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Robert Bergquist

Publications and source records attributed to Robert Bergquist.

12 recordsLinked to original sources

Application of dipstick dye immunoassay (DDIA) kit for the diagnosis of schistosomiasis mekongi.

The dipstick dye immunoassay (DDIA), developed in China for the detection of antibodies against Schistosoma japonicum, relies on soluble egg antigen (SEA) labelled with a colloidal dye. This assay is not only rapid, simple and inexpensive, but also particularly useful for screening in the field. In order to determine whether S. japonicum antigens are sufficiently cross-reactive to make the assay applicable for the diagnosis also of S. mekongi a DDIA approach based on the S. japonicum SEA was tried in cohorts of healthy and infected people living in areas non-endemic and endemic with regard to schistosomiasis mekongi in Cambodia and Laos. A sensitivity of 97.1% was recorded when testing Cambodian subjects, correctly diagnosing 33 out of 34 infected people. When the assay was applied in Laos, a sensitivity of 98.6% (69/70) was found. None of 114 residents living in a non-endemic area in Cambodia tested positive. A cross-reaction of 18.3% was found in patients infected with Opisthorchis viverrini. The results support the notion that the DDIA using S. japonicum SEA antigens can safely be implemented for the diagnosis of schistosomiasis mekongi, but care is needed in the interpretation of results obtained from areas that are co-endemic for O. viverrini.

Antibodies, Helminth↗

The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention: a new administrative structure for schistosomiasis control.

Since more than 5 decades, the overall responsibility for the national programme on schistosomiasis control in China resides at the government level, i.e. Ministry of Health. Day-to-day activities are carried out by independent provincial parasitic institutes situated in the endemic areas. Along with the general economic development and the steady progress in the medical sciences, successful developments in control and research of the parasitic diseases in the country were achieved. This necessitated a corresponding reorganization of the administrative structures which has taken place at several levels. In January 2002, the Chinese Centre for Disease Control and Prevention was reorganized and the Institute of Parasitic Diseases in Shanghai became part of this new organization under the name of the National Institute of Parasitic Diseases to better reflect its new role. By assigning all administrative tasks regarding research and control of parasitic diseases under the umbrella of one administrative central laboratory, the new task force for epidemiological surveys and direction of parasitic control programmes is well suited to respond to the daunting challenges of the future. The new institution has only existed for a few years but has already become a well-functioning force with a broad contact net of national and international experts on research and control of parasitic diseases.

Academies and Institutes↗

Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model.

Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1-3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

Animals↗

In vitro cellular and humoral responses to Schistosoma mansoni vaccine candidate antigens.

Few studies comparing schistosomiasis vaccine candidate antigens between laboratories have been carried out and published. Generally, only the investigators who discovered the molecules have evaluated them in either experimental animal models or in human correlate studies. In an attempt to identify responses against specific antigens and investigate their association with resistance versus susceptibility to re-infection, we studied the serological reactions and the cytokine responses stimulated by a panel of 10 candidate vaccine molecules in 225 long-term residents of an area endemic for Schistosoma mansoni in Egypt. The panel consisted of four recombinant antigens (Sm62-Irv5, Sm37-G3PDH, Sm28-GST and Sm14-FABP), one full-length native protein (Sm97-paramyosin), two synthetic peptides (MAP3 and MAP4) and three unpublished antigens (PR52-filamin, PL45-phosphoglycerate kinase, PN18-cyclophilin). Two different study designs, one based on retrospective and the other on prospective parasitological data were applied in the evaluation of the immune responses. Using historical data collected over the previous 5 years, correlations between frequency of re-infection and antigen-specific immune responses were investigated. In the prospective arm of the study, the subjects were followed over time after treatment with praziquantel with periodic immunological tests and stool examinations. Thus, highly specific humoral and cellular immune reactions in response to the 10 antigens described above could be correlated, both prospectively and retrospectively, with detailed epidemiological data covering a 66-month period. The immune response profiles produced were unique to each antigen but no clear "winner" or "winners" were identified. However, markers for both resistance and susceptibility to re-infection were identified for each molecule indicating which types of responses to aim for in vaccination and which ones to avoid. The insights gained from this approach should be useful for antigen selection and ultimately for vaccine formulation prior to Phase I/II trials in humans.

Adolescent↗

Schistosomiasis control in the 21st century. Proceedings of the International Symposium on Schistosomiasis, Shanghai, July 4-6, 2001.

A total of 120 papers were presented at the International Symposium on Schistosomiasis which was held in Shanghai, July 4-6, 2001 with the theme of Schistosomiasis Control in the 21st Century. In order to focus more attention on the new challenges in control programmes for schistosomiasis as well as show the priority of research areas in new century, we summarize the advances of control programmes and researches in nine areas, including (1) Status of schistosomiasis control programmes; (2) Progress in applied field research; (3) Biology and control approaches of snail hosts; (4) Novel approaches for schistosomiasis control; (5) Pathogenesis and morbidity of the disease; (6) Immunology and vaccine development; (7) Screening of population for chemotherapy in low transmission areas; (8) Sustainable intervention methods in different endemic settings; (9) Impact of animal schistosomiasis on agricultural development and importance of its control; (10) GIS/RS application and environmental changes.

Animals↗

Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia.

Two decades ago, a group of Chinese scientists discovered the antischistosomal properties of artemether, a derivative of the antimalarial drug artemisinin. However, it was only recently that the importance of this finding was recognized internationally, following a collaborative effort between Chinese, European and African scientists, who investigated the effects of artemether against the major human schistosome species. Laboratory studies revealed that artemether exhibits the highest activity against juvenile stages of the parasites, while adult worms are significantly less susceptible. There was no indication of neurotoxicity following repeated high doses of artemether given fortnightly for up to 5 months. Randomized controlled clinical trials confirmed that artemether, orally administered at a dose of 6 mg/kg once every 2-3 weeks, results in no drug-related adverse effects, and significantly reduces the incidence and intensity of schistosome infections. The risk that these treatment regimens might select for resistance, particularly for resistant-plasmodia, appears to be low. Combined treatment with artemether and praziquantel, given to animals harbouring juvenile and adult schistosome worms, resulted in significantly higher worm burden reductions than each drug administered singly. In conclusion, artemether-integrated with other control strategies-has considerable potential for reducing the current burden of schistosomiasis in different epidemiological settings.

Administration, Oral↗

Mathematical modelling of schistosomiasis japonica: comparison of control strategies in the People's Republic of China.

We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-yearly mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped; (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible.

Animals↗

Blueprint for schistosomiasis vaccine development.

A number of different schistosome antigens are capable of partially protecting experimental animals from challenge infection. More than 100 such antigens have been identified, about 15% of which are strongly protective and deemed promising though they do not reach the level close to sterile immunity seen after vaccination with irradiated cercariae. Studies of human correlate reactions, i.e. serological reactions and cytokine responses to schistosomiasis antigens, in individuals living in areas endemic for schistosomiasis have shown associations between certain antigen-specific immune responses and lack of re-infection over time. This approach was applied in Brazil and Egypt where it was possible to epidemiologically follow cohorts of individuals in endemic areas for extended periods of time correlating infection status with immune responses against a panel of well-researched, highly purified vaccine candidates. The immune correlates found were unique to each antigen and could be either positive or negative, i.e. associated with resistance or with susceptibility to re-infection. However, few antigens were clear-cut in this respect, i.e. the majority of them induced ambiguous responses. For example, a single antigen might have a significant positive correlation when antigen-driven interferon (INF)-gamma production is measured but also show a significant negative correlation with respect to the IgG1 titre induced. These observations suggest that there are desirable, antigen-specific immune responses that would be valuable in a vaccine but they also indicate that there are responses that must be avoided. The insights gained should be useful not only for antigen selection but also for vaccine formulation prior to Phase I/II trials in humans. It would be of great value if similar independent, long-term human correlate studies could also be undertaken in areas endemic for Schistosoma japonicum.

Animals↗

Potential long-term toxicity of repeated orally administered doses of artemether in rats.

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of reticulocyte counts and reversible increases in hemoglobin levels. Liver and kidney function and histopathological examination showed no differences between treated and untreated rats. Administration of 400 mg/kg artemether resulted in transient focal vesicle degeneration of the liver or slight damage to the proprius layer lamina of intestinal villi. No damage to the central nervous system tissues, including cerebrum, cerebellum, midbrain, thalamus, pons, medulla oblongata, and spinal cord, was seen at either concentration. There were no alterations in electrocardiograms during the 6-month treatment period. We conclude that 80 mg/kg artemether administered once every 2 weeks is safe, and doses of 400 mg/kg do not result in evidence of neurotoxicology.

Administration, Oral↗

Conquering schistosomiasis in China: the long march.

The last half-century of schistosomiasis control activities in China have brought down the overall prevalence of human infection with Schistosoma japonicum to less than 10% of the level initially documented in the mid 1950s. Importantly, this reduction is not only, or even mainly, due to the advent of praziquantel in the 1970s and its subsequent dramatic fall in price. Instead, it is the result of a sustained, multifaceted national strategy, adapted to different eco-epidemiological settings, which has been versatile enough to permit subtle adjustments over time as the nature of the challenge changed. Consequently, prevalence has been falling relatively smoothly over the whole period rather than suddenly dropping when mass chemotherapy became feasible. Thus, early recognition of the huge public health and economic significance of the disease, and the corresponding political will to do something about it,underpinned this success. In addition, intersectoral collaboration and community participation played important roles in forming a sustained commitment to a working control strategy based on local resources. The unfolding story is presented from the early years' strong focus on snail control, by means of environmental management, to the last period of praziquantel-based morbidity control carried out under the 10-year World Bank Loan Project (WBLP). An important legacy of the WBLP is the understanding that a research component would sustain control measures and enable future progress. We are now witnessing the payoffs of this forward thinking in the form of a new promising class of drugs, improved diagnostics, and budding vaccine development in addition to novel ways of disease risk prediction and transmission control using satellite-based remote sensing. Different aspects of social and economic approaches are also covered and the importance of health promotion and education is emphasized. Issuing from the review is a set of recommendations, which might further consolidate current control activities, with the ultimate aim to eliminate schistosomiasis from the Chinese mainland.

Animals↗