3:00 on Tuesday and Wednesday.  I would be glad to meet to review and cover the parasitology that was not covered today (schistosomes) as well as the self study organisms, as well as anything else that is on your minds before the final exams.  I would prefer Wed. since I have a Tue. commitment at 4:00 in the Cancer/Genetics Bldg., whereas I am free for the afternoon on Wed. 

3.  It appeared that the vast majority of students in class today wanted to have our mycology/parasitology part of the exam first, followed by the Shelf exam.  We will therefore do that.  For the students who get extra time, as I said in class, this apparently will not work out, and you have to complete the Shelf exam first.  We can discuss this further if needed. 

12/4: Q: I'm confused about strongyloides.  The notes say they don't require maturation in the soil.  They also say that larvae in soil mature to filariform (infective) larvae.  So...is it the case that the rhabditiform larvea CAN be infective through direct spread, but will nonetheless mature to infective filariform larvae in soil if given the chance?

A: Let's compare Strongyloides to hookworms.  Hookworm eggs are passed into the soil where they hatch filariform larvae that are infective through the skin.  Hookworms therefore have to remain in the soil long enough under the right conditions for the hatching and maturation to occur.

 Strongyloides eggs hatch in the intestinal wall/lumen releasing non-infectious rhabditiform larvae.  Until they turn into filariform larvae, they cannot cross tissue, so they cannot cause auto/hyperinfection.  In the soil the rhabditiform larvae can either morph into infectious filariform larvae or adults.  The filariform larvae are ready to go.  The adults can lead an independent life in the soil, creating rhabditiform larvae and ultimately filariform larvae.  Why they don't call the rhabditiform-filariform transition "maturation", I don't know.  Actually, I just re-looked at the book, and it is way oversimplified.  Take a look at this page from the CDC, which very clearly shows and describes the life cycle, in agreement with what I wrote (if you can't simply click on the link you likely will need to cut and paste the link in to pieces).

http://www.dpd.cdc.gov/dpdx/HTML/Strongyloidiasis.asp?body=Frames/S-Z/Strongyloidiasis/body_Strongyloidiasis_page1.htm

 Again, the book oversimplifies and does not address the necessary rhabd-filariform transition.

12/3: Q: In the handout version of Dr. Wingard's slides, the last slide on page 7 ("clinical clues to fungal infections" doesn't have chart headings (make the info somewhat useless!).  It's not in his powerpoint handout. Should we assume that we're not responsible for the information in that slide?

A: I see what you're talking about.  He didn't discuss it in lecture, and you don't have access to the original PowerPoint, so you can X through that slide.