U.S. flag

An official website of the United States government

Skip to main content
Return to topReturn to top

Contents

CHAPTER V

Q Fever

Charles A. Ragan, Jr., M.D.

OCCURRENCE

Q fever first appeared among Allied troops in 1944 and 1945when several sharp outbreaks occurred in the Mediterranean (formerly NorthAfrican) Theater of Operations, U.S. Army.1That it was not identified immediately was doubtless related to the fact thatthis rickettsial disease had first been described in 1937,2and that, with the exception of laboratory infections,3the disease had been reported only from Queensland, Australia, as occurringnaturally in human beings. The author was present as Chief, Medical Service,15th Field Hospital in Italy, when some of the first military patients wereseen, and it must be confessed that there was no realization at that time thatan unusual situation was developing. In retrospect, it is of interest to reflectupon the interplay of serendipity, error (a single positive Weil-Felixreaction), and the presence of Maj. Frederick C. Robbins, MC, in Naples that ledto the realization that we were dealing, not with common primary atypicalpneumonia, but with Q fever, appearing naturally in a locality far distant fromQueensland. Subsequently, the disease was recognized in southern Italy, Greece,and Panama. Since World War II, Q fever has been recognized in California.4

Apennines outbreaks-The15th Field Hospital was set up in December 1944 as a three-platoon unitacting as a medical evacuation unit behind the U.S. II Corps in the Apenninesnorth of Florence. The hospital was studying the feasibility of early return toduty of patients with various psychosomatic problems related to combat fatigue.In addition to such patients, there were others with trenchfoot, infectioushepatitis, and primary atypical pneumonia.

1Unless otherwise noted, the material presented in this chapter was taken mainly from a series of articles which appeared in the American Journal of Hygiene, volume 44, July 1946, pp. 1-182.
2(1) Derrick, E. H.: "Q" Fever, A New Fever Entity; Clinical Features, Diagnosis and Laboratory Investigation. M.J. Australia 2: 281-299, 21 Aug. 1937. (2) Burnet, F. M., and Freeman, M.: Experimental Studies on the Virus of "Q" Fever. M.J. Australia 2: 299-305, 21 Aug. 1937.
3(1) Cox, H. R.: A Filter-Passing Infectious Agent Isolated From Ticks. III. Description of Organism and Cultivation Experiments. Pub. Health Rep. 53: 2270-2276, 30 Dec. 1938. (2) Dyer, R. E.: A Filter-Passing Infectious Agent Isolated From Ticks. IV. Human Infection. Pub. Health Rep. 53: 2277-2282, 30 Dec. 1938. (3) Hornibrook, J. W., and Nelson, K. R.: An Institutional Outbreak of Pneumonitis. I. Epidemiological and Clinical Studies. Pub. Health Rep. 55: 1936-1944, 25 Oct. 1940. (4) Dyer, R. E., Topping, N. H., and Bengtson, I. A.: An Institutional Outbreak of Pneumonitis. II. Isolation and Identification of Causative Agent. Pub. Health Rep. 55: 1945-1954, 25 Oct. 1940. (5) Lillie, R. D., Perrin, T. L., and Armstrong, C.: An Institutional Outbreak of Pneumonitis. III. Histopathology in Man and Rhesus Monkeys in the Pneumonitis Due To the Virus of "Q" Fever. Pub. Health Rep. 56: 149-155, 24 Jan. 1941.
4Clark, W. H., Lennette, E. H., and Meiklejohn, G.: Q Fever in California. III. Aureomycin in the Therapy of Q fever. A.M.A. Arch. Int. Med. 87: 204-217, February 1951.


104

Radiological facilities under the direction of Capt. Stanley M. Wyman, MC,were excellent.

In late February 1945, an officer from Headquarters Company, 339th Infantry,was admitted with high fever and general malaise without localizing symptoms, apicture suggesting the preicteric phase of infectious hepatitis. A roentgenogramof the chest at admission was interpreted as normal. A macular erythematous rashappeared transiently, and typhus was then considered in differential diagnosis,because several of the medical officers in the 15th Field Hospital had had dutyin North Africa and had seen the disease in native populations. For this reason,a Weil-Felix test was done and was reported as positive in a significantly hightiter from the 2d Medical Laboratory in Florence. Shortly thereafter, a secondroentgenogram of the chest revealed an area of pneumonic consolidation, and apresumptive diagnosis of primary atypical pneumonia was made.

Within the next month, 32 additional members of Headquarters Company, 339thInfantry, were admitted with febrile illness, and 20 more patients from thisunit were seen in other Fifth U.S. Army hospitals with similar symptoms. MajorRobbins of the 15th Medical General Laboratory in Naples came to investigate thereported positive Weil-Felix reaction. From the blood of one of the patientswith pneumonitis, a strain of rickettsia characterized as Rickettsia burneti wasisolated by inoculation into guinea pigs and subsequent transfer to chick embryoyolk sac. This was established as the Henzerling strain. Sera were obtained from28 patients during acute illness and convalescence, and convalescent sampleswere obtained from 25 other patients. Complement-fixing antibodies to theHenzerling strain were found in the sera of all 53 patients.

A second outbreak, originating in the same vicinity, was observed in April1945 in the 3d Battalion, 362d Infantry, involving 267 patients of whom 80 werepersonally observed in the 15th Field Hospital. Sera of the acute disease andconvalescence were obtained from 29 unselected cases, and a rising titer ofcomplement-fixing antibodies to the Henzerling strain was demonstrated. ThePaige strain of R. burneti was isolated from one patient in this group.In this epidemic, 70 percent of the patients not personally observed werereported as having atypical pneumonia or pneumonitis, and the remainder haddiagnoses of fever of undetermined origin, infectious hepatitis withoutjaundice, or upper respiratory infection. Occasionally, no final diagnosis wasmade.

In a survey carried out by Major Robbins, Lt. Col. Ross L.Gauld, MC, and Capt. (later Maj.) Frank B. Warner, MC, several localities appearto be epidemiologically implicated in the high incidence of disease seen inthese two outbreaks. Insects in the presumed areas of infection were numerousbut no specific rickettsial vectors were discovered and the spraying of DDT(dichlorodiphenyltrichloroethane) did not modify the pattern of the outbreak inthe 339th Infantry. An incubation period varying from 14 to


105

26 days, with a peak at 19 to 20 days, was suggested by this epidemic. Nocases developed in medical personnel caring for these patients. It was notedthat the implicated areas were dusty, but no attempt was made to recover thereckettsia from dust. Rickettsia was successfully recovered from dust inCalifornia by DeLay, Lennette, and DeOme in 1950.5High complement-fixing antibody titers to the Henzerling strain were found in agroup of civilians from the epidemic area. Several other outbreaks, which weresimilar in their clinical and epidemiological features but not provedserologically, occurred in small units in northern Italy and Corsica. Alloutbreaks seemed to be related to dusty habitations.

Laboratory outbreaks-In June, July, andAugust, 1945, a laboratory outbreak of 20 cases developed in the 15th MedicalGeneral Laboratory in Naples. This epidemic was well documented by Major Robbinsand was shown to have originated in the room of the laboratory where theHenzerling and Paige strains were being studied in guinea pigs and embryonatehens' eggs. The Seale strain of R. burneti was isolated in this epidemic,and rickettsiae were isolated from 16 of the 20 patients as early as the secondday of disease and as late as the eighth. Complement-fixing antibodies to theHenzerling strain of rickettsia were absent in sera taken before the 7th to the13th day of disease but were present with later specimens. The peak of theantibody response was reached on about the 21st day with a tendency to diminishafter the 30th day. The disease contracted in the laboratory appeared to besomewhat more severe than that seen in the field, possibly owing to a greaterinitial exposure to the infectious agent; however, four patients, proved to beharboring rickettsia and sick with fever and malaise, developed noroentgenologic evidence of pneumonia.

Outbreaks originating in Greece-Duringthe outbreaks north of Florence, it was learned that an epidemic of 40 cases ofpneumonitis had appeared in one company of a battalion of British paratrooperswho had come to Rome, Italy, from Athens, Greece, in January 1945. The outbreakappeared to have developed in Athens, and the men recalled exposure to dust inan abandoned silk mill used as a bivouac. Dr. J. Caminop?tros of the PasteurInstitute in Athens had obtained from the blood of patients with "Balkangrippe" an agent producing a transmissible febrile disease in guinea pigs.Guinea pig blood was sent by him to the Commission on Acute RespiratoryDiseases, Army Epidemiological Board (Board for the Investigation and Control ofInfluenza and Other Epidemic Diseases in the Army), and from this, a rickettsiastrain similar to R. burneti was isolated at the Commission laboratoriesat Fort Bragg, N.C. A laboratory outbreak caused by the "Balkangrippe" strain of Q fever occurred in the personnel in this laboratorybefore the rickettsia had been definitely characterized from the material sentfrom Greece. As was so often the case with these epidemics of

5DeLay, P. D., Lennette, E. H., and DeOme, K. B.: Q Fever in California. II. The Recovery of Coxiella Burneti from Naturally-Infected Air-Borne Dust. J. Immunol. 65: 211-220, August 1950.


106

Q fever, the diagnosis was made in retrospect. Convalescentserum obtained from 35 of the British paratroopers who had been sick inAthens and Rome and sera from 43 well soldiers of the same battalion weretested for agglutinating antibodies to the "Balkan grippe" strain atFort Bragg. Significant elevations were found in 29 of the 35 recovered cases,while only 9 of 43 men who had not been ill showed a high titer. Presumably,therefore, the epidemic in British paratroopers represented an infection withthe "Balkan grippe" strain contracted in Athens.

Outbreak in Zone of Interior-An outbreakof Q fever was observed at Camp Patrick Henry, Va., in May and June 1945, afterapproximately 7,500 troops returning from southern Italy had disembarked. Thedisease was apparently confined to five squadrons of an air force group. Carefulcase finding in one squadron revealed 143 patients-anattack rate of 38 percent. Agglutinating antibodies to the "Balkangrippe" strain of R. burnetti were found, as werecomplement-fixing antibodies to the Australian strain, but no organism wasisolated. The outbreak seemed to be related to a particular bivouac area, atGrottaglie Air Base near Taranto in southern Italy. Again, no cases developed inmedical personnel caring for these patients.

Other outbreaks-A singlecase of pneumonia was studied in Panama from which a strain of rickettsiasimilar to R. burneti was isolated. The British Army in 1944 hadobserved in the Mediterranean area several sharply localized epidemics of"atypical pneumonia" characterized by a high attack rate-upto 50 percent of a unit. These may have represented Q fever, but noserological proof for this was obtained.

CLINICAL FEATURES

Mode of onset-In northern Italy,the disease was characteristically sudden in onset and the exact hour wasfrequently known. At Camp Patrick Henry, in contrast, 70 percent of the patientsnoted a gradual onset. These, however, represented the milder cases discoveredby careful case-finding studies and would not have been observed in theApennines epidemic in which only patients with complaints sufficient to requirehospitalization were seen. The early symptoms were nonspecific-chilliness,sweats, general malaise, weakness, fatigue, muscular aches, frontal headache,and anorexia. Pain in the chest when present was variable in intensity, rangingfrom a vague to a definitely pleuritic character.

Symptoms.-Although theonset was usually sudden, it was seldom severe enough to cause prostration, andthe patient often continued duty for 12 to 72 hours. The nonspecific symptomspersisted and became more pronounced with the ensuing rise in temperature. Frankrigor was seldom experienced. Frontal headache was common and severe, as in manyrickettsial diseases, and a majority of the patients complained of retro-orbitalpain aggravated by coughing. Anorexia was the only common gastrointestinalsymptom. A moderately dry cough frequently developed on the fifth or sixth daybut was


107

not an outstanding feature. Approximately 20 percent of the patients who werecarefully observed raised small amounts of blood-streaked sputum. Vague pain inthe chest of the type described at the onset persisted, but true pleuritic painwas not common and was rarely severe, responding to aspirin and codeine therapy.

Physical findings-Temperature onadmission ranged between 101? and 105? F. The curve was irregular,extremely sensitive in a transient fashion to salicylates, and persisted from 4to 15 days. It returned to normal by lysis with an occasional crisis. Slightrelative bradycardia, normal respiratory rate, and absence of cyanosis anddyspnea were usual. A cutaneous rash was seen only in the first patient.Physical findings in the chest were normal or only minimally altered. Crepitantrales and slight diminution of breath sounds or dullness were occasionallynoted, after the roentgenogram called attention to abnormalities. Coryza andpharyngitis were not encountered although vesicles on the pharyngeal mucuousmembrane were noted in the epidemic in British paratroopers. Splenomegaly wasrare save in the British paratroopers who also had generalized glandularenlargement. Herpes simplex was not observed. Nuchal rigidity of moderateintensity was seen occasionally, but in six patients, lumbar punctures yieldednormal spinal fluid. Guinea pigs inoculated with one of these fluids obtainedfrom a patient in the Apennines outbreak had a transmissible disease, butserological proof for its rickettsial origin, that is, cross-immunity, was notobtained.

Roentgenological findings-The pneumonicinfiltration as seen in roentgenograms was characteristic. Its incidence in allthe outbreaks was not determined, but 80 percent of the proved cases in theNaples laboratory outbreak and 90 percent of those at Camp Patrick Henry showedsuch infiltration. The shadows were homogeneous, of a ground glass appearanceand patchy in distribution, involving only a small portion of a lobe.Atelectasis with shift of an interlobar septum was frequently seen. In Italy, inmost instances, lesions of a single lobe were observed, but occasionally, twolobes were affected. At Camp Patrick Henry, 60 percent of the patients hadmultilobar involvement. Lower lobe involvement predominated. There was nocorrelation between the extent of involvement demonstrated by roentgenogram andthe severity of the disease. The roentgenogram of the chest on admission wasfrequently clear, with shadows appearing on the third or fourth, andoccasionally as late as the sixth, day of the disease. Shadows consistent withsmall amounts of pleural fluid were seen in approximately 10 percent of thepatients. The roentgenographic changes tended to be persistent and, frequently,were still present when the patient was discharged after an average stay of 22days in the hospital. Resolution occurred by a gradual clearing of the involvedarea.

Course and convalescence-Withdefervescence, the symptoms rapidly subsided leaving only weakness, which variedwith the severity of the disease. The duration of asthenia ranged from a day to3 weeks. Loss in weight


108

commensurate with a febrile illness associated with anorexiawas usually observed. No deaths, no recurrences, and only one possiblecomplication were seen in military personnel. The complication was a severeesophagitis in one patient in the Naples laboratory outbreak. The great majorityof patients returned promptly to full duty.

Laboratory findings-Increase in numbersof leukocytes, polymorphonuclear leukocytosis, and anemia were not observed. Theurine was normal except for occasional mild albuminuria at the height of fever.The erythrocyte sedimentation rate was moderately rapid during the acute phaseof illness and became normal promptly after recovery. Blood cultures weresterile; enteric agglutinations, Proteus OX-19, OX-2, and OX-Kagglutination (save in the original Apennines patient), coccidioidin skin tests,and throat cultures were negative. Cold agglutinins, antibodies to influenza Aand B, treatment with the sulfonamides or penicillin were noted.

Treatment.-Treatment was symptomatic,and no beneficial effects of treatment with the sulfonamides or penicillin werenoted.

EPIDEMIOLOGY

The Henzerling strain isolated in Italy, the "Balkan grippe" strainfrom Greece, and the strains isolated in the laboratory outbreak at Fort Braggand in Panama were similar in immunological specificity (complete reciprocalcross-immunity) to the rickettsia isolated by Dyer6(the American strain) although there were great variations in the sensitivity ofthe antigens. Cross-immunity between the Australian7and American strains had previously been demonstrated. It therefore seemsreasonable to assume that the rickettsial disease seen in the Mediterranean areaand in Panama characterized by pneumonitis was Q fever. The relationship of Qfever to the usual form of primary atypical pneumonia was investigatedserologically, and it was found to be close in endemic areas such as Caserta,Italy, but not in nonendemic areas such as the Eastern United States.

Mode of transmission-Inthe original cases from Australia, pneumonitis was not mentioned. The disease,there, is tickborne to cattle with a reservoir in bandicoots. The infection inman is aberrant, and the Australian workers postulated that the inhalation ofdried tick feces present on the hides of cattle was the route of infection inhuman disease. Pneumonitis was first recognized in the laboratory epidemic atthe National Institute of Health, U.S. Public Health Service,8and in retrospect, it appears that this was probably a dustborne rickettsialinfection. No insect vectors were implicated in the Italian or Greek disease,but dusty habitations were noted. Retrospectively, in view of the isolation ofrickettsiae from dust in California,9 it

6See footnote 3, (2), p. 103.
7See footnote 2 (2), p. 103.
8See footnote 3 (3), p. 103.
9See footnote 5, p. 105.


109

seems fair to assume that pneumonic Q fever may represent an infection inwhich the pulmonary infiltrate represents the primary lesion, as does the escharin fi?vre boutonneuse and rickettsialpox.

Military significance-The militaryimplications of this disease can be far-reaching. It occurs in sharp outbreaksand, although rarely fatal, can completely incapacitate an entire unit forcombat. A satisfactory form of prophylaxis was not at hand during the war years.Since World War II, it has been shown that oxytetracycline (Terramycin) andchlortetracycline (Aureomycin) are effective in the treatment of Q fever.10The avoidance of dusty bivouacs in habitations where sheep, goats, or cattlehave been kept may help, and disturbing of such dust by vigorous proceduresshould particularly be avoided.

10(1) Stokes, M. G. P.: Q Fever in Britain. Brit. M. Bull. 9: 231-233, 1953. (2) See footnote 4, p. 103.

RETURN TO TABLE OF CONTENTS