Aim
To investigate the relationship between plasma and cyst concentrations of albendazolesulphoxide (ASO) and their effects on parasitological findings and disease recurrence in patients with liver hydatidosis.
Methods
The study was conducted at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević,” Zagreb, Croatia, between August 2006 and January 2011. Consecutive patients (N = 48, age 6-77 years) were treated with albendazole (3 × 5 mg/kg/d) over 28 days before surgical cyst removal (n = 34) or percutaneous evacuation (PAIR) (n = 14). Plasma ASO was determined on days 10 and 28 of treatment and cyst concentrations at surgery/PAIR.
Results
Disease recurred in 3 surgically treated patients. Variability of ASO concentrations was substantial. Plasma concentrations on day 10 were higher than on day 28 (geometric means ratio [GMR] 2.00; 95%CI 1.38-2.91,
P < 0.001) and higher than cyst concentrations at the time of treatment (GMR = 1.58, 1.01-2.34,
P = 0.045). Higher cyst (but not plasma) concentrations were independently associated with lower odds of protoscolex motility (OR = 0.23, 0.01-0.70,
P < 0.001) and higher odds of protoscolex destruction (OR = 1.17, 1.04-1.46,
P < 0.001). With adjustment for age and protoscolex motility, higher day 10 plasma concentrations (but not cyst concentrations) were associated with lower odds of disease recurrence (OR = 0.49, 0.09-0.97,
P = 0.035). Plasma concentrations did not predict cyst concentrations.
Conclusion
Viability of protoscolices progressively decreased with increasing ASO concentrations in the cyst. Data strongly suggested that higher plasma concentrations reduced the risk of disease recurrence.Echinococcosis or hydatid cyst disease is an anthropozoonosis caused by the larvae of
E. granulosus,
E. multilocularis,
E. vogeli, and
E. oligarthus (
1). In transient hosts (eg, sheep, cattle, pigs, humans), the parasite develops in the form of hydatid cyst(s) of different sizes. The cyst consists of the outer layer (ectocyst), made of dense fibrous tissue; the middle layer (endocyst), which is elastic and lamellar in structure; and the inner (germinative) layer, which gives rise to buds that develop into scolices. The cyst content is hydatid fluid, produced by the germinative layer. In humans, the most commonly invaded organs are the liver and the lungs, but practically all organs can be affected (
1-
3). In Croatia, the disease is caused exclusively by
E. granulosus. According to the European Hospital Morbidity Database (
4) for the period 2010-2012, age-adjusted annual hospital admission rates due to echinococcosis (ICD-B67) in Croatia varied between 0.011 and 0.0167/1000 population (ie, between 51 and 86 cases/y), indicating that the diseases is relatively rare but still stably present.Treatments for hydatid cyst disease include surgical removal of the cyst(s) (still most commonly used method); percutaneous aspiration of the cyst with instillation of a scolicidal agent (95% ethanol or hypertonic saline [15%-20%] or albendazole), ie, the PAIR (puncture, aspiration, instillation, and re-aspiration) procedure, which seems to have greater clinical efficacy and lower rate of complications than the surgical procedure; and treatment with benzimidazole anthelmintic drugs. The latter, pharmacological option might be used as a monotreatment in the case of smaller cysts or when invasive approaches are not feasible, but it is typically adjunctive treatment to surgery or PAIR used to prevent dissemination of scolices from ruptured cysts. In this setting, benzoimidazoles are used over at least 4 weeks before the definitive treatment (
5-
8). Among benzoimidazoles, albendazole is considered a cornerstone pharmacological treatment of echinococcosis. Although some controversies still exist regarding optimal dosing, the most widely accepted regimen implies administration of 10-15 mg/kg/d (
5-
8). Upon oral ingestion (with a fatty meal to increase bioavailability), albendazole is rapidly metabolized (first-pass metabolism in the liver) into the active form albendazolesulphoxide (ASO), which inhibits tubuline polymerization in the parasite microtubules and inactivates cell division (
9). Greater systemic bioavailability is considered an important advantage of albendazole over mebendazole, the other member of the group (
9). Although ASO has been shown to penetrate both the hepatic and non-hepatic cysts (
9,
10), the prognostic value of plasma and/or cyst concentrations has not been elucidated. Therefore, we aimed to relate ASO concentrations in the plasma and in the cysts, and to investigate their relationship with the parasitological and clinical outcomes in patients with liver hydatidosis treated with albendazole over one month prior to surgical treatment or PAIR.
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