Hydatid disease - still a global problem

Along with rabbits, foxes and numerous noxious weeds, one of the unintended gifts that Europeans gave to Australia in the early days of the nascent nation was Echinococcus granulosus, contained within the organs of imported sheep¹. The parasite found its new home very much to its liking, not only becoming highly prevalent in sheep but also establishing itself in wildlife populations such that much of the transmission that occurs nowadays in Australia is sylvatic^1,2.

Until recently four species of Echinococcus parasite were considered to infect humans. The genetically polymorphic species E. granulosus is responsible for the vast majority of human infections; is the only species that is distributed globally and the only species endemic in Australia. E. granulosus has a two host lifecycle, with dogs and other canids acting as definitive hosts, harbouring the small tapeworm in the intestine. Parasite eggs are released in the dog’s faeces and, should these be eaten by a suitable species of intermediate host, the parasite establishes in the tissues as a larval stage forming a cyst. The lifecycle is complete when infected tissues of the intermediate hosts are ingested by a dog and the parasite matures into the sexually reproducing adult tapeworm. Infection in the intermediate hosts has long been known as hydatid disease; the term cystic echinococcosis is now coming into common usage also. Many different herbivorous mammalian species have been described as intermediate hosts for E. granulosus, including domesticated sheep, goats, cattle, buffaloes, pigs, camelids, cervids and horses.

Hydatid disease in humans manifests as fluid filled cysts, most commonly occurring in the liver and lung, but also occasionally occurring in any tissue site including heart, brain or bone. The symptoms and other medical sequelae of hydatid disease depend on many factors including the number, location and size of the cysts. For a proportion of patients, infection can be treated effectively with benzimidazole drugs, however for the majority of cases chemotherapy has little or no effect on the parasite. Some cases of infection in the liver can be treated effectively via percutaneous surgical procedures however surgical resection remains the mainstay for treatment. One interesting discovery arising from decades of monitoring of asymptomatic hydatid patients in the Rio Negro province of Argentina has been that more than 20% of patients with simple, viable hydatid cysts were observed to have their cysts undergo total involution over a 5 year period in which no intervention was undertaken³. Watch and wait is now the recommended procedure. The personal cost of hydatid disease for many individual patients is enormous. Frequently patients undergo multiple rounds of surgery. The global burden arising from of E. granulosus infections has been estimated to be in excess of 1-3 million DALYs lost annually and financial losses of $2 billion annually⁴. The infection continues to be highly prevalent in many parts of the world and may be increasing in prevalence in some areas⁵.

From the earliest times of scientific study, it was realized that E. granulosus showed a high degree of morphological variability and differences in host specificity. Analysis of DNA sequence variability identified a number of genetic types and although there was initially confusion about the validity of some of the genotypes that were described, and their host associations, it is now becoming accepted that there are sev eral different genotypes among what had been referred to as E. granulosus and that differences in relation to some of these genotypes warrant delineation as separate species⁶. Genotyping of hydatid cysts from human cases has identified that the genotype most commonly infecting sheep, E. granulosus sensu strictu, is responsible for the vast majority of human infections and that the only other genotype to cause a significant number of human cases is E. canadensis G6/7, which is transmitted commonly by camels and pigs acting as intermediate hosts.

Recognition that hydatid disease was a major cause of human mortality in Iceland in the1800’s led to a control program being established in 1863 by a Danish veterinarian, Harald Krabbe, based mostly on public education⁷. During the 1950’s and 60’s interest in hydatid disease control was heightened. Informal hydatid control activities became widespread in New Zealand after 1947 leading to a formal government supported control campaign from 1959. Some 43 years after the initiation of the formal CE control campaign, New Zealand declared provisional freedom from hydatid disease in September 2002⁸. Encouraged by the control activities in New Zealand, hydatid control was instigated in Tasmania leading to the declaration of provisional freedom from E. granulosus in February 1996⁹. Numerous other hydatid control activities have been initiated in countries or regions of the world, but most have had limited success¹⁰. Certain peculiarities of the social situation in Iceland contributed to the success of that campaign whereas public education has not been successful elsewhere¹¹. The campaigns undertaken in New Zealand and Tasmania were advantaged by having continuous government support, adequate funding, no wildlife reservoir and being undertaken in island situations.

The hydatid control programs in New Zealand and Tasmania relied heavily of treatment of dogs to remove E. granulosus infections, other dog control initiatives and care not to feed dogs with untreated offal. Dog control has also been effective in a limited number of other places; for example, in the Greek controlled areas of Cyprus dog control was brought about by euthanasia, mostly by shooting, of 82,984 dogs¹². In the year 1971 alone, 27,552 dogs were destroyed, equating to 75 dogs every day. However in many other parts of the world where hydatid disease remains highly prevalent, it is virtually impossible to control dogs. Social and political factors are such that even un-owned, semi-wild dogs are protected by the community which will resist strongly either dog euthanasia or even sterilization. Other factors that have contributed to a limited effectiveness of many attempts to control E. granulosus are the long duration required by campaigns that rely on dog control and the need to treat dogs with anthelmintic frequently so that they cannot become infected with gravid worms¹¹.

There is renewed hope for reducing human cystic echinococcosis following the development of an effective vaccine that can greatly reduce infections in animal intermediate hosts^13,14. Early data from use of the vaccine against naturally-acquired infections indicate that it can be used to reduce disease transmission¹⁵. Mathematical modeling suggests that application of the vaccine in livestock together with a limited (twice yearly) treatment of dogs with anthelmintic would bring about a high level of control of E. granulosus within 5-7 years¹⁶. Efforts are now underway to undertake carefully controlled studies to gather solid scientific evidence to determine whether this control scenario would be as effective as the model predicts. If it is effective, it would provide a blueprint for renewed control programs and a reduction in the global burden of human cystic echinococcosis.

From an Australian perspective, much of the transmission of E. granulosus that now occurs on the continent occurs through the sylvatic cycle involving wild dogs, dingos and macropod marsupials, mostly in the mountainous areas along the eastern coast¹. While the EG95 vaccine can protect macropods against E. granulosus infection¹⁷ and control of echinococcosis is feasible in wild canids¹⁸, it seems unlikely that the extent of the problem in Australia would lead to wide scale control activities in wild animals unless specific genera are threatened with extinction due to hydatid disease.

Figure 1. . Echinococcus granulosus adult worms recovered from the small intestine of a naturally infected dingo from the Kosciuszko National Park. More than 300,000 mature worms were present in this one animal and heavy infections are common in wild dogs and dingoes in eastern Australia. Sylvatic transmission of the parasite on the Australian mainland is likely to hamper chances for elimination of locally acquired hydatid disease from e Australia.