Eradication of Taenia solium cysticercosis: a role for vaccination of pigs.

Neurocysticercosis due to Taenia solium is an important cause of human morbidity and mortality, particularly in Latin America and parts of Africa and Asia. The disease has been recognised as potentially eradicable. Emphasis has been placed on control of the parasite through mass chemotherapy of human populations to remove tapeworm carriers. This strategy does not control the source of tapeworm infections, cysticercosis in pigs, and parasite transmission may continue due to incomplete chemotherapy coverage of human tapeworm carriers or because of immigration of tapeworm carriers into control areas. Exceptionally effective, practical vaccines have been developed against cysticercosis in sheep and cattle and a recent trial has proved recombinant antigens to be effective against Taenia solium cysticercosis in pigs. A new strategy for eradication of Taenia solium is proposed, based principally on a combined approach of chemotherapy of human tapeworm carriers and vaccination of all pigs at risk of infection.     

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.     

Application of antigens from Taenia hydatigena cyst fluid for the immunodiagnosis of human hydatidosis

Fluid was collected from cysts of Taenia hydatigena in 60 adult sheep and fluid from each animal pooled separately. By double diffusion antigen 5 was demonstrated in all pools but one. The criteria are described for selection and standardization of these preparations for use as antigens for the immunodiagnosis of human hydatid disease. Sera from 50 persons harbouring hydatid cysts and from 50 patients with other disease conditions were examined by the arc-5 double-diffusion test, using two antigens prepared from Echinococcus granulosus and T. hydatigena cyst fluids, respectively. The results showed that a higher diagnostic sensitivity was obtained with the hydatid antigen. The significance of the findings is discussed in terms of their application to human immunodiagnosis in areas where hydatidosis, but not cysticercosis, is rare in livestock.     

Immunological responses and potency of the EG95NC− recombinant sheep vaccine against cystic echinococcosis

Cystic echinococcosis (CE) is a zoonotic disease caused by the cestode parasite Echinococcus granulosus. The disease has an important impact on human health as well as economic costs including the cost of treatment as well as loss of productivity for the livestock industry. In many parts of the world where the disease is endemic, sheep and other livestock play an important role in the parasite's transmission. A vaccine to protect livestock against CE can be effective in reducing transmission and economic costs of the disease. A recombinant antigen vaccine has been developed against infection with E. granulosus (EG95) which could potentially be used to reduce the level of E. granulosus transmission and decrease the incidence of human infections. Further development of the EG95 recombinant vaccine as a combined product with clostridial vaccine antigens is one potential strategy which could improve application of the hydatid vaccine by providing an indirect economic incentive to livestock owners to vaccinate against CE. In this study we investigated the efficacy of the EG95 recombinant vaccine produced in Morocco by vaccination of sheep, including a combined vaccine incorporating EG95 and clostridia antigens. Vaccination with EG95 either as a monovalent vaccine or combined with clostridia antigens, protected sheep against a challenge infection with E. granulosus eggs and induced a strong, long lasting, and specific antibody response against the EG95 antigen.     

Immunology and molecular biology of Echinococcus infections

Echinococcus spp. are the etiological agents of hydatid disease in man and other intermediate hosts. Many questions regarding the factors which determine susceptibility/resistance to hydatid disease, and the factors which influence the viability and fertility of hydatid cysts, remain to be answered. Recent research into the effects of hydatid infection on the immune system of the host has provided some insights into the host-parasite relationships. Immunochemical and recombinant DNA techniques are being applied to improve diagnosis of hydatidosis in man and E. granulosus infection in dogs, and also in the development of vaccines against infection with taeniid cestode larvae. The successes which have been achieved in these areas are likely to provide valuable tools for the control of cystic hydatidosis in man. These recent studies in the areas of immunobiology, serological diagnosis and vaccination are reviewed.     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Serodiagnosis of Echinococcosis by ELISA Using Cystic Fluid from Uzbekistan Sheep

According to increase of travel, the cases of imported echinococcosis have been increasing in Korea. The present study was undertaken to develop a serodiagnostic system for echinococcosis in Korea. For diagnosis of echinococcosis, the fluid of Echinococcus granulosus hydatid cysts was collected from naturally infected sheep in Uzbekistan. Also serum samples of infected patients who were surgically confirmed were collected in a hospital in Tashkent, Uzbekistan. According to the absorbance of 59 echinococcosis positive and 39 negative control serum samples, the cut-off value was determined as 0.27. The sensitivity and specificity of ELISA with hydatid fluid antigen were 91.5% and 96%, respectively. The antigen cross-reacted with the serum of some cysticercosis or clonorchiasis patients. However, immunoblot analysis on the cystic fluid recognized antigenic proteins of 7-, 16-, and 24-kDa bands in their dominant protein quantity and strong blotting reactivity. In conclusion, the present ELISA system using hydatid cyst fluid antigen from Uzbekistan sheep is sensitive and specific for diagnosis of echinococcosis cases.     

Control of hydatid disease in Wales.

OBJECTIVES--To evaluate the success of the south Powys hydatid control programme by analysis of trends in cystic disease in humans and sheep and dog infestation. DESIGN--A review of hospital admissions for human hydatid disease in 1984-90, abattoir prevalence surveys of hydatid cysts in adult sheep, arecoline acetarsol and coproantigen surveys of prevalence of Echinococcus infestation in dogs. SETTING--All hospitals in England and Wales, three abattoirs, and dog populations in mid ands south east Wales. SUBJECTS--Residents of England and Wales admitted to hospital between 1984 and 1990 with a new diagnosis of human hydatid disease (International Classification of Diseases (ICD), ninth revision, code 122) acquired in the United Kingdom. RESULTS--The average annual incidence of human hydatid disease in Powys, mid-Wales, fell from 3.9x10(-5) in 1974-83 to 2.3x10(-5) in 1984-90. Age specific incidence rates in Wales declined over this period only in children, and no cases occurred in children (<15 years) in Powys. Two Welsh children who lived in Gwent and mid-Glamorgan were infected. Prevalence of hydatid cysts in old sheep from south Wales declined during the control period, but in 1993 prevalence of cysts was 13%. Prevalence of E granulosus infestation was zero in the control area in 1993, but it was 2.4% in Powys dogs outside the control area in 1989 and 9.2% in dogs in Gwent in 1991. CONCLUSIONS--Human hydatid disease has been successfully controlled in south Powys but cystic echinococcosis is still endemic in sheep in mid-Wales, and there is a focus of infection in humans, sheep, and dogs in the bordering areas of Gwent and mid-Glamorgan. There is considerable potential for an upsurge in human cases if control measures are relaxed.     

Overview of vaccines and vaccination

Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the kind of the immune responses generated by those vaccines, which are so effective. To date, all licensed vaccines generate especially specific antibodies, which attach to the infectious agent and therefore can very largely prevent infection. These vaccines have been so effective in developed countries in preventing mortality after a subsequent infection that attempts are being made to develop vaccines against many of the remaining infectious agents. Many of the latter are difficult to manipulate; they can cause persisting infections or show great antigenic variation. A range of new approaches to improve selected immune responses, such as immunization with DNA or chimeric live vectors, viral or bacterial, are under intense scrutiny, as well as genomic analysis of the agent.     

Diva vaccines that reduce virus transmission.

This brief review deals with the effect of diva (Differentiating Infected from VAccinated individuals) vaccines (also termed marker vaccines) on transmission of herpesviruses and pestiviruses in swine and cattle. Pseudorabies and bovine herpesvirus 1 diva vaccines have been demonstrated to reduce transmission of wild-type virus in populations of pigs and cattle in the laboratory as well as in the field. A subunit diva vaccine based on the immunodominant E2 protein of classical swine fever virus that is expressed in the baculovirus system may reduce transmission of wild-type virus among pigs and also transmission from mother to foetuses. A similar diva vaccine against bovine virus diarrhoea infections protected sheep against transplacental transmission of antigenically homologous wild-type virus. Diva vaccines along with their companion diagnostic tests can play a role in control of infections, ultimately leading to eradication of viruses.     

Cytolytic CD4 cells: Direct mediators in infectious disease and malignancy

CD4 T cells have traditionally been regarded as helpers and regulators of adaptive immune responses; however, a novel role for CD4 T cells as direct mediators of protection against viral infections has emerged. CD4 T cells with cytolytic potential have been described for almost 40 years, but their role in host protection against infectious disease is only beginning to be realized. In this review, we describe the current literature identifying these cells in patients with various infections, mouse models of viral infection and our own work investigating the development of cytolytic CD4 cells in vivo and in vitro. CD4 CTL are no longer considered an artefact of cell culture and may play a physiological role in viral infections such as EBV, CMV, HIV and influenza. Therefore, vaccine strategies aimed at targeting CD4 CTL should be developed in conjunction with vaccines incorporating B cell and CD8 CTL epitopes.     

Assessment of prevalence of hydatidosis in slaughtered Sawakny sheep in Riyadh city,Saudi Arabia

Hydatidosis, or echincoccosis, is a serious medical and veterinary problem in many countries, particularly those with rural communities where there is a greater contact between dogs and domestic animals. Domestic livestock act as intermediate hosts which are the main reservoir for the disease in humans. It is therefore very important to estimate the prevalence of hydatid cysts in slaughtered animals since it can be transmitted to humans through dogs, which act as the final host for the disease. From this point of view, the present study was suggested to determine the prevalence of hydatidosis in Sawakny sheep slaughtered in Riyadh city, Saudi Arabia. During the course of the study 12,569 Sawakny sheep were inspected for hydatidosis infection. An overall prevalence of 1.06% was detected among the examined sheep, with the highest prevalence occurring in winter (1.38%) and lowest prevalence in summer (0.67%). Sheep aged 6–12 months had a higher rate of infection than older animals, and males were the predominant carriers of infection (97.7%) compared to females (2.3%). The liver was the most infected organ (79.1%), followed by the lungs (14.6%), while concurrent infections of both the liver and the lungs occurred in 6% of cases. The fertility and viability rates of hydatid cysts in the liver (70.1% and 85.1% respectively) were higher than that in any other organs. In conclusion, it is evident that fertile cysts in slaughtered sheep could have an important role in the continuation of hydatid cyst transmission to humans through dogs. Considerable effort should be devoted to controlling the transmission of cysts from abattoirs by the secure disposal of infected offal. In addition, plans are required for further epidemiological studies and control programs.     

In vitro oncosphere-killing assays to determine immunity to the larvae of Taenia pisiformis, Taenia ovis, Taenia saginata, and Taenia solium

Taeniid cestodes infect humans and livestock, causing considerable morbidity and mortality, as well as economic loss. Substantial progress has been made toward the production of recombinant vaccines against cysticercosis in livestock animals. Further development of these vaccines would be aided if a reliable in vitro test were available to measure host-protective immune responses in vaccinated animals. Here, we describe in vitro oncosphere-killing assays for the quantification of host-protective serum antibodies against Taenia pisiformis, Taenia ovis, Taenia saginata, and Taenia solium in rabbits, sheep, cattle, and pigs, respectively. Activated oncospheres of T. pisiformis, T. ovis, T. saginata, and T. solium were incubated in vitro in culture medium, test serum, and a source of complement, and oncosphere killing was assessed after 10 days of culture. In vitro oncosphere killing reflected the presence of specific antibody, and the oncosphere-killing assay typically indicated immunity to the homologous parasite that had been determined in vivo. This study describes the first reliable oncosphere-killing assays for T. pisiformis, T. ovis, T. saginata, and T. solium. These assays will be used for further research into the optimization of recombinant vaccines against cysticercosis.     

Flavobacterium psychrophilum vaccine development: a difficult task

Bacterial cold water disease (BCWD) is a globally distributed freshwater fish disease caused by the Gram-negative bacterium Flavobacterium psychrophilum. It is a particularly devastating infection in fry salmonids and may lead to high levels of mortality. In spite of its economic impact on fish farms, neither the biology of the bacterium nor the bacterium–host interactions are well understood. This review provides a synopsis of the major problems related to critical remaining questions about research into the use of vaccines against F. psychrophilum and the development of a commercial vaccine against this disease. Studies using sera from convalescent rainbow trout have shown the antigenic properties of different proteins such as OmpH, OmpA and FspA, as well as low and high molecular mass lipopolysaccharide of F. psychrophilum, which are potential candidates for subunit vaccines. Inactivated F. psychrophilum bacterins have been successfully tested as vaccines under laboratory conditions by both immersion and intraperitoneal routes. However, the efficacy and the practical usefulness of these preparations still have to be proved. The use of attenuated and wild-type strains to immunize fish showed that these systems offer high levels of protection. Nevertheless, their application clashes with the regulations for environmental protection in many countries. In conclusion, protective vaccines against BCWD are theoretically possible, but substantial efforts still have to be made in order to permit the development of a commercial vaccine.     

Molecular and genetic characterisation of the host-protective oncosphere antigens of taeniid cestode parasites

Highly effective recombinant vaccines have been developed against Taenia ovis infection in sheep, Taenia saginata infection in cattle, Taenia solium infection in pigs, Echinococcus granulosus and Echinococcus multilocularis infections in a variety of intermediate host species. These vaccines have been based on the identification and expression in Escherichia coli of antigens derived from the oncosphere life cycle stage, contained within the parasites' eggs. Investigation of the molecular aspects of these proteins and the genes encoding them have revealed a number of common features, including the presence of a predicted secretory signal sequence, and one or two copies of a fibronectin type III domain, each encoded by separate exons within the associated gene. Evidence has been obtained to confirm glycosylation of some of these antigens. Ongoing investigations will shed light on the biological roles played by the proteins within the parasites and the mechanism by which they make the parasites vulnerable to vaccine-induced immune responses.     

Further studies on an intermediate host murine model showing that a primary Echinococcus granulosus infection is protective against subsequent oncospheral challenge

We describe the use of a murine model to evaluate resistance against subsequent challenge following a primary infection with oncospheres of Echinococcus granulosus. Mice (Kunming strain) were infected with hatched oncospheres of Echinococcus granulosus; 21 days later a second challenge was given by a different route of infection. A primary infection by intraperitoneal (i.p.) injection stimulated 100 and 90.5% protection in terms of reduced cyst numbers against a secondary infection given subcutaneously (s.c.) or intravenously (i.v.), respectively. A primary infection given s.c. followed by i.p. or i.v. challenge resulted in 84.0 and 100% protection, respectively. Intravenous infection followed by i.p. or s.c. challenge resulted in 98.5 and 69.4% protection, respectively. With the i.v. route of infection, almost all resultant cysts were present in the lungs. The data show that a primary infection with oncospheres can induce total or a high degree of protection against a subsequent challenge and confirms that natural (concomitant) immunity can be stimulated in the intermediate host as the result of a primary infection. This may explain the decline in hydatid infection in sheep older than 2 years in hyper-endemic areas such as those found in Xingjiang, China. These older sheep may have been earlier infected and have subsequently self-cured, with the primary infection stimulating an immune response that protects the intermediate host animals from further infection.     

Microdevices for examining immunological responses of single cells to HIV

More than 60 million people in the world have been diagnosed with HIV infections since the virus was recognized as the causative agent of AIDS in the 1980s. Even though more than half of the infected patients have died, effective disease treatment and prevention measures have not been established. ART (antiretroviral therapy) is the only proven HIV treatment that sustains the suppression of patient viraemia. Current routine approaches to treat HIV infections are targeted at developing vaccines that will induce humoral or cell memory immune responses. However, developing an effective vaccine has been challenging because the HIV mutates rapidly, which allows the virus to evade immune surveillances established against the previous strain. In addition, the virus is able to quickly establish a reservoir and treatment is difficult because of the general lack of knowledge about HIV immune response mechanisms. This review introduces common disease symptoms and the progression of HIV infection with a brief summary of the current treatment approaches. Different cellular immune responses against HIV are also discussed, with emphasis on a nanotechnology research that has focused on probing T-cell response to HIV infection. Furthermore, we discuss recent noteworthy nanotechnology updates on T-cell response screening that is focused on HIV infection. Finally, we review potential future treatment strategies based on the correlations between T-cell response and HIV infection.     

Vaccine strategies for Cowdria ruminantium infections and their application to other ehrlichial infections.

Suman Mahan and co-authors review the strategies applied to develop improved vaccines for Cowdria ruminantium infections (heartwater). Inactivated vaccines using cell-cultured C. ruminantium organisms combined with an adjuvant are capable of protecting goats, sheep and cattle against lethal C. ruminantium challenge. Immune responses induced with this vaccine, or after recovery from infection, target outer membrane proteins of C. ruminantium, in particular the major antigenic protein 1 (MAP-1). Genetic immunizations with the gene encoding MAP-1 induce protective T helper cell type 1 responses against lethal challenge in a mouse model. Similarly, homologues of MAP-1 in other phylogenetically and antigenically related ehrlichial agents such as Anaplasma marginale and Ehrlichia chaffeensis are also targets of protective responses. Given the antigenic similarities between the related ehrlichial agents, common strategies of vaccine development could be applied against these agents that cause infections of importance in animals and humans.     

Purification and partial immunochemical characterization of a low molecular mass, diagnostic Echinococcus granulosus immunogen for sheep hydatidosis

Abstract A hydatid specific antigen of 8 kDa molecular mass was affinity-purified from crude hydatid cyst fluid. Some of the epitopes recognised by antibodies in the sera from sheep with hydatidosis were periodate-sensitive. The purified 8 kDa antigen was observed to be a thermo-stable glycoprotein in its immunochemical characteristics. By immunofluorescence on acetone-fixed protoscolices anti-8 kDa monospecific IgG antibodies indicated the existence of the 8 kDa molecule on the hooklets of protoscolices. The purified antigen was used in an enzyme-linked immunosorbent assay for the detection of specific antibodies in sera from sheep hydatidosis. Eighteen (90%) of 20 sera from sheep hydatidosis had antibodies to purified 8 kDa antigen while none of the sera from other parasitic infections or uninfected animals had any detectable levels of antibodies to 8 kDa antigen. Thus, the data on localization and recognition of hydatid specific 8 kDa molecule suggested that this may be one of the major molecules for specific immunodiagnosis and for modulating the hydatid disease process in infected hosts.