The newly completed whole genome sequence of Schistosoma haematobium, the leading cause of human schistosomiasis and an emerging co-factor in Africa’s AIDS and cancer epidemics, together with rapidly advancing genetic manipulation technologies, is providing new insights that could lead to the development of a new generation of tools for eliminating this ancient scourge.
Today, more than 90% of the roughly 200 million cases of schistosomiasis occur in Africa , , of which approximately two-thirds are caused by Schistosoma haematobium , the etiologic agent of urogenital schistosomiasis. More recently, Charles King and his colleagues have suggested that the number of cases of S. haematobium may be much greater than previously believed, even possibly double or triple that of earlier prevalence estimates.
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Schistosomiasis, also known as bilharzia or “snail fever,” is a parasitic disease carried by fresh water snails. It is transmitted by contact with contaminated fresh water, so swimming, bathing, fishing and even domestic chores such as laundry and herding livestock can put people at risk of contracting the disease. Schistosomiasis infects more than 400 million people, mostly in sub-Sarahan Africa, where it is one of the most common parasitic infections on the continent.
But one form of the disease has particular repercussions for women and their health and reproductive systems — FGS. It causes horrific pain and bleeding in the uterus, cervix and lower genital tract, not to mention social stigma and depression. Right now, more than 100 million women and girls in Africa could suffer from this form of schistosomiasis.
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Nigeria has the greatest number of intestinal helminth infections, i.e., ascariasis, hookworm, and trichuriasis, among all African nations, ranking fourth or fifth globally behind only the much higher populated middle-income Asian nations, such as China, India, and Indonesia. Nigeria also has the greatest number of cases of schistosomiasis worldwide, with both intestinal schistosomiasis caused by Schistosoma mansoni and the urogenital schistosomiasis caused by Schistosoma haematobium endemic to that country. In terms of the high prevalence vector-borne NTDs, Nigeria has the greatest number of cases of LF and onchocerciasis in Africa, ranking globally third and first, respectively, and accounting for one-fourth or more of the global disease burden from these two NTDs.
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The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund’s adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.
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Founded in 1969, the Organisation of the Islamic Conference (OIC) is comprised of 57 nations that together represent the second largest international organization after the United Nations. According to their Web site, the OIC serves as the “collective voice of the Muslim world,” both protecting its interests and settling conflicts and disputes between member states. In addition to several important and prosperous oil- and gas-producing nations in the Middle East, the OIC nations also include some of the world’s poorest countries as well as large middle-income countries with regions of great poverty. In these geographic areas of poverty are also found some of the highest infection rates and endemicity of the neglected tropical diseases (NTDs).
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Despite new information that the disease burden of schistosomiasis in Africa may be equivalent to malaria or HIV/AIDS and a simple annual anthelminthic treatment for this disease is available for less than 50 cents per person including delivery costs, we now know that fewer than 5% of the infected population is receiving coverage. To date, this situation represents one of the first great failures of the “global health decade” that began in 2000. The scaling up of praziquantel manufacture and distribution, together with operational research and new product research and development, would represent a global assault on schistosomiasis.
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