In order to investigate efficacy of praziquantel (biltricide) on morbidity related to Schistosoma haematobium infection, 300 subjects of which 219 had eggs in the urine were examined for urinary eggs, blood and protein before and three months after treatment. Haematuria and proteinuria disappeared in 80.4% and 75.5% of the studied subjects respectively. The disappearance rates were not related to pre-treatment levels of haematuria and proteinuria. The rates both for haematuria and proteinuria were significantly lower in the age group 15 years and over than in the younger age group. Parasitologically, praziquantel cured 85.3% of the egg positives and reduced the mean egg count by 98.2%

Aoki Yoshiki

Gatika S. M.

Gyoten Jun-Ichi

Katsumata Tatsuya

Kiliku F. M.

Kimura Eisaku

Migwi D. K.

Muhoho N.

Mutua W. R.

Uga Shoji

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Trop. Med., 35 (2), 83-90, June, 1993 83Change in Haematuria and Proteinuria Levels inUrinary Schistosomiasis after Treatment with Praziquantel-Population-based Study in a Kenyan Community-F. M. KILIKU1. D. K. MIGWI1, W. R. MUTUA1, S. M. GATIKA1, N. MUHOHO1,Eisaku KIMURA2, Tatsuya KATSUMATA2, Shoji UGA3. Jun-ichi GYOTEN4and Yoshiki AOKI2Centre for Microbiology Research, Kenya Medical Research Institute,P.O. Box 54840, Nairobi, Kenyadepartment of Parasitokgy, Institute of Tropical Medicine, Nagasaki University,Nagasaki, JapanDepartment of Medical Zoology, School of Medicine, Kobe University,Kobe, JapanDepartment of Parasitology, School of Medicine, Ehime University,Shigenobu, Onsen-gun, Ehime, JapanAbstract: In order to investigate efficacy of praziquantel (biltricide) on morbidity relatedto Schistosoma haematobium infection, 300 subjects of which 219 had eggs in the urine wereexamined for urinary eggs, blood and protein before and three months after treatment.Haematuria and proteinuria disappeared in 80.4% and 75.5% of the studied subjects respec-tively. The disappearance rates were not related to pre-treatment levels of haematuria andproteinuria. The rates both for haematuria and proteinuria were significantly lower in theage group 15 years and over than in the younger age group. Parasitologically, praziquantelcured 85.3% of the egg positives and reduced the mean egg count by 98.2%.Key words: Urinary Schistosomiasis, Praziquantel, Change, haematuria, ProteinuriaINTRODUCTIONThe infection of Schistosoma haematobium causes variety of pathological changes in theurinary system, some of which are polypoid lesions, ulcer, calcification of the bladder,deformity of the ureter. The changes may be found even among very young children of threeyears (Forsyth and Bradley, 1966), and the consequences must be serious if patients are le允untreated for years. A significant mortality related to urinary schistosomiasis was reported(Forsyth and Bradley, 1966; Smith et al, 1974; Wilkins et al., 1985). The transmissinn nf仙p~~~~~~~~~~~~~~~~~~~~~~~~~~~~■~~~~~~~■~~~~~~~~~~~~~~~･･･`･･････-･･･････-･･･････-This study was carried out in Mwachinga, Kwale District, Coast Province, Kenya under KEMRI〝ICASchistosomiasis Research and Control Project.Received for Publication August 10, 1993.contribution No. 2872 from the Institute of Tropical Medicine, Nagasaki University.84disease continues as long as parasite eggs are excreted into snail habitats. Therefore, a ra-tional chemotherapy should aim to cure the sick individuals, and to reduce egg excretion at acommunity level. An evaluation study of any anti-schistosomal drug should be based on thesetwo points.praziquantel has been shown to be a very potent drug against S. haematobium. Manyworkers have reported high parasitological cure rate and egg reduction. However, population-based studies on the effects on morbidity are limited (Mott et al, 1985). With a purpose of in-vestigation clinical effects of praziquantel, we examined 300 subjects for urinary eggs, bloodand protein, before and three months after treatment with praziquantel in a Kenyan commum-ty with a moderate infection.MATERIALS AND METHODSA total of 915 people were examined for urinary blood and protein using Uro-LabstixH (MILES-SANKYO CO. LTD.) This type of reagent strip could also test glucose and pHbut these parameters were however not considered in this study since they did not havedirect effect in diagnosis of the infection. Examination of S. haematobium egg was ac-complished by nuclepore membrane filtration method in the months of June and July. Treat-ment with praziquantel as a single dose of 40mg/kg body weight was done in July andAugust to all egg-positive persons found in the June and July servey and egg-negative per-sons of age 5 to 15 years.Three months later, urine examination was repeated and covered 635 people. The datapresented in this paper is for 300 s叫ects of all ages who attended both血しe examinationbefore and after treatment.Egg counts per 10 ml of urine was obtained from single random urine specimens ex-creted between 10.30 and 12.30 hours.Haematuria and proteinuria were graded as -, -/+, 1+, 2+, 3+.Haematuria -/+ up and proteinuria 1+ up were regarded as pathological and theirlower levels as normal. Calculation of disappearance rates of haematuria and proteimina wasbased on these criteria. For mean egg count, geometric mean of egg counts was used. Tocompare cure rates, chi-square test was used, and to compare reduction in egg count pre-and post-treatment by sex and age group, t-test was used.RESULTSEffects of praziquantel on egg excretionA total of 300 persons analysed consisted of 130 males and 168 females (data by sexfor two individual was not available). In this group, 101 males and 116 females were eggpositive. Data by age included 184 children of 0-14 years, and 115 persons who were 15years and above (data by age for one person was not available). A hundred and thi吋onepersons of 0-14 years and 87 individuals in the higher age group were egg positive.85On average, the number of egg-j一ositive persons reduced by 85.3% and there was nodifference by sex and age group. The mean egg count reduced by 98.2% on the average. Asignificant di触rence (p<0.001) was found between subjects below 14 years and above 15years age groups, though the difference in % reduction was very small (99.0 vs. 95.6, TableuChanges in egg counts before and after treatment are set out in Table 2. The rate ofmoderate- to high-count positives reduced from 71.7% before treatment to 3.2% after treat-ment. Cure rate of the egg positive cases increased as urinary egg excretion decreased(p<0.005). Only 3 out of 81 origial negatives (3.7%) turned positive after treatment.Effects on haematuria and proteinuriaChanges in levels of haematuria before and after treatment are shown in Table 3. InTable 1. Effects of praziquantel in reducing the number of egg-positive persons and mean egg count three months aftertreatmentNo. Positive Mean egg count*Male BeforeAfter% ReductionFemale BeforeAfter% ReductionTotal =　　　　BeforeAfter% Reduction101　　　　　　　69.013　　　　　　　　1.387.1　　　　　　98.1116　　　　　　　86.519　　　　　　　　1.583.6　　　　　　98.321732　　　　　　　1.485.3　　　　　　　98.2- 14 Yrs.　　　BeforeAfter% Reduction1.5 - Yrs.　　BeforeAfter% ReductionTotal * *　　　　BeforeAfter% Reduction131　　　　　　141.121　　　　　　　1.484.0　　　　　　99.087　　　　　　　　32. 111　　　　　　　1.487.4　　　　　　95.6218　　　　　　　78. 132　　　　　　　1.485.3　　　　　　　5.2: Geometric mean of (egg count + 1) was calculated to include theegg negatives after treatment.: Two persons with unknown sex and one with unknown age areexcluded.86those cases with a pre-treatment haematuria of -/+ or up, the disappearance rate ofhaematuria was 80.4%. This rate of disappearance was irrespective of pre-treatment levels.1In heavy haematuria cases (2+ up) haematuria decreased from 52.3% before treatment to6.5% after treatment. Twelve cases or 8.2% of the original 147 haematuria negative casesturned -/+ or up after treatment.In table 4, changes in levels of proteinuria before and after treatment are shown.Among the subjects with 1 + up before treatment, the disappearance rate was 75.0%. No dif-ference was found in between 1+ and 2+ levels of pre-treatment proteinuria. Rate of heavyproteinuria (2+ up) decreased from 33.1% to 3.2% after treatment. Twenty five or 14.2% ofthe 176 original proteinuria negative cases turned 1+ up after treatment.Table 5. shows the rate of disappearance of haematuria and proteinuria compared bysex and age group. After praziquantel administration no differences in the disappearance rateTable 2. Change of egg counts before and three months after treatment with praziquantelpre-treatment egg count/10 ml01-279.2)93.1)3(7. 7)3913.0}5(6(2101-50047(82. 5)8(14.0)2(3.5)571-25　　　26-10055　　　　　58J.7)　(95. 1)5　　　　　　3J.I)　　(4.9)2　　　　　　0(3.2)　　(0.0)62　　　　　610 Total265{88. 3}26{8.7}9{3.0}300{100}78(96. 3)1(1.22(2.5)81OPost-treatment 1 - 25egg count/10 m126-Total({27. 0}　　{20. 7}　　{20. 3}　　{19. 0}( ) : percentage of the total at each level of pre-treatment egg count.{　} : percentage of the grand total (300).Table 3. Change of levels of haematuria before and three months after treatment with praziquantelpre-treatment haematuna2+40(78. 4)4(7.8)3(5.9)4(7. 8)51Total258{86. 0}17{5.7}12{4.0}13{4.3}300{100}-/+　　　1+ 3+25(83. 3)0(0.0)3(10.0)2(6. 7)30Post-treatmenthaematuna-/+1+135(91. 8)6(4.1)3(2.0)2+up3(2.0)37(86. 0)5(ll.61(2.3)0(0.0)21(72. 4)2(6. 9)2(6.9)4(13.8)29{9.7]Total147{49.0}43{14.3}{10.0}　　　{17.0}( ) : percentage of the total at each level of haematuria.{　} : percentage of the grand total (300).87Table 4. Change of levels of proteinuria before and three months after treatment with praziquantelPre-treatment proteinurianegative 1 +　　　　　2 + up TotalP ost-treatm entprotemunanegative1+2+UP151(85. 8)23(13.1)2(1.1)66(79. 5)15(18.1)2(2.4)27(65. 9)12(29. 3)2(4.9)244{81.3}50{16.7}6{2.0}Tota1　　　　176　　　　　　83　　　　　　4 1{58. 7}　　　　{27. 7}　　　　{13. 7}300{100}negative: Proteinuria - and -/+ are combined.( ) : Percentage of the total at each level of proteinuria.{　} : Percentage of the grand total.Table 5. Comparison of disappearance rates in haematuria and proteinuria after treatment with prazi･quantel according to sex and age groupSex Age groupMale Female　　　-14 Yrs.　15- Yrs.79.7　　　　　).5　　　　　Us　　　　　64.7'(64)　　　(87)　　(101)　　　(51)76.4　　　　　73.1　　　　81.2'　　　　60.5'(55)　　　(67)　　　(85)　　　(38)Total).4(153)75.0(124)Haematuria% Cured(No. subject)ProteinuriaCured(No. subject)…: Difference significant at l% levelDifference significant at 5% level.Two persons with unknown sex and one with unknown age are excluded.of haematuria and proteinuria was noted between sex. When compared by age there was asignificant difference of haematuria between the older age group (15 years & over) and theyounger group (14 years & below) (p<0.01) with the older group showing 64.7% as com-pared to 88.1% in the younger age group. Proteinuria disappeared in 75.0% of the studiedsubjects. Again, a significant difference was found by age group, with older age group show-mg 60.5% compared to 81.2% of the younger age (p<o.o5).DISCUSSIONThe present study confirmed the efficacy of praziquantel on parasitological indices, thatis, very high cure rate (85.39及b) and egg reduction rate (98.79及b), in a Kenyan community threemonths a触r treatment. However, there was no difference in cure rate between the youngand older age groups in their pre-treatment averages of egg count. Both sexes had similar88cure rate. The percentage reduction in egg count was found to be very high (98.79及b). No dif-ference was noted between sex or age. These findings are largely in accordance with thepast data (Davis et al, 1979; McMahon and Kolstrup, 1979; Ejezie and Okeke, 1987),although much lower cure rates were reported by some authors (Pugh and Teesdale, 1983;wilkins and Moore, 1987).Haematuria and proteinuria disappeared in 80.4% and 75.0% of subjects after treat-ment respectively. The disappearance was not related to pretreatment levels oi! urinary bloodand protein, or sex. However, the disappearance rates both in haematuria and protemunawere significantly lower in the older age group than in the 0-4 years group. In a similarstudy by Mott et al, (1985), haematuria and proteinuria by reagent strips disappeared respec-tively in 65-73% and 69-72% of subjects after treatment, and the rates of improvementwere similar in all pre-treatment age group. Haematuria was found to be associated stronglywith hyperaemia and ulcer of the urinary bladder (Abdel-Salam and Ehsan 1978). Differentstages of ulcers of the bladder (Lichtenberg, et al, 1971) and urolithiasis will also causehaematuria. Urinary protein was reported to be of postrenal origin (Doehring et al, 1985),but the kidney might be also involved (Edington et al, 1970; Lehman et al, 1970; Greenhamand Cameron, 1980). Direct relationship between severity of pathology and intensity of infec-tion was shown (Forsyth and McDonald, 1965; Lichtenberg et al, 1971, Abdel-Salam a符dEhsan, 1978; Warren et al, 1979). The disappearance or reduction in urinary blood and pro-tein, together with the marked reduction of egg counts, following praziquantel treatment in-dicate overall improvement of the pathological changes. Several ra舶ological andultrasonographical studies which showed rapid disappearance of abnormality after treatmentsupport his findings (Oyediran et al, 1975; Farid et al, 1984; Doehring et al, 1985).The clinical improvement was particularly good in children with hi|h egg counts whentreated at early stages of the disease (Lehman et al, 1973). On the other hand, these changesmight become irreversible if patients were left untreated for many years (Forsyth andMcDonald, 1966; McDonald et al, 1968). Therefore, treating patients at early stages ofpathological changes must have substantial benefit, and our study血owed praziquantel wassufficiently effective.significantly lower rates of disappearance in haematuria and proteinuria in the olderage group were observed in our study. Lehman et al. (1973) reported the linear increase ofobstructive uropathy, bladder calcification, ureterolithiasis and - bladder retention by age.Lichtenberg et al (1971) observed much higher egg deposition in the bladder tissue in adultsthan in children. More irreversible nature of adult pathology seems to be relate to ourresults.AKNOWLEDGEMENTSThis study was undertaken as part of KEMRI/JICA Schistosomiasis Research and Con-trol Project. The authors are deeply indebted to Director, KEMRI for allowing this work tobe published. Special thanks to Dr P G Waiyaki for his advise and supervision, local leaders89and health personnel, Kenyan and Japanese colleagues for their co-operation an卓 technicalassistance.REFERENCES1 ) Abdel-Salam, E. & Ehsan, A. (1978): Cystoscopic picture of Schistosoma haematobium in Egyptianchildren correlated to intensity of infection and morbidity. Am. J. Trop. Med. Hyg., 27, 774-778.2 ) Davis, A., Biles, J.E. & Ulrich, A. M. (1979): Initial experiences with praziquantel in the treatmentof human infections due to Schistosoma haematobium. Bull. WHO., 57, 773-779.3 ) Doehring, E., Ehrich, J.H.HリVaster, U., Feldmeir, HリPoggensee, U. & Brodehl, J. (1985): Pro-temuria, haematuria, and leukocyturia in children with mixed urinary and intestinal schistosomiasis.28, 520-525.4 ) Doehring, EリReider, F., SchmidトEhry, G. & Ehrich, J.H.H. (1985): Reduction of pathological fin-dings urine and bladder lesions in infection with Schistosoma haematobium after treatment with prazi-quantel. J. Infect. Dis. 152, 807-810.5 ) Edington, G.M., Lichtenberg, F.V., Nwabuebo, I., Taylor, J.R. & Smith, J.H. (1970): Pathologic ef-fects of schistosomiasis in lbadan, Western State of Nigeria I. Incidence and intensity of infection;distribution and severity of lesions. Am. J. Trop. Med. Hyg. 19, 982-995.6 ) Ejezie, G.C. & Okeke, G.C.E. (1987): Chemotherapy in the control of urinary schistosomiasis iiNigeria. J. Trop. Med. Hyg., 90, 149-151.7 ) Farid, Z., El-Masry, Z.AリBassily, S., Trabolsi, B. & Wallace, C.K. (1984): Treatment of bilharzialobstructive uropathy with praziquantel. J. Infect. Dis. 150, 307-308.8 ) Forsyth, D.M. & McDonald, G. (1965): Urological complications of endemic schistomiasis in school -children Part 1. Usagara School. Trans. Roy. Soc. Trop. Med. Hyg. 59, 171-178.9 ) Forsyth, D.M. & McDonald, G. (1966): Urological complications of endemic schistosomiasis inschoolchildren Part 2. Donge Shool, Zanzibar. Trans. Roy. Soc. Trop. Hed. Hyg. 60, 568-578.10) Forsyth, D.M. & Bradley, D.J. (1966): The consequences of bilharziasis medical and public health im-portance in north-west Tanzania. Bull. WHO., 34, 715-735.ll) Greenham, R. & Cameron, A.H. (1980): Schistosoma haematobium and the nephrotic syndrome.Trans. Roy. Soc. Trop. Med. Hyg., 74, 609-613.12) Lehman, J.S.Jr., Farid, Z., Bassily, S. & Kent, B.C. (1970). Renal function in urinaryschistosomiasis. Am. J. Trop. Med. Hyg., 19, 1001-1006.13) Lehman, J.S.Jr., Farid, Z., Smith, J.H., Bassily, S. & El-Masry, N.A. (1973): Urinary schistosomiasisin Egypt: Clinical, radiological, bacteriological and parasitological correlations. Trans. Roy. Soc.Trop. Med. Hyg., 67, 384-399.14) Lichtenberg, F.V., Edington, G.M. Nwabuebo, I., Taylor. J.R. & Smith, J.H. (1971): Pathological ef-feet of schistosomiasis in lbadan, Western State of Nigeria I. Pathogenesis of lesions of the bladderand ureters. Am. J. Trop. Med. Hyg., 20, 244-254.15) McDonald, G., Forsyth, D.A. & Rashid, C. (1968): Urological complications of endemicschistosomiasis in school children Part 4. As modified by treatment. Trans. Roy. Soc. Trop. Med.Hyg., 62. 775-781.9016) McMahon, J.E. & Kolstrup, N. (1979): Praziquantel: a new schistosomicide against Schistosomahaematobium. Br. Med. J., 2, 1396-1399.17) Mott, K.E., Dixon, H., Osei･tutu, E., England, E.G. & Davis, A. (1985): Effect praziquantel onhematuria and proteinuria in urinary schistosomiasis. Am. J. Trop. Med. Hyg., 34, 1119-1126.18) Oyediran, A.B.O.O., Abayomi, I.O., Akinkugbe, O.O., Bohrer, S.P. & Lucas, A.O. (1975):Renographic studies in vesical schistomiasis in children. Am. J. Trop. Med. Hyg., 24, 274-279.19) Pugh, R.N.H. & Teesdale, C.H. (1983): Single dose oral treatment in urinary schistosomiasis: a dou-ble blind trial. Br. Med. J., 286, 429-432.20) Smith, J. H., Kamel, I.A., Elwi, A. & Lichtenberg, F.V. (1974): A quantitative post mortem analysisof urinary schistosomiasis in Egypt I. Pathology and pathogenesis. Am. J. Trop. 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Change in Haematuria and Proteinuria Levels in Urinary Schistosomiasis after Treatment with Praziquantel : Population-based Study in a Kenyan Community

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Change in Haematuria and Proteinuria Levels in Urinary Schistosomiasis after Treatment with Praziquantel : Population-based Study in a Kenyan Community

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