CHAPTER II
Coccidioidomycosis
Roger O. Egeberg, M.D.
The full clinical picture of coccidioidomycosis had been puttogether only a short time before the entry of the United States into World WarII, and the very name was unfamiliar to the majority of physicians in the UnitedStates as the country began to take action against the eventuality of war.
What, then, was known to students of the disease as theUnited States began to mobilize and to prepare for training? By 1940-41, theclinical picture was fairly clear. It was recognized that coccidioidomycosis wasa disease with an acute, relatively benign initial phase, usually localized inthe lungs, and frequently associated with erythema nodosum. This acute phase wasfollowed in a few patients by a generalized spread throughout the body withdeath occurring in more than 50 percent of white patients and in almost alldark-skinned patients. The causative agent was a biphasic fungus, Coccidioidesimmitis, which had been recovered from the soil of certain arid regions andfrom rodents. There were obvious similarities to tuberculosis, but analogieshere were in many respects misleading.
HISTORICAL NOTE
In 1892, Posada1 and,later in the same year, Wernicke2 describeda round parasite found on section in the autopsies of patients dying of adisease not unlike tuberculosis. This work was done in Argentina, and thepatients were seen at infrequent but fairly regular intervals. In California, in1894, Rixford3 and, in 1896, Rixford and Gilchrist4 were impressed with thesimilarity of this round parasite, which they also had seen at the autopsytable, to coccidiosis, a parasitic disease of chickens, and accordingly called
1Posada, A.: Un Nuevo Caso de Micosis Fungoidea con Psorospermias. An. d. Circ. Med. Argent. 15: 585-597, 1892. Cited by Moore, M.: Blastomycosis,Coccidioidal Granuloma, and Paracoccidioidal Granuloma. Arch. Dermat. & Syph.38: 163-190, August 1938.
2Wernicke, R.: Ueber einenProtozoenbefund bei Mycosis fungoides. Centralbl. f. Bakt. 12: 859-861, 28 Dec. 1892. Cited by Moore, M.:Blastomycosis, Coccidioidal Granuloma, and Paracoccioidal Granuloma. Arch.Dermat. & Syph. 38: 163-190, August 1938.
3Rixford, E.: A Case of Protozoic Dermatitis. Occidental M.Times 8: 704-707, December 1894. Cited by Smith, C. E.: The Epidemiology ofAcute Coccidioidomycosis With Erythema Nodosum ("San Joaquin" or"Valley Fever"). Am. J. Pub. Health 30: 600-611, June 1940.
4Rixford, E., and Gilchrist, T. C.: Two Cases ofProtozoan (Coccidioidal) Infection of the Skin and Other Organs. Johns HopkinsHosp. Rep. 1: 209-268, 1896. Cited by Smith, C. E.: The Epidemiology of AcuteCoccidioidomycosis With Erythema Nodosum ("San Joaquin" or"Valley Fever"). Am. J. Pub. Health 30: 600-611, June 1940.
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it Coccidioides. The disease, coccidioidal granuloma,was usually fatal and for years was described sporadically in the literature,almost always from post mortem examination. In 1900, Oph?ls and Moffitt5 showedclearly in a simple experiment that the spherules recovered from diseased tissuecould develop into a mycelial mat and that Coccidioides was therefore a"mould."
Early in the settling of the southern part of the San JoaquinValley, Calif., people noted a nonrecurring, relatively mild disease, primarilyrespiratory in nature, with symptoms similar to a cold or la grippe andassociated with red "bumps" on the legs or with a blotchy eruption.This illness was called "Valley Fever," was common, and was consideredto be a mild local condition. These "two" diseases continued to makethemselves felt, side by side, one common, more of a nuisance or discomfort, theother relatively rare, severe, wasting, and usually ending in death.
In 1935 and 1936, Gifford and Dickson began to relate the twoclinical pictures and in 1937-38 published their very important papers showingthat coccidioidal granuloma was a relatively rare spread of the early milddisease and never occurred without the other.6 This immediatelyfocused more attention on the primary form with the grave threat overhanging it,in what Dr. Karl F. Meyer of The George Williams Hooper Foundation, Universityof California Medical Center, San Francisco, Calif., in discussion called"the renaissance of the disease." With this much fuller clinicalpicture, with the total number of patients infected with the fungus very muchgreater than previously thought, and with the great gaps of information still tobe filled in, interest was aroused, cases were better described, symptomatologybecame better known, and the time relationship between the two stages becameevident.
By 1940-41, it was possible to define the disease as aninfection caused by the fungus C. immitis, characterized by an acuterespiratory syndrome simulating a cold, influenza, or pneumonia and infrequentlyprogressing to a generalized chronic infection of a granulomatous type fatal inwell over 50 percent of the cases.
CAUSATIVE AGENT
Coccidioides immitis is a biphasic fungus growing as amycelial mat with aerial hyphae in its saprophytic phase-as on culture media-andas spherules which multiply by endosporulation in the animal body.
5Oph?ls, W., and Moffitt, H. C.: A New Pathogenic Mould.Phila. M. J. 5: 1471-1472, 30 Jan. 1900. Cited by Smith, C. E.: TheEpidemiology of Acute Coccidioidomycosis With Erythema Nodosum ("SanJoaquin" or "Valley Fever"). Am. J. Pub. Health 30: 600-611,June 1940.
6(1) Gifford, M. A.: San Joaquin Fever. In Annual Report, Kern County Health Department for Fiscal Year July 1, 1935, to June 30, 1936,pp.22-23, and for Fiscal Year July 1, 1936, to June 30, 1937, pp. 39-54. (2) Dickson, E. C.: "ValleyFever" of San Joaquin Valley and Fungus Coccidioides. California& West. Med. 47: 151-155, September 1937. (3) Dickson, E. C.:Coccidioidomycosis. J.A.M.A. 111: 1362-1364, 8 Oct. 1938. (4) Dickson, E. C., and Gifford, M.A.: Coccidioides Infection (Coccidioidomycosis); II. The Primary Type of Infection. Arch.Int. Med. 62: 853-871, November 1938.
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In its mycelial phase, the micro-organism sustains itselfunder a wide variety of meager nutritional situations. It remains alive in drysoils, even washed beach sand, in moderate temperatures for at least 7 years.Its ability to withstand higher temperatures is related to humidity. It growsabundantly in a pH range of 2.02 to 12.13.
FIGURE 11.-Sputumculture of C. immitis on Sabouraud's medium, showing white, cottony fungus growth.
On modified Sabouraud's medium, the mycelial mat or phallusmay vary in appearance, but most commonly it is white and fluffy from above,very slightly yellowed underneath, and frequently has a whiteness and translucence resembling a naphthalene mothball broken in two(fig. 11). A speck fished from a 10- to 20-day-old colony and teased in a dropof water on a slide has a very characteristic appearance when viewed under thedry high power of a microscope. In varying amounts scattered through therelatively dense mycelial mat are hyphae, with the following characteristics:
1. They branch at right angles.
2. They have swellings at irregular intervals best describedas "racqueting."
3. They are segmented, and the more mature areas show anincreasing difference between adjacent segments, so that every other one becomesbarrel shaped while the ones in between atrophy. It is these barrel-shapedsegments (arthrospores) that can infect animals or man or repeat the saprophyticcycle.
A culture of more than 10 days becomes increasingly dangerousas a source of laboratory infection, and a 4-week-old culture while showing thecharacteristics best is a menace (fig. 12).
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The home of the mycelial or saprophytic phase of the fungusnow appears to be the soil of the endemic areas, where it can be recovered in ashigh as 40 percent of soil samples collected from the surface in the earlysummer. In the parasitic phase, in the tissues of man or lower animal, thearthrospores quickly round out into spherules, usually from 20 to 40 microns indiameter, which have a very characteristic doubly refractile wall. As thesemature septae form within them and gradually wall off, approximately
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70 small pieces, which round out to become endospores, growto the size of mature spherules and in turn endosporulate (fig. 13). Notinfrequently, growth in a pulmonary cavity may resemble the saprophytic stagewith mycelia and formation of hyphae, but it is doubtful that these ripen. Itis thus apparent that spread of this disease is not by contagion from man to manbut from the environment to man by inhalation of the arthrospores.
SYMPTOMATOLOGY
The symptoms and signs of coccidioidomycosis, in its primaryphase, are best described as mimicing a cold, influenza, or primary atypicalpneumonia; in its disseminated phase, as a generalized tuberculosis. About 60percent of those infected, as evidenced by changing skin reactivity tococcidioidin, have no symptoms. In that 40 percent of infected people who becomeill, the onset of coccidioidomycosis may be acute or gradual, and the patientsexhibit one or more, or a combination of, symptoms, as follows:
1. Fever is relatively mild and most common. Usually, thetemperature is not above 102? F., but it may reach 105? F. The fever lasts ashort time-from 4 to 5 days in most instances-but may continue as a lowgrade fever for several months in uncomplicated primary coccidioidomycosis.
2. Chest pain varies from a mild sense of constriction to apain severe enough to be mistaken for a myocardial infarction or an acuteabdominal condition.
3. Cough, although most frequently present, is not veryannoying to the patient. It is more often dry than productive. The slight amountof mucoid or mucopurulent sputum commonly raised frequently grows C.immitis on culture.
4. Arthralgia in the back or the peripheral joints is similarto the aching common in mild influenza and responds readily to salicylates.
5. Headache is usually mild and transitory; sometimes verysevere, almost neuralgic in character. It is most often frontal, or when verysevere postorbital, like the headache associated with malarial chills.
The symptoms just described occur in more than two-thirds ofthe patients. Malaise, of varying degree, chills, night sweats, anorexia, andpharyngitis occur in about one-third of the patients. Erythema nodosum (theearly trademark of the disease), erythema multiforme, and urticaria-all ofgood prognostic significance-are seen in less than one-fifth of the patients,erythema nodosum occurring three times as often in women as in men.
The findings on physical examination vary somewhat with thesymptoms and range from a reddened throat without exudate to the dullness, ralesand rubs of a frank pneumonia, and include the allergic manifestations oferythema, nodosum or multiforme, and urticaria. Conjunctivitis is notinfrequent, and pleural effusion can occur.
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LABORATORY EXAMINATIONS
Although the diagnostic proof of coccidioidomycosis could besaid to depend on finding the spherule (fig. 14) in sputum, discharge or pleuralfluid, or by growing out the saprophytic phase from such materials andidentifying the spherule after animal passage, there are other tests that aremost important. These are the coccidioidin skin test, the precipitin test, andthe complement fixation test.
Coccidioidin test.-The intracutaneous test withcoccidioidin, performed and read like the tuberculin test, is the means ofdetermining whether a person has been infected with C. immitis. Of thegreatest value in an epidemiologic survey, the coccidioidin test is also veryuseful as a diagnostic tool and in some cases indicates a degree of resistance.The reaction is almost always positive in a person who has been infected withthe specific agent, although there is a slight cross-reactivity withhistoplasmin or haplosporangin extract, and in an overwhelming disseminated caseof coccidioidomycosis the reaction may be negative. Otherwise, this is a verydependable test; it can be repeated regularly without creating a positivereaction in a noninfected subject, while a reaction, once positive,
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will remain positive for many years, if not for life. Thematerial for the test can be obtained commercially, but in the early days of itsuse it was usually obtained from Dr. Charles E. Smith, Department of PublicHealth and Preventive Medicine, Stanford University School of Medicine, Calif.The material is prepared by growing 10 strains of C. immitis on the sameasparagin culture medium used for making tuberculin. Grown for 1 to 2 months, itis tested at intervals, and when shown to be potent the suspension and extractare filtered through a Berkefeld filter and diluted with aqueous Merthiolate(thimerosal) to a concentrate of 1: 10,000. This is standardized on infected andon normal individuals. This dilution is then referred to as undilutedcoccidioidin and is very stable, keeping its potency at room temperature for atleast 4 years. For testing purposes, it is diluted in normal saline to 1: 100and to 1: 1,000. The 1: 100 dilution is used for routine testing. The reactionis read at 36 to 48 hours.
Knowledge was at first inadequate concerning the immunologicmeaning of the coccidioidin test and, particularly, of its implications for thesoldier newly arrived in endemic regions. Subsequently, the importantobservation was made that the disease might occur, but did not progress to thesevere disseminated form, in those who were positive to coccidioidin on theirarrival at their posts. Dissemination occurred only in those who arriveduninfected, acquired infection, and then disseminated.7 Furthermore, it was foundthat dissemination rarely occurred in patients with primary infectionaccompanied by erythema nodosum which was an early manifestation associated withhigh sensitivity to coccidioidin. The reaction was frequently weak or negativein cases of severe (anergic) disseminated disease. When negative personnel wereretested, the incidence of change to a positive reaction indicated a higherincidence of the completely "inapparent" or asymptomatic than of theclinically recognizable disease.
Aronson and his associates,8 in studies of large population groups in various parts of the United States including Alaska, had provided evidence that "clinched"9 the question of the specificity of the coccidioidin test, in proper dosage. Within their wider field of inquiry, they found a significant incidence, notably in a highly endemic region of Arizona, of calcified pulmonary nodules in persons negative to tuberculin, positive to coccidioidin. Forbus and Bestebreurtje10 found little evidence of calcifi-
7Smith, C. E., Beard, R. R., and Saito, M. T.: Pathogenesis of Coccidioidomycosis With Special Reference to Pulmonary Cavitation. Ann. Int. Med. 29: 623-655, October 1948.
8Aronson, J. D., Saylor, R. M., and Parr, E. I.: Relationshipof Coccidioidomycosis to Calcified Pulmonary Nodules. Arch. Path. 34: 31-48,July 1942.
9Smith, C. E., Whiting, E. G., Baker, E. E., Rosenberger, H.G., Beard, R. R., and Saito, M. T.: The Use of Coccidioidin. Am. Rev. Tuberc57: 330-360, April 1948. (Studies supported from 1937 to 1941 by the RosenbergFoundation, subsequently an activity of the Commission on Acute RespiratoryDiseases, Army Epidemiological Board, Office of The Surgeon General, carried outby the Department of Public Health and Preventive Medicine, Stanford UniversitySchool of Medicine.)
10Forbus, W. D., and Bestebreurtje,A. M.: Coccidioidomycosis; A Study of 95 Cases of the Disseminated Type WithSpecial Reference to the Pathogenesis of the Disease. Mil. Surgeon 99: 653-719,November 1946.
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cation in their autopsy material which was, however, derivedfrom fatal disseminated cases. Studying the primary disease in persons who,positive to coccidioidin, died of other causes, Butt and Hoffman11 foundcalcified nodules interpreted as residua of healed or arrestedcoccidioidomycosis. Cox and Smith12 identifiedarrested lesions, some of them calcified which had been mistaken fortuberculosis in roentgenograms and at autopsy, and, from one such calcifiedlesion, Smith13 reportedrecovery of viable Coccidioides.
Precipitin test-The precipitintest becomes positive within the first month of the disease, and, no matter whatthe course of the disease is, it becomes negative again in 3 months. Its valuelies in establishing the fact that a given symptom picture represents the acutephase of coccidioidomycosis. In the presence of nonspecific symptoms and apositive cutaneous reaction to coccidioidin, a positive precipitin reactionwould indicate that the patient has a recently acquired case ofcoccidioidomycosis. This test is of no prognostic significance.
Complement fixation test-Thecomplement fixation test is of both diagnostic and prognostic significance. Itstiter rises with the severity of the infection, also beginning in the firstmonth but continuing, and persisting possibly, for months or many years. Ingeneral, complement fixation in titers above 1-6 indicates disseminateddisease. Except in a severe disseminated case with anergy, the complementfixation and precipitin tests will give negative results when the cutaneousreaction to coccidioidin is negative.
Erythrocyte sedimentation rate-Elevation ofthe erythrocyte sedimentation rate in acute primary infection is of prognosticsignificance and useful in following the course of primary or disseminatedcoccidioidomycosis.
CLINICAL COURSE
The benign primary form of the disease may occur withoutsymptoms, its only evidence being the change from a negative to a positivereaction to coccidioidin. The course of a clinically apparent but uncomplicatedcase of primary coccidioidomycosis varies from a mild picture resembling a coldto a moderately severe case of bronchopneumonia with fever, cough, chest pain,headache, generalized aching, and malaise. The duration is related to theseverity and may be for 2 or 3 days, or may last for 4 or 5 weeks with low gradefever.
11Butt, E. M., and Hoffman, A. M.: Healed or Arrested Coccidioidomycosis; Correlation of Coccidioidin Skin Tests With Autopsy Findings. Am. J. Path. 21: 485-505, May 1945.
12Cox, A. J., and Smith, C. E.: Arrested Pulmonary Coccidioidal Granuloma. Arch. Path. 27: 717-735, 1939.
13Smith, C. E.: Parallelism ofCoccidioidal and Tuberculous Infections. Radiology 38: 643-648, June 1942.
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A number of complications may be associated with the primaryphase, and these should not be confused with dissemination. Excavation may occurin a pneumonia area or, more frequently, may appear as a tension cavity withlittle surrounding infiltration. It does not have the worrisome connotation of atuberculous cavity but usually heals in from 4 to 8 months with or without bedrest. Excavation, as observed for years, has not resulted in dissemination norhas it been a source of infection in others.14 Hemorrhage may beassociated with the cavity, and this is occasionally severe. A bronchopleuralfistula may result from the cavity and this in turn may lead to empyema orpyopneumothorax. All of these may occur and the patient be quite ill but stillwith a primary coccidioidomycosis and with an excellent prognosis. Iftroublesome, these manifestations may be relieved by surgery.
Not until the disease passes through the hilar lymph glandsand leaves the chest, most frequently causing an abscess in the leftsupraclavicular area, has dissemination occurred. When this happens, theprognosis has suddenly changed, and what was a benign disease with virtually nomortality has now become a malignant disease with a mortality of 50 percent forwhite patients and up to 85 percent in the dark-skinned races. Disseminationoccurs in a little over 1 percent of the clinically diagnosed white patients, infrom 3 to 4 percent of clinically diagnosed Spanish-American patients, from 12to 14 percent of clinically diagnosed Negroes, and in almost all Filipinosclinically diagnosed.
The disseminated disease is protean in its manifestations.Abscesses may form anywhere in the body (fig. 15), including the subcutaneoustissues, muscle, bone, organs, and the central nervous system. The pericardiumand the myocardium may be affected, and meningitis is a common cause of death.Bony lesions (fig. 16) are usually multiple and are cystlike, sharplycircumscribed lesions with minimal surrounding reaction. They occur mostcommonly in the prominences of cancellous bones. In the long bones, they aremore frequently formed near the ends of, and may extend into, the joints.
The course of disseminated coccidioidomycosis may be steadilyand rapidly downhill with meningitis and death occurring in 3 to 4 months fromthe onset of the primary disease, or it may follow a very slow course withremissions and exacerbations (figs. 17 through 20). There may even be periods ofa year or two when the disease is apparently gone, only to return with theopening up of a fistulous tract from some active bony lesion.
14The possibility of spread fromperson to person cannot be completely dismissed in view of the demonstration, ina few postwar cases, of the mycelial form of Coccidioidesin pulmonary cavities (see footnote 7, p. 55. Reported also by (1)Greer, S. J., Forsee, J. H., and Mahon, H. W.: Surgical Management of PulmonaryCoccidioidomycosis in Focalized Lesions. J. Thoracic Surg. 18: 589-601,October 1949; (2) Weisel, W., and Owen, G. C.: Pulmonary Resection forCoccidioidomycosis: Report of a Case. J. Thoracic Surg. 18: 678, October 1949).Nevertheless, Schwarz and Muth (Schwarz, J., and Muth, J.:Coccidioidomycosis: A Review. Am. J.M. Sc. 221: 89-107, January 1951), in theirreview, could still say "secondary infections in families of patients havenever been demonstrated."
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FIGURE 15.-Characteristic skin granulomata onthe forehead. This patient also had a smaller skin lesion on the trunk and hadroentgenographicevidence of pulmonary infiltration with hilar gland involvement.
The course may be associated with a minimum of temperatureelevation or the temperature may be high. Increasing weakness, lassitude,anorexia, and loss of weight are typical. Individual abscesses may healspontaneously in from 4 to 6 months or faster when irrigated, but new ones come.Bony lesions show healing and new bone formation, but new lesions form.Meningitis is like a tuberculous meningitis with the major
FIGURE 16.-Cystlike areas of destruction in thedistal tibia, malleoli, and talus.
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danger from loculation, obstruction, and increasedintracranial pressure. It is almost always fatal.
The course of disseminated coccidioidomycosis is bestfollowed by careful observation of the changing clinical picture and by the useof the complement fixation test, the latter being the best index of course andprognosis. A rising titer of complement fixation is definitely indicative of aspreading infection. A rising titer in the presence of a weakening coccidioidinskin reaction is a matter of very grave concern, usually followed by death in amonth or two.
In Army experience, the disseminated phase, when it occurred,followed close upon the heels of the primary phase. A study15of the autopsy and biopsy material from cases in militarypersonnel, including all fatal cases, suggested that the danger ofdissemination (endogenous spread) would remain, long after the war, in personswho had been exposed in endemic areas. Clinical observations, however, confirmedby the passage of time, does not indicate that this danger exists in those whodid not promptly show themselves, by dissemination, to be "immunologicallydefective" with respect to this disease.16
OBSERVATION AND EXPERIENCE
As knowledge of the disease gradually increased during some50 years, roentgenographic studies lagged behind clinical investigation untilthe war provided opportunity to make serial studies of suitable patients inconsiderable numbers (figs. 21 through 30). It was generally agreed that thediagnosis could not be made from roentgenograms alone. Carter,17 in1931, noted that the pulmonary lesions might resemble tuberculosis or might evenmore closely resemble blastomycosis. Rosenberg and his associates,18 ina study at the Mayo Clinic, Rochester, Minn., in 1942, noted that differentialdiagnosis between blastomycosis, coccidioidomycosis, and torulosis fromroentgenographic appearances was difficult or, in some cases, impossible.Carter,19 in 1942, commented, as follows:
15See footnote 10, p. 55.
16"Army experience * * * has indicated that disseminationoccurs soon after the first infection * * * frequently within a matter of weeksand infrequently after months. It rarely occurs in the second year afterinfection * * *. Oncedissemination ensues, the risk of continued dissemination is great thoughremission may occur. * * * none of our militarycoccidioidal patients, of whom we had records of thousands, has ever beenreported to us as having undergone a postwar dissemination. * * * We have neverseen dissemination occur in a patient with coccidioidal excavation. RecentlyKurz and Loud have reported one [a postwar case, with recovery, of granulomatouscutaneous lesion developing at the site of a trauma, published in the 23 October1947 issue of the New England Journal of Medicine], a very unusualcase." (Cited from report by Smith and his associates, footnote 7, p.55.)
17Carter, R. A.: Coccidioidal Granuloma: RoentgenDiagnosis. Am. J. Roentgenol. 25: 715-738, June 1931.
18Rosenberg, E. F., Dockerty, M. D., and Meyerding, H. W.: Coccidioidal Arthritis. Arch. Int. Med. 69: 238-250, February 1942.
19Carter, R. A.: Roentgen Diagnosis of Fungous Infectionsof Lungs With Special Reference to Coccidioidomycosis. Radiology 38: 639-659,June 1942.
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Fungus diseases of the lungs share with tuberculosis thecharacteristics to be expected when there is organized cellular response toinfection. These include involvement of the lymph nodes; persistent parenchymallesions of many forms, massive, nodular and miliary; variously appearing diffuseinfiltrations, none of them characteristic of any specific disease. Thepredilections of these differ somewhat from disease to disease.
Carter noted that cases showing in the late stage ofdissemination a miliary lesion in the lungs associated with meningitis wereespecially likely to be mistaken for tuberculosis. Such late pulmonaryinvolvement often occurred as a result of hematogenous spread.
The Army control program, with its coccidioidin tests andrepeated roentgenographic examinations, discovered several hundred clinical andseveral thousand subclinical cases. Observation of cases in hospital showed theshort, self-limited course in the majority, while a small percentage persistedfor many weeks or months, and a few ended fatally. Colburn20 studied 75 cases inArmy personnel roentgenographically, with careful followup observations; theclinical details were reported by Goldstein and Louie.21 The pulmonary changescleared completely within 3 or 4 months, and all 75 patients were eventuallyreturned to duty, although dissemination did occur in one case.22 Atthe Regional Hospital, Santa Ana Army Air Base, Calif., to which most of thesevere or prolonged cases were transferred, another study was made by Jamison23of 96 such cases observed closely in roentgenogramsfor periods of from 2 to 21 months.
Among these, there was a group of 23 cases with nodularparenchymal lesions, situated most frequently in the midpart of the lung, lessoften in the lower part, least often in the apical and subapical regions. In asecond group of 35 cases, there were thin-walled, cystlike cavities, occurringless often in the upper than in the middle field of the lung and least often inthe lower. In a third group, there was persistent pneumonitis, ranging fromlesions occupying a third of the lung to small foci in the hilum. These wereprimary infections that had "failed to resolve or focalize as nodular orcystic lesions." In the 12 cases of disseminated disease, there wasconspicuous involvement of lymph nodes and, finally, a rapidly developingmiliary spread, becoming confluent. The roentgenographic appearances asdescribed were often not dissimilar to tuberculosis but differed widely fromtuberculosis in their clinical and epidemiologic significance.
Cavities, as has been noted, may go entirely unnoticedclinically, or may cause some inconvenience, but present no serious threat tolife or to public health, persisting sometimes for months, or for years,24 andfinally
20Colburn, J. R.:Roentgenological Types of Pulmonary Lesions in Primary Coccidioidomycosis. Am.J. Roentgenol. 51: 1-8, January 1944.
21Goldstein, D. M., and Louie, S.: Primary PulmonaryCoccidioidomycosis; Report of an Epidemic of 75 Cases. War Med. 4: 299-317, September 1943.
22Extended studies have shown a more favorable course indisseminations occurring at a considerable interval after the initialinfection.
23Jamison, H. W.: A Roentgen Study of Chronic PulmonaryCoccidioidomycosis. Am. J. Roentgenol. 55: 396-412, April 1946.
24See footnote 7, p. 55.
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FIGURE 22.-Primarycoccidioidomycosis. Fuzzyperibronchial right hilar thickening.
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FIGURE 25.-Primary coccidioidomycosis. Small amount of infiltration at the left base associated with slight pleural effusion.
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closing without rest or other treatment. Some provoke coughand hemoptysis, some are associated with chest pain or weakness, and in thesecases surgery may be done. Experience during and immediately following World WarII showed that there was no danger of endogenous spread following surgery andthat other complications can now be prevented by the use of chemotherapy.25The typical coccidioidal cavity, repeatedly observed in Army studies,26is thin walled, cystlike, not surrounded by infiltration, oftenfluctuating, sometimes widely. Cavities developing as central excavation ofnodular foci are smaller and their walls are thicker.
In studies of the bones and joints, it was again founddifficult or impossible to make the diagnosis on the roentgenographic evidencealone (fig. 31).27 From theinvestigation at the Mayo Clinic are drawn the following comments on thearthritic changes observed in roentgenograms:
Early lesions are characterized by regions of destruction inarticular surfaces, often with evidence of swelling of overlying soft tissues.Cartilage may be destroyed and joint spaces narrowed * * *. Later lesions in joints may cause complete disappearanceof joint spaces, more extensive zones of destruction in articular spaces and, insome instances, ankylosis. These lesions have been commonly mistaken for thoseof tuberculous arthritis. Carter pointed out that arthritis both in coccidioidalgranuloma and in tuberculosis * * * showslittle tendency to heal by production of bone * * *. Taylor found the destructive process in bones,as shown by roentgenograms, to be distinguished by an intensity and rapidity ofdevelopment not often noted in the presence of tuberculosis.
Such lesions, Rosenberg and his associates stated:
* * * are fairly commonlyencountered [in the chronic granulomatous phase ofcoccidioidomycosis]. Among 256 cases tabulated in the report of the CaliforniaDepartment of Public Health in 1931, involvement of joints was noted in 79 * * *.Often,several joints are involved at one time. Affected joints have in this particularphase of the disease first the appearance of acute, later of chronic, arthritis.Early, the joints are swollen and red; later, fluctuation may appear. Nodularlesions may develop in the skin overlying affected joints ** * may ulcerate and discharge pus containing C. immitis. McMaster and Gilfillanexpressed the opinion that joints may be primarily affected by directinvolvement of the synovial membrane or infection may extend to joints fromadjacent foci of coccidioidal osteomyelitis.
Similarly, in 1942, Benninghoven and Miller28 described joint involvement as of-
Two distinctly different types: (a) purely synovial, (b) synovial with subarticular destruction indistinguishable from tuberculosis. Usually synovial involvement is seen as a large swelling of the joint capsule. Occasionally there is periosteal new bone formation on adjacent bone. This is thought to be a reactive rather than an infective process. In the
25See footnote 21, p. 62.
26(1) Winn, W. A.: Pulmonary Cavitation AssociatedWith Coccidioidal Infection. Arch. Int. Med. 68: 1179-1214, 1941. (2) Winn, W. A., and Johnson, G. H.: Primary Coccidioidomycosis; Roentgenographic Study of 40 Cases. Ann. Int. Med.17: 407-422, September 1942. (3) Sweigert, C. F., Turner, J. W., and Gillespie, J. B.: Clinical and Roentgenological Aspects ofCoccidioidomycosis. Am. J.M. Sc. 212: 652-673, December 1946.
27(1) Benninghoven, C. D., and Miller, E. R.: Coccidioidal Infection inBone. Radiology 38: 663-668, June 1942. (2) Carter, R. A.: InfectiousGranulomas of Bones and Joints, With Special Reference to CoccidioidalGranuloma. Radiology 23: 1-16, July 1934.
28See footnote 27 (1).
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lesions that are indistinguishable from tuberculosis there iscapsular swelling, marked periarticular osteoporosis, with cartilage andsubarticular destruction of bone on both sides of the joint.
The investigators at the Mayo Clinic, turning to the benignprimary disease, the "valley fever" of earlier writers, refer to itsacute onset, with malaise, general aches and pains, "toxic erythema,"sore throat, fever, and occasionally signs of bronchopneumonia. From 8 to 15days after onset, at a time when there appears to be a general improvement ofthe patient's condition, lesions typical of erythema nodosum may appear,mainly on the shins, occasionally elsewhere. Roentgenographic examination of thethorax at this time usually discloses opaque regions that suggest the diagnosisof tuberculosis. Signs of acute arthritis develop in about one-third of thesepatients, usually appearing simultaneously with the erythema nodosum.29Joints are tender to pressure, painful on motion, and sometimes slightlyswollen. Effusion and suppuration are not observed. Sometimes arthritis,conjunctivitis, and erythema nodosum appear together, persist about a month, anddisappear at approximately the same time. In these cases, with theircharacteristically uneventful clearing, there is no residual damage or deformityof joints. Among older people, the arthritis was said to be more prolonged.
PATHOLOGY
Thus, knowledge of coccidioidomycosis, during little morethan the half century since the problem was recognized, has necessarily beenderived chiefly from clinical studies with, increasingly, roentgenographicobservation. The anatomic changes seen in the severe disseminated form of thedisease in material collected at the Army Institute of Pathology, Washington,D.C. (50 cases with autopsy, 45 with biopsy only), were reported and illustratedin detail at the close of World War II.30 Anatomicchanges in the mild uneventful case, or in the asymptomatic cases, could not beso studied except in the rarer event of observations made on persons known tohave been positive to coccidioidin, negative to tuberculin (without tuberculousanergy), and coming to autopsy by reason of other causes.31
The pathologic picture of the primary coccidioidal infection as seen in infected animals is that of an interstitial pneumonia, and the response may be leukocytic. Disseminated coccidioidomycosis as seen in man at the autopsy table is as its earlier named indicated-a granulomatous disease, and strikingly similar to tuberculosis-with the spherule to be seen in the tubercle. The spread at first is probably lymphatic to the supraclavic-
29Faber, H. K., Smith, C. E., and Dickson, E. C.: Acute Coccidioidomycosis With Erythema Nodosum in Children. J. Pediat. 15: 153-171, August 1939.
30See footnote 10, p. 55.
31See footnote 11, p. 56.
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ular area, but after this first extrapulmonary abscess itspreads to the rest of the body through the bloodstream. No system, organ, ortissue seems immune, and the lesions are seen everywhere. Suppuration ischaracteristic of the bone involvement which otherwise resembles osteomyelitis.The typical elementary lesion of disseminated coccidioidomycosis is a smalltubercle, granulomatous, with proliferation of epithelioid cells (fig. 32) andwith giant cells containing spherules scattered in the caseous material. In thelungs, there may be areas of focal suppuration with thickening of the alveolarwall, together with fibroblastic proliferation, edema, and infiltration ofplasma cells and neutrophiles in the interstitial tissues.
Diagnosis
The diagnosis of primary coccidioidomycosis is made on thebasis of the clinical picture, following opportunity for infection, inconjunction with a changing (negative to positive) coccidioidin skin test and apositive precipitin test. Its corroboration depends on culturing C. immitis from
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the sputum, gastric washings, or pleural fluid and byidentifying the doubly refractile walled spherule in mice or guinea pigsinoculated with the culture.
The diagnosis of disseminated coccidioidomycosis depends onthe development of its protean clinical picture and the increasing titerof complement fixation, 1-16 usually being taken as the differential point. Inthe disseminated disease, the fungus may be grown from sinus discharge,biopsies, pleural effusion, or spinal fluid. Roentgenographic evidence of bonyor soft-tissue lesions are of definite assistance in making a diagnosis ofdisseminated disease. Pulmonary infiltrations of coccidioidomycosis cannot bedifferentiated from other diseases of the lungs by roentgenographic evidencealone.
Treatment
The treatment of primary coccidioidomycosis during World WarII was essentially symptomatic, aspirin being the most useful single drug, butthe possibility of dissemination was never forgotten and, if symptoms persistedor there was a rising complement fixation titer, conservative handlingconsisting primarily of bed rest and good diet was considered important.Temperature, leukocyte count, and sedimentation rates were useful guides indetermining how much activity should be allowed. In general, with a slightelevation of temperature, an elevated white blood count, an elevatedsedimentation rate, and a rising titer of complement fixation, the patient waskept in bed to lessen the possibility of dissemination.
Many methods of therapy have been hopefully instituted in aneffort to cure disseminated coccidioidomycosis. Few have been of any specificvalue, until recently, in the treatment of this phase of the disease.32Ofall, effective results have been obtained with one basic regimen; namely, bedrest and supportive measures-the only real treatment of tuberculosis of a fewdecades ago. Many are the patients who have seemed moribund, with complementfixation in titers about 1:256, with numerous draining sinuses, with continualelevations of temperature, and with extreme loss of weight, who on bed rest plusa high-protein, high-caloric diet, and supplemental vitamins have improvedclinically and serologically and have left the hospital apparently cured.
32The advent of the antibiotic Amphotericin B,related tostreptomycin, and its effective use in the care of coccidioidomycosis patients, took place subsequent tosubmission of this chapter for publication. Amphotericin B is, apparently, theonly effective drug thus far. Results are reported as excellent in earlyinfections and encouraging even in chronic cases, although not as dramatic asthose obtained in chronic blastomycosis with the drug.-A.L.A.
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COCCIDIOIDOMYCOSIS IN THE ARMY AIR FORCES33
In 1940-41, the Army Air Forces began establishingairfields in the San Joaquin Valley as a first step in its training program. Thehigh percentage of days with good flying weather and the unlimited space foremergency landing fields made this country very desirable for training. Thisregion was part of the Ninth Corps Area (later the Ninth Service Command). Dr.Walter T. Harrison, the U.S. Public Health Service liaison officer in the Officeof the Surgeon, Ninth Corps Area, alerted both the surgeon of the corps area andthe headquarters staff of the West Coast Training Center to the environmentalhealth hazard-coccidioidomycosis.
Dr. Smith, professor of public health at Stanford UniversitySchool of Medicine, had just published (June 1940) in the American Journal ofPublic Health his study of the epidemiology of acute coccidioidomycosis witherythema nodosum in the San Joaquin Valley. This was a broad, 17-month study inKern and Tulare Counties of 432 patients with the disease called San JoaquinValley fever (with erythema nodosum), or valley fever, or desert rheumatism, andfrequently confused with influenza, pneumonia, tuberculosis, measles, smallpox,poliomyelitis, typhoid fever, and syphilis. Dr. Smith observed that theincubation period was from 1 to 3 weeks, most frequently 2, and thatcoccidioidin sensitivity was established about 2 weeks after onset of symptomswith a variation of 2 to 17 days. He learned that erythema nodosum wasassociated with the hypersensitivity of a freshly acquired coccidioidin reaction and that this reaction,like tuberculin sensitivity, was of long duration. His study also indicated thatthe disease was acquired by inhalation of chlamydospores, that spherules orendospores did not pass the disease from host to host, and that the seasonalincidence of the disease was related to the climate and agricultural activitieswith a peak in the dusty windy fall and an ebb in the wet winter. The benign"valley fever," as measured by patients with erythema nodosum, wasshown to be most common in white females while the coccidioidal granuloma, ordisseminated form, was most common in dark-skinned males. Approximately 50percent of patients acquiring the disease had lived in the Valley less than 1year and only one-ninth over 10 years. This led to the conclusion that mostresidents of the region were infected eventually, with 5 percent or lessdeveloping erythema nodosum. Therefore, these 432 patients with erythema nodosumrepresent 8 to 10,000 patients with coccidioidomycosis.
Of the ecology of the micro-organism, little was known. Ithad been isolated from soil, though with difficulty, and it was known to be abi-
33For information to supplement the discussion ofcoccidioidomycosis in the Army Air Forces, Army Ground Forces (pp. 81-85), andprisoners of war (pp. 85-89), aspresented in this volume, reference is made to Smith, Charles Edward: Coccidioidomycosis. In Medical Department, United States Army. PreventiveMedicine in World War II. Volume IV. Communicable Diseases. Washington: U.S.Government Printing Office, 1958, pp. 285-316.
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phasic fungus. The prevailing theory, based on animaltrapping, considered rodents (particularly pocket mice and kangaroo rats) as thereservoir hosts of the disease.
The timely publication of this well-studied series helped tolessen the impact of the unfamiliar disease on the Armed Forces and provided abroad scientific basis for further study.
Because of his knowledge of the disease, Dr. Smith wasbrought into the problem as it concerned the command active in the area. Ameeting was arranged for Dr. Smith to discuss the matter with the headquartersstaff of the West Coast Training Center-Brig. Gen. Henry W. Harms, CommandingGeneral; Lt. Col. (later Brig. Gen.) Charles R. Glenn, MC, Senior FlightSurgeon; and Maj. Otis B. Schreuder, MC. After consultation, it was decided thata detailed study, clinical and epidemiologic, should be made.
Early Planning
On 24 February 1941, Col. H. R. Beery, MC, Surgeon, NinthCorps Area, wrote to Col. (later Brig. Gen.) Charles C. Hillman, MC, Assistantto The Surgeon General, enclosing a copy of Smith's paper on epidemiology. Inhis letter, Colonel Beery pointed out that the weather, which elsewhere had beenbad for flying, was excellent where the San Joaquin Valley flying fields werebeing built. He further advised:
* * * J. P. Leake, Medical Director,U.S. Public Health, on duty in Office of The Surgeon General of that Serviceis familiar with the condition existing in the Valley. ** * Colonel [(later Brig. Gen.) Condon C.] McCornack,Surgeon 4th Army, is familiar with the situation and will see that no ArmyManeuvers are held in the affected area * * *. The Board appointed by this headquarters for the purposeof locating new camp sites will leave the San Joaquin Valley out of the picture.
The Surgeon General's Office concurred in the thought thatthe Air Corps was justified in developing flying fields in the Valley and alsowith Colonel McCornack's decision not to hold Army maneuvers there.
At the same time that this problem was being approached andstudied through the normal Army channels, it also became the subject of interestto the Commission on Epidemiological Survey, Board for the Investigation ofEpidemic Diseases in the Army, Preventive Medicine Division, Office of TheSurgeon General. This body, wisely created under the leadership of Dr. FrancisBlake and Dr. Stanhope Bayne-Jones for the purposes that the name implies,established a division in the Ninth Corps Area with Dr. Edwin W. Schultz, asdirector, and Dr. Edward B. Shaw and Dr. Smith, as members. A program wasplanned that would minimize coccidioidal infection in the San Joaquin Valley andat the same time carry on research into its epidemiology. This plan of study wasworked out by Drs. Smith, Bayne-Jones, and Blake and approved on
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21 June 1941 by the Commission on Epidemiological Survey.Less orthodox channels, more sensitive to time and based on need and friendship,were also established between the Office of The Surgeon General (Col. (laterBrig. Gen.) James S. Simmons, MC) and the West Coast Training Center.
Dr. Smith had been working on a grant from the RosenbergFoundation. This grant was generously continued and supported the work at theairfields for the first 4 months, until more logical support could be obtainedfrom the Army. Whether one wants to call this private injection into the greatwar machinery of the nation "pump priming" or "fusing," itserved a great and helpful purpose and brought about a considerable speeding upof the work at a time when many decisions involving large masses of troops werebeing made every day.
It was planned through the coccidioidin test to learn who hador had not had the disease before coming to stations in the infected areas and,by repeated testing of "negatives" until they changed to"positives," to determine the proportion of those infected who reallybecame ill with definite symptoms. The investigators expected to learn thevariation in infection rate at different times of the year, and what influencedthat rate. And it was hoped that they might evaluate the early and conservativetreatment of the disease, and any other treatment that might shorten its courseor save life in the disseminated disease. The study was in fact to throwimportant light on the meaning of the coccidioidin reaction and on the nature ofresistance in this disease (pp. 54-56).
Institution of Program, West Coast Training Center
As this study got underway, it did so against a backgroundfamiliar to most people going through Army training; namely, dust (four plus) ormud (four plus). When the program was started in July 1941 at Minter Field,Bakersfield, Calif., the background and the foreground were dust, with tents,informal equipment, and a frontier atmosphere of something great about tohappen. The permanent staff of the Minter Field and the Gardner Field at Taft,Calif., was skin tested with coccidioidin, and 20 percent of those not alreadyinfected were found to convert from a negative to a positive reaction in thenext 6 weeks.
It was soon apparent that the infection rate forcoccidioidomycosis was highest at the two airfields nearest Bakersfield; namely,Gardner and Minter. (It is also apparent from the correspondence that more thanone person in Washington, D.C., thought "Bakersfield" was yet anotherflying field.) The airfield at Lemoore, Calif., 50 miles to the north, had alower rate, and the one at Merced in the northern part of the San JoaquinValley, less than 150 miles from Gardner, had no coccidioidomycosis that wasindubitably incurred at that field.
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The study showed a seasonal variation in infection rate witha high in the latter part of the summer toward the end of the dry season and alow in the wet winter and spring. During the period when much building was inprogress, the dust or mud was terrific, and in the dusty month of August 1941over 5 percent of the susceptible personnel at Minter Field were infected. Withthe tapering off of construction, the planting of lawns, the paving of roads andairstrips, the change from field to aquatic sports and, of course, possibleother factors, the incidence of coccidioidal infections was halved.
At a later period during the war, Dr. Smith noted one otherpossible factor influencing the infection rate; namely, that the 2 years withthe highest incidence were preceded by the wettest winters. This extra rain, hethought, might help the growth of the fungus in nature (wherever that might be).Subsequent work would indicate that he was right.
On 20 October 1941, Dr. Smith wrote to Dr. Bayne-Jones,Department of Bacteriology, Yale University School of Medicine, New Haven,Conn., and director of the Commission on Epidemiological Survey, brieflyoutlining the progress of the coccidioidomycosis study up to that time. In thisletter, as in others, Dr. Smith emphasized the intense interest and enthusiasticcooperation given the study by Colonel Glenn. Colonel Glenn, being a personalfriend of Colonel Simmons, also was frequently able to shorten the line ofcommunication without giving offense. Again, as in other letters, Dr. Smithspoke appreciatively of the great contributions made, both administratively andprofessionally, by Major Schreuder and by the flight surgeons of the two basictraining centers (Maj. (later Lt. Col.) John E. Roberts, MC, and Maj. (later Lt.Col.) Robert R. Estill, MC) and their staffs, and praised the warm cooperationof the numerous doctors, aidmen, and others who made this work possible.
Dr. Smith reported that more than 2,000 men had been testedwith coccidioidin. Handicapped by their irregular arrivals at camp and thefrequent shifts of men from organization, the investigators concentrated on skintesting the recent arrivals. Until the population of the camps could bestabilized, it was thought useless to attempt to retest any who did not haveclinical symptoms. Under these difficult conditions, some significantobservations were nonetheless made as follows:
The men from the east and midwest are all negative tococcidioidin. Quite a few from central and western Texas, New Mexico, andArizona and, of course, the San Joaquin Valley of California react to thematerial. Besides these areas we have had a few reactors from Nevada,Southern Utah, Idaho and Montana, indicating the possibility of these areasas previously unrecognized endemic foci. However, the numbers from thesesparsely settled regions are still too small and only when we have the campsfully tested should we have a sufficiently large group from which to draw anydeductions. Thus any comments at the present time on the distribution ofthe positive reactors of the "control" test would seem to mepremature.
When we were down in the middle of September there hadbeen a recent sharp increase in the number of cases of coccidioidalinfection and during the week we saw ten
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active cases at the Bakersfield Camp. As we hoped, the factthat the men had been tested with the coccidioidin proved a very great practicaluse in establishing diagnosis, for all that was necessary was to repeat thetest and when it was positive, in view of previous negative record a copy ofwhich is on file at the camp, a diagnosis was established.
The work of testing, tabulating, evaluating symptoms andtreatment, and pointing up new areas of endemicity continued. This was not easyand was opportunist work as the Army moved personnel in and out. Dr. Smithcontinued to supply the coccidioidin and to perform the serology in hislaboratory at Stanford University. In July 1942, the Commission onEpidemiological Survey took over the financial responsibility for the work beingdone by him and his coworkers under Contract W709 md-294.
On 2 January 1942, Dr. Schultz forwarded through Dr.Bayne-Jones, to Dr. Blake, President, Board for the Investigation of EpidemicDiseases, U.S. Army, a report prepared by Dr. Smith on the investigation ofcoccidioidomycosis in the Kern County, Calif., Air Corps Basic Flying Schools,West Coast Training Center, July through November 1941. In this complete reportof the work so far accomplished, Dr. Smith brought out the method by which thecoccidioidin-testing program was carried out, this being the basis for study ofthe epidemiology of this disease.
Following visits made solely for the purpose of educatingmedical officers on coccidioidomycosis, coccidioidin testing had been started onthe Bakersfield group (Minter Field) on 13 July and on the Taft group (GardnerField) on 20 July. The patients sick with the disease were seen in consultation.Lists of all nonreactor's were kept at the station hospitals, and, if a manwith a negative skin reaction appeared at sick call with specific symptoms, aretest with coccidioidin usually established the diagnosis (by a positivereaction) or ruled it out (by continued negative reaction). Skin-testing surveysbeing done for epidemiologic reasons thus became a very important part in thelaboratory diagnosis of coccidioidomycosis.
The correlation between the positive skin reactions andresidence at the time of entry into the Army indicated that Arizona andCalifornia had heavily infected populations, with Texas showing 12 percent ofits men positive. In striking contrast were the consistently negative resultsfound in men coming from the Eastern or Mideastern States, bearing out otherevidence that the distribution of C. immitis is restricted to arid, dustyregions. The study also, and very importantly, indicated a high degree ofspecificity of the coccidioidin skin test, and, because relatively few reactorscould recall any specific illness suggesting their primary infection, it broughtout the relative infrequency with which the infection is recognized. Thediagnosis of primary coccidioidomycosis was made in 66 cases, of which 44required hospitalization with an average stay of 14 days.
Because it was still not feasible to do repeat testing in anorganized way, it was thought that many "converters" were missed,having changed over without being sick. October was the peak of the season andwith the onset of winter rains the incidence dropped very markedly. Over half of
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those who became ill with the disease had been in camp lessthan 2 months. Smith suggested that, because of the immunity conferred by asingle infection, the personnel in these endemic areas be stabilized, includingthe medical personnel for the additional purpose that they become increasinglyexpert in recognizing and handling the disease. He recommended that the diseasebe treated with respect because of the possibility of dissemination. Hereiterated that except for the Air Corps training fields large concentrations ofsoldiers should avoid the San Joaquin Valley and finally advised that Dr.Harrison (p. 73) should continue to be consulted regarding any plans or problemsthat might have to do with coccidioidomycosis.
On 6 February 1942, Colonel Simmons, through Lt. (later Lt.Col.) Douglass W. Walker, MC, asked Dr. Smith if he could furnish moreup-to-date information concerning the areas of endemicity of coccidioidomycosisand what hazards there might be in having concentrations of troops stationed insuch areas, particularly in California, Arizona, New Mexico, and Texas.
On 2 March 1942, Dr. Smith answered that coccidioidomycosiswas present in the southern half of the San Joaquin Valley and in Stanislaus,Merced, Madera, San Benito, Fresno, Kings, Tulare, and Kern Counties-beingmost intense in the last three (the south end of the San Joaquin Valley). Hestated further that coccidioidin testing at the San Joaquin Valley airfields hadshown occasional cases from the eastern half of Monterey, San Luis Obispo, SantaBarbara, and Ventura Counties, and further south and east in the northern partof Los Angeles County and in San Bernardino, Riverside, Imperial, and San DiegoCounties. With reference to all the endemic areas he recommended that except foraviation training, which made the need very great, the following areas should beavoided for large encampments: (1) The San Joaquin Valley of California, (2) thesouthern half of Arizona, (3) the southern tip of Nevada, (4) the vicinity ofSt. George, Utah, (5) the southern half of New Mexico, and (6) Texas, the regionfrom San Angelo, west and south. He ended his letter by saying: "We arestill in quest of why the fungus is found where it is, what restricts itsdistribution and where it actually grows in nature."
The Syllabus
During the summer of 1942, a syllabus on coccidioidomycosiswas prepared. It was published and distributed by Headquarters, West Coast ArmyAir Forces Training Center, in October of that year. It was revised in September1943, and in March 1944 the publication of a third edition was made possible bythe Josiah Macy, Jr. Foundation. Originally prepared by the surgeon of thecommand (Colonel Glenn and later Col. Michael G. Healey, MC), it was enlarged inscope and detail by Maj. (later Lt. Col.) Norman Nixon, MC. It was wellillustrated by plates showing cultural
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characteristics of the fungus and by roentgenograms creditedto Dr. R. A. Carter at the Los Angeles County Hospital,Los Angeles, Calif., and to Maj. Horace W. Jamison, MC. A map showed endemicareas. A graph indicated seasonal incidence. There was anextensive bibliography.
In substance, the syllabus was an excellent handbook on thedisease, covering symptoms, diagnostic procedures, course,and criteria for discharge from hospital. It also pointed out the militarysignificance of coccidioidomycosis; namely, that the total number of deathswould be low, the morbidity would be high, and the period of hospitalization,rather prolonged. All enlisted personnel and officers were to be tested withcoccidioidin on their arrival at a station and twiceyearly thereafter, and the reactions recorded on the individual's servicerecord and his immunization register MD Form 81. The responsibility forreporting and control was placed on the medical officerspecifically assigned to the coccidioidomycosis problem at each of the fields,and he in turn was to be responsible to the coccidioidomycosis control officerof the West Coast Army Air Forces Training Center, at the Santa Ana Air Base. Bythe time of issue of the second edition, the term "CoccidioidomycosisControl Officer" was as generally accepted in the endemic areas as "V.D. Control Officer."
The authors described the two clinical forms as (1) primarycoccidioidomycosis, the acute, benign, self-limitedrespiratory infection and (2) progressive coccidioidomycosis, thechronic, disseminated, usually fatal illness, manifested by cutaneous,subcutaneous, visceral, and osseous lesions, occurring in certain individuals asone continuous progressive disease, although the serious form may not berecognized as such until several weeks or months haveelapsed. Continued spread of infiltration suggests theprogressive form, and the discovery of extrapulmonary foci confirms it. Deathusually occurs in such cases after a course of many weeks' to 6 months'duration. Rarely, a patient will focalize his disseminating disease, usuallyafter prolonged rest in bed, and make a complete recovery. The great majority ofprimary infiltrations, however, do not go on to dissemination butwill disappear completely in 5 or 6 weeks. In some ofthese cases, residual cavities will persist, but thebenign nature of these is indicated by their clinical course and lowsedimentation rate.
They noted, on the other hand, the high susceptibility ofdark-skinned persons to disseminating disease, advisingagainst the use of Negro troops. They noted how infection is acquired byinhalation of dust containing the tiny live chlamydospores coming from the soilin endemic areas, and that some 90 percent of persons who have been resident inheavily endemic regions will react to coccidioidin. They summarized theimportant points, from the point of view of the military surgeon, to be (1) therecognition of the disease, (2) the prompt hospitalization of all clinical casesuntil the sedimentation rate becomes normal, and (3) the ability to distinguishthis condition from tuberculosis, which it so closelyresembles.
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There are many aids to differentiation from tuberculosis oncethe essential differences have been clearly established.First is the difference in epidemiology as this diseasespreads from environment to man rather than from man to man. There is thestriking immunologic difference in that the initial infection with the fungusconfers permanent resistance against subsequent infection. Although peopleliving in endemic areas (the San Joaquin Valley and southern Arizona) arerepeatedly exposed to contaminated dust throughout their lives, the incidence ofserious disease is low, probably not more than 1 case of the progressive form to500 of the benign primary form.
By March 1943, there had been 253 clinical cases ofcoccidioidomycosis at the Minter, Gardner, and Lemoore Fields. There had beennone at Merced. There were 125 cases in personnel of the Air Forces at Minterbetween July 1941 and March 1943, 61 at Gardner, and 67 at Lemoore. There werethree cases of disseminated coccidioidomycosis with two deaths. The big monthsfor coccidioidomycosis were from June through November with the emphasis inSeptember and October. The infection rate at the three fields was approximately20 percent per year, Minter and Gardner having the highest. It was observed thatrecruits from Merced County rarely showed evidence ofhaving had coccidioidal infection; no clinical infections occurred at MercedArmy Air Field and only seven changeovers.
Dr. Smith gave great credit to the persistence andcooperation of the following medical officers in carrying out thecoccidioidomycosis-control program-Lt. Col. John E. Roberts, Lt. Col. A. L.Jennings, and Maj. Edward C. Donohoe, all successively atMinter Field; Lt. Col. Robert R. Estill, Lt. Col. AlbertPhillips, successively at Gardner Field; Lt. Col. Edward Padden, at Lemoore; Lt.Col. M. U. Prescott and Lt. Col. Neil Johnson, at Merced.The designated coccidioidomycosis-control officers who took a leadingpart in the program were Maj. Russell W. Mapes, at Minter; Lt. David L. Thurman,at Gardner; Maj. J. Murray Kinsman, at Lemoore; and Capt. Harvey A. Woods, atMerced. All these medical officers, themselves subject torapid turnover, were quick to grasp the problems before them and persistent incarrying out the work.
Again on 1 June 1943, Maj. Forrest M. Willet, MC, chief ofthe medical service at the Station Hospital, March Field, near Riverside,Calif., replying, through the Air Surgeon, to an inquiry from the Office of TheSurgeon General, told of a recent increase in cases inconnection with construction of an airfield at Banning,Calif., where Company B of the 856th Engineer Battalion (Aviation) had joinedCompany C on 24 April. These were Negro troops.Three weeks later, several patients with clinical coccidioidomycosis wereadmitted to the station hospital. The medical staff thereupon tested allmembers of the 856th Engineer Battalion with coccidioidin,finding a large number of positive reactors, all of whomhad been in endemic areas before coming to March Field.
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A number of soldiers from Company B who had failed to reactto coccidioidin entered the hospital later with the clinical disease. Company Aof that battalion did not go to Banning and coccidioidomycosis developed in onlyone of its personnel, a man who had gone to Banning on a visit. A new outfit,198 soldiers, moved in to replace the 856th Engineers. They were given thecutaneous test and there were three positive reactors, all of whom hadpreviously been in endemic areas. It was planned to repeat such skin teststwice for the purpose of definitely proving Banning anendemic area.
With so much interest, widened by the experience of the Army,in a disease local by nature, many papers appeared in medical journals. Thesevarious publications34 helped alert the physicians of the country to the disease-itsepidemiology, diagnosis, clinical course, and hazards.
COCCIDIOIDOMYCOSIS IN THE ARMY GROUND FORCES
Early Cases
On 1 December 1941, a report was forwarded to the Office ofThe Surgeon General through channels from Camp Roberts, Calif. It was written byLt. Robert M. Shelton, MC, and later formed the basis of an excellent paper.35The first case had been discovered in April 1941 among the troops there,whose training was in large part carried on in the area east of U.S. Highway101, which included some of the rather dry country of the Coast Range. A numberof other cases were seen in the Station Hospital, and a skin-testing survey wasbegun in June 1941. In all, 888 men were tested; 3 months later 736 of thenegative reactors were retested, and of these 14 were found to react to coccidioidin. Allowing for thosewho might have been exposed elsewhere, the result pointed to an annual incidenceof approximately 6 or 8 percent, indicating that 1,000 men would become infectedannually at Camp Roberts. This report prompted a continuation of the survey.
During 1942 and the first half of 1943, coccidioidomycosisappeared sporadically in ground force units bordering the endemic areas and most
34Many of these reports and studies have been cited inthis chapter. Among others appearing in 1943-44 were (1) Smith. C. E.:Coccidioidomycosis. M. Clin. North America 27: 790-807, May 1943; (2) Colburn, J. R.: Roentgenological Types of Pulmonary Lesions in Primary Coccidioidomycosis. Am. J. Roentgenol. 51: 1-8, January 1944; (3) Goldstein, D. M., and McDonald, J. B.:Primary Pulmonary Coccidioidomycosis; Follow-Up of 75 Cases, With 10 More Cases From New EndemicAreas. J.A.M.A. 124: 557-561, 26 Feb. 1944; (4) Lee, R. V.: Coccidioidomycosisin Western Flying Training Command. California & West. Med. 61: 133-134, September 1944; (5) Quill, L. M., and Burch,J. C.: Surgical Manifestations of Coccidioidomycosis. Ann. Surg. 120: 670-679,October 1944; and (6) Denenholz, E. J., and Cheney, G.: Diagnosis and Treatmentof Chronic Coccidioidomycosis. Arch. Int. Med. 74:311-330, November 1944.
In July 1943, Colonel Bayne-Jones prepared an excellentchapter on "Coccidioidomycosis" for General Simmons' revision of "Laboratory Methods of the UnitedStates Army." This chapter included exposition of the initial or primaryinfection, the progressive or disseminated infection, the distribution, and themode of spread, with fairly detailed laboratory instructions covering techniquesfrom the growth of the fungus to the preparation of coccidioidin and theperformance of the precipitin and complement fixation tests.
35Shelton, R. M.: Survey of Coccidioidomycosis at CampRoberts, California. J.A.M.A. 118: 1186-1190, 4 Apr. 1942.
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probably associated with travel through them by individualsor small groups.
Desert Training
In the latter part of 1942 and early 1943, a desert trainingcenter was created for the purpose of preparing troops for the terrain and theextremes of heat and dryness which they might encounter if fighting continued inNorth Africa. This area was a large one in the lower Mojave Desert west ofBlythe and northeast of the Salton Sea. It included the Pallen Mountains, theGranite Mountains, and the Iron Mountains, and all the dry springs and dry lakebeds in an area 3 or 4 thousand square miles in extent. With such an assignmentand such country, the trainees were really put through their paces. As more andmore troops came in, ultimately reaching 80,000 and including at least one Negrodivision, it was obvious to those interested in coccidioidomycosis that parts ofthis region were highly endemic for the disease, particularly certain camps nearYuma and the area near Pallen Pass west of Blythe. Thedistribution would indeed seem to be very spotty butintense where it existed, thus offering opportunities to avoid small heavilyinfested areas.
On 26 March 1943, the following communication went from theOffice of The Surgeon General to the Surgeon, Army Ground Forces:
1. This office has recently been informed that a number ofcases of acute coccidioidomycosis (Valley Fever) have recently occurred introops maneuvering in the Desert Training area in Southern California. This areais somewhat beyond the highly endemic San Joaquin Valley, and while cases havebeen reported in this region, it has not hitherto been considered thatcoccidioidomycosis constitutes a serious threat to persons living within thisarea.
2. In view of the above, it is requested that fullinformation as to the extent of any recent outbreak of coccidioidomycosis amongtroops in this area be obtained. It is believed that Major Roswell K. Brown, M.C., Desert Warfare Board, Camp Young, California, is acquainted with thissituation.
The first action in this was apparently taken in December ofthat year, according to a memorandum for file on a conference with the GroundSurgeon, Col. William E. Shambora, MC, on 23 December 1943,to determine the policy of his office with respect tococcidioidomycosis control in Ground Forces organizations. For the conferees,including Maj. (later Lt. Col.) Aims C. McGuinness, MC, Colonel Shamboraobtained the following information from Col. Frank S. Matlack, Surgeon,Headquarters, Communications Zone, California-Arizona Maneuver Area, Banning,Calif.:
a. All pertinent information furnished the Ground Surgeon bythe S.G.O. has been forwarded to units maneuvering in the endemic legions.
b. A meeting of all battalion andregimental surgeons, and hospital medical officers of troops on maneuvers inthis region was held. Full details on the endemicity and recognition ofcoccidioidomycosis were present at this meeting. The services of Dr. CharlesE. Smith have been utilized.
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c. Information about the diseasehas also been furnished to line officers.
d. A large number of cases ofcoccidioidomycosis have recently occurred in troops in thevicinity of Yuma, Arizona. Efforts are being made to locate this source ofinfection more accurately.
e. Commanding officers responsible for the selection ofmaneuvers sites will be advised concerning the avoidance of endemic regions.There is no doubt that such advice will be followed so far as it is consistentwith military necessity.
It was agreed that an exchange of all pertinent informationon this subject reaching either the Surgeon General's Office or the GroundSurgeon's office should be kept up.
Coccidioidomycosis-control programs were instituted in theCommunications Zone of the California-Arizona Maneuver Area in the summer of1943, but efforts to institute it in the real desert training center were refused,and, except for the information given physicians in this area, no real cooperationwas established.
Coccidioidomycosis was picked up from New Jersey to thewestern Pacific in troops who had been in this area. Oneof the most significant reports came from Fort Bragg,N.C., in the following letter from Dr. Theodore J. Abernathy to Dr. Smith, inearly 1944:
Recently, a case of coccidioidomycosis was discovered on thewards of the Station Hospital at Fort Bragg. This patient was suffering from theprimary form of the disease, characterized by a circumscribed pneumonic lesionin which cavitation was demonstrated roentgenographically. A skin test withCoccidioidin, 1-100 dilution, done at the height of the disease, was positive. * * *[Other tests notcompleted.]
Checking back on this patient's army experience it waslearned that he was one of a group of Field Artillery trainees, recruitedlargely from Michigan, Ohio and Illinois, who had spent three months (22 Augustto 24 November) at Camp Iron Mountain, California, participating in desertmaneuvers. Further investigation of 35 additional patients from this same group,now stationed at Fort Bragg and admitted within the past week because of variousmedical and surgical complaints, has disclosed five positive reactors toCoccidioidin (14.2 percent). One patient who gave the strongest positivereaction was admitted with a presumptive diagnosis of rheumatic fever, and thetest was exceedingly valuable in pointing toward the true nature of the disease.
Available information which we have at our disposal isthat Camp Iron Mountain is located in the extreme south-easterly portion ofCalifornia close to the Arizona border. According to the syllabus oncoccidioidomycosis (AAFWFTC), this area is in close proximity to an endemicfocus of the disease in Arizona. Do you have any reports indicating that casesof coccidioidomycosis may have originated in Camp Iron Mountain or in the desertmaneuver area? Have you any information regarding a control program in thiscamp and the results of same, if attempted?
We are considering enlarging the present study to include theskin testing of a large number of men who were at Camp Iron Mountain * * *.
Cases were picked up also at Camp Dix, N.J., in Hawaii, andin the western Pacific in members of the 77th InfantryDivision who had gone through the desert maneuvers. Further testing reported ina later letter from Dr. Abernathy showed that over 15 percent of 555 men fromone field artillery battalion coming from the desert maneuver area reactedpositively to coccidioidin. By 16 March, Dr. Abernathy reported to Colonel
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(later Brigadier General) Bayne-Jones on cavalry units thathad been stationed in the California-Arizona Maneuver Areaat Camp Hyder (halfway between Yuma and Phoenix), Camp Laguna (27 miles north ofYuma), and Camp Pilot Knob. Positive skin reactors inthese groups were as follows: 28.6 percent of 70 men in the 11th Group; 23.8 percent of 736men in the 36th Squadron; and 20.6 percent of 786 men of the 44thSquadron. Plans to examine by roentgenogram the 337 positive reactors dissolvedwhen the three organizations were sent to four different places.
A letter from Maj. (later Lt. Col.) George A. Young, Jr., MC,Consultant, Headquarters, Communications Zone, California-Arizona Maneuver Area,to Dr. Smith is quoted at length as indicating the efforts so many of us madefor months and years to open the ears of the fire-eating trainers to ourmessage.
Your letter of 12 Jan. 44 to Lt. Col. Manjos has beenforwarded to this headquarters for reply. Following my letter to you of 29 July43, we initiated a program for the study of coccidioidomycosis in the DesertTraining Center * * *. Unfortunatelythis headquarters has jurisdiction only over Communications Zoneinstallations and when we attempted to extend the program to the entire desertwe were informed by the Desert Training Center that: "1. Not favorablyconsidered. 2. There is not sufficient data to indicate an urgent need of thiswork and with the present shortage of Medical Officers in DTC it is notconsidered that this diversion of personnel is practical. 3. If research andinvestigation of special problems in DTC are indicated, it should be doneunder the direction of the Surgeon General by especially trained and assignedpersonnel." The foregoing required us to continue our project in anunofficial status and limit our activities to the Communications Zone. Withinthe past month we succeeded in convincing the DTC as to the importance of theproblem of coccidioidomycosis and it will now be possible to more thoroughlyapproach the problem. What factual information we have accumulated from thepresent study was forwarded to the Army Ground Forces, 3 Jan 44 ** *. To this can be added the following statementswhich are considered to be sound, but which are, as yet, unsupported bysufficient factual data:
a. The maneuver area proper, indicated on map ** *, is highlyendemic. Supporting this statement is the fact that a division of Negrotroops was stationed at Camp Clipper for three (3) months withoutexperiencing significant coccidioidal infection; then, beginning three weeksafter they participated in exercises in the maneuver area proper thirty (30)cases of coccidioidomycosis were admitted to one of our hospitals. Thesesoldiers were acutely ill and were admitted with transfer diagnoses such asatypical pneumonia, lobar pneumonia, bronchitis, etc. Obviously many hundreds ofmilder cases are going unrecognized. It would appear most reasonable thatthe cases described by Dr. Abernathy represent troops recently in the formalmaneuver area, and that the maneuver area and not their camp site was theendemic legion. It is my personal belief that a great many soldiers areleaving this area with unrecognized smouldering infections which becomemanifest at a new station. Not every medical installation will be as alertas the Ft. Bragg group and recognize the disease.
b. The entire area between Yuma and Hyder, Arizona isheavily endemic. Over two hundred cases of the disease occurred in troopsstationed at Camp Hyder. These cases were diagnosed by the 32nd EvacuationHospital; but because they were a combat zone unit, we received no data andcould not include them in any official report. * * * [howeverthere is] a more satisfactory liaison now established between the two zones ** *. Incidentally eight (8) nurses of the 32dEvacuation Hospital developed coccidioidomycosis. The hospital was locatedbetween Horn and Hyder, Arizona.
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c. Pomona, Camp Young, Thermal and San Bernardino are areasof very low or no endemicity. This statement is based on the absence ofchangeover's after serial skin tests (3, 6, 9, and 12 weeks) and is supportedby the absence of any proven cases from the areas noted.
d. Supporting the belief that Desert Center, Granite,Coxcomb, and Camp Young are innocuous areas is the experience of the StationHospital SCU 1925 which hospitalized soldiers from the areas mentioned duringthe period 15 July 42 to 15 Feb 43. After receipt of some coccidioidin we requestedfrom you, Capt. Elmer Brock, our radiologist, skin tested in all casesshowing pulmonary pathology-no positive reactions were demonstrated.
At the present time our general hospitals arefunctioning under a 45 day evacuation policy, this has necessitated theevacuation of coccidioidomycosis patients to hospitals outside of oursupervision. In an attempt to centralize these patients, we have establisheda policy wherein all such cases are evacuated to the Camp Haan [Calif.]Station Hospital. Reports from your laboratory are then forwarded to CampHaan. Dr. Rutherford and Mr. Copper from USC visited us frequently in Banningcollecting rodents and plants from the area of Banning airstrip. A recentconversation with Dr. Kessel indicates as yet they have grown nococcidioides. It is Dr. Rutherford's plan to carry out his rodent surveyin all proven endemic areas.
The preceding paragraphs contain the pertinent data andimpressions we have obtained. I feel certain that much of this is unknown to theSurgeon General's Office; however any official communication by us isprecluded [by the disapproval by the Desert Training Center] * * *.
* * * This office will continue tosupervise the program which, however, it is felt will now continue underits own momentum. We have purposely made each hospital and laboratory feel thiswas their program and that all data at this office are available to them. Ibelieve that many will publish articles on the subject. We have requested aninformal summary from each general hospital and the mobile laboratory, a copyof which will be furnished you.
It is my belief that the medico-military aspects ofcoccidioidomycosis in this area are now obvious and appropriate stepsshould soon follow. It would appear wise to consider the transition of thisstudy into State Health channels as it is possible that the presentlaboratory facilities will not always exist * * *.
May I express the deep appreciation we all feel for thegenerous manner in which you have aided us. We regret exceedingly thatthe suggestions included in your letter of July could not be carried outfor the entire desert. I feel that we have finally hacked out some datainstead of obtaining the clean cut results that might have been accomplished.
A plan was projected for continuation of the work ifnecessary by the use of mobile laboratories, but none were to be assigned to theCommunications Zone, as the whole desert training program was being given up andthe area was to be completely evacuated by 1 May 1944.
COCCIDIOIDOMYCOSIS IN PRISONERS OF WAR
In a report dated 4 February 1944, Col. Verne R. Mason, MC,medical consultant to the Ninth Service Command, brought to The Surgeon General'sattention the fact that there was a large number of patients withcoccidioidomycosis among the prisoners of war at Florence, Ariz. He noted, inpart, as follows:
There are 89 patients with tuberculosis in the hospital.Of these, 2 are Japanese, a number are German, and the remainder areItalian. In addition to these patients, there
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are a large number with primary pulmonary coccidioidomycosis.A number of patients have both active tuberculosis and coccidioidomycosis.Some have developed coccidioidomycosis of pulmonary type while in thehospital under treatment for active tuberculosis. A recent survey of 557enlisted men of this SCU [Service Command Unit] was made. Of this number 54percent had a positive coccidioidin test. The percent with positive tests variesdirectly with the length of time at this camp. The effects of co-incidental orcontemporary coccidioidomycosis on the course of active tuberculosis may bestudied well at this station. At present one Italian prisoner has the rapidlyfatal acute disseminating type of coccidioidomycosis with miliary pulmonarylesions and pustular dermal lesions.
By 23 February, Dr. Smith was in Florence, at the request ofthe Preventive Medicine Service of the Surgeon General'sOffice, and, on 3 March 1944, made a report to The Surgeon General throughColonel Bayne-Jones. After careful study of the patients in theStation Hospital at Florence and a review of the many relevant factors, he madethe following comments and recommendations:
Probably two-thirds to three-quarters of new arrivals fromnon-endemic areas can be expected to become infected during a year. Had thisfact been realized prior to the location of the Camp, another choice might havebeen made. However, * * * mypersonal recommendation would be to continue the Camp but to develop a ControlProgram based upon repeated coccidioidin testing, detection of clinicalcoccidioidomycosis and prompt treatment. This is the plan which was developed aspart of the work of the Commission on Epidemiological Survey in the San JoaquinValley and which was expanded and applied by the entire Western Flying TrainingCommand. The plan has been discussed with Lieutenant Colonel Bernadine and hismedical personnel and they will welcome it ** *. The Station Hospital laboratory is alreadyprepared to carry on its part, with sedimentation tests ** * culturing * * * andproper collection of blood specimens * * * incase of diagnostic doubt. Arrangements have been made to send us positivecultures for animal confirmation as well as blood for the serological testing.It is most important that sufficient medical personnel be available so the CampSurgeon can designate one man to be in charge of the Program. It should not takemore than one-third of his time * * *. The Camp Hospital is developing into an importanttuberculosis sanitarium with enthusiastic chest specialists experienced insurvey work * * *.
[It seems not improbable, and because of the climate notillogical] that the Florence Station Hospital is destined to be made thetuberculosis sanitarium for Prisoners-of-war. However, coccidioidomycosis posestwo complicating considerations. First, can people acquire coccidioidomycosiswhen merely staying indoors in the hospital ward? Second, if they should acquirea coccidioidal infection, would it adversely affect their "cure" fortuberculosis?
The decision made shortly thereafter in the Office of TheSurgeon General was announced in a memorandum from theMedicine Division to the Hospital Division, on 24 March 1944, as follows:
A conference was called by Brigadier Generals Bayne-Jones andMorgan for the purpose of considering the removal of the tuberculosis center forprisoners-of-war from the Station Hospital at Florence, Arizona, to anotherlocation. Evidence has been acquired recently which indicates that the incidenceof coccidioidal infection at Florence, Arizona, is high. It has been shown thatpatients in the Station Hospital there have acquired the infection in residence.It was agreed that prisoner-of-war patients with tuberculosis should beprotected from this additional health hazard. Therefore, the conferenceunanimously recommends that the tuberculosis center for prisoners-of-warbe moved from the Florence, Arizona, Station Hospital and located elsewhere.
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In May 1945, the incidence of coccidioidomycosis at CampCooke, Prisoner of War Center (San Luis Obispo County, Calif.), beganto rise, 162 cases occurring. In the subsequent 3 months,investigation by Dr. Smith for the Surgeon General's Office, and by others,determined that these cases were incurred by prisoners working near Shafterin the San Joaquin Valley in one of the subsidiary prisoner-of-war camps.These prisoners and those at Lamont were digging potatoes and working cotton andother crops. Similar conditions obtained at some of the subsidiary camps aroundFlorence. Dr. Smith, consulted from the field, explained thedifficulty and the amount of personnel necessary to set up acoccidioidomycosis-control program among these scattered installations. When itwas pointed out to the commanding officers of the prisoner-of-war camps that therate at Camp Cooke alone was higher than for all the rest of the Army, theprisoners of war were withdrawn from work in the Shafter and Lamont areas.
The war was now drawing to a close and with it the immediateconcern of the Army with this disease of arid regions. The time was approachingwhen we could all "go back to hoeing our own potatoes" and allow thesearch for a living to bring fresh divisions of civilians into the endemic areas-butof their own volition.
On 31 August 1944, Capt. Louis Schneider, MC, radiologist atthe Separation Center, Fort Dix, N.J., wrote Dr. Smith aletter which is a good preamble to the conclusion of the story ofcoccidioidomycosis in World War II. The letter follows.
As you know, routine chest films will be taken on all servicemen and women who will be demobilized through these centers. In the course ofthese examinations, we have come across and will continue to come acrosssoldiers who months ago recovered from a case of Primary Coccidioidomycosis andnow have residual pulmonary lesions which are undoubtedly not active, and thoughthey have not regressed by comparison of serial roentgenograms, the pulmonaryshadows have neither broken down or extended. From my present knowledge itwould appear safe to discharge these individuals, appreciating that theymay therefore go out into any civil employment with little fear of reactivation.Of course it would be wise, it seems to me, to follow these cases with serialchest radiographs at Veterans Hospitals' out-patient departments much aswe do with arrested cases of pulmonary tuberculosis. In this connection, youradvice and comment in regard to the handling and after-handling of such separateeswill be appreciated.
This letter, as concerned with a matter of policy regardingthe separation of Army personnel with roentgenographic evidence ofresidual coccidioidal lesions, was referred by Dr. Smith to Generals Morgan andBayne-Jones of the Office of The Surgeon General, and to Dr. Blake as Presidentof the Board for the investigation of Epidemic Diseases, U.S. Army. In his replyof 6 September 1944 to Captain Schneider, Dr. Smith gave his personal opinion,as follows:
First, may I express great pleasure and congratulate youupon your discernment in your evaluation of the pathogenesis ofcoccidioidal infection. Unfortunately, even in the newly revised edition ofCecil's text the opinion is expressed that many soldiers who acquiredcoccidioidomycosis in the Service will break down with a disseminated infection
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in civilian life. Such an expression is ill founded and verydamaging. As you indicated, even with coccidioidal nummular lesionsremaining, men can be discharged without fear of disseminating coccidioidalinfection. There does remain the very slight possibility of a cavity developing.This complication is so rare, generally developing within a few months afterthe infection, while the nummular lesions may continue so long (many years),that it would be impractical to continue the man in the Service until theroentgenogram is clear. The one safeguard I would recommend is that suggested byyou, serial chest roentgenograms at Veterans Hospitals, say every sixmonths. There should be no question of compensation or pension, as these lesionsare not incapacitating. Particular pains should be taken to reassure these mennot only for their peace of mind but also to keep them out of the hands ofshyster lawyers or even misinformed medical men who * ** may try to make invalids out of these utterlyhealthy veterans. If any specific problems arise, please feel free to writeme. I do feel quite certain that the Fort Dix separatees will be handled wisely.
General Bayne-Jones referred Dr. Smith's letter with itsenclosures to Col. Esmond R. Long, MC, Deputy Chief, Professional Service,Office of The Surgeon General. Colonel Long, visiting the Fort Dix separationcenter, primarily to look over the chest X-ray work, spent some time withCaptain Schneider, who again raised the same question. Colonel Long concurred inthe general opinion that no public health problem was involved and was inclinedto think also that the medical problem would not be serious. "The Army isnot going to discharge men with active coccidioidomycosis, and men with scarredlesions are not likely to break down," He observed that the Army could notinsure followup examinations although each separatee, being informed of hisright to medical care under the Veterans' Administration, might be advised tohave periodic checkups for appropriate conditions, of which coccidioidomycosiswas only one in several.
On that sensible note, the experience of the Army withcoccidioidomycosis was brought to a close. There remains only to summarizestatistics before bringing to its close this historical sketch. During theyears 1942-45, the admission rate per 1,000 troops per year (based on thetotal number of cases reported in the Army in the continental United States andthe strength of the Ninth Service Command) ranged from 0.2 to 2.8 per month,being greater than 1 in 22 months and greater than 2 in 6 months of the span of37 months. The Marines, in the small detachments scattered through the endemicareas, and specifically those reported by Lt. Cdr. E. F. Pfanner, MC, USNR,at Mojave, Calif., and by the U.S. Navy, in some of its inland installations,such as Inyokern, Calif., encountered the disease but in number's insufficientto warrant very active countermeasures.
We have thus again one of the few unequivocally good thingsthat sometimes come out of modern war, more knowledge of a disease process. Inthis instance, a gradual accumulation of knowledge, accelerated by work doneshortly before the war, was further accelerated as a medical problem of localinterest affecting the Army. It has been suggested36thatgeneral interest may continue as the modern habit of travel brings intoendemic
36Jamison, H. W., and Carter, R. A.: RoentgenFindingsin Early Coccidioidomycosis. Radiology 48: 323-332, April 1947.
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regions increasing numbers of people who, like the youngsoldiers negative to coccidioidin, are highly susceptible. However that may be,better understanding has been achieved of one of the diseases that attack thelungs, with the immediate gain of increased clinical competence and with widerimplications for comparative research.
