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Echinococcus granulosus infection: the challenge of surgical treatment.

BACKGROUND: Cystic echinococcosis (CE) is a worldwide zoonosis caused by larval stages of the cestode Echinococcus granulosus. Surgery, chemotherapy, and interventional procedures are the therapeutic options. Surgery can cure the patient if the parasite is removed entirely. However, the technical procedures are inconsistent and comprise partial liver resection or opening of the parasitic cyst and removal of the parasite. Laparotomy is the most common approach. In selected cases laparoscopic methods are successful. Retrospective studies outweigh prospective ones by far. However, proper management gives favorable results. METHODS: We critically review the literature and present a brief summary of current surgical strategy and focus on issues relevant for surgeons: diagnosis, indication for medical treatment, indication for surgical treatment, surgical procedures, scolicidal agents, morbidity, mortality, recurrence, perioperative medication, standards. RESULTS: All surgical procedures aim at the complete removal of the parasite. Liver resection and pericystectomy are procedures that resect the closed cysts with a fairly wide safety margin. A meta-analysis shows the best results regarding lethality (1.2%), morbidity (11.7%), and recurrence rates (2%) for resective operations. However, most surgeons consider these methods as too radical for a benign disease. Procedures that remove the parasite and keep the pericyst (=cystectomy) are easier to carry out than resective ones. The meta-analysis presented revealed a lethality of 2%, morbidity of 23%, and recurrence rate of 10.4% for these operations. Omentoplasty is the option of choice for the management of the remaining cyst cavity. Despite alternative procedures surgery is the treatment of choice. Supportive measures comprise the use of scolicidal agents and postoperative benzimidazole administration. However, a critical review of the literature disclosed a lack of scientific confirmation of established treatment modalities and procedures. The results of ultrasound imaging were classified and correlated to the developmental phases of CE. CONCLUSIONS: Cystectomy and omentoplasty for CE should be the standard surgical procedure because it is safe, simple, and effective and meets all criteria of surgical treatment for hydatid disease: entire elimination of the parasite, no intraoperative spillage especially by using a cone, and saving healthy tissue. Pericystectomy should be used for peripherally located liver cysts that are surrounded by parenchyma only partially. Ultrasonic classification of the parasitic lesion should be used as a guideline for therapeutic measures.

Animals↗

Evaluation of the efficacy of emodepside+praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats.

Emodepside+praziquantel topical solution was developed to provide broad-spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and praziquantel (12 mg/kg) (Profender, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis, or experimental infections with Echinococcus multilocularis that were placebo-controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+praziquantel topical solution was 100% against D. caninum and T. taeniaeformis, and 98.5- 100% against E. multilocularis. No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+praziquantel topical solution was safe and highly effective against cestode infections.

Administration, Topical↗

Dose dependency of prednisolone tertiary-butylacetate (PTBA) treatment on the establishment and site predilection of Echinococcus multilocularis in an alternative definitive host model using Mongolian gerbil (Meriones unguiculatus).

Mongolian gerbils (Meriones unguiculatus) were orally inoculated with 10,000 protoscoleces of Echinococcus multilocularis per head after being divided into five groups (A E). Each group was dosed with prednisolone tertiary-butylacetate (PTBA) as follows: A, 0 mg; B, 0.5 mg; C, 2 mg; D, 5 mg; and E, 10 mg/head. All animals were injected subcutaneously with control solvent or PTBA every other day from 6 days pre- to 6 days post-infection. Autopsy was performed at 7 days post-infection. Doses of PTBA and the number of worms recovered showed a positive correlation (r = 0.929, P < 0.0001). In groups A, B and C, the predilection site of the worms in the small intestine could not be determined, while in group D the worms were found more in the anterior part. In group E, the predilection site was the anterior part, followed by the middle and the posterior parts of the small intestine (Fisher's test: P < 0.01). The number of worms recovered from the anterior and the middle part of the small intestine also correlated positively with PTBA dose (anterior part: r = 0.930, P < 0.0001, middle part: r = 0.917, P < 0.0001). All groups of the PTBA-treated animals showed significant loss of weight compared to the nontreated animals (P < 0.01).

Animals↗

H and 13C n.m.r. studies of serum from normal and Echinococcus multilocularis infected jirds.

The major components of the 13C and high field region of the 1H nuclear magnetic resonance (n.m.r.) spectra of normal and Echinococcus multilocularis infected jirds were identified and compared. Substantial depletion of the glucose and fatty acid chains from lower density lipoproteins was detected in sera from infected animals. In addition, this proliferating metacestode markedly changed the appearance of the spectral region recently assigned to N-acetyl protons of carbohydrate side chains of N-acetylated glycoproteins.

Animals↗

Parasitological serendipity: from Schistocephalus to Echinococcus.

Attention is drawn to the situation nowadays, whereby workers are encouraged to undertake research which appears useful or of economic importance, although the History of Science indicates that many major discoveries have been the result of 'serendipity'--'the chance observation falling on the receptive eye'. Some of the more important examples in Medicine and Parasitology are reviewed. The author then relates how he was given a stickleback infected with the plerocercoid of Schistocephalus solidus, an episode which eventually led to the successful in vitro culture of the adult of this species. Attention is also drawn to the largely unrecognized work of the Danish Veterinarian, P. C. Abildgaard, who in 1789 demonstrated that this species completed its life cycle in a bird, thus establishing, for the first time, the transmission of a parasite from one host to another. The in vitro culture of S. solidus led to the development of successful in vitro techniques for Ligula intestinalis and for Echinococcus granulosus and E. multilocularis. The observation that E. granulosus of horse origin failed to grow in vitro led eventually to the concept of physiological 'strains' of E. granulosus, now a subject of much international research.

Animals↗

Natural Echinococcus multilocularis infection in a Norway rat, Rattus norvegicus, in southern Hokkaido, Japan.

Forty-two rats, Rattus norvegicus, captured at a garbage dump in southern Hokkaido, Japan, were examined, and one was found to be infected with Echinococcus multilocularis. The lesions were found in the liver, lung, mesenteric lymph nodes, greater omentum and also free in the abdominal cavity. No necrosis was observed in any of the lesions, and inflammatory reactions were mild. Protoscoleces were observed in the large liver cysts. A homogenate of these cysts, when transplanted into the abdominal cavity of three Mongolian gerbils and a rat, yielded numerous fully developed protoscoleces at 4-7 months post-inoculation. Judging from this, it is postulated that the rat could become a natural intermediate host for E. multilocularis in this area.

Animals↗

Rates of reinfection with Echinococcus granulosus, Taenia hydatigena, taenia ovis and other cestodes in a rural dog population in Uruguay.

A survey was undertaken to determine both the prevalence of, and reinfection rates with Echinococcus granulosus and other cestodes in the Department of Florida, Uruguay. Baseline prevalence was determined in 303 rural dogs which then, in 4 groups, were re-examined 2, 4, 8 or 12 months later. Baseline prevalences for E. granulosus, Taenia hydatigena, Taenia ovis and Dipylidium caninum were 13.2, 13.9, 2.3 and 13.2%, respectively. The frequency distribution of E. granulosus was over-dispersed. Dogs in the population became infected with E. granulosus between 2 and 4 months after treatment (prevalences at 2, 4, 8 and 12 months were 0, 6.8, 18.6 and 27.9%, respectively). There was no indication that there was a predisposition of dogs to infection with the Odds Ratio being 1.0. Dogs were infected with T. hydatigena and D. caninum within 2 months and with T. ovis between 2 and 4 months after treatment. The implications of these different rates of reinfection in the dog population on anthelmintic control strategies against cystic echinococcosis are discussed.

Age Factors↗

Maternal transfer of protection from Echinococcus granulosus infection in sheep.

Although passive immunity against larval metacestodes of the genus Taenia is well established, the transfer of immunity against Echinococcus granulosus infection has not been demonstrated convincingly. The immune status of newborn lambs born to ewes that had been infected or immunised with E granulosus eggs or oncospheres was investigated. The ewes and their six- to eight-day-old lambs were subsequently challenged. Lambs born to triply infected ewes were 80 per cent protected from a challenge infection whereas lambs born to simply infected ewes were only 45 per cent protected. Lambs born to ewes that had been immunised with preparations of sonicated oncospheres had the lowest levels of immunity. The infected ewes were challenged intramuscularly with activated oncospheres and showed some degree of immunity. Ewes which had received oncospheres solubilised in sodium dodecylsulphate or sonicated oncospheres were protected from subsequent oral challenge by 60 to 66 per cent. Radial immunodiffusion revealed that lambs with statistically significantly lower levels of IgG were more susceptible to challenge. However, the degree of protection did not show a simple relationship to the titre of antibody, as determined by an ELISA using a solubilised antigen.

Animals↗

In vitro culture of Echinococcus multilocularis: protoscolicidal action of praziquantel and albendazole sulphoxide.

The metacestode stage of Echinococcus multilocularis was cultured in vitro. Sensitivity of protoscoleces to the presence of albendazole sulphoxide, praziquantel and methanol was assessed. 10 micrograms/litre of praziquantel or 500 micrograms/litre of albendazole sulphoxide significantly reduced protoscolex viability. The presence of methanol (at 0.25%) had no significant effect. In vitro culture of E. multilocularis can be used to assess possible chemotherapeutic agents.

Albendazole↗

Chemotherapy of Echinococcus infection in man with albendazole.

Since 1983 data have been collected on the outcome of treatment of apparently active Echinococcus granulosus hydatid cysts with albendazole. Most patients received 800 mg albendazole daily in cycles of 28 d with 14 d between cycles, with a mean duration of 2.5 cycles (range 1-12). From an initial set of over 500 cases, 253 patients were evaluated for efficacy, with 269 hepatic, 86 pulmonary, 50 peritoneal and 51 cysts at other sites being individually assessed. 72 patients (28.5%) were regarded as cured, 129 (51%) as improved, 46 (18.1%) as unchanged and 6 (2.4%) were worse. 47 patients underwent surgery after treatment and viability was demonstrated in only 5 cysts (10.6%). Recurrence was observed in 4 of 29 non-surgical cases (13.8%) from whom a follow-up of at least 24 months was available. 35 cases of E. multilocularis infection were assessed, with cure in 2, improvements in 4, stabilization in 25 and progression in 4 cases. Side effects of treatment were uncommon. Liver function abnormalities occurred in about 20% (4% withdrawn) and there was a tendency for leucopenia to occur in E. multilocularis patients. Albendazole appears to be effective both for chemotherapy in inoperable cases of hydatid disease and for prophylaxis before surgery.

Albendazole↗

Seroprevalence of Echinococcus granulosus infection in a Uruguayan rural human population.

Serological tests using hydatid cyst fluid (HCF) are useful as a primary screen for detecting asymptomatic infections due to Echinococcus granulosus in human populations. An enzyme-linked immunosorbent assay (ELISA) performed with whole sheep HCF was used to determine the prevalence of hydatid antibodies in a rural human population in Uruguay. In order to eliminate cross-reactions with sheep proteins in HCF, 1% normal sheep serum was added to each human serum before testing. ELISA seropositives were further tested using the double diffusion test (DD5) and confirmed where possible by ultrasound and X-ray examination. Serum samples were obtained from 420 individuals inhabiting rural areas in the Department of Paysandu (160), Rivera (21) and San José (239). An overall seroprevalence of 1.24% was obtained. Two of 17 seroreactors were subsequently proven to have hydatidosis. These results confirm and extend previous studies indicating an unusually high prevalence of E. granulosus infection in the Uruguayan population.

Adult↗

Giant cerebral Echinococcus cyst with galactorrhea and amenorrhea.

A case of giant left-sided frontal cerebral Echinococcus cyst causing headaches, galactorrhea--amenorrhea, secondary sterility, and gain in weight in an adult female patient is reported. The operative removal of this huge cyst led to complete neurological and endocrinologic recovery.

Adult↗

Primary infection of dogs with Echinococcus granulosus: systemic and local (Peyer's patches) immune responses.

Local and systemic lymphocyte proliferation and antibody production were tested in five dogs 35 days after primary experimental infection with Echinococcus granulosus. A significant cell proliferation was demonstrated by [3H] thymidine incorporation in mesenteric, popliteal and/or Peyer's patches (PPs) cells in response to E. granulosus protoscolex or adult worm antigen in three of five infected dogs, but not in five control animals. In contrast, blood mononuclear cells responded very weakly in only two of the infected dogs to parasite antigens. Elevated levels (compared with preinfection status) of protoscolex- and adult worm antigen-specific serum IgG were detected (ELISA) in four of the five dogs 35 days after infection. Furthermore, slightly elevated levels of parasite-specific IgE and IgA were observed in the sera of three and four in four infected dogs, respectively. Specific serum IgM was not significantly higher 35 days after infection than before infection. Local antibody production was studied in vitro using PPs, mesenteric and popliteal cells isolated from three infected and three uninfected dogs by ELISA using adult worm antigen. In two of three cultures of unstimulated PPs cells of infected dogs, parasite-specific IgG was detectable. Parasite-specific IgA and IgM were detected in one of the unstimulated PPs cell culture derived from an infected dog. Following in vitro stimulation with parasite antigen, PPs cells from two infected dogs showed increased parasite-specific IgG and PPs cells of all three infected dogs produced parasite-specific IgA. PPs cells from uninfected dogs did not produce significant quantities of parasite-specific antibodies and cells from mesenteric and popliteal lymph nodes of infected or uninfected dogs neither produced antibodies whilst in in vitro cultures.

Animals↗

Comment on the status of Echinococcus granulosus in the UK.

Echinococcus granulosus is composed of a complex of strains, the status of which has caused controversy and doubt. All have different characteristics which have arisen from animal husbandry practices, resulting in isolation and restriction of gene flow, and/or from the reproductive characteristics of the organisms. Whatever the mechanism for strain variation, Don McManus, Alan Lymbery and Andrew Thompson have no doubts that distinct variants occur in spite of a recent publication that suggests there is only one form of E. granulosus in the UK.

Journal Article↗

Echinococcus multilocularis in germany: increased awareness or spreading of a parasite?

The 'small fox tapeworm' Echinococcus multilocularis has recently become a matter of intense interest in Germany. A long-term increase of its prevalence in foxes has been noted in the well-known endemic areas in Southern Germany, and reports on the occurrence of the parasite in other parts of the country suggest that the parasite is actually much more widespread than previously thought. As nearly all of the relevant studies are published in the German language in a veterinary journal and in the hunting press, accessibility to the information is limited. Richard Lucius and Brigit Bilger here describe the situation, and discuss the possible reasons and consequences.

Journal Article↗

Protective immune mechanisms against the metacestode of Echinococcus multilocularis.

Infection with the larval stage of the fox tapeworm Echinococcus multilocularis results in a life-threatening hepatic disease concerning humans and intermediate rodent hosts. Immunoepidemiological surveys provided information that a large proportion of infected individuals may demonstrate either constitutional resistance to early post-oncospheral development of the parasite or late resistance to disease by exhibiting an intrahepatic died-out parasite lesion. Similar events have been found in secondary infections of laboratory rodents. Dissection of humoral and cell-mediated immune responses in susceptible versus resistant individuals provides insight into immunological pathways associated with the different outcome of infection. Survival strategy of the metacestode obviously focuses on the crucial role played by the parasite laminated layer. This layer protects the metacestode from host effector mechanisms which can potentially kill the proliferating germinative compartments in case of resistant hosts. Bruno Gottstein and Richard Felleisen here discuss the need to search for more parameters discriminating between the different immune pathways in order to find out (immunogenetic?) predispositions responsible for the respective phenomena.

Journal Article↗

Indirect fluorescent antibody test for the detection of antibodies to Echinococcus granulosus in experimentally infected pups.

Adult parasites of Echinococcus granulosus of buffalo origin were used as antigen in the indirect fluorescent antibody test (IFA) for detection of antibodies to E. granulosus in experimentally infected pups. The technique permitted detection of antibodies on Day 5 post-infection (p.i.) and up to Day 80 p.i. in infected animals. The antigen-antibody reaction was characterized by the appearance of a specific brilliant greenish yellow fluorescence on the embryophore of mature eggs present within and outside the gravid segment of the cestode. A maximum antibody titre of 1:320 at Day 50 p.i. was observed in the infected pups, coinciding with maturation of adult worms in the intestine of the host.

Animals↗