- Email: [email protected]
Q Fever
630
conclusion is inescapable that, unless many recently upgraded hospitals are to be deliberately downgraded, some of their specialised work will have to be done by doctors who have no further expectation of becoming consultants. Ways have to be found by which it can be done well and willingly, and by which the transit of many hospital registrars into general practice can be made at least tolerable. The need here is for constructive suggestions, and we welcome those put forward by Dr. TALBOT
The
months
longer. In some patients this vague dis. punctuated by a genuine relapse with fever and a return of theoriginal symptoms, and a few have had relapses occasionally for years.4 A tentative diagnosis of Q fever can be confirmed by isolating the organism or by demonstrating the highly specific complement-fixing antibodies which appear in the serum during convalescence. In this country the Virus Reference Laboratory of the Public Health Laboratory Service, examining sera from some ROGERS on p. 641. 700 patients with acute infective respiratory disease, found that about 3% had a significant titre to R. burneti.5 Of the 300 patients clinicallydiagnosed Q Fever as having " atypical or virus pneumonia," there was THOUGH it may be one of the rarer infectious serological evidence of infection with influenza virus diseases, Q fever is attracting world-wide attention, in 16%, with a virus of the psittacosis-ornithosis partly because of its remarkable and varied epidemio- group in 2%, and with R. burileti in 5%; while 11% logy and partly because of the unorthodox character had either cold hsemagglutinins, Streptococcus MG. of the causative organism, Rickettsia burneti. agglutinins,6 or both. Cold and Strep. MG. agglutinins Clinically it has few striking characteristics, and it were rarely observed in association with a positive must be sought among patients with " pyrexia of specific complement-fixation test for influenza, psittaundetermined origin " or with " primary atypical cosis-ornithosis, or R. burneti. It seems, therefore, pneumonia." Generally the illness begins abruptly first that R. burneti is not a common cause of atypical with a particularly severe headache, sometimes pneumonia in Great Britain, and secondly that the accompanied by photophobia. The headache may likelihood of any particular case of atypical pneumonia indeed be so intense that meningitis is suspected, but being one of Q fever is small if the patient has a a spinal tap rarely reveals an increase of cells in the positive cold haemagglutinin or Strep. MG. agglutinin cerebrospinal fluid. There is high fever, and profuse test. sweating as the temperature fluctuates from 103-4°F Cases of Q fever have now been found in Kent, to normal during the course of a day or less. " Burning Devon, Somerset, Gloucestershire, Wiltshire, Denbigheyes," lacrimation, and conjunctivitis may add to shire, and Oxfordshire. Papers in our columns have the patient’s discomfort, but he has none of the upper described the detection of the first cases,7 the clinical respiratory symptoms of influenza or febrile features of the cases,8 and the isolationof R. burneti The illness lasts on the average some catarrh." from one of the patients ; and a few months ago we twelve days, the temperature falling by lysis. Between reviewed the epidemiology of the disease.10 This week the third and sixth days, or thereabouts, there may we communications on the properties of some publish be a little cough,and on careful examination a few R. strains of and on the spread of the burzeti, English fine rales will be heard in the chest; but the signs are disease in one of the outbreaks. The story of how slight in relation to the extent of the lung lesion infection passed from a patient to a ward nurse and revealed by X rays. Pneumonia is present in about three members of the staff of the pathological depart70-80% of patients, including some of those with a. ment at the Royal Cancer Hospital is of interest very mild general illness ; in fact in one large outbecause human-to-human spread of infection is rare break1 radiography was used for discovering cases. in Q fever. Infection of persons performing a necropsy But Q fever is more than an infection of the lung : is perhaps rather a special instance of case-to-case R. bumeti can be recovered from the blood-stream spread which has occurred elsewhere 4 11 but infection during the fever and from the urine during early of ward staff is exceptional, though DEUTSCH and convalescence. and consequently lesions may be an incident in a, PETERSON 12 have lately spread widely. MoESCHLIN and KOSZEWSKIin 50 Californian hospital when recorded three nurses developed Q cases with serologically proven Q fever, reported 9 fever from fourteen to twenty-three days after first with complications (5 thrombophlebitis with pulattending a patient with the disease. The infectiousness monary embolism, 3 epididymitis, 1 encephalitis, and of a minority of cases of Q fever is not fully explained, 1 pancreatitis). All these extrapulmonary complicabut it is possibly related to the severity of the illness, tions appeared after the fourteenth day of illness, to the amount of sputum produced, or to the cleanThe findings when the lung lesion was resolving. liness with which urine is passed. The " source case of WHITTICK,3 who in a fatal case demonstrated at the Royal Cancer Hospital was producing sputum riekettsiae in the lung, spleen, brain, testis, and kidney, and was incontinent of urine at the end of his illness. suggest that the lesions outside the lungs are probably and though DEUTSCH and PETERSON do not say due to the rickettsia itself. This occurrence does much whether their patient was producing sputum he was to modify an impression, gained largely from studies 4. Beck, M. D., Bell, J. A., Shaw, E. W., Huebner, R. J. Publ. of the disease in young and healthy troops, that Q Hlth Rep., Wash. 1949, 64, 41. fever is necessarily benign and trivial. Convalescence 5. See Brit. med. J. 1950, ii. 282. 6. Thomas, L., Mirick, G. S., Curnen, E. C., Ziegler, J. E., Horsfall, is often marked by loss of weight, muscular pains, F. L. jun. Science, 1943, 98, 566. 7. Stoker, M. G. P. Lancet, 1949, i, 178. lassitude, and easy fatiguability which can last three 8. Harman, J. B. Ibid, ii, 1028. "
"
ability
or
is
"
’’
Amer. J. Hyg. 1946, Feinstein, M., Yesner, R., Marks, J. L. 44, 72. 2. Moeschlin, von S., Koszewski, B. J. Schweiz. med. Wschr. 1950, 80, 929. 3. Whittick, J. W. Brit. med. J. 1950, i. 979. 1.
F. O., Marmion, B. P., Stoker, M. G. P. Ibid. 1026. 10. Ibid, 1950, i, 960. 11. Huebner, R. J., cited by Deutsch and Peterson (ref. 12). 12. Deutsch, D. L., Peterson, E. T. J. Amer. med. Ass. 1950. 143. 9. MacCallum, p.
348.
631
evidently very ill. These examples of human-tohuman spread should not distract attention from the fact that most patients with Q fever seem to acquire their infection from animals, either by consuming infected raw cow’s milk 13 or by inhaling dust containing R. burneti.13 Until recently the sources of rickettsiae in the dust were somewhat obscure ; for only tick excreta,14colostrum, and milk 15 had been shown to contain the organism. But the finding of s large numbers of rickettsiae in the placenta of cows 16 and sheep,17 and the isolation of the organism from the faeces and nasopharyngeal secretions of sheep,17 helps to remove this difficulty. DELAY et aP8 in Northern California provided direct proof of the presence of R. burneti in dust when they isolated the organism from air samples collected on a dairy farm and on a sheep ranch, where human cases of Q fever had occurred. Treatment with chloramphenicol orAureomycin’ has given promising results, and a prophylactic vaccine has been prepared from killed and purified rickettsial suspensions grown in the yolk sac of the chick embryo. MEIKLEJOHN and LENNETTE 19 report that in their laboratory, though an unimmunised serologist contracted the disease, there have been no cases among immunised workers-an observation which is possibly significant in view of the notorious infectiousness of R. burneti in the laboratory. Controlled data on the protective effect of the vaccine might be obtained by offering inoculation to workers in industries such as slaughtering, dairying, and meat-packing, where the occupational risk of Q fever may be high.13
Flame Photometry THE growing list of disorders associated with disturbances in the potassium and sodium contents of the body-fluids already includes the oedemas, uraemias, several forms of dehydration, defects in carbohydrate metabolism and in suprarenal function, and many others. Hitherto, investigators in this field have been hampered by the tedious and difficult chemical techniques used for estimating sodium and potassium in blood and urine. But thanks to the recent developments in the physical method of flame photometry these determinations can now be done simply and rapidly, and instead of being essentially research procedures they will soon be part of the routine work of a biochemical laboratory. The flame photometer measures the intensity of light emitted when solutions of certain metallic salts are sprayed into a flame. Twenty years ago LUNDEGÁRDH 20 developed an apparatus in which the spectrum produced in this way was photographed and compared with similar spectra from standard solutions.
In the various types of modern instrulight from the flame falls on a photocell and the spraying and burning conditions are kept
ments 21-23 the
13. Bell, J. A., Beck, M. D., Huebner, R. J. Ibid, 142, 868. 14. Derrick, E. H. J. Hyg., Camb. 1943, 43, 357. 15. Huebner, R. J., Jellison, W. L., Beck, M. D., Parker, R. R., Shepard, C. C. Publ. Hlth Rep., Wash. 1948, 63, 214. 16. Luoto, L., Huebner, R. J. Ibid, 1950, 65, 541. 17. Lennette, E. H. Bact. Rev. 1950, 14, 249. 18. DeLay, P. D., Lennette, E. H., DeOrme, K. B. J. Immunol. 1950, 65, 211. 19. Meiklejohn, G., Lennette, E. H. Amer. J. Hyg. 1950, 52, 54. 20. Lundegårdh, H. G. Die quantitative Spektralanalyse derElemente.
Jena, 1934. 21. Barnes, R. B., Richardson, D., Berry, J. W., Hood, R. L. Industr. engng Chem. (Anal.), 1945, 17, 605. 22. Willebrands, A. F. jun. Rec. Trav. chim. 1950, 69, 799. 23. Domingo, W. R., Klyne, W. Biochem. J. 1949, 45, 400.
so that the current produced gives a direct of the concentration of the metal in solution. Commercial models of the flame photometer are now widely used in the United States, and several British instrument-makers are exploring the possibilities of building them here. Meanwhile, many homemade instruments are already working in British hospitals, and Dr. SPENCER describes one of them in this issue (p. 623). His experience agrees with th4,-of others 24 in showing that for estimations of the alkali metals flame photometry is as reliable as the chemical methods and it is probably more reliable in the hands of all but the most expert technicians. It also saves a great deal of time, for a technician with a photometer can easily do 20 determinations of sodium or potassium in serum in two or three hours, whereas this number of chemical estimations would take a day or more. A single determination can be completed with the flame photometer within a quarter of an hour of the laboratory receiving the blood; so in an emergency the clinician can find out his patient’s serum-sodium or serum-potassium level in time to act on the information. Such rapid analyses are vital in the cases of potassium lack which may arise, for example, during recovery from diabetic also in coma or after diarrhoea and vomiting 25 ; salt from as a result of patients suffering depletion low-sodium diets or mercurial diuretics 26 ; and in cases of uremia.27 Turning to the working details of a photometer, the solution to be analysed (plasma, serum, or urine must first be diluted with water) is blown or sucked into a carefully controlled flame burning coal-gas, acetylene, or butane. The light from the flame is passed either through colour filters, as in colorimeters, or through a spectrometer, to isolate - the light of the wave-length characteristic of the metal being determined. This light then falls on a photosensitive element (a selenium barrier-layer cell or a phototube) and the current is measured, with or without amplification, on a galvanometer. The chief difficulty lies in keeping the spraying and burning conditions constant. Some flame photometers, including Dr. SPENCER’s, add a known amount of some " foreign " element, such as lithium, to the solutions, so that most of the instrumental errors affect the readings from this " internal standard " as well as those from the test solutions, and are therefore cancelled out. The safest method of operation with all instruments, however, is to take readings with a standard solution of about the same strength as the test solution before or after each test. The presence of foreign elements in the solutions tested affects the light. emission of sodium and potassium, and it is necessary to find out for each photometer what effects the foreign constituents of blood and urine have on the results. In some instruments sodium increases the light emission of potassium.23 2s Interference of this kind can easily be corrected by preparing standard solutions of, say, potassium salts containing the interfering elements in the proportions present in normal serum.
constant measure
24. Hald, P. M. J. biol. Chem. 1947, 167, 499. Abul-Fadl, M. A. M. Biochem. J. 1949, 44, 282. 25. Leading article, Lancet, Sept. 9, 1950, p. 369. 26. Schroeder, H. A. J. Amer. med. Ass. 1949, 141, 117. 27. Hoff, H. E., Smith, P. K., Winkler, A. W. J. clin. Invest. 1941, 20, 607. 28. Proehl, E. C., Nelson, W. P. Amer. J. clin. Path. 1950, 20, 806.
conclusion is inescapable that, unless many recently upgraded hospitals are to be deliberately downgraded, some of their specialised work will have to be done by doctors who have no further expectation of becoming consultants. Ways have to be found by which it can be done well and willingly, and by which the transit of many hospital registrars into general practice can be made at least tolerable. The need here is for constructive suggestions, and we welcome those put forward by Dr. TALBOT
The
months
longer. In some patients this vague dis. punctuated by a genuine relapse with fever and a return of theoriginal symptoms, and a few have had relapses occasionally for years.4 A tentative diagnosis of Q fever can be confirmed by isolating the organism or by demonstrating the highly specific complement-fixing antibodies which appear in the serum during convalescence. In this country the Virus Reference Laboratory of the Public Health Laboratory Service, examining sera from some ROGERS on p. 641. 700 patients with acute infective respiratory disease, found that about 3% had a significant titre to R. burneti.5 Of the 300 patients clinicallydiagnosed Q Fever as having " atypical or virus pneumonia," there was THOUGH it may be one of the rarer infectious serological evidence of infection with influenza virus diseases, Q fever is attracting world-wide attention, in 16%, with a virus of the psittacosis-ornithosis partly because of its remarkable and varied epidemio- group in 2%, and with R. burileti in 5%; while 11% logy and partly because of the unorthodox character had either cold hsemagglutinins, Streptococcus MG. of the causative organism, Rickettsia burneti. agglutinins,6 or both. Cold and Strep. MG. agglutinins Clinically it has few striking characteristics, and it were rarely observed in association with a positive must be sought among patients with " pyrexia of specific complement-fixation test for influenza, psittaundetermined origin " or with " primary atypical cosis-ornithosis, or R. burneti. It seems, therefore, pneumonia." Generally the illness begins abruptly first that R. burneti is not a common cause of atypical with a particularly severe headache, sometimes pneumonia in Great Britain, and secondly that the accompanied by photophobia. The headache may likelihood of any particular case of atypical pneumonia indeed be so intense that meningitis is suspected, but being one of Q fever is small if the patient has a a spinal tap rarely reveals an increase of cells in the positive cold haemagglutinin or Strep. MG. agglutinin cerebrospinal fluid. There is high fever, and profuse test. sweating as the temperature fluctuates from 103-4°F Cases of Q fever have now been found in Kent, to normal during the course of a day or less. " Burning Devon, Somerset, Gloucestershire, Wiltshire, Denbigheyes," lacrimation, and conjunctivitis may add to shire, and Oxfordshire. Papers in our columns have the patient’s discomfort, but he has none of the upper described the detection of the first cases,7 the clinical respiratory symptoms of influenza or febrile features of the cases,8 and the isolationof R. burneti The illness lasts on the average some catarrh." from one of the patients ; and a few months ago we twelve days, the temperature falling by lysis. Between reviewed the epidemiology of the disease.10 This week the third and sixth days, or thereabouts, there may we communications on the properties of some publish be a little cough,and on careful examination a few R. strains of and on the spread of the burzeti, English fine rales will be heard in the chest; but the signs are disease in one of the outbreaks. The story of how slight in relation to the extent of the lung lesion infection passed from a patient to a ward nurse and revealed by X rays. Pneumonia is present in about three members of the staff of the pathological depart70-80% of patients, including some of those with a. ment at the Royal Cancer Hospital is of interest very mild general illness ; in fact in one large outbecause human-to-human spread of infection is rare break1 radiography was used for discovering cases. in Q fever. Infection of persons performing a necropsy But Q fever is more than an infection of the lung : is perhaps rather a special instance of case-to-case R. bumeti can be recovered from the blood-stream spread which has occurred elsewhere 4 11 but infection during the fever and from the urine during early of ward staff is exceptional, though DEUTSCH and convalescence. and consequently lesions may be an incident in a, PETERSON 12 have lately spread widely. MoESCHLIN and KOSZEWSKIin 50 Californian hospital when recorded three nurses developed Q cases with serologically proven Q fever, reported 9 fever from fourteen to twenty-three days after first with complications (5 thrombophlebitis with pulattending a patient with the disease. The infectiousness monary embolism, 3 epididymitis, 1 encephalitis, and of a minority of cases of Q fever is not fully explained, 1 pancreatitis). All these extrapulmonary complicabut it is possibly related to the severity of the illness, tions appeared after the fourteenth day of illness, to the amount of sputum produced, or to the cleanThe findings when the lung lesion was resolving. liness with which urine is passed. The " source case of WHITTICK,3 who in a fatal case demonstrated at the Royal Cancer Hospital was producing sputum riekettsiae in the lung, spleen, brain, testis, and kidney, and was incontinent of urine at the end of his illness. suggest that the lesions outside the lungs are probably and though DEUTSCH and PETERSON do not say due to the rickettsia itself. This occurrence does much whether their patient was producing sputum he was to modify an impression, gained largely from studies 4. Beck, M. D., Bell, J. A., Shaw, E. W., Huebner, R. J. Publ. of the disease in young and healthy troops, that Q Hlth Rep., Wash. 1949, 64, 41. fever is necessarily benign and trivial. Convalescence 5. See Brit. med. J. 1950, ii. 282. 6. Thomas, L., Mirick, G. S., Curnen, E. C., Ziegler, J. E., Horsfall, is often marked by loss of weight, muscular pains, F. L. jun. Science, 1943, 98, 566. 7. Stoker, M. G. P. Lancet, 1949, i, 178. lassitude, and easy fatiguability which can last three 8. Harman, J. B. Ibid, ii, 1028. "
"
ability
or
is
"
’’
Amer. J. Hyg. 1946, Feinstein, M., Yesner, R., Marks, J. L. 44, 72. 2. Moeschlin, von S., Koszewski, B. J. Schweiz. med. Wschr. 1950, 80, 929. 3. Whittick, J. W. Brit. med. J. 1950, i. 979. 1.
F. O., Marmion, B. P., Stoker, M. G. P. Ibid. 1026. 10. Ibid, 1950, i, 960. 11. Huebner, R. J., cited by Deutsch and Peterson (ref. 12). 12. Deutsch, D. L., Peterson, E. T. J. Amer. med. Ass. 1950. 143. 9. MacCallum, p.
348.
631
evidently very ill. These examples of human-tohuman spread should not distract attention from the fact that most patients with Q fever seem to acquire their infection from animals, either by consuming infected raw cow’s milk 13 or by inhaling dust containing R. burneti.13 Until recently the sources of rickettsiae in the dust were somewhat obscure ; for only tick excreta,14colostrum, and milk 15 had been shown to contain the organism. But the finding of s large numbers of rickettsiae in the placenta of cows 16 and sheep,17 and the isolation of the organism from the faeces and nasopharyngeal secretions of sheep,17 helps to remove this difficulty. DELAY et aP8 in Northern California provided direct proof of the presence of R. burneti in dust when they isolated the organism from air samples collected on a dairy farm and on a sheep ranch, where human cases of Q fever had occurred. Treatment with chloramphenicol orAureomycin’ has given promising results, and a prophylactic vaccine has been prepared from killed and purified rickettsial suspensions grown in the yolk sac of the chick embryo. MEIKLEJOHN and LENNETTE 19 report that in their laboratory, though an unimmunised serologist contracted the disease, there have been no cases among immunised workers-an observation which is possibly significant in view of the notorious infectiousness of R. burneti in the laboratory. Controlled data on the protective effect of the vaccine might be obtained by offering inoculation to workers in industries such as slaughtering, dairying, and meat-packing, where the occupational risk of Q fever may be high.13
Flame Photometry THE growing list of disorders associated with disturbances in the potassium and sodium contents of the body-fluids already includes the oedemas, uraemias, several forms of dehydration, defects in carbohydrate metabolism and in suprarenal function, and many others. Hitherto, investigators in this field have been hampered by the tedious and difficult chemical techniques used for estimating sodium and potassium in blood and urine. But thanks to the recent developments in the physical method of flame photometry these determinations can now be done simply and rapidly, and instead of being essentially research procedures they will soon be part of the routine work of a biochemical laboratory. The flame photometer measures the intensity of light emitted when solutions of certain metallic salts are sprayed into a flame. Twenty years ago LUNDEGÁRDH 20 developed an apparatus in which the spectrum produced in this way was photographed and compared with similar spectra from standard solutions.
In the various types of modern instrulight from the flame falls on a photocell and the spraying and burning conditions are kept
ments 21-23 the
13. Bell, J. A., Beck, M. D., Huebner, R. J. Ibid, 142, 868. 14. Derrick, E. H. J. Hyg., Camb. 1943, 43, 357. 15. Huebner, R. J., Jellison, W. L., Beck, M. D., Parker, R. R., Shepard, C. C. Publ. Hlth Rep., Wash. 1948, 63, 214. 16. Luoto, L., Huebner, R. J. Ibid, 1950, 65, 541. 17. Lennette, E. H. Bact. Rev. 1950, 14, 249. 18. DeLay, P. D., Lennette, E. H., DeOrme, K. B. J. Immunol. 1950, 65, 211. 19. Meiklejohn, G., Lennette, E. H. Amer. J. Hyg. 1950, 52, 54. 20. Lundegårdh, H. G. Die quantitative Spektralanalyse derElemente.
Jena, 1934. 21. Barnes, R. B., Richardson, D., Berry, J. W., Hood, R. L. Industr. engng Chem. (Anal.), 1945, 17, 605. 22. Willebrands, A. F. jun. Rec. Trav. chim. 1950, 69, 799. 23. Domingo, W. R., Klyne, W. Biochem. J. 1949, 45, 400.
so that the current produced gives a direct of the concentration of the metal in solution. Commercial models of the flame photometer are now widely used in the United States, and several British instrument-makers are exploring the possibilities of building them here. Meanwhile, many homemade instruments are already working in British hospitals, and Dr. SPENCER describes one of them in this issue (p. 623). His experience agrees with th4,-of others 24 in showing that for estimations of the alkali metals flame photometry is as reliable as the chemical methods and it is probably more reliable in the hands of all but the most expert technicians. It also saves a great deal of time, for a technician with a photometer can easily do 20 determinations of sodium or potassium in serum in two or three hours, whereas this number of chemical estimations would take a day or more. A single determination can be completed with the flame photometer within a quarter of an hour of the laboratory receiving the blood; so in an emergency the clinician can find out his patient’s serum-sodium or serum-potassium level in time to act on the information. Such rapid analyses are vital in the cases of potassium lack which may arise, for example, during recovery from diabetic also in coma or after diarrhoea and vomiting 25 ; salt from as a result of patients suffering depletion low-sodium diets or mercurial diuretics 26 ; and in cases of uremia.27 Turning to the working details of a photometer, the solution to be analysed (plasma, serum, or urine must first be diluted with water) is blown or sucked into a carefully controlled flame burning coal-gas, acetylene, or butane. The light from the flame is passed either through colour filters, as in colorimeters, or through a spectrometer, to isolate - the light of the wave-length characteristic of the metal being determined. This light then falls on a photosensitive element (a selenium barrier-layer cell or a phototube) and the current is measured, with or without amplification, on a galvanometer. The chief difficulty lies in keeping the spraying and burning conditions constant. Some flame photometers, including Dr. SPENCER’s, add a known amount of some " foreign " element, such as lithium, to the solutions, so that most of the instrumental errors affect the readings from this " internal standard " as well as those from the test solutions, and are therefore cancelled out. The safest method of operation with all instruments, however, is to take readings with a standard solution of about the same strength as the test solution before or after each test. The presence of foreign elements in the solutions tested affects the light. emission of sodium and potassium, and it is necessary to find out for each photometer what effects the foreign constituents of blood and urine have on the results. In some instruments sodium increases the light emission of potassium.23 2s Interference of this kind can easily be corrected by preparing standard solutions of, say, potassium salts containing the interfering elements in the proportions present in normal serum.
constant measure
24. Hald, P. M. J. biol. Chem. 1947, 167, 499. Abul-Fadl, M. A. M. Biochem. J. 1949, 44, 282. 25. Leading article, Lancet, Sept. 9, 1950, p. 369. 26. Schroeder, H. A. J. Amer. med. Ass. 1949, 141, 117. 27. Hoff, H. E., Smith, P. K., Winkler, A. W. J. clin. Invest. 1941, 20, 607. 28. Proehl, E. C., Nelson, W. P. Amer. J. clin. Path. 1950, 20, 806.