Reversibility of urinary tract abnormalities due to Schistosoma haematobium infection

Kidney International, Vol. 30 (1986), pp. 582—585

Reversibility of urinary tract abnormalities due to Schistosoma haematobium infection EKKEHARD DOEHRING, JOCHEN H.H. EHRICH, and HANS J. BREMER Department of Pediatric Nephrology and Metabolic Disorders, Medizinische Hochschule, 3000 Hannover 61, and Department of General Pediatrics, Metabolic Disorders, Nutrition and Nephrology, University of Dbsseldotf, 4000 Düsseldorf!, Federal Republic of Germany

Reversibility of urinary tract abnormalities due to Schistosoma haematobium infection. In view of the controversial results regarding reversibility of urinary tract lesions due to Schistosoma haematobium infection, 103 patients in the People's Republic of Congo were followed up one year after treatment with Praziquantel (40 mg/kg body wt) by means of ultrasonography. The study group consisted mainly of children. Before therapy a total of 113 lesions were detected in the lower urinary tract. These consisted of bladder wall enlargements (N = 53), enlargements of the bladder wall in combination with singular (N = 16) or multiple polyps (N 30), vesical calcifications (N = 10), and cases with cystitis cystica (N = 4). One year after therapy, a drastic reduction of ova output was observed, and only eight pathological abnormalities of the lower urinary tract were still detectable. Vesical calcifications persisted in four out often cases. Urinary tract obstructions of different degrees (N = 42) showed a comparably marked reversibility. It was concluded that, in children, the resolution of bladder lesions induced by urinary schistosomiasis resulted in reversibility of urinary tract obstructions one year after treatment with Praziquantel.

induced by Schistosoma huematohium infection. Details of this investigation are published elsewhere [8]. The study was conducted parallel to the bilateral German—Congolese antischistosomiasis control program "Lutte contre Ia Schistosomiase". A prevalence of urinary schistosomiasis of 10% was found in the study area, Bouansa, when 10 ml urine samples of more than

90% of the cities' total population of 7000 inhabitants were examined. In the course of the concomitant vertical mass treatment program, all infected individuals discovered in

Bouansa and surrounding villages were treated with Praziquantel (40 mg/kg body wt). A subset of 213, mostly heavily infected patients was extensively examined, including abdominal ultrasonography [8]. Of

those, 126 predominantly young patients were found to have pathological ultrasonographical findings of the urinary tract before therapy, which were attributable to S. haematobiurn infection. All 213 patients initially admitted to the study were

Previous investigations about urinary schistosomiasis have treated with Praziquantel (40 mg/kg body wt) under surveillance of the main investigator in June 1984, clearly shown that egg output and pathological urine findings 103 patients could be followed—up I 1 months after therapy such as proteinuria, hematuria, and leukocyturia are reversible and underwent a second ultrasonographical examination. The after antisehistosomal treatment 1—31. Controversial results, age range was from six to 65 years, but only 11 patients were however, have been published regarding the prognosis of older than 18 years. Informed consent was obtained in French urinary tract lesions following treatment. Davis found no reducfrom the parents or family representatives after explanation of tion of obstructive uropathy after therapy 4], whereas other studies indicated reversibility of pathological findings in the the diagnostic procedure. upper and lower urinary tract [5—7].

Urine examination

The present investigation provides parasitological and ultrasonographical follow—up data of urinary tract abnormalities

in patients with Schistosorna haematobiu,n infection one year after therapy with Praziquantel.

Urine samples were collected on two consecutive days between 11 a.m. and 2 p.m., because of the day—to—day and circadian variation of ova output and pathological urine findings

[9, 10]. Number and viability of eggs was assessed by a

Methods

sensitive filtration technique [11]. Proteinuria was quantita-

Study area and patients The investigations were conducted in Bouansa in the People's Republic of Congo, an area with S. haernatobium infection

tively determined after centrifugation of urine by the Coomassie

blue dye binding test [12]. Erythrocyturia and leukocyturia were quantified in a Neubauer chamber.

only, but not S. mansoni or S. intercalatum. A community study was performed between May and July 1984 assessing pathological ultrasonographical findings of the urinary tract

Ultrasound examination

During follow—up studies in May 1985, a portable digital gray—scale ultrasound unit with a 3.5 MHz linear array real time

scanner was used (Fa. Hellige, Freiburg, FRG). The bladder Received for publication July 19, 1985, and in revised form March 4, 1986

was evaluated only when filled with urine, and the bladder wall

© 1986 by the International Society of Nephrology

bladder. Pathological findings in the lower urinary tract were

thickness (BWT) was measured in the dorsal part of the 582

583

Reversibility of urinary tract lesions

Table 1. Egg output, proteinuria, erythrocyturia and leukocyturia of 103 patients with urinary schistosomiasis before and one year after treatment with Praziquantel (medians and 95% confidence limits) Before therapy

After therapy

(June 1984)

(May 1985)

N=103

Number of patients excreting viable ova Median ova output (eggs/b ml) Median proteinuria (mg/liter) Median erythrocyturia (cells/1d) Median leukocyturia (cells/1.d)

103

246 (154—300) 630 (410—840) 972 (720—1188) 468 (412—648)

Table 2. Frequency of pathological ultrasonographical findings of the lower urinary tract in 103 patients with urinary schistosomiasis before and one year after application of Praziquantel Number of patients with urinary tract lesions

N=103 26 0 (0—0) 68 (56—80) 0 (0—1)

Isolated bladder wall enlargement (BWE) BWE plus singular polyp BWE plus multiple polyps Vesical calcifications Cystitis cystica

Before therapy

After therapy

1984

1985

53 16

3

30

0 4 0

10

4

1

0

(0—3)

Table 3. Bladder wall thickness in mm before and one year after treatment with Praziquantel in groups of patients showing different vesical lesions before therapy

classified as reported in previous publications by our working

Bladder wall thickness in mm

group on ultrasonography in urinary schistosomiasis [8, 13—15].

Isolated bladder wall enlargement (BWE) was defined as a continuously enlarged bladder wall in excess of 5 mm with a smooth or partly wave—like inner contour. When circumscript mucosa dilatations protruded more than 5 mm from the inner bladder wall into the bladder lumen, this was classified as BWE in combination with singular or multiple polyps, since such polyps were always associated with BWE. Vesicle calcifications were sonographically characterized as minute spots of high echogenicity, usually without distal shadowing [13, 14]. Cystitis cystica was diagnosed when several small echo—free holes without pulsations were detected in an enlarged bladder wall, mimicking an almost sieve—like appearance [13]. In the upper urinary tract, a continuous dilatation of the renal

Patients with isolated BWE

(N = 53)

Patients with BWE plus singular polyp (N = 16) Patients with BWE plus multiple polyps (N = 30)

Before therapy

After therapy

1984

1985

7 7—8 8

3—4

8—9

2—4

10 9—10

3—4

3

4 3

than 100 eggs per 10 ml. Accordingly, physiological proteinuria,

erythrocyturia, and leukocyturia were found one year after therapy. This reduction of urine findings was paralleled by a

collecting system in excess of 5 mm plus dilatation of the marked reversibility of pathological ultrasonographical abnorpelvicalyceal structures was regarded suggestive of urinary malities in the lower urinary tract (Table 2), In 1984, 103 tract obstruction grade 1. The confirmative criterium for the patients revealed a total number of 113 pathological vesical diagnosis of urinary tract obstruction (UTO) was considered a persistence of this dilatation of the renal pelvis 30 minutes after voiding of the bladder, since ureterovesical reflux was then thought to be most unlikely. UTO II was diagnosed when the dilatation of the renal collecting system was more than 1 cm in combination with a marked prominence of the pelvicalyceal structures. UTO Grade III occurred when, in addition to UTO II, the ipsilateral ureter could be visualized on its total exten-

lesions, whereas only eight sonographical abnormalities of the

lower urinary tract were detected in 1985. These consisted mainly of isolated bladder wall enlargements and vesical calcifications. The only singular polyp, during follow—up investiga-

tions, was encountered in a patient who showed active S. haematobium infection, that is, 71 viable ova per 10 ml urine. In order to provide quantitative data concerning the reduc-

tion of bladder wall enlargement (BWE) after therapy, the sion into the lower pelvis and demonstrated in the dorsal medians and 95% confidence limits (95% CL) of bladder wall thickness (BWT) before and after therapy were calculated perivesical area. Statistical evaluation Results of ova output, pathological urine findings, bladder wall enlargements and dilatations of the renal collecting system were calculated as medians and 95% confidence limits. Significance of difference was tested with the Wilcoxon matched pairs signed rank test.

(Table 3). Patients with isolated BWE showed a median BWT of 7 mm (95% CL 7-8) in 1984, as opposed to 3 mm (95% CL 3-4) one year after therapy. The corresponding values for the groups with BWE plus singular or multiple polyps were 8 mm (95% CL 8-9) and 10 mm (95% CL 9-10) before therapy, as compared to 4 mm (95% CL 2-4) and 3 mm (95% CL 3-4) one year later. The

differences of BWT before and after administration of

Praziquantel were significant (P < 0.001) for all three groups of Results patients. Urinary tract obstruction (UTO) reversed in the great majorTreatment with Praziquantel (40 mg/kg body wt) resulted in a

marked reduction of egg excretion and pathological urine

ity of patients one year after treatment (Table 4). Before

findings one year after therapy (Table 1). In the study group the therapy, 37 patients had a total of 42 kidneys with median ova output in 1984 was 246 per 10 ml urine and nil in ultrasonographically—defined obstructive uropathy, including 1985. Twenty—six patients still passed viable ova (range 0.1 to five cases with bilateral UTO. One year later UTO persisted in 160 per 10 ml urine), but only one of them had an output of more four patients. A ten—year—old boy with UTO grade III in 1984

584

Doehring ci of

Table 4. Frequency of urinary tract obstruction in 103 patients with urinary schistosomiasis before and after therapy with Praziquantel

rounding human habitats. In contrast, reinfection under

Number of kidneys with or without UTO

pected to begin four months after antischistosomal therapy [31. Davis [4] found no reversibility of urinary tract abnormalities in 20 to 40-year—old patients after therapy with antimonials. It

UTO absent

UTO grade 1 UTO grade 11 UTO grade III

Before therapy

After therapy

1984

1985

164

25

201 4

12

1

5

0

hyperendemic conditions without mass treatment can be ex-

has been repeatedly pointed out that fibrotic changes of the lower urinary tract caused by long—standing disease in adults would not resolve, whereas obstruction of urine flow caused by vesical polyps and edema would be reversible [6, 7, 19]. In our

opinion, therefore, the age of patients under investigation is very important.

Three other studies have indicated regression of bladder

still revealed UTO grade II at the time of follow—up. In all other polyps in individual patients after administration of antimonials cases the dilatation of the renal collecting system was mild (that [5, 23, 24]. The most striking effect of Praziquantel on the lower is, less than 8 mm). One patient without UTO in 1984 revealed urinary tract was the almost radical and longstanding reversia dilatation of the renal sinus of 7 mm one year after treatment. bility of bladder polyps. The only vesical polyp encountered This patient showed no BWE and no excretion of S. during follow—up was seen in a patient with apparent schistohoematobium ova. somal reinfection. The present study together with a pilot The median dilatation of the renal collecting system before investigation on six patients of the same study area [15] seem to therapy was 8 mm (95% CL 7-9) in patients with UTO grade I, he the first to sonographically evaluate the effect of Prazi-

14 mm (95% CL 12-17) as well as 20 mm (95% CL 14-25) in quantel on urinary tract lesions in patients with urinary schisthose with UTO grade II and grade III. A significant reduction tosomiasis. of the values to 1 mm (95% CL 0-3), 2 mm (95% CL 0-3) and 2 The remarkably low amount of persons with bladder wall enlargements after therapy, which was detected in only four out mm (95% CL 0-12), was seen a year later (P < 0.00 1). of 103 patients during follow—up, was considered insignificant Discussion

The results of this study indicate reversibility of urinary tract abnormalities in young patients with S. haernatobium infection one year after treatment with Praziquantel. This is in accord-

and unrelated to urinary schistosomiasis except in one case. This percentage may indicate the spontaneous occurrence of bladder wall enlargements in the study area. Examination of an

age matched group of healthy Congolese controls without ance with a radiological study by Farid et al [16] and other urinary schistosomiasis and patients with only minimal Schisinvestigators who have administered antischistosomal drugs tosoma haernatobium infection (that is, excretion of less than other than Praziquantel [5—7, 17—20]. By contrast, different 20 eggs per 10 ml urine) showed a comparable rate of bladder studies reported no or substantially less reversibility of urinary tract lesions following treatment [4, 21, 221. In comparing the different results of these investigations, the number of patients examined, the effectiveness of therapy, the interval of follow— up, the prevalence of disease in the study area including the chance of reinfection, and the age of the patients investigated, have to be taken into consideration. Some authors have only reported on relatively small numbers of patients, that is, less than 10 patients [5, 16, 17].

wall enlargements of 4% [8].

Calcifications of the bladder showed the highest rate of persistence. This finding is in accordance with other studies [4, 6, 21], and can be explained by the fact that vesical calcifica-

tions represent calcified ova which remain trapped in the bladder tissue [251.

Urinary tract obstruction represents the most important

functional impairment of S. haematobium infection involving the potential risk of renal dysfunction [261 and a considerable The studies of MacDonald and Forsyth as well as mortality rate [27, 28]. In all patients of this study moderate and MacDonald, Forsyth, and Rashid [21, 22], indicating persis- severe urinary tract obstruction markedly regressed after thertence of urinary tract abnormalities after treatment with apy. Only one patient was left with a definite residual lesion of antimonials, were performed on a comparable number of pa- the upper urinary tract. Three children still revealed mild tients as in the present investigation. Their differing results may dilatations of the renal collecting system one year after therapy. partly be explained by the fact that more advanced antischisto- This significant reversibility of obstructive uropathy was somal compounds such as Praziquantel have a higher efficiency thought to he due to the resolution of inflammatory and than antimonials. Reinfection may have interfered with the polypoid changes in the lower urinary tract. MacDonald and Forsyth [211 assessed the effect of resolution of pathological lesions in the investigation of MacDonald and Forsyth [21], as suggested by a 40% prevalence of antischistosomal therapy on urinary tract lesions by radiologiurinary schistosomiasis at their time of follow—up. Reinfection cal techniques and pointed out the high organizational effort of of urinary schistosomiasis in our study area was very low due to such an approach. In the present investigation, the use of a a primarily low prevalence of disease and vertical control portable ultrasound unit proved to be a practical diagnostic tool measures in the form of mass treatment performed in 1984. to evaluate pathological abnormalities induced by urinary schisThus, the great majority of infected patients in the investigated tosomiasis. This was also described by Degremont et al [29]. city were effectively treated. The transmission rate of urinary Furthermore, in the present study ultrasonography, which is schistosomiasi s, therefore, substantially declined and immedi- much easier to perform especially under field conditions, was ate reimportation of disease transmission from neighbouring shown to be a rapid method for follow—up examinations of villages was unlikely, since mass treatment also enclosed stir- patients. The results of our data support modern concepts of

Reversibility of urinary tract lesions

combatting against urinary schistosomiasis, which try to reduce morbidity with effective mass chemotherapy [301. The importance of early antischistosomal treatment in childhood, when

pathological conditions are still reversible, is emphasized. Ultrasonography may serve as an important diagnostic method of nephrological surveys in the tropics. Acknowledgments This study was supported by Deutsche Forschungsgemeinschaft

grant number Do 288 1-I, Gesellschaft der Freunde der Medizinischen

Hochschule Hannover and Nordwestdeutsche Gesellschaft für Kinderheilkunde, FRG. The ultrasound unit was provided by Fa.

Hellige, Freiburg, FRG. We are indebted to Mister Sorge for preparing the ultrasound apparatus for use in the tropics. We thank the Ministries of Scientific Research, Brazzaville for logistical assistance. The laboratory help of Dr. M. Leichsenring and Mr. T. Kracke and the excellent secretarial work of Mrs. Martin are acknowledged.

Reprint request to Dr. E. Doehring, Department of Pediatric Nephrology and Metabolic Disorders, Medizinische Hochschule, Konstanty—Gut.schow—Str. 8, 3 Hannover 61, Federal Republic of Germany

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