What’s the deal with inverted typhoid?

Maybe it’s just lack of familiarity with other disciplines’ historical documents, but I feel like old medical and biological articles are particularly thick with phrases that are totally opaque now, but were self-evident to the people of the time. Phrases like “inverted typhoid” represent a type of jargon that is specific not just to a certain profession, but to a certain profession at a certain time in history.

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First of all, what’s “typhoid”? Typhoid fever is a disease characterized by fever. There are other symptoms, like distended abdomen, diarrhea, elevated heart rate, “rose spots” on the abdomen, bacilli in the blood, and borborygmus. And positive results from molecular tests that range from the century-old Widal test for agglutinating antibody, to blood levels of liver enzymes. But the fever itself is a major part of the diagnosis.

This free chapter from 1990’s Clinical Methods (published by Butterworth, Boston) gives an overview of the different fevers caused by different diseases. Fever is typically lowest in the morning and highest in the evening, in a healthy person. Many sources say the typical range is between 0.5 and 1 degree Celsius, though this chapter says it can be as high as 1.5°C. Diagnoses based on various fevers can include:

Although not diagnostic, at times fever curves can be suggestive. Hectic fevers, because of wide swings in temperature, are often associated with chills and sweats. This pattern is thought to be very suggestive of an abscess or pyogenic infection such as pyelonephritis and ascending cholangitis, but may also be seen with tuberculosis, hypernephromas, lymphomas, and drug reactions.

…

Relapsing fevers may be seen in rat-bite fever, malaria, cholangitis, infections with Borrelia recurrentis, Hodgkin’s disease (Pel-Ebstein fever), and other neoplasms.

Historically, some diseases are described as having characteristic fever patterns. The double quotidian fever of gonococcal endocarditis has two spikes in a 24-hour period. Fever at 48-hour intervals suggests Plasmodium vivax or P. ovale; 72-hour intervals suggest P. malariae, while P. falciparum often has an unsynchronized intermittent fever.

So, you’ve got relapsing fever, hectic fever, double quotidian fever, and so on. What’s the pattern of typhoid fever? In his 1901 book Typhoid Fever and Typhus Fever, Heinrich Curschmann of the University of Leipzig gives some examples.

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Here’s someone who came down with typhoid when he was recovering from “polyarthritis”, which is why they were already measuring his temperature. In all these graphs, the body temperature was measured once in the morning and once in the evening. Note that this guy starts out with small fluctuations between morning (low) and evening (high), and the difference between morning and evening gets exaggerated when the fever begins.

Here’s the plateau stage of the fever, following the familiar “Wunderlich curve”. The difference between morning and evening continues to grow, even as the temperature itself levels off and gradually decreases.

Here’s a guy who was thought to be faking illness but was brought to the hospital anyway. The point of this graph is that in his first week in the hospital he was not showing a particularly high temperature, but the large daily fluctuations should have been a warning sign that he might have typhoid.

The “typhoid” pattern is a large fluctuation between morning temperature (low) and evening temperature (high). The period of low temperature can also be thought of as the “pre-dawn” or “night”, as the nadir is usually around 4 AM. Terms vary.

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Looking at it from that perspective, it makes sense that there would be something called “inverted typhoid”. This term means a pattern in which the fever is highest in the morning, and reaches a low point in the evening.

Here’s some examples.

From John McCaw’s 1914 Diseases of Children:

During the Second Week: The spleen is enlarged and tender, the abdomen is uniformly swollen, and gurgling in the right iliac fossa is present. The bowels may be relaxed, but quite as often they are constipated. Headache subsides, and delirium at night takes its place. The expression is dull, the decubitus dorsal, the cheeks are flushed, and the child is indifferent to its surroundings, but not in any apparent suffering. Thirst is considerable, and the skin is dry. The temperature varies from 101.5°F to 105°F, rising towards evening and falling again in the early morning, but throughout the attack the highest temperature may be recorded in the morning (inverted typhoid).

From the 1913 Journal of the Indiana State Medical Association:

Dr. Bruggeman: Had patient with a deep phlegmon of the palmar fascia which was incised and drained. Perfect recovery from hand. Two weeks later dull pain in right hypochondrium. Urine normal. Blood showed slight leukocytosis. Examination negative. Lowest temperature from 101 to 103; no chill. Temperature is of the inverted typhoid type. Widal negative. Leukocytosis diminished.

From the 1884 Dublin Journal of Medical Science (describing a fever that isn’t necessarily infectious at all):

Temperature in Insanity.— Extended contributions to this subject have recently been made by Bechterew (Archiv für Psychiatrie, Bd. XIII.) and Hebold. Bechterew has taken the temperature of the rectum with all the precautions suggested by Liebermeister. He finds that in the first stage of melancholia the temperature usually remains normal, or may even rise above it. It has been observed as high as 104°F. By melancholia Bechterew evidently means all cases with delusions of persecution and depression. …In the convalescent period the temperature is usually normal. Sometimes the temperature is extremely variable at the outset of this period, and this usually denotes a sudden improvement in the patient’s condition. In the excited or stuporose period an inverted typhoid fever curve is often noticeable.

In 1867’s Notes on Asiatic Cholera, John Charles Peters viewed “inverted cholera” yet another way.

Some physicians believe that cholera is in some strange way mixed up with intermittent and remittent fevers in India in the East; and with typhoid fever in Europe and the West. Others have even gone so far as to describe cholera as an inverted typhoid fever; it commences with profuse discharges, and the latter is apt to end with them; the one has collapse before the fever, and the other afterwards, &c.; the causes of both are said to be similar with the difference of climate only.

Coincidentally, the first convenient clinical thermometer was manufactured in 1867! So Dr. Peters was writing this in a world before typhoid was known to have an easily-measured daily fever cycle. Even then, it was a disease with a standard pattern of symptoms to which other diseases could be compared and contrasted.

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Okay. “Inverted typhoid” is a symptom, that is not necessarily indicative of typhoid, or even of infection. It means high fever in the morning, and not so high in the evening.

But when you look into “inverted typhoid”, the most significant article on the subject is a piece in the 1898 Medical Record, by Max Goltman of the Shelby County Poor and Insane Asylum, Memphis, Tennessee. For more about the Glasgow-born Dr. Goltman, see the Jewish Historical Society of Memphis and the Mid-South.

Dr. Goltman’s definition of “inverted typhoid” is different.

On September 25, 1897, I was called to see Arthur Z—–, thirteen years of age, white. He was born and brought up in Memphis, and was bright, exceedingly energetic, and of a very nervous temperament. …

He had been indisposed, more or less, for about two weeks prior to my first visit, complaining of throbbing headaches, which were worse in the afternoon and after exercise; and there were loss of appetite, lassitude, drowsiness, disturbed sleep, constipation, and feverishness. Being an ardent cyclist, he made frequent trips far into the country in the hot sun. He recollected having partaken, on several such occasions, of both milk and water at a roadhouse where there had been sickness in the family for some time.

I diagnosed malaria, and prescribed a saline purge and quinine in three-grain capsules every four hours, an ice cap to the head, and a cool bath. About six hours later I received word that the patient was resting nicely and was nearly, but not quite, free from fever. On September 26th he had another chill, which was of a much milder character than that of the preceding day. The quinine was continued until twenty-four grains were taken. This kept the patient comfortable, but with a temperature ranging from 99° to 101°F until September 29th, when he had another violent chill, followed in a short time by fever of 104.8°F. On being informed of this, I made an examination of the blood for malaria.

What seemed like a typical case of malaria is not following the normal pattern, so he looks to see if it really is malaria. The parasites are clearly there in the blood cells. But the symptoms keep changing. I’m no doctor, let alone a 19th-century doctor, so I don’t know why he suspected that malaria was “not accounting for the symptoms present”. Maybe the patient was no longer having chills. Anyway, three days after seeing malaria under the microscope, he looked for other pathogens, and the Widal reaction showed clear signs of typhoid.

But the fever didn’t follow the typhoid pattern any more than it followed the malaria pattern. Here’s Goltman’s temperature chart of “inverted typhoid”.

As you can see, Arthur Z—- starts out with a fever. But the “Rose Spots” noted on Day 6, normally found in the plateau stage of typhoid fever, are here accompanied by a decrease in fever, quickly reaching sub-normal temperature. At this point Arthur had probably been switched from quinine to heavy doses of cathartics, with the goal of maximizing bowel movements to get rid of the bacteria.

I [have] discussed the eliminative treatment of typhoid fever very extensively, and urged the adoption of the saline cathartics for the purpose of elimination in preference to anything else. I have no reason to change the opinion then expressed. They are undoubtedly best and safest. The patient may get tired of salts; then, for a day or two, calomel may be substituted in broken doses until the bowels move. A good mixture to employ is a drachm each of Epsom salts, Rochelle salts, and compound licorice syrup, repeated if necessary. Four or five movements a day are desirable. This is my main treatment; everything else is subservient to it.

And indeed, as the patient “got tired of salts”, he replaced the cathartic salts with one dose of strychnine, followed by calomel. This coincides exactly with the body temperature returning to normal. Whether the treatment helped or hurt, who knows. The point is that we have, as Dr. Goltman says in his somewhat flowery conclusion, “an Æsculapian paradox — a fever without fever”. In other words, a case of inverted typhoid.

One more quote.

Gentlemen, we have here for analysis a case of atypical typhoid fever ushered in by the clear-cut paroxysms of a malarial infection, which was demonstrated beyond the shadow of a doubt by microscopic examination of the stained and fresh blood of the patient. More typical organisms I have never seen … Having made such a diagnosis in this case, it was somewhat humiliating to be compelled apparently to recede from my position, and inform the anxious family that they had now to nurse a case of typhoid fever. Dr. Pheemster has, however, told me of a similar instance occurring at St. Joseph’s Hospital, and the literature of the subject teems with similar cases, which, unlike my own, however, are somewhat lacking in scientific data and therefore of doubtful value.

First of all, I highly doubt there was ever a person named “Dr. Pheemster”. That sounds like a Robert Benchley character. Second of all, is it necessary to claim that yours is the only reliable case report ever published? It’s not like you have lots of data either. Just one temperature chart.

Finally, another frequently re-printed study, originally in JAMA, mentioned “inverted typhoid” in passing. This was by Dr. George Boody, recounting a typhoid outbreak at the Iowa State Hospital for the Insane (now the Independence Mental Health Institute). Dr. Boody includes a multi-week fever curve similar to that of Dr. Goltman, indicating that to him the term refers to a case of typhoid that progresses from fever to sub-normal temperature. He doesn’t mention malaria or any other comorbidities, saying simply that “[c]ases of typhoid fever are comparatively quite rare, and the subject is deserving of thorough investigation as often and wherever an epidemic occurs… In these two epidemics it occurred but once in forty-three cases.”

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So, we have “inverted typhoid” meaning a case of typhoid where the fever goes down rather than up, because of malaria. Or it means a case where the fever is high in the morning rather than the evening. Or it means a case that does not involve actual typhoid, just a typhoid-esque fever pattern.

Good thing nobody uses the term anymore! Instead, we use the term “typhus inversus”, which meant the same thing as “inverted typhoid” back in Dr. Goltman’s day. Now “inverted typhoid” has died out, but “typhus inversus” remains.

From Khan Abdul Kalam Azad (2011), Changing trends in pattern of presentation with different types of pyrexia and approach to be made. J Dhaka Med Coll 20(1):1-3 (available here):

A diurnal pattern also known as typhus inversus, is the reverse of normal circadian pattern in which the highest temperature is in the morning. It can be found in miliary TB, hepatic abscesses and endocarditis.

The same definition is in ML Kulkarni (2008), Clinical Methods in Paediatrics: Physical Examination of Children (Jaypee Brothers Medical Publishers, New Delhi), page 61 (partially available here), and in the fourth edition of Moffet’s Pediatric Infectious Diseases: A Problem-oriented Approach (2005) by Fisher, Boyce and Moffet (partially available here).

Calling it “typhus inversus” is less confusing than implying that the person suffering from TB or salmonellosis also has some odd form of typhoid.

But it’s still confusing.

What’s a “full-sized drop” in nanoliters?

A lot has been made nowadays about reproducibility, and how for some reason the most interesting scientific results are often the least reproducible. Evidently when there’s huge pressure to generate a certain graph containing certain data, either to give yourself a chance at fame and fortune or to give yourself a chance to have your lab and scientific career continue to exist, sometimes the graph does not represent the sort of objective reality that exists throughout space and time. This can be because of wishful thinking, because of selective use of the data that seems most solid, because of variables we never considered which later turn out to be crucial, who knows what else.

There have always been experiments where different labs get different results. Often we say that “in our hands,” we get Result X, but another laboratory gets Result Y, and we can say this without accusing anyone of malfeasance. It’s acceptable to get different results.

But nowadays, a scientist has no excuse when his contemporaries can’t even figure out how to replicate an experiment. A hundred years ago, it was more tricky. Even if you wrote and asked for a detailed protocol, it would probably involve terms that had no exact meaning. The topic under discussion today is the word “drop”.

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In the December 1910 issue of the JAMA organ Archives of Internal Medicine, Drs. C. C. Bass and John A. Watkins wrote up (1) a new quick-and-easy test for typhoid that they had developed in the laboratories of Tulane University. The abstract is here, with subscription required to read the article. But this volume is old enough that it’s out of copyright and should be in Google Books. Though to be honest I can’t find it there and only found it at archive.org.

Over the ensuing years many doctors’ offices used it with more or less success, but as you might expect, many found they were unable to get results and went back to their old routine of sending samples to a clinical lab and waiting a day or two.Even though Bass and Watkins went to the trouble of including highly mundane photographs of things like proper slide-rocking procedure, people couldn’t figure out what exactly they were supposed to do. The text still contains phrases like “two to three drops of an equal number of bacilli units and agglutinin units sufficiently dilute to prevent rapid agglutination”. And “this one-quarter drop of blood is about the quantity we use in making blood slides in examinations for malaria, differential counts, etc.” The instructions are easy to understand, but really to communicate this sort of information you have to show people and let them practice it.

As a result, the 1910s saw some skeptical questions came in to the miscellaneous letters section of JAMA, sometimes with fairly impatient replies from the editors.

The editors of JAMA explain in detail the benefits of the Bass-Watkins test. (citation #2)

Following the usual routine of randomly skimming randomly selected old journals, I found a follow-up piece in the July 1918 New Orleans Medical and Surgical Journal (3) which goes into further detail trying to delineate concepts like “drop”. The author (presenter, rather, since this is the transcript of a talk which was followed by comments) is one of Bass and Watkins’s junior colleagues at Tulane, Foster M. Johns. Here’s what he says.

In the eight years that have elapsed since the publication of this article, this reaction has constantly grown in favor of the clinicians of the South, in spite of many improper lots of reagent supplied by private laboratories, my own included, as well as the various biological houses. During this time the test has been in constant use in the laboratories of clinical medicine with which I am connected, and it is with the belief that this reaction offers an easier, quicker and even more accurate reaction to not only the clinicians, but the trained laboratory worker as well, that I have prepared this discussion of a well-known test. During this time the few faults in technic and production brought out by continual use have been met and overcome, with the exception of a technic that will insure the uniform production of a stock suspension of typhoid bacilli that will keep well under the ordinary conventions of usage.

…

As simple as the technic sounds, there is often considerable difficulty in doing a simple thing. Taking up the test step by step, I will endeavor to point out the places where error may creep in. To begin with, an absolutely clean slide, freshly washed with soap and water to remove the grease and dust, most be used. Now, we require one-quarter of a drop of blood on the center of the slide. This is a quantity almost impossible to describe to one not accustomed to the routine making of proper blood smears, but practically it is easily approximated. Squeeze a quantity of blood out of a puncture on the finger or ear lobe that will not quite drop off, and then barely touch the slide to it. The quantity adhering to the slide will vary from one-quarter up to one-half of one drop. In either instance, for practical purposes, the end result will not be influenced… The actual dilution of the organisms will not be disturbed by either of the quantities of blood, as the blood is then spread roughly over the middle third of the slide and allowed to dry.

Now, one drop of plain water is added. Drops can vary enormously in size, and while, if the proportions in the test were carried out to suit, no harm would ensue, still, for working purposes, we need a full-sized drop. In this instance the standard drop is measured by preferably using the ordinary medicine dropper held almost parallel to the table, so that the drop collects on the side of the elongated glass tip of the dropper.

Full-sized drop? Quarter drop? A quarter drop is not a drop divided into fourths, but a drop that will not quite drop off? Or do you really mean a “finger or ear lobe that will not quite drop off”? In which case the real concern may be not typhoid, but leprosy.

Instead of all this … wouldn’t it be easier to measure volume in microliters?

I know nothing about the history of scientific equipment, but Wikipedia reports that there were no micropipettes until 1960.  I don’t think there were syringes capable of measuring volumes on the level of a drop, either. And if there were such devices, they were far from disposable, and would need to be cleaned and dried between uses.

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What is a drop anyway? And what was the smallest amount of volume that could be accurately measured a hundred years ago?

Again to the Wikipedia, which claims that today there is a medical definition of “drop” as 50 microliters. That means a quarter drop is 12.5 microliters, which sounds like about the right amount for a blood smear that you would quickly look at under a microscope.

Apothecaries traditionally were able to make much more precise measurements of weight than of volume. The common measurement of a “grain” is equal to 1/20 of a scruple, or 1/60 of a dram. And a dram is only 1/8 of an ounce, so there are 480 grains in an ounce, making a grain about 64 milligrams, under the old system where there were 12 ounces in a pound and a pound was about 1/3 of today’s kilogram.

Meanwhile, for liquids, people didn’t have too much trouble measuring in terms of scruples (slightly more than a cc or milliliter). But the minim, the volumetric equivalent of the grain, was only invented around the beginning of the 19th century, and required quite specialized equipment. Being the equivalent of a grain, the minim is about 64 microliters, or roughly… a drop. So it just made sense to refer to things in terms of drops. But when you factor in surface tension, temperature, the size of the vessel from which the drop is dropping… it’s always a judgment call. As the old saying goes, blood has a higher viscosity and specific density than water.

So those of us with access to space-age technology like micropipettes (and disposable anything) should count our blessings.

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1. Bass CC, Watkins AA (1910). A quick macroscopic typhoid agglutination test. Arch Inter Med VI(6):717-729.

2. from “Miscellany”, September 5th (1914). Value of von Pirquet reaction in adults / Reliability of Bass-Watkins test. J Am Med Assoc LXIII(10):883.

3. Johns FM (1918). The Bass-Watkins agglutination test for typhoid. New Orleans Med Surg J LXXI(1):22-27.

The care and feeding of typhoid carriers

Ralph McBurney, Professor Emeritus

Under discussion this week is an article by Ralph McBurney. Not Ralph McBurney (1902-2009) the centenarian beekeeper, but Ralph McBurney (1883-1964) the professor of bacteriology, who taught at the University of Alabama from 1921 to 1954. First at the Tuscaloosa campus, then at the Medical College of Alabama when that was founded, and he was chair of the department when the medical campus moved to Birmingham in 1945.

As reported in the Harvard Crimson of October 16, 1930, Professor McBurney was accepted for a Research Fellowship at the Harvard School of Public Health. He used this opportunity to do a study on typhoid carriers and whether climate could affect their excretion of the bacterium (1) (subscription required).

To me it looks like a weird project, and Google Scholar lists no papers citing it, so let’s give it some attention.

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It seems that state governments, or at least the Massachusetts government, had registers of known typhoid carriers, who were sort of the long-term HIV non-progressors of their day. What is it about these people? What makes them special? Are they a menace? How can we make them less menacing?

McBurney starts the paper with three main justifications.

First, you can alter the intestinal flora of dogs by putting them in a “summer room” (95 degrees, 90% humidity, compared to the “ordinary temperature room” of 68 degrees and 40%). In the sauna they end up experiencing more replication of the Bacillus prodigiosus with which you spiked their hamburger. This was demonstrated by Lloyd Arnold of the University of Illinois (2), who made very good-looking graphs by 1929 standards.

Figures from Arnold (1929), “Alterations in the Endogenous etc. etc.”

Second, an epidemiological study linking environmental factors to diarrhea in Boston (3) found that “the seasonal occurrence depended more on absolute humidity than anything else”. So this sort of thing is affected by climate in humans as well.

Third, with regard to typhoid, everyone knows about “the periodicity of the carrier state”. Nowadays the word “periodicity” is usually used for a disease that produces a regular cycle of illness, followed by recovery, followed by illness again as the immune system wanes or the pathogen changes slightly, followed by recovery again, etc. The big example is malaria. But even with malaria, people use the word “periodicity” to refer to two things: the multi-week intervals between relapses (great review here (4)), or the two- or three-day intervals between fever flareups during a single period of illness (modeled here (5)). I don’t know if McBurney has a specific pattern in mind, where typhoid carriers regularly alternate between excreting bacteria and not excreting bacteria, or if he’s just saying “Sometimes they’re highly contagious, sometimes they aren’t”.

So he decides to move beyond Arnold’s dog studies and do human experiments. Not by keeping people in “summer rooms” for weeks at a time, or introducing acids and bases into their digestive tract through artificial fistulae. In fact most of the work consisted of recruiting a few registered typhoid carriers, convincing them to send stool samples, and getting them to fill out questionnaires about “conditions such a headache, nausea, vomiting, diarrhea, constipation, taking of laxative, intestinal upset, worry, loss of sleep, fatigue, chilling, condition of living and working quarters as regards comfort, presence of colds, etc.” The study started with 8 patients, and 3 more were added in the fourth month

The stool samples were tested for typhoid positivity and those results were correlated to the questionnaire results to see what sort of health conditions were correlated with the times people were excreting the bacteria. McBurney also compared the health and bacterial info to “weather reports kindly furnished by the U.S. Weather Bureau at Boston through the courtesy of G.A. Loveland, meteorologist”, to see if it correlated with heat or humidity or low-pressure systems or dewpoint or whatever.

This went on for a year, from December through November, though I don’t think he ever says what year it was. Some time between 1930 and 1937.

* * *

One problem with the study is that he didn’t think of measuring how many typhoid colonies were in the stool until it was too late. He just looked for positive vs. negative. Since the vast majority of samples were positive, it was hard to correlate the few negative ones to anything. Meanwhile four patients had nothing but negative samples, so those couldn’t be correlated to anything either.

Unfortunately, the percentage of typhoid colonies on weekly platings was not considered until the 29th week; so no comparison can be drawn between the effect of cold and of warm weather on numbers of organisms.

On the other hand, counting the colonies probably would have been unreliable, changing based on how long the sample was in the mail and other factors. Whereas positive or negative status did not change as a result of mail delays.

It is interesting to note here that during the Christmas holiday several of the specimens were delayed in the mails as much as 6 to 8 days. However, from those showing positive stools, this lapse of time did not cause negative findings with the collecting medium used.

So there were not many correlations. Here’s the three conclusions I see:

1. Female carriers had a higher frequency of positive samples (90% compared to 75% in men). Also, it’s known that women are more likely to be carriers. These two factors go together.

2. Two patients, who had produced mostly typhoid-laden samples, had their gallbladders removed, and afterwards all their samples were negative. This isn’t even mentioned in the text, just in the legend of the table. Isn’t that significant?

3. One family was trying to engage in some skulduggery to get off the government list of unclean citizens.

Stools from carrier 7, an 8-year old boy, from March 16 to August 23, (22 weeks), were negative for a period no longer than 2 weeks in succession, whereas following this period all specimens submitted (10) were successively negative. There is reason to believe that there may have been a substitution of this boy’s stool by some other member of the family. This is based upon past history and the fact that, coincident with these negatives, an attempt to reopen the issue with the Massachusetts State Health Department for his admission to public school, to which he had been excluded, was made.

* * *

Now we can move on to the lab experiments.

In March, Experiment A transpired. Carriers #5 and #10 (males aged 29 and 16) were invited to the Harvard campus, having been chosen based on status as an intermittent carrier (67% of stools positive) and negative carrier (ex-carrier?) (0% of stools positive). They were “placed in an automatically controlled hot room for 6 1/2 hours at a constant temperature and relative humidity of 95 F., and 90% respectively.” After 6 1/2 hours, was there an increase in typhoid bacilli among their excretions?

For carrier #5, there was. Then it went down again 24 hours later. Carrier #10 was still negative.

Again, McBurney decided he should have done something more, which would be to continue the measurements beyond the 24-hour mark. So Experiment B was created. This was the same as Experiment A, except that it also included Carrier #3 (94% of stools positive). Carrier #5 once again had increased typhoid excretion, which continued at the 36-hour and 53-hour timepoints. However, Carrier #3 “gave a decrease”. With the expansion of the sample size from 1 to 2, the effect was no longer evident, and it was concluded that heat and humidity had a negligible impact on the ability of typhoid carriers to infect their neighbors.

Heat and humidity would certainly help the bacteria survive once it leaves the host, though. And what about the data from dogs? Climate must still be important.

What was disappointing here was the failure to find a way to predict what conditions made carriers more of a risk, and the failure to see any pattern in the “periodicity” of typhoid shedding. Typhoid carriers still exist (for details, see the 20oo paper by Asma Ismail of the University of Science, Malaysia (6)), but we still don’t know much about why a carrier is more of a risk at some times than at others. If McBurney’s experiment was repeated with a sample size of 200 rather than 2 it might help.

* * *

1. McBurney R (1937). Typhoid carriers: A study of environmental and other factors bearing upon periodicity. J Inf Dis 61(1):122-128.

2. Arnold L (1929). Alterations in the endogenous enteric bacterial flora and microbic permeability of the intestinal wall in relation to the nutritional and meteorological changes. J Hyg (Lond) 29(1):82-116.

3. Grover JI (1916). A study of diarrheas in Boston for 1915. JAMA LXVII(22):1562-1567.

4. White NJ (2011). Determinants of relapse periodicity in Plasmodium vivax malaria. Malaria J 10:297

5. Su Y, Ruan S, Wei J (2011). Periodicity and synchronization in blood-stage malaria infection. J Math Biol 63(3):557-574.

6. Ismail A (2000). New advances in the diagnosis of typhoid and detection of typhoid carriers. Malays J Med Sci 7(2):3-8.

Retro-Infographic: Typhoid in Cleveland, 1916

Here’s a great, great figure. Most papers from this era don’t even have figures, let alone this kind of thing.

The Cleveland Medical Journal only had a couple real articles per issue. It contained mostly news and synopses of articles in more prestigious journals. But they outdid themselves with the annual summary of the city’s typhoid outbreak. It’s hard to interpret without the legend, but this figure is fantastic. I especially like the black bar that serves as a physical representation of the sheet of ice covering Lake Erie at the specified dates.

* * *

Here’s the previous year’s, and the following year’s. Not as comprehensive, and not as clear because you have to turn the page to see the legend. These are well-designed, but for R.G. Perkins of the Cleveland Department of Health’s Bureau of Laboratories, his creative zenith was the 1916 typhoid report.

(Of course, the overall high point of the Great War-era Cleveland Medical Journal was another 1917 article on the subject of “The Spontaneous Explosion of Artificial Eyes”, by the intrepid Roy B. Metz. But that’s a story for another day.)

* * *

* * *

Sources:

Fulk ME, Perkins RG (1917), Typhoid fever in Cleveland in 1916. Cleveland Med J XVI(5): 326-336.

Frey JG, Perkins RG (1916). Typhoid fever in Cleveland in 1915. Cleveland Med J XV(7): 443-452.

Fulk ME, Perkins RG (1918). Typhoid fever in Cleveland in 1917. Cleveland Med J XVII(6): 359-369.