Epidemiology of Cancer: Spatial-Tern Poral Aggregation
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Formal Discussion of: Epidemiology of Cancer: Spatial-Tern poral Aggregation ALEXANDER D. LANGMUIR Communicable Disease Center, Public Health Service, Atlanta, Georgia As a practicing epidemiologist who has devoted his pneumonia, primary pulmonary tuberculosis, Fort Bragg entire career to the acute communicable diseases, my fever, and acute glomerulonephritis. one qualification to speak before this group is the fact During the mid to late 1930's when pneumococcal anti that my telephone was one of the early relay stations in serum became a practical therapeutic procedure, the spe the line of communication leading to the field investigation cific typing of cases of lobar pneumonia became a common of the Niles, Illinois, leukemia cluster. practice, particularly in New York State, where a state Dr. Shimkin's paper is thorough, comprehensive, and wide program was developed under the direction of Dr. penetrating. It reflects the long years of intense study E. S. Rogers. Clusters of Types I, II, and V pneumococcal and the substantial contributions he has made. Instead pneumonia were recognized with increasing frequency, of attempting to embellish selected points he has de more in some years than in others. These were studied veloped, I believe I can be more constructive by concen at every opportunity even though the available methods trating on a single area. I propose to discuss the cluster were quite primitive. Contacts among cases were phenomenon as an epidemiologic concept in the hope that searched for but only rarely found. Family and com some analogies from experiences in acute communicable munity contacts carried type-specific pneumococci at diseases may be of broad interest and possibly of some greater than average frequency. Some epidemics, but application to the study of leukemia and other types of not all, were preceded by a recognizable outbreak of an clusters of neoplastic diseases. acute febrile respiratory infection of unknown etiology. Basically, a cluster is the most elemental form of spa The concept that this might have been specific viral tial-temporal aggregation. To the practicing epidemiolo influenza did not enter our thinking at the time. After gist, the occurrence of a cluster means that one of 3 all, viruses, other than rabies, were something being mechanisms is operating : (a) A normal mode of spread studied at the Rockefeller Institute by such people as and degree of exposure may be acting in a peculiarly sus Francis and Horsfall. We were not able to develop a good ceptible population. A measles epidemic in a nursery hypothesis to account for the many clusters of pneumo would be a good example of such a cluster. (b) An un coccal pneumonia we had studied. usual mode of spread, intensity of exposure, or the Some 5 years later when I was a member of the Com presence of some additional contributing factor may be mission on Acute Respiratory Diseases at Fort Bragg, acting in a normally susceptible population. The con the speculative idea was put forth that such clusters were a sumption of raw clams or oysters contaminated with manifestation of underlying influenza viral infection. hepatitis virus would be a current example. (c) The The happy thought then was recalled that as part of the play of chance alone may lead to the apparent but investigation of one of the clusters of Type I pneumonia purely coincidental clustering of wholly unrelated cases. in New York State, blood specimens had been collected This is the explanation that some epidemiologists offer for on 2 occasions from a sample of the general population. the reported leukemia clusters. These were secured and tested. They revealed that in The investigation of a bona fide cluster or microepi fluenza B had indeed been present concurrently. Then, demic is often most rewarding. Important factors and and my main point is only then, did we examine the dates significant interrelationships may become apparent that of occurrence of all known pneumonia clusters and find would be lost in the study of an equal number of endemic that practically all had occurred when viral influenza cases, or an equal-sized sample of a macroepidemic. The was known to be widely prevalent in the country. Sup investigation of a false cluster may, of course, be frustrat port for the speculative idea was in hand. ing indeed because the expected common factor that one is The effect of this very simple little discovery was quite searching for may be nonexistent. But, even so, the electric on our group. Now there was at least a working orderly study of any grouping of cases is probably a worth hypothesis to account for pneumonia clusters. It was while procedure and is likely to be productive if carried possible to plan expansive protocols and to look for viral out imaginatively by an enterprising epidemiologist. influenza in future clusters with a sense of purpose and When one reviews developments in the field of the acute direction, and yet all of the essential facts had been known infectious diseases during the past quarter century, cluster and the actual specimens collected a full 4 years before. effects have played an important role. I would like to The next cluster phenomenon I would like to recount is summarize the salient facts in 4 examples chosen from part of a health officer's routine follow-up of a case of areas of my own personal involvement : pneumococcal pulmonary tuberculosis reported in an inmate of a school I 384 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1965 American Association for Cancer Research. LANGMrnR—Formal Discussion of Spatial-Temporal Aggregation 1385 for juvenile delinquent boys in Somers, New York, in other exotic insects. Dr. Hugh Tatlock and I even tabu June, 1942. About 200 boys, ages 12 to 16, were housed in lated the register of men who went swimming in the pond. 7 roomy cottages of modern design with high ceilings, We showed that attack rates among swimmers were large windows, and ample space. Tuberculin tests re markedly higher than among nonswimmers, but we were vealed the normal prevalence of tuberculin sensitivity of at a loss to offer a possible explanation. It didn't enter 30—40% among the boys in all cottages but the one where our consciousness that this disease could be a form of the open case had occurred. In this cottage, 100 % of leptospirosis. the boys were l)Ositive. At that point in my story I It was 1951 before workers at the Walter Reed Institute entered the army and was unable to follow up this event, who had carefully maintained this delicate agent revealed but the question remained in my mind of how 100 % of that it was Leptospira aulumnalis. Then and only then the boys in such a generally favorable environment could did the significance of the swimming dawn on us. Here have become infected. There was no good explanation is an example of the failure of epidemiologists to practice that I could see. their profession competently. We waited for the autopsy It was not until 1948, when I became familiar with the to be performed in the laboratory before reaching a diagno studies of Wells and Ratcliffe and later with the brilliantly sis we should have suspected from the epidemiologic quantitative studies of Lurie, that the concept dawned evidence alone. that naturally occurring pulmonary tuberculosis could The final cluster I wish to report again deals with my be an intrinsically airborne infection. During the 1950's, own personal experience. It, too, is embarrassing in retro the exhaustive studies of Riley and O'Grady in Baltimore spect. In February, 1949, while I was at Johns Hopkins went much further to elucidate an exact mechanism of University, I received an invitation to investigate the occur natural airborne tuberculous infection of both man and rence of 4 cases of acute glomerulonephritis in a rural animals. area of Harford County some 30 miles from Baltimore. I In a review of the literature recently conducted by Dr. had never heard of a cluster of nephritis, but I remember Edith I\@I.Lincoln, literally hundreds of epidemics of tuber specifically saying to Dr. Kenneth M. Maxcy that perhaps culous infection have been recorded where excessively this would be a lead to a nephritogenic strain of the hemo high rates, if not 100 %, of localized groups of persons lytic streptococcus. I already had a well-developed have become tuberculin sensitive after exposure in a working hypothesis before I embarked on the study. A closed space to an open sputum-positive case. It is field inquiry confirmed the original report. The 4 cases slowly becoming ap@)reciated that the most comprehen were indeed classical acute glomerulonephritis. Cultures sive and coherent theory of spread of pulmonary tuberculo taken at the elementary school revealed from 35 to 50% sis blames the inhalation of small aerosol particles rather of children in the various grades to be carriers of fl-hemo than the vague but still popular concept of prolomred lytic streptococci. A survey of the school children in intimate contact. cludiiig collection of a morning urine specimen revealed a This is a field in which I have played essentially no moderate incidence of nondescript respiratory disease active role. I have merely sat on the sidelines as an and an amazing amount of microscopic hematuria with intently interested bystander and watched the haltingly out significant amounts of albumin. A large selection slow acceptance of this view. The essential point is that of the streptococcal isolates was sent by the Maryland State the critical examination of clusters of infection coupled Health Department to the Communicable Disease Cen with brilliant experimental studies has led to a radical ter for specific typing, and in due time the report was revision of commonly accepted concepts regarding the received that Type 12 was the dominant strain.