Epidemiology and approach treatment of human cystic echinococcosis: case series

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1 Artículo Original Epidemiology and approach treatment of human cystic echinococcosis: case series DOPCHIZ M.C. 1,2, ALBANI C. 1,2, RIVA E. 2,3, ELISSONDO M.C. 1,2, LAVALLÉN C.M. 1,2 and DENEGRI G. 1,2 1 Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Mar del Plata, Buenos Aires, Argentina. 2 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. 3 Departamento de Sanidad Animal y Medicina Preventiva, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Bs Aires, Tandil, Bs Aires, Argentina. ABSTRACT Cystic echinococcosis (CE) is a zoonoses of worldwide distribution caused mainly by the metacestode Echinococcus granulosus. In Argentina, its distribution reaches endemic levels. The aims of this study were to investigate the trends in confirmed cases of human CE recorded in Hospital Privado de Comunidad (HPC) in Mar del Plata city during a period of 28 years ( ) and to study demographic and clinical characteristics of cases together with epidemiological factors associated with the disease. Clinical records of operated and/or diagnosed patients were reviewed with regard to this disease. One hundred and fifteen cases (57.4% women; mean age years) were included in this retrospective study, 80% of which lived in urban areas. In 76.5% of the cases, ultrasonography was used to diagnose the disease. Hepatic location was the most frequently seen. Ninety point four per cent of the total diagnosed CE patients received any approach due to illness, 47.1% received surgical treatment and 19.2% pharmacological treatment. The mean length of hospital stay was 15 days. The average incidence for the period was 3.6 and 1.3 in HPC and Official Notification respectively. Our study showed that since the permanence of CE in the region is mainly due to the natural transmission of the parasite in the absence of control and prevention measures, health authorities should implement the necessary strategies in the study area. Key words: Cystic echinococcosis, Echinococcus granulosus, Epidemiology, Treatment, Zoonoses. RESUMEN La echinococosis quística (EC) es una zoonosis de distribución mundial, causada principalmente por el metacesto de Echinococcus granulosus. En Argentina, su distribución alcanza niveles endémicos. Received: 30 December Accepted 05 de Mayo Corresponing: Dra. Marcela Cecilia Dopchiz Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata. Funes 3350, 7600, Mar del Plata, Buenos Aires, Argentina. Tel int450, Fax: mdopchiz@mdp.edu.ar Sponsorships: This work was supported by Fundación Roemmers and Universidad Nacional de Mar del Plata (15/E353), Argentina. 74

2 CYSTIC ECHINOCOCCOSIS: EPIDEMIOLOGY AND TREATMENT Los objetivos de este estudio fueron investigar las tendencias en los casos confirmados de EC humanos registrados en el Hospital Privado de Comunidad (HPC) de la ciudad de Mar del Plata durante un período de 28 años ( ) y estudiar las características demográficas y clínicas de los casos, junto con los factores epidemiológicos asociados a la enfermedad. Se revisaron todas las historias clínicas de pacientes operados y/o diagnosticados. Ciento quince casos (57,4% mujeres, promedio de edad 61,3+17,1 años) fueron incluidos en este estudio retrospectivo, el 80% de los cuales vivía en zonas urbanas. En el 76,5% de los casos, se utilizó la ultrasonografía para diagnosticar la enfermedad. La localización hepática fue la más frecuente. Noventa punto cuatro por ciento del total de pacientes diagnosticados con EC recibió algún tratamiento debido a la enfermedad, el 47,1% recibió tratamiento quirúrgico y 19,2% tratamiento farmacológico. La media de días de internación fue de 15 días. La incidencia promedio para el período fue de 3.6 y 1.3 en HPC y según Notificación Oficial respectivamente. Nuestro estudio mostró que la permanencia de la EC en la región se debe principalmente a la transmisión natural del parásito en ausencia de medidas de control y prevención. Se recomienda que las autoridades de salud debieran implementar las estrategias necesarias en el área de estudio. Palabras clave: Echinococcosis quística, Echinococcus granulosus, Zoonosis, Epidemiología, Tratamiento. INTRODUCTION Cystic echinococcosis (CE) is an infection of humans and herbivorous animals caused by the larval stage of the parasite Echinococcus granulosus (Batsch 1786), which has worldwide importance and a broad distribution (Thompson, 2002; Xiao et al, 2005; FAO, 2007). This parasite requires two mammalian hosts to complete its life cycle. The hermaphroditic adult commonly develops in the dog s or fox s intestine, whereas the metacestode larva (hydatid cyst containing protoscoleces produced by asexual multiplication) develops in the viscera of many ungulates and man. The CE has spread to all continents and is an important public health and economic problem in many areas throughout the world, including the Pampas region. Three provinces of central Argentina are located in this region: Buenos Aires, the south of Santa Fe and Córdoba (MSAL-OPS, 2009). The southeast of the Buenos Aires province has important touristic centres which result attractive to elderly people. The economic and geographical structure contributes to the high immigration. The result is that people from 60 years-old represent the 60% of the population pyramid. This area also constitutes an excellent agricultural region with abundant extensive breeding of bovine cattle and ovine livestock. Close contact between man, dog and livestock, home slaughtering for human consumption and feeding dogs with offal are widespread habits that ensure the maintenance of the parasite s cycle in Buenos Aires rural areas. In urban areas the transmission is favored by poor sanitary conditions in some slaughter houses and illegal home slaughtering. Thus, climate and sociocultural factors contribute to the endemic status of CE in the southeast of Buenos Aires province. In endemic regions the major part of infections is acquired during childhood but can occur at any age. Human infection has socio-economic consequences related to costs of hospitalization and diagnosis, surgical fees, loss of working days, disability and mortality. Livestock infection reduces yield and quality of meat, milk and wool. The precise quantification of losses caused by CE depends on the knowledge about the rates of infection in human and animal populations (Batelli, 2001). The most commonly used index of human infection is the review of hospital records of CE cases. Although this method has limitations, data of annual rates have proved to be of great value for providing epidemiological information that can be useful to show the disease evolution (Pierangeli et al, 2007). Brunetti and co-workers (2010) proposed a new CE classification which summarizes the previously given by Gharbi et al, (1981) and WHO-IWGE (1996). The aim was to establish an expert consensus for diagnosis and treatment of CE in humans 75

3 M. C. DOPCHIZ et al. and facilitate the interpretation of epidemiological and clinical studies through the world. This classification divides the cyst type in 3 groups: undifferentiated: CL (cyst lesion), actives: CE1 and CE3 which ma y be differentiated into CE3a (with detached endocyst) and CE3b (predominantly solid with daughter vesicles) and inactive CE4 and CE5. CE1 and CE3a are early stages and CE4 and CE5 late stages (Brunetti et al, 2010). More than 2000 cases of human CE are reported in South America every year (Eckert and Deplazes, 2004). In Argentina, the CE is a notifiable disease and confirmed cases are reported weekly to the Ministry of Health of the Nation by completing the official form (C2 Form). The global annual incidence of surgical/treatment cases of human CE in Argentina in 2004 was one per inhabitants according to official reports (Echegoyen, 2004). However, national incidence rates of surgical cases do not show an accurate picture since the whole population is considered, including a large number of people with low risk of infection (FAO, 2007). In Argentina, CE is widespread and some areas are considered endemic. In 2001, 355 cases were notified using the C2 form, of which 46.5% came from Patagonian provinces, 38% from the central provinces (Buenos Aires, Córdoba, San Luis and Mendoza) and 15.5% from the northern provinces of Argentina (MSAL, 2001). In Buenos Aires, 294 new cases were reported between 1997 and 2001, with an annual incidence rate of 0.3/ in 2000 and 4/ in 2001 (MSAL, 2001). Epidemiological studies of CE were carried out in the south east region of Buenos Aires showing a serious situation in health centres in Mar del Plata city due to the number of diagnosed cases between (Elissondo et al, 2002; 2003). There are case studies on pediatric CE and CE in adult people in two state hospitals covering the period (Dopchiz et al, 2007; 2009). However, there have not been cases of CE reported in private hospitals of reference for over 10 years. The disease is also endemic in the region for cattle and pigs. Prevalence according to post-mortem inspection in abattoirs ranged between 12% to 16% for cattle and pig respectively. E. granulosus antigens were also detected in dog s feces, in fields and squares from General Pueyrredón district (Dopchiz, 2006; Dopchiz et al., 2002). Although there have been cases of CE, there are currently no provincial control programmes. In order to gain a better knowledge about the epidemiology of hydatidosis in the southeast of Buenos Aires province, the purposes of this study were to investigate the trends in confirmed cases of human CE recorded in Hospital Privado de Comunidad (HPC) in Mar del Plata city during a period of 28 years ( ) and to study demographic and clinical characteristics of cases together with epidemiological factors associated with the disease. MATERIAL AND METHODS Study area and population The study area was in Mar del Plata and its surrounding, a major tourist sea town located in General Pueyrredón, on the southeast coast of Buenos Aires province, Argentina (38 S; W) (Figure 1). The study was carried out in HPC, a 240-bed acute hospital which serves more than 20% of the population from the study area, 61% of whom are older than 60 years. The hospital currently offers services in the three levels of care that correspond to a general acute hospital, a service of preventive Figure 1. Geographic procedence of the examined cases. 76

4 CYSTIC ECHINOCOCCOSIS: EPIDEMIOLOGY AND TREATMENT medicine and a special program for the elderly. During summer, the hospital also serves retired people in transit and those affiliated to other medical institutions that have pre-paid contracts with the Hospital Foundation. HPC is also a reference centre for patients from several areas counties that compound the Sanitary Region VIII. The total population considered for this study consisted in 20% of the population of the region estimated in 2002 to be inhabitants, of which were males and females (INDEC, 2001). Study design and data collection: A retrospective, observational and analytical study of cases series was carried out in HPC. Data was obtained from secondary information source. The inclusion criterion was to consider all the medical records of patients of HPC with CE confirmed between 1974 and A data file was completed for each patient, containing personal information: age and occupation at hospitalary admission, sex, domicile, origin (rural/urban), diagnostic methods, number, characteristics and location of cysts as well as type of treatment received. When was possible the cysts type was classified according to proposed from Brunetti et al, (2010). All records were provided for the statistics service with permission of Teaching and Investigation Department. Data analysis: The mean annual incidence (MAI) of CE in HPC was calculated using data from the National Population and Household Census, 2001 (INDEC, 2001). Official notification (ON) records were used to compare the MAI of CE between 1998 and 2002 with the MAI of CE in HPC during the same period (INE, 2002). For analytical purposes, the population was divided by age groups of 10 years each and in some cases the study period was restricted to a span of five years: Epi Info 2000 (Centers for Disease Control, Atlanta, USA) was used for single variate analysis. Differences between groups were compared by the Chi-square (χ 2 ) test or the Kruskal Wallis test in case of non parametric distribution and it was considered statistically significant when p < Linear regression studies were undertaken using the R statistical software (R Development Core Team, 2007). Differences in cyst location frequencies and age media were analyzed by Student s t test. From analysis of media comparison between two groups the F statistic was obtained. RESULTS In this retrospective, observational and analytical study of cases series, a total of 115 patient records with confirmed CE in HPC were identified and examined over the 28 year period ( ). The average incidence for the period was 1,98 per inhabitants when the total population was considered. Distribution of cases by sex, occupation, age and place of residence: Women represented 57.4% of cases although did not show any statistically significant difference by sex ( 2 = 2.44; p = 0.12). According to reading of the records at time of the study, the most prevalent occupations were: retired (23.5%), homemaker (20.9%), rural worker (5.2%), student (3.5%), several occupations, like: truck driver, trader, employed, gastronomic worker, freelancer, metalworker, hairdresser, plumber (24.3%). Age and sex distribution and the male/female ratio by age groups are shown in Figure 2. The age of the cases ranged from 9 to 86 years, with a mean age of 61.3 ± 17.1 years and a median of 65 years. Age groups and were the most frequents and represented 28% and 29% respectively of the total number of cases. Age groups between 60 and 89 showed the highest MAI. The male/female ratio among total cases was 0.74, while the gender ratio in the population was 0.93 showing no gender significative differences (χ 2 = 1.39, p>0.05). Distribution of the cases by place of residence indicated that 80% of the patients lived in an urban Figure 2. Distribution of the 115 CE cases by human CE cases by age, sex and mean annual incidence (MAI). *was calculated considering 20% of Sanitary Region VIII population using data from the National Population and Household Census, 2001 (INDEC, 2001). 77

5 M. C. DOPCHIZ et al. Table 1. Distribution of the 115 cases of CE by cyst location diagnosed in HPC during Location Frequency % Liver Lung Liver - othera Bone Epigastric Gallbladder Hypochondric Lung - liver Liver - kidney Peritoneum Soft tisúes Total aothers: hypochondric, groin, pelvis, pleura, gallbladder. area, 18% in a rural area and 2% on the outskirts of urban areas. Cyst location, diagnostic techniques and treatment chose: To diagnose the disease, ultrasonography alone or combined with other diagnostic techniques was the chosen method in 76.5% of the patients. In 34.8% of the cases, a combination of axial computed tomography and ultrasonography was used. The use of X-ray alone or combined with other diagnostic techniques was the chosen method in 13.1% of the patients. The immunological techniques of Arco5 or latex were used with others imagenologic technics in 21.7% of the patients. Others diagnostic methods used in lower proportion were nuclear magnetic resonance, fluoroscopy and cholecystography. As regards cyst location, the average ratio liver-lung infection was 11:1. Eighty eight (76.5%) patients presented only 1 cyst, 16 (13.9%) patients 2 cysts, 8 (7%) patients 3 cysts and 3 (2.67%) patients multiple cysts (Table 1). Ninety point four per cent of the total diagnosed CE patients received any approach due to illness, 47.1% received surgical treatment and 19.2% pharmacological treatment. All patients who received drug therapy underwent surgery except one with CE4 type cyst who received albendazole for three cycles of thirty days. Table 2 summarizes the type of treatment received. In 77.4% of diagnosed patients, it was possible to obtain information about the cyst type. Within this group, 100% of the patients with cyst type CE1 and CE3b were operated and 33.4% and 52.6% received drug treatment respectively. To the type CE4 20% (2/10) of the cases received surgical and drug treatment. Interestingly 70% and 88.7% of the cases with cyst type CE4 and CE5 respectively received the watch and wait approach. In relation to patients with cysts type CE5, 11.3% were operated and none received drug treatment. Nine point six per cent of the total diagnosed CE patients not received treatment due to illness. The cysts of one of those patients were typified. The approach received for the CE patients treated was analyzed considering the most frequent localizations (liver and lung). Eighty seven point seven per cent (79/90) and 100% (8/8) patients with liver and lung localization respectively were treated for CE. For liver localization, in 86% of the cases was possible to obtain information about the cyst type. Within this group, 100% of the patients with Table 2. Distribution of the diagnosed and treated cases of CE according cysts type and the approach carried out in HPC during Approach Cyst type a Total CE1 CE3b CE4 CE5 N/C Surgical Treatment Watch and wait Nº Cases a patients with at least one cyst type based on Brunetti et al., N/C non classified 78

6 CYSTIC ECHINOCOCCOSIS: EPIDEMIOLOGY AND TREATMENT cyst type CE1 and CE3b were operated and 100% and 38.5% received drug treatment respectively. To the type CE4 20% (2/10) of the cases received surgical and drug treatment. Interestingly 62.5% and 86.9% of the cases with cyst type CE4 and CE5 received the watch and wait approach. In relation to patients with cysts type CE5 in liver localization, 13% were operated and none received drug treatment. In reference to eight patients with lung localization, in seven of them (87.5%) was possible to obtain information about the cyst type. Within this group, all of the patients with cyst type CE1 and CE3b were operated and one and two received drug treatment respectively. Analysis of age-group distribution of treated patients by cyst type classification showed statistically significative differences (X (3 ) Kruskal-Wallis =23.4, p < ). When the age-group were analyzed separately we found only statically significative differences between cyst type CE4 and CE5 (F = 4.37, p < 0,05) and also when we analyzed CE1 + CE3b and CE4 + CE5 differences (X (1 ) Kruskal- Wallis =17.5, p < ) (Figure 3). The mean number of operations per patient was 1.7, with a range from 1 to 8 making a total of 82 surgeries, and one non operated patient received pharmacological treatment with albendazole. Forty nine per cent of the treated patients were admitted into the hospital and stayed for differ ent periods, ranging from four to 50 days with a mean of 15 days (25th percentile = 8; 75th percentile = 20). From a total of 115 patients, 13.9% died of other diseases like cancer, general deterioration, cardio-respiratory arrest, acute bronchitis. In four cases, cause of death was not filed in the medical records. Figure 3. Boxsplot by age of CE treated cases according to the cyst type classification in HPC. The ends of the box represent the first and third quartile, : range, º :extreme value, :Age mean a patients with at least one cyst classified according to Brunetti et al, Figure 4. Annual incidence of human CE registered and annual incidence according to on in the study region. 79

7 M. C. DOPCHIZ et al. Temporal distribution of HPC and ON cases: MAI of CE in HPC and from the ON during the period covered by this study was shown in Figure 4. MAI in HPC ranged between zero to 5.3, when variations of MAI were analyzed within 5 years period, a significant increase was determined between 1974 and 2002 ( 2 = 4.3 p < 0.01). The analysis showed a positive correlation in the MAI through the time (Pearson* = , p < CI 95%). The average incidence for the period was 3.6 and 1.3 in HPC and ON respectively. HPC incidence was significantly different compared with the ON ( 2 = 6.86 p < 0.01). DISCUSSION The present study is a retrospective, observational and analytical study of cases series of human CE epidemiological data carried out in the HPC of Mar del Plata city and surrounding areas, in the Buenos Aires province. The HPC is an important hospital in this area which attends 20% of Mar del Plata s population and also is an important reference centre for patients from several surrounding areas. The average annual incidence of CE for the period was 1.98 per inhabitants in the HPC. This rate could be under-estimated and the number of cases could be higher as it only reflects symptomatic cases that reach medical attention or surgery and represents a small proportion of the actual number of cases. This situation could be due to CE is a chronic disease and frequently generates asymptomatic cases that can represent up to 60% of the total number of cases (Pawlowski et al, 2001; Frider and LarriAge-group distribution showed that the etiological agent was present in all age groups. The finding of a low frequency in children in HPC does not reflect the situation because for the period were reported 44 cases of pediatric CE (Dopchiz et al, 2009). The most diagnosticated age group was years-old since it evidenced the highest frequencies and MAI. This could be due to the slow course of development for the CE and also coincides with the age pyramid of the population in the studies area, which is constituted for a high percentage of adult people (INDEC, 2001). In the case of human CE, the high frequency of exposure at an early age could be explained by behavioral characteristics (close child-dog relationship). The potential of parasitism as a biological phenomenon is related primarily to ecological barriers and then to phylogenetic and/ or physiological constraints (Wisnivesky, 2003; Denegri, 2008). Although the distribution of cases by sex showed no statistically significant differences, women cases had more frequency. This agrees with Elissondo et al, (2002; 2003) and Dopchiz et al, (2007), who studied this illness in health centres in the same region. These results also are consistent with reports from Palestine, Iraq, Jordan, United Kingdom, China, Middle East and North Africa (Dowling and Torgerson, 2000; Saeed et al, 2000; Abu-Hasan et al, 2002; Al Qaoud et al, 2003; Yang et al, 2006). However, this finding contrasts with recent reports from pediatric study in the same region (Dopchiz et al, 2009) and in Kyrgystan where CE is an emerging disease and the number of surgical cases in adult men is higher than in women (Torgerson et al, 2003). In the present study, we observed that within the female group, most of the cases occurred in women who did household chores; while within the male group, retired workers presented most of the cases. More than a matter of gender, CE infection is closely related to people with high risk factors such as contaminated soil or contact with infected dogs with parasite eggs. Nonetheless, the transmission of this illness through water and inadequate washing of raw vegetables cannot be ruled out, since zoonotic parasites have been reported to be present in vegetables for human consumption (Slifko et al, 2000, Martínez Fernández, 2002). CE is generally considered a rural disease because of the characteristics of its transmission cycle, which involves dogs and domestic herbivorous animals (cattle, sheep, pigs and so on) (McManus et al, 2003). This study reported that the occupations of 21% of the study patients were unknown due to the fact that in many cases the anamnesis was incomplete. To find association between occupation and the adquisition time of the disease must be available the information of the occupation at the time of first diagnosis and in this study are not given in the records. With respect to the distribution of the patients according to their place of residence, it was ob- 80

8 CYSTIC ECHINOCOCCOSIS: EPIDEMIOLOGY AND TREATMENT served that the majority of them lived in urban areas. It is possible that urban residents may have been in contact with E. granulosus eggs in the city. Dopchiz (2006) and Dopchiz et al, (2002) reported the presence of antigens of E. granulosus in soil samples from squares and dogs feces in Mar del Plata city. We cannot rule d out the possibility that the disease was diagnosed in people wh o have acquired it previously while they lived in other regions, and later settled down in this city. Ultrasound alone or in combination with other techniques (such as axial computed tomography, immunological techniques etc.) is the method most frequently used to diagnose the disease. Ultrasound is widely known because of its low cost, speed in obtaining results and high sensitivity and specificity (Eckert and Deplazes, 2004; Frider and Larrieu, 2010). In this study, serological techniques have been little used. The cysts had more frequently a hepatic location followed by pulmonary and hepatic-other locations (Table 1), in agreement with other studies in Argentina (Elissondo et al, 2002; 2003; Pierangeli et al, 2007; Dopchiz et al, 2007; 2009) and other countries throughout the world as Palestine, Australia, Chile, Iraq, Jordan, China and Kyrgystan (Jenkins and Power, 1996; Aliaga and Oberg, 2000; Saeed et al, 2000; Abu-Hasan et al, 2002; Al-Qaoud et al, 2003; Torgerson et al, 2003; Yang et al, 2006). In reference to the liver/lung ratio found in this study, it is one of the highest values reported by Larrieu and Frider (2001) in a bibliographical review considering 9770 hydatidosis patients from Uruguay, Argentina, Tanzania, New Zealand, Israel, Jordan, Australia, Bulgaria, Turkey and Iran. They informed a general ratio of 2.5:1, which included values ranging from 0.89:1 to 12:1. In many cases, the resistance shown by the liver tissue surrounding the cyst determines a slow growth or even avoids the growth for many years. Therefore, this explains the high percentage of hepatic cysts that remain asymptomatic while supporting a balance parasite/host during the hosts life (Frider 2002; Frider and Larrieu, 2010). The lungs show lowresistance to the growth of the hydatid cyst due to their elasticity. This situation allows a proportional increase of the cyst size, and its consequence is the manifestation of clinical symptomatology in a great percentage of the total cases (Salviti et al, 2002). Studies of longitudinal follow up by ultrasonography in patients with asymptomatic hydatid cysts, have demonstrated that in a period of 14 years, 67% of the carriers persisted without developing symptoms (Frider et al, 1999). To date there is no better approach of treatment for CE. Treatment indications are complex and are based on cyst characteristics, available medical/ surgical expertise and equipment, and adherence of patients to long-term monitoring. In this study the CE diagnosed cases were divided in treated and untreated for the disease. Surgery was the chosen method in 47% of the treated patients while pre and post-surgical chemotherapy treatment was relatively limited in the health centre. It is important to note that in the years of this study drug use was relatively new and very limited. In addition, the availability of albendazole was very limited in Argentina. The application of disease approach was significant in relation to the cyst type and localization. In general most of the patients with cyst type CE1 and CE3b received any surgical or drug treatment and with cyst type CE4 and CE5 underwent the watch and wait approach. This situation coincides with the stage specific treatment suggested by Brunetti et al. (2010). As regards to the treatment strategy the worldwide experts propose that although surgery must be carefully evaluated in relation with other options, it is the first choice for complicated cyst. In the liver, it is indicated for: (1) removal of large CE2-CE3b cysts with multiple daughter vesicles; (2) single liver cysts situated superficially, that may be broken spontaneously or as a result of trauma when protoscolices are not available; (3) infected cysts, when protoscolices are not available; (4) cysts communicating with the biliary tree and (5) cysts exerting pressure on adjacent vital organs. With regard to the drug treatment benzimidazole (BMZ) are indicated for inoperable patients with liver or lung CE; patients with multiple cysts in two or more organs, or peritoneal cysts. Small (< 5 cm) CE1 and CE3a cysts in the liver and lung respond favorably to BMZ alone (Vutova et al, 1999; Dogru et al, 2005). However not all the cases need surgical or drug treatment. It has seen that when inactive cysts are not complicated, mostly CE4 and CE5 cyst type, the best option is a long-term follow-up of patients with US imaging (Frider and Larrieu, 2010). If we take into account the length of hospital stay, the total number of operations and the number 81

9 M. C. DOPCHIZ et al. of operations per patient, we can observe the high cost of this disease for the institution and the important social impact (Larrieu et al, 2004; FAO 2007). The annual incidence values for the entire region had a positive correlation through the study period. More over the incidence value was significantly higher in 2002 when it was compared with 1974 year. At a certain period of time, the incidence values can increase or decrease and they might be used as indicators of the efficiency of control programmes. This fact is shown by many authors in the worldwide literature. For the last decade variable annual incidences were described in the Patagonic provinces of Argentina like Tierra del Fuego, Chubut, Neuquen, and Rio Negro. All of them, are provinces under control programs and these incidence values are decreasing (Larrieu et al, 2000; Eckert et al, 2001; Pierangeli et al, 2007; Zanini et al, 2009). The above mentioned indicates th e progress achieved in control programs that were designed for and are being implemented in these regions. However, despite the existence of control programs, CE remains an important public health problem in several countries of South America. In Chile MAI is stable since 1992 (between 2 and 2.5/100000) although values up to 38.5/ were reported in the IX Region of Araucania, bounding with Neuquén, in the period (Aliaga and Oberg, 2000). In Uruguay annual incidence was 6.5/ in 1997; in Perú (1992) 1.1 and in Rio Grande do Sul, Brazil (1991) 0.54 (Eckert et al, 2001). It is important to note that although CE is a disease of obligatory notification in Argentina, not all cases are reported, as we showed in Figure 4 where the MAI was compare between the HPC and the ON. Whereas data from public hospitals are systematically recorded in Mar del Plata, private hospitals fail in notification to the sanitary authorities. Thus deficiencies in official records should also be taken into account. Despite the above mentioned limitations, data of annual incidence remain a useful tool to evaluate the regional epidemiological situation of the disease (Jenkins and Power, 1996). The fact that in this study incidence rates had an increased growth show that CE is transmitted naturally in the absence of control and prevention measures. This conclusion is supported by previously published results for the study area where were shown new pediatric cases, high prevalence rate in cattle and presence of eggs parasites (Dopchiz, 2006, Dopchiz et al, 2009). In order to have a real view of the situation of this zoonoses and if there is actual disease transmission, more epidemiological studies must be conducted to know the characteristics of the local transmission cycle in the bovine cattle, in other intermediate hosts as well as in the definitive host, and to know better the cultural behaviours of the communities. REFERENCES 1. ABU-HASAN N, DARAGMEH M, ADWAN K, AL- QOUAD K, ABDEL-HAFEZ SK Human cystic echinococcosis in the West Bank of Palestine: surgical incidence and seroepidemiological study. Parasitol Res 88: AL-QAOUD KM, CRAIG PS, ABDEL-HAFEZ SK Retrospective surgical incidence and case distribution of cystic echinococcosis in Jordan between 1994 and Acta Trop 87: ALIAGA F, OBERG C Epidemiología de la hidatidosis humana en la IX Región de la Araucanía, Chile Bol Chile Parasitol 55: BATTELLI G Socio-economic impact of the Echinococcus granulosus infection. In: WHO/OIE Manual on echinococcosis in humans and animals (Eckert, J.; Gemmell, M.A.; Meslin, F.X. and Pawlowski, Z., Eds). Geneva, Paris BRUNETTI E, KERN P, VUITTON DA Writing Panel for the WHO-IWGE. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Act Trop 114: DENEGRI G Fundamentación epistemológica de la parasitología. Epistemologic Foundation of Parasitology) (Bilingual Edition). Editorial de la Universidad Nacional de Mar del Plata (EUDEM)-Editorial Martin, Mar del Plata, Argentina, 208 pp. 7. DOGRU D, KIPER N, OZCELIK U, YALCIN E, GOC- MEN A Medical treatment of pulmonary hydatid disease: for which child? Parasitol Int 54: DOPCHIZ MC Aspectos epidemiológicos de la hidatidosis/echinococcosis en el sudeste de la provincia de Buenos Aires. Mar del Plata, Buenos Aires, Argentina, PhD Thesis, Universidad Nacional de Mar del Plata, Martín press, Mar del Plata, Argentina, 201 pp. 9. DOPCHIZ MC, ELISSONDO MC, ANDRESIUK MV, MAIORINI E, GUTIERREZ A, MUZULIN P, ROSENZVIT M, LAVALLÉN CM, DENEGRI G Study of hydatidosis pediatric cases in the Southeast region of the Buenos Aires province, Argentina. Rev Argent Microbiol 41: DOPCHIZ MC, ELISSONDO MC, DENEGRI G Consideraciones epidemiológicas de la hidatidosisechinococcosis en el sudeste de la provincia de Buenos Aires. In: Situación de la hidatidosis-echinococcosis en la República Argentina (Denegri, G.; Elissondo, M.C. and Dopchiz M.C., Eds). Martin, Mar del Plata

10 CYSTIC ECHINOCOCCOSIS: EPIDEMIOLOGY AND TREATMENT 11. DOPCHIZ MC, ELISSONDO MC, ROSSIN MA, DENEGRI G Hydatidosis cases in one of Mar del Plata City Hospitals, Buenos Aires, Argentina. Rev Soc Bras Med Trop 40(6): DOWLING PM, TORGERSON PR A cross sectional survey to determine the risk factors associated with human cystic echinococcosis in an endemic area of mid-wales. Ann Trop Med Parasitol 94: ECHEGOYEN MC Situación de los Países. Argentina. In: Informe del Proyecto Subregional Cono Sur de Control y Vigilancia de la hidatidosis. Argentina, Brasil, Chile y Uruguay (Pan American Health Organization, Eds), Montevideo, Uruguay, PHAO ECKERT J, DEPLAZES P Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev 17: ECKERT J, SCHANTZ PM, GASSER RB, TOR- GERSON PR, BESSONOV AS, MOVSESSIAN SO, THAKUR A, GRIMM F, NIKOGOSSIAN MA Geographic distribution and prevalence. 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Martin, Mar del Plata FRIDER B, LARRIEU E Treatment of liver hydatidosis: How to treat an asymptomatic carrier? World J Gastroenterol 16: FRIDER B, LARRIEU E, ODRIOZOLA M Long-term outcome of asymptomatic liver hydatidosis. J Hepatol 30: GHARBI HA, HASSINE W, BRAUNER MW, DU- PUCH K Ultrasound examination of the hydatic liver. Radiology 139: INDEC (Instituto Nacional de Estadísticas y Censos de la República Argentina) Censo Nacional de Población, Hogares y Viviendas. [Cited 2002 Sept 12] Available from: INE (Instituto Nacional de Epidemiología) Notificación Epidemiológica Región Sanitaria VIII INE Ministerio de Salud de la Nación, Argentina 43 pp. 25. JENKINS DJ, POWER K Human hydatidosis in New South Wales and the Australian Capital Territory, Med J Aust 164: LARRIEU E, BELLOTO A, ARÁMBULO III P, TAMAYO H Echinococcosis quística: Epidemiología y control en América del Sur. Parasitol Latinoam 59: LARRIEU EJ, COSTA MT, CANTONI G, LABANCHI JL, BIGATTI R, PÉREZ A, ARAYA D, MANCINI S, HERRERO E, TALMON G, ROMERO S, THACUR A Control program of hydatid disease in the province of Río Negro Argentina Bol Chil Parasitol 55: LARRIEU EJ, FRIDER B Human cystic echinococcosis: contributions to the natural history of the disease. Ann Trop Med Parasitol 95: MARTÍNEZ FERNÁNDEZ AR. Agua y transmisión alimentaria. In: Monografía XI: La Salud, prioridad en el VI Programa de Medio Ambiente de la Unión Europea (Villanua Fungairiño, L., Ed). Madrid, Real Academia Nacional de Farmacia press; 2002 [cited 2006 Jul 22]. Available from: publi/mono/011/011htm, 45 pp. 30. MCMANUS DP, ZHANG WLIJ, BARTLEY PB Echinococcosis. J Lancet 362: MSAL (Ministerio de Salud de la Nación) Boletín Epidemiológico Nacional [Cited 2002 May 5] Available from: htm/site/estadísticas.asp. 32. 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11 M. C. DOPCHIZ et al. 38. SLIFKO TR, SMITH HV, ROSE JB Emerging parasite zoonoses associated with water and food. Int J Parasitol 30: THOMPSON RCA Rediscovering parasites using molecular tools-towards revising de taxonomy of Echinococcus, Giardia and Criptosporidium. Int J Parasitol 32: TORGERSON PR, KARAEVA RR, CORKERI N, AB- DYJAPAROV TA, KUTTUBAEV OT, SHAIKENOV BS Human cystic echinococcosis in Kyrgystan: an epidemiological study. Acta Trop 85: VUTOVA K, MECHKOV G, VACHKOV P, PETKOV R, GEORGIEV P, HANDJIEV S, IVANOV A, TODO- ROV T Effect of mebendazole on human cystic echinococcosis: the role of dosage and treatment duration. Ann Trop Med Parasitol 93: WHO-Informal Working Group on Echinococcosis Guidelines for treatment of cystic and alveolar echinococcosis in humans. Bull. WHO 74, WISNIVESKY C Ecología y epidemiología de las infecciones parasitarias, Libro Universitario Regional, Cartago 398 pp. 44. XIAO N, QIU J, NAKAO M, LI T, YANG W, CHEN X, SCHANTZ PM, CRAIG PS, ITO A Echinococcus shiquicus n. sp., a taeniid cestode from Tibetan fox and plateau pika in China. Int J Parasitol 35: YANG YR, CHENG L, YANG SK, PAN X, SUN T, LI X, HU S, ZHAO R, CRAIG PS, VUITTON DA, MCMANUS DP A hospital-based retrospective survey of human cystic and alveolar echinococcosis in Ningxia Hui Autonomous Region, PR China. Acta Trop 97: ZANINI F, SUÁREZ C, PÉREZ H, ELISSONDO MC Epidemiological surveillance of cystic echinococcosis in rural population of Tierra del Fuego, Argentina, Parasitol Int 58: Acknowledgments: The authors express there gratitude to Dr. Maxit from the Hospital Privado de Comunidad. We also thank Lic. Natalia Fredes and Dr. Nahuel Farias for their contribution in statistics and Prof. Liliana Bordoni and Dr. Edmundo Larrieu for revising critical this manuscript. This study formed part of the doctoral thesis of Dr. Marcela Dopchiz. 84

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