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ANTIBIOTIC THERAPY OF TUBERCULOSIS OF THE FEMALE GENITALIA
1165
ORIGINAL ARTICLES
The rash was usually fully developed in twenty-four hours. Its total duration was in most of my cases fortyeight hours, but in some it had already disappeared in twenty-four hours ; in a few others it lasted up to seventytwo hours. It did not appear to itch ; it was not followed by
desquamation babies.
Immunity The fact that roseola infantum rarely occurs after the age of 3 years suggests that by that time nearly all children have become immune to it, but, since only a minority of children suffer from a typical attack, it appears that by the age of 3 years many have become immune through a modified illness, either without a rash or with a very sparse or fleeting one. On the other hand Wesselhoeft (1951) suggests that roseola infantum might occur in older children and adults without a rash or with a nocturnal rash only. This would put roseola infantum in the exceptional position of being an exanthematic disease occurring in one age-group usually with a rash and in the rest usually without a rash or with a nocturnal rash only, which seems to me unlikely.
Diagnosis In the presence of an otherwise unexplained persistent in a child. of the most susceptible age-group, with enlarged lymph-glands at the back of head or neck, the diagnosis of roseola infantum should be considered among other causes of pyrexia of unknown origin. A well-marked leucopenia with relative lymphocytosis would support the diagnosis. Once the rash has appeared, mainly rubella, measles, and drug rashes have to be considered in the differential diagnosis. Though the rash of roseola infantum is very similar to the rash of german measles or very mild measles it does not affect the face or only very slightly. In roseola infantum catarrhal symptoms are absent or at the most very mild ; there are no Koplik’s spots. The most important characteristic of roseola infantum is that the rash appears when the child is beginning to recover, whereas in rubella the pyrexia and the rash coincide, and in measles the rash appears while the illness is reaching its climax.
pyrexia possibly
Summary Roseola infantum is
a
occurring nearly exclusively of it
M.D.
were
seen
common infective disease, in the first 3 years of life ;
in twelve years of
general
practice.
Complications reported
are
The treatment is
very rare ;
Strasbourg
From the Maternity Hospital, Hadera, Israel
Cases of roseola infantum without rash have been by other observers during epidemics in homes for
cases
I. HALBRECHT
pigmentation.
or
?011
50
ANTIBIOTIC THERAPY OF TUBERCULOSIS OF THE FEMALE GENITALIA
no
fatal
cases
have been
symptomatic.
ALMOST five years have
elapsed since our first results streptomycin treatment of 12 cases of latent female genital tuberculosis were published (Halbrecht 1951). of
more cases of tuberculosis of the female genitalia in all its stages and have followed up some of them for more than five years since the start of antibiotic treatment. Almost all of these patients sought our help not because of genital tuberculosis, of which they were hardly, if at all, aware, but because of sterility. Thus, the assessment of any treatment of female genital tuberculosis must take into account not only its ability to cure the tuberculosis but also its effect on the sterility, which is the main complication of the tuberculosis.
We’ have since treated 62
Diagnosis It is generally agreed that in the first stages of tuberculosis the fallopian tubes alone are involved, and that endometrial tuberculosis represents a later stage, the tuberculosis spreading slowly but continuously by contact from the endosalpinx to the endometrium (Sutherland 1943, Sharman 1944, Halbrecht 1946, Berblinger 1946, Liljedahl and Ryden 1950, Schockaert 1951). It is therefore obvious that, in female genital tuberculosis, the earlier the antibiotic treatment is instituted the more likely it is to be successful, especially so far as sterility is concerned. For this reason we tried to diagnose the tuberculosis, which is asymptomatic in more than 90% of cases, by culture of menstrual and intermenstrual discharges. By this method it is possible to diagnose genital tuberculosis in its early, pre-endometrial, stage in a considerable number of cases. Material
We treated with streptomycin and p-aminosalicylic acid (P.A.S.) 74 cases of female genital tuberculosis, of which 21 were discovered in the tubal stage and 49 in the endometrial stage, and 4 were exudative cases with more or less large tumours in the adnexa (table i). Methods
patients were treated by daily injections of streptomycin 1 g. alone. Each of them received 45 g. The 62 other patients received a combined treatment of streptomycin 1 g. thrice a week to a total of 45-50 g. and P.A.S. 12 g. daily to a total of 800-900 g. Our first 12
BIBLIOGRAPHY
Banks, H. S. (1949) Common Infectious Diseases. London. Barenberg, L. H., Greenspan, L. (1939) Amer. J. Dis. Child. 58, 983. Berenberg, W., Wright, S., Janeway, C. A. (1949) New Engl. J. Med. 241, 253. B. B. jun. (1941) N.Y. St. J. med. 41, 1854. British Medical Journal (1950) ii, 876. Clemens, H. H. (1945) J. Pediat. 26, 66. Conte, A. N., Uzmann, J. W., Ware, G. W. (1944) Arch. Pediat.
Breese,
61, 559.
Craddock, D. (1953)
An Introduction to General
Practice, London ;
p. 480.
— (1955) Brit. med. J. i, 1219. Cushing, H. B. (1927) Canad. med. Ass. J. 17, 905. Cutts, M. (1938) Ann. intern. Med. 11, 1752. Dickey, L. B. (1945) Stanf. med. Bull. 3, 37. Faber, H. K., Dickey, L. B. (1927) Arch. Pediat. 44, 491. Farber, S. (1938) New Engl. J. Med. 219, 836. Glanzmann, E. (1924) Schweiz med. Wschr. 54, 589. (1934) In Handbuch innerer Medizin. Edited by G. von Bergmann and R. Staehelin. 3rd ed., Berlin; vol. I, p. 420. Greenthal, R. M. (1922) Amer. J. Dis. Child. 23, 63. Harries. E. H. R., Mitman, M. (1947) Clinical Practice in Infectious Disease. Edinburgh. Heiman, H. (1925) Arch. Pediat. 42, 447. —
Hynes, M. (1940) Lancet, ii, 679. Jackson, D. C. (1949) Med. J. Aust. ii, 52. James, U., Freier, A. (1949) Arch. Dis. Childh. 24, 54. Jennings, R. E. (1940) J. med. Soc. N.J. 37, 577. Kempe, C. H., Shaw, E. B., Jackson, J. R., Silver, H. K. (1950) J. Pediat. 37, 561. Levy, D. J. (1921) J. Amer. med. Ass. 77, 1785. McQuitty, E. L. (1955) Brit. med. J. i, 1005. Park, J. H. jun., Michael, J. C. (1922) Amer. J. Dis. Child. 23, 63. Rosenblum, J. (1945) Ibid, 69, 234. Ruh, H. O., Garvin, J. A. (1923) Arch. Pediat. 40, 151. Schlesinger, B. (1937) Brit. med. J. i, 298. Veeder, B. S., Hempelmann, T. C. (1921) J. Amer. med. Ass. 77, 1787.
Wallfield, M. J. (1934) J. Pediat. 5, 800. Wesselhoeft, C. (1951) In Banks, H. S. Modern Practice in Infectious Fevers. London ; vol II. Westcott, T. S. (1921) Amer. J. med. Sci. 162, 367. Yoshina, T. (1942) Hawaii med. J. 1, 235. Zahorsky, J. (1910) Pediat. 22, 60. (1925) Arch. Pediat. 42, 610. (1940) Ibid, 57, 405. (1947) Ibid, 64, 579. (1948) In Brennemann Practice of Pædiatrics. Hagerstown, Md.; vol. II, chapter 21. —
—
—
—
1166
ORIGINAL ARTICLES
TABLE I-CLASSIFICATION OF CASES BY METHOD OF DIAGNOSIS
discharges, whereas endometrial biopsy repeatedly negative after the treatment. In 3 of the 8 cases in which endometrial tuberculosis recurred the first endometrial biopsy after treatment was negative, and only the second, done six months later, showed endometrial tuberculosis. Long before the posi. tive endometrial biopsy, cultures of menstrual discharges were positive for tuberculosis in these 3 cases. It therefore seems that antibiotic treatment is more effective in curing intermenstrual was
11 patients in whom this first course of antibiotic treatment was unsuccessful received a second course of treatment consisting of streptomycin 60-75 g. and P.A.S. 1200 g. In 6 cases the streptomycin was discontinued before 30 g. had been given, because vestibular symptoms ,
appeared. cases
discharges. In 7 of the 21 cases of isolated tubal tuberculosis positive cultures of the genital discharges showed a TABLE
IV-RESULTS
OF
ANTIBIOTIC
of tuberculosis within two and the start of the treatment. recurrence
Results
Only 68 of the 74 patients received the full treatment of 45 g., which is the minimum needed to cure latent tuberculosis of the female genitalia. Nevertheless I here results the report (table 11) obtained, in all 74 cases, TABLE II-RESULTS AND FOLLOW-UP
including the 6 in which only about 30 g. of streptomycin was given, because I have been impressed by the lasting successful results in some patients with even this small amount of streptomycin. In 48 of the 74 patients, treated with streptomycin alone or in combination with P.A.S., no signs of genital tuberculosis could be discovered from one to six years after the treatment. Of these 48 patients 7 were under continuous observation for more than five years after the treatment, 11 for more than four years, 8 for more than three years, 11 for than two years, 8 for more than a year, and 3 for year. 3 of the 6 patients who did not receive more than 30 g. of streptomycin were free from any signs of genital tuberculosis for more than three years, whereas the 3 others showed a recurrence of tuberculosis before the end of the second year after the treatment. Endometrial Tuberculosis (table 111) Tuberculosis recurred in 16 of 49 patients who had endometrial tuberculosis before the treatment. In only 8 of these was the recurrence endometrial ; in the other 8 it was tubal, found by positive culture of menstrual and
TREATMENT
IN
TUBAL
TUBERCULOSIS
in which endometrial
biopsy had revealed endometrial tuberculosis, biopsy was repeated at sixmonth intervals after the treatment. In cases in which cultures of menstrual discharges had been positive, cultures were repeated every month during the first year and every two or three months in the years following the treatment. In
endometrial than tubal tuberculosis. Tubal Tuberculosis (table m) The only means of diagnosing female genital tuberculosis in the tubal stage, before involvement of the endometrium, is culture of menstrual and intermenstrual
a
half years of
Exudative Tuberculosis In 4 cases bimanual genital examination revealed a tumour of the adnexa which was clinically thought to be tuberculous. The diagnosis was confirmed by positive culture of the menstrual discharges. Each of these 4 patients received 60-75 g. of streptomycin and 1200 g. of P.A.S. In 2 cases the tumour disappeared completely, and in the 2 others it diminished but did not disappear. In 3 of the 4 cases culture of the menstrual discharges became positive from six to eighteen months after the treatment. Effect of Antibiotic Treatrnent on Sterility caused by Genital Tuberculosis 7 ectopic and 5 intra-uterine pregnancies followed the antibiotic treatment of genital tuberculosis in the 74 patients. They were distributed as follows : 5 ectopic and 3 intra-uterine pregnancies occurred in 7 patients with isolated tubal tuberculosis. The 3 intra-uterine TABLE
V-RESULTSr OF SECOND COURSE OF ANTIBIOTIC TREATMENT
more
a
TABLE
III-RESULTS
OF
ANTIBIOTIC
TREATMENT
ENDOMETRIAL TUBERCULOSIS
IN
went to their end, full-term healthy babies being born. 2 ectopic and 2 intra-uterine pregnancies occurred in 4 patients with -endometrial tuberculosis who had been completely cured by the antibiotic treatment. The 2 intrauterine pcega’amcies -ended in miscarriages in the third and fourth months.
pregnancies
Histological -examination of the tubes in the 7 ectopic pregnancies revealed the persistence of tuberculosis in the walls of the tubes in 1 case and no tuberculosis in the others. Histological examination of curettage material in the 2 cases of miscarriage did not reveal any tuberculosis. 3 ectopic pregnancies occurred immediately after the antibiotic treatment, and the other 4 one or two years after the treatment. Both full-term pregnancies in the patients with healed tubal tuberculosis and both miscarriages in the patients with healed endometrial tuberculosis occurred in the second year after the treatment.
1167
ORIGINAL ARTICLES
CQ1trse 11 of the 26
of Treatment (table v) patients in whom the first series of streptomycin injections did not cure the genital tuberculosis received a second course, which consisted of streptomycin 60 g. and P.A.S. 1200 g. In 5 of these patients the second
tuberculosis recurred within a year from the start of the second course. The 6 other patients are free from tuberculosis from two to four years after the second course, but none of them has
yet conceived.
Q FEVER IN NAKURU, KENYA A. L. CRADDOCK O.B.E., M.B. Lond. GENERAL
JAMES GEAR M.B. Witw’srand, D.P.H., D.T.M. & DEPUTY
Discussion
Xo treatment of female genital tuberculosis can be properly assessed except by comparing its results with the incidence of spontaneous healing of this disease and the occurrence of pregnancies in untreated cases. Spontaneous healing of female genital tuberculosis is very rare but undoubtedly takes place. In 6 of 90 cases of untreated endometrial tuberculosis and in 1 case of tubal tuberculosis spontaneous healing could be assumed on the basis of repeated negative endometrial biopsies and a great number of negative cultures of the menstrual discharges made repeatedly during at least from two to five years after the diagnosis of genital tuberculosis had been established by a positive endometrial biopsy or by positive cultures of the genital discharges. No patient with apparently healed endometrial tuberculosis conceived, whereas the patient with healed tubal tuberculosis conceived and was successfully delivered. Thus it seems that spontaneous healing of endometrial tuberculosis does not improve the chances of pregnancy in these patients. On the other hand, in cases in which spontaneous healing starts in the earliest, or tubal, stage, when functional restitutio ad integrum of the tubes is still possible, pregnancy may take place.
PRACTITIONER, NAKURU
H., Dip. Bact.
DIRECTOR, SOUTH AFRICAN INSTITUTE RESEARCH, JOHANNESBURG
FOR MEDICAL
SooN after arrival in Nakuru three years ago, one of us (A. L. C.) was struck by the frequency of an acute febrile illness with pneumonic features, which was usually regarded as virus pneumonia. It strongly resembled Q fever, and the help of the other (J. H. S. G.) was enlisted to confirm its cause. Tests soon showed that many cases were in fact infections with Rickettsia burneti, and there is no doubt that this disease is endemic in the locality. Nakuru itself is a large market town a hundred miles north-west of Nairobi, surrounded by an extensive dairyfarming area occupying the floor and slopes of the Rift Valley. Cattle are a well-recognised source of infection (Harvey et al. 1951, Marmion et al. 1953).. Q fever among Europeans in Nakuru is as a rule easily recognisable. The onset is sudden, and the characteristic features are rigors with drenching sweats, and intense headache. Cough is usual, and the sputum is often bloodstained, but these features are less constant than the rigors and headache. Malaria has always to be excluded, but Q fever can usually be distinguished by the fact that the rigors and profuse sweats often occur two or three times in twenty-four hours (see figure).
Conclusions
Analysis of the results. of antibiotic treatment of female genital tuberculosis leads to the following conclusions :
(1) The combined treatment of female genital tuberculosis with streptomycin 45 g. and P.A.S. 800 g. led to healing of the disease in about 65% of cases. (2) More than half the patients in whom the first course of antibiotic treatment was ineffective benefited from a second course of streptomycin and P.A.S. (3) Healing of female genital tuberculosis cannot be considered definite until at least three years have elapsed since the start of treatment. (4) For this reason all the patients must remain under strict observation, and endometrial biopsies and cultures of the menstrual discharges must be repeated at regular intervals during the first five years after treatment. A second course of streptomycin and P.A.S. should be given as soon as the first signs of recurrence of tuberculosis are discovered, whether on endometrial biopsy or in cultures of the menstrual discharges. (5) Cultures of the menstrual discharges were much more valuable than endometrial biopsy in discovering recurrence of female genital tuberculosis. (6) there is no doubt that in some cases antibiotic treatment cured the sterility caused by genital tuberculosis, especially in the tubal stage. (7) Antibiotic treatment was followed by ectopic pregnancy more often than by intra-uterine pregnancy. (8) 3 intra-uterine pregnancies after antibiotic treatment went to term in genital tuberculosis healed at the tubal stage, whereas in both cases of healed endometrial tuberculosis pregnancy ended in a miscarriage. Summary In 48 of 74 women with genital tuberculosis treated with streptomycin and P.A.s. the disease did not recur after a first course of antibiotic treatment consisting of streptomycin 45 g. and P.A.s. 800 g. In 6 of 11 women given a second course, which consisted of streptomycin 60 g. and P.A.S. 1200 g. the genital tuberculosis was cured. 7 ectopic and 5 intra-uterine pregnancies occurred in 11 of the patients in whom the genital tuberculosis was cured by antibiotic treatment.
chart of case 8, showing six peaks of temperaPulse-rate did not rise above 96 during this
Four-hourly temperature ture in 60 hours.
period.
Relative bradycardia is another valuable distinguishing feature. In the past two years 9 cases with typical features and confirmatory complement-fixation titres have been encountered, and 4 more in which the diagnosis is probable, though the titre was below the level (1 in 100) which we have taken as conclusive (see table). Illustrative
Case-report in table), felt perfectly well until the -
A man, aged 33(case 4 evening of Nov. 18, 1952, when he had a violent attack of shivering. He went to bed, felt hot, and sweated profusely. During the night he had another violent attack of shivering, followed by a rise of temperature and copious sweating. Next day he felt better though he still had fever. On the morning of the 20th he had another severe rigor with temperature 105°F, followed again by a drenching sweat. His temperature remained about 102°F until the morning of the 22nd when DR. HALBRECHT: REFERENCES
Berblinger, W. (1946) Schweiz. med. Wschr. 76, 1171. Halbrecht, I. (1946) Ibid, p. 708. (1951) Lancet, i, 85. Liljedahl, S. O., Ryden, A. B. V. (1950) Acta obstet, gynec. scand. 30, —
359.
Schockaert, J. A. (1951) Minerva ginec. 3, 507. Sharman, A. (1944) J. Obstet. Gynœc., Brit. Emp. 51, 85. Sutherland, A. M. (1943) Ibid, 50, 161.
ORIGINAL ARTICLES
The rash was usually fully developed in twenty-four hours. Its total duration was in most of my cases fortyeight hours, but in some it had already disappeared in twenty-four hours ; in a few others it lasted up to seventytwo hours. It did not appear to itch ; it was not followed by
desquamation babies.
Immunity The fact that roseola infantum rarely occurs after the age of 3 years suggests that by that time nearly all children have become immune to it, but, since only a minority of children suffer from a typical attack, it appears that by the age of 3 years many have become immune through a modified illness, either without a rash or with a very sparse or fleeting one. On the other hand Wesselhoeft (1951) suggests that roseola infantum might occur in older children and adults without a rash or with a nocturnal rash only. This would put roseola infantum in the exceptional position of being an exanthematic disease occurring in one age-group usually with a rash and in the rest usually without a rash or with a nocturnal rash only, which seems to me unlikely.
Diagnosis In the presence of an otherwise unexplained persistent in a child. of the most susceptible age-group, with enlarged lymph-glands at the back of head or neck, the diagnosis of roseola infantum should be considered among other causes of pyrexia of unknown origin. A well-marked leucopenia with relative lymphocytosis would support the diagnosis. Once the rash has appeared, mainly rubella, measles, and drug rashes have to be considered in the differential diagnosis. Though the rash of roseola infantum is very similar to the rash of german measles or very mild measles it does not affect the face or only very slightly. In roseola infantum catarrhal symptoms are absent or at the most very mild ; there are no Koplik’s spots. The most important characteristic of roseola infantum is that the rash appears when the child is beginning to recover, whereas in rubella the pyrexia and the rash coincide, and in measles the rash appears while the illness is reaching its climax.
pyrexia possibly
Summary Roseola infantum is
a
occurring nearly exclusively of it
M.D.
were
seen
common infective disease, in the first 3 years of life ;
in twelve years of
general
practice.
Complications reported
are
The treatment is
very rare ;
Strasbourg
From the Maternity Hospital, Hadera, Israel
Cases of roseola infantum without rash have been by other observers during epidemics in homes for
cases
I. HALBRECHT
pigmentation.
or
?011
50
ANTIBIOTIC THERAPY OF TUBERCULOSIS OF THE FEMALE GENITALIA
no
fatal
cases
have been
symptomatic.
ALMOST five years have
elapsed since our first results streptomycin treatment of 12 cases of latent female genital tuberculosis were published (Halbrecht 1951). of
more cases of tuberculosis of the female genitalia in all its stages and have followed up some of them for more than five years since the start of antibiotic treatment. Almost all of these patients sought our help not because of genital tuberculosis, of which they were hardly, if at all, aware, but because of sterility. Thus, the assessment of any treatment of female genital tuberculosis must take into account not only its ability to cure the tuberculosis but also its effect on the sterility, which is the main complication of the tuberculosis.
We’ have since treated 62
Diagnosis It is generally agreed that in the first stages of tuberculosis the fallopian tubes alone are involved, and that endometrial tuberculosis represents a later stage, the tuberculosis spreading slowly but continuously by contact from the endosalpinx to the endometrium (Sutherland 1943, Sharman 1944, Halbrecht 1946, Berblinger 1946, Liljedahl and Ryden 1950, Schockaert 1951). It is therefore obvious that, in female genital tuberculosis, the earlier the antibiotic treatment is instituted the more likely it is to be successful, especially so far as sterility is concerned. For this reason we tried to diagnose the tuberculosis, which is asymptomatic in more than 90% of cases, by culture of menstrual and intermenstrual discharges. By this method it is possible to diagnose genital tuberculosis in its early, pre-endometrial, stage in a considerable number of cases. Material
We treated with streptomycin and p-aminosalicylic acid (P.A.S.) 74 cases of female genital tuberculosis, of which 21 were discovered in the tubal stage and 49 in the endometrial stage, and 4 were exudative cases with more or less large tumours in the adnexa (table i). Methods
patients were treated by daily injections of streptomycin 1 g. alone. Each of them received 45 g. The 62 other patients received a combined treatment of streptomycin 1 g. thrice a week to a total of 45-50 g. and P.A.S. 12 g. daily to a total of 800-900 g. Our first 12
BIBLIOGRAPHY
Banks, H. S. (1949) Common Infectious Diseases. London. Barenberg, L. H., Greenspan, L. (1939) Amer. J. Dis. Child. 58, 983. Berenberg, W., Wright, S., Janeway, C. A. (1949) New Engl. J. Med. 241, 253. B. B. jun. (1941) N.Y. St. J. med. 41, 1854. British Medical Journal (1950) ii, 876. Clemens, H. H. (1945) J. Pediat. 26, 66. Conte, A. N., Uzmann, J. W., Ware, G. W. (1944) Arch. Pediat.
Breese,
61, 559.
Craddock, D. (1953)
An Introduction to General
Practice, London ;
p. 480.
— (1955) Brit. med. J. i, 1219. Cushing, H. B. (1927) Canad. med. Ass. J. 17, 905. Cutts, M. (1938) Ann. intern. Med. 11, 1752. Dickey, L. B. (1945) Stanf. med. Bull. 3, 37. Faber, H. K., Dickey, L. B. (1927) Arch. Pediat. 44, 491. Farber, S. (1938) New Engl. J. Med. 219, 836. Glanzmann, E. (1924) Schweiz med. Wschr. 54, 589. (1934) In Handbuch innerer Medizin. Edited by G. von Bergmann and R. Staehelin. 3rd ed., Berlin; vol. I, p. 420. Greenthal, R. M. (1922) Amer. J. Dis. Child. 23, 63. Harries. E. H. R., Mitman, M. (1947) Clinical Practice in Infectious Disease. Edinburgh. Heiman, H. (1925) Arch. Pediat. 42, 447. —
Hynes, M. (1940) Lancet, ii, 679. Jackson, D. C. (1949) Med. J. Aust. ii, 52. James, U., Freier, A. (1949) Arch. Dis. Childh. 24, 54. Jennings, R. E. (1940) J. med. Soc. N.J. 37, 577. Kempe, C. H., Shaw, E. B., Jackson, J. R., Silver, H. K. (1950) J. Pediat. 37, 561. Levy, D. J. (1921) J. Amer. med. Ass. 77, 1785. McQuitty, E. L. (1955) Brit. med. J. i, 1005. Park, J. H. jun., Michael, J. C. (1922) Amer. J. Dis. Child. 23, 63. Rosenblum, J. (1945) Ibid, 69, 234. Ruh, H. O., Garvin, J. A. (1923) Arch. Pediat. 40, 151. Schlesinger, B. (1937) Brit. med. J. i, 298. Veeder, B. S., Hempelmann, T. C. (1921) J. Amer. med. Ass. 77, 1787.
Wallfield, M. J. (1934) J. Pediat. 5, 800. Wesselhoeft, C. (1951) In Banks, H. S. Modern Practice in Infectious Fevers. London ; vol II. Westcott, T. S. (1921) Amer. J. med. Sci. 162, 367. Yoshina, T. (1942) Hawaii med. J. 1, 235. Zahorsky, J. (1910) Pediat. 22, 60. (1925) Arch. Pediat. 42, 610. (1940) Ibid, 57, 405. (1947) Ibid, 64, 579. (1948) In Brennemann Practice of Pædiatrics. Hagerstown, Md.; vol. II, chapter 21. —
—
—
—
1166
ORIGINAL ARTICLES
TABLE I-CLASSIFICATION OF CASES BY METHOD OF DIAGNOSIS
discharges, whereas endometrial biopsy repeatedly negative after the treatment. In 3 of the 8 cases in which endometrial tuberculosis recurred the first endometrial biopsy after treatment was negative, and only the second, done six months later, showed endometrial tuberculosis. Long before the posi. tive endometrial biopsy, cultures of menstrual discharges were positive for tuberculosis in these 3 cases. It therefore seems that antibiotic treatment is more effective in curing intermenstrual was
11 patients in whom this first course of antibiotic treatment was unsuccessful received a second course of treatment consisting of streptomycin 60-75 g. and P.A.S. 1200 g. In 6 cases the streptomycin was discontinued before 30 g. had been given, because vestibular symptoms ,
appeared. cases
discharges. In 7 of the 21 cases of isolated tubal tuberculosis positive cultures of the genital discharges showed a TABLE
IV-RESULTS
OF
ANTIBIOTIC
of tuberculosis within two and the start of the treatment. recurrence
Results
Only 68 of the 74 patients received the full treatment of 45 g., which is the minimum needed to cure latent tuberculosis of the female genitalia. Nevertheless I here results the report (table 11) obtained, in all 74 cases, TABLE II-RESULTS AND FOLLOW-UP
including the 6 in which only about 30 g. of streptomycin was given, because I have been impressed by the lasting successful results in some patients with even this small amount of streptomycin. In 48 of the 74 patients, treated with streptomycin alone or in combination with P.A.S., no signs of genital tuberculosis could be discovered from one to six years after the treatment. Of these 48 patients 7 were under continuous observation for more than five years after the treatment, 11 for more than four years, 8 for more than three years, 11 for than two years, 8 for more than a year, and 3 for year. 3 of the 6 patients who did not receive more than 30 g. of streptomycin were free from any signs of genital tuberculosis for more than three years, whereas the 3 others showed a recurrence of tuberculosis before the end of the second year after the treatment. Endometrial Tuberculosis (table 111) Tuberculosis recurred in 16 of 49 patients who had endometrial tuberculosis before the treatment. In only 8 of these was the recurrence endometrial ; in the other 8 it was tubal, found by positive culture of menstrual and
TREATMENT
IN
TUBAL
TUBERCULOSIS
in which endometrial
biopsy had revealed endometrial tuberculosis, biopsy was repeated at sixmonth intervals after the treatment. In cases in which cultures of menstrual discharges had been positive, cultures were repeated every month during the first year and every two or three months in the years following the treatment. In
endometrial than tubal tuberculosis. Tubal Tuberculosis (table m) The only means of diagnosing female genital tuberculosis in the tubal stage, before involvement of the endometrium, is culture of menstrual and intermenstrual
a
half years of
Exudative Tuberculosis In 4 cases bimanual genital examination revealed a tumour of the adnexa which was clinically thought to be tuberculous. The diagnosis was confirmed by positive culture of the menstrual discharges. Each of these 4 patients received 60-75 g. of streptomycin and 1200 g. of P.A.S. In 2 cases the tumour disappeared completely, and in the 2 others it diminished but did not disappear. In 3 of the 4 cases culture of the menstrual discharges became positive from six to eighteen months after the treatment. Effect of Antibiotic Treatrnent on Sterility caused by Genital Tuberculosis 7 ectopic and 5 intra-uterine pregnancies followed the antibiotic treatment of genital tuberculosis in the 74 patients. They were distributed as follows : 5 ectopic and 3 intra-uterine pregnancies occurred in 7 patients with isolated tubal tuberculosis. The 3 intra-uterine TABLE
V-RESULTSr OF SECOND COURSE OF ANTIBIOTIC TREATMENT
more
a
TABLE
III-RESULTS
OF
ANTIBIOTIC
TREATMENT
ENDOMETRIAL TUBERCULOSIS
IN
went to their end, full-term healthy babies being born. 2 ectopic and 2 intra-uterine pregnancies occurred in 4 patients with -endometrial tuberculosis who had been completely cured by the antibiotic treatment. The 2 intrauterine pcega’amcies -ended in miscarriages in the third and fourth months.
pregnancies
Histological -examination of the tubes in the 7 ectopic pregnancies revealed the persistence of tuberculosis in the walls of the tubes in 1 case and no tuberculosis in the others. Histological examination of curettage material in the 2 cases of miscarriage did not reveal any tuberculosis. 3 ectopic pregnancies occurred immediately after the antibiotic treatment, and the other 4 one or two years after the treatment. Both full-term pregnancies in the patients with healed tubal tuberculosis and both miscarriages in the patients with healed endometrial tuberculosis occurred in the second year after the treatment.
1167
ORIGINAL ARTICLES
CQ1trse 11 of the 26
of Treatment (table v) patients in whom the first series of streptomycin injections did not cure the genital tuberculosis received a second course, which consisted of streptomycin 60 g. and P.A.S. 1200 g. In 5 of these patients the second
tuberculosis recurred within a year from the start of the second course. The 6 other patients are free from tuberculosis from two to four years after the second course, but none of them has
yet conceived.
Q FEVER IN NAKURU, KENYA A. L. CRADDOCK O.B.E., M.B. Lond. GENERAL
JAMES GEAR M.B. Witw’srand, D.P.H., D.T.M. & DEPUTY
Discussion
Xo treatment of female genital tuberculosis can be properly assessed except by comparing its results with the incidence of spontaneous healing of this disease and the occurrence of pregnancies in untreated cases. Spontaneous healing of female genital tuberculosis is very rare but undoubtedly takes place. In 6 of 90 cases of untreated endometrial tuberculosis and in 1 case of tubal tuberculosis spontaneous healing could be assumed on the basis of repeated negative endometrial biopsies and a great number of negative cultures of the menstrual discharges made repeatedly during at least from two to five years after the diagnosis of genital tuberculosis had been established by a positive endometrial biopsy or by positive cultures of the genital discharges. No patient with apparently healed endometrial tuberculosis conceived, whereas the patient with healed tubal tuberculosis conceived and was successfully delivered. Thus it seems that spontaneous healing of endometrial tuberculosis does not improve the chances of pregnancy in these patients. On the other hand, in cases in which spontaneous healing starts in the earliest, or tubal, stage, when functional restitutio ad integrum of the tubes is still possible, pregnancy may take place.
PRACTITIONER, NAKURU
H., Dip. Bact.
DIRECTOR, SOUTH AFRICAN INSTITUTE RESEARCH, JOHANNESBURG
FOR MEDICAL
SooN after arrival in Nakuru three years ago, one of us (A. L. C.) was struck by the frequency of an acute febrile illness with pneumonic features, which was usually regarded as virus pneumonia. It strongly resembled Q fever, and the help of the other (J. H. S. G.) was enlisted to confirm its cause. Tests soon showed that many cases were in fact infections with Rickettsia burneti, and there is no doubt that this disease is endemic in the locality. Nakuru itself is a large market town a hundred miles north-west of Nairobi, surrounded by an extensive dairyfarming area occupying the floor and slopes of the Rift Valley. Cattle are a well-recognised source of infection (Harvey et al. 1951, Marmion et al. 1953).. Q fever among Europeans in Nakuru is as a rule easily recognisable. The onset is sudden, and the characteristic features are rigors with drenching sweats, and intense headache. Cough is usual, and the sputum is often bloodstained, but these features are less constant than the rigors and headache. Malaria has always to be excluded, but Q fever can usually be distinguished by the fact that the rigors and profuse sweats often occur two or three times in twenty-four hours (see figure).
Conclusions
Analysis of the results. of antibiotic treatment of female genital tuberculosis leads to the following conclusions :
(1) The combined treatment of female genital tuberculosis with streptomycin 45 g. and P.A.S. 800 g. led to healing of the disease in about 65% of cases. (2) More than half the patients in whom the first course of antibiotic treatment was ineffective benefited from a second course of streptomycin and P.A.S. (3) Healing of female genital tuberculosis cannot be considered definite until at least three years have elapsed since the start of treatment. (4) For this reason all the patients must remain under strict observation, and endometrial biopsies and cultures of the menstrual discharges must be repeated at regular intervals during the first five years after treatment. A second course of streptomycin and P.A.S. should be given as soon as the first signs of recurrence of tuberculosis are discovered, whether on endometrial biopsy or in cultures of the menstrual discharges. (5) Cultures of the menstrual discharges were much more valuable than endometrial biopsy in discovering recurrence of female genital tuberculosis. (6) there is no doubt that in some cases antibiotic treatment cured the sterility caused by genital tuberculosis, especially in the tubal stage. (7) Antibiotic treatment was followed by ectopic pregnancy more often than by intra-uterine pregnancy. (8) 3 intra-uterine pregnancies after antibiotic treatment went to term in genital tuberculosis healed at the tubal stage, whereas in both cases of healed endometrial tuberculosis pregnancy ended in a miscarriage. Summary In 48 of 74 women with genital tuberculosis treated with streptomycin and P.A.s. the disease did not recur after a first course of antibiotic treatment consisting of streptomycin 45 g. and P.A.s. 800 g. In 6 of 11 women given a second course, which consisted of streptomycin 60 g. and P.A.S. 1200 g. the genital tuberculosis was cured. 7 ectopic and 5 intra-uterine pregnancies occurred in 11 of the patients in whom the genital tuberculosis was cured by antibiotic treatment.
chart of case 8, showing six peaks of temperaPulse-rate did not rise above 96 during this
Four-hourly temperature ture in 60 hours.
period.
Relative bradycardia is another valuable distinguishing feature. In the past two years 9 cases with typical features and confirmatory complement-fixation titres have been encountered, and 4 more in which the diagnosis is probable, though the titre was below the level (1 in 100) which we have taken as conclusive (see table). Illustrative
Case-report in table), felt perfectly well until the -
A man, aged 33(case 4 evening of Nov. 18, 1952, when he had a violent attack of shivering. He went to bed, felt hot, and sweated profusely. During the night he had another violent attack of shivering, followed by a rise of temperature and copious sweating. Next day he felt better though he still had fever. On the morning of the 20th he had another severe rigor with temperature 105°F, followed again by a drenching sweat. His temperature remained about 102°F until the morning of the 22nd when DR. HALBRECHT: REFERENCES
Berblinger, W. (1946) Schweiz. med. Wschr. 76, 1171. Halbrecht, I. (1946) Ibid, p. 708. (1951) Lancet, i, 85. Liljedahl, S. O., Ryden, A. B. V. (1950) Acta obstet, gynec. scand. 30, —
359.
Schockaert, J. A. (1951) Minerva ginec. 3, 507. Sharman, A. (1944) J. Obstet. Gynœc., Brit. Emp. 51, 85. Sutherland, A. M. (1943) Ibid, 50, 161.