358 will become widespread in centres specialising in the treatment of acute leukaemia and aplastic anaemia. We thank colleagues in several London hospitals for prodetails of the responses to granulocyte transfusions of patients under their care, especially Prof. J. W. Stewart and Dr Michael Rudolph of the Middlesex Hospital, Dr Judith Chessells and Dr Peter Kearney of the Hospital for Sick Children, Dr R. P. Britt of Hillingdon Hospital, and Dr D. A. Curnock of St. Helier Hospital, Carshalton, Surrey. IrradiaIntion of cells was carried out by Mr George Harding. valuable secretarial assistance was given by Miss Maureen Robson. R. M. L. is in receipt of a fellowship from the Leukaemia Research Fund. Requests for reprints should be addressed to R. M. L.
viding
REFERENCES 1. 2.
3. 4.
5. 6. 7. 8. 9.
10.
Bodey, G. P., Gehan, E. A., Freireich, E. J., Frei, E. Am. J. med. Sci. 1971, 262, 138. Levine, A. S., Siegel, S. E., Schreiber, A. D., Hauser, J., Preisler, H., Goldstein, I. M., Seidler, F., Simon, R., Perry, S., Bennet, J. E., Henderson, E. S. New Engl. J. Med. 1973, 288, 477. Levine, A. S., Schimpff, S. C., Graw, R. G., Jr., Young, R. C. Sem. Hemat. 1974, 11, 141. Tattersall, M. H. N., Spiers, A. S. D., Darrell, J. H. Lancet, 1972, i, 162. Graw, R. G., Jr., Herzig, G. P., Eisel, R. J., Perry, S. Transfusion, 1971, 11, 94. Goldman, J. M., Catovsky, D. Br. J. Hœmat. 1972, 23, suppl. p. 223. Freireich, E. J., Judson, G., Levin, R. H. Cancer Res. 1965, 25, 1516. Lowenthal, R. M., Park, D. S. Transfusion (in the press). Lowenthal, R. M., Buskard, N. A., Park, D. S., Goldman, J. M. in Leucocytes: separation, collection and transfusion (proceedings of the international symposium on Leucocyte Separation and Transfusion, London, September, 1974) (edited by J. M. Goldman and R. M. Lowenthal). London (in the press). Levine, A. S., Graw, R. G., Jr., Young, R. C. Sem. Hemat. 1972, 9, 141.
11. 12. 13. 14. 15. 16. 17.
Bodey, G. P., Buckley, M., Sathe, Y. S., Freireich, E. J. Ann. intern. Med. 1966, 64, 328. Graw, R. G., Jr., Herzig, G., Perry, S., Henderson, E. S. New Engl. J. Med. 1972, 287, 367. Graw, R. G., Jr., Buckner, C. D., Whang-Peng, J., Leventhal, B. G., Krüger, G., Bevard, C., Henderson, E. S. Lancet, 1970, ii, 338. McCullough, J., Carter, S. J., Quie, P. G. Blood, 1974, 43, 207. McCredie, K. B. Personal communication. Goldstein, I. M., Eyre, H. J., Terasaki, P. I., Henderson, E. S., Graw, R. G., Jr. Transfusion, 1971, 11, 19. Hester, J. P., Rossen, R. O. Paper read at an American Association for Cancer Research meeting, held in Houston, Texas, in March, 1974.
CONTROLLED TRIAL OF THERAPY IN COVERT BACTERIURIA OF CHILDHOOD D. C. L. SAVAGE* G. HOWIE M. I. WILSON K. ADLER University Departments of Child Health, Radiology, and Bacteriology, Ninewells Hospital, Dundee
renal growth was similar to that in normal children. It is suggested that for most of these children therapy is not essential, and that when renal changes occur they are of little or no significance. Prescriptive screening for covert bacteriuria of childhood cannot be recommended at present.
Introduction COVERT bacteriuria is defined as significant bacteriuria detected during a screening programme.1 Others have referred to it as asymptomatic urinary-tract infection,2-4 but we prefer the term " covert ", since many of these children have symptoms referrable to the lower urinary tract.1 The clinical and radiological findings in this condition, and the effect of therapy upon it, are now well documented.l,2.5-7 Since 5-10% of girls develop covert bacteriuria during their school years/,2 it is important to decide whether prescriptive screening is necessary. (Prescriptive screening is defined as a screening programme which has as its primary aim a direct contribution to the health of the individual.) In this decision, the results of a controlled trial of therapy in covert bacteriuria are essential, for it will allow the natural history of the condition to be determined, and will establish the effect of therapy upon the natural history. In a continuing study into the epidemiology of covert bacteriuria of childhood/,5--7 we have included a controlled trial of therapy, and now report the results in sixty-three primary-school girls, who have been followed up for a mean period of over 3 years. Patients and Methods Patients The children were those found to have covert bacteriuria during the screening of 5-year-old girls entering Dundee schools in 1969 and 1970, and those children in the 1968 cohort detected during rescreening in 1969 and 1970. The children were allocated by random numbers to a control group or to a treated group, except for those with a past history of urinary-tract infection or those who were found to be unwell. On these criteria, 6 were transferred to a group who received therapy and who have been
reported elsewhere.5,6 Sixty-three children
entered the study (age range 5 years to 7 years 10 months); thirty-four in the control group (mean age 5 years 10 months) and twenty-nine in the treated group (mean age 6 years 3 months). Informed
parental
consent was
allowed their child’s
Sixty-three girls with covert bacteriSum ary uria were included in a controlled trial of therapy. Recurrent infection in the treated group was common, and was not significantly different from the rate of persistent infection in the untreated control group. Two children in each group developed clinical pyelonephritis; the others have remained healthy and all of them have a normal rate of growth. 2 years after diagnosis three of the thirty-four children in the control group and one of twenty-six children in the treated group have radiological evidence of new scars of pyelonephritis. These changes were relatively minor and in both groups of children *
Present address: Bristol Bristol BS2 8BJ.
Royal Hospital
for Sick
Children,
always obtained, and all parents
participation
in the trial.
Methods The study population, the method of presentation of the programme, the collection of urine specimens, and the bacteriological details and the urological investigations have been described elsewhere.1 All the children had an initial intravenous pyelogram and micturating cystourethrogram; this was repeated 2 The X-rays were reported by one of us years later. (G. H.) without knowledge of the group in which the child had been placed. Rolleston’s classification for vesicoureteric refluxand Hodson’s criteria for the diagnosis of radiological pyelonephritis9 were used. Pyelonephritis was graded anatomically, the kidney being divided into thirds; one-third involvement was regarded as minimal pyelonephritis, two-thirds moderate pyelonephritis, and involvement in each third indicated severe pyelonephritis.
359 Where the
kidney’s
upper and lower
delineated, the renal length 0-25
was
pole
measured
to
was
clearly
the
nearest
TABLE I-PERSISTENCE OF INFECTION IN CONTROL GROUP COMPARED WITH FREQUENCY OF RECURRENCE OF INFECTION IN TREATED GROUP
cm.
Treatment In the treated group, children with normal intravenous pyelograms and micturating cystograms received 3 months’ chemotherapy initially and after their first relapse; later relapses led to 6 months’ therapy. Children with radiological evidence of pyelonephritis and/or vesicoureteric reflux received 6 months’ chemotherapy; after relapse 612 months’ therapy was given. The chemotherapeutic agents were ampicillin, nitrofurantoin, or co-trimoxazole (trimethoprim and sulphamethoxazole). The dosage of drugs (prescribed on the basis ofsensitivity pattern) in this age-group were: ampicillin 250 mg. four times a day for 2 weeks with no prophylaxis; nitrofurantoin 8 mg. per kg. per 24 hours for 2 weeks followed by half this dose prophylactically for the next 10 weeks; or trimethoprim 40 mg. and sulphamethoxazole 200 mg. three times a day for 2 weeks followed by 10 weeks’ prophylaxis with 20-40 mg. trimethoprim and 100-200 mg. sulphamethoxazole twice a day. The children were encouraged to increase their fluid intake, and to micturate frequently; the last dose of medicine was taken after emptying the bladder at bedtime. Those with vesicoureteric reflux were advised to practise triple micturition.
Results
Sixty-three children entered the trials. Four controls have moved from the area and three have not attended for follow-up. In the treated group three children have moved from the area and one has not attended follow-up. In both groups, the mean period of follow-up is 44 months (range 28-68 months).
children were further subdivided into those with normal and those with abnormal radiology, there was no significant difference between the two groups.
Surgery No child has
required surgery. Persistent or Recurrent Infection The persistence of infection in the control
group and the recurrence-rate of infection in the treated group are shown in table i. The only significant difference in the rate of infection was in the first 6 months of therapy (P
viding
REFERENCES 1. 2.
3. 4.
5. 6. 7. 8. 9.
10.
Bodey, G. P., Gehan, E. A., Freireich, E. J., Frei, E. Am. J. med. Sci. 1971, 262, 138. Levine, A. S., Siegel, S. E., Schreiber, A. D., Hauser, J., Preisler, H., Goldstein, I. M., Seidler, F., Simon, R., Perry, S., Bennet, J. E., Henderson, E. S. New Engl. J. Med. 1973, 288, 477. Levine, A. S., Schimpff, S. C., Graw, R. G., Jr., Young, R. C. Sem. Hemat. 1974, 11, 141. Tattersall, M. H. N., Spiers, A. S. D., Darrell, J. H. Lancet, 1972, i, 162. Graw, R. G., Jr., Herzig, G. P., Eisel, R. J., Perry, S. Transfusion, 1971, 11, 94. Goldman, J. M., Catovsky, D. Br. J. Hœmat. 1972, 23, suppl. p. 223. Freireich, E. J., Judson, G., Levin, R. H. Cancer Res. 1965, 25, 1516. Lowenthal, R. M., Park, D. S. Transfusion (in the press). Lowenthal, R. M., Buskard, N. A., Park, D. S., Goldman, J. M. in Leucocytes: separation, collection and transfusion (proceedings of the international symposium on Leucocyte Separation and Transfusion, London, September, 1974) (edited by J. M. Goldman and R. M. Lowenthal). London (in the press). Levine, A. S., Graw, R. G., Jr., Young, R. C. Sem. Hemat. 1972, 9, 141.
11. 12. 13. 14. 15. 16. 17.
Bodey, G. P., Buckley, M., Sathe, Y. S., Freireich, E. J. Ann. intern. Med. 1966, 64, 328. Graw, R. G., Jr., Herzig, G., Perry, S., Henderson, E. S. New Engl. J. Med. 1972, 287, 367. Graw, R. G., Jr., Buckner, C. D., Whang-Peng, J., Leventhal, B. G., Krüger, G., Bevard, C., Henderson, E. S. Lancet, 1970, ii, 338. McCullough, J., Carter, S. J., Quie, P. G. Blood, 1974, 43, 207. McCredie, K. B. Personal communication. Goldstein, I. M., Eyre, H. J., Terasaki, P. I., Henderson, E. S., Graw, R. G., Jr. Transfusion, 1971, 11, 19. Hester, J. P., Rossen, R. O. Paper read at an American Association for Cancer Research meeting, held in Houston, Texas, in March, 1974.
CONTROLLED TRIAL OF THERAPY IN COVERT BACTERIURIA OF CHILDHOOD D. C. L. SAVAGE* G. HOWIE M. I. WILSON K. ADLER University Departments of Child Health, Radiology, and Bacteriology, Ninewells Hospital, Dundee
renal growth was similar to that in normal children. It is suggested that for most of these children therapy is not essential, and that when renal changes occur they are of little or no significance. Prescriptive screening for covert bacteriuria of childhood cannot be recommended at present.
Introduction COVERT bacteriuria is defined as significant bacteriuria detected during a screening programme.1 Others have referred to it as asymptomatic urinary-tract infection,2-4 but we prefer the term " covert ", since many of these children have symptoms referrable to the lower urinary tract.1 The clinical and radiological findings in this condition, and the effect of therapy upon it, are now well documented.l,2.5-7 Since 5-10% of girls develop covert bacteriuria during their school years/,2 it is important to decide whether prescriptive screening is necessary. (Prescriptive screening is defined as a screening programme which has as its primary aim a direct contribution to the health of the individual.) In this decision, the results of a controlled trial of therapy in covert bacteriuria are essential, for it will allow the natural history of the condition to be determined, and will establish the effect of therapy upon the natural history. In a continuing study into the epidemiology of covert bacteriuria of childhood/,5--7 we have included a controlled trial of therapy, and now report the results in sixty-three primary-school girls, who have been followed up for a mean period of over 3 years. Patients and Methods Patients The children were those found to have covert bacteriuria during the screening of 5-year-old girls entering Dundee schools in 1969 and 1970, and those children in the 1968 cohort detected during rescreening in 1969 and 1970. The children were allocated by random numbers to a control group or to a treated group, except for those with a past history of urinary-tract infection or those who were found to be unwell. On these criteria, 6 were transferred to a group who received therapy and who have been
reported elsewhere.5,6 Sixty-three children
entered the study (age range 5 years to 7 years 10 months); thirty-four in the control group (mean age 5 years 10 months) and twenty-nine in the treated group (mean age 6 years 3 months). Informed
parental
consent was
allowed their child’s
Sixty-three girls with covert bacteriSum ary uria were included in a controlled trial of therapy. Recurrent infection in the treated group was common, and was not significantly different from the rate of persistent infection in the untreated control group. Two children in each group developed clinical pyelonephritis; the others have remained healthy and all of them have a normal rate of growth. 2 years after diagnosis three of the thirty-four children in the control group and one of twenty-six children in the treated group have radiological evidence of new scars of pyelonephritis. These changes were relatively minor and in both groups of children *
Present address: Bristol Bristol BS2 8BJ.
Royal Hospital
for Sick
Children,
always obtained, and all parents
participation
in the trial.
Methods The study population, the method of presentation of the programme, the collection of urine specimens, and the bacteriological details and the urological investigations have been described elsewhere.1 All the children had an initial intravenous pyelogram and micturating cystourethrogram; this was repeated 2 The X-rays were reported by one of us years later. (G. H.) without knowledge of the group in which the child had been placed. Rolleston’s classification for vesicoureteric refluxand Hodson’s criteria for the diagnosis of radiological pyelonephritis9 were used. Pyelonephritis was graded anatomically, the kidney being divided into thirds; one-third involvement was regarded as minimal pyelonephritis, two-thirds moderate pyelonephritis, and involvement in each third indicated severe pyelonephritis.
359 Where the
kidney’s
upper and lower
delineated, the renal length 0-25
was
pole
measured
to
was
clearly
the
nearest
TABLE I-PERSISTENCE OF INFECTION IN CONTROL GROUP COMPARED WITH FREQUENCY OF RECURRENCE OF INFECTION IN TREATED GROUP
cm.
Treatment In the treated group, children with normal intravenous pyelograms and micturating cystograms received 3 months’ chemotherapy initially and after their first relapse; later relapses led to 6 months’ therapy. Children with radiological evidence of pyelonephritis and/or vesicoureteric reflux received 6 months’ chemotherapy; after relapse 612 months’ therapy was given. The chemotherapeutic agents were ampicillin, nitrofurantoin, or co-trimoxazole (trimethoprim and sulphamethoxazole). The dosage of drugs (prescribed on the basis ofsensitivity pattern) in this age-group were: ampicillin 250 mg. four times a day for 2 weeks with no prophylaxis; nitrofurantoin 8 mg. per kg. per 24 hours for 2 weeks followed by half this dose prophylactically for the next 10 weeks; or trimethoprim 40 mg. and sulphamethoxazole 200 mg. three times a day for 2 weeks followed by 10 weeks’ prophylaxis with 20-40 mg. trimethoprim and 100-200 mg. sulphamethoxazole twice a day. The children were encouraged to increase their fluid intake, and to micturate frequently; the last dose of medicine was taken after emptying the bladder at bedtime. Those with vesicoureteric reflux were advised to practise triple micturition.
Results
Sixty-three children entered the trials. Four controls have moved from the area and three have not attended for follow-up. In the treated group three children have moved from the area and one has not attended follow-up. In both groups, the mean period of follow-up is 44 months (range 28-68 months).
children were further subdivided into those with normal and those with abnormal radiology, there was no significant difference between the two groups.
Surgery No child has
required surgery. Persistent or Recurrent Infection The persistence of infection in the control
group and the recurrence-rate of infection in the treated group are shown in table i. The only significant difference in the rate of infection was in the first 6 months of therapy (P
