On Episode 13 we’re knee-deep in micro and infectious disease, talking about gonorrhea, skin infections, herpes, zoonoses, and a variety of other tidbits.
Apologies to Haldane and Fisher
To start the episode off, I wanted to make a quick apology for an inaccuracy in episode 005 — I incorrectly mentioned in that episode that JBS Haldane was the originator of p=0.05, when it fact it was one of the other founders of population genetics (Ronald Fisher). See the show notes for EP005 for more details on this. To make amends, I wanted to actually mention a few of the things Haldane is noted for, because the guy had a wild, wild life.
Resource
Sanford Guide to Antimicrobial Therapy → Here’s a link to a short youtube video showing how to use the guide. As you might expect, PDF copies are available in the usual places, or you can get a print copy that fits in a whitecoat pocket.
Curing HIV
The second-ever case of cured HIV has now been reported, which is an important step toward a permanent cure. We deferred a detailed discussion of this to a later episode since we have an HIV episode coming up in just a week or two.
Cellulitis, impetigo, eryspelas, oh my!
We talked for a little while about skin infections, particularly cellulitis. This is a common primary care and ED complaint, and one that doesn’t get much focus on medical school. It might be an observation bias on my part, but it seems like despite its commonality, its also often misdiagnosed by clinicians, and (if so) that might point to the importance of trying to seed some diagnostic pearls. If the ‘cellulitis’ is bilateral, consider stasis dermatitis, as true bilateral cellulitis is quite rare. If it can be ‘cured’ by elevating the affected limb above the heart for several minutes, again, consider that it probably isn’t cellulitis. If the borders are well demarcated, consider erysipelas. Tx: cephalexin, 1 gram po qid. Also we mentioned necrotizing fasciitis, periorbital cellulitis, etc. Preseptal cellulitis tenderness, swelling, warmth, discoloration of the eyelid. Visual acuity not affected and ocular movement is intact. Orbital cellulitis is a medical emergency and can be delineated by complaints of pain upon eye movement, ophthalmoplegia, proptosis, and visual symptoms. Ischemic retinopathy and optic neuropathy. Lastly, we chatted about an article on “the Closed Eyes Sign” that hasn’t stood the test of time very well (with regard to its characterization of patients and their “non-organic” pain), but does make an interesting point about taking in a number of observations when doing a physical exam.
Encephalitis lethargica
[excerpt from: A Short History of Nearly Everything, by Bill Bryson]
“In 1916 people in Europe and America began to come down with a strange sleeping sickness, which became known as encephalitis lethargica. Victims would go to sleep and not wake up. They could be roused without great difficulty to take food or go to the lavatory, and would answer questions sensibly—they knew who and where they were—though their manner was always apathetic.
However, the moment they were permitted to rest, they would sink at once back into deepest slumber and remain in that state for as long as they were left. Some went on in this manner for months before dying. A very few survived and regained consciousness but not their former liveliness. They existed in a state of profound apathy, “like extinct volcanoes,” in the words of one doctor. In ten years the disease killed some five million people and then quietly went away. It didn’t get much lasting attention because in the meantime an even worse epidemic—indeed, the worst in history—swept across the world.”
[excerpt from: Awakenings, by Oliver Sacks]
“They would be conscious and aware – yet not fully awake; they would sit motionless and speechless all day in their chairs, totally lacking energy, impetus, initiative, motive, appetite, affect or desire; they registered what went on about them without active attention, and with profound indifference. They neither conveyed nor felt the feeling of life; they were as insubstantial as ghosts, and as passive as zombies.”
Two papers we briefly mentioned or alluded to:
- Dourmashkin, et al. “Evidence for an enterovirus as the cause of encephalitis lethargica.” BMC Infect Dis. 2012.
- Reid, et al. 2001. “Experimenting on the Past: The Enigma of von Economo’s Encephalitis Lethargica.”
EBM
For EBM this week we discussed the landmark 2003 BMJ review paper, “Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials.”
GONORRHEA AND… STUFF
“Azithromycin susceptibility in Neisseria gonorrhoeae and seasonal macrolide use.” J Infect Dis. 2019.
“We speculate that the seasonal pattern in MICs arises because N. gonorrhoeae hosts are more likely to use macrolides for respiratory complaints in winter than in summer, subjecting N. gonorrhoeae to a seasonal “bystander effect” in which the bacteria experience additional antibiotic pressure in the winter for reasons unrelated to gonorrhea. To link the individual-level and population-level effects, we used a back-of-the-envelope calculation. Our observed 12.8 macrolide claims per 1,000 people per month means that less than 2% of people claimed a macrolide in a given month. A 10% increase in macrolide use then roughly corresponds to an extra 0.2% of people claiming a macrolide. If, as per the estimate from the Dutch individual-level study,3 azithromycin MICs double among N. gonorrhoeae carriers in the last month, then the mean N. gonorrhoeae MIC will increase by 0.2%. On a baseline of 0.2 μg/ml, a 0.2% increase corresponds to 0.0004 μg/ml, which is smaller than but comparable to our result of 0.0015 μg/ml. While acknowledging that ecological designs do not enable individual-level inference, our results suggest that the small, observed seasonal variation in azithromycin MICs is compatible with large, individual-level variations in MICs.”
Alex’s CNN article on drug-resistant gonorrhea: https://www.cnn.com/2018/03/28/health/uk-man-multidrug-resistant-gonorrhea-intl/index.html … it turns out that this has been brewing for a while. There were 70 cases in england over 3 years. On further research I found a strain susceptible to only ertapenem first written up in 2012.
We didn’t get a chance to talk about this article, but it’s worth glancing at the quote below (with emphasis added by me) → “Adherence to CDC Recommendations for the Treatment of Uncomplicated Gonorrhea.” MMWR. 2016.
CDC reviewed enhanced data collected on a random sample of reported cases of gonorrhea in seven jurisdictions participating in the STD Surveillance Network and estimated the proportion of patients who received the CDC-recommended regimen for uncomplicated gonorrhea, by patient characteristics and diagnosing facility type. In 2016, the majority of reported patients with gonorrhea (81%) received the recommended regimen. There were no differences in the proportion of patients receiving the recommended regimen by age or race/ethnicity; however, patients diagnosed with gonorrhea in STD (91%) or family planning/reproductive health (94%) clinics were more likely to receive this regimen than were patients diagnosed in other provider settings (80%).
⮑ 20% of clinics screw up the GC Rx!
Pearl
Shingrix vaccination is way better than the one that came before it. To that extent that many people are advised to get revaccinated. A few notes on other things we mentioned (or meant to mention)…
- Ramsay-Hunt
- Statin use and shingles ( https://www.ncbi.nlm.nih.gov/pubmed/27292233 )
- Severe shingles or multidermatomal → suspicious for HIV
- Postherpetic neuralgia is terrible. Prevent with recomb vaccine. Tx shingles with acyclovir.
Malaria for treating neurosyphilis?!
“A much clearer understanding of relapse in P. vivax malaria was to come from Julius Wagner-Jauregg’s discovery that malaria could cure neurosyphilis. Between the 1920s and the 1950s thousands of patients confined in mental hospitals with neurosyphilis were treated with malaria (malaria therapy). General paralysis of the insane was then a uniformly lethal condition, and at least half the malaria therapy treated patents were improved and over one fifth were cured.” SOURCE: White, NJ. “Determinants of relapse periodicity in Plasmodium vivax malaria.” Malaria Journal. 2011.
“…in 1917, the Austrian neuro-psychiatrist Julius Wagner-Jauregg pointed out the therapeutic value of malaria inoculation in the treatment of dementia paralytica. In 1927, Wagner Jauregg received for this work the Nobel Prize in Medicine, being actually the first psychiatrist to win the Nobel Prize … Wagner Jauregg’s therapy was highly admired and was used on neurosyphilis cases well onto the 1950’s. However, with the introduction of penicillin in syphilis’ treatment, fever therapy effectively ended. Wagner-Jauregg’s study led to all the methods of stress therapy used in psychiatry, as electric shock, and insulin.” SOURCE: https://www.ncbi.nlm.nih.gov/pubmed/24185088
Alex’s ethical neurosyphilis paper → “Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953.”
Kim’s FEMA racism article → NPR Investigations: “Search The Thousands Of Disaster Buyouts FEMA Didn’t Want You To See”
“Up to the time of writing, a sufficient period has elapsed to enable a judgment to be formed regarding the effect of the malaria treatment in respect of eighty-four patients suffering from general paralysis. Having ourselves no special knowledge of this disease, we have, in presenting these results (apart from those of the few cases treated by us in a general hospital), relied entirely on the judgment of the medical officers in charge of the patients at the various mental hospitals. Summarising the opinion of these experts, we find that, of the eighty-four patients treated, fourteen (16.6%) have died, most of them immediately, or “shortly after the completion of the course of malaria treatment; although all these cases had been treated with quinine before death and parasites had disappeared from the blood, nevertheless it is impossible to affirm that in none of them was death accelerated by the malaria. No noticeable change in mental or physical condition has been observed in twenty (23.8%) ; with regard to these cases, however, it is to be borne in mind, as the mental hospital doctors have frequently pointed out, that in the ordinary course of events, many of them would now be dead. In ten (11.9%) there is definite physical improvement, but no change in the mental condition. In seventeen (20.2%) there is great physical and distinct mental improvement. Finally, in twentythree (27.4%), the mental and physical improvement has been so great that the patients have been, or are about to be, discharged from the mental hospitals. It is to be noted that in a number of the cases the improvement has been maintained for many months—in some for as long as a year—and that quite a number are back at their old occupations. As time goes on, it may be found possible to discharge still others of these eighty-four eases for, as Wagner-Jauregg writes: “The maximum of the improvement does not manifest itself at once at the end of the period of fever but does later. On the contrary the improvement continues often for a long period so that in many cases the result seemed to be an incomplete one where later, however, a complete remission came to pass.” Whether the improvement is temporary or permanent time alone can decide, but the results already achieved can only be regarded as remarkable, when it is realised that no patient suffering from general paralysis had previously been discharged from the mental hospitals in question.” [SOURCE: Yorke W, & Macfie JWS. (1924). “Observations on malaria made during treatment of general paralysis.” Transactions of the Royal Society of Tropical Medicine and Hygiene, 18(1-2), 13–33. doi:10.1016/s0035-9203(24)90664-x]
| (Addie’s transcription of the data from the paragraph above) | ||
| n=( ) | (%) | Outcome |
| 14 | 16.6 | Death |
| 20 | 23.8 | No change |
| 10 | 11.9 | Definite physical improvement, no mental improvement |
| 17 | 20.2 | Great physical improvement, definite mental improvement |
| 23 | 27.4 | Mental + physical improvement so great they are discharged (unprecedented outcome) |
Vocab
Aphthous (as in, “Aphthous ulcers”)
Zoonoses
Zoonoses Word Association + The Black Death → Yersinia pestis
“The symptoms were not the same as in the East, where a gush of blood from the nose was the plain sign of inevitable death; but it began both in men and women with certain swellings in the groin or under the armpit. They grew to the size of a small apple or an egg, more or less, and were vulgarly called tumours. In a short space of time these tumours spread from the two parts named all over the body. Soon after this the symptoms changed and black or purple spots appeared on the arms or thighs or any other part of the body, sometimes a few large ones, sometimes many little ones. These spots were a certain sign of death, just as the original tumour had been and still remained.” (SOURCE)
- Rabbits → Francisella tularensis “Francis the rabbit”
- Cows, goats, pigs → Brucella “Bruce the cow”
- Cat scratch → Bartonella
- Sporothrix → not a zoonosis exactly, but I have had a number of preceptors who mention this zebra
— Episode credits —
Hosted by Addie, Kim, and Alex. Audio production and editing by Addie. Show notes written by Addie. Theme music (Too Cool, and Laserpack) by Kevin MacLeod of incompetech.com, licensed under Creative Commons: By Attribution 3.0 License.