CO-OPERATIVE STUDIES
A number of teams, involved in the WHO-IWGE, have initiated co-operative studies, especially in the field of epidemiology. Some examples or given in the following sections, with summary of the work (or PhD Master degree/MD or other report summary when available).
Co-operative study on genetic analysis of E. granulosus isolates from animals and human hydatid fluid in Nepal
Co-operative study on prevalence and strain differentiation of E. granulosus in Ethiopia.
Abstract (M Sc Thesis of PK Kostei)
The current prevalence status of hydatid disease in cattle and sheep and echinococcosis in dogs in Assela, Makale and Debre Zeit areas of Ethiopia was assessed in this study. These areas represent three different agro-ecological zones in Ethiopia. In addition, larval isolates of E. granulosus from these areas were collected and subjected to RAPD-PCR assay in an attempt to determine their genetic diversity.
A total of 749 cattle, 429 sheep and 51 goats were examined for hydatidosis. Of the total cattle, 209 were from Assela, 433 from Makale and 197 from Debre Zeit. All the sheep and goats were from Addis Ababa abattoir although they were brought from different parts of the country. Prevalences of bovine hydatidosis of 60.8% (127) in Assela, 19.9% (86) in Makale and 28% (30) in Debre Zeit were found in this study. Sheep and goats had prevalences of 9.1% (39) and 5.9% (3), respectively. There was a significant difference between the prevalence of bovine hydatidosis in Assela from those of Makale and Debre Zeit (P< 0.05).
Of the infected cattle, 13.4% (17) in Assela, 23.3% (20) in Makale, and 10% (3) in Debre Zeit harboured at least one fertile hydatid cyst. 59% (23) sheep harboured fertile cysts and no goat was found to have fertile cysts. There was a significant difference in the percentage of infected sheep with fertile cysts from the same group of cattle originating from the three study areas (P< 0.05). The percentage fertility of the total cysts examined were 4.2%, 6.8% and 5.5% in Assela, Makale and Debre Zeit, respectively. Out of this 56.5% in Assela, 65.4% in Makale and 66.7% in Debre Zeit were viable. From the sheep examined, 43.6% had fertile cysts with viability of 90.7%. The lung was the most affected organ in both species.
A total of 44 dogs, 14 from Assela, 15 from Makale, and 15 from Debre Zeit were examined for canine echinococcosis. The prevalence of the infection was 50% (7) in Assela, 20% (3) in Makale and 33.3% (5) in Debre Zeit. There was no significant difference between these prevalence rates although noticeable differences in the worm burdens among the three areas were observed.
The results of the questionnaire survey indicated a considerable human – dog – livestock interaction. The public health importance of the disease is almost completely unknown by the peasants. Stray or straying dogs is a common problem and dogs have free access to infected organs. Besides, hospital records and interviews with physicians indicate that hydatidosis is of considerable importance especially in Assela.
Results of the morphological study on the adult parasites are comparable to those that have been described by several authors for E. granulosus. RAPD-PCR assay with the isolates showed at least three characteristic banding patterns with four different randomly chosen oligonucleotide primers. This suggests the existence of at least three strains namely the sheep, the cattle and, with reservations, the camel strains. The sheep and cattle strains are infective to humans. These results, however, need to be complemented by other DNA studies to elucidate these strain differences. In addition, the role of other intermediate and definitive hosts both domestic and wild require assessment in order to gain a better understanding on the transmission dynamics of echinococcosis.
However, this study has shown that E. granulosus is of veterinary and public health importance. Control measures are therefore recommended which includes public awareness education programme, revision of meat inspection legislation and a more aggressive dog control effort that includes a reduction of stray or straying dog population.
Co-operative study on epidemiology of alveolar echinococcosis in Gansu, PR China
PS Craig and M. Rogan, Salford University, UK
P. Giraudoux, B. Bartholomot, DA Vuitton, Université de Franche-Comté, France
C. MacPherson, Winward Research Center, Grenada, Carribbean’s
Shi Da Zhong, Li Fu Rong, Lanzhou Medical College
A preliminary evaluation of the study (1994-1998) was given at the " National and International Meeting on transmission, diagnosis and treatment for Echinococcus infections and echinococcosis", Urumqi, PR China, 1998
The abstract of a submitted paper on the results of the screening program is given below :
Combined ultrasonographic and serological screening of hepatic alveolar echinococcosis in central China
Bartholomot Brigitte, 1 MD, Vuitton Dominique A,1 MD PhD, Harraga Said, 1PhD, Da Zhong Shi,2 MD, Giraudoux Patrick, 1 PhD, Barnish Guy, 3 PhD, Yun Hai Wang, 4 MD, Macpherson Calum NL, 5 PhD, and Craig Philip S, 6 PhD.
Alveolar echinococcosis (AE) is a relatively rare zoonotic helminthic disease which mimics a cancer. A focus of high prevalence of the disease was suggested at the beginning of the seventies in a number of provinces in central China. A systematic screening program was undertaken from 1994 to 1997 in two districts of south Gansu Province. The aim of the present study was to estimate the prevalence of E. multilocularis infection in this area, and to evaluate the feasibility and diagnostic value of the association of ultrasonography with serology for the screening of AE in rural communities distant from any medical center or hospital. After answering an epidemiological questionnaire, 2,482 volunteers from 28 villages were given a liver scan by ultrasonography (US) using a portable scanner. ELISA serology for antibody activity was performed on whole blood collected on filter paper in all subjects, and on serum from the subjects with an abnormal US image and from randomised subjects without typical lesions. At least one abnormal US image was observed in every 630 subjects screened. A typical lesion of progressive AE was disclosed in 84 subjects (3.4%): 52 women and 32 men, mean age 38.7 years (range 12-70 years). In addition to calcifications associated with typical aspects of AE lesions, different types of calcifications were observed in 451 examined subjects. Nodular hyperechoic well limited angioma-like lesions, under 2cm diameter, were disclosed in 40 subjects. Serology was negative in 3 patients with typical and large size lesions characteristic of AE who would, therefore, have been missed at a serological screening.
The results of this study on a large population of an endemic area confirms that US is feasible and efficient in AE mass screening and may bring instant diagnosis of the disease at low cost and more accurately than serology which has been widely used in AE screenings for the past 20 years. Interpretation of isolated calcifications (abortive forms?) and of hyperechoic nodules (early cases?), both of them frequently associated with a positive serology, needs a prolonged follow-up of the screened subjects, to assess the actual prevalence of AE in this Chinese community which currently appears to have the highest E. multilocularis human infection rate in the world.
Co-operative study on epidemiology of alveolar and cystic echinococcosis in Xinjiang, PR China
PS Craig and M. Rogan, Salford University, UK
P. Giraudoux, B. Bartholomot, DA Vuitton, Université de Franche-Comté, France
Wen Hao, Wang Ynn Hai, Shou Hong Xia, Yang Weng Guang, Xinjiang Medical University
A preliminary evaluation of the study (1994-1998) was given at the " National and International Meeting on transmission, diagnosis and treatment for Echinococcus infections and echinococcosis", Urumqi, PR China, 1998
Epidemiology of AE in Xinjiang is the subject of a PH D Thesis by Zhou Hong Xia (Xinjiang Medical University/Université de Franche-Comté) to be presented in 2000.
Co-operative study on epidemiology of alveolar and cystic echinococcosis in Sichuan and Qinghai, PR China
PMS Schantz, NCID, CDC, Atlanta, USA
Qiu Jiamin, Sichuan Institute of Parasitic diseases, Chengdu, PR China
Liu Fengjie, National Hydatid Disease Center,Urumqi, PR China
Wan Hu, Qinghai medical College, Xining, PR China
A Ito, Asahikawa Medical College, Gifu Japan
Preliminary results of a combined ultrasonoraphic, radiographic and serologic epidemiological survey in Tibetan populations of Sichuan and Qinghai were given at the National Symposium on Strategy of Hydatid Disease Control, Urumqi, PR China, 1999 and at the International Congress of Hydatidology, Bariloche, 1999. They indicate a high prevalence of both CE and AE in some districts of Sichuan and Qinghai, and confirm that echinococcosis is a significant problem for Public Health in these areas.
A more detailed and coordinated ecological and socio-economic research on CE and AE in Western China is currently planned which would take benefit of the experience gained by all Chinese, UK, French, American and Japanese teams involved in field work in this part of the world.
A joint study has also been carried out on the efficacy of oxfendazole on experimental alveolar echinococcosis in mice. This bendizimidazole compound, that was proved to be very efficient on cystic echinococcosis in sheep using a once-weekly dosage, seems also promising for the treatment of alveolar echinococcosis, as shown in this abstract:
Oxfendazole Studies in China (Qiu J, Schantz P, Wang Q, He J, Chen X, Liu
F. Oxfendazole treatment for experimental alveolar echinococcosis in mice.
J Pract Parasit Dis 1999;7:116-9.):
Comparative anthelmintic activity of albendazole and oxfendazole against E
multilocularis in rodent model. The first experiment was designed to
evaluate the effect of albendazole for prophylaxis, i.e., to protect field
workers in contaminated areas. Two groups of rodents were started on daily
oral doses of albendazole prior to infection with eggs of E. multilocularis.
Group A received the drug starting 12 hours before infection and Group B
received it starting 20 hours prior to infection; the drug was given daily
for 7 days. Group C (controls) received no drug. The animals were killed
45 days after the beginning of the experiment and the mass of parasitic
lesions were markedly decreased in the treated animals in comparison to the
control group. This experiment showed that albendazole was only partially
effective for preventing establishment of infection and inhibiting growth in
those that became infected. The experiment will be repeated with some
variation to further define the potential prophylactic potential of
albendazole. In another experiment we looked at the comparative
echinococcicidal efficacy of albendazole and oxfendazole for E.
multilocularis. Four groups of 10 mice were infected by intraperitoneal
inoculation of larval tissue. Beginning 5 days after larval implantation,
oxfendazole was administered to two groups at a daily dose of 75 or 150
mg/kg/body weight by subcutaneous injection of oxfendazole suspension. A
third group received albendazole at a dose of 150 mg per kg bodyweight. All
treated animals received drug for 28 days. The fourth group served as
controls. The animals were killed at 45 days post infection. All animals
receiving oxfendazole survived the experiment and the larval mass found at
the end of the experiment appeared dead and markedly reduced in volume in
comparison with those in non-treated control mice. 50% of the mice receiving
no drug (controls) and 20% of those receiving albendazole died during the
course of the experiment. Larval tissue in surviving mice receiving
albendazole was reduced in size in comparison to that in the control mice,
however, some tissue appeared viable. This preliminary finding is very
encouraging and suggests that oxfendazole may be a more effective
benzimidazole compound than others (albendazole and mebendazole) currently
used for chemotherapy of echinococcossis. Further experiments are planned.
Towards a Network of teams involved in research, surveillance, prevention and control of echinococcosis in PR China?
Public health importance of echinococcosis in PR China has raised the attention of Health and Agriculture authorities at the Government level and WHO has been asked to send an expert to a common meeting of Health bureaus representatives from endemic Provinces of China, organised Health Bureau of Xinjiang Uygur Autonomous Region, on May 14-17 .Minutes of the Meeting are given below. A detailed report was sent by DA Vuitton who attended the Meeting to the WHO bureau for the Western Pacific Region, Manila, The Philippines.
Minute of the National Symposium on Strategy of Hydatid Disease Control
(May14-17, 1999, Urumchi China P. R.)
Sponsored by Ministry of Health, the People's Republic of China and WHO, a "National Symposium on Strategy of Hydatid Disease Control", hosted by Health Bureau of Xinjiang Uygur Autonomous Region, was held during May14 to 17, 1999 in Urumchi, the People's Republic of China. The symposium was held in accordance with the cooperation agreement of the Chinese Government and WHO. Total 59 representatives and experts from 13 provinces and autonomous regions, including Tibet, Gansu, Qinghai, Ningxia, Sichuan, Hebei, Shandong, Heilongjiang, Jilin, Yunnan,,Beijing, Shanghai and Xinjiang, participated the Symposium. Dr.D.A.Vuitton, coordinator of WHO informal working group on echinococcosis had also taken part in the Symposium. Main topics of the Symposium were concentrated on: (a) to study and analyze the current situation of echinococcosis prevalence and control in China; (b) considering with the current situation of the reform and development of the health services in China, to find out relevant measures and strategies for better implementing of "the ninth five-year hydatid disease control plan"; (c) to discuss measures of reinforcing cooperation and experience exchanging amongst the epidemic areas; (d) to exchange experiences and progresses on hydatid disease control and research, and to study current situation of the ongoing control and scientific research programs in China.
At the opening session of the Symposium, on behalf of the autonomous regional government, Mr. Ma Qing, deputy chief of the administrative office, the people's government of Xinjiang Uygur Autonomous Region, made a welcome remark to the Symposium. Dr. Fen Zhen, director of the Institute of Parasitic Diseases Research, Chinese Academy of Preventive Medical Science, had also addressed to the Symposium. He conveyed regards from the Ministry of Health, to all the experts and health workers who are working at different levels of the country for their hard working and devotion to the hydatid disease control and research. He also expressed gratitude to the Health Bureau of Xinjiang and the National Hydatid Disease Center for their supports made for the successful opening of the symposium. Dr. Fen Zhen believed that the symposium would play an important role in the control and research of echinococcosis in China.
Representatives from Xinjiang, Tibet, Gansu, Qinghai, Ningxia and Sichuan reported the progresses of their hydatid disease control programs to the meeting respectively. Experts from universities, hydatid disease control and research institutes, agriculture and veterinary institutes were also invited to give lectures and reports on special topics to the symposium, concerned with epidemiological reports, progresses in immunological diagnosis, chemotherapy research, PAIR treatment, and strategy for hydatid disease control etc. On May 16, all the representatives were invited to Hutubi County, (70km west of Urumchi) and visited the prototype field working sites on chemotherapy research, and observed the implanting operation of an experimental research on effectiveness of taeniafuge by implanting "long term Praziquantel dispensers" for dogs.
In afternoons of May15 and 16, discussions on strategy of hydatid disease control had been held respectively. Participants expressed opinions and suggestions on control strategies, based on the characteristics and prevalence situation of the disease, experiences gained from control activities, problems and difficulties remained in each provinces and autonomous regions. According to the estimations made by the participants, there are about 50million people inhibited in the epidemic areas in China, who are in the risk of hydatid disease, and the number of patients in the country is estimated about 500,000 to 600,000. The participants had greatly concerned the current epidemic situation of hydatid disease in our country. Since most of the high prevalence areas of the disease in the country are minority people inhabited areas, though not densely populated, but the widely spreading of the disease, is one of the most serious animal-born parasitic disease, and is harmful for the people’s health and local agriculture and animal husbandry production. Great attention should be paid by governments at different levels.
The participants considered that problems remained in hydatid disease control in China mainly are: (a) Governments of different levels have not paid enough attention on hydatid disease control. Well-planned control work has not actually been carried out. (b) lack of funding is one of the most important obstacles for the smooth implementation of hydatid disease control. (c) The two big systems of health and agriculture have not well cooperated for hydatid disease control, which cost problems for effective implementation and sustainability of the disease control program. (d) The disease control and scientific research team is not stable enough.
In conclusion, the symposium considered, control strategies oriented by dog control measures including providing taeniacide and strengthening dog registration and administration, improving animal slaughtering, supported with health education, patient screen and treatment, and disease surveillance, had been proved as successful control measures. Those measures should be continuously carried out in accordance with various local situations in different areas.
The symposium suggested that following measures should be taken:
1) It is necessary to establish close cooperative mechanism and networks on hydatid disease control, surveillance and scientific research, and enabled the regular information and experiences exchanging on progress of control and research program.
2) The Health Ministry should organize relevant experts to carry out a research work on the current situation and prevalence trend of the disease, the social and economic losses caused by the epidemic, and the cost-economic benefits from the control program. Based on the research, control strategies and measures should be worked out for our country.
3) The collaboration between health and agriculture departments should be tightened in order to reduce infectious rate, to protect health of human being and domestic animal.
4) A working group should be organized for working out the tenth five years control plan of echinococcosis.
5) To organize scientific researches on key issues and obstacles concerned with the disease control, take measures to accelerate the practical application of scientific achievements.
6) To reinforce polices of governments at different levels, for better finical support to the disease control activities, meanwhile, to take measures of encourage local health setups to raise funds by carrying out services and widen the source of funding.
7) To take measures for improving staff training, control team building, and stabilizing the disease control and research work forces.
8) The international cooperation is a very important way to improve current situation of short of funding and to try to carry out some urgent work at present.
9) The symposium suggests, the Health Ministry should work on further cooperating with WHO on staff training and lab research for hydatid disease control.
All the participants considered the symposium was successful and necessary with its earnest, solemn and compact style.
With efforts made by all the participants, hosted by the Health Bureau of Xinjiang Uygur Autonomous Region and Xinjiang Endemic Disease Institute, the symposium has achieved its goal.
Prepared by: Participants of "National Symposium on Strategy of Hydatid Disease Control"
Other co-operative studies are being done in Northern Africa, Middle-East countries, Western Africa, Northern/East Africa (Morocco, Mauritania) …with local teams and UK, Italian, French teams…and certainly others!
If you want these studies be mentioned in EchinoNews, or to give preliminary results, to ask for complementary expertise, or for any help…this section is open to you! EurEchinoReg: pilot programme for the epidemio-surveillance of alveolar echinococosis in Europe.This group has originally been set up to develop the goals of the WHO-IWGE, as far as the problem of alveolar echinococcosis in Europe is concerned. The first step consisted of a "pilot study" of epidemio-surveillance of AE in Europe, supported by the European Commission DG V (co-ordination: DA Vuitton). The second step is a coordinated research program submitted to the EC DG XII (Vth Framework Program "Quality of life and management of living resources) (co-ordination: P Kern).
List of the sub-registries participating in the project "EurEchinoReg" The complete list of all national centres (in Vienna, Brussels and Liège, Rome, Salford and Bern) and sentinel centres (in Warsaw, Poznan, Prague, Kosice, Thessaloniki, Izmir) is available by contacting the sub-registers, or on the website: www.eurechinoreg.org. These centres may serve as "resource centres" for all colleagues who would need help on particular aspects of AE diagnosis, treatment or epidemiology.
Sub-registries for human cases
Prof. Peter Kern: coordinator
Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.( PEG ),
Sektion Antiparasitäre Chemotherapie, Arbeitsgemeinschaft Echinokokkose and
Sektion Infektiologie und Klin. Immunologie, Medizinische Universitätsklinik und Poliklinik, Robert-Koch-Str 8, D - 89081 Ulm Tel : 49.731.50.24420 Fax : 49.731.50.24422
e-mail : peter.kern@medizin.uni-ulm.de
Dr. Petra Kern
: collection of dataEuropäisches Echinokokkose Register
Abteilung Biometrie und Medizinische Dokumentation,
Universität Ulm, Schwabstr. 13, D - 89075 Ulm Tel : 49.731.50.26897 Fax : 49.731.50.26902
e-mail : echinoreg@medizin.uni-ulm.de
Prof. Dominique A. Vuitton : coordinator
WHO Collaborating Centre for Prevention and Treatment of Human Echinococcosis.
and"Health and Rural Environment – University of Franche-Comté" research Unit;
Faculté de Médecine et de Pharmacie, Université de Franche-Comté, Place St Jacques,
F - 25030 Besançon, France Tel : 33.3.81.66.55.72 Fax : 33.3.81.66.55.70
e-mail : dominique.vuitton@univ-fcomte.fr
Dr. Karine Bardonnet
: collection of dataLaboratoire de Parasitologie, CHU Jean Minjoz, Bd Fleming, F - 25000 Besançon
Tel : 33.381.66.82.86 Fax : 33.381.66.89.14e-mail : karine.bardonnet@ufc-chu.univ-fcomte.fr
Dr. Oleg Blagosklonov
: webmasterWHO collaborating centre, Faculté de Médecine et de Pharmacie, Place St Jacques,
F - 25030 Besançon Tel : 33 3 81 66 56 97 Fax : 33 3 81 66 55 70
e-mail : Oleg.Blagosklonov@univ-fcomte.fr
Sub-registries for animal epidemiology
Prof. Patrick Giraudoux
: coordinatorWHO collaborating centre, Laboratory of Biology and Ecology, Faculté des Sciences,
Université de Franche-Comté, Place Leclerc, F - 25030 Besançon Cedex
Tel : 33.3.81.66.57.45 Fax : 33.3.81.66.56.98
e-mail : Patrick.Giraudoux@univ-fcomte.fr
Dr. Thomas Romig : coordinator
Institut für Zoologie ( Parasitologie ),
Universität Hohenheim, Emil Wolff Str 34, D - 70599 Stuttgart
Tel : 49.711.459.3076 Fax : 49.711.459.2276
e-mail : romig@uni-hohenheim.de
Preliminary report
(June 1999)The European collaboration in EurEchinoReg made available the information on 579 patients
with alveolar echinococcosis ( AE ) throughout Europe including Turkey. This is the far largest number of cases ever assembled in the endemic foci of the European Union and border countries. The conditions leading to diagnosis of AE are available for 378 patients in the European countries. Most patients were diagnosed with AE in the age range from 50 to 70. However, the recruitment in Germany indicates a shift towards younger age groups ( < 40 ). In parallel, the prevalence for the fox-tapeworm has steadily been increasing during the last 10 –15 years indicating probably the recent increased risk to the public. The circumstances of AE diagnosis was evaluated. In contrast to the published literature, 70 % of the patients were referred to health centres because they had symptoms, 25% without. In nearly all cases the primary infected organ was the liver, primary extrahepatic manifestation of disease occurred in 2,6 %. This figure is higher than previously anticipated. Most impressively, at the time of diagnosis 12,4 % of patients had already metastatic spread of the disease. According to the data set 9% did not receive specific treatment for AE. This first glance on the data readily indicates the necessity of a centralised European institution such as the EurEchinoReg Registry. The implementation of the infrastructure was therefore the action which is now the platform of communication between different EU countries. Based upon the experience of the pilot project, new questionnaires adapted to case reporting by family physicians and/or by the patients themselves were developed. The detailed questionnaires will be used in the future for the study of a cohort of patients in order to better study and evaluate the treatment strategies. A regular follow-up of all registered patients will be undertaken every two years by sending a specific questionnaire to the patients family physician or Reference Centre physician, upon agreement by the patient. Because of the short time-period available for the collection of cases, not all complete files of AE patients have been entered in the register ; especially, epidemiological data are still missing for many cases, and correctness of the diagnosis of AE for some cases reported from non-endemic areas has to be checked. The definitive evaluation will only be achieved in 2000 but the data collected so far point out to the occurrence of AE in a EU country which was not previously known as endemic, Belgium, and of infected foxes in a country where they were not infected in the past, the Netherlands. Human cases and fox infection also exist now in the border countries of central Europe. Fox infection in EU and Swiss cities (Stuttgart and Zurich) was demonstrated.
During its first year, the pilot programme has achieved a series of goals: (1) the infrastructure of a network has been established, (2) actions have been taken to set up national reference centres, (3) a common definition of AE cases and a common staging system (PNM) have been elaborated and evaluated, (4) updated maps of endemic areas have been drawn, (5) new trends in the incidence of human cases and animal infection have been clearly disclosed.
Surveillance of emerging AE cases in non-endemic areas or in "low-risk" populations appears necessary from both the observation of isolated AE cases in these settings during the past few years and the trends in the infection of foxes in endemic and non-endemic areas. The Web Site www.eurechinoreg.org should facilitate the information on the disease in these areas so that both populations and physicians can be aware of it and refer new cases to the Register. For this purpose, the Web Site will be linked to other medical Web Sites, and especially to the "Orphanet" Web Site on rare and orphan diseases, set up by the French Inserm (http://orphanet.infobiogen.fr), and as soon as it is developed, to the European rare diseases database (program of Community action 1999-2003 on Rare Diseases in the context of the framework for action in the field of public health). The network would take benefit of its inclusion in a wider system for epidemiological surveillance and control of communicable diseases at the EU level.