Annals of Tropical Medicine & Parasitology
ISSN: 0003-4983 (Print) 1364-8594 (Online) Journal homepage: http://www.tandfonline.com/loi/ypgh19
Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole U. G. Meneghelli, A. L. C. Martinelli, A. D. Bellucci, M. G. Villanova, M. A. S. Llorach Velludo & J. E. Magro To cite this article: U. G. Meneghelli, A. L. C. Martinelli, A. D. Bellucci, M. G. Villanova, M. A. S. Llorach Velludo & J. E. Magro (1992) Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole, Annals of Tropical Medicine & Parasitology, 86:2, 151-156, DOI: 10.1080/00034983.1992.11812645 To link to this article: http://dx.doi.org/10.1080/00034983.1992.11812645
Published online: 15 Nov 2016.
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Citing articles: 9 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ypgh19 Download by: [Australian Catholic University]
Date: 20 August 2017, At: 18:01
Annals of Tropical Medicine and Parasitology, Vol. 86, No.2, 151-156 (1992)
Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole BY U. G. MENEGHELLI, A. L. C. MARTINELLI, A. D. BELLUCCI, M. G. VILLANOVA
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
Department of Internal Medicine, Facuity ofMedicine ofRibeirao Pre to, University ofSao Paulo, 14049 Ribeirao Preto, Sao Paulo, Brazil M.A. S. LLORACH VELLUDO
Department ofPathology, Faculty ofMedicine ofRibeirao Preto, University of Sao Paulo AND]. E. MAGRO
Ministry ofLabor and Social Welfare, 29001 Victoria, ES, Brazil Received 24 June 1991, Revised IS January 1992, Accepted S February 1992
Six patients with polycystic hydatid disease (PHD) were treated with 10 mg kg- 1 day- 1 albendazole. One patient was treated continuously for eight months and another for three months. In three other patients treatment was discontinuous, consisting of a series of at least three 30-day cycles separated by 15 days without treatment. The last patient was treated continuously with 12 mg kg- 1 day- 1 albendazole for 51 days and then with three 30-day cycles of treatment with 10 mg kg- 1 day- 1 separated by IS-day drug-free intervals. Followup ranged from IQ-30 months. Considerable clinical improvement and cyst reduction or disappearance occurred in four patients. Clinical improvement, but no changes in the hepatic alterations detected by computerized tomography, occurred in the other two patients, although a pulmonary cyst disappeared in one of them. Adverse effects were proteinuria, alopecia, leucopenia, itching and discrete elevation in aspartate transaminase, all of them reversed after the end of treatment. These results indicate that albendazole is effective for the treatment of PHD.
Polycystic hydatid disease (PHD) is caused by Echinococcus vogeli, the intermediate host of which is the paca (Cuniculus paca ), a wild rodent widely distributed throughout the Americas. PHD occurs mainly in the Amazon Region (D' Alessandro et a!., 1979), with the highest prevalence apparently in the State of Acre, Brazil (Meneghelli et a!., 1992; J. E. Magro, unpubl. obs.). Surgical treatment of PHD is frequently unfeasible because the multiple cysts involve extensive portions of the liver and other organs 0003-4983j92/020151 +06 $03.00/0
or are disseminated throughout the peritoneum. Attempts have therefore been made to treat the disease with drugs toxic to the larval form of Echinococcus. Albendazole, a benzimidazole carbamate, has been shown to be such a drug, and has proved effective in the treatment of hydatid disease produced by E. granulosus, as first observed by Saimot et a!. (1983), Morris and Dykes (1983), and Morris et a!. (1984). In the present report we show that albendazole was effective in the treatment of patients with PHD. © 1992 Liverpool School of Tropical Medicine
152
MENEGHELLI ET AL.
TABLE 1 Clinical and laboratory data ofpatients with PHD
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
Case
2
Age (years)
Sex
Duration of symptoms
Major clinical and laboratory manifestations
20
M
5 months
Abdominal pain and masses; low levels ofHb, serum albumin; high levels of eosinophils, y-globulin, ESR,AP*
Liver, mesentery, spleen, pancreas
30
F
3 years
Anorexia, jaundice, hepatomegaly, splenomegaly, oesophageal varices; low levels ofHb, serum albumin, WBC; high levels of AST, bilirubin, y-globulin, AP,
Liver
Organs involved
y-GT 3
35
M
4 years
Epigastric painless tumouration; high levels of eosinophils
Liver
4
58
F
3 years
Chest and epigastric pain, haemoptysis; laboratory tests not available
Lungs, liver
5
34
M
6 months
Epigastrium and right hypocondrium pain, jaundice, itching, choluria, weight loss, haemoptysis, hepatomegaly; high levels of eosinophils, bilirubin, AST, y-GT, AP, y-globulin
Lung, liver
6
38
F
1·5 years
Epigastrium and right hypocondrium pain, hepatomegaly; high levels of eosinophils, AP,
Liver
y-GT *AP, Alkaline phosphatase.
MATERIALS AND METHODS The study was conducted on six of seven patients with PHD, diagnosed by histopathological examination of cysts removed during exploratory laparotomy. All were from the State of Acre, Amazon Region of Brazil, and are the cases described by Meneghelli eta/. ( 1992). One of the seven patients was cured by surgical removal of peritoneal cysts, and Table I presents the age and sex, duration of symptoms, involved organs, and a brief summary of clinical and laboratory data for the other six patients obtained before chemotherapy. Albendazole was admin-
istered orally, usually at a daily dose of lO mg kg-I, divided into two or three portions. Two patients were given this dose continuously, one for eight months (case I) and one for three months (case 4). One patient (case 2) was initially scheduled to receive continuous treatment with a higher dose (l2mgkg- 1 day- 1), but treatment was interrupted after 51 days because of side effects. The remaining patients (cases 3, 5 and 6) were submitted to at least three 30-day periods of treatment separated by 15-day intervals; and case 2 was submitted to the same regimen commencing 15 days after the cessation of the continuous treatment.
ALBENDAZOLE IN POLYCYSTIC HYDATID DISEASE
153
TABLE2 Results obtained with albendazole for the treatment ofPHD
Case
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
2
3 4 5 6
Results
Follow-up (months)
Success
14
Partial success Success Success Partial success Success
24 24 24
30 10
Adverse reactions AST levels four times normal; proteinuria (950 mg in 24 hours) Leucopenia (1000 per mm3); alopecia AST levels twice normal; itching Data not available Absent Absent
Treatment was evaluated using criteria similar to those proposed by Davis eta/. (1986) and Todorov eta!. (1988), i.e. 'success' was defined as disappearance or significant reduction in size of cysts or abdominal masses as determined by palpation and/or by imaging diagnostic procedures (computerized tomography or ultrasound) and by clinical improvement; 'partial success' as clinical improvement with negligible changes in abdominal masses or cysts; and 'no success' as unchanged size of cysts or abdominal masses, unchanged or worsened clinical picture, or drug intolerance requiring discontinuation of treatment. Cases l, 2, 3, 5 and 6 were first evaluated 1399 days after the beginning of treatment while in-patients at the University Hospital of the Faculty of Medicine of Ribeirao Preto (UHFMRP). Case 4 was treated in Rio Branco, Acre and admitted to UHFMRP for evaluation one year after treatment. Three patients were admitted again to UHFMRP, thus permitting a follow-up of 14 to 30 months. The other three patients were unable to return to UHFMRP, but they reported on their condition of health from their State Gf residence.
RESULTS Albendazole had favourable therapeutic effects in all six PHD cases studied (Table 2). Successful treatment was obtained in four patients (cases 1, 3, 4 and 6), and partial success in two (cases 2
and 5); there were no cases of unsuccessful treatment. In the four cases in which treatment was successful, the clinical course was characterized by the disappearance of pain, reduction of abdominal masses, and considerable improvement in general condition within the first few weeks of drug use. Reduced cyst number and size were confirmed on the 70th day of treatment in case 1 (Fig. 1), and complete cyst disappearance occurred nine months after the end of treatment in case 4 (Fig. 2). In case 6, the radiological picture remained unchanged despite a considerable improvement of symptoms and a marked reduction in palpable mass size. In case 3 it was not possible to perform imaging procedures. The high eosinophilia and low levels of albuminaemia and haemoglobin in case 1, and the high eosinophilia in case 6, became normal. These two patients were followed for 10-24 months after treatment and found to be asymptomatic and apparently cured, having fully resumed their professional activities. The two patients whose treatment was a partial success presented disappearance (case 2) or improvement (case 5) of abdominal pain, as well as recovery of appetite and of general condition. In addition, case 5 presented reduced bilirubinaemia and full regression of the pulmonary cyst. Case 2, followed up for two years, was clinically stable and asymptomatic, with slight hyperbilirubinemia and unchanged hepatomegaly, portal hypertension and liver aspect upon computerized tomography. At the end of 30 months
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
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Fig. 1. Computerized tomography scan of case 1. (A), Pretreatment: rounded, hypoechoic formations in the peritoneum and hepatic parenchyma; (B), 70 days after the beginning of treatment; reduction in number and size of peritoneal and hepatic cyst images.
and after two series of albendazole treatment, case 5 had unchanged hepatomegaly, hepatic cholestasis and portal hypertension, probably due to the extensive involvement of the left lobe, the damaged bile ducts, and the development of secondary biliary cirrhosis in the right lobe. Adverse effects of the drugs were observed in three of the six patients. The leucopenia present
in case 2 increased following treatment with 12 mg kg- 1 day-', and treatment was stopped. Once the leucocyte levels recovered, albendazole treatment was reintroduced at a dosage of 10 mg kg- 1 day -I and administered over 30-day periods, and there was no further increase in leucopenia. Alopecia also occurred in this patient. Itching and increased serum AST levels
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ALBENDAZOLEINPOLYCYSTICHYDATIDDISEASE
155
Fig. 2. Computerized tomography scan of case 4. Approximately one year after the beginning of treatment, cyst images are absent and bizarre calcifications are visible in the right liver lobe.
were observed in case 3. Serum AST was also increased in case 1, together with discrete proteinuria. All the adverse effects were reversed after discontinuation of the drug. DISCUSSION Experience accumulated over the last few years has clearly confirmed that albendazole has beneficial effects in the treatment of cystic hydatid disease (Morris et a/., 1985; Davis et a/., 1986; Okelo, 1986; Todorov eta!., 1988; Horton, 1989; De Rosa and Teggi, 1990). Experimental (Taylor et a/., 1988, 1989) and clinical (Wilson eta/., 1987) resultshavealso shown thatalbendazole may have lethal effects on E. multilocularis in alveolar hydatid disease. While we recognize the many difficulties involved in evaluating the effectiveness of chemotherapy against hyatid disease, as pointed out by De Rosa and Teggi (1990), we are convinced that albendazole was effective in the treatment of the six PHD cases reported here. According to the criteria adopted to evaluate the present results, all six patients improved after albendazole treatment, particularly patients 1, 3, 4 and 5, who were considered cured. Although it may be assumed that a parasitologi-
cal cure occurred in the other two cases, extensive and generalized residual lesions in case 2 and involvement of the right hepatic duct in case 5 prevented a full recovery. We believe that the therapeutic alternative for these two cases is a liver transplant. The only other report of albendazole treatment of a (possible) case of PHD is that by Timerman eta/. (1986), who observed marked cyst reduction and clinical improvement. In another case of PHD (Ferreira et a/., 1987), treatment with mebendazole for one year failed and the patient died. The adverse side effects of albendazole which we observed in some of our patients have also been reported by others (Morris et a/., 1985; Davis et a/., 1986; Horton, 1989; De Rosa and Teggi, 1990). However, they did not prevent continuation of treatment and were reversible after discontinuation of the drug. We conclude that albendazole is effective in the treatment of PHD. The dose most frequently used was lOmgkg- day- 1 divided into two or three daily fractions. None of the patients received albendazole for less than 90 days, consecutive or not. Good results were obtained whether the drug was administered continuously or at intervals. Although side effects were
156
MENEGHELLI ET AL.
observed in both treatment schedules, the most significant ones occurred in a patient submitted to continuous treatment. We are grateful to Smith Kline & Cia., Rio de Janeiro, RJ, for
ACKNOWLEDGEMENTS.
kindly donating albendazole (Zentel). Financial support was provided by 'Funda.yao de Apoio ao Ensino, Pesquisa e Assistencia' (FAEPA) of our University Hospital. We are indebted to Edneia Fabbris Verceze and Regina Helena Bertoli for typing the manuscript.
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
REFERENCES D'ALESSANDRO, A., RAusCH, R. L., CUELLO, C. & ARISTAZABAL, N. (1979). Echinococcus vogeli in man, with a review of polycystic hydatid disease in Colombia and neighboring countries. American Journal of
Tropical and Medical Hygiene, 28,303-317. DAVIS, A., PAWLOWSKI, Z. S. & DIXON, H. (1986). Multicentre clinical trials of benzimidazole carbamates in human echinococcosis. Bulletin of the World Health Organization, 64, 383-388. DE RosA, F. & TEGGI, A. (1990). Treatment of Echinococcus granulosus hydatid disease with Albendazole.
Annals of Tropical Medicine and Parasitology, 84, 467--472. FERREIRA, M. S., RocHA, A., GoN~LVES, E. G., CARVALHO, A. M., NISHIOKA, S. A. & ANDRADE, N. B. (1987). Urn caso de hidatidose policistica autoctone de Minas Gerais, Brasil. Revista da Sociedade
Brasileira de Medicina Tropical, 20, 181-186. HORTON, R. J. (1989). Chemotherapy of echinococcus infection in man with Albendazole. Transactions of the
Royal Society of Tropical Medicine and Hygiene, 83, 97-102.
u.
s.,
MENEGHELLI, G., MARTINELLI, A. L. c., LLORACH-VELLUDO, M.A. BELLUCCI, A. D., MAGRO, J. E. & BARBO, M. L. P. (1992). Polycystic hydatid disease (Echinococcus vogel1). Clinical, laboratory and morphological findings in 9 Brazilian patients. Journal ofHepatology, 14, 203-210. MoRRIS, D. L. & DYKES, P. W. (1983). Albendazole in hydatid disease. Results of treatment in 22 patients.
Gut, 24, 79-85.
MORRIS, D. L., DYKES, P. w., MARRINER, S., BOGAN, J., BURROWS, F., SKEENE-SMITH, H. & CLARKSON, M. J. (1985). Albendazole-objective evidence of response in human hydatid disease. Journal of the
American Medical Association, 253, 2053-2057. MoRRIS, D. L., SKEENE-SMITH, H., HAYNES, A. & BURROWS, F. G. 0. (1984). Abdominal hydatid disease: computed tomographic and ultrasound changes during Albendazole therapy. Clinical Radiology, 35,
297-300. 0KELO, G. B. A. (1986). Hydatid disease: research and control in Turkana. III. Albendazole in the treatment of inoperable hydatid disease in Kenya-a report on 12 cases. Transactions ofthe Royal Society ofTropical
Medicine and Hygiene, 80, 193-195.
SAIMOT, A. G., MEULEMANS, A., UEMIEUX, A. c., GIOVANANGELI, M. D., HAY, J. M., DELAITRE, B. & CoULAUD, J. P. (1983). Albendazole as a potential treatment for human hydatidosis. Lancet, ii,
652--656. TAYLOR, D. H., MORRIS, D. L., REFFIN, D. & RICHARDS, K. S. (1989). Comparison of Albendazole, mebendazole and praziquantel chemotherapy of Echinococcus multilocularis in a gerbil model. Gut, 30,
1401-1405. TAYLOR, D. H., MORRIS, D. L., RICHARDS, K. S. & REFFIN, D. (1988). Echinococcus multilocularis: in vivo results of therapy with Albendazole and praziquantel. Transactions of the Royal Society of Tropical
Medicine and Hygiene, 82, 611--615. TIMERMAN, A., ANDRADE, D. R., HuTZLER, R. V., MARINHO, I. S. & ULIANA, S. R. B. (1986). Terapeutica de hidatidose hepatica com albendazol: relata de I caso. IX Brazilian Congress ofHepatology, Sao Paulo (Abstract). ToDOROV, T., VuTOVA, K., PETKOV, D., MECHKOV, G. & KoLEY, K. (1988). Albendazole treatment of human cystic echinococcis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 82,
453--459. WILSON, ]. F., RAuscH, R. L., McMAHoN, B. ]., ScHANTz, P. M., TRUJILLO, D. E. & O'GoRMAN, M. A. (1987). Albendazole therapy in alveolar hydatid disease: a report offavorable results in two patients after short-term therapy. American Journal of Tropical Medicine and Hygiene, 37, 162-168.
ISSN: 0003-4983 (Print) 1364-8594 (Online) Journal homepage: http://www.tandfonline.com/loi/ypgh19
Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole U. G. Meneghelli, A. L. C. Martinelli, A. D. Bellucci, M. G. Villanova, M. A. S. Llorach Velludo & J. E. Magro To cite this article: U. G. Meneghelli, A. L. C. Martinelli, A. D. Bellucci, M. G. Villanova, M. A. S. Llorach Velludo & J. E. Magro (1992) Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole, Annals of Tropical Medicine & Parasitology, 86:2, 151-156, DOI: 10.1080/00034983.1992.11812645 To link to this article: http://dx.doi.org/10.1080/00034983.1992.11812645
Published online: 15 Nov 2016.
Submit your article to this journal
Article views: 1
View related articles
Citing articles: 9 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ypgh19 Download by: [Australian Catholic University]
Date: 20 August 2017, At: 18:01
Annals of Tropical Medicine and Parasitology, Vol. 86, No.2, 151-156 (1992)
Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole BY U. G. MENEGHELLI, A. L. C. MARTINELLI, A. D. BELLUCCI, M. G. VILLANOVA
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
Department of Internal Medicine, Facuity ofMedicine ofRibeirao Pre to, University ofSao Paulo, 14049 Ribeirao Preto, Sao Paulo, Brazil M.A. S. LLORACH VELLUDO
Department ofPathology, Faculty ofMedicine ofRibeirao Preto, University of Sao Paulo AND]. E. MAGRO
Ministry ofLabor and Social Welfare, 29001 Victoria, ES, Brazil Received 24 June 1991, Revised IS January 1992, Accepted S February 1992
Six patients with polycystic hydatid disease (PHD) were treated with 10 mg kg- 1 day- 1 albendazole. One patient was treated continuously for eight months and another for three months. In three other patients treatment was discontinuous, consisting of a series of at least three 30-day cycles separated by 15 days without treatment. The last patient was treated continuously with 12 mg kg- 1 day- 1 albendazole for 51 days and then with three 30-day cycles of treatment with 10 mg kg- 1 day- 1 separated by IS-day drug-free intervals. Followup ranged from IQ-30 months. Considerable clinical improvement and cyst reduction or disappearance occurred in four patients. Clinical improvement, but no changes in the hepatic alterations detected by computerized tomography, occurred in the other two patients, although a pulmonary cyst disappeared in one of them. Adverse effects were proteinuria, alopecia, leucopenia, itching and discrete elevation in aspartate transaminase, all of them reversed after the end of treatment. These results indicate that albendazole is effective for the treatment of PHD.
Polycystic hydatid disease (PHD) is caused by Echinococcus vogeli, the intermediate host of which is the paca (Cuniculus paca ), a wild rodent widely distributed throughout the Americas. PHD occurs mainly in the Amazon Region (D' Alessandro et a!., 1979), with the highest prevalence apparently in the State of Acre, Brazil (Meneghelli et a!., 1992; J. E. Magro, unpubl. obs.). Surgical treatment of PHD is frequently unfeasible because the multiple cysts involve extensive portions of the liver and other organs 0003-4983j92/020151 +06 $03.00/0
or are disseminated throughout the peritoneum. Attempts have therefore been made to treat the disease with drugs toxic to the larval form of Echinococcus. Albendazole, a benzimidazole carbamate, has been shown to be such a drug, and has proved effective in the treatment of hydatid disease produced by E. granulosus, as first observed by Saimot et a!. (1983), Morris and Dykes (1983), and Morris et a!. (1984). In the present report we show that albendazole was effective in the treatment of patients with PHD. © 1992 Liverpool School of Tropical Medicine
152
MENEGHELLI ET AL.
TABLE 1 Clinical and laboratory data ofpatients with PHD
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
Case
2
Age (years)
Sex
Duration of symptoms
Major clinical and laboratory manifestations
20
M
5 months
Abdominal pain and masses; low levels ofHb, serum albumin; high levels of eosinophils, y-globulin, ESR,AP*
Liver, mesentery, spleen, pancreas
30
F
3 years
Anorexia, jaundice, hepatomegaly, splenomegaly, oesophageal varices; low levels ofHb, serum albumin, WBC; high levels of AST, bilirubin, y-globulin, AP,
Liver
Organs involved
y-GT 3
35
M
4 years
Epigastric painless tumouration; high levels of eosinophils
Liver
4
58
F
3 years
Chest and epigastric pain, haemoptysis; laboratory tests not available
Lungs, liver
5
34
M
6 months
Epigastrium and right hypocondrium pain, jaundice, itching, choluria, weight loss, haemoptysis, hepatomegaly; high levels of eosinophils, bilirubin, AST, y-GT, AP, y-globulin
Lung, liver
6
38
F
1·5 years
Epigastrium and right hypocondrium pain, hepatomegaly; high levels of eosinophils, AP,
Liver
y-GT *AP, Alkaline phosphatase.
MATERIALS AND METHODS The study was conducted on six of seven patients with PHD, diagnosed by histopathological examination of cysts removed during exploratory laparotomy. All were from the State of Acre, Amazon Region of Brazil, and are the cases described by Meneghelli eta/. ( 1992). One of the seven patients was cured by surgical removal of peritoneal cysts, and Table I presents the age and sex, duration of symptoms, involved organs, and a brief summary of clinical and laboratory data for the other six patients obtained before chemotherapy. Albendazole was admin-
istered orally, usually at a daily dose of lO mg kg-I, divided into two or three portions. Two patients were given this dose continuously, one for eight months (case I) and one for three months (case 4). One patient (case 2) was initially scheduled to receive continuous treatment with a higher dose (l2mgkg- 1 day- 1), but treatment was interrupted after 51 days because of side effects. The remaining patients (cases 3, 5 and 6) were submitted to at least three 30-day periods of treatment separated by 15-day intervals; and case 2 was submitted to the same regimen commencing 15 days after the cessation of the continuous treatment.
ALBENDAZOLE IN POLYCYSTIC HYDATID DISEASE
153
TABLE2 Results obtained with albendazole for the treatment ofPHD
Case
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
2
3 4 5 6
Results
Follow-up (months)
Success
14
Partial success Success Success Partial success Success
24 24 24
30 10
Adverse reactions AST levels four times normal; proteinuria (950 mg in 24 hours) Leucopenia (1000 per mm3); alopecia AST levels twice normal; itching Data not available Absent Absent
Treatment was evaluated using criteria similar to those proposed by Davis eta/. (1986) and Todorov eta!. (1988), i.e. 'success' was defined as disappearance or significant reduction in size of cysts or abdominal masses as determined by palpation and/or by imaging diagnostic procedures (computerized tomography or ultrasound) and by clinical improvement; 'partial success' as clinical improvement with negligible changes in abdominal masses or cysts; and 'no success' as unchanged size of cysts or abdominal masses, unchanged or worsened clinical picture, or drug intolerance requiring discontinuation of treatment. Cases l, 2, 3, 5 and 6 were first evaluated 1399 days after the beginning of treatment while in-patients at the University Hospital of the Faculty of Medicine of Ribeirao Preto (UHFMRP). Case 4 was treated in Rio Branco, Acre and admitted to UHFMRP for evaluation one year after treatment. Three patients were admitted again to UHFMRP, thus permitting a follow-up of 14 to 30 months. The other three patients were unable to return to UHFMRP, but they reported on their condition of health from their State Gf residence.
RESULTS Albendazole had favourable therapeutic effects in all six PHD cases studied (Table 2). Successful treatment was obtained in four patients (cases 1, 3, 4 and 6), and partial success in two (cases 2
and 5); there were no cases of unsuccessful treatment. In the four cases in which treatment was successful, the clinical course was characterized by the disappearance of pain, reduction of abdominal masses, and considerable improvement in general condition within the first few weeks of drug use. Reduced cyst number and size were confirmed on the 70th day of treatment in case 1 (Fig. 1), and complete cyst disappearance occurred nine months after the end of treatment in case 4 (Fig. 2). In case 6, the radiological picture remained unchanged despite a considerable improvement of symptoms and a marked reduction in palpable mass size. In case 3 it was not possible to perform imaging procedures. The high eosinophilia and low levels of albuminaemia and haemoglobin in case 1, and the high eosinophilia in case 6, became normal. These two patients were followed for 10-24 months after treatment and found to be asymptomatic and apparently cured, having fully resumed their professional activities. The two patients whose treatment was a partial success presented disappearance (case 2) or improvement (case 5) of abdominal pain, as well as recovery of appetite and of general condition. In addition, case 5 presented reduced bilirubinaemia and full regression of the pulmonary cyst. Case 2, followed up for two years, was clinically stable and asymptomatic, with slight hyperbilirubinemia and unchanged hepatomegaly, portal hypertension and liver aspect upon computerized tomography. At the end of 30 months
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
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MENEGHELLI ET AL.
Fig. 1. Computerized tomography scan of case 1. (A), Pretreatment: rounded, hypoechoic formations in the peritoneum and hepatic parenchyma; (B), 70 days after the beginning of treatment; reduction in number and size of peritoneal and hepatic cyst images.
and after two series of albendazole treatment, case 5 had unchanged hepatomegaly, hepatic cholestasis and portal hypertension, probably due to the extensive involvement of the left lobe, the damaged bile ducts, and the development of secondary biliary cirrhosis in the right lobe. Adverse effects of the drugs were observed in three of the six patients. The leucopenia present
in case 2 increased following treatment with 12 mg kg- 1 day-', and treatment was stopped. Once the leucocyte levels recovered, albendazole treatment was reintroduced at a dosage of 10 mg kg- 1 day -I and administered over 30-day periods, and there was no further increase in leucopenia. Alopecia also occurred in this patient. Itching and increased serum AST levels
Downloaded by [Australian Catholic University] at 18:02 20 August 2017
ALBENDAZOLEINPOLYCYSTICHYDATIDDISEASE
155
Fig. 2. Computerized tomography scan of case 4. Approximately one year after the beginning of treatment, cyst images are absent and bizarre calcifications are visible in the right liver lobe.
were observed in case 3. Serum AST was also increased in case 1, together with discrete proteinuria. All the adverse effects were reversed after discontinuation of the drug. DISCUSSION Experience accumulated over the last few years has clearly confirmed that albendazole has beneficial effects in the treatment of cystic hydatid disease (Morris et a/., 1985; Davis et a/., 1986; Okelo, 1986; Todorov eta!., 1988; Horton, 1989; De Rosa and Teggi, 1990). Experimental (Taylor et a/., 1988, 1989) and clinical (Wilson eta/., 1987) resultshavealso shown thatalbendazole may have lethal effects on E. multilocularis in alveolar hydatid disease. While we recognize the many difficulties involved in evaluating the effectiveness of chemotherapy against hyatid disease, as pointed out by De Rosa and Teggi (1990), we are convinced that albendazole was effective in the treatment of the six PHD cases reported here. According to the criteria adopted to evaluate the present results, all six patients improved after albendazole treatment, particularly patients 1, 3, 4 and 5, who were considered cured. Although it may be assumed that a parasitologi-
cal cure occurred in the other two cases, extensive and generalized residual lesions in case 2 and involvement of the right hepatic duct in case 5 prevented a full recovery. We believe that the therapeutic alternative for these two cases is a liver transplant. The only other report of albendazole treatment of a (possible) case of PHD is that by Timerman eta/. (1986), who observed marked cyst reduction and clinical improvement. In another case of PHD (Ferreira et a/., 1987), treatment with mebendazole for one year failed and the patient died. The adverse side effects of albendazole which we observed in some of our patients have also been reported by others (Morris et a/., 1985; Davis et a/., 1986; Horton, 1989; De Rosa and Teggi, 1990). However, they did not prevent continuation of treatment and were reversible after discontinuation of the drug. We conclude that albendazole is effective in the treatment of PHD. The dose most frequently used was lOmgkg- day- 1 divided into two or three daily fractions. None of the patients received albendazole for less than 90 days, consecutive or not. Good results were obtained whether the drug was administered continuously or at intervals. Although side effects were
156
MENEGHELLI ET AL.
observed in both treatment schedules, the most significant ones occurred in a patient submitted to continuous treatment. We are grateful to Smith Kline & Cia., Rio de Janeiro, RJ, for
ACKNOWLEDGEMENTS.
kindly donating albendazole (Zentel). Financial support was provided by 'Funda.yao de Apoio ao Ensino, Pesquisa e Assistencia' (FAEPA) of our University Hospital. We are indebted to Edneia Fabbris Verceze and Regina Helena Bertoli for typing the manuscript.
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