REDUCTION OF MORBIDITY IN HEPATOSPLENIC
SCHISTOSOMIASIS M ANSONI A FTER TREATM ENT WITH
PRAZIQUANTEL: A LONG TERM STUDY
Ana Lúcia C. Domingues and Amaury D. Coutinho
F o r t y - t w o w ith h e p a to s p le n ic p a t i e n t s tr e a t e d w ith p r a z i q u a n t e l a n d f o l l o w e d u p f o r 5 y e a r s . O n e h a l f o f th e p a t i e n t s r e c e iv e d a s in g le 3 0 m g / k g d o s e a n d th e o th e r h a lf , t w o d o s e s o f 2 5 m g / k g g i v e n 4 h r s a p a rt. A c c o r d i n g to H o f f m a n a n d K a t o - K a t z s to o l e x a m s , a n 8 3 .3 % c u r e rate, w a s o b s e r v e d a f t e r tw e lv e m o n th s . S t o o l e gg c o u n ts in c a s e s o f i n c o m p le te c u re w e re g r e a t l y re d u c e d . L i v e r f u n c t i o n , a s a s s e s s e d b y s e r u m le v e ls o f a s p a r t a t e a m in o tr a n s fe r a s e , a la n i n e a m in o tr a n s fe r a s e , g a m m a g l u t a m y l t r a n s f e r a s e a n d a l k a l i n e p h o s p h a t a s e a c tiv itie s a s w e ll a s a l b u m i n a n d g a m m a g l o b u l i n s h o w e d m a r k e d i m p r o v e m e n t a f t e r o n e y e a r . H e p a t o m e g a l y w a s r e d u c e d in 8 1 . 0 % o f p a t i e n t s a n d s p l e n o m e g a l y in 7 8 .8 % . S p l e e n re g r e s s io n w a s c o m p le te in 1 5 . 1 % o f th e to ta l, a n d in 1 8 . 5 % o f t h o s e w ith c o m p e n s a t e d h e p a to s p le n ic d is e a s e . A s a r e s u l t o f th e s e o b s e r v a tio n s , th e a u t h o r s r e c o m e n d e a r ly tr e a t m e n t w it h a n t i - s c h i s t o s o m a l m e d ic a tio n , e i t h e r o x a m n i q u i n e o r p r a z i q u a n t e l , to h a l t p r o g r e s s i o n o f d i s e a s e a n d r e d u c e s p le n o m e g a ly .
K e y - w o r d s : H e p a t o s p l e n i c s c h i s t o s o m i a s i s m a n s o n i. T r e a tm e n t. R e v e r s io n .
Specific treatment of patients with hepatosple- nic schistosomiasis (HS) has been the subject of many therapeutic trials including those using a n t i m o n y 25 32( Niridazole12, hycanthone1 5, oxamniquine6 13151819 and praziquantel^ ^ 33 Results have often been favourable though most post-treatment periods of observation have been limited to the short term.
The object of this investigation was to study the effect of praziquantel chemotherapy on HS schisto somiasis, by assessing long-term therapeutic efficacy and clinical response using tests of liver function, regression in hepatomegaly/splenomegaly and stool egg counts.
M A TERIA L A N D M ETH O D S
Forty-two patients with chronic hepatosplenic schistosomiasis were treated in the Hospital das Clínicas of the Universidade Federal of Pernambuco. These patients came from areas in the Northeast of Brazil (States of Pernambuco and Alagoas) where schistosomiasis mansoni is hyperendemic.
Twenty-one of the patients were given a single oral 30mg/kg dose of praziquantel; the other half, two doses of 25mg/kg, each given four hours apart.
D epartm en t o f Internal M edicine o f the U niversidade F ed e ral o f P ernam buco, R ecife, P E , Brazil.
E nd ereço para correspondência: D r. A m aury D . Coutinho. C entro de P esq u isas “ A g g eu M agalhães” ,/F I O C R U Z . CP: 7 4 7 2 - 5 0 7 3 0 R ecife, P E , Brasil.
R eceb id o para publicação em 2 1 /0 6 /9 0 .
Thirty-one of the patients were females; eleven were males. In endemic areas, in Northeast Brazil females tend to predominate among HS patients. Ages of the patients ranged from ten to forty-six, with an average age of t w e n t y -four, and a standard deviation of about three years (Table 1).
T able 1 - A g e d is tr ib u tio n a n d m e a n n u m b e r o f e g g s in s to o l in 4 2 p a t ie n t s w ith s c h is to s o m ia s is m a n so n i.
A g e Range N.° patients % M ean number o feggs/g feces
1 0 - 1 9 13 30.95 2,7 6 8 2 0 - 2 9 17 4 0 .4 8 2 ,4 8 4
3 0 - 3 9 10 23 .8 1 613
4 0 - 4 6 2 4 .7 6 152
Total 42* 1 0 0 .0 0
* A verage age: 2 4 y; S - 2.75
D o m in g u e s A L C , C o u tin h o A D . R e d u c tio n o f m o r b id ity in h e p a to s p le n ic s c h is to s o m ia s is m a n s o n i a f te r tr e a tm e n t w ith p r a z iq u a n te l: a lo n g te r m s tu d y . R e v is ta d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 3 : 1 0 1 - 1 0 7 , a b r-ju n , 1 9 9 0
in the mid-clavicular line, to the point of its mayimgl palpable dimension.
Parasitological exam of the feces was always carried out by the same laboratory techniciân, Maria Eliete Fernandes, using the Hoffman sedimentation technique20 and the Kato quantitative method as modified by Katz and others22. Counts of S. m a n s o n i
eggs per gram of feces were averaged from three different parts of the same faecal sample.
Liver function was assessed by measuring as partate aminotransferase (AST), alanine aminotrans ferase (ALT), gammaglutamyl transferase (YGT) arid alkaline phosphatase (AP) activities in serum using an optimized kinetic method at 25°C. Bilirubin, both total and direct fraction (BT, BD) were measured by the Mallory-Evelyn technique; bromosulphalein (BSP) retention by Seligson’s technique, with quantitation performed 45 minutes after introduction of 5mg/kg of dye. Serum proteins were quantitated by electro phoresis using an alkaline sodium Veronal buffer, pH 8.6 from a Ponceau-stained cellulose acetate strip.
Statistical methods were the Students’ t and Wilcoxon test, taking 0.05 as level of significance.
RESULTS
T h e r a p e u tic e ffi c a c y
The mean number of eggs in stool, pre-treat ment, was much higher among the 10-19 and 20-29 year age groups (Table 1). The distribution of patients according to pre-treatment egg count is showed in Table 2. Twenty-two patients, or 52.4% of the total, had over one thousand egg/gram of feces.
Table 2 - D i s t r i b u t i o n o f p a t ie n t s a c c o r d in g to e g g c o u n t b e fo re tr e a tm e n t
T able 3 - C u r e r a te a t d iffe r e n t tim e p e r i o d s a f te r tr e a tm e n t 2 w ith p r a z iq u a n t e l
N ? o f eggs per
gram o f feces* N.° o f cases % T otal
less than 100 4 9 .5 2 100 - 5 0 0 11 2 6 .1 9 501 - 1 ,0 0 0 5 1 1 .9 0 1,001 - 5 ,0 0 0 16 3 8 .1 0 more than 5 ,0 0 0 6 14.29
T otal 4 2
* G eom etric m ean o f three counts by the K ato-K atz techni que.
The number of patients available for follow up is shown in Table 3. Along with cure-rates for each corresponding period of observation. Unfortunately most patients were lost for follow up after the first year due to the moving the “ Hospital das Clinicas” to a new building far from the old one.
3 months 37 35 9 4 .6
6 m onths 40 35 87.5
12m onths 42 35 83.3
5 years 9 9 1 0 0 .0 0
Seven patients who were not completely cured showed a marked reduction in stool egg counts six or twelve months after praziquantel treatment (Table IV). Patients RJ S and ASM, the youngest of the seven patients not cured had the lowest reduction in egg count.
T able 4 - R e la tio n s h ip o f p a t i e n t a g e to r e d u c tio n in egg c o u n ts in p a t ie n t s n o t c u r e d a fte r th e ra p y .
Patient A ge M ean number o f eggs B efore After
% Reduction
Control period (m onths)
M JA 23 15,7 1 2 * 6 4 9 9 .6 6 M JF S 2 0 5 ,5 5 6 152 97.3 6 E A F 14 2 ,7 6 8 16 9 4 .4 6
E A F 13 3 ,5 1 2 96 97.3 6
JM S 13 8 ,3 4 5 3 6 0 9 5 .7 12 R JS 12 1 ,0 4 8 2 0 8 80.1 12
A S M 12 6 6 4 144 78.3 6
* Probable reinfection. Second treatment.
All patients not cured initially received a second course of praziquantel at the same dosage, six to twelve months after the first one. All become stool negative after the second treatm ent
L i v e r f u n c t i o n te s ts
Table 5 shows the results of the liver function tests, before treatment and one year later. Statistically significant changes occurred with AST, ALT, A P and gamma globulin (Y GLOB).Albumin (ALB) levels increased significantly. However, YGT, BSP, BT and BD showed no changes.
Six patients had individual AST values of over 40 IU before treatm ent One year later, only one had an elevated level. Two had A LT values over 50 IU before treatment. One year later both patients had normal levels of activity.
Twenty out of 33 patients, 60.6%, had indivi dual A P values over 200 IU before treatment. One
T able 5 - M e a n v a lu e s o f A m in o tr a n s f e r a s e ( A S T ) , A la n in e a m in o tr a n s f e r a s e (A L T ), A lk a lin e p h o s p h a t a s e (A P ), A lb u m in (A L B ), G a m m a g lo b u lin ( Y G lo b ), G a m m a g lu ta m y l tr a n s fe r a s e ( Y G T ), B ilir u b in ( B T ) a n d B r o m o s u lp h a le in ( B S P ) b e fo re a n d in th e f i r s t y e a r a f te r tre a tm e n t.
T est N.° o f
cases
Before treatm ent
After treatm ent
Statistical
T est P
A S T 34 2 1 .9 7 1 6 .9 4 W ilcoxon 0 .0 2 0
A L T 34 1 9 .7 0 15.91 W ilco x o n 0 .0 3 2
A P 29 3 1 3 .9 5 2 6 8 .7 2 W ilcoxon 0 .0 0 7 5
A L B 35 3 .2 8 3.53 t student 0.001
Y G lob 35 2 .4 3 2.01 t student 0.01
Y G T 22 2 3 .0 3 2 3 .3 4 W ilcoxon 0 .0 5 0
B T 32 0 .8 1 0 .8 8 W ilcoxon 0 .2 2 9
B D 32 0 .3 0 0 .2 8 W ilco x o n 0 .8 5 0
B S P 22 5.61 6 .5 6 W ilcoxon 0 .1 0 6
N orm al values: A ST : 5 -17 IU . A L T : 5 -23 IU . A P: 4 0 -1 9 0 IU . YG T: 6 -2 8 IU . BSP: 6% or less dye retention.
year after, 15 out of 29 or 51.7%, still had elevated values.
Ten individuals had elevated Y GLOB values between 2.5 dl and 3.0 dl one year later five out of these 10 patients had normal values. In addition, six other patients had values greater than 3.0 dl; one year later, only two of these six patients had abnormal values.
Four patients had individual ALB levels under 2.5 dl before treatment; one year later, none were below that level. Ten had ALB levels between 2.5 dl and 3.0 dl before treatment; one year later, only four were below 3.0 dl.
Individual Y G T values varied widely, both before and after treatm ent In nearly every case, BT,
BD and BSP values were normal or near-normal before and after chemotherapy.
R e d u c t i o n o f h e p a to m e g a ly a n d s p le n o m e g a ly
As shown in Table 6, liver size was reduced in 81.0% of patients after one year though only nine of 42 patients could be followed through the fifth year. Liver size was reduced in eight of these nine patients. Comparison of average liver size before treatment with level size one year and five years later (Table 7) showed statistically significant reduction during the follow-up period. N o patient, however, had complete regression to normal.
T able 6 - E v o l u t i o n o f liv e r a n d s p le e n s i z e in th e f i r s t a n d f i f th y e a r a f te r tre a m e n t.
____________ F irst year___________ F ifth year______
Change Liver Spleen Liver Spleen
in size N.° % n.° % NP % N ? %
N o n e 8 19M 7 2 L 2 1 I l lT l 2 3 3 3
D e crea se 34 8 1 .0 26 7 8 .8 8 8 8 .9 4 6 6 .7
T otal 4 2 --- 33 + 9 6 + +
---+ N in e and ---+ ---+ three patients had undergone splenectom y.
As shown in Table 6 reduction of splenomegaly occurred in 78.8% of the patients one year after chemotherapy. In five of the 42 patients studied (15.1%), reduction was complete and the spleen was no longer palpable. After five years, four,out of six had smaller spleens (Table 6). Statistically significant reduction in average spleen size was detected one and five years after treatment (Table 7).
There was no correlation between hepatome galy or splenomegaly reduction and patient age, degree of infection, Y GLOB and A P levels.
E f f e c t o f t r e a t m e n t o n o th e r c l i n i c a l f o r m s
D o m in g u e s A L C , C o u tin h o A D . R e d u c tio n o f m o r b id ity in h e p a to s p le n ic s c h is to s o m ia s is m a n s o n i a f te r tr e a tm e n t w ith p r a z iq u a n te l: a lo n g te r m s tu d y . R e v is ta d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 3 : 1 0 1 - 1 0 7 , a b r-ju n , 1 9 9 0
T a b le 1 - M e a n v a lu e s a n d s t a n d a r d d e v ia tio n o f liv e r a n d s p le e n s i z e in c e n tim e te r s, b e fo re tre a tm e n t, o n e y e a r a n d f i v e y e a r s a f te r p r a z iq u a n te l.
First year F ifth year
Liver (N.°= 4l) Spleen (N.° = 3 3 ) Liver (N.° = 9) Spleen (N.° 6) Before After Before After B efore After Before After
X 8.27 5 .6 7 8.97 6 .2 6 8 .6 7 5.33 8.08 6.1 7
s 2.2 0 2 .1 4 4.87 4 .6 6 1.85 1.22 4 .6 2 4 .8 7
F irst year. W ilcoxon p < 0 .0 0 0 0 3 ; F ifth year. W ilcoxon for the liven p < 0 .0 1 .
ning of the disease after treatment. Five had been splenectomised before treatm ent Of the remaining twenty seven, five or 18.5 % had a spleen which was no longer palpable after treatm ent That is, there was regression to the hepato-intestinal stage.
Seven of the 42 patients studied has a history of upper gastro-intestinal hemorrhage before prazi quantel treatment, five had hematemesis, two had melena. Bleeding recurred in three of the seven, 42.9%, after chemotherapy. Four of 35 (11.4%) who had no hemorrhage before treatment had gastro intestinal hemorrhage after treatment. These dife- rences were statistically significant
One HS case demonstrated marked growth retardation. A t age sixteen he was lm29cm tall, and weighed only 28.5kg. Two years after praziquantel treatment he had grown 12 cm, and put on 8 kg.
In another case, HBsAg was detected in the blood before treatm ent Two years after treatment there was no change in liver function parameters and HBS Ag was still present A liver biopsy 10 months after treatment showed persistent chronic hepatitis and moderate portal fibrosis.
Among the remaining 10 more complicated patients, five had the so-called intermediate or transi tional HS form14. In this HS form, patients have transitory symptoms of hepatic decompensation, such as oedema and ascites, which regress with supportive clinical therapy. These patients did not show further clinical deterioration after praziquantel treatment. However, liver function tests did not return completely to normal, as the AST, ALT, BT, BD, BSP and Y GLOB remained mildly abnormal and ALB remained under 3g%.
One fourteen-year-old patient had prolonged fever and diarrhea before treatm ent A hemoculture showed S a l m o n e l l a sp. He was treated with antibio tics, then praziquantel. His response was satisfactory.
Three cases had in addition to HS, the hyper tensive cardio-pulmonary complication and another patient had the cyanotic form of Schistosomiasis. Two of the three patients had severe pulmonary arterial hypertension with signs and symptoms of cardiac
insufficiency, which were not affected by specific treatment One died of cardiac insufficiency eighteen months after treatm ent The third patient, with mo derate pulmonary hypertension, gradually improved over a 2.1/2 year period of observation.
An eighteen-year-old patient with the cyanotic form showed, by the end of the first year, a significant reduction in spleen size, and in cyanosis.
DISCUSSION
After twelve months of follow-up, 83.0% of the patients had no eggs in their stools in the present study. Note that our patients live in an area of hyperendemic schistosomiasis, and are often highly infected (see Table 2), especially under 30 years of age (Table 1). All but one of the seven who were not completely cured were heavily infected before treatment with over 1,000 eggs/g of faces (Table 4). This inverse relationship between percentage of cure rate and degree of infection had previously been observed by Prata et al.29 Consistent with results of others23 35 we found that young patients had lower cure rates and lower reduc tion in egg counts (Table 4). This indicates that children need larger doses, at least 60 mg/kg of praziquantel.
Four patients who failed therapy were adminis tered repeat doses of praziquantel and were cured six months later. W e believe that second treatment after six months is sufficient Cunha et al.17 however, hold an alternative view. They administered praziquantel (60mg/kg each day) for three days, measuring cure rates by rectal biopsy, which they believe to be more accurate.
Usually, patients, if reinfected, have low egg counts7 21. This usually high level may be due to the sple nectomy after praziquantel treatment which may have changed her immunological response. After a further dose of praziquantel, she immediately exhibited symptoms of coughing, dyspnea, wheezing and abdo minal pain. We have in a previous study11 referred to this as a hypersensitivity reaction to dead parasite antigens after treatment in some patients.
There have been few long-term studies of liver function in man after schistosomiasis chemothe rapy13 16 28 32. In the present study we report significant reductions in pre-treatment AST, ALT, Y GT, AP, and Y GLOB and an increase in serum ALB. This evidence of improvement in liver function may well be due to a reduction in schistosomiasis hepatic inflamatory response after treatment, as has been observed in mice infected with S . m a n s o n i31 36 and in chimpanzees with S', j a p o n i c u m30. But improved liver function may also be due to regression of schistosomiasis intra-hepatic vascular lesions, as has been seen in mice after chemotherapy3.
Experiments in animals, mainly mice, had shown the beneficial effects of specific treatment in prevention and reversion of hepatosplenomegaly, portal hypertension and hepatic fibrosis8 9 27 36 Similarly studies in man, have shown good results with different drugs on prevention and regression of hepa tosplenomegaly, during short periods of obser vation6 13 18. Analysis of ourresults show reduction in liver size in 81.0% of cases one year after treatment, and of spleen size in 78.8%. Reduction in spleen size was complete in 15.1% of the total of cases, and in 18.5% of compensated HS patients. In our previous studies with oxamniquine and prazinquantel, regres sion of liver and spleen was less marked after six months: 50.3% and 62.1% for the liver, 53.5 and 57.4% for the spleen13 16. Also, during the first six months after treatment, no cases of complete regres sion of splenomegaly were observed. On the other hand, as Tables VI and VII show, hepatosplenic regression, in the few cases followed up to five years, was similar to one year of observation. Thus, our data would indicate that hepatosplenic regression following specific therapy needs an extended period of obser vation: one year at least.
Our data is similar to observations recently published by Bina and Prata6 in younger patients and by Dietze and Prata18 in patients with milder degrees of splenomegaly. In fact, in the five cases in our study with total regression of the spleen, spleen size before treatment was between 3.5 cm and 5 cm. This suggests that the smaller the spleen size the greater the chance of complete regression.
However, we observed in our present study, as did Dietze and P rata18 that even older patients of forty-one and forty-six years of age could show a reduction of hepatosplenomegaly. Furthermore, there was a thirty-nine-old among our five cases of complete splenic regression. We suggest therefore that specific chemotherapy should be administered to all HS pa tients in whom no special contra indications apply. The effects of treatment should be observed for at least twelve months before any eletive surgery is contem plated, with exception of cases with history of gastro intestinal hemorrhage (see later).
We observed no correlation between reduction of hepatomegaly or splenomegaly and degree of infec tion. This lack of correlation agrees with the findings of Bina and Prata6. We found the same lack of correla tion with respect to Y GLOB and AP, commonly believed to be good indicators of active hepatic schistosomiasis.
Also noteworthy is the high level of parasite infection frequently recorded in our HS patients, 52.4% of whom had a test count of over 1.000 eggs/gram of feces. This phenomenon had already been recorded as far back as 1962 by Kloetzel24, and had been confirmed by o th e rs^ 26 34. This rela tionships between degree of schistosomiasis infection and development of hepatomegaly has been more marked in younger patients (see Table 1 and 3 and Katz et al23, Sturroch et al.3^ This relationship, however, does not always apply in all situations. We noted in the present study, for example, cases with markedly enlarged spleens, yet with low Kato-Katz counts, Kloetzel24 2^ in field studies, has already drawn attention to the sharp drop in egg counts in the feces of children between ten and fourtheen, coinciding with the development of splenomegaly.
In the present study, we followed one case in which there was marked improvement in growth after specific treatment. Such improvement was previously observed by us13 after treatment with other anti schistosomiasis drugs, such as oxamniquine, and had also been observed by Bina and Prata6.
D o m in g u e s A L C , C o u tin h o A D . R e d u c tio n o f m o r b id ity in h e p a to s p le n ic s c h is to s o m ia s is m a n s o n i a f te r tr e a tm e n t w ith p r a z iq u a n te l: a lo n g te r m s tu d y . R e v is ta d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 3 : 1 0 1 - 1 0 7 , a b r-ju n , 1 9 9 0
In our most advanced cases of HS, where hepatic decompensation was present, as well as in those with the fully-developed cardiopulmonary form, we found little or no clinical improvement after specific chemotherapy. This finding has already been referred to in clinical and experimental studies by Warren & Klein37; Sadun et al.30; Coutinho & Dominguesl3 and Almeida & Andrade2.
From observations made in the present study, from our previous observations, and from those of our colleagues, we recommend that specific antischis- tosomal treatment with either oxamniquine or pra ziquantel, should be administered, as soon as possible, except when there are special contraindications. We recommend prompt treatment, particularly in cases of children and teenagers with high levels of infection to arrest the progress of the disease. Even when the stage of the disease is advanced, specific treatment, which is generally well tolerated, should be tried, as some beneficial effect may follow. In addition no deteriora tion in the condition of the patient due to treatment with either oxamniquine or praziquantel has been observed.
RESUMO
Q u a r e n ta e d o i s p a c i e n t e s e s q u is to s s o m ó tic o s h e p a to s p lê n íc o s , t r a t a d o s c o m p r a z i q u a n t e l , f o r a m
a c o m p a n h a d o s p o r c in c o a n o s. M e t a d e d o s p a c i e n te s re c e b e u u m a d o s e s i m p l e s d e 3 0 m g / k g ; a o u tr a m e ta d e , re c e b eu d u a s d o s e s d e 2 5 m g / k g d a d a s c o m
in te r v a lo s d e 4 h o r a s . A t a x a d e cu ra , d e a c o r d o c o m o s e x a m e s d e f e z e s p e l o s m é to d o s d e H o f f m a n c o ls e
d e K a t o - K a t z , d u r a n t e 1 2 m e s e s f o i d e 8 3 ,3 % . N o s
c a s o s c o m c u r a in c o m p le ta , o s o v o s c o n ta d o s n a s f e z e s f o r a m m u i t o r e d u z id o s . A f u n ç ã o h e p á tic a , e s t i m a d a p e l o n ív e l, n o so ro , d e a s p a r ta to a m i n o
t r a n s fe r a s e,, a l a m i n a a m in o tr a n s fe r a s e , g a m a g lu -t a m il-tr a n s fe r a s e e f o s f a -t a s e a lc a l i n a b e m c o m o , d e a l b u m i n a e g a m a g l o b u l i n a m o s tr o u a c e n tu a d a m e lh o r a a p ó s u m a n o . H e p a t o m e g a l i a f o i r e d u z id a e m 8 1 , 0 % d o s p a c i e n t e s e e s p le n o m e g a lia e m 7 8 ,8 % .
A re g re ssã o d o b a ç o f o i c o m p le ta e m 1 5 , 1 % d o t o t a l e e m 1 8 ,5 % d a q u e l e s c o m f o r m a h e p a to s p lê n ic a c o m p e n s a d a . C o m o r e s u lta d o d e s ta s o b se rv a ç õ e s, o s
a u to r e s r e c o m e n d a m t r a ta m e n to p r e c o c e c o m m e d i
c a ç ã o a n ti e s q u i s t o s s o m ó t i c a c o m o x a m n i q u i n e o u p r a z i q u a n t e l p a r a in te r r o m p e r a p r o g r e s s ã o d a d o e n
ç a e r e d u z i r h e p a to m e g a lia e e s p le n o m e g a li a .
P a la v r a s - c h a v e s : E s q u i s t o s s o m o s e m a n s o n i h e p a to s p lê n ic a . T r a ta m e n to . R e v e r s ã o .
R E F E R E N C E S
1. A b d a lla h A , S a ifM ,K o u r a M . T h e r o le o f chem otherapy in the control o f schistosom iasis: experience in Egypt. Brasília M éd ica 11:4 9 -5 4 , 1975.
2. A lm eid a M A C , A ndrade Z A . E ffect o f chem otherapy on experim ental pulm onary schistosom iasis. T he Am erican Journal o f T ropical M edicine and H ygiene 3 2
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