Liver cysts caused by E. granulosus in Xinjiang, Peoples Republic of China Eleonor Sjöstrand and Monica Olsson Dept. of Infectious Diseases Sahlgrenska Academy University of Gothenburg Sweden Supervisors: Professor Rune Andersson, Research and Development Center, Skaraborg Hospital, Skövde Dept. of Infectious Diseases, Sahlgrenska Academy at University of Gothenburg, Sweden. Professor Wen Hao, Director of The First Affiliated Hospital of Xinjiang, Medical University, Urumqi, Peoples Republic of China.
1. Abstract Worldwide, E. granulosus is an important zoonotic pathogen causing serious disease to humans living in hyper endemic areas. It is found in all five continents and is frequent amongst herdsmen since the sheep is an important intermediate host to this parasite. The present study was done in Urumqi situated in Xinjiang, Peoples Republic of China. This is a high endemic area for E. granulosus where they have a great experience of diagnosing and treating this disease. The study was conducted between 8 th of November until 15 th of December 2004 at the First Affiliated Hospital of Xinjiang. During this time we visited the Hydatid Research Institute and observed experienced physicians in treatment of patients with Echinococcosis. 56 patient files from patients treated for Cystic Echinococcosis (CE) in the liver were examined with help from a Chinese translator. Data found in the patient files showed that people living in rural areas, especially the North of Xinjiang are more often infected with CE. This goes hand in hand with occupation since in North of Xinjiang people are mostly farmers and herdsmen. Surprisingly the official workers represented an equally large group. Gender and age didn t seem to play any significant role in catching the disease. However, since there normally is an incubation time of several years cysts are seldom found in children below ten years of age. Nowadays many children are diagnosed before occurrence of symptoms due to screening projects in schools. The most typical symptom was extension pain in the right upper abdomen, shown by 35 of the patients. Sometimes vomiting and jaundice occurred, caused by the pressure of large cysts on organs surrounding the liver. In two cases there was a rupture of a cyst, giving symptoms as unconsciousness, fever and shaking. Patients mostly tend to seek medical care within a year after onset of symptoms. The main diagnostic tool for CE is ultrasound that gives an image very typical for this kind of cyst, and it was used in 48 out of 56 cases. Looking closer on eosinophiles as a diagnostic tool we found that only 50 % of recorded values were elevated. If we looked upon the elevated values it was the percentage of total leukocyte count that were elevated, the absolute count was normal or only slightly elevated. This indicates that using eosinophiles as a diagnostic tool is very limited. Although cysts can be found in almost any site of the body, most often they will be found in liver (65%), lung, brain or abdomen. CE in the liver seems to prefer the right lobe. Cyst size varied from 40mm-228mm, and 19 patients had more than one cyst. Operation is the most important treatment method for CE, and endocystectomi, where the inner cyst layer is removed is the most common operation technique, combined with medication. The median number of hospitalisation time was 13 days. We found nearly 20% of recurrence. To prevent this disease, actions like screening project amongst schoolchildren and farmers, health education, research in finding a good screening test to identify infected dogs and taking care of viscera during slaughter are taken. 2
2. Table of Contents 1. Abstract 2 2. Table of Contents 3 3. Introduction 4 3.1 Xinjiang 4 3.2 Echinococcosis 4 Geographical Distribution 5 Life Cycle of Echinococcus 6 The Hydatid Cyst 8 Diagnosis 8 Symptoms 9 Treatment 9 4. Aims of the Study 11 5. Methods 11 6. Results and Discussion 12 6.1 Age 12 6.2 Gender 13 6.3 Occupation 13 6.4 Residence Area 14 6.5 Symptoms 14 6.6 Patients Delay 15 6.7 Diagnosis 17 Diagnotic Tools 18 Eosinophiles 19 6.8 Cyst Location and Cyst Size 20 6.9 Treatment Methods 21 6.10 Hospitalisation Time 22 6.11 Recurrence 22 6.12 Prevention 23 7. Acknowledgements 25 8. References 26 9. Appendix 27 3
3. Introduction 3.1 Xinjiang In Xinjiang vast desserts and arid plains stretch for thousands of kilometres before ending abruptly at the foot of towering mountain ranges 7. Xingiang is an autonomous region situated in the North Western corner of People Republic of China. It shares an international border with eight other nations and is the largest province in China. The province was made an autonomous region in 1955. Today its population is 19.1 million inhabitants. This is a multinational area as well as multi ethnic. There are over 40 different minority groups like Uygurs, Mongols, Kazaks, Khalkas Tajiks, Xibo, Tataer, Wuzibiekes and Russians living side by side in this region. The number of minorities in Xinjiang is above 62% of the total population. The Uygur are the major ethnic group in Xinjiang. From the history, influenced by the religion, culture, historical events, geographical elements, the habits, etiquettes and culture are different between the minorities. This is a region with a rich and long history, for instance the silk road passing through this region by the first century BC. Xinjiang in the Peoples Republic of China is one area with high prevalens for echinococcosis. Annual incidence rate for E. granulosus in parts of Xinjiang is 197 cases per 100,000 persons 11 especially in the Northern parts of Xinjiang where people mainly are herdsmen. The Capital of this province is Urumqi with 1 million inhabitants. Figure 1. Hyadatid endemic area in Cina ; 21 provinces and regions (87%) 3.2 Echinococcosis Echinococcosis or hydatidosis is a parasite infection caused by a cestode belonging to the genus Echinococcus. It is the smallest tapeworm in the Taeniidae family reaching only 3-6 mm in length as fully mature 8. 4
There are two major species of medical and public health importance; Echinococcus granulosus causing Cystic Echinococcosis (CE), and Echinococcus multilocularis causing Alveolar Echinococcosis (AE). There is also a third species, Echinococcus vogeli, but it is often considered as a subspecies to E. granulosus. In fact, there appear to be many subspecies (at least nine have been identified within E. granulosus) of both E. granulosus and E. multilocularis, with differences in host specificity 12. Echinococcosis is a zoonosis, i.e. it infects both humans and animals. Naturally it is transferred between herbivores and carnivores while humans are normally considered as a dead-end, infected as a mistake. Several animals act as possible targets for the parasite, e.g. sheep, goat, horse, cattle, swine, hare, rat and camel as intermediate hosts and dog, wolf, fox and cat as definite hosts. For E. granulosus the most common definitive host is the domestic dog, and sheep the normal intermediate host. Geographical Distribution Figure 2. Worldwide distribution of cystic echinococcosis Hyperendemic Endemic Low endemic Unknown E. granulosus practically has a worldwide geographical distribution, found in many areas of Africa, China, South America, Australia, New Zeeland, Mediterranean, Eastern Europe as 5
well as in parts of the western United States, more frequently in rural areas where dogs are used to herd sheep. Communities involved in sheep farming harbour the highest rate of infection. E. multilocularis having the fox as the main definitive host almost exclusively occurs in the northern hemisphere, including parts of central Europe and the northern parts of Europe, Asia, and North America. Life Cycle of Echinococcus The adult E. granulosus worm (fig.3) is very small, and consists of only three proglottids, an immature, a mature and a gravid proglottid, containing eggs 12. Gravid proglottids detach from the end of the worm and liberate eggs into the lumen of the intestine. The eggs are released in the faeces and ingested e.g. via contaminated grass by the intermediate host, or accidentally by a human being 9. Eggs are highly resistant to drought or freezing, being able to survive on the ground for up to a year 12. When reaching the small intestine they hatch and releases oncospheres that penetrates the mucosa. They migrate passively through blood or lymphatic system until reaching an organ suitable for settling (in about 65% this is the liver 12 ). The oncosphere develops into a hydatid (metacestode) cyst, gradually enlarging. As it matures it fills with fluid and infective protoscolices. Ingesting cyst-containing organs from dead herbivores infects carnivores as definite hosts. After ingestion the protoscolices evaginate and attach to the mucosa, develop into a sexually mature stage in 7 to 9 weeks 12. E. multilocularis has roughly the same life cycle, with the exception of cyst formation. Instead, it grows in an infiltratory manner much more aggressive than E. granulosus, resulting in tumour-like invasion of surrounding connective tissue. It consists of numerous cavities containing a gelatinous matrix within which brood capsules and protoscolices are developed 6. The growth is very rapid compared to that of E. granulosus. Figure 3. Adult worm 6
Figure 4. Life cycle of E. granulosus 7
The Hydatid Cyst The cyst develops into a unilocular fluid-filled bladder comprised of a three-layer capsule (Fig.5). The outer layer is fibrous and produced by the host itself, helping the parasite to evade the immune system. The two other layers are parasite-derived, one acellular laminated and one inner nucleated. From the nucleated germinal layer brood capsules containing protoscolices (hydatid sand) bud off and form daughter cysts that will eventually fill the interior 6. It takes approximately 1 to 2 years for the cyst to produce infective protoscolices 12. Each protoscolix has the ability to grow into an adult worm, and a cyst may contain thousands. The size of the cysts show a high variability, mostly depending on the organ infected. The largest found in liver may be approximately 20 cm in diameter whereas there has been a case report of a cyst as large as 50 cm in diameter growing in the peritoneal cavity, containing 16 litres of fluid 12. There are great fluctuations in growth rate as well. It is not uncommon that a cyst maintains the same size for years and all of a sudden it re-enters the enlargement process. Germinal layer Laminated layer Fibrous capsula Protoscolices Brood capsule, containing protoscolices Figure 5. The cyst consists of several layers Diagnosis The diagnosis is most easily set by ultrasound or other imaging techniques such as CT-scan or MRI, combined with case history. Serology tests such as ELISA or immunoblotting can be used in addition, being 80-100% sensitive for liver cysts but only 50-56% for lungs and other organs 5. False positive reactions may occur in persons with other tapeworm infections, cancer, or chronic immune disorders 2. Whether the patient has detectable antibodies depend on the physical location, integrity and viability of the cyst 2. Patients with senescent, calcified or dead cysts usually are sero-negative. Patients with alveolar echinococcosis have most of the time detectable antibodies. 8
Fine needle biopsy should be avoided if dealing with E. granulosus since there is a great danger of leakage with subsequent allergic reactions and secondary recurrence. Symptoms Following exposition to tapeworm eggs there usually is a long period of asymptomatic disease development. Cysts growing for several years without causing any discomfort to the affected person are not uncommon, and sometimes the cysts remain permanently silent. Up to 60% of all cystic echinococcosis cases may be asymptomatic, although several of them later enter a symptomatic stage 1. Cysts with a diameter below 5 cm normally tend to be asymptomatic, but hydatid cysts have the ability to grow quite large 8. A great part of the patients treated for hydatid disease get their diagnosis incidentally, seeking medical care for other reasons. The time at when a previously silent cyst gives rise to pathology depends both on the size of the cyst, but also on its location, making presenting symptoms of cystic echinococcosis highly variable 4. Most presenting features are caused by the pressure that the enlarged cyst expels on its surroundings, but may also appear if there is a rupture of a cyst. Since the liver is the most commonly involved organ (together with lung stands for more than 90 % of reported cases 1 ), symptoms leading to diagnosis mostly includes abdominal pain, jaundice (caused by biliary duct obstruction) or a palpable mass in the hepatic area 2. Cysts in the liver may also cause cirrhosis. Cysts located in the lungs may cause breathing problems, cough, chest pain and hemoptysis. When growing in the heart, cysts may give rise to earlier pathology than when in the liver or lungs, such as ischaemic syndromes with compression of the coronary artery, systemic or pulmonary embolism and inflammation of the pericardium. If bones are infected it may lead to a weakening or destruction of bone tissue, causing thin and fragile bones with spontaneous fractures as a result. Further frequent symptoms are loss of appetite, weight loss and weakening. If the cyst is damaged, there may be a leakage of fluid from inside. This fluid contains antigens that are highly toxic, causing allergic reactions like fever, asthma, urticaria, eosinophilia and in some cases anaphylactic shock 2. E. multilocularis also goes with abdominal pain, biliary obstruction and vomiting. Methastases in brain or lungs are even more severe, giving symptoms as cough, hemoptysis, paralysis or mental confusion 10. It is frequently mistaken as cancer. Treatment Surgery Surgical excision is the first choice of therapy, although removal of the cyst in not always 100 % curable. After surgery, medication is a good complement to prevent the cyst from recurring. 9
An alternative to surgery is the PAIR method 1, i.e. puncturing the cyst under ultrasound guidance, aspiration of fluid, injection of protoscolicide, and reaspiration of cyst contents. When treating E. multilocularis, medication together with radical surgery gives the best chance of cure even though it many times ends up being palliative. Early diagnosis is crucial. Figure 6. Dr Jingming Zhao performing a cyst operation Medication Most widely used are two benzimidazole compounds, Albendazole and Mebendazole. They both penetrate into the cysts, but the therapeutic doses are very high with side-effects such as leucopenia, hair loss and hepatotoxicity 4. They seem to be not truly parasiticidal but rather parasitistatic agents, working at their best in combination with surgery. All patients should have regular monitoring of leukocyte counts and liver function tests. Albendazole is the first drug of choice as it is best absorbed. Preferable it should be given up to six months after surgery. Mebendazole is more effective on all other kinds of worms but tapeworms. Still it can be used as a second choice using higher doses. Praziquantel has been used with albendazole for combined treatment of cystic echinococcosis and early trial in man shows improved efficiacy over albendazole alone 1. 10
4. Aims of the Study The aims of this study were to describe the following aspects of liver cysts due to E. granulosus in Xinjiang: The clinical spectra. The epidemiology. The treatment, and evaluate the results. Prevention strategies. 5. Methods By help of the computer system we identified the patients treated for liver cysts at the First Affiliated Hospital of Xinjiang due to echinococcosis, between January and July 2004. All together 74 patients were identified. The patient files on 56 out of these patients were translated to English, and examined for statistics regarding symptoms, treatment and disease characteristics (See appendix for more detailed information). The remaining 18 had to be excluded due to lack of translators. In addition, we participated in the daily activities at the hospital. Experienced physicians were observed during operations where cysts were removed. 11
6. Results and Discussion 6.1 Age The age distribution is shown in Fig 7, and could reflect the fact that younger people may stay asymptomatic for years and that older people have already been treated, or that there is an increased mortality connected to the disease. It could also be that people at higher age are less exposed to the parasites. The median age was 34.5 years. Age distribution Number of patients 14 12 10 Figure 7 8 6 4 2 0 10 to 15 16 to 20 21 to 25 26 to 30 31 to 35 36 to 40 41 to 45 46 to 50 51 to 55 56 to 60 61 to 65 66 to 70 71 to 75 Age(years) We conclude that small children (<10 years) don t get any symptoms until later on in life, even though they probably get the infection early in childhood and have several years of asymptomatic cyst development. They are therefore not visible in our material. More and more children are diagnosed before symptoms occur because of successful screening projects that are carried out in schools in high-risk areas. From the diagram it seems like there is a peak at the age of 31 to 35 and a dip at the age of 41 to 45. This is probably due to the low number of patients in our study group, and no significant conclusions can be drawn from this data. It seems like age doesn t play any significant role in catching the disease. It is evenly distributed from 10 years of age. 12
6.2 Gender Our patient data indicates that there is no clear predominance of any sex among infected people. In our material, there were 25 males and 31 females, illustrated in the figure below. Gender distribution F 55% M 45% Figure 8 6.3 Occupation Occupation police business factory worker Profession teacher retired something else student official worker farmer/cattle/fish 0 2 4 6 8 10 12 14 Patients Figure 9 It is obvious that the farmer/cattle/fishermen group is the most common amongst patients with echinococcosis (Fig.9). This is what one could expect since they live and work in the endemic areas for echinococcus. Surprisingly, official workers represent an equally large patient group as the farmers. Knowing that official workers have free medical care in China, this perhaps is not that striking at all. They will of course seek medical care without worrying about the economic side of it. Some of the official workers found their cysts by incidence during physical 13
examinations before even getting any symptoms. And some of the official workers have residual cysts from operations performed earlier. Farmers and other people in China have to pay their medical treatment by themselves, which of course mean that some people never or very seldom seek medical attention. One question is how the official workers get infected. The only thing we know about the official workers are that they are paid by the government and have a reasonable salary, free medical care and a good pension when retiring, we don t know anything about their lifestyle or family background that could help us finding out how they got this parasite. We could just assume that those who get this infection, in one or another way have been in contact with animals infected with echinococcus or contaminated food. The student group is the third largest group in our study group (8 persons). Four of these are children 10-13 years old, that were diagnosed during screening projects performed in schools situated in high-risk areas for echinococcosis. Usually cysts are not discovered until later, giving rise to symptoms. 6.4 Residence Area As expected, it was shown that a majority of patients treated for cystic disease (70 %) live apart from urban areas (Fig.10). Within the city, there is a low risk of catching the disease due to an absence of sheep and dogs. It isn t known whether the 25 % of the infected persons living in Urumqi have had any contact with the countryside, i. e. relatives living there or other reasons to visit high-risk areas, or if they have grown up in rural areas. Urumqi 25% South 21% Not known 5% North 49% Countryside 70% Figure 10 It may be assumed that people living inside the city more frequently seek medical care than people from remote areas. If so, there would be a greater number of undiagnosed cysts at the countryside, causing 25 % to be a falsely high rate of infected people living in urban areas. 6.5 Symptoms As seen below (Table1), there is a wide range of symptoms caused by hydatid cysts. Because a specific organ, in this study liver, had to be chosen before getting access to patient files, the symptoms described here almost exclusively arise from liver cysts. 14
The far most common symptom within our study group was extension pain in the right upper abdominal area. 35 of the patients had this sign of disease, several of them ignoring it for quite a long time, since this symptom is more uncomfortable than painful. Symptoms: No. of patients: extension pain right upper 35 abdomen Incidentally (physical 12 exam/screening) jaundice 4 vomiting 3 rupture (fever, shaking, 2 unconscious) weak 2 mass 2 itching 1 lost appetite 1 mass visible 1 fistula to skin 1 fever 1 dyspnea/chest squeezing 1 Two cases of cyst rupture were recorded, one spontaneous and one after a car accident, giving rise to symptoms such as fever, shaking and unconsciousness. Jaundice is caused if pressure from the cyst blocks gall secretion. It requires quite a large cyst, and is most of the time preceded by other symptoms such as abdominal pain. The rarest case found was a cyst making a fistula to the skin. This phenomenon is very uncommon. However, five years ago the same patient had another cyst operation and also this time the cyst was discovered as a skin fistula. Table 1. Clinical symptoms among 56 patients with livercysts caused by E. granulosus Several of the patients didn t have any symptoms, but were discovered as infected during physical examination. 6.6 Patients Delay One of the parameters that were examined was the length of the period from when the patients first got their cyst-derived symptoms until they sought medical care for it. From 10 of the patient files no information about this matter could be achieved. Out of the remaining 46, 20 persons went to the hospital within a month, 22 waited up to a year and four persons withstood their symptoms for a longer period (Fig.11). This could be considered as quite a long time with signs of disease without seeking care for it. The most obvious danger of not having cystic disease diagnosed is a possible rupture of a cyst that could lead to anaphylactic shock and death. Besides this, the condition is likely uncomfortable for the patient for a long period even before it stresses medical help. 15
Symptoms derived from cystic disease are caused by the growing hydatid mass. Since the vegetative process mostly proceeds very slowly, there isn t a big change in the patient s condition from one day to another. This may cause a delay in reaction to body signals. Another factor that may retard the decision to see a physician is the low gravity of symptoms. The patients often sense a diffuse extension pain in their right upper abdomen, which from the beginning isn t serious enough be a hindrance in daily life. Changed or intensified symptoms act as signals to seek medical care. These changes could for example be a sudden jaundice, vomiting or exceptional weakness. Time before seeking medical care: Number of persons Symptom time: 20 22 10 4 < 1 month < 1 year > 1 year not known Figur 11 As seen above (Fig.11) it is almost equally common to visit a hospital within a month after appearance of symptoms, as between a month and a year after. In spite of this, none of the 14 farmers included in this study went to a physician the first month. The professions of those who did were mainly students or official workers. This, however, could have a natural explanation. Students at school are subjected to free screening for echinococcosis, and official workers get annual complimentary physical examinations. Within these occasions it happens that cysts are discovered even before onset of symptoms, and they are quickly taken care of. People that don t get examinations for free probably endure their symptoms for a longer period, hoping for them to diminish over time. One could expect females to wait for a longer time than males, suspecting pregnancy since the symptoms of cysts could to some extent resemble this condition. This assumption wasn t reflected in our results. In fact, 54 percentages of the females went to the hospital within the first month. This compared to 30 percentages of the males. On the other hand all three patients that waited for two years were females. This however, shouldn t be due to pregnancy assumptions. 16
When age is taken into consideration, there is an interesting tendency of younger people seeking care quickest. The patients were divided into two groups (over and under median age) and compared in the figure below (Fig12). There was a hypothesis that screening projects at school would lower the age of the patients seeking care shortly after that a cyst has been revealed. That is, because cysts found during physical examination are often subjected to surgery within a few weeks. This showed not to be the case. 12 cases of echinococcosis were discovered incidentally. The patients were in four cases students; five official workers, one something else and the remaining two were a factory worker and a teacher. Half of the patients with incidentally found cysts were below median age, and the other half subsequently above. This means there is something else causing this age dependency. It could of course be a coincidence due to a small data material. Another theory is that people are more aware of signs of disease as younger, and that they are taken more serious at a low age. A factor that always has to be taken into consideration is the economy of the patient. Employees below 35 years are more likely to be disposed to a greater salary than older persons. Number of patients 16 14 12 10 8 6 4 2 0 < 1 month 1month -1year > 1 year < 1 month 1 year > 1 year Time before seeking care Patient age: Up to 34 years Over 35 years Figure 12 6.7 Diagnosis At the First Affiliated Hospital of Xinjiang they usually diagnosed Cystic Echinococcosis using ultrasound exclusively. More difficult to diagnose is the Alveolar Echinococcosis which can resemble malignant tumors. In our research we focus on Cystic Echinococcosis situated in the liver since this is the most common form of Hydatid disease in this region. 17
Diagostic tools used for diagnosing Echinococcosis. Symptoms Ultra sound CT MRI Blood samples 1. Liver tests 2. Electrolytes 3. Blood count 4. Coagulation tests 5. Serology DIGFA; Dot Immuno Gold Filtration Assay. This is a patented rapid diagnostic kit for echinococcosis developed at The Clinical Hydatid Research Institute of Xinjiang ELISA; Enzyme Linked Immuno Sorbent Assay Diagnostic Tools In our research we found that almost all the liver cysts were diagnosed by ultrasound. It was used in 48 out of the 56 cases. Cystic Echinococcosis is usually very easy to recognise and diagnose on the ultrasound image, having typical features such as a doubled layered fluid filled cyst. Only rarely it can be some difficulties to differentiate them from congenital cysts or malignant cysts. Therefore, if the ultrasound reveals a cyst difficult to differentiate it can be confirmed with serology. Serological tests that are used are the rapid kit DIGFA and ELISA tests. In some cases where the cyst was situated in a complicated place there was also a CT-scan or MRI examination. Since these are more expensive methods they are not performed routinely at the hospital. CT was used in 24 cases and MRI in 3. Blood samples that are taken are several. These tests are not diagnostic for echinococcois. They are taken to help the doctors in treating symptoms that the patient can suffer from as a consequence from the cyst and its location. Blood samples that usually are taken includes liver tests, (ASAT, ALAT, GGT, ALP, Bilirubin, Albumin and Hepatitis serology), electrolytes (Na, K, Ca, K, Creatinin), blood count (Hb, LPK, Diff, TPK) and coagulation tests(aptt, INR). The results from the different parameters vary depending on were the cyst are located. If the cyst is situated in the liver obstructing important vessels and ducts one could see a rise in the liver enzymes. Since eosinophiles are sensitive to parasites we decided to take a closer look at this parameter in the diagnosis of Echinococcosis. 18
Eosinophiles Eosinophile count is a diagnostic value that often is elevated when infected with parasites. When we looked at eosinophiles on patients that had been treated for cystic echinococcosis we found that out of 48 patients with eos-results recorded in their files 25 were within normal range. It shows that 50% could not have been diagnosed from an eos-count only. Looking only at the eos-counts that were elevated it showed that the percentage count is elevated while the absolute count is normal or only slightly elevated. So if one should draw any conclusions out of this data it would be that; as a diagnostic tool eosinofile count is of limited value and if it is used one should look at the percentage of the total leukocyte count. Elevated Percentage(>2.9%) & Normal absolute count (0.0-0.7) Elevated Percentage(>2.9%) & Elevated absolute count (>0.7) Normal Percentage (<2.9%) & Elevated absolute count (>0.7) 3,04% 3.30%, 0.81 1,23%, 1,08 3.18% 8.51%, 0.71 3.84% 9.41%, 0.85 3,97% 10.6%, 0.82 3.34% 12,06%, 0,85 4.43% 14,63%, 0,80 4,69% 15,48%, 1,34 5,16% 16,13%, 1,18 5,43% 17,18%, 1,44 7,50% 17.94%, 2.17 7,54% 37,41% Table 2. If eos count was elevated it could mostly be detected by the percentage of total leukocyte count. 19
6.8 Cyst Location and Cyst Size Our patient files covers patients (56) treated for liver cysts, the organ that is predominantly the site of this parasite. See table below for data collected in Xinjiang from 4827 patients during the time between 1957 and 2001. It shows that 63% of the Hydatid cysts are located in the liver (Table 3). Summary of 4827 Hydatid Patients in XMUH Between 1957-2001 57yr.- 60yr.- 65yr.-70yr.-75yr.-80yr.-85yr.-90yr.-95yr.-TotalComponent Location Ratio (%) Liver 20 86 220 373 382 444 452 570 607 3154 65.34 Lung 7 21 105 141 264 204 173 118 86 1119 23.18 Brain 0 3 8 10 10 19 21 13 16 100 2.07 Abdomen 3 7 20 12 19 13 19 12 9 114 2.36 Others 1 9 16 21 39 23 95 69 67 340 7.05 Total 31 126 369 557 714 703 760 782 785 4827 Component ratio 0.64 2.61 7.64 11.54 14.79 14.57 15.75 16.2 16.26 100 cases 700 600 500 400 300 200 100 0 57yr.- 60yr.- 65yr.- 70yr.- 75yr.- 80yr.- 85yr.- 90yr.- 95yr.- Liver Lung Brain Abdomen Others Table 3 We found that the parasite had a preference for the right lobe. Out of 56 cases there were 30 cysts situated in the right lobe, 12 in the left lobe and 14 unknown in the patient file (Fig.13). Cyst size varied from 40 mm to 228 mm in size showing that cysts that don t give rise to any symptoms can grow very large. Cyst location in liver left lobe right lobe Not know n Figure 13 20
Most commonly patients are treated for a single cyst in the liver though sometimes this cyst contains multiple cysts inside itself (13 out of 56). But occasionally the patients have several cysts not only in the liver. Other locations where cysts were found when the patient had multiple cysts were the abdominal cavity, spleen, lung, pelvis, kidney and the right mediastinum. 19 patients had more than one cyst. Looking closer at this we could see that 48% of the men had more than one cyst and 28% of the women had more than one cyst. 6.9 Treatment Methods As discussed before, surgery is the main method used for treatment, and the best way to accomplish a definite cure. Operations are performed when cysts give rise to symptoms or, if incidentally found, are roughly larger than five centimetres in diameter. Two techniques used at the First Aff. Hospital of Xinjiang: 1. Endocystectomi 2. Pericystectomi 1. The most common technique used today is endocystectomy where you remove only the inner cyst layer. After opening the cyst the liquid inside the cyst is removed with a suction pipe. The inner layer is then taken out. Remainder of the cyst is then carefully cleaned and dried with tissue pads sucked in 20 % saline. To kill rests of proteoscoleses, the cyst is then filled with 20% saline for 15 minutes. A drainage tube is then put into the cyst and placed throw the abdominal wall. Since the cystic fluid is highly toxic a spillage during operation may cause an anaphylactic shock and must for this reason be strictly avoided. 2. Pericystectomy where you remove the whole cyst, the outer layer as well as the inner one. First you do the procedure as described above, and thereafter you resect the fibrous cyst wall. Out of the two kinds of standard techniques, the far most commonly used was endocystectomy. 42 of the patients were subjected to this method. In 36 cases endocystectomy was the only method used removing one or several cysts, 9 patients got only pericystectomy, and during six operations with patients carrying multiple cysts, endocystectomy was used for some of them and pericystectomy for some. The choice of technique depends mostly on the location of the cyst but also on the skill of the surgeon. Pericystectomy is technically more complicated, but still is to prefer due to a lower rate of post operation complications. It lowers the relapse rate and infections due to fistula formation with the gallbladder. Despite the many advantages linked to pericystectomy, there is an emphasis on performing endocystectomy. The operation time for each cyst is far much longer with pericystectomy, which gives a reason to choose the other method, especially when dealing with patients carrying several cysts. As mentioned before, there is a safety reason not to do pericystectomy 21
when the cyst is not easily accessible. The procedure is associated with higher risks for complications such as severe bleeding. In one case right lobe hepatectomy was carried out. This procedure is mostly, combined with medication, an attempt to cure alveolar echinococcosis. In four cases there was no operation done. Three of these weren t infected with cystic echinococcosis, but alveolar. This form is most of the time not satisfactory cured by surgery. Instead it is treated by medication. One of these patients was urgently in need of a liver transplantation, but couldn t afford such an expensive intervention. The fourth patient not undergoing operation had a cyst that was already dead, i.e. had been calcified and was no longer being a threat. It was found by incidence and was completely asymptomatic. As calcified, cysts are only removed if causing any kind of discomfort. The standard procedure when leaving the hospital is an ultrasound check-up three months later, and another one after half a year. After the operation it is strongly recommended to medicate with albendazole for half a year to reduce the risk of recurrence. Whether this prescription is followed by the patient or not doesn t show in patient files. However, since it is a very expensive treatment one could speculate that it most of the time is ignored by the patient for economical reasons. 6.10 Hospitalisation Time After the cyst has been taken care of during operation the patients recover at the hospital, spending a median number of 13 days there. During surgery a drainage tube is inserted into the cavity remaining after endocystectomy. This to prevent gall salts from causing tissue inflammation if a fistula appears. The fluid from the drainage tube should be less than 50 ml per day before it is removed. It is just as important that the liquid arising from the cavity is without any signs of infection, or the patient should be treated with antibiotics. Biliary leakage and infection after surgery are two of the possible complications that will prolong the stay at the hospital. Whether or not a cholecystectomy is do not influence on the hospitalisation time. Economical aspects also showed to be of secondary importance. When looking at the time farmers, which should be the less wealthy among the patients, spent at in-department it is clear that just half of them stayed a shorter period than the median time. There was a tendency towards a longer hospital stay among the women. 40 percent of the males and 58 percent of the females stayed for a longer time than 13 days (n.s.) 22
6.11 Recurrence In our data, 45 patients had never been treated for cystic disease before. Nine patients had gone through an operation once before, usually some ten years ago, and two persons had been treated four previous times. This means that there is a near 20 percent of recurrence. There are several possible explanations for this. During operation there is always a risk of contamination. If there is a cyst rupture the contents will spread in the abdominal cavity, giving rise to several new cysts. Patients living in endemic areas getting their first cyst from the neighbourhood still after treatment are easily subjected to re-infection. 6.12 Prevention Prevention and control program supported by the government are important in the efforts to fight a worldwide health problem like the Hydatide disease. Worldwide there haven t been many but some successful projects in eradication or reducing the Echinococcosis, for example in Iceland (1950s) and New Zealand (control programme instigated 1959) 1. In the Northern part of Sweden occasionally there is found patients amongst people holding reindeers. It has successfully been eradicated destroying or burying offal during reindeer slaughter preventing dogs to ingest it 3. Health education amongst the population is important. Health education includes information about the importance in hand washing, washing food carefully and improved sanitation as well as screening of the population. Screening is done in the population amongst school children and herdsmen. Screening tools in the region of Xinjiang are ultrasound and the rapid kit DIGFA. The Clinical Hydatide Research Institute in Xinjiang has international collaborations with for example Chinese, British, and Japanese teams. Many patients are identified during these screening programs since one can have cysts for 10 to 20 years without symptoms. Identifying populations with a high prevalence for the parasite are helpful in the prevention work that is done including health education and isolating dogs that spread the disease to humans. Today the only way to identify infected dogs is to open up them surgically and analyse the mucosa of the intestines. This of course is a complicated procedure. Therefore research is done in finding a screening method using the dog faeces. Infected dogs and foxes are treated with arecoline hydrobromide or praziquantel or use of praziquantel-impregnated baits 1. There are also attempts to reduce the fox and dog populations. Taking care of viscera during slaughter is especially important since dogs get the parasite eating the infected intestines from sheep. Major efforts are done in finding vaccines to humans, dogs and sheep. There has been a successful development in the recombinant vaccin, designated EG95. This vaccin has been shown to confer a high degree of protection against different geographical isolates of E. granulosus 1. 23
Figure 14. View from Hongsan Park in Urumqi. 24
7. Acknowledgement We would like to thank our Swedish supervisor prof. Rune Andersson for sending us to China to do this research about Echinococcosis. Always helpful, encouraging and positive to our ideas. Prof. Wen Hao who helped us during our work at the First Affiliated Hospital has been very supportive and given us lots of information about the Hydatide disease. You also engaged the right staff to give us the assistance that we needed and invited us to social arrangements. Prof. Hong Zheng who showed us great enthusiasm in educating us in the principles of anestesiology and the basic surgical principles. We had the opportunity to attend during several operations especially removal of hydatid cysts together with Dr.Jingming Zhao who is an expert at the surgical Dept. of Hydatid Diseases. Despite some language problems we learned the procedure to remove cystic echinococcosis. Dr Mamatjan who was an invaluable help in translating the Chinese patient files to English. You also introduced us to the Uygur culture when inviting us to a traditional Uygur wedding. Zhang Yan you became our friend in all kinds of situations. Translating, showing us the Hydatid Dep.Research Laboratory, inviting us to your home, sightseeing to Turphan, shopping and so on. Vice Director Kaiser we will always remember you for you kindness and willingness to help us during our stay in Urumqi. There are so many persons that we had the opportunity to meet and helped us during our stay in China. We cannot mention all but Dr. Zuan Yan, Dr Cao Xing Hua, Dr Pezula, Dr Lin are some of the staff that we will send our thanks to. Mr. Ma Dong, we want to thank you for inviting us to the Chinese table, always smiling and generous. Last but not least thanks to our families and friends at home who supported us to go to China. 25
8. References 1 Donald P Mc Manus, Wenbao Zhang, Jun Li, Paul B Bartly. Seminar Echinococcosis. The Lancet 2003; 362:1295-1304 2 Parasites and Health; Echinococcosis. http://www.dpd.cdc.gov 3 Smittsskyddsinstitutet; Ekinokockinfektioner. http://www.smittsskyddsinstitutet.se 4 Bruno Gottstein, Jürg Reichenc, Mansons Tropical Diseases 20 th edtion 1996.WB Saunders Company Ltd.: Echinococcosis/Hydatidosis;1486-1501 5 Amy Roberts,FNP & Charles Kemp, FNP-Louise Herrington school of Nursing at Baylor, Echinococcosis (Hydatid disease). http://www3.baylor.edu 6 Wenbao Zhang, Jun Li, Donald P.Mc Manus. Concepts in Immunology and Diagnosis of Hydatid Disease. Clinical Microbiology Reviews, January 2003,p.18-36, Vol.16, No.1 7 Lonely Planet, China 8 th edition 2002: Xinjiang;839-874 8 Graphic Images of parasites, Echinococcus granulosus (hydatid disease or hydatidois). http://www.biosci.ohio-state.edu 9 M J Kumar, K Toe, R D Banjerjee. Case report. Hydatid cyst of liver. Postgraduate Medical Journal 2003;79:113-114 10 Jiang CP.Case reports. Two cases of liver alveolar echinococcosis associated with simultaneous lung and brain metastases. Chin Med J 2002;115(12):1898-1901 11 Enrico Brunetti et.al. Cystic Echinococcosis, http://www.emedicine.com 12 Cam.University Schistosome Research Group. Helminthology and General Parasitology Pages. The Cestodes (Tapeworms). Echinococcus sp.(hydatid disease) http://www.path.cam.ac.uk 26
Appendix Data collected from patient files: Personal information: Sex: Age: Profession: Living area: Medical information: Symptoms/reason for hospitalisation: Time with symptoms before seeking medical care: Diagnostic methods used: First time cystic disease/recurrence: Hospitalisation time: Cyst location: Cyst size: Treatment method: Eosinophiles (percentage and count): Supplementary information: 27