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Outbreak of Histoplasmosis Associated with the 1970 Earth Day Activities

ALAN L. BRODSKY, M.D.*

MICHAEL B. GREGG, M.D.

MATTHEW S. LOEWENSTEIN, M.D.t

LEO KAUFMAN, Ph.D.

GEORGE F. MALLISON, M.P.H.

Atlanta, Georgia

An outbreak of histoplasmosis occurred in early May 1970 at a junior high school in Delaware, Ohio; clinical illness occurred in 384 (40 per cent) of the students and faculty, with probably an equal number of subclinical cases. The mode of spread was airborne and was shown epidemiologically to be related to activities on Earth Day, April 22, 1970, when the courtyard in the center of the school, an old bird roost, was raked and swept. Contamination of the entire school building with courtyard air occurred via the school’s forced air ventilation system with intakes in the courtyard. Soil samples from the courtyard were positive for Histoplasma capsulatum, but random samples from other areas around the building were negative. In two persons in the building only on April 22, the typical illness developed. Features of the outbreak have important implications for clini- cians and public health officials.

From the Viral Diseases Branch, Epidemiol- ogy Program, Center for Disease Control, Health Services and Mental Health Adminis- tration, Public Health Service, U.S. Depart- ment of Health, Education and Welfare, At- lanta, Georgia 30333. Requests for reprints should be addressed to Dr. Michael B. Gregg, Viral Diseases Branch, Epidemiology Program, Center for Disease Control, Atlan- ta, Georgia 30333. Manuscript received NO- vember 2, 1972; accepted November 9, 1972. ._.-.

*Present address: Rheumatology Division, University of Texas Southwestern Medical School, Dallas, Texas 75235.

tPresent address: Boston City Hospital, 818 Harrison Avenue, Boston, Massachu- setts 02118.

Contaminated starling roosts, particularly in urban areas, are now among the major sources of epidemic histoplasmosis [l] in contrast to the chicken and pigeon roosts in rural settings implicated in earlier studies [2]. An explosive outbreak of respiratory illness localized at a junior high school was recently in- vestigated and found to be an epidemic of histoplasmosis related to cleaning activities in a starling and blackbird roost area. The well defined nature of the outbreak provided an unusual opportunity to study the epidemiology of the airborne route of fungus dissemination as well as the clinical and laboratory diagnostic features of acute histoplasmosis.

It seems somewhat paradoxic in light of the current interest in environmental contamination that as the result of a well meant attempt at cleaning up the environment, the largest number of clinical cases of histoplasmosis ever to be reported in a single epidemic occurred.

BACKGROUND

Delaware, Ohio, a town of approximately 15,000 persons, is the county seat of Delaware County (population 45,000) and is located-in the central portion of the-state. The town has five elementary schools, an intermediate school (the Willis Intermediate School, grades 6-8), a high school (Hayes High, grades g-12), a parochial school (grades l-8) and a liberal arts college (Ohio Wesleyan University) (Figure 1) .

March 1973 The American Journal of Medicine Volume 54 333

HISTOPLASMOSIS ASSOCIATED WITH EARTH DAY ACTIVITIES-BRODSKY ET AL.

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Figure 1. Schools in De/a ware, Ohio.

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Figure 2. Layout of Willis Intermediate School.

334 March 1973 The American Journal of Medicine Volume 54

The Willis School is housed in two buildings, a 2 l/2 “new” building (circa 1933) and a 3 story “old” building (circa 1867), which are connected by a long first floor hall (Figure 2). The sixth grade is housed in the old building, and each stu-

dent has his own individual schedule of classes.

The seventh and eighth grades are housed in the

new building, and these students move as a unit

to various classrooms throughout this building.

The sixth grade uses the cafeteria, auditorium and

gym in the new building. When an alarming increase in absenteeism oc-

curred relatively suddenly and involved only the

Willis School, local and state health officials were notified. Preliminary investigation conducted by

the Ohio Department of Health on May 12, 1970,

showed that the water in the Willis School was

free of coliform contamination, and 18 throat-

wash specimens processed virologically and bac-

teriologically yielded no isolates.. Further epide-

miologic investigation was then carried out.

METHODS

Questionnaire Data. A questionnaire was designed to obtain specific information regarding the nature and duration of the clinical illness, secondary spread and possible modes of spread. It was administered to all full-time and part-time students and faculty of the Wil- lis School, and to several other groups having varying degrees of contact with the affected school.*

From the questionnaire data an attempt was made to divide the school population into those who were clinically ill and those who were well. Anyone who had any two of the three symptoms of fever, headache and chest pain was considered to be clinically ill. Absentee Data. Absenteeism by date was examined for each city school during the epidemic period; student visits to the student health service at Ohio Wes- leyan University were similarly analyzed. Serologic Data. Serum samples were obtained from 200 students selected at random at the Willis School and were screened by standard complement fixation technics [3] for antibodies to a battery of respiratory agents, including influenza, para influenza, adenovirus, Mycoplasma, selected Coxsackievirus and echo- virus strains, Cl fever, psittacosis and histoplasmosis. Serum was also tested by agar gel immunodiffusion

*Specific groups questioned: (1) High school students who took shop and cosmetology at the Willis School half a day each day. The shop is located along the corridor between the old and new buildings, and the cosmetology room is on the ground floor of the old building. Both groups ate lunch in the cafeteria. (2) Tutors from the college and high school who helped slow learners one afternoon a week. (3) Substitute teachers during the period between April 20 and May 8. (4) Person? living on the same block as the Willis school (the “neighborhood category”) who were available for questioning. (5) Faculty and staff from the high school.


technics for the presence of histoplasmosis M and H precipitin bands [5]. Serum samples were also obtained from persons in groups 1,2,3 and 5 (as pre- viously described under questionnaire data) as well as from 50 ninth grade (high school) controls selected at random.

For the purpose of this study a positive test for histoplasmosis was defined as complement fixation titer of 1:32 or greater for the yeast form and the my- celial (histoplasmin) antigens, and/or the presence in serum of M or H bands by immunodiffusion technics. Skin Test Data. A histoplasmosis skin test survey was conducted four and a half months after the epidemic peak for all students in the school system to compare rates for the affected and nonaffected schools. In addition, an estimate of the degree of susceptibility of the intermediate school students was de- duced by this method. A permission slip was sent home with each student in the school system; all students whose parents signed the slips were tested. Environmental Studies. Airflow studies were per- formed by smoke bomb technics to investigate possible spread of contaminated air via the school’s forced- air ventilation system as well as other modes of flow.

A search for possible sources of fungal contamination included collection of samples of soil and bird

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8C

70

60

30

20

IO

29 ‘30 ’ / 2.3 4’5’6’ 7’ 8’9 ‘10’,,‘l2’l3’14’15‘16’

4PRIL MAY

Figure 3. Histoplasmosis cases, by date of onset, Willis students, April 29-May 16, 1970.



260

240

220

200

60

40

20

0

APRIL MAY

Figure 4. Absenteeism by date, Willis School, April l-May 22, 1970.

droppings from 73 sites around the Willis school buildings, including each area of bushes and trees, the parking lots, the center courtyard and the air ducts.

RESULTS

The Epidemic. The epidemic was explosive in

nature as can be seen from the epidemic curve

by date of onset (Figure 3). Most cases occurred

on May 6, 7 and 8, with the shape of the curve strongly suggesting a common source outbreak.

Although fewer cases had their onset on May 9

and 10, this is probably an artifact due to the fact

that these were weekend days and also that the questionnaire was filled out three weeks after the

peak of the epidemic. The epidemic curve taken from the question-

naire data is well corroborated by the absentee data (Figure 4) for the Willis School. The usual

base line level of absenteeism appeared to be in the range of 45 to 85 students per day. However,

on May 7, 144 students were absent, approximately double the base line, and on May 8, 249 were absent, approximately four times the base line. Absenteeism remained elevated during the

following week but declined to near base.line levels thereafter. These data underestimate absen-

teeism, since they include only persons absent at

the beginning of the day but not those who left

during the day. It was estimated that more than

100 persons went home from school during the

morning of May 8 causing school officials to ad-

journ classes at 1:00 PM.

Absentee data obtained from each of the other

schools in the city for a comparable period of

time indicated no increase in absenteeism at any of the elementary schools (which primarily serve

local neighborhoods), and no increase at the high

school (which serves all areas). In addition, the

number of students visiting the student health ser-

vice at Ohio Wesleyan University, examined by

date, showed no peak during the comparable pe-

riod. Furthermore, each of the 17 local physicians

was questioned, and none could recall treating a case of similar illness (the “Willis flu,” as it was

called) in a person who was not affiliated with the Willis School.

Clinical Picture. From personal interviews and the questionnaires, a typical clinical picture emerged. Illness was characterized by fever, headache and chest pain; coryza, sore throat and

gastrointestinal symptoms were usually absent.

Fever and headache affected 92 and 95 per cent



of ill persons, respectively, and chest pain affected 63 per cent (Table I). Only 56 per cent of the patients had all three symptoms, i.e., fever, headache and chest pain. Anorexia, nausea and cough were also present in more than half of the patients. Seventy-seven per cent were sick enough to stay home from school.

The chest pain was rather peculiar in nature, characterized as a discomfort in the anterior portion of the chest on deep inspiration; it was defi- nitely not pleuritic. The cough, when present, appeared later in the course of the illness, usually after two or three days. It was hacking, dry and nonproductive, and was seldom associated with significant disability.

Figure 5 shows the duration of illness in the students at the Willis School. More than three fourths of the persons affected were ill a week or less. A few persons noted prolonged (more than one month) asthenia, with intermittent low grade fever and easy fatigability. All recovered com- pletely within two months. Five persons were hos- pitalized but only one for longer than a week. Risk of Illness by Association with Willis School. Once it had been established that the illness was associated only with the Willis School, illness rates were analyzed tor each of the various groups associated with the school (Table II) to assess the relative risk conferred by this association. Rates of illness were high in the first four of these categories (Willis students) being generally higher in girls than in boys. In addition, rates were lower over-all in successive grades being highest in the sixth grade (55 per cent) and lower in the seventh (35 per cent) and eighth (34 per cent) grades. A total of 353 Willis students were clinically affected by the epidemic illness. The Willis

TABLE I Symptoms of 353 Patients with Histoplasmosis (Willis Intermediate School Students), April-May 1970

Symptom Present Absent

Per cent Unknown Present

Fever 324 19 10 92 Chills 224 104 25 63

Malaise 226 115 12 64

Headache 335 16 2 95

Myalgia 132 185 36 37

Chest pain 221 120 12 63

Cough 186 149 18 53

Sore throat 148 195 10 42

Coryza 123 207 23 35

Nausea 208 132 13 59

Vomiting 81 260 12 23

Anorexia 251 a4 ia 71

Stiff neck 103 229 21 29

faculty also had a high rate of illness (39 per cent), similar to that in the seventh and eighth grade students.

Rates of illness for other groups varied (Table II) according to the degree and type of association. In the cosmetologists and shop students rates were comparable to those in Willis students (52 and 44 per cent, respectively). Generally low rates of illness were found in all other groups in- terviewed.

Illness rates analyzed by classroom disclosed that no localized area of the school conferred any special risk. Analysis of questionnaires indicated two additional facts: illness rates were similar among those who bought their lunch at school and those who brought it from home; and also there was minimal, if any, secondary spread to family members.

FURTHER EPIDEMIOLOGIC INVESTIGATION

From the questionnaire and absentee data it was apparent that the epidemic of respiratory illness characterized by headache, fever and chest pain had a common source. It was not related to food, and on culture water from the Willis School water fountains was free of coliform contamination. These factors suggested that the mode of spread was airborne and perhaps related to some common event still to be uncovered.

Events were sought during the three weeks prior to the epidemic at which large numbers of students might have shared exposure. This time period was selected to include the incubation period for most common infectious agents. There were no assemblies and no unusual large group gatherings, such as picnics, dances or the like.

DLJAnTlON fDlYS2

Figure 5. Histoplasmosis cases, by duration of illness, Willis students.



TABLE II Risk of Illness by Association with the Willis TABLE Ill Serologic Results of Groups Surveyed, Bela- School, April-May 1970 ware, Ohio, April-May 1970

6th grade

M

F

T

7th grade

M

F

T

8th grade

M

F

T All Willis

students

M

F

T

Willis faculty

and staff

M

F

T

Cosmetology

F

Shop M

Tutors

M

F

T

Substitutes

M

F

T Neighborhood

M

F

T

Hayes faculty and staff

M

F

T __._~ ____

65 76 141 46 85 49 134 63

150 125 275 55

39 104 143 27 66 95 161 41

106 201 307 35

43 93 136 32 55 98 153 36 98 192 290 34

152 273 425 36 211 242 453 47 353 519 872 41

7 18 25 28 23 26 49 47 30 47 77 39

11

4

0 4 4

0 2 2

0 1

1

1

4

5

10 21

5 9

10

31

41

10

35

45

2 2

14 16

16 18

20 20

24 25

44 45

26 27

23 27

49 54

52

44

0 11 9

0 13 11

0 4 2

4 15 9

Group Ill Well Total*

No. of Patients Per cent

III

NOTE: M = male; F = female; T = totals.

* Illness status could be determined for all Willis students,

but sex and class distribution were not available for some.

Therefore the total c.olumns include all students, unknowns

in addition to the sum of males and females or the sum of the

grades.

The only unusual events were on Earth Day, April

22, 1970, a day dedicated to cleaning up the envi-

ronment and saving it from pollution. Earth Day Activities. The sixth graders were di-

vided into groups and cleaned up at the five local parks. Rates of illness by park visited were rough- ly comparable, however, and the students brought nothing back to the building with them.

Group Surveyed

Serologic Results (no.)

Positive Negative Total

Per cent Positive

Willis Students

Male Female

Total Willis Faculty

Hayes 9th grade Hayes faculty

Cosmetology and shop

79 20 99 80 87 10 97 90

166 30 196 85 25 12 37 68

5 46 51 10 1 22 23 4

12 7 19 63

TABLE IV Serologic Results by Grade and Clinical Status, Willis Students, April-May 1970

Laboratory Geometric Mean Results (no.) Titer

-___-.____~

Grade and Posi- Nega- Total Per cent Histo- Clinical Status tive tive Tested Positive Yeast plasmin

6th grade

III 28 . . . 28

Well 17 6 23

Total 45 6 51 7th grade

Ill 22 2 24 Well 26 8 34

Total 48 10 58

8th grade

Ill 25 1 26

Well 27 4 31

Total 52 5 57 Willis School

Ill 75 3 78

Well 70 18 88

Tota I 145 21 166

100 99.0 7.04

74 21.6 5.57

88 . . . . . .

92 56.4 5.66

76 22.8 6.31

83 . . . . . .

96 80.6 9.51

87 28.6 6.40

91 . . . . . .

96 78.1 7.28

80 24.4 6.14

87.3 . . . . . .

Most of the seventh and eighth graders cleaned

up their lockers only. However, one group of eighth grade students attempted more vigorous

clean-up work; a group of special education stu-

dents volunteered to clean up around the building;

they raked and swept up dirt, leaves and debris.

They also worked in the courtyard located in the center of the school buildings (Figure 2). This

courtyard had not been cleaned for some 20 years, and was known to be an old roost for various species of birds, including starlings, grackles

and other black birds. It was said that bird drop-

pings were so thick in years past that the trees

turned almost white. Afternoon classes were fre- quently disrupted by the noise of the birds. The special education student group spent most of their time on April 22 and 23 on their cleaning activities but were in the courtyard cleaning only between noon and 1: 15 PM each day. The sixth



TABLE V Clinical Status and Presence or Absence of Precipitin Bands in Serum, Willis Students

_____ Precipitin Band (no.)

Clinical M and Per cent Per cent Status M H H None Total M H

III 54 0 11 23 8% 73.0 12.55

Well 60 2 5 30 97 67.0 7.2 Unknown 4 0 0 5 9 44.4 0 Total 11% 2 16 5% 194 69.1 9.3

TABLE VI Seroconversions After Four Weeks,* Willis Students

No. Specimens Showing

Laboratory In- De- Per cent Tesl crease crease Stable Total Increase

Yeast antigen a 2 64 74 10.8 CF

Histoplasmin antigen CF 14 0 60 74 18.8

M band precipltins 9 5 60 74 12.2

H band precipltins 2 1 71 74 2.7

* Fourfold change in titer, or change in presence of M and H bands. Initial serum drawn 20 days after peak of epidemic; second serum drawn four weeks later. CF = complement fixation.

grade, which had returned from the parks by 1l:OO AM, ate lunch in the cafeteria during part of the time the courtyard cleaning was going on.

Absentee data analyzed in terms of protection from illness by date of previous absence suggested that being absent in the interim between April 22 and 24 might have conferred some degree of protection.

The number of students absent for 2 or 3 con- secutive days was quite small, however; one person, who was absent from April 22 through 24 and who ultimately became ill later, had a negative skin test for histoplasmosis, suggesting that her illness might have been unrelated to the outbreak. The absentee data also suggested that the infective agent was present for more than one day and perhaps for more than two days.

Two substitute teachers who were in the school building on April 22 only became ill with typical symptoms, whereas all substitute teachers who were present during the week before or the two weeks after remained well (there were no substitutes on April 23).

LABORATORY DATA

Serologic Results. The initial 200 serum samples were screened by complement fixation technics

TABLE VII Skin Test Results by Grade and Sex, Public Schools, Delaware, Ohio

Nega- Per cent

Grade, Sex and School Positive tive Total Positive

First 11 147 15% 7.0 Second 11 167 17% 6.2

Third 15 159 174 8.6 Fourth 29 172 201 14.4 Fifth 21 156 177 11.9

_

Elementary schools M 52 389 441 11.8 F 35 412 447 7.8

T a7 801 88% 9.8

Sixth 153 22 175 87.4 Seventh 157 24 181 86.7 Eighth 89 2% 117 76.1

Willis Intermediate School M 167 25 192 87.0 F 232 49 281 82.6

T 399 74 473 84.4

Ninth 26 65 91 28.6

Tenth 23 50 73 31.5

Twelfth 1% 49 67 26.9

Hayes High School M 32 65 97 33.0

F 35 99 134 26.1

T 72 164 231 31.2

NOTE: M = male, F = female, T = totals.

for antibodies to common variants of influenza, parainfluenza, adenovirus, selected strains of echo and Coxsackieviruses, 0 fever, psittacosis, mycoplasma and Histoplasma capsulatum. Blood was drawn 20 days after the peak of the epidemic. Consistently high antibody titers were found only for histoplasmosis.

The results (Table Ill) indicated (1) the over-all rate of positive serums was 85 per cent for Willis students (80 per cent for males, 90 per cent for females) and 68 per cent for Willis faculty; (2) the rate for ninth grade controls was 10 per cent; (3) the cosmetology and shop students had a rate ot 63 per cent, not significantly different from that for the Willis students. Table IV gives a further breakdown for the Willis students in terms of ill and well status, and the data indicate that students had nearly a 100 per cent chance of having a positive serum if they were ill and about a 75 per cent chance if they were well. The geometric mean titers for ill and well persons are statistically significantly different for the yeast form antigen but only of borderline significance for the histoplasmin antigen. (In the seventh grade the histoplasmin geometric mean titers were higher for well persons than for ill persons.) Also, the presence of M or H immunodiffusion precipitin bands in the



serum (Table V) was not helpful in separating ill persons from well persons.

The results of a follow-up serologic survey of 74 Willis students (of 196 initially surveyed) four weeks after the first survey are given in Table VI; these data indicate that rises in titer and develop- ment of M and H band precipitins were still occur- ring during the interval. There were fourfold rises in eight yeast and 14 histoplasmin complement fixation tests (11 and 19 per cent, respectively, of those tested). M bands appeared in the serum of nine persons (12 per cent) and H bands in the serum of two (3 per cent). Skin Test Results. Once the diagnosis was established by serologic methods, a skin test program was initiated to assess susceptibility levels to histoplasmosis and to obtain another estimate of over-all (subclinical and clinical) illness rates.

from there into the cafeteria where all students ate. (The courtyard was being raked and swept when students were in the cafeteria.)

The results (Table VII) indicated a gradual increase in the rate of positive serums for grades 1 through 5, with a marked increase for Willis Inter- mediate School students and lower rates for high school students. For the sixth, seventh and eighth grades, the rate of positive serums was about 90 per cent. Environmental Studies. The airflow patterns of the school were studied in detail to uncover possible sources of H. capsulatum and mechanisms of spread.

Four of 10 soil samples collected from the courtyard were positive by culture for H. capsula- turn. One sample from one of the fans was positive, but 62 samples from elsewhere around the school building were negative. Other Laboratory Results. Because the “Willis flu” was originally considered to be a form of influenza or nonspecific upper respiratory tract illness, and was mild and self limited in nature, relatively few clinical laboratory studies were per- formed during acute illnesses. Only 36 per cent of the affected students consulted a physician, and most of these contacts were by telephone. Eleven persons had chest roentgenograms, of which nine were abnormal. Three persons had only hilar ade- nopathy; two had only patchy, scattered, small ir- regular, stellate infiltrates; and four had adenopa- thy and infiltrates. No leukocytosis was noted in the six persons tested, although lymphocytosis and shifts to the left were each present in two persons.

COMMENTS

Two of the air intakes for the forced-air ventilating system of the new building are located in the courtyard in the center of the buildings (Fig- ure 2). Smoke bomb experiments demonstrated that air enters these intakes and travels through concrete plenums to fans in the basement of the new building. These fans then force the air through ducts that ventilate individual classrooms as well as the cafeteria in the new building but not in the old building. Some of the forced air that ventilates classrooms is exhausted through grills connected to ducts, without exhaust fans, that open on to the building roof.

An epidemic of respiratory illness occurred over a relatively short period of time a.nd affected 383 students and faculty with clinical illness at a single school. The illness was characterized clinically by fever, chills, headache, malaise and chest pain. The mode of spread could not be related to food or water but rather was airborne.

Forced air is not supplied to the old building. Thus, it was postulated that air might move from the forced air ventilated new building to the old building because of the difference in pressures. Additional smoke bomb tests demonstrated that the air introduced into the new building from the courtyard did subsequently move through the con- necting first floor hall into the old building and was then distributed to each of the three floors by stack effect.

Serologic and skin test surveys indicated that from 85 to 90 per cent of persons in the building were infected with H. capsulatum, probably of recent onset in most. The courtyard in the center of the school buildings, an old bird roost, was raked and swept up on Earth Day, April 22, 1970, and again on April 23. Smoke bomb tests showed that contamination of both the old and new school buildings with courtyard air was possible via the forced-air ventilating system of the new building with intakes on the courtyard. Soil samples from the courtyard and from one of the fans were positive for H. capsulatum by culture, but samples from elsewhere around the school building were negative.

The kitchen and cafeteria are adjacent to the courtyard (Figure 2). Because of high tempera- tures in the kitchen, one of two exhaust fans had been turned around in early April so that it was blowing courtyard air directly into the kitchen and

Since the onset of illness in most persons occurred within 10 to 15 days after Earth Day, the presumed incubation period is consistent with that recognized for histoplasmosis (five to 15) days. In two substitute teachers in the building only on April 22 acute histoplasmosis developed, whereas substitute teachers present on other days did not become ill.

In this outbreak more than 380 clinical cases of


histoplasmosis were identified, the largest number ever to be reported in a single outbreak. In addition, there were probably an equal number of subclinical cases, since the numbers of positive skin reactors and serologically positive persons ranged between 85 to 90 per cent, far higher rates than in comparison groups. A number of aspects of the investigation deserve further comment. Risk of Illness Through Association with Willis School. The likelihood of clinical illness devel- oping seems to have been largely dependent on being in the building, and particularly the cafeteria, on April 22. Comparable clinical attack rates were expected and found in the shop and cosmetology students, since these groups ate in the cafeteria daily with the rest of the Willis students and presumably had a similar degree of exposure. Sex and Age as Factors in Expression of Clinical I Ilness. The higher rates of clinical illness for girls (Table II) are in contrast to the relatively un- iform rates for both sexes by skin testing (Table VI I) and by serologic survey (Table I I I). The rea- son for these discrepancies is unknown. Although elementary school boys had a slightly higher rate of positive skin tests, this difference is not of suffi- cient magnitude to account for the differential attack rate on the basis of susceptibility differences. It is possible that although males and females are equally susceptible to infection, females are more likely to manifest clinical illness. Similar argu- ments may be invoked regarding the differential clinical attack rates for the sixth grade versus the seventh and eighth grades since skin test and serologic results were quite similar in each. Lack of Severity of the Illness. Only one patient required prolonged hospitalization (approximately one month), and none required treatment with amphotericin l3. In most the clinical illness lasted less than a week. Although the rate of clinical illness was only 40 per cent, the rate of positive skin tests was 84.4 per cent over-all and the rate of positive serums was 84.7 per cent over-all, in- dicating a high rate of subclinical infection. Indi- vidual host resistance factors as well as size of inoculum may have played a part in determining the expression of illness. Sex and age (grade) may have constituted some of these factors.

It is worthwhile to emphasize that the clinical illness in most of these cases was mild enough to be considered a nonspecific “flu-like” syndrome. Histoplasmosis is almost never included in the differential diagnosis of mild “flu-like” syndromes, probably because much of the literature on this illness focuses upon the chronic pulmonary or disseminated forms of the disease and not upon the much more common upper respiratory (or

even subclinical) form. The findings in this report should serve to remind physicians of the nonspecific nature of the acute respiratory illness and its usually mild and self-limited course.

Although the incidence of erythema nodosum and erythema multiforme has been estimated to be approximately 1 per 200 skin test converters, these features were not found in the patients in the current study. We might have expected approximately four cases. These may simply not have been recognized or by chance may not have occurred. Chest Pain as a Symptom. The nonpleuritic pain in the anterior portion of the chest described in this outbreak was rather distinctive in nature and, when present, was usually the most prominent clinical feature. This is not generally described as a classic feature of histoplasmosis, although Wil- cox et al. [1,4] did note pain in anterior portion of the chest in six of their 19 patients. The pathogen- esis is not known, but one might speculate that sudden increase in hilar lymph node size may play a part. The prominence of this symptom in this particular outbreak suggests that it should be spe- cifically looked for in future outbreaks of respiratory illness as a different diagnostic point. Criteria for Serologic Positivity. Since this area of central Ohio is known to be highly endemic for histoplasmosis, and since serologic tests may re- main positive for a variable length of time [5-71, it was decided to use a relatively high titer (1:32) as the lower limit of positivity in an attempt to separate recent cases from older ones. Since a titer of 1:8 may be considered presumptive evi- dence of infection [5], a number of valid cases were probably ignored by these strict criteria. Hopefully, however, some of the more chronic cases were excluded. The 85 per cent positivity rate for Willis students contrasted with the 10 per cent positivity rate for ninth grade controls suggests the criteria were useful in this regard. The yeast form titer under these circumstances seemed to be much more sensitive than the histoplasmin titer (150 of 196 positive versus six of 196 positive, respectively) and was also more specific in distinguishing ill persons from well persons. The presence in the serum of an M band was more sensitive than that of an H band (144 of 194 versus 18 of 194, respectively), but neither was ef- fective in distinguishing ill persons from well persons. Rates of Positive Skin Tests. Usual rates of positive skin tests for residents of Delaware County have been reported to be 70 to 79 per cent [6] (Navy recruits) and 65 per cent [7] (Ohio State students). The rate of only about 30 per cent in the high school students is thus hard to explain. It




is probably due to the fact that the figures quoted in the literature refer to all of Delaware County, whereas the current data apply only to the city of Delaware (one third of the total county population). Since rural residents are probably more likely to be exposed to H. capsulatum, this may account for the difference. Control Measures. To eliminate environmental fungal contamination, the courtyard was treated with three separate applications of 3 per cent formalin. This procedure has been shown to be ef- fective in eradicating H. capsulatum from the soil [8,9]. The relatively localized source of contamination in this outbreak seemed to be an ideal tar- get for formalin decontamination. Follow-up studies at regular intervals will be conducted. Samples were negative at monthly intervals for the first six months after spraying.

In view of the emerging pattern of histoplasmosis in which urban starling and blackbird roost

are assuming a more important role, public health officials would do well to advise caution in construction and cleaning activities in known bird roost areas in the histoplasmosis endemic por- tions of this country.

ACKNOWLEDGMENT

We wish to express our thanks to John H. Acker- man, M.D., State Epidemiologist, Ohio Depart- ment of Health and members of staff, particularly William H. Halferty, who provided valuable assis- tance during the course of the investigation. We also wish to thank Fred E. Tosh, M.D., Chief, Mycology Section, Ecological Investigations Pro- gram, CDC, for culturing soil samples, and Samu- el Saslow, M.D., Professor of Medicine, Ohio State University, for his advice regarding laboratory diagnosis of histoplasmosis.

REFERENCES

1. Sarosi GA, Parker JD, Tosh FE: Histoplasmosis outbreaks, their patterns, Proceedings of the Second Na- tional Conference on Histoplasmosis, Atlanta, 1969. National Communicable Disease Center (Ajello L, Chick EW, Furcolow ML, eds), Springfield, Ill., Charles C Thomas, 1969, p 123.

2. Lehan PH, Furcolow ML: Epidemic of histoplasmosis. J Clin Dis 5: 503, 1957.

3. U.S. Public Health Service Publication No. 1228, Standardized Diagnostic Complement Fixation Method and Adaptation to Micro Test, Washington, D.C., U.S. Government Printing Office, 1965.

4. Wilcox KR, Waisbren BA, Martin J: The Walworth, Wis- consin. epidemic of histoplasmosis. Ann Intern Med 49: 388, 1958.

5. Kaufman L: Serology of systemic fungus diseases. Public

State Med J 48: 229, 1959. 8. Weeks RJ, Tosh FE: Control of epidemic foci of Histo-

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Edwards LB, Acquaviva FA, Livesay VT, et al.: An atlas

National Communicable Disease Center, (Ajello L, Chick EW, Furcolow ML, eds), Springfield, Ill., Charles C Thomas, 1968, p 184.

of sensitivity to tuberculin PPD-B and histoplasmin in

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Saslaw S, Prior JA: The relationship of proved histoplasmosis to histoplasmin skin sensitivity in Ohio. Ohio


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