Metabolic fingerprinting analysis can offer insights into underlying reactions in a biological system; hence it is crucial to the understanding of disease pathogenesis and could provide useful tools for discovering biomarkers. We sought to examine the urine and plasma metabolome in individuals affected by urogenital schistosomiasis and its associated-bladder pathologies. Blood and midstream urine were obtained from volunteers who matched our inclusion criteria among residents from Eggua, southwestern Nigeria. Samples were screened by urinalysis, microscopy, PCR and ultrasonography, and categorised as advanced (urogenital schistosomiasis associated-bladder pathologies), infection-only (urogenital schistosomiasis alone) and controls (no infection and no pathology). Metabolites were extracted and data acquired with ultra high-performance liquid chromatography coupled with Thermo Q-Exactive orbitrap HRMS. Data was analysed with MetaboAnalyst, Workflow4Metabolomics, HMDB, LipidMaps and other bioinformatics tools, with univariate and multivariate statistics for metabolite selection. There were low levels of host sex steroids, and high levels of several benzenoids, catechols and lipids (including ganglioside, phosphatidylcholine and phosphatidylethanolamine), in infection-only and advanced cases (FDR2, delta>2.0). Metabolites involved in biochemical pathways related to chorismate production were abundant in controls, while those related to choline and sphingolipid metabolism were upregulated in advanced cases (FDR<0.05). Some of these human host and Schistosoma haematobium molecules, including catechol estrogens, were good markers to distinguish infection-only and advanced cases. Altered glycerophospholipid and sphingolipid metabolism could be key factors promoting the development of bladder pathologies and tumours during urogenital schistosomiasis. Obtaining specific molecules having a strong association with a disease condition i.e. biomarkers, is usually a major step to developing new modes of therapy or diagnosis for the disease. In this study, samples from individuals with S. haematobium infection, some of whom had developed bladder pathologies, were compared to controls. From the blood and urine samples analysed by mass spectrometry, we highlight important human and Schistosoma haematobium metabolites, small molecules smaller in size than most proteins, which associate strongly with individuals having schistosomiasis induced-pathology or schistosomiasis alone. This report of the potential biomarkers will also add to the current understanding of the molecular events leading to schistosome associated-bladder cancer.

Approximately one-third of the world’s human population is estimated to have been exposed to the parasite Toxoplasma gondii. Its prevalence is reportedly high in Ethiopia (74.80%) and Zimbabwe (68.58%), and is 40.40% in Nigeria. The adverse effect of this parasite includes a serious congenital disease in the developing fetus of pregnant women. After several efforts to eliminate the disease, only one licensed vaccine ‘Toxovax’ has been used to avoid congenital infections in sheep. The vaccine has been adjudged expensive coupled with adverse effects and short shelf life. The potential of vaccine to likely revert to virulent strain is a major reason why it has not been found suitable for human use, hence the need for a vaccine that will induce T and B memory cells capable of eliciting longtime immunity against the infection. This study presents immunoinformatics approaches to design a T. gondii-oriented multiepitope subunit vaccine with focus on micronemal proteins for the vaccine construct. The designed vaccine was subjected to antigenicity, immunogenicity, allergenicity and physicochemical parameter analyses. A 657-amino acid multiepitope vaccine was designed with the antigenicity probability of 0.803. The vaccine construct was classified as stable, non-allergenic, and highly immunogenic, thereby indicating the safety of the vaccine construct for human use.

Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis. Schistosomiasis, caused by S. haematobium, causes inflammation in the bladder and is common in tropical areas such as Nigeria. Undetected schistosomiasis can lead to inflammation in the bladder which may lead to bladder cancer. Diagnosis of bladder cancer in areas with common urinary schistosomiasis is difficult because the two diseases share many common symptoms. It is therefore important to identify biomarkers that could be used for early diagnosis of both schistosomiasis and schistosomiasis-associated bladder cancer. We chose a proteomic approach to identify these candidate biomarkers in a clinical cohort of urine samples obtained in Nigeria. We found several parasite- and host-specific protein biomarkers that could have diagnostic potential in a urine-based test for schistosomiasis, and schistosomiasis-associated bladder cancer. These include proteins that may also have application in drug or vaccine development. This study is one of the first to catalogue the urinary proteomes of people affected by this neglected tropical disease.

Screening forSchistosoma haematobiuminfection and its possible morbidity was carried out in 257 adult participants in Eggua community, Ogun State, Nigeria. Parasitological assessment for the presence of ova ofS. haematobiumin urine and abdominopelvic ultrasonographic examination for bladder and secondary kidney pathology were carried out.S. haematobiumprevalence of 25.68% (66/257) was recorded among the participants. There was a significantly higher prevalence of 69.2% of urinary schistosomiasis in the females than the prevalence of 31.8% in males (P=0.902). The intensity of infections was mostly light (55) (21.8%) compared to heavy (10) (3.9%) with the mean intensity of 16.7 eggs/10 mL urine. Structural bladder pathology prevalence among participants was 33.9%. The bladder and kidney pathologies observed by ultrasound in subjects withS. haematobiuminfections included abnormal bladder wall thickness (59%), abnormal bladder shape (15.2%), bladder wall irregularities (15.2%), bladder masses (1.5%), bladder calcification (1.5%), and hydronephrosis (3%). Infection withS. haematobiumwas associated with bladder pathology. Higher frequencies of bladder abnormalities were observed more in the participants with light intensity ofS. haematobiuminfection than in those with heavy infection. More bladder pathology was also seen in women than in men, although this was not statistically significant. In conclusion, there is evidence that the development of bladder pathology may be associated withS. haematobiuminfection.

Stimulation and generation of T and B cell-mediated long-term immune response are essential for the curbing of a deadly virus such as SAR-CoV-2 (Severe Acute Respiratory Corona Virus 2). Immunoinformatics approach in vaccine design takes advantage of antigenic and non-allergenic epitopes present on the spike glycoprotein of SARS-CoV-2 to elicit immune responses. T cells and B cells epitopes were predicted, and the selected residues were subjected to allergenicity, antigenicity and toxicity screening which were linked by appropriate linkers to form a multi-epitope subunit vaccine. The physiochemical properties of the vaccine construct were analyzed, and the molecular weight, molecular formula, theoretical isoelectric point value, half-life, solubility score, instability index, aliphatic index and GRAVY were predicted. The vaccine structure was constructed, refined, validated, and disulfide engineered to get the best model. Molecular binding simulation and molecular dynamics simulation were carried out to predict the stability and binding affinity of the vaccine construct with TLRs. Codon acclimatization and in silico cloning were performed to confirm the vaccine expression and potency. Results obtained indicated that this novel vaccine candidate is non-toxic, capable of initiating the immunogenic response and will not induce an allergic reaction. The highest binding energy was observed in TLR4 (Toll-like Receptor 4) (−1398.1), and the least is TLR 2 (−1479.6). The steady rise in Th (T-helper) cell population with memory development was noticed, and IFN-g (Interferon gamma) was provoked after simulation. At this point, the vaccine candidate awaits animal trial to validate its efficacy and safety for use in the prevention of the novel COVID-19 (Coronavirus Disease 2019) infections.