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TWiP 33 Letters

Howie writes:


Great podcast!!!

A while ago, Dick made a comment along the lines that Sir Ronald Ross was a dim bulb. Ross did much more than "just" discover that bird malaria is transmitted by mosquitos. He was a closet mathematicians and published about 20 papers and books on pure mathematics (see http://people.math.gatech.edu/~weiss/Site/Ross_math_files/Ross%20List%20of%20Mathematical%20works.pdf).

He was also a superb infectious disease transmission modeler.

Germ theory was developed in the 1850s. Before then, people believed that diseases such as cholera were caused by a miasma, a noxious form of bad air. About 60 years latter, Ronald Ross, a public health physician, developed two ODE (ordinary differential equation) transmission models for malaria [Ross, 1910] that made the following predictions:

Germ theory was developed in the 1850s. Before then, people believed that diseases such as cholera were caused by a miasma, a noxious form of bad air. About 60 years latter, Ronald Ross, a public health physician, developed two ODE (ordinary differential equation) transmission models for malaria [Ross, 1910] that made the following predictions:

1: One does not need to kill all the mosquitos in an area to prevent malaria epidemics. There is a threshold value of vector capacity,  below which the disease quickly dies out in humans. This conclusion was at first rejected by the experts, but proved correct by field trials in Malaysia where malaria transmission essentially ceased after draining the mosquito larval habitats.

2: Malaria can not be eradicated by treating humans alone. Even if the number of infected humans is reduced by 99%, if the mosquito population remains unchanged, then the disease prevalence will rebound to its former value.

3: The endemic level of infections is lower for longer lasting infections, e.g., it is lower for P. vivax than for P. faciparum infections.

Of course, mathematical models can not prove anything, but they generated novel hypotheses which were found to be correct and saved countless lives.

Ross was also the first to present a mechanistic model of the transmission of a generic infectious disease.

Not bad for a dim bulb!

Please, never stop TWIVing.


Professor of Mathematics

Georgia Institute of Technology

Spencer writes:

Dear TWIP,

I really enjoyed your analysis of the Malaria Vaccine article from the New England Journal of Medicine.    You guys had an interesting discussion about the different phases of clinical trials and I thought it was incumbent upon me to clarify these phases.  As a clinical investigator, I oversee several Phase 1 clinical trials.  A Phase 1 trial is a dose escalation trial:  It is simply carried out to assess safety at various potential clinical doses of a compound.  Obviously, before a compound makes it to such a trial, there has been some demonstration of effectiveness in animal models, or some reasonable suspicion that the compound will be a useful treatment for the disease.  Phase 1 studies are small - typically 20-80 people and it is in this phase that side effects can first be seen.  A Phase 2 trial targets the maximum tolerated safe dose in a specific population that either has the disease or is at risk for the disease.    There are usually 100-300 people in a Phase 2 tri al.  In addition to looking at continued safety at the studied dose, the compound in question is studied for its effectiveness in treating the condition or disease in this phase.  In Phase 3, the compound is compared to standard of care treatment, often in a head-to-head blinded fashion.  In some cases, there is no defined standard of care treatment.  Alternatively, in some cases, such as you discussed about HIV, it would be unethical to withhold conventional treatment while evaluating the new compound.  This makes Phase 3 trials very difficult to complete.  Also, Phase 3 trials usually require thousands of participants and take a long time.  Phase 4 trials are post-marketing trials.  The compound has already been approved for sale and prescription by the Food and Drug Administration.  Many of the side effects and sometimes disasters associated with some medications are not apparent until the drug is taken by 10s of thousands of people after it is already released.  I hope this is helpful to listeners and I just want to remind you guys that there are still some interesting parasitic lifecycles and histories to discuss for which we are still waiting.  Keep up the great work.

Jim writes:

I was jolted to hear the casual mention in TWIP 28 by Dr Gwadz of chiggers and scrub typhus.  I thought chiggers were one of the local pests I could ignore other than itching during routine encounters with them each summer.  This summer at the worst point I had over 50 on two legs despite deet all over my shoes, socks and lower pant legs.  One or perhaps two adjacent bites produced a large blister in contrast with the usual small, red, itchy nodules.  No other symptoms, but now I'll be alert associated symptoms.  During scrub typhus research with Google I saw instructions for soldiers about tucking trousers into the tops of their boots as a protective measure.  I assume this is the reason for "blousing boots" done by the Army, but don't recall ever hearing that was the reason.

Another great TWIP, by the way.  A small group discussion seems to produce the most interesting results.

Thanks again.


Smithfield, VA

Michael writes:

I love TWiP!

I am starting my parasitology class (for a Medical Lab program) this fall. I am also excited to be able to learn and understand many more of the details now that I have the basics down because of TWiP.

I also have enjoyed being able to use all of the TWi_ podcasts to form questions for my friend in Physician Assistant school who then often asks her classmates the same questions (I bring up topics you say are not often taught in medical schools and the unusual cases, and put them into a type of case study, adding the most vague hints as she and they get stumped). Due to your podcasts I will be able to better grasp everything I learn and be able to help impart critical thinking skills to other health care professionals.

Also, Do I remember hearing that a 6th ed may be coming out of the Parasitic Diseases book? I would love to add that to my studies! If so, any idea when? Did you say it may be avaliable on ibooks? I also encourage you to consider Kindle, for it is easier to read the text on a Kindle, and anyone with a computer, ipad, iphone, android, ect. Can get the free Kindle app and read it and view any color pictures.

I would still like a higher frequency, but so long as you just don't stop, I will be happy with whatever you can do!

Anything associated with Infectious Diseases and how humans interact with and are affected by them is my passion!

Thank you for giving me chopped and dried wood to put onto the fire!


Jim writes: (incomparable TWiP 30)

Just incomparable!  Pure knowledge; so much expertise in one place; another podcast in my Best Podcasts folder.  All the TWIV, TWIP and TWIM podcasts are great, but they are readily accessed, too, so far, and I'm capturing a collection of less easily retrieved audio files for times when I can pass on the collection to interested folks which has already occurred twice.  A couple TWIP's are there to capture attention and alert listeners to where similar files are available.  I'm sure your backup plan is excellent, Vince, but I'll happily store copies of everything, if you need another remote site.


Smithfield, VA

Alan writes:

What creature/parasite/worm can I catch from eating a cockroach snack late at night?

I can't decide which entertainment personality I like more, Vince or Des Pom. Its not just the subject its you guys that I listen to.

Have fun,


P.S. I am with Dixon on the orchids.

Scott writes:

Hi guys!

This article popped up on a facebook feed I subscribe to; probably you already are familiar with the material, but just in case I thought I would pass it along. I have an interest, but no expertise, in tropical medicine, and would like to hear your opinions.


Ricardo writes:


Alex writes:

Hello Doctor Racaniello and Despommier,

Curious if you might have some incites on a particular malaria life cycle. I've been reading on Plasmodium vivax.  We know that Plasmodium vivax can relapse via the hidden agents stored in the liver, termed 'hypnozoites'. But time and time again through multiple sources it's stated that vivax malaria relapses much more quickly in patients in tropical regions over non-tropical regions, on the magnitude of several months.  For the life of me I cannot explain this, the parasite would seemingly detect the same body temperature and conditions within the host regardless of where they are living. I have two theories here; Perhaps the hosts are indeed different, with varied levels of nutrition and other factors causing the hypnozoites to convert earlier in tropical cases and later in better nourished non-tropical cases. Or, on the other hand, the cases of "relapses" could be muddled by actual cases of re-infection. Since you are more likely to get an infection in a tropical region the relapse rates seem lower in non-tropical regions. Any thoughts?

In TWIP#31, Doctor Despommier mentioned that a man by the name of 'Macgregor' conducted a statistical analysis to determine the number of cases needed to maintain malaria infection within the population?  I was unable to find this paper, and curious if you might be able to link in within the show-notes next time.  I'm extremely interested to see these figures. It seems to me that we might be on the cusp of a medical paradigm, with a vaccine that's 50% effective it may be the extra push with the combination of mechanical preventative strategies (bed nets, ect.) needed to eradicate the disease.  Is there such a thing as 'vector-based herd immunity'?  Conventionally, 85% of individuals within a population must be immune to maintain herd immunity within the entire population.  I know this is complicated by the fact that it must be essentially eradicated within two populations (humans and mosquitoes), and therefore likely to result in a much higher threshold of immunity.

Keep up the great work!

Todd writes:

I'm reading this article and take a small issue with item #5 :


The first part of this paragraph makes perfect sense:

If it's parasites or other risks associated with sushi that worry you more than mercury, Andy Bellatti suggests you put your mind at ease. "Fish served in sushi restaurants has been previously flash frozen, which kills parasites as effectively as cooking," he explains.

Particularly confusing to me though, and if memory serves, contrary to a comment that Dick made about farmed fish (though I think it was in reference to a sheep borne parasite (liver fluke maybe?)) is the second part of the paragraph:

[Andy] also points to Steven Shaw's book Asian Dining Rules: Essential Eating Strategies for Eating Out at Japanese, Chinese, Southeast Asian, Korean, and Indian Restaurants, which explains that most fish used for sushi in restaurants around the world are farmed to avoid the problems with parasites in wild fish. "Fish like tuna are not particularly susceptible to parasites because they dwell in very deep and cold waters. Sushi restaurants typically use farmed salmon to avoid the parasite problems wild salmon have," he explains. The fish that are at times likely to have parasites, like cod or other whitefish, aren't used for sushi anyway and are generally served fully cooked.

I suspect it is more about which parasite they're referring to than the absolute of "all parasites."  Can you clear up my confusion?

Keep up the great work guys!  TWIP and TWIV are both part of my commute routine.  It makes me wish my drive was longer...well...maybe not...but your penchant for educating the masses is earning you karma points daily!


P.S. Ronald Jenkees *ROCKS*!  You should hear his unreleased music, which he has linked from his website.

Luca writes:

Dear Vincent and Dick,

Once again I write to you after listening to TWIP episode 32, where Vincent went off on a tangent to discover the meaning of acta in the various scientific journals.

Here I am to shine some light upon it. As an Italian, I learned that word in primary school, when we were taught that every day, in Ancient Rome, all that had been discussed and decided in the Senate would be put up on a poster in the Forum, the public square, so that the people could know about it. This was called Acta Diurna (loosely, record of the day) - of course there's a wikipedia page for it: Here it is! http://en.wikipedia.org/wiki/Acta_Diurna. It goes into much more detail than I ever would be able to. I probably got it wrong in some details, too. Primary school was long time ago.

Once again thanks for your constant, excellent work in education and public outreach, I have now expanded my weekly podcast schedule to include TwiM, but I have to admit that TWiP is still my favourite.

All the best


PS: here's an added bonus - I knew the meaning of Despommiers, but was curious about Racaniello, so looked it up online - there's no meaning as far as I can tell, although to me it sounds like some kind of edible root in Italian. However, I found the Racaniello coat of arm, in the corresponding wikipedia page - http://en.wikipedia.org/wiki/Racaniello - did you know about it? And you have a (rather mean) family motto, too: Dominus exquisitus artis saeviter quis revocas malum memet (I possess a refined art, that to hurt cruelly whoever does me evil). Cheery-o!


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