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Progress in diagnosis, treatment and elimination of echinococcosis and cysticercosis.

Here I review the current status of geographical occurrence and public health significance of echinococcosis (Echinococcus spp. infections) and cysticercosis (Taenia solium infection) with special emphasis on the remarkable technologic progress achieved in recent decades that has led to greater understanding of the biology and epidemiology of these cestode infections. The greatest remaining challenges are to apply this knowledge and technology to improved medical management and prevention of these infections.

Animals↗

Imaging aspects and non-surgical interventional treatment in human alveolar echinococcosis.

Alveolar echinococcosis (AE) of the liver caused by the metacestode of the fox tapeworm Echinococcus multilocularis is characterized by a multivesicular structure surrounded by an extensive fibro-inflammatory host reaction. The lesions behave like a slow-growing liver cancer, without sharp limits between the parasitic tissue and the liver parenchyma. Invasion of biliary and vascular walls is another hallmark of this severe disease. Moreover, the poor vascularization of the parasitic mass often leads to necrosis in the central part of the lesion. This explains why liver abscess due to superimposed bacterial infection of the necrotic area may occur in this disease. Currently, a range of imaging techniques can be used at the different stages of management of AE. For diagnosis, ultrasonography remains the first line examination. For a more accurate disease evaluation, aiming to guide the surgical strategy, computerized tomography, Magnetic Resonance (MR) imaging, including cholangio-MR imaging are of importance, providing useful complementary information. More recently, Positive-Emission Tomography using [18F] fluoro-deoxyglucose has been developed for the follow-up of inoperable AE patients under long-term benzimidazoles therapy. This approach seems very promising to assess inflammatory activity and thereby to indirectly depict parasitic activity. Non-surgical interventional procedures, mainly percutaneous biliary and/or centro-parasitic abscesses drainages, are currently a major aspect in the care of incurable AE patients and have largely contributed to the improvement of survival in this situation during the past 20 years. They may also be used as a bridge before a curative surgical procedure in symptomatic patients presenting a life-threatening bacterial and/or fungal infection. It is also very useful in inoperable patients to overcome similar infectious episodes.

Animals↗

Orthotopic liver transplantation for incurable alveolar echinococcosis: report of five cases from west China.

Alveolar echinococcosis of the liver, caused by the larval stage of Echinococcus multilocularis, has the characteristics of a slow-growing liver cancer. The aim of the present work was to report a series of patients who received orthotopic liver transplantation (OLT) for life-threatening disease. Our article summarizes the medical history, diagnosis, treatment, and prognosis of five patients who received OLT between 2001 and 2002. Most patients had a long history of symptomatic disease (iterative cholangitis, obstructive jaundice) and repeated abdominal surgery. One patient died during the hospitalization mostly related to bacterial infection and multiple organ failure. Another accidental death happened 3 months later from heart failure. Three patients are alive in good condition verifying that OLT is a feasible option for these end-stage cases. In general, combination therapy-chemotherapy, interventional therapy, radical surgery or/and OLT at an early stage-is proposed in advanced cases of which OLT has clearly played a vital role. Despite major technical difficulties, OLT for incurable disease is feasible. Specific management is needed to improve the results: earlier decision for OLT in symptomatic disease, routine pre- and post-transplant therapy, reduced immunosuppression, and regular follow-up.

Adolescent↗

Human cystic echinococcosis in two Mongolian communities in Hobukesar (China) and Bulgan (Mongolia).

In order to investigate the prevalence of human cystic echinococcosis (CE) in traditional Mongolian communities in western Mongolia and Xinjiang (northwest China), studies were carried out between 1995 and 2000, on two ethnically identical populations in Hobukesar (China) and Bulgan (Mongolia). The prevalence of human hepatic CE in the two communities was significantly different. In Hobukesar, human CE prevalence by ultrasound was 2.7% (49/1844), while in Bulgan it was 0.2% (4/1609) (P<0.001). Dog surveys showed that coproantigen-positive rates or dog necropsy positives were similar in both communities (35.0% in Hobukesar and 35.7% in Bulgan). Comparing possible risk factors, there appeared to be some significant differences between the two communities, which might contribute to the observed difference in CE prevalence. These included: the proportion of herdsman or farmers recorded; the proportions of dog ownership and livestock ownership; and the proportion of families practising home slaughter. The presence of a Russian dog-dosing programme up to the mid-1980s may explain the lower prevalence of human CE in the Bulgan population; no similar programme operated in the China-administered Hobukesar community.

Animals↗

Repeated treatment of cystic echinococcosis in patients with a long-term immunological response after successful surgical cyst removal.

Six cystic echinococcosis patients underwent surgery for the removal of echinococcal cysts. All were treated with albendazole prior to and following treatment. After surgery, no cysts were detected in five of the six patients examined. Both ELISA and immunoblot analysis have been used to determine specific IgG, IgG4 and IgE activities. Total elimination of IgG and IgG4 was not achieved in any of the patients studied. Prior to the first surgery/treatment, specific IgG, IgG4 and IgE antibodies were demonstrated in all patients, except one who did not show any IgE activity. The first treatment was followed by highly elevated IgE in two patients; in one of them it was further combined with an apparent decrease in IgG activity. Repeated treatment with albendazole given 0.8-8.5 years after the first treatment/surgery was followed by either moderate or highly reduced IgE activity in two patients, respectively, and a slight increase in IgG4 in another patient. A third course of treatment, given 2-2.5 years after the second treatment, barely affected the antibody activities. The present study suggests that anti-echinoccocal antibody activity may remain high many years after successful cyst removal. Determination of IgG, IgG4 and IgE responses is preferable for the assessment of treatment results. The presence of anti-echinococcal antibodies after surgery with no cyst detection does not necessarily indicate an active echinococcal infection.

Adult↗

Diagnosis of cystic echinococcosis on sheep farms in the south of Argentina: areas with a control program.

In 2000 Guarnera et al. proposed using ELISA in canine faeces collected from the ground to detect dogs infected with Echinococcus granulosus, thus determining sheep farms with active transmission. The objective was to evaluate the prevalence of E. granulosus infection in sheep farms of the Patagonia. Sheep farms were randomly selected in the Provinces of Río Negro, Chubut, Neuquén, Santa Cruz and Tierra del Fuego (areas with control programs) and La Pampa (comparison area). From one to three samples of fecal matter were obtained for each sheep farm, which were processed by means of copro-ELISA test with confirmation of positive samples by copro-Western blot. A total of 1042 samples were obtained from 352 sheep farms, 26 (7.3%) proving positive. Of these 5 (6.3%) were from La Pampa, 9 (13.8%) from Neuquén, 4 (4.7%) from Río Negro, 2 (2.9%) from Chubut, 1 (5.9%) from Santa Cruz and 5 (13.9%) from Tierra del Fuego. The identification of parasitized dogs is an essential activity upon which rests the strategy of control and surveillance. Arecoline tests or coproantigen test with fecal matter obtained directly from the dog contribute information on individual prevalence, while the use of coproantigens detected in ground-collected samples transfers the dog unit of observation to units of greater epidemiological value. In the present experience, the technique employed seems promising for its application in systems of epidemiological surveillance of cystic echinococcosis and in drawing a baseline on which to measure the progress of control programs in the Argentine Patagonia in subsequent years.

Animals↗

Canine echinococcosis in northwest Libya: assessment of coproantigen ELISA, and a survey of infection with analysis of risk-factors.

In order to determine the prevalence and risk factors for canine echinococcosis in different endemic localities in the Tripoli area of northwest Libya, stray dogs were examined post-mortem, and owned dogs screened for Echinococcus granulosus infection using a standardised genus specific coproantigen ELISA. The prevalence of E. granulosus infection at necropsy in stray-dogs was 25.8% (15/58, 95% CI 15.3-39.0%), and 21.6% (72/334, 95% CI 17.3-26.4%) of owned dogs tested were positive by coproantigen ELISA. Sheepdogs appeared to have a significantly higher copro-positive prevalence (19/19 positive, p=0.003), compared to 23.6% of other dog classes (e.g. 52/220 guard dogs and household pets). Worm burdens in necropsied dogs ranged from 29 to 2900 (mean 1064) and were positively correlated to coproantigen ELISA OD values (r(s)=0.87, p<0.001), but negatively correlated with dog age (r(s)=-0.69, p=0.001). Dog age was a significant factor in copro-prevalence as there was an increasing coproantigen-positive tendency in younger dogs (< or =5 years, p=0.04). A total of 45/132 (34%, 95% CI 25.9-42.1%) of farms/homestead had at least one dog that was coproantigen positive. Overall copro-prevalence in dogs by locality varied, with Alkhums (Leptis-Magna) district having the highest copro-prevalence at 38.7% (24/62, 95% CI 26.6-50.8%) (p=0.001). Coproantigen testing of a cohort of owned dogs before and approximately 15 months after praziquantel treatment showed a significant decrease in the coproantigen positive rate from 21.6% (72/334) to 9% (21/233) post-treatment. The overall E. granulosus coproantigen positive rate ('re-infection rate') within the same cohort of dogs was 22 % (10/45) by 15 months post-treatment. Significant risk factors for a copro-positive owned dog were associated with non-restraint of dogs, and owners that did not de-worm their dogs. Home slaughtering of livestock and lack of knowledge about E. granulosus transmission were also significant risk factors for a canine coproantigen positive result.

Age Factors↗

Serological diagnosis of canine alveolar echinococcosis.

Canine alveolar echinococcosis (AE) is a rare liver disease caused by the larval stage (metacestode) of E. multilocularis. Its diagnosis so far is rather difficult and invasive. Imaging techniques for the diagnosis have been described recently and in this study, the serological diagnosis of canine AE was evaluated in 30 dogs with confirmed AE using ELISA based on seven different antigens (E. multilocularis-antigens: Em2G11, EmII/3-10, protoscolex (EmP), excretory/secretory and adult integument (EmAd/I); E. granulosus antigens: hydatid fluid (EgHF) and antigen B (EgAgB)) and by the detection of circulating Em2G11-antigen. EmII/3-10 and Em2G11-based tests detected AE in 50 and 53%. The combined serological investigation for specific circulating Em2G11-antigen and specific antibodies against this antigen showed a sensitivity of 77%. This strategy is useful in animals with large parasite masses and ascites. The highest sensitivities for AE were obtained by the EmAd/I and the EmP antigens (97 and 93% sensitivity) with high specificities in the control group of 76 dogs (100 and 98.7%, respectively). Heterologous E. granulosus antigens (EgHF and EgAgB) showed low sensitivities (43 and 50%, respectively) with high numbers of unspecific reactions (>16%) in the control group. In the follow-up of four dogs, the serological reaction patterns against the antigens Em2G11, EmP and EmAd/I showed some correlations with the development of the parasite mass. Intestinal infections cannot be differentiated from AE by most antigens (except EmII/3-10) and have to be excluded by the absence of coproantigens or DNA of E. multilocularis in faecal samples.

Animals↗

Ultrasonographic screening for cystic echinococcosis in sheep in Tunisia.

Sheep from the areas of Fondouk-Jeddid, Bir Mchergua and El Fahs, located in the Northeast of Tunisia, were examined by ultrasonography between 2001 and 2004 in order to assess their infection with Echinococcus granulosus, the agent of hydatid disease, and to evaluate this method as an efficient aire for hydatid cysts. A total of 1039 sheep, aged between 1 and 14 years was examined. The highest prevalence was found in sheep aged more than 8 years. The least infected animals were aged between 1 and 2 years. All hydatid cysts detected by ultrasound were located in the liver. In all age-groups, the dead cysts were more numerous than viable cysts. Eighteen positive sheep were autopsied and a comparison between ultrasound and autopsy results was performed. The results showed a prevalence of about 40% for the three areas. Ultrasonography allowed the cysts, deep or superficial to localize in the central or left part in relation to the caudal vena cava of the animals. Consequently, all the cysts were not detected with this technique. This work shows that ultrasonography confirms the importance of ovine hydatid cyst in Tunisia and that its use as a mass screening approach for cystic echinococcosis in sheep could be helpful for the monitoring of this disease in a hydatid control program without great stress for the animals.

Age Factors↗

Ovine echinococcosis I. Immunological diagnosis by enzyme immunoassay.

Immunodiagnosis in sheep presents problems of sensitivity and specificity, limiting its applicability in surveillance systems. The objective of this study was to develop a sensitive, specific and accessible technique for diagnosing cystic echinococcosis in naturally infected sheep and to evaluate the validity of necropsy as a reference test. A total of 247 sheep were studied at slaughterhouses, confirming the parasitological diagnosis with histology. Serum was processed with enzyme immunoassay (EIA) using three antigen preparations: total hydatid liquid (LHT), purified fraction of LHT (S2B) and purified lipoprotein (B). Western Blot (WB) was used as a control. EIA proved effective for differentiating Echinococcus granulosus from larval stage of Taenia hydatigena and intestinal cestodes in all three antigen preparations. Serums from macroscopically negative sheep were reactive to EIA and positive with WB. In the whole flock, sensitivity was 89.2% for LHT, 80.0% for S2B and 86.4% for B. Sensitivity in lambs was 78.6% for LHT, 75.0% for S2B and 64.3% for B. Macroscopic diagnosis at the time of slaughter was found to have limitations as a reference test for immunodiagnosis of cystic equinococcosis in sheep, so it was necessary to include histology and WB as reference tests. LHT was the antigen preparation of greatest value and EIA proved to be a sensitive and specific technique, adequate for surveillance systems and for evaluating control programmes.

Abattoirs↗

An epidemiological and ecological study of human alveolar echinococcosis transmission in south Gansu, China.

Human alveolar echinococcosis (AE) is usually a rare, highly pathogenic zoonotic disease, transmitted across the northern hemisphere between fox and rodent hosts. In China the first cases were described in 1965; however very few epidemiological studies have been undertaken since. Following identification in 1991 of a serious focus of human AE in south Gansu province, detailed village-based community and ecological studies were carried out between 1994 and 1997. Hepatic ultrasound mass screening with serological testing (five tests) identified 84/2482 new AE cases (3%). An overall prevalence of 4.1% (135/3331) was recorded for the area when previous cases were also included. Based on a seropositive result only, without an ultrasound scan indication, no additional AE cases were identified. Of the evolutive AE cases, 96% were seropositive in at least one test, while up 15-20% of individuals who exhibited hepatic calcified lesions and 12-15% exhibiting hepatic nodular lesions were seropositive for specific Em2 or Em18 antibodies. Village (n=31) human AE prevalence rates varied from 0 to 15.8%. Questionnaire analysis indicated that total number of dogs owned over a period was a risk factor (P<0.006), but not a history of red fox hunting (P>0.6). Rodent ecology studies revealed an association between density indices of voles (Microtus limnophilus) and village AE prevalence rates, on the one hand, and village landscape characterised by a ratio of scrub/grassland to total area above 50% (P<0.005). Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture. This in turn probably results in creation of optimal peri-domestic habitats for rodents that serve as intermediate host species (such as M. limnophilus) and subsequent development of a peri-domestic cycle involving dogs.

Adult↗

Prevalence of cystic echinococcosis among Muslim and Jewish populations in southern Israel.

Following a review of records at the Soroka University Medical Center (SUMC) showing a recent increase in the annual incidence of hydatidosis among the Bedouin population of southern Israel, a seroepidemiological survey was conducted. A total of 1439 blood samples were collected from Bedouins and Jews living in the Negev area in southern Israel. An enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G, indirect haemagglutination (IHA) and immunoelectrophoresis (IEP) were used to detect anti-Echinococcus granulosus antibodies. The seroprevalence in the Bedouin group was 0.68% (7/1026), including two children under the age of 10. Among Jews, a seroprevalence of 0.5% was recorded in patients over 60 years of age only. A high rate of infection was shown in goats and sheep slaughtered in abattoirs in Bedouin localities. The results indicate that echinococcosis is a common disease in the Muslim communities of southern Israel.

Adolescent↗

Survey on cystic echinococcosis in Tibetans, West China.

Human cystic echinococcosis (CE) is a serious public health problem in West China. The Tibetan has a nature relation with these definitive and intermediate hosts in West China. Although Tibet is CE endemic, a few community studies have been reported. Eight hundred and eighty two Tibetans residing in the three rural communes of Tianzhu County, Gansu province of West China were investigated by serology and ultrasound scanning. 11.2% serum antibody positive rate in ELISA test was found out, and a 12.1% ultrasound rate of hepatic CE was found in the sero-positive population. Seropositivity rates varied for communes between 7.6 and 13.7%. Overall, females had a significantly greater risk of infection than males-ratio was about 2:1. The local behaviors were investigated and showed that family dog and grazing could not effect the infectious rates, but the number of sheep owned a family had a positive correlation with the infection rates. The infectious rate of hunting population was significantly higher than that of no-hunting population. The educated level of Tibetans in school had no effect on the infected rates.

Adolescent↗

Progress in control of cystic echinococcosis in La Rioja, Spain: decline in infection prevalences in human and animal hosts and economic costs and benefits.

The Autonomous Community of La Rioja is a region in the north of Spain where the mean annual number of surgical cases of cystic echinococcosis (CE) was 50 (19 per 100000 inhabitants) during the years 1984-1987. This high clinical incidence prompted local authorities to implement a control program in 1986, whose methods and results are reported here. Initially, the program consisted in documenting the prevalence of CE in sheep and humans, communicating an awareness of the disease risks among the population, and treating all registered dogs with praziquantel at intervals of 45 days. Stray dogs were collected systematically, euthanized, and their intestines were examined for Echinococcus granulosus infection. Epidemiological data collected during the course of the program demonstrated that the major reservoirs of E. granulosus were the stray dogs, precisely the ones not receiving periodic praziquantel treatment. Therefore, the program emphasis was shifted to targeting critical points in the transmission of E. granulosus, including improved control of stray dogs, echinococcidal treatments of working sheep dogs, providing means for safe disposal of slaughtered sheep offal and safe disposal of dead sheep in sanitary pits. These measures led to a decline in prevalence of E. granulosus in dogs from 7.0% at the beginning of the program to 0.2% in 2000, i.e. a reduction of 97.2%. Prevalence of infection in adult sheep declined from 82.3 to 20.3%, i.e. a reduction of 75.4%, while the mean number of cysts per infected animal decreased from 6.5% to 0.58 (91% reduction). The rate of diagnoses of new cases in humans between these two dates dropped by 78.9%, from 19 to 4 per 100000 population. In terms of economic costs, these reductions were estimated to yield an increasing cumulative cost/benefit balance that was already positive on year 8 of the program (1994), and that reached 1.96 in year 2000.

Animals↗

Albendazole-soybean oil emulsion for the treatment of human cystic echinococcosis: evaluation of bioavailability and bioequivalence.

A single 12.5 mg/kg dose of albendazole (Abz) in tablet form (AbzT) followed 2 weeks later by an equivalent dose of Abz emulsified in 30% soybean oil (AbzE) was administered orally 2 h after the first morning meal to 7 male adult patients with cystic echinococcosis caused by Echinococcus granulosus. Serum samples were taken 1, 3, 5, 7, 8, 9, 11, 14, 18, 24, 36, and 48 h post medication from each patient to measure the serum concentrations of albendazole sulfoxide (AbzSOX), the principal bioactive metabolite of Abz. AbzSOX concentrations were measured by reverse phase HPLC. The data were subjected to pharmacokinetic analysis to compare the relative bioavailability and bioequivalence of AbzT and AbzE. The results demonstrated that the mean peak concentrations (C(max)) for AbzT and AbzE were 1.06+/-0.38 mg/l and 1.71+/-0.47 mg/l, respectively; the area under the concentration-time curves (AUC) were 13.24+/-4.93 mg x h/l and 21.01+/-7.54 mg x h/l, respectively. The relative bioavailability of AbzE was F(Flu)=1.59. Two one-sided tests procedure and (1-2 alpha) 90% confidence interval methods were used to evaluate the bioequivalence of AbzE and AbzT. The results demonstrated that the bioavailability of AbzE was greater than AbzT.

Administration, Oral↗

Benzimidazole treatment of cystic echinococcosis.

Hydatidosis (cystic echinococcosis, CE) constitutes a serious public health problem worldwide. Total surgical removal of a hydatid cyst is still considered the gold standard treatment for CE. Percutaneous treatment (PAIR), using either hypertonic saline or alcohol as a larvacidal agent, appears to be an additional effective form of treatment. Benzimidazoles (albendazole, ABZ; mebendazole, MBZ), given either alone or combined with praziquantel (PZ) are currently used for the treatment of non-surgical cases and as a supplementary treatment prior and post-surgery. Combined chemotherapy was found to be more effective than either of the agents given alone. ABZ is easily absorbed and more effective than MBZ. ABZ (12-15 mg/kg/day) and MBZ (30-70 mg/kg/day) given for 14-20 days prior to surgery and continued for an additional 3-24 months in a cyclic monthly form were found effective against the disease. Either increased or decreased circulating antigen levels, which consequently cause changes in the humoral (IgG, IgG1, IgG4, IgE) immune responses, have a prognostic value in successfully treated CE cases. However, although the cellular immune response to echinococcal antigens decreased in improved or cured CE patients, it was not considered of practical use in determining treatment efficacy. In certain cases successful treatment was also followed by elevated eosinophilia and erythrocyte sedimentation rates. In the present article, the mechanism of drug activities as well as the development of resistance against the drugs available are further discussed.

Albendazole↗

International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings.

The increased knowledge of the natural history of cystic echinococcosis (CE) by the recent expansion in the use of ultrasound (US) in field and clinical studies has necessitated the development of a new WHO standardised classification of US images. Use of such a classification will enable clinicians to examine recommended clinical procedures for the different cyst types. It will also allow scientists to compare data on the occurrence of cyst types in different parts of the world providing evidence to examine strain differences in the causative organism Echinococcus granulosus. The classification proposed follows that of the first classification developed by Gharbi et al. [Radiology 139 (1981) 459] which has been widely used, but in modified forms, since its publication. The classification presented here is intended for use in field epidemiological studies as well as for clinical investigators. The classification is intended to follow the natural history of CE and starts with undifferentiated simple cysts, as presumably hydatid cysts evolve from these structures. These simple cysts, however, may be due to a number of different aetiologies (parasitic lesions, congenital disorders, biliary cysts or neoplasms) and, therefore, require further diagnostic tests to reveal their identity. As their origin is uncertain they are not given the designation of a CE type lesion, and, in the proposed classification, should be recorded as cystic lesions (CL). The first clinical group starts with cyst types CE 1 and 2 and such cysts are active, usually fertile cysts containing viable protoscoleces. CE Type 3 are cysts entering a transitional stage where the integrity of the cyst has been compromised either by the host or by chemotherapy and this transitional stage is assigned to the second clinical group. The third clinical group comprises CE Types 4 and 5 which are inactive cysts which have normally lost their fertility and are degenerative. The use of the standardised US classification will facilitate the application of uniform standards and principles of treatment currently recommended for each cyst type.

Animals↗

The changing epidemiology of echinococcosis in Kazakhstan due to transformation of farming practices.

In recent years there has been a substantial increase in cystic echinococcosis in Kazakhstan. There are several factors that have contributed to this change in the epidemiology of the disease. The primary reason was the degradation of traditional nomadic system of livestock breeding and closing of large collective farms. Small private farms have started to keep stock year round in closer proximity to permanent human habitation. Furthermore, routine anthelmintic prophylaxis of dogs has been abandoned and there is inadequate control over the use and disposal of animal carcasses. Large mechanized slaughterhouses are no longer operational. Now more people (7-8 times) and more dogs (8-10 times) participate in the husbandry of 1000 sheep, than during Soviet administration. Because of the close association of dogs with man there is the potential for a substantial increase in eggs and of Echinococcus in immediate environment of inhabited houses. Soil samples taken from 61% of yards of village homes contained taeniid eggs and from 35% of yards from around farmsteads. During an examination of 1464 village dogs the average rate of infection with Echinococcus granulosus was 5.8%, whilst the prevalence in 607 shepherd dogs was 23.2%. At present, these dogs represent a major source of infection for people with this dangerous parasite. Examination of hospital records suggested that children and people in occupations associated with animal husbandry were at most risk of infection.

Adolescent↗