Marshall W. Lightowlers

Prevention and control of cystic echinococcosis

Human cystic echinococcosis (hydatid disease) continues to be a substantial cause of morbidity and mortality in many parts of the world. Elimination is difficult to obtain and it is estimated that, using current control options, achieving such a goal will take around 20 years of sustained efforts. Since the introduction of current (and past) hydatid control campaigns, there have been clear technological improvements made in the diagnosis and treatment of human and animal cystic echinococcosis, the diagnosis of canine echinococcosis, and the genetic characterisation of strains and vaccination against Echinococcus granulosus in animals. Incorporation of these new measures could increase the efficiency of hydatid control programmes, potentially reducing the time required to achieve effective prevention of disease transmission to as little as 5-10 years.

Vaccination against hydatidosis using a defined recombinant antigen

Echinococcus granulosus is the causative agent of hydatid disease in humans and animals. Natural transmission of the parasite occurs between dogs as definitive hosts and animal intermediate hosts. There is an urgent need for improved methods to control the parasites transmission. Here we describe the development of a vaccine based on a cloned recombinant antigen from the parasite egg (oncosphere). Sheep vaccinated with the antigen, designated EG95, are protected (mean 96–98%) against hydatidosis developing from an experimental challenge infection with E. granulosus eggs. The vaccine will provide a valuable new tool to aid in control of transmission of this important human pathogen. It also has the potential to prevent hydatid disease directly through vaccination of humans.

Excretory–secretory products of helminth parasites: effects on host immune responses

Parasitic helminths excrete or secrete (ES) a variety of molecules into their mammalian hosts. The effects of these ES products on the hosts immune responses are reviewed. Investigations into the source of antigenic or immunoregulatory ES products have identified the cuticular and tegumental surfaces of some nematodes and trematodes respectively as being important sources of ES products; other ES molecules are released through specialized excretory or secretory organs. It is proposed that the active shedding of surface antigens may serve as an important source of parasite antigens available to the immune system in a form in which they can be taken up and processed by antigen-presenting dendritic cells, macrophages and certain B cells for presentation to T helper cells. The ES products of nematodes, trematodes and cestodes contribute to immune evasion strategies of the parasites through mechanisms including shedding of surface-bound ligands and cells, alteration of lymphocyte, macrophage and granulocyte functions and modulation of complement and other host inflammatory responses. Immunopathology may be induced by ES products as in the development of granulomas around entrapped schistosome eggs. In some host-parasite systems ES antigens may induce host-protective immune responses and this source of protective antigens has been utilized in the successful vaccination against helminth infections, particularly against infection with trichurid nematodes and the metacestode stage of cestode parasites. The use of ES antigens in immunodiagnosis of helminth infection is also briefly discussed.

Induction of Protection against Porcine Cysticercosis by Vaccination with Recombinant Oncosphere Antigens

ABSTRACT Two recombinant Taenia solium oncosphere antigens, designated TSOL18 and TSOL45-1A, were investigated as vaccines to prevent transmission of the zoonotic disease cysticercosis through pigs. Both antigens were effective in inducing very high levels of protection (up to 100%) in three independent vaccine trials in pigs against experimental challenge infection with T. solium eggs, which were undertaken in Mexico and Cameroon. This is the highest level of protection that has been achieved against T. solium infection in pigs by vaccination with a defined antigen. TSOL18 and TSOL45-1A provide the basis for development of a highly effective practical vaccine that could assist in the control and, potentially, the eradication of human neurocysticercosis.

Subunit composition and specificity of the major cyst fluid antigens of Echinococcus granulosus

The subunit composition and specificity of the major Echinococcus granulosus cyst fluid antigens were determined by immunochemical analysis using murine monoclonal antibodies against Antigen 5 and Antigen B and human sera. Immune complexes cut out from immunoelectrophoresis gels and murine hybridomas were used as a source of specific anti-Antigen 5 and anti-Antigen B antibodies. Immunoprecipitation and Western blot analyses in sodium dodecyl sulphate-polyacrylamide gels using these reagents identified Antigen 5 to be a heterodimer composed of 24-kDa and 38-kDa subunits linked by disulphide bonding. Antigen B comprised a regularly spaced group of molecules with the smallest subunit estimated to be 8 kDa and the other components each differing in size by approximately 8 kDa, i.e., 16 kDa, 24 kDa, 32 kDa etc.; all possibly derived from the 8-kDa monomer. The relative abundance of the Antigen B subunits decreased asymptotically with increasing molecular weight. Neither the Antigen 5 nor the Antigen B subunit was specific for E. granulosus. Both antigens generated readily detectable levels of specific antibody in the sera of patients with Echinococcus multilocularis, Echinococcus vogeli or E. granulosus infection. Relatively high levels of antibody to Antigen 5 were also detected in the sera of patients infected with Taenia solium. The presence of phosphorylcholine epitope(s) on Antigen 5 was confirmed.

Vaccination trials in Australia and Argentina confirm the effectiveness of the EG95 hydatid vaccine in sheep.

Experimental vaccine trials against hydatid disease have been undertaken in sheep using the EG95 recombinant vaccine. Challenge infection was with viable Echinococcus granulosus eggs obtained from a New Zealand isolate (dog/sheep cycle), an Australian isolate (dingo/wallaby cycle) and an Argentine isolate (dog/sheep cycle). Vaccination with EG95 conferred a high degree of protection against challenge with all three parasite isolates (protection range 96-100%). Taken together, the trials demonstrated that 86% of vaccinated sheep were completely free of viable hydatid cysts when examined approximately 1 year after challenge infection. Vaccination reduced the number of viable cysts by 99.3% compared with unvaccinated controls. These results suggest that the EG95 vaccine could have wide applicability as a new tool for use in hydatid control campaigns.

Vaccines to combat the neglected tropical diseases

Summary:  The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low‐ and middle‐income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world’s poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non‐profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access.

Neurocysticercosis: regional status, epidemiology, impact and control measures in the Americas

The analysis of epidemiological data concerning human cysticercosis point to important advances in understanding the magnitude and distribution of this parasitic disease in Latin America, as well as the relationship of the elements that conform the life cycle of Taenia solium. The data indicate that the main risk factor for acquiring human neurocysticercosis and swine cysticercosis is the presence of the tapeworm carrier in the household. Therefore, several intervention measures for the control of cysticercosis have been evaluated: mass treatment in order to cure tapeworm carriers, health education towards understanding the risk factors, pig control by restraining them, experimental vaccination of pigs and treatment of swine cysticercosis. In this paper, we review the information obtained in these areas. We hope it will be useful in other endemic countries that wish to elaborate an action plan for the control and ultimate eradication of T. solium.

Eradication of Taenia solium cysticercosis: A role for vaccination of pigs

Taenia solium is the causative agent of neurocysticercosis, a disease responsible for substantial human morbidity and mortality. It is a zoonotic parasite, involving pigs as intermediate hosts. The parasites full life cycle is restricted to poor people in developing countries. Attempts to date to control transmission of the parasite have been relatively poorly effective and not sustainable. Over the past decade research has been undertaken to develop practical vaccines for use in pigs to prevent transmission of T. solium. The most effective of these vaccines in controlled experimental trials has been the TSOL18 vaccine. More recently, TSOL18 has been proven to be highly effective against naturally acquired infection with T. solium in pigs. Application of TSOL18 together with a single treatment of pigs with oxfendazole achieved the complete elimination of transmission of the parasite by pigs involved in the field trial. This strategy may provide a relatively low cost and sustainable control tool which could assist towards the goal of achieving eradication of the parasite. An assessment is made of the potential value of various control measures that are available for T. solium, and two options are suggested as potential parasite control programs.

Vaccination Against Cysticercosis and Hydatid Disease

Infections with the larval stages of taeniid cestode parasites cause substantial human morbidity as well as economic losses in domestic livestock species. Despite ongoing efforts around the world, few countries have been able substantially to reduce or eradicate these infections through the use of anthelmintics and lifestyle changes. Vaccines offer an additional potential tool to assist with the control of parasite transmission. Here, Marshall Lightowlers and colleagues review the substantial progress that has been made towards developing practical vaccines against hydatid disease in sheep and cysticercosis in sheep and cattle. Recombinant antigens have been used to induce more than 90% protection against challenge infections. Such success in animals encourages investigation of the potential use of vaccines in humans to prevent hydatid disease arising from infection with Echinococcus granulosus and cysticercosis from infection with Taenia solium.