Abstract
Human echinococcosis is a zoonotic infection caused by larval forms (metacestodes) of tapeworms of the genus Echinococcus. Among the recognised species, Echinococcus granulosus and E. multilocularis are of considerable medical importance, causing cystic and alveolar echinococcosis (AE and CE), respectively. The factors of immunology, host-genetic inherits, and Echinococcus genetic-diversity and adaption clearly influence infectious establishment and disease progression. However, subtle mechanisms between host and parasite interactions/relationships are still open to study for answers. Despite the global burden, echinococcosis remains a neglected zoonosis. The importance of environmental factors influencing the transmission intensity and distribution of Echinococcus species is increasingly being recognised. The intervention strategies for this public health threat have integrated host immune-genetic research, parasite adaptation, and genetic diversity analysis, as well as the transmission dynamic investigations; the limitations of current control programmes are clearly presented in this study that hampers the elimination of Echinococcus species worldwide. Continuous efforts by multidiscipline researches are needed.
Keywords
- Echinococcus species
- host immunology and genetics
- Echinococcus genetic diversity and adaptation
- intervention strategies
1. Introduction
The zoonotic disease of echinococcosis (hydatidosis) is one of the most important parasitic helminth diseases, with over three million people infected worldwide. The two major species infecting man are
2. Transmission of Echinococcus species
All
For
Human echinococcosis occurs through the ingestion of
3. Epidemiology in Australia and China
Cosmopolite distribution of
3.1. In Australia
3.2. In China
There are approximately 1.3 million people with echinococcosis in China, where the disease burden is greater than that of any other country. Of the 33 provinces, autonomous regions, and municipalities in China, at least 20 are considered to be endemic for
4. Pathogenesis of human echinococcosis
The initial phase of a primary infection is always asymptomatic for both AE and CE in humans and may remain so for a matter of months up to many (typically more than 10) years.
The metacestodes of
In CE,
5. Disease diagnosis and severity
Patients with AE and CE are diagnosed based on clinical parameters including assessment of hepatomegaly, jaundice and upper abdominal complaints, as well as by imaging techniques such as ultrasound (US), computed tomography (CT) scans and magnetic resonance imaging (MR). ELISA-based detection of serum
To assess the degree of hepatic involvement of the parasite mass, AE patients are classified according to PNM (P: hepatic localization of parasite; N: extrahepatic involvement of neighbouring organs; M: absence or presence of distant metastases) and staged as P1, P2, P3, or P4 as recommended by WHO guidelines and the European Network for concerted surveillance of alveolar echinococcosis classification. For CE patients, classification of disease is based on liver lesion type (CE1, CE2, CE3, CE4 and CE5) at initial diagnosis, as proposed by the WHO Informal Group on Echinococcosis.
6. Susceptibility of human echinococcosis
Despite its public health significance, the susceptibility of human echinococcosis is poorly understood. The general factors that may render an individual more susceptible include malnutrition, co-infection, and immuno-suppression caused by other diseases or through the use of immuno-suppressive drugs. Several reports of children with cystic echinococcosis were predominantly located in the lungs. The reason for lung hydatidosis in children may be explained by either the weaker immune capability in their respiratory system or the faster cyst growth rate (or both) in young ages than that in adults. Pregnancy has also been thought to increase risk of infection or aggravate the disease due to the impaired cellular immunity frequently observed in pregnant women.
6.1. Host immunology
Immuno-suppression is frequently observed in patients with severe AE or CE. High levels of circulating
6.2. Host genetics
Despite the high morbidity and mortality associated with echinococcosis, relatively few studies to date have investigated the genetics underlying human susceptibility to the disease.
The case-control studies of candidate genes that have been previously undertaken have identified a number of associations with susceptibility to human echinococcosis in the HLA region for both AE and CE. Of these, however, many have not been replicated, likely reflecting the complexities and diversities of host susceptibility in different ethnic populations, different environmental conditions, and exposure to different
7. Echinococcus adaptation/genetics
The extensive genetic variation of
8. Public health threat
To date, over five species are recognized in the genus and four species are already revealed to be involved in human diseases. The most common forms are
However, human behavioural changes with economic, technological development, and the spatial expansion of agriculture promoted encroachment into wildlife habits, driven by increasing human population, leading to ecosystem changes and bringing human, domestic animals into closer proximity to wildlife. Many recently emerged zoonoses originated in wildlife have been reported.
9. Intervention strategies
9.1. Immunological/genetic research
Many studies of echinococcosis have provided significant information on risk factors of infection, as well as on socio-economic influences and ecological determinants of parasite transmission. The new immunological/genetic research components for new therapeutic targets, in combination with standard imaging techniques, will enable rapid and efficient evaluation of echinococcosis patients. This will not only greatly assist in monitoring disease progression and treatment efficacy, but also in the development and deployment of new control strategies and disease surveillance fundamental to reducing morbidity caused by long-term chronic infection and at a low cost to the health care systems of areas where echinococcosis is endemic. Further, the genetic study aims that identification of the genes involved in disease susceptibility can provide valuable insight into the protective and pathogenic mechanisms involved in the different clinical outcomes of echinococcosis. Understanding these processes can provide novel therapeutic targets that are essential for the long-term control of the disease worldwide. A significant, but essential challenge will be to develop strategies for translating knowledge of novel susceptibility genes into improved patient outcomes from both AE and CE. Given the considerable inter-individual variation observed in susceptibility to the different clinical phenotypes and their associated clinical outcomes, it is anticipated that subtle manipulation of the host immune response will translate into clinical benefits. Genomics offers a powerful approach to dissect the relevant pathways and may offer novel therapeutic targets for new drugs against both AE and CE, which are urgently needed as the current albendazole treatment is far from satisfactory. Definition of the molecules and pathways that are important in individual patients may eventually lead to a personalised approach to care, with therapy tailored on the basis of an individual’s genetic background.
9.2. Animal host intervention
Various methods for animal host interventions have been employed in echinococcosis endemic regions, for example, the culling of dogs/foxes for CE/AE, culling of rodents for AE, and the anthelminthic treatment (with praziquantel (PZQ)) of dog/foxes for CE/AE. Vaccine development has been ongoing and whilst a vaccine targeting the definitive dog/fox hosts could be a “magic bullet”, all current candidates have low efficacy. A highly efficacious sheep vaccine for
9.3. Comprehensive intervention and limitation
The use of geographic information system (GIS) have become more common as a tool for public health investigations due to the increase in number and quality of satellites used for terrestrial observation. These systems integrate the use of geographic positions sensors (GPS) tool for infectious disease studies, including
To date, only five islands (Iceland, New Zealand, Tasmania, Falkland Islands, and Cyprus) have been able to successfully control echinococcosis. Control programmes were predominantly based on health education and control or elimination of home slaughter of sheep, with behaviour change, is central to their success.
Despite the range of intervention strategies, control in endemic regions of the world (especially the poor rural areas) has proved difficult, as demonstrated by the increasing number of cases over the last decade. This failure to effectively control echinococcosis can be attributed to a number of causes: 1) culling of animals has ethical challenges (e.g., use of rodenticides in NHAR resulted in the poisoning of domestic dogs); 2) PZQ is effective in killing adult
10. Conclusion
Hydatid disease is a major cause of morbidity and mortality in many parts of the world. Although immunological research has provided important insight into the mechanisms of immunity in CE and AE, the genetic variants within the host-participating genes may be too subtle or too few to cause much effect on individual risk. The genotypic variation of
Acknowledgments
Fund support from the National Health Medical Research Councils (NHMRCs, APP1009539), Australia, and National Nature Science Foundation of China (NNSFC, 30960339).
References
- 1.
Zhang W, Ross AG, McManus DP: Mechanisms of immunity in hydatid disease: Implications for vaccine development. Journal of immunology 2008, 181(10):6679–6685. - 2.
McManus DP, Zhang W, Li J, Bartley PB: Echinococcosis. Lancet 2003, 362(9392):1295–1304. - 3.
Budke CM, Deplazes P, Torgerson PR: Global socioeconomic impact of cystic echinococcosis. Emerging infectious diseases 2006, 12(2):296–303. - 4.
Brunetti E, Kern P, Vuitton DA, Writing Panel for the W-I: Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta tropica 2010, 114(1):1–16. - 5.
Brunetti E, Junghanss T: Update on cystic hydatid disease. Current opinion in infectious diseases 2009, 22(5):497–502. - 6.
Torgerson PR, Schweiger A, Deplazes P, Pohar M, Reichen J, Ammann RW, Tarr PE, Halkik N, Mullhaupt B: Alveolar echinococcosis: From a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years. Journal of hepatology 2008, 49(1):72–77. - 7.
Torgerson PR, Keller K, Magnotta M, Ragland N: The global burden of alveolar echinococcosis. PLoS neglected tropical diseases 2010, 4(6):e722. - 8.
D'Alessandro A, Rausch RL: New aspects of neotropical polycystic ( Echinococcus vogeli ) and unicystic (Echinococcus oligarthrus ) echinococcosis.Clin Microbiol Rev 2008, 21(2):380–401. - 9.
Kern P: Clinical features and treatment of alveolar echinococcosis. Curr Opin Infect Dis 2010, 23(5):505–512. - 10.
Barnes TS, Hinds LA, Jenkins DJ, Coleman GT, Colebrook AL, Kyngdon CT, Gauci CG, Lightowlers MW: Efficacy of the EG95 hydatid vaccine in a macropodid host, the tammar wallaby. Parasitology 2009, 136(4):461–468. - 11.
Jenkins DJ, Allen L, Goullet M: Encroachment of Echinococcus granulosus into urban areas in eastern Queensland, Australia.Aust Vet J 2008, 86(8):294–300. - 12.
Jenkins DJ: Echinococcus granulosus in Australia, widespread and doing well!Parasitol Int 2006, 55 Suppl:S203–206. - 13.
Gottstein B: [Epidemiology and systematics of cystic and alveolar hydatid disease]. Chirurg 2000, 71(1):1–8. - 14.
Yang YR, McManus DP, Huang Y, Heath DD: Echinococcus granulosus infection and options for control of cystic echinococcosis in Tibetan communities of Western Sichuan Province, China.PLoS neglected tropical diseases 2009, 3(4):e426. - 15.
Vuitton DA, Zhou H, Bresson-Hadni S, Wang Q, Piarroux M, Raoul F, Giraudoux P: Epidemiology of alveolar echinococcosis with particular reference to China and Europe. Parasitology 2003, 127 Suppl:S87–107. - 16.
Jimenez S, Perez A, Gil H, Schantz P, Ramalle E, Juste R: Progress in control of cystic echinococcosis in La Rioja, Spain: Decline in infection prevalences in human and animal hosts and economic costs and benefits. Acta Trop 2002, 83(3):213–221. - 17.
Vuitton DA, Wang Q, Zhou HX, Raoul F, Knapp J, Bresson-Hadni S, Wen H, Giraudoux P: A historical view of alveolar echinococcosis, 160 years after the discovery of the first case in humans: Part 1. What have we learnt on the distribution of the disease and on its parasitic agent? Chin Med J (Engl) 2011, 124(18):2943–2953. - 18.
Wang YH, Rogan MT, Vuitton DA, Wen H, Bartholomot B, Macpherson CN, Zou PF, Ding ZX, Zhou HX, Zhang XF et al .: Cystic echinococcosis in semi-nomadic pastoral communities in north-west China.Trans R Soc Trop Med Hyg 2001, 95(2):153–158. - 19.
Barnes TS, Goldizen AW, Morton JM, Coleman GT: Cystic echinococcosis in a wild population of the brush-tailed rock-wallaby (Petrogale penicillata), a threatened macropodid. Parasitology 2008, 135(6):715–723. - 20.
Jenkins DJ, Romig T, Thompson RC: Emergence/re-emergence of Echinococcus spp.—A global update.Int J Parasitol 2005, 35(11-12):1205–1219. - 21.
Jenkins DJ: Cystic Echinococcosis in Australia: The current situation. Southeast Asian J Trop Med Public Health 2004, 35(1). - 22.
Budke CM, Jiamin Q, Qian W, Torgerson PR: Economic effects of echinococcosis in a disease-endemic region of the Tibetan Plateau. The American journal of tropical medicine and hygiene 2005, 73(1):2–10. - 23.
Yang YR, Craig PS, Sun T, Vuitton DA, Giraudoux P, Jones MK, Williams GM, McManus DP: Echinococcosis in Ningxia Hui Autonomous Region, northwest China. Transactions of the Royal Society of Tropical Medicine and Hygiene 2008, 102(4):319–328. - 24.
Li T, Chen X, Zhen R, Qiu J, Qiu D, Xiao N, Ito A, Wang H, Giraudoux P, Sako Y et al. : Widespread co-endemicity of human cystic and alveolar echinococcosis on the eastern Tibetan Plateau, northwest Sichuan/southeast Qinghai, China.Acta tropica 2010, 113(3):248–256. - 25.
Craig PS, Li T, Qiu J, Zhen R, Wang Q, Giraudoux P, Ito A, Heath D, Warnock B, Schantz P et al. : Echinococcosis and Tibetan communities.Emerging infectious diseases 2008, 14(10):1674–1675. - 26.
Yang YR, Liu XZ, Vuitton DA, Bartholomot B, Wang YH, Ito A, Craig PS, McManus DP: Simultaneous alveolar and cystic echinococcosis of the liver. Transactions of the Royal Society of Tropical Medicine and Hygiene 2006, 100(6):597–600. - 27.
Zhang T, Yang D, Zeng Z, Zhao W, Liu A, Piao D, Jiang T, Cao J, Shen Y, Liu H et al. : Genetic characterization of human-derived hydatid cysts ofEchinococcus granulosus sensu lato in Heilongjiang Province and the first report of G7 genotype ofE. canadensis in humans in China.PloS one 2014, 9(10):e109059. - 28.
Zheng Q, Vanderslott S, Jiang B, Xu LL, Liu CS, Huo LL, Duan LP, Wu NB, Li SZ, Xia ZG et al. : Research gaps for three main tropical diseases in the People's Republic of China.Infectious diseases of poverty 2013, 2(1):15. - 29.
Moro P, Schantz PM: Echinococcosis: A review. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2009, 13(2):125–133. - 30.
De U: Rare primary extrahepatic intra-abdominal hydatid cysts. Tropical doctor 2009, 39(3):172–175. - 31.
McManus DP, Li Z, Yang S, Gray DJ, Yang YR: Case studies emphasising the difficulties in the diagnosis and management of alveolar echinococcosis in rural China. Parasites & vectors 2011, 4:196. - 32.
Yang YR, Cheng L, Yang SK, Pan X, Sun T, Li X, Hu S, Zhao R, Craig PS, Vuitton DA et al. : A hospital-based retrospective survey of human cystic and alveolar echinococcosis in Ningxia Hui Autonomous Region, PR China.Acta tropica 2006, 97(3):284–291. - 33.
Macpherson CN, Bartholomot B, Frider B: Application of ultrasound in diagnosis, treatment, epidemiology, public health and control of Echinococcus granulosus andE. multilocularis. Parasitology 2003, 127 Suppl:S21–35. - 34.
Kern P, Wen H, Sato N, Vuitton DA, Gruener B, Shao Y, Delabrousse E, Kratzer W, Bresson-Hadni S: WHO classification of alveolar echinococcosis: principles and application. Parasitology international 2006, 55 Suppl:S283–287. - 35.
Powanda MC, Beisel WR: Hypothesis: leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor modulates the development of nonspecific and specific immunity and affects nutritional status. The American journal of clinical nutrition 1982, 35(4):762–768. - 36.
Sailer M, Soelder B, Allerberger F, Zaknun D, Feichtinger H, Gottstein B: Alveolar echinococcosis of the liver in a six-year-old girl with acquired immunodeficiency syndrome. The Journal of pediatrics 1997, 130(2):320–323. - 37.
Yang YR, Gray DJ, Ellis MK, Yang SK, Craig PS, McManus DP: Human cases of simultaneous echinococcosis and tuberculosis—Significance and extent in China. Parasites & vectors 2009, 2(1):53. - 38.
Kern P, Bardonnet K, Renner E, Auer H, Pawlowski Z, Ammann RW, Vuitton DA, Kern P, European Echinococcosis R: European echinococcosis registry: Human alveolar echinococcosis, Europe, 1982-2000. Emerging infectious diseases 2003, 9(3):343–349. - 39.
Matsaniotis N, Karpathios T, Koutoyzis J, Nicolaidou P, Fretzayas A, Papadellis F, Thomaidis T: Hydatid disease in Greek children. The American journal of tropical medicine and hygiene 1983, 32(5):1075–1078. - 40.
Romig T, Zeyhle E, Macpherson CN, Rees PH, Were JB: Cyst growth and spontaneous cure in hydatid disease. Lancet 1986, 1(8485):861. - 41.
Srour SF, Sayfan J: Echinococcosis of the spleen during pregnancy. The Israel Medical Association journal : IMAJ 2001, 3(4):290–291. - 42.
Vuitton DA, Zhang SL, Yang Y, Godot V, Beurton I, Mantion G, Bresson-Hadni S: Survival strategy of Echinococcus multilocularis in the human host.Parasitology international 2006, 55 Suppl:S51–55. - 43.
Kacprzak E, Stefaniak J: Evaluating the activity of liver cystic echinococcosis using the delayed-hypersensitivity skin reaction to common antigens. Annals of tropical medicine and parasitology 1995, 89(1):25–29. - 44.
Kolligs FT, Gerbes AL, Durr EM, Schauer R, Kessler M, Jelinek T, Loscher T, Bilzer M: [52-year-old patient with subcutaneous space-occupying lesion in immunosuppression]. Der Internist 2003, 44(6):740–745. - 45.
Bonifacino R, Carter SD, Craig PS, Almeida I, Da Rosa D: Assessment of the immunological surveillance value of humoral and lymphocyte assays in severe human cystic echinococcosis. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000, 94(1):97–102. - 46.
Rigano R, Profumo E, Ioppolo S, Notargiacomo S, Teggi A, Siracusano A: Cytokine patterns in seropositive and seronegative patients with Echinococcus granulosus infection.Immunology letters 1998, 64(1):5–8. - 47.
Ortona E, Margutti P, Delunardo F, Nobili V, Profumo E, Rigano R, Buttari B, Carulli G, Azzara A, Teggi A et al. : Screening of anEchinococcus granulosus cDNA library with IgG4 from patients with cystic echinococcosis identifies a new tegumental protein involved in the immune escape.Clinical and experimental immunology 2005, 142(3):528–538. - 48.
Rigano R, Buttari B, De Falco E, Profumo E, Ortona E, Margutti P, Scotta C, Teggi A, Siracusano A: Echinococcus granulosus -specific T-cell lines derived from patients at various clinical stages of cystic echinococcosis.Parasite immunology 2004, 26(1):45–52. - 49.
Rigano R, Ioppolo S, Ortona E, Margutti P, Profumo E, Ali MD, Di Vico B, Teggi A, Siracusano A: Long-term serological evaluation of patients with cystic echinococcosis treated with benzimidazole carbamates. Clinical and experimental immunology 2002, 129(3):485–492. - 50.
Bresson-Hadni S, Vuitton DA, Bartholomot B, Heyd B, Godart D, Meyer JP, Hrusovsky S, Becker MC, Mantion G, Lenys D et al. : A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.European journal of gastroenterology & hepatology 2000, 12(3):327–336. - 51.
Mondragon-de-la-Pena C, Ramos-Solis S, Barbosa-Cisneros O, Rodriguez-Padilla C, Tavizon-Garcia P, Herrera-Esparza R: Echinococcus granulosus down regulates the hepatic expression of inflammatory cytokines IL-6 and TNF alpha in BALB/c mice.Parasite 2002, 9(4):351–356. - 52.
Harraga S, Godot V, Bresson-Hadni S, Mantion G, Vuitton DA: Profile of cytokine production within the periparasitic granuloma in human alveolar echinococcosis. Acta tropica 2003, 85(2):231–236. - 53.
Rigano R, Profumo E, Bruschi F, Carulli G, Azzara A, Ioppolo S, Buttari B, Ortona E, Margutti P, Teggi A et al. : Modulation of human immune response byEchinococcus granulosus antigen B and its possible role in evading host defenses.Infection and immunity 2001, 69(1):288–296. - 54.
Godot V, Harraga S, Beurton I, Deschaseaux M, Sarciron E, Gottstein B, Vuitton DA: Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. I. Comparison of patients with progressive and abortive lesions.Clinical and experimental immunology 2000, 121(3):484–490. - 55.
Rigano R, Profumo E, Ioppolo S, Notargiacomo S, Ortona E, Teggi A, Siracusano A: Immunological markers indicating the effectiveness of pharmacological treatment in human hydatid disease. Clinical and experimental immunology 1995, 102(2):281–285. - 56.
Daeki AO, Craig PS, Shambesh MK: IgG-subclass antibody responses and the natural history of hepatic cystic echinococcosis in asymptomatic patients. Annals of tropical medicine and parasitology 2000, 94(4):319–328. - 57.
Dreweck CM, Luder CG, Soboslay PT, Kern P: Subclass-specific serological reactivity and IgG4-specific antigen recognition in human echinococcosis. Tropical medicine & international health: TM & IH 1997, 2(8):779–787. - 58.
Dixon JB: Echinococcosis. Comparative immunology, microbiology and infectious diseases 1997, 20(1):87–94. - 59.
Al-Ghoury AB, El-Hamshary EM, Azazy AA, Hussein EM, Rayan HZ: HLA class II alleles: susceptibility or resistance to cystic echinococcosis in Yemeni patients. Parasitol Res 2010, 107(2):355–361. - 60.
Aydinli B, Pirim I, Polat KY, Gursan N, Atamanalp SS, Ezer M, Donmez R: Association between hepatic alveolar echinococcosis and frequency of human leukocyte antigen class I and II alleles in Turkish patients. Hepatol Res 2007, 37(10):806–810. - 61.
Eiermann TH, Bettens F, Tiberghien P, Schmitz K, Beurton I, Bresson-Hadni S, Ammann RW, Goldmann SF, Vuitton DA, Gottstein B et al. : HLA and alveolar echinococcosis.Tissue Antigens 1998, 52(2):124–129. - 62.
Li F, Shi Y, Shi D, Vuitton DA, Craig PS: HLA-DRB1 allele in 35 patients with alveolar echinococcosis in Gansu Province of China. Chin Med J (Engl) 2003, 116(10):1557-1560. - 63.
Li F, Shi Y, Shi D: [Association of HLA-DRB1 allele and the susceptibility to alveolar echinococcosis in the west of China]. Zhonghua Yi Xue Za Zhi 2000, 80(6):414–416. - 64.
Kiper N, Gerceker F, Utine E, Yalcin E, Pekcan S, Cobanoglu N, Aslan A, Kose M, Dogru D, Ozcelik U et al. : TAP1 and TAP2 gene polymorphisms in childhood cystic echinococcosis.Parasitol Int 2010, 59(2):283–285. - 65.
Zhang S, Penfornis A, Harraga S, Chabod J, Beurton I, Bresson-Hadni S, Tiberghien P, Kern P, Vuitton DA: Polymorphisms of the TAP1 and TAP2 genes in human alveolar echinococcosis. Eur J Immunogenet 2003, 30(2):133–139. - 66.
Emery I, Leclerc C, Houin R, Vuitton DA, Liance M: Lack of H-2 gene influence on mouse susceptibility to secondary alveolar echinococcosis. Int J Parasitol 1997, 27(11):1433–1436. - 67.
Nakao R, Kameda Y, Kouguchi H, Matsumoto J, Dang Z, Simon AY, Torigoe D, Sasaki N, Oku Y, Sugimoto C et al. : Identification of genetic loci affecting the establishment and development ofEchinococcus multilocularis larvae in mice.Int J Parasitol 2011, 41(11):1121–1128. - 68.
Hemer S, Konrad C, Spiliotis M, Koziol U, Schaack D, Forster S, Gelmedin V, Stadelmann B, Dandekar T, Hemphill A et al. : Host insulin stimulatesEchinococcus multilocularis insulin signalling pathways and larval development.BMC biology 2014, 12:5. - 69.
McManus DP, Thompson RC: Molecular epidemiology of cystic echinococcosis. Parasitology 2003, 127 Suppl:S37-51. - 70.
Parkinson J, Wasmuth JD, Salinas G, Bizarro CV, Sanford C, Berriman M, Ferreira HB, Zaha A, Blaxter ML, Maizels RM et al. : A transcriptomic analysis ofEchinococcus granulosus larval stages: implications for parasite biology and host adaptation.PLoS neglected tropical diseases 2012, 6(11):e1897. - 71.
Siles-Lucas M, Nunes CP, Zaha A: Comparative analysis of the 14-3-3 gene and its expression in Echinococcus granulosus andEchinococcus multilocularis metacestodes.Parasitology 2001, 122(Pt 3):281–287. - 72.
Huttner M, Nakao M, Wassermann T, Siefert L, Boomker JD, Dinkel A, Sako Y, Mackenstedt U, Romig T, Ito A: Genetic characterization and phylogenetic position of Echinococcus felidis (Cestoda: Taeniidae) from the African lion.International journal for parasitology 2008, 38(7):861–868. - 73.
Xiao N, Qiu J, Nakao M, Li T, Yang W, Chen X, Schantz PM, Craig PS, Ito A: Echinococcus shiquicus , a new species from the Qinghai-Tibet plateau region of China: discovery and epidemiological implications.Parasitology international 2006, 55 Suppl:S233–236. - 74.
Jones BA, Grace D, Kock R, Alonso S, Rushton J, Said MY, McKeever D, Mutua F, Young J, McDermott J et al. : Zoonosis emergence linked to agricultural intensification and environmental change.Proceedings of the National Academy of Sciences of the United States of America 2013, 110(21):8399–8404. - 75.
McManus DP, Gray DJ, Zhang W, Yang Y: Diagnosis, treatment, and management of echinococcosis. Bmj 2012, 344:e3866. - 76.
Yang YR, Clements AC, Gray DJ, Atkinson JA, Williams GM, Barnes TS, McManus DP: Impact of anthropogenic and natural environmental changes on Echinococcus transmission in Ningxia Hui Autonomous Region, the People's Republic of China.Parasites & vectors 2012, 5:146. - 77.
Yang Y, Ellis MK, McManus DP: Immunogenetics of human echinococcosis. Trends in parasitology 2012, 28(10):447–454. - 78.
Zhang W, Zhang Z, Shi B, Li J, You H, Tulson G, Dang X, Song Y, Yimiti T, Wang J et al. : Vaccination of dogs againstEchinococcus granulosus , the cause of cystic hydatid disease in humans.The Journal of infectious diseases 2006, 194(7):966–974. - 79.
Lightowlers MW: Vaccination against hydatid disease. Developments in biologicals 2002, 110:81–87. - 80.
Larrieu E, Herrero E, Mujica G, Labanchi JL, Araya D, Grizmado C, Calabro A, Talmon G, Ruesta G, Perez A et al. : Pilot field trial of the EG95 vaccine against ovine cystic echinococcosis in Rio Negro, Argentina: early impact and preliminary data.Acta tropica 2013, 127(2):143–151. - 81.
Heath DD, Robinson C, Lightowlers MW: Maternal antibody parameters of cattle and calves receiving EG95 vaccine to protect against Echinococcus granulosus .Vaccine 2012, 30(50):7321–7326. - 82.
Pleydell DR, Yang YR, Danson FM, Raoul F, Craig PS, McManus DP, Vuitton DA, Wang Q, Giraudoux P: Landscape composition and spatial prediction of alveolar echinococcosis in southern Ningxia, China. PLoS neglected tropical diseases 2008, 2(9):e287. - 83.
Graham AJ, Danson FM, Giraudoux P, Craig PS: Ecological epidemiology: landscape metrics and human alveolar echinococossis. Acta tropica 2004, 91(3):267–278. - 84.
Giraudoux P, Raoul F, Afonso E, Ziadinov I, Yang Y, Li L, Li T, Quere JP, Feng X, Wang Q et al : Transmission ecosystems ofEchinococcus multilocularis in China and Central Asia.Parasitology 2013, 140(13):1655–1666. - 85.
Atkinson JA, Williams GM, Yakob L, Clements AC, Barnes TS, McManus DP, Yang YR, Gray DJ: Synthesising 30 years of mathematical modelling of Echinococcus transmission. PLoS neglected tropical diseases 2013, 7(8):e2386. - 86.
Atkinson JA, Gray DJ, Clements AC, Barnes TS, McManus DP, Yang YR: Environmental changes impacting Echinococcus transmission: research to support predictive surveillance and control.Global change biology 2013, 19(3):677–688. - 87.
Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA, Garcia HH, Gavidia CM, Gilman RH, Gonzalez AE, Lorca M, Naquira C et a l.: Prevention and control of cystic echinococcosis. The Lancet Infectious diseases 2007, 7(6):385–394. - 88.
Heath D, Yang W, Li T, Xiao Y, Chen X, Huang Y, Yang Y, Wang Q, Qiu J: Control of hydatidosis. Parasitology international 2006, 55 Suppl:S247–252.