Download Snippets from the Past: 70 Years Ago in the Journal

American Journal of Epidemiology
Copyright © 2001 by the Johns Hopkins University Bloomberg School of Public Health
All rights reserved
Vol. 154, No. 10
Printed in U.S.A.
Snippets from the Past Comstock
Snippets from the Past: 70 Years Ago in the Journal
George W. Comstock
In 1931, the American Journal of Hygiene published 98
articles. They still tended to be long, averaging just over 16
pages; most dealt with parasitology, entomology, and bacteriology. The proportion of female first authors among those
with full first names given dropped slightly, to eight out of
64 as compared with 13 out of 60 in 1930. In marked contrast to today’s Journal articles, 46 of the 98 articles had
only one author; 34 had only two authors, and 18 had 3–7
authors.
The puzzling fact “that malaria has practically disappeared from certain regions of Europe in recent times without any intentional effort to dislodge it” was discussed by
the prominent malariologist L. W. Hackett and his coauthor
A. Missiroli in a paper presented at the Second International
Congress on Malaria in Algiers (1). The borders of these
low-malaria areas were often clearly defined and were
located within malarious areas. They were home to large
numbers of an indoor biting malaria carrier, Anopheles maculipennis. In their study area of “anophelism without
malaria,” the authors noted that stabling of domestic animals
might be an important factor in the near-disappearance of
human malaria. Some strains of A. maculipennis were so
strongly attracted to the odor of farm animals that they
rarely bit humans. The increasing practice of concentrating
animals in stables or pens in or near human dwellings
provided such a good source of blood meals for these mosquitos that over a long period of time they outbred the mosquitos that preferred human blood, thus accounting for the
low proportion of mosquitos found to have bitten humans.
In these “islands” of low malaria incidence, the excess of
mosquitos that preferred farm animal blood was thought to
have reached a point at which human-to-human transmission was no longer sufficiently common to maintain a high
proportion of malarious persons.
Diphtheria was still an important cause of childhood
death in 1930, despite the fact that knowledge about this disease was more complete than that for most infectious diseases. The question posed by Ida May Stevens, in what
appears to have been her doctoral thesis, was whether diphtheria deaths were due to the lack of some important piece
of knowledge or to the inadequate application of what was
presently known (2). Inquiries were sent to the 4,694 physicians who had reported a case of diphtheria to the California
State Board of Health during the first 4 months of 1924. The
response rate was 64.4 percent. The case fatality among persons for whom a case history was received was 0.8 percent.
Young age and treatment delay were found to be important
determinants of fatal outcome. Treatment after the fifth day
showed little if any benefit. Case fatality was highest in rural
areas, but only among persons under the age of 20 years.
In an attempt to confirm a report by Schick and Topper
that 82 percent of children in New York City developed
immunity to diphtheria within 6 months after tonsillectomy
(3), Wheeler et al. conducted a study in Baltimore, Maryland,
among 710 schoolchildren and 232 medical students from
the Johns Hopkins University School of Medicine (4).
Schoolchildren who had had their tonsils removed were trivially and nonsignificantly more likely to be Schick testnegative (immune) than those who still had their tonsils,
while the opposite (but still trivial) situation was found
among the medical students. Because these findings differed
greatly from those of the New York report, the authors concluded with a now-familiar statement: “The need for further
observations on the subject is obvious.”
“There is an almost universal conviction that there exists a
positive relation between density of population and mortality… Once such an idea merges itself into the great body of
human beliefs, it is difficult to dislodge” (5, p. 781). The
author of this statement, Thomas Leblanc of Tohoku Imperial
University and the University of Cincinnati, attributed the
first scientific expression of this relation to William Farr,
England’s prominent 19th century vital statistician. In his
First Annual Report of the Registrar General, Farr noted that
urban death rates were higher than rates in rural areas (6). He
quantified the relation in Farr’s Law, which, as ultimately
amended, stated that the death rate varies as the 0.12 power of
the population density (7). Leblanc chose to test this relation
in Japan because of its excellent vital statistics system. If population density did indeed affect mortality, he felt it would be
most likely to be manifest in Japan, which had a mean population density of 960 persons per square kilometer, with
marked variations from district to district. He found no association between mortality and population density in the 90
cities with more than 50,000 people, while in rural areas,
there was a slight but nonsignificant tendency for the most
densely populated areas to have the lowest death rates. It was
clear that Farr’s Law did not apply in Japan.
Another idea that has lodged itself in human beliefs is that
changes in the weather are associated with the onset of
Received for publication and accepted for publication September
14, 2001.
From the Department of Epidemiology, Bloomberg School of
Public Health, Johns Hopkins University, Baltimore, MD.
Reprint requests to Dr. George W. Comstock, Training Center for
Public Health Research, Washington County Health Department,
Hagerstown, MD 21742-2067 (e-mail: [email protected]).
951
952
Comstock
upper respiratory tract infections. Gafafer examined this
relation during a period of 82 weeks in a group of “about
350” medical personnel and in “approximately 500” individuals in “about 100” families living in Baltimore (8).
Thirteen weather characteristics were measured. Increases
in upper respiratory infection were found to be associated
with decreases in temperature and sunshine to a considerable degree during the warm period (April–October) but to
only a slight degree during the cold period (October–April).
Another widespread and persistent belief is that judicious
exposure to ultraviolet radiation is beneficial to health and is
likely to prevent respiratory infection. Hardy and Chapman,
after reviewing the conflicting evidence for this belief, set
out to test it in experiments with rabbits, using an organism
natural to rabbits (Bacterium lepisepticum, now called
Pasteurella multocida) and one not normally found among
them (Pneumococcus type 1) (9). After comparing a variety
of responses to each of these two infectious agents, the
authors concluded that “the weight of evidence here, as elsewhere, is on the negative side.”
In what must have been one of the earliest controlled trials, James Doull and colleagues observed a group of 363
adult volunteers over a 35-week period from the end of
September 1929 to the end of May 1930 (10). By a strictly
random procedure, 179 persons were allocated to the irradiated group and 184 to the control group. “A vigorous effort
was made to secure reports of all cases of upper respiratory
disease (common colds).” The total incidence of illness was
slightly higher for the irradiated persons than for the controls: 78.6 attacks per 1,000 for the 169 irradiated persons
who had had 10 or more treatments; 61.9 per 1,000 for the
10 persons who had had fewer than 10 treatments; and 71.9
per 1,000 for the untreated controls. Severity and duration of
illnesses were similar in the treated and control groups.
(Note: Doull et al. described what appears to have been a
properly controlled trial carried out in England by Dora
Colebrook and reported in the Medical Research Council
Special Report Series, No. 131, 1929.)
Joseph Aronson from the Henry Phipps Institute of
Philadelphia reported the results of tuberculin test surveys
conducted in three rural counties in the southeastern United
States using carefully standardized preparations of Koch’s
old tuberculin (11). The first test dose administered was 0.01
mg of tuberculin in 0.1 ml of diluent injected intracutaneously. If no redness or edema was observed 48 hours after
the initial test, a second test with 1.0 mg of tuberculin, also
in 0.1 ml of diluent, was administered. Participation was
best among 5- to 14-year-old schoolchildren. The age- and
sex-adjusted prevalence of a positive reaction to the 0.01mg dose was 14.2 percent among White children and 29.0
percent among Black children. Among nonreactors to the
low dose, the proportions who reacted only to the 1.0-mg
dose of old tuberculin were similar among Whites and
Blacks: 40.2 percent and 38.0 percent, respectively—a
strange finding if reactions to either dose were due to
Mycobacterium tuberculosis. While Aronson noted that the
Black children had stronger and more severe reactions to the
tuberculin, he associated this with the tendency of Blacks to
have more acute types of tuberculosis than Whites. A
reanalysis of Aronson’s data using the age- and raceadjusted prevalences of reactions to either the 0.01-mg dose
or the 1.0-mg dose as indicators of tuberculous infection, as
was done at that time, shows that the estimated average
annual rate of becoming infected was 6.4 percent for Whites
and 7.7 percent for Blacks. However, thanks to the definitive studies of Carroll Palmer and Lydia Edwards, we now
know that reactions to only the 1.0-mg dose are almost
always due to infections with nontuberculous mycobacteria
(12). Based on reactions to the low dose only, more accurate
estimates of the average annual rates of infection with M.
tuberculosis are 1.5 percent per year and 3.4 percent per
year among White children and Black children, respectively.
Tuberculosis was better controlled in 1930 than we realized
at the time.
In view of the 1999 statement of the American Academy of
Pediatrics and the US Public Health Service calling for the
removal of thimerosal from vaccines (13), it is worth noting
that two of the early reports on its use appeared in the Journal
during 1931. Merthiolate, as thimerosal was known then, was
found by work done in the research laboratories of the Eli
Lilly Company to have unusual properties which made it
“well adapted to tissue antisepsis” (14). Furthermore, as older
members of our profession can attest, it did not sting like
iodine when applied to local cuts and abrasions. In a second
paper, Jamieson and Powell reported that the “low degree of
toxicity of Merthiolate together with its harmlessness toward
labile antigen fractions and antibodies, and freedom from protein precipitating properties, indicated that it would be much
superior to phenol and cresol as a preservative for biological
products” (15, p. 223). However, in their evaluation of
merthiolate, the authors made no mention of any long-term
observations for chronic effects. They and their contemporaries would have been amazed at a recent review which
concluded that, as a result of the use of thimerosal as a preservative in vaccines, “infants may be exposed to cumulative
levels of mercury during the first six months of life that
exceed EPA recommendations” (13). The times, they are
a’changing…
REFERENCES
1. Hackett LW, Missiroli A. The natural disappearance of malaria
in certain regions of Europe. Am J Hyg 1931;13:57–78.
2. Stevens IM. An analysis of 3,122 diphtheria case histories. Am
J Hyg 1931;13:392–414.
3. Schick B, Topper A. Effect of tonsillectomy and of adenoidectomy on diphtheria immunity. Am J Dis Child 1929;38:929–34.
4. Wheeler RE, Doull JA, Frost WH. Antitoxic immunity to diphtheria in relation to tonsillectomy. Am J Hyg 1931;14:555–9.
5. Leblanc TJ. Density of population, mortality and certain other
phenomena in Japan. Am J Hyg 1931;13:781–802.
6. Eyler JM. Victorian social medicine: the ideas and methods of
William Farr. Baltimore, MD: The Johns Hopkins University
Press, 1979:129.
7. Eyler JM. Victorian social medicine: the ideas and methods of
William Farr. Baltimore, MD: The Johns Hopkins University
Press, 1979:145, 231.
8. Gafafer WM. Upper respiratory disease (common cold) and the
weather: Baltimore, 1928–1930. Am J Hyg 1931;13:771–80.
9. Hardy M, Chapman J. Ultra-violet radiation and resistance to
infection: intranasal infection with the pneumococcus and with
Am J Epidemiol Vol. 154, No. 10, 2001
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Bacterium lepisepticum in the rabbit. Am J Hyg 1931;13:
255–80.
10. Doull JA, Hardy M, Clark JH, et al. The effect of irradiation
with ultraviolet light on the frequency of attacks of upper respiratory disease (common colds). Am J Hyg 1931;13:460–77.
11. Aronson JD. Incidence of tuberculous infection in some communities of the South. Am J Hyg 1931;14:374–93.
12. Palmer CE, Edwards LB, Hopwood L, et al. Experimental and
Am J Epidemiol Vol. 154, No. 10, 2001
epidemiologic basis for the interpretation of tuberculin sensitivity. J Pediatr 1959;55:413–29.
13. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in
childhood vaccines. Pediatrics 2001;107:1147–54.
14. Powell HM, Jamieson WA. Merthiolate as a germicide. Am J
Hyg 1931;13:296–310.
15. Jamieson WA, Powell HM. Merthiolate as a preservative for
biological products. Am J Hyg 1931;14:218–24.