IRREVERSIBLE DAMAGE BY SCHISTOSOMA HÆMATOBIUM IN SCHOOLCHILDREN

IRREVERSIBLE DAMAGE BY SCHISTOSOMA HÆMATOBIUM IN SCHOOLCHILDREN D. M. FORSYTH M.R.C.P.E., D.T.M. & H. D. J. BRADLEY* M.A., M.B. Cantab. From the Bilharzia Research Unit of the Ross Institute of Tropical Hygiene hamatobium infection undoubtedly Schistosoma THOUGH causes grave harm to some of the people it infects, and the literature contains many accounts of the lesions, there is no quantitative evidence of its impact on whole communities.

Many estimates based

on

ordinary physical examination

have shown little or no difference in the relative health of infected and uninfected children. Severe fibrotic lesions of the bladder, ureters, and renal pelves are common necropsy findings; and this has led to the belief that these

people; but our survey which included virtually the entire population of four schools showed that serious lesions are common

in children. Methods

1032 children attending the four primary schools of the area formerly known as the Bukumbi chiefdom were investigated. This district of 100 square miles lies 15 miles south of Mwanza at the southern tip of Lake Victoria, in Tanganyika (map). The children usually attend school for four years. Their average age at entrance is 9, but a few children of 16 or 17 may be found in the

higher

standards.

Faeces were examined for eggs of S. mansoni by a minor modification of the technique of Ridley and Hawgood (1956) in which 2 ml. ’Teepol ’ are added to a litre of the formol saline for sedimentation. Urines were examined for eggs of S. hematobium qualitatively by microscopic examination of the whole centrifuged deposit from 10 ml. samples. For quantitative examination all urine passed between noon and 2 P.M. was collected. During these hours egg output is maximal (Stimmel and Scott 1956, Jordan 1961, Onori 1962) and least variable (Bradley 1963). If eggs were found in the centrifuged deposit of a 10 ml. aliquot another sample was examined and the eggs were counted using Bradley’s technique

(Bradley 1962, 1964). Intravenous urography was carried out on pupils who were admitted to hospital on the previous afternoon, starved, and purged. All children were examined clinically in a standardised manner: their heights and weights were measured and their haemoglobin was estimated using the M.R.C. greywedge photometer. The precise ages of the few children who had been baptised at birth was determined from church registers. To detect pulmonary hypertension, standard-lead electrocardiograms were recorded and where these suggested right-ventricular preponderance a posteroanterior skiagram of the chest was taken. To investigate possible bacterial superinfection of urinary tracts damaged by bilharzia, urine samples were plated on MacConkey agar. The plates were examined after twenty-four and forty-eight hours’ incubation. Wherever organisms were grown an attempt was made to obtain a second urine sample from the pupil for further study. Lassitude may be a leading symptom of bilharzial disease, and a battery of objective tests were designed to measure this (Bradley 1962). Results

Parasitological Findings -

the main ill effects. In attempting to assess the publichealth importance of the infection much of our attention has therefore been directed to the prevalence of this type of lesion. We first assumed that it would be found mainly if not exclusively in grown-up and especially in older are

*

address: Department of Medical Microbiology, Makarere University College Medical School, Kampala, Uganda.

Present

Jackson, W. P. U. (1957) Lancet, i, 1086. Jesserer, H., Swoboda, W. (1959) Klin. Wschr. 37, 84. Lachmann, A. (1941) Acta med. scand. suppl. 121. Liu, S. H., Chu, H. I. (1943) Medicine, Baltimore, 22, 103. MacGregor, M. E., Whitehead, T. P. (1954) Arch. Dis. Childh. 29, 398. McLean, F. C. (1941) J. Amer. med. Ass. 117, 609. Robinson, P. K., Carmichael, E. A., Cumings, J. N. (1954) Quart. J. Med. 23, 383.

Salveson, H. A., Böe, J. (1953a) Acta. med. scand. 146, 290. — — (1953b) Acta endocr., Kbh. 14, 214. Terepka, O. R., Chen, P. S., Jorgensen, B. (1961) Endocrinology, 68, Wade, J. S. (1961) Brit. J. Surg. 48, 24. Wells, G. C. (1962) Brit. med. J. ii, 937. Williams, T., Wood, C. (1959) Arch. Dis. Childh. 34, 302.

996.

Two species of schistosome occur in man in the Bukumbi area-mansoni and haematobium. Whenever possible, stool specimens of three consecutive days were examined for the presence of S. mansoni. Among 611 scholars this parasite was not very prevalent; the egg output of infected individuals was low; and no serious syndrome directly attributable to the infection was seen. Hyperendemic malaria made it impossible to assess the

significance of hepatosplenomegaly. Urinary bilharzial infection is common: tableI gives the results from 767 pupils who provided urine samples on three consecutive days. At first these urines were not examined quantitatively for eggs of S. haematobium; and, by the time technical difficulties had been overcome, the picture may have been modified by the treatment given at the request of the parents of infected children (Forsyth and Bradley 1964b). The incoming students of standards I and II had received no treatment, and a single midday urine specimen

was

collected from each. At

one

school

170 TABLE I-INCIDENCE

OF

SCHISTOSOME

* i/T = Infected/total.

eggs were found in the urines of 58 out of 66, at another in 38 out of 89. Egg output varied between 2 and 3920 per 10 ml. urine.

Radiological Findings 252 children between 10 and 16 (96% of the possible total) were examined radiologically. At the first school significant abnormalities were found in 20 out of 100 pupils: they included bladder calcification (8), persistent ureteral deformity (5), bladder calcification with unilateral hydronephrosis (2), bladder calcification with unilateral hydroureter (2), bilateral hydronephrosis (1), unilateral hydronephrosis (1), and non-functioning kidney (1) (Forsyth and Bradley 1964a). At the second school 15 out of 98 children had similar though less severe changes. At the third and fourth schools 4

out

of 54 showed

some

radiological abnormality. Clinical

Findings

In

only 12% of the children was the age known accurately, and too few of these were free from infection to act as controls. The school populations were not homogeneous, differences in physique being observed between the apparently uninfected children of the same age at different schools. The children of standards II, III, and iv were grouped according to the egg output in a single sample of midday urine taken at the end of a year over which growth had been measured. As shown in table 11 the growth-rate is progressively reduced as the egg TABLE

Discussion

INFECTION IN THE SCHOOL-

CHILDREN

II-GROWTH-RATES OVER ONE YEAR OF CHILDREN GROUPED ACCORDING TO URINARY EGG LOAD

Our survey describes an association between urinary bilharzial infection and ill health in the children of a community. The most striking finding was the high incidence of lesions revealed by intravenous urography. There are other causes of vesical, ureteral, and renal damage in childhood, but only bilharzia could account for the shockingly large numbers. Three methods were used to estimate the proportion of children attending primary school. Data from the regional educational officer gave an overall figure of 77 %, but these covered a larger area than the one we surveyed. A calculation from the total census population and assumed data for its age structure (following Wilson 1962) gave a figure of 50% and this corresponded with the estimate of Jordan (1963) and our own impressions. No evidence suggests that school attendance increases the intensity of the infection and the opposite may well be true. The subjects of this investigation were the population actually attending school, the " healthy " and " normal " children of the area. Those ill enough to be absent for the three weeks of the investigation and the chronically ill would be omitted from the sample. All doubtful lesions seen on radiography were grouped with the normals. No ureteric lesion was reported unless it was clearly visible on at least two of the three urograms, and bladder calcification was recorded only when the shadow was unmistakeable. These methods of sampling and reporting combined to make an overestimate of the prevalence of lesions highly

improbable. The radiological lesions described have been well discussed by Makar (1955), Sayegh (1950), and Honey and Gelfand (1960); but their prevalence has usually been recorded in hospital series against a poorly defined epidemiological background and their public-health importance has therefore remained uncertain. Nabawy and his colleagues (1961), working in a paediatric hospital in Egypt, reported that most children with delayed skeletal maturation had serious manifestations of bilharziasis. Of 108 patients voiding eggs of S. haematobium in the urine, 32 had calcification of the bladder and 4 also had hydronephrosis (Nabawy et al. 1961). Honey and Gelfand (1960) recorded that bladder calcification was seen in 16% of patients undergoing routine abdominal radiography at Harare Hospital. In South Africa Elsdon-Dew (1958) found that urinary schistosomiasis was of little public-health importance, and Gordon (1953) could find no reliable evidence of loss of man-power caused by the parasite in the Sudan. In Tanganyika almost all clinicians-Meredith being a notable exceptionregard urinary bilharzial disease as of little importance

(Forsyth 1963). load increases. The differences do not seem to be accounted for by concomitant variations of growth and infection level with age; but one cannot dismiss this possibility when the exact age of so few children is known. The electrocardiograms and skiagrams of 1032 children showed no instance of pulmonary hypertension. Of the 97 children whose urine was plated, 3 had massive bacterial infections: urography showed a double kidney in one and it was suggestive of early unilateral hydronephrosis in another. From several other children organisms were grown in moderate numbers. Children who had demonstrable urological damage were not abnormal as regards height, weight, and haemoglobin levels; and attendance registers showed that they were not absent from school more often than the rest of the class. Too few children from each group attended for examination to evaluate the results of lassitude tests.

history of the illness; and given for any of the urological lesions were demon-

Little is known of the natural an accurate

prognosis

cannot

be

children in whom gross strated radiologically. Yet one cannot consider with equanimity the future of the 15-20% of " normal " pupils, now aged about 14, who have such changes. Almost inevitably the lives of all of them will be shortened. It is significant that more lesions were found in a school where the incidence of infection is 94% and the mean egg output is 517 per 10 ml. midday urine than at another where the incidence is " only " 64% and the mean egg output is 325. The causes for the apparent association between a diminishing growth-rate and the excretion of larger numbers of eggs of S. haematobium is not known. Loss of blood and protein in the urine caused by the passage of ova through the walls of the bladder and ureters may upset protein balance, already precarious because of a poor diet.

171

No case of pulmonary hypertension was seen, and it is clear that in our area this is not a major complication. So far as is known, bilharzia infection has been stable in the area for many years (Blair 1956), more especially since 1948, the year of birth of the oldest child examined. In 1949 the incidence was estimated at 92-7% (East Africa Medical Survey 1948-49).

Summary An account is given of the effects produced by bilharzia in the schoolchildren of the community of Bukumbi in

Tanganyika. Infection with S. mansoni presents

no

significant health

problem. school, where the incidence of infection with S. haematobium is 94%, a minimum of 20% of apparently healthy schoolchildren about the age of 14 have significant irreversible damage to their urinary tracts. At a nearby school where the incidence of infection is 64%, 15 % of the pupils of similar ages have demonstrable urological lesions. At two other schools in the area comparable figures were At

one

obtained. The growth of infected children is diminished in direct proportion to the number of eggs which they are voiding. We are grateful to Dr. P. Jordan, director of the East African Institute for Medical Research, for kindly providing laboratory and other facilities; to Mrs. J. Phillips, S.R.N., Mrs. E. Armstrong, S.R.N., and Dr. W. Roberts for technical assistance; to Dr. R. Mol and Dr. P. C. M. Mol, the regional administration, and the staff of the schools for cooperation; and to Mr. David Band and Prof. G. Macdonald for continued help and advice. The Bilharzia Research Unit of the Ross Institute of Tropical Hygiene is supported financially by the Rockefeller Foundation, H.M. Treasury, and the World Health Organisation. REFERENCES

Blair, D. M. (1956) Bull. World Hlth Org. 15, 203. Bradley, D. J. (1962) Annual report, for 1961-62, of East African Institute for Medical Research. (1963) E. Afr. med. J. 40, 240. (1964) Trans. R. Soc. trop. Med. Hyg. (in the press). East African Medical Survey (1948-49) Annual report. Elsdon-Dew, R. (1958) S. Afr. J. Sci. 54, 43. Forsyth, D. M. (1963) E. Afr. med. J. 40, 261. Bradley, D. J. (1964a) Trans. R. Soc. trop. Med. Hyg. -

-

-

—

Medical Research. (1963) E. Afr. med. J. 40, 250. Makar, N. (1955) Urological Aspects of Bilharziasis in Egypt. Cairo. Nabawy, M., Garr, M., Ragab, M. M. (1961) J. trop. Med. Hyg. 64, 271, 314. Onori, E. (1962) Ann. trop. Med. Parasit. 56, 292. Ridley, D. S., Hawgood, B. C. (1956) J. clin. Path. 9, 74. Sayegh, E. S. (1950) J. Urol. 63, 353. Stimmel. C. M., Scott, J. A. (1956) Tex. Rep. Biol. Med. 14, 440. Wilson, T. (1962) Ann. trop. Med. Parasit. 56, 191. -

LONG-TERM RESULTS OF TREATING URINARY SCHISTOSOMIASIS ENDEMIC IN PRIMARY-SCHOOL CHILDREN D. M. FORSYTH M.R.C.P.E., D.T.M. & H. DAVID. J. BRADLEY M.A., M.B. Cantab. From the Bilharzia Research Unit of the Ross Institute of Tropical Hygiene

REPORTS

on the efficacy of schistosomicides have been concerned with immediate "cure"-rates. Our aim has been to measure the benefits of therapy in an endemic area during a longer period and to compare the apparent incidence of the infection, egg loads, and growth, in groups who have received curative treatment or suppressive management, or who have acted as controls. It was desirable that the selected regimes should be

largely

antimonyl dimercaptosuccinate (TWSb/6,’Astiban’) has not only an impressive record in the literature but also the advantage that it can be given by intramuscular injection. This drug was therefore used throughout. Logistic considerations limited the number of people who could be given " curative " treatment. The epidemiological background with an interim report on the early stages of the survey was given by Forsyth, Bradley, and Phillips (1964). Methods

1032 children were investigated at the four schools mentioned in our foregoing paper. Our methods of investigation have been described. The 850 children who were found to have urinary infection were divided into those who showed a coincident infection with S. mansoni and those who did not. At three of the schools every sixth injected child received " curative " treatment and the rest had " suppressive management " or acted as controls. At the fourth school children who were voiding viable eggs of S. haematobium in the urine either received " modified suppressive management " or acted as controls.

Regimes Curative treatment.-Children were admitted to hospital and given five consecutive daily intramuscular injections of sodium antimonyl dimercaptosuccinate, 6 mg. per kg. body-weight. For all injections 2 g. of the drug was dissolved in a mixture of 8 ml. sterile distilled water and 2 ml. 2% procaine hydrochloride (Forsyth 1961). Untoward side-effects were recorded daily after questioning in a standard manner. Electrocardiograms were taken daily from each child. Suppressive management.-Each child received twelve similar intramuscular injections at monthly intervals. Modified suppressive management.-The monthly dosage of the drug was raised to 10 mg. per kg. body-weight over a

comparable period. (in the press).

(1964b) Lancet, ii, 171. Gordon, R. M. (1953) Trop. Dis. Bull. 50, 129. Honey, R., Gelfand, M. (1960) The Urological Aspects of Bilharziasis in Rhodesia. Edinburgh. Jordan, P. (1961) Annual report, for 1960-61, of East African Institute for —

established methods, safe, convenient to administer, and have few side-effects. The antimonials are the most potent of the known schistosomicides and of these sodium

Controls received twelve monthly injections of sterile distilled water.

Technique of Assessment For qualitative examination 10 ml. urine was centrifuged and the complete deposit was examined for eggs of S. hamatobium. For quantitative examination a single specimen was collected from each child at some time between noon and 2 P.M. In the final assessment of all schools the centrifuged deposit from a 10 ml. aliquot of the shaken specimen was inspected under the microscope. If eggs of S. hcematobium were seen the remainder of the specimen was examined by Bradley’s quantitative technique (Bradley 1962, 1964). Haemoglobin estimations were made on capillary blood using the M.R.C. grey-wedge

photometer. Results

Of the 102 children who were started on curative treatment, 77 completed the course. Therapy was well tolerated. The incidence of side-effects is given in the table. Of 434 children who were started on suppressive management 3 died of unrelated causes (as did 1 control), SIDE-EFFECTS

EXPERIENCED

DURING

ANTIMONYL DIMERCAPTOSUCCINATE

CURATIVE

(%

COURSE

OF

OF TOTAL NUMBER

SODIUM

TREATED)