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      Species-Specific Immunity Induced by Infection with Entamoeba histolytica and Entamoeba moshkovskii in Mice

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          Abstract

          Entamoeba histolytica, the parasitic amoeba responsible for amoebiasis, causes approximately 100,000 deaths every year. There is currently no vaccine against this parasite. We have previously shown that intracecal inoculation of E. histolytica trophozoites leads to chronic and non-healing cecitis in mice. Entamoeba moshkovskii, a closely related amoeba, also causes diarrhea and other intestinal disorders in this model. Here, we investigated the effect of infection followed by drug-cure of these species on the induction of immunity against homologous or heterologous species challenge. Mice were infected with E. histolytica or E. moshkovskii and treated with metronidazole 14 days later. Re-challenge with E. histolytica or E. moshkovskii was conducted seven or 28 days following confirmation of the clearance of amoebae, and the degree of protection compared to non-exposed control mice was evaluated. We show that primary infection with these amoebae induces a species-specific immune response which protects against challenge with the homologous, but not a heterologous species. These findings pave the way, therefore, for the identification of novel amoebae antigens that may become the targets of vaccines and provide a useful platform to investigate host protective immunity to Entamoeba infections.

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          Most cited references23

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          WHO estimates of the causes of death in children.

          Child survival efforts can be effective only if they are based on accurate information about causes of deaths. Here, we report on a 4-year effort by WHO to improve the accuracy of this information. WHO established the external Child Health Epidemiology Reference Group (CHERG) in 2001 to develop estimates of the proportion of deaths in children younger than age 5 years attributable to pneumonia, diarrhoea, malaria, measles, and the major causes of death in the first 28 days of life. Various methods, including single-cause and multi-cause proportionate mortality models, were used. The role of undernutrition as an underlying cause of death was estimated in collaboration with CHERG. In 2000-03, six causes accounted for 73% of the 10.6 million yearly deaths in children younger than age 5 years: pneumonia (19%), diarrhoea (18%), malaria (8%), neonatal pneumonia or sepsis (10%), preterm delivery (10%), and asphyxia at birth (8%). The four communicable disease categories account for more than half (54%) of all child deaths. The greatest communicable disease killers are similar in all WHO regions with the exception of malaria; 94% of global deaths attributable to this disease occur in the Africa region. Undernutrition is an underlying cause of 53% of all deaths in children younger than age 5 years. Achievement of the millennium development goal of reducing child mortality by two-thirds from the 1990 rate will depend on renewed efforts to prevent and control pneumonia, diarrhoea, and undernutrition in all WHO regions, and malaria in the Africa region. In all regions, deaths in the neonatal period, primarily due to preterm delivery, sepsis or pneumonia, and birth asphyxia should also be addressed. These estimates of the causes of child deaths should be used to guide public-health policies and programmes.
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            Malnutrition as an enteric infectious disease with long-term effects on child development.

            Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of potentially lifelong functional disability. Yet, a rate-limiting step in achieving normal nutrition may be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal. In malnourished individuals, the infections are even more devastating. This review documents the evidence that intestinal infections lead to malnutrition and that malnutrition worsens intestinal infections. The clinical data presented here derive largely from long-term cohort studies that are supported by controlled animal studies. Also reviewed are the mechanisms by which enteric infections lead to undernutrition and by which malnutrition worsens enteric infections, with implications for potential novel interventions. Further intervention studies are needed to document the relevance of these mechanisms and, most importantly, to interrupt the vicious diarrhea-malnutrition cycle so children may develop their full potential.
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              A new medium for the axenic cultivation of Entamoeba histolytica and other Entamoeba.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                29 November 2013
                : 8
                : 11
                : e82025
                Affiliations
                [1 ]Department of Parasitology, Nagasaki University, Nagasaki, Japan
                [2 ]Malaria Unit, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan
                [3 ]Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma, Japan
                [4 ]Department of Tropical Medicine and Parasitology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
                [5 ]Global COE Program, Nagasaki University, Nagasaki, Japan
                Obihiro University of Agriculture and Veterinary Medicine, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CS SH. Performed the experiments: CS TI KS MH TT SK. Analyzed the data: CS RC HH SH. Contributed reagents/materials/analysis tools: CS SK SH. Wrote the manuscript: CS RC SH.

                Article
                PONE-D-13-35194
                10.1371/journal.pone.0082025
                3843725
                24312397
                8245a91a-3029-4026-90f2-8fae286ebca0
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 August 2013
                : 24 October 2013
                Funding
                The work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from MEXT (21022037 to S.H.), http://www.mext.go.jp/english/, Grants-in-Aid for International Scientific Research (B) from JSPS (20406008, 23406009 to S.H.), http://www.jsps.go.jp/english/index.html, a Health Labour Sciences Research Grant (H20-Shinkoh-Ippan-016, H23-Shinkoh-Ippan-014 to S.H.), http://www.mhlw.go.jp/english/, the Takeda Foundation http://www.takeda-sci.or.jp/, the Uehara Foundation, (to S. H.) http://www.ueharazaidan.or.jp/, the Global COE Program, Nagasaki University, supported by MEXT (to S. H.) http://www.jsps.go.jp/j-globalcoe/ and the Sasakawa Foundation (Scientific Research Grant from The Japan Science Society) (to C.S.), http://www.jss.or.jp/ikusei/sasakawa/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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