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

Reversibility of urinary tract abnormalities due to Schistosomahaematobium 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 GeneralPediatrics, Metabolic Disorders, Nutrition and Nephrology, University of Dbsseldotf, 4000 Düsseldorf!, Federal Republic of Germany

Reversibility of urinary tract abnormalities due to Schistosomahaematobium infection. In view of the controversial results regardingreversibility of urinary tract lesions due to Schistosoma haematobiuminfection, 103 patients in the People's Republic of Congo were followedup one year after treatment with Praziquantel (40 mg/kg body wt) bymeans of ultrasonography. The study group consisted mainly of chil-dren. Before therapy a total of 113 lesions were detected in the lowerurinary 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 caseswith cystitis cystica (N = 4). One year after therapy, a drastic reductionof ova output was observed, and only eight pathological abnormalitiesof the lower urinary tract were still detectable. Vesical calcificationspersisted in four out often cases. Urinary tract obstructions of differentdegrees (N = 42) showed a comparably marked reversibility. It wasconcluded that, in children, the resolution of bladder lesions induced byurinary schistosomiasis resulted in reversibility of urinary tract obstruc-tions one year after treatment with Praziquantel.

Previous investigations about urinary schistosomiasis haveclearly shown that egg output and pathological urine findingssuch as proteinuria, hematuria, and leukocyturia are reversibleafter antisehistosomal treatment 1—31. Controversial results,however, have been published regarding the prognosis ofurinary tract lesions following treatment. Davis found no reduc-tion of obstructive uropathy after therapy 4], whereas otherstudies indicated reversibility of pathological findings in theupper and lower urinary tract [5—7].

The present investigation provides parasitological andultrasonographical follow—up data of urinary tract abnormalitiesin patients with Schistosorna haematobiu,n infection one yearafter therapy with Praziquantel.

Methods

Study area and patientsThe investigations were conducted in Bouansa in the Peo-

ple's Republic of Congo, an area with S. haernatobium infectiononly, but not S. mansoni or S. intercalatum. A communitystudy was performed between May and July 1984 assessingpathological ultrasonographical findings of the urinary tract

Received for publication July 19, 1985,and in revised form March 4, 1986

© 1986 by the International Society of Nephrology

induced by Schistosoma huematohium infection. Details of thisinvestigation are published elsewhere [8]. The study was con-ducted parallel to the bilateral German—Congolese antischisto-somiasis control program "Lutte contre Ia Schistosomiase". Aprevalence of urinary schistosomiasis of 10% was found in thestudy area, Bouansa, when 10 ml urine samples of more than90% of the cities' total population of 7000 inhabitants wereexamined. In the course of the concomitant vertical masstreatment program, all infected individuals discovered inBouansa and surrounding villages were treated withPraziquantel (40 mg/kg body wt).

A subset of 213, mostly heavily infected patients was exten-sively examined, including abdominal ultrasonography [8]. Ofthose, 126 predominantly young patients were found to havepathological ultrasonographical findings of the urinary tractbefore therapy, which were attributable to S. haematobiurninfection. All 213 patients initially admitted to the study weretreated with Praziquantel (40 mg/kg body wt) under surveillanceof the main investigator in June 1984,

103 patients could be followed—up I 1 months after therapyand underwent a second ultrasonographical examination. Theage range was from six to 65 years, but only 11 patients wereolder than 18 years. Informed consent was obtained in Frenchfrom the parents or family representatives after explanation ofthe diagnostic procedure.

Urine examination

Urine samples were collected on two consecutive days be-tween 11 a.m. and 2 p.m., because of the day—to—day andcircadian variation of ova output and pathological urine findings[9, 10]. Number and viability of eggs was assessed by asensitive filtration technique [11]. Proteinuria was quantita-tively determined after centrifugation of urine by the Coomassieblue dye binding test [12]. Erythrocyturia and leukocyturiawere quantified in a Neubauer chamber.

Ultrasound examination

During follow—up studies in May 1985, a portable digitalgray—scale ultrasound unit with a 3.5 MHz linear array real timescanner was used (Fa. Hellige, Freiburg, FRG). The bladderwas evaluated only when filled with urine, and the bladder wallthickness (BWT) was measured in the dorsal part of thebladder. Pathological findings in the lower urinary tract were

582

Reversibility of urinary tract lesions 583

Table 1. Egg output, proteinuria, erythrocyturia and leukocyturia of103 patients with urinary schistosomiasis before and one year aftertreatment with Praziquantel (medians and 95% confidence limits)

Before therapy After therapy(June 1984) (May 1985)N=103 N=103

Number of patients excretingviable ova 103 26

Median ova output (eggs/b ml) 246 0(154—300) (0—0)

Median proteinuria (mg/liter) 630 68(410—840) (56—80)

Median erythrocyturia (cells/1d) 972 0(720—1188) (0—1)

Median leukocyturia (cells/1.d) 468 0(412—648) (0—3)

classified as reported in previous publications by our workinggroup on ultrasonography in urinary schistosomiasis [8, 13—15].

Isolated bladder wall enlargement (BWE) was defined as acontinuously enlarged bladder wall in excess of 5 mm with asmooth or partly wave—like inner contour. When circumscriptmucosa dilatations protruded more than 5 mm from the innerbladder wall into the bladder lumen, this was classified as BWEin combination with singular or multiple polyps, since suchpolyps were always associated with BWE. Vesicle calcifica-tions were sonographically characterized as minute spots ofhigh echogenicity, usually without distal shadowing [13, 14].Cystitis cystica was diagnosed when several small echo—freeholes without pulsations were detected in an enlarged bladderwall, mimicking an almost sieve—like appearance [13].

In the upper urinary tract, a continuous dilatation of the renalcollecting system in excess of 5 mm plus dilatation of thepelvicalyceal structures was regarded suggestive of urinarytract obstruction grade 1. The confirmative criterium for thediagnosis of urinary tract obstruction (UTO) was considered apersistence of this dilatation of the renal pelvis 30 minutes aftervoiding of the bladder, since ureterovesical reflux was thenthought to be most unlikely. UTO II was diagnosed when thedilatation of the renal collecting system was more than 1 cm incombination with a marked prominence of the pelvicalycealstructures. UTO Grade III occurred when, in addition to UTOII, the ipsilateral ureter could be visualized on its total exten-sion into the lower pelvis and demonstrated in the dorsalperivesical area.

Statistical evaluationResults of ova output, pathological urine findings, bladder

wall enlargements and dilatations of the renal collecting systemwere calculated as medians and 95% confidence limits. Signif-icance of difference was tested with the Wilcoxon matchedpairs signed rank test.

Results

Treatment with Praziquantel (40 mg/kg body wt) resulted in amarked reduction of egg excretion and pathological urinefindings one year after therapy (Table 1). In the study group themedian ova output in 1984 was 246 per 10 ml urine and nil in1985. Twenty—six patients still passed viable ova (range 0.1 to160 per 10 ml urine), but only one of them had an output of more

Table 2. Frequency of pathological ultrasonographical findings of thelower urinary tract in 103 patients with urinary schistosomiasis before

and one year after application of Praziquantel

Number of patients with urinarytract lesions

Before therapy After therapy1984 1985

Isolated bladder wall enlargement(BWE) 53 3

BWE plus singular polyp 16 1

BWE plus multiple polyps 30 0Vesical calcifications 10 4Cystitis cystica 4 0

Table 3. Bladder wall thickness in mm before and one year aftertreatment with Praziquantel in groups of patients showing different

vesical lesions before therapy

Bladder wall thickness in mm

Before therapy1984

After therapy1985

Patients with isolated BWE(N = 53)

Patients with BWE plussingular polyp (N = 16)

Patients with BWE plusmultiple polyps (N = 30)

77—8

88—9

109—10

33—4

42—4

33—4

than 100 eggs per 10 ml. Accordingly, physiological proteinuria,erythrocyturia, and leukocyturia were found one year aftertherapy. This reduction of urine findings was paralleled by amarked reversibility of pathological ultrasonographical abnor-malities in the lower urinary tract (Table 2), In 1984, 103patients revealed a total number of 113 pathological vesicallesions, whereas only eight sonographical abnormalities of thelower urinary tract were detected in 1985. These consistedmainly of isolated bladder wall enlargements and vesical calci-fications. 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, themedians and 95% confidence limits (95% CL) of bladder wallthickness (BWT) before and after therapy were calculated(Table 3). Patients with isolated BWE showed a median BWT of7 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 groupswith BWE plus singular or multiple polyps were 8 mm (95% CL8-9) and 10 mm (95% CL 9-10) before therapy, as compared to4 mm (95% CL 2-4) and 3 mm (95% CL 3-4) one year later. Thedifferences of BWT before and after administration ofPraziquantel were significant (P < 0.001) for all three groups ofpatients.

Urinary tract obstruction (UTO) reversed in the great major-ity of patients one year after treatment (Table 4). Beforetherapy, 37 patients had a total of 42 kidneys withultrasonographically—defined obstructive uropathy, includingfive cases with bilateral UTO. One year later UTO persisted infour 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 withurinary schistosomiasis before and after therapy with Praziquantel

Number of kidneys with or without UTO

Before therapy1984

After therapy1985

UTO absentUTO grade 1

UTO grade 11

UTO grade III

164

25

125

2014

1

0

still revealed UTO grade II at the time of follow—up. In all othercases the dilatation of the renal collecting system was mild (thatis, less than 8 mm). One patient without UTO in 1984 revealeda dilatation of the renal sinus of 7 mm one year after treatment.This patient showed no BWE and no excretion of S.hoematobium ova.

The median dilatation of the renal collecting system beforetherapy was 8 mm (95% CL 7-9) in patients with UTO grade I,14 mm (95% CL 12-17) as well as 20 mm (95% CL 14-25) inthose with UTO grade II and grade III. A significant reductionof the values to 1 mm (95% CL 0-3), 2 mm (95% CL 0-3) and 2mm (95% CL 0-12), was seen a year later (P < 0.00 1).

Discussion

The results of this study indicate reversibility of urinary tractabnormalities in young patients with S. haernatobium infectionone year after treatment with Praziquantel. This is in accord-ance with a radiological study by Farid et al [16] and otherinvestigators who have administered antischistosomal drugsother than Praziquantel [5—7, 17—20]. By contrast, differentstudies reported no or substantially less reversibility of urinarytract lesions following treatment [4, 21, 221. In comparing thedifferent results of these investigations, the number of patientsexamined, the effectiveness of therapy, the interval of follow—up, the prevalence of disease in the study area including thechance of reinfection, and the age of the patients investigated,have to be taken into consideration. Some authors have onlyreported on relatively small numbers of patients, that is, lessthan 10 patients [5, 16, 17].

The studies of MacDonald and Forsyth as well asMacDonald, Forsyth, and Rashid [21, 22], indicating persis-tence of urinary tract abnormalities after treatment withantimonials, were performed on a comparable number of pa-tients as in the present investigation. Their differing results maypartly be explained by the fact that more advanced antischisto-somal compounds such as Praziquantel have a higher efficiencythan antimonials. Reinfection may have interfered with theresolution of pathological lesions in the investigation of Mac-Donald and Forsyth [21], as suggested by a 40% prevalence ofurinary schistosomiasis at their time of follow—up. Reinfectionof urinary schistosomiasis in our study area was very low due toa primarily low prevalence of disease and vertical controlmeasures in the form of mass treatment performed in 1984.Thus, the great majority of infected patients in the investigatedcity were effectively treated. The transmission rate of urinaryschistosomiasi s, therefore, substantially declined and immedi-ate reimportation of disease transmission from neighbouringvillages was unlikely, since mass treatment also enclosed stir-

rounding human habitats. In contrast, reinfection underhyperendemic conditions without mass treatment can be ex-pected to begin four months after antischistosomal therapy [31.

Davis [4] found no reversibility of urinary tract abnormalitiesin 20 to 40-year—old patients after therapy with antimonials. Ithas been repeatedly pointed out that fibrotic changes of thelower urinary tract caused by long—standing disease in adultswould not resolve, whereas obstruction of urine flow caused byvesical polyps and edema would be reversible [6, 7, 19]. In ouropinion, therefore, the age of patients under investigation isvery important.

Three other studies have indicated regression of bladderpolyps in individual patients after administration of antimonials[5, 23, 24]. The most striking effect of Praziquantel on the lowerurinary tract was the almost radical and longstanding reversi-bility of bladder polyps. The only vesical polyp encounteredduring follow—up was seen in a patient with apparent schisto-somal reinfection. The present study together with a pilotinvestigation on six patients of the same study area [15] seem tohe the first to sonographically evaluate the effect of Prazi-quantel on urinary tract lesions in patients with urinary schis-tosomiasis.

The remarkably low amount of persons with bladder wallenlargements after therapy, which was detected in only four outof 103 patients during follow—up, was considered insignificantand unrelated to urinary schistosomiasis except in one case.This percentage may indicate the spontaneous occurrence ofbladder wall enlargements in the study area. Examination of anage matched group of healthy Congolese controls withouturinary schistosomiasis and patients with only minimal Schis-tosoma haernatobium infection (that is, excretion of less than20 eggs per 10 ml urine) showed a comparable rate of bladderwall enlargements of 4% [8].

Calcifications of the bladder showed the highest rate ofpersistence. 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 thebladder tissue [251.

Urinary tract obstruction represents the most importantfunctional impairment of S. haematobium infection involvingthe potential risk of renal dysfunction [261 and a considerablemortality rate [27, 28]. In all patients of this study moderate andsevere urinary tract obstruction markedly regressed after ther-apy. Only one patient was left with a definite residual lesion ofthe upper urinary tract. Three children still revealed milddilatations of the renal collecting system one year after therapy.This significant reversibility of obstructive uropathy wasthought to he due to the resolution of inflammatory andpolypoid changes in the lower urinary tract.

MacDonald and Forsyth [211 assessed the effect ofantischistosomal therapy on urinary tract lesions by radiologi-cal techniques and pointed out the high organizational effort ofsuch an approach. In the present investigation, the use of aportable ultrasound unit proved to be a practical diagnostic toolto evaluate pathological abnormalities induced by urinary schis-tosomiasis. This was also described by Degremont et al [29].Furthermore, in the present study ultrasonography, which ismuch easier to perform especially under field conditions, wasshown to be a rapid method for follow—up examinations ofpatients. The results of our data support modern concepts of

Reversibility of urinary tract lesions 585

combatting against urinary schistosomiasis, which try to reducemorbidity with effective mass chemotherapy [301. The impor-tance of early antischistosomal treatment in childhood, whenpathological conditions are still reversible, is emphasized.Ultrasonography may serve as an important diagnostic methodof nephrological surveys in the tropics.

Acknowledgments

This study was supported by Deutsche Forschungsgemeinschaftgrant number Do 288 1-I, Gesellschaft der Freunde der MedizinischenHochschule Hannover and Nordwestdeutsche Gesellschaft fürKinderheilkunde, FRG. The ultrasound unit was provided by Fa.Hellige, Freiburg, FRG. We are indebted to Mister Sorge for preparingthe ultrasound apparatus for use in the tropics. We thank the Ministriesof Scientific Research, Brazzaville for logistical assistance. The labo-ratory help of Dr. M. Leichsenring and Mr. T. Kracke and the excellentsecretarial work of Mrs. Martin are acknowledged.

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

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