Schistosomiasis is endemic in most sub-Saharan African countries, including Ghana, where the need for effective control involving preventive chemotherapy was indicated by the WHO. Mass drug administration commenced in 2008 and has continued since then in Ghana, but the country remains highly endemic. Here, we review the literature on schistosomiasis to identify research and knowledge gaps potentially affecting disease control. A total of 100 Ghana-related schistosomiasis literature sources were reviewed, showing that most studies were conducted on epidemiology, control of transmission and diagnosis. By contrast, many aspects of this disease remain neglected, including livestock schistosomiasis and its zoonotic potential, recent distribution of disease vectors or widely overlooked genital schistosomiasis. Stratified by region, the highest number of studies focus on Greater Accra, while studies are limited or absent for several other regions. Although this review shows apparent progress in terms of schistosomiasis research and control, a considerable amount of work remains to achieve at least a reduction in the prevalence of the disease, which affects a significant proportion of the population. National epidemiological data based on a nationwide survey, integrated control and improved monitoring and evaluation must be ensured.

Background Glutamate carboxypeptidase 2 (GCP2) belongs to the M28B metalloprotease subfamily encompassing a variety of zinc-dependent exopeptidases that can be found in many eukaryotes, including unicellular organisms. Limited information exists on the physiological functions of GCP2 orthologs in mammalian tissues outside of the brain and intestine, and such data are completely absent for non-mammalian species. Here, we investigate GCP2 orthologs found in trematodes, not only as putative instrumental molecules for defining their basal function(s) but also as drug targets. Methods Identified genes encoding M28B proteases Schistosoma mansoni and Fasciola hepatica genomes were analyzed and annotated. Homology modeling was used to create three-dimensional models of SmM28B and FhM28B proteins using published X-ray structures as the template. For S. mansoni, RT-qPCR was used to evaluate gene expression profiles, and, by RNAi, we exploited the possible impact of knockdown on the viability of worms. Enzymes from both parasite species were cloned for recombinant expression. Polyclonal antibodies raised against purified recombinant enzymes and RNA probes were used for localization studies in both parasite species. Results Single genes encoding M28B metalloproteases were identified in the genomes of S. mansoni and F. hepatica. Homology models revealed the conserved three-dimensional fold as well as the organization of the di-zinc active site. Putative peptidase activities of purified recombinant proteins were assayed using peptidic libraries, yet no specific substrate was identified, pointing towards the likely stringent substrate specificity of the enzymes. The orthologs were found to be localized in reproductive, digestive, nervous, and sensory organs as well as parenchymal cells. Knockdown of gene expression by RNAi silencing revealed that the genes studied were non-essential for trematode survival under laboratory conditions, reflecting similar findings for GCP2 KO mice. Conclusions Our study offers the first insight to our knowledge into M28B protease orthologs found in trematodes. Conservation of their three-dimensional structure, as well as tissue expression pattern, suggests that trematode GCP2 orthologs may have functions similar to their mammalian counterparts and can thus serve as valuable models for future studies aimed at clarifying the physiological role(s) of GCP2 and related subfamily proteases. Graphical Abstract