The association of systemic inflammation and cognitive functions of pre-school aged children residing in a Schistosoma haematobium endemic area in Zimbabwe.

Background: Cognitive function is negatively impacted by schistosomiasis and might be caused by systemic inflammation which has been hypothesized to be one of the mechanisms driving cognitive decline, This study explored the association of systemic inflammatory biomarkers; interleukin (IL)-10, IL-6, IL-17, transforming growth factor (TGF-ß), tumor necrosis factor (TNF-α), C-reactive protein (CRP) and hematological parameters with cognitive performance of preschool-aged children (PSAC) from an Schistosoma haematobium endemic area. Methods: The Griffith III tool was used to measure the cognitive performance of 136 PSAC. Whole blood and sera were collected and used to quantify levels of IL-10, TNF-α, IL-6, TGF-ß, IL-17 A and CRP using the enzyme-linked immunosorbent assay and hematological parameters using the hematology analyzer. Spearman correlation analysis was used to determine the relationship between each inflammatory biomarker and cognitive performance. Multivariate logistic regression analysis was used to determine whether systemic inflammation due to S. haematobium infection affected cognitive performance in PSAC. Results: Higher levels of TNF-α and IL-6, were correlated with lower performance in the Foundations of Learning domain (r = -0.30; p < 0.001 and r = -0.26; p < 0.001), respectively. Low cognitive performance in the Eye-Hand-Coordination Domain was observed in PSAC with high levels of the following inflammatory biomarkers that showed negative correlations to performance; TNF-α (r = -0.26; p < 0.001), IL-6 (r = -0.29; p < 0.001), IL-10 (r = -0.18; p < 0.04), WBC (r = -0.29; p < 0.001), neutrophils (r = -0.21; p = 0.01) and lymphocytes (r = -0.25; p = 0.003) The General Development Domain correlated with TNF-α (r = -0.28; p < 0.001) and IL-6 (r = -0.30; p < 0.001). TGF-ß, L-17A and MXD had no significant correlations to performance in any of the cognitive domains. The overall general development of PSAC was negatively impacted by S. haematobium infections (OR = 7.6; p = 0.008) and (OR = 5.6; p = 0.03) where the PSAC had higher levels of TNF-α and IL-6 respectively. Conclusion: Systemic inflammation and S. haematobium infections are negatively associated with cognitive function. We recommend the inclusion of PSAC into mass drug treatment programs.

Diagnostic performances of Schistosoma haematobium and Schistosoma mansoni recombinant proteins, peptides and chimeric proteins antibody based tests. Systematic scoping review.

BACKGROUND: Traditional diagnostic tests for schistosome infections are suboptimal, particularly when the parasite burden is low. In the present review we sought to identify recombinant proteins, peptides, and chimeric proteins with potential to be used as sensitive and specific diagnostic tools for schistosomiasis. METHODS: The review was guided by PRISMA-ScR guidelines, Arksey and O'Malley's framework, and guidelines from the Joanna Briggs Institute. Five databases were searched: Cochrane library, PubMed, EMBASE, PsycInfo and CINAHL, alongside preprints. Identified literature were assessed by two reviewers for inclusion. A narrative summary was used to interpret the tabulated results. RESULTS: Diagnostic performances were reported as specificities, sensitivities, and AUC. The AUC for S. haematobium recombinant antigens ranged from 0.65 to 0.98, and 0.69 to 0.96 for urine IgG ELISA. S. mansoni recombinant antigens had sensitivities ranging from 65.3% to 100% and specificities ranging from 57.4% to 100%. Except for 4 peptides which had poor diagnostic performances, most peptides had sensitivities ranging from 67.71% to 96.15% and specificities ranging from 69.23% to 100%. S. mansoni chimeric protein was reported to have a sensitivity of 86.8% and a specificity of 94.2%. CONCLUSION: The tetraspanin CD63 antigen had the best diagnostic performance for S. haematobium. The tetraspanin CD63 antigen Serum IgG POC-ICTs had a sensitivity of 89% and a specificity of 100%. Peptide Smp_150390.1 (216-230) serum based IgG ELISA had the best diagnostic performance for S. mansoni with a sensitivity of 96.15% and a specificity of 100%. Peptides were reported to demonstrate good to excellent diagnostic performances. S. mansoni multi-peptide chimeric protein further improved the diagnostic accuracy of synthetic peptides. Together with the advantages associated with urine sampling technique, we recommend development of multi-peptide chimeric proteins urine based point of care tools.

Peptide microarray analysis of in-silico predicted B-cell epitopes in SARS-CoV-2 sero-positive healthcare workers in Bulawayo, Zimbabwe.

Immunogenic peptides that mimic linear B-cell epitopes coupled with immunoassay validation may improve serological tests for emerging diseases. This study reports a general approach for profiling linear B-cell epitopes derived from SARS-CoV-2 using an in-silico method and peptide microarray immunoassay, using healthcare workers' SARS-CoV-2 sero-positive sera. SARS-CoV-2 was tested using rapid chromatographic immunoassays and real-time reverse-transcriptase polymerase chain reaction. Immunogenic peptides mimicking linear B-cell epitopes were predicted in-silico using ABCpred. Peptides with the lowest sequence identity with human protein and proteins from other human pathogens were selected using the NCBI Protein BLAST. IgG and IgM antibodies against the SARS-CoV-2 spike protein, membrane glycoprotein and nucleocapsid derived peptides were measured in sera using peptide microarray immunoassay. Fifty-three healthcare workers included in the study were RT-PCR negative for SARS-CoV-2. Using rapid chromatographic immunoassays, 10 were SARS-CoV-2 IgM sero-positive and 7 were SARS-CoV-2 IgG sero-positive. From a total of 10 SARS-CoV-2 peptides contained on the microarray, 3 (QTH34388.1-1-14, QTN64908.1-135-148, and QLL35955.1-22-35) showed reactivity against IgG. Three peptides (QSM17284.1-76-89, QTN64908.1-135-148 and QPK73947.1-8-21) also showed reactivity against IgM. Based on the results we predicted one peptide (QSM17284.1-76-89) that had an acceptable diagnostic performance. Peptide QSM17284.1-76-89 was able to detect IgM antibodies against SARS-CoV-2 with area under the curve (AUC) 0.781 when compared to commercial antibody tests. In conclusion in silico peptide prediction and peptide microarray technology may provide a platform for the development of serological tests for emerging infectious diseases such as COVID-19. However, we recommend using at least three in-silico peptide prediction tools to improve the sensitivity and specificity of B-cell epitope prediction, to predict peptides with excellent diagnostic performances.

Biochemical profile of paediatric adamantinomatous craniopharyngiomas: A prospective cohort study.

Introduction: Craniopharyngioma is a rare brain tumour. Despite being histologically benign, it behaves aggressively and is often difficult to manage. Descriptive epidemiological data on the tumour is lacking in sub-Saharan Africa, and there is none for Zimbabwe. The tumour usually has a cystic component that has been raising interest in the past decade. Few studies have looked at the biochemical composition thereof. This study aims to give a landscape view of craniopharyngiomas (CPs) in Zimbabwe and then profile the biochemical properties of the cystic component of paediatric adamantinomatous craniopharyngioma. Methodology: A prospective cohort study was done in Zimbabwe over a 2-year period to study the epidemiological distribution of craniopharyngioma and examine the biochemical composition of adamantinomatous craniopharyngioma cystic fluid in the paediatric population. Fifteen patients were recruited who had craniopharyngiomas, and of those, nine paediatric adamantinomatous craniopharyngiomas had fluid analysed for biochemical components. SPSS statistical package was used to analyse the data. Descriptive statistics were used for epidemiological data. Results: The incidence of CP was calculated to be 0.53 per million person-years. Incidence among the paediatric population 0-14 years was 1.2 per 100,000 person-years. Several biological components were found to be elevated significantly compared to serum and cerebral spinal fluid (CSF). These are sodium, potassium, urea, alkaline phosphatase, phosphate, magnesium, albumin, gamma-glutamyl transferase, calcium, low-density lipids, and glucose. Conclusion: The incidence of CP in Zimbabwe is similar to the rest of the world. Some biochemical components have been noted to be markedly elevated in the cystic fluid and were mirroring serum rather than CSF in concentration.

Multiplex peptide microarray profiling of antibody reactivity against neglected tropical diseases derived B-cell epitopes for serodiagnosis in Zimbabwe.

INTRODUCTION: Peptides (B-cell epitopes) have broad applications in disease diagnosis and surveillance of pathogen exposure. In this framework, we present a pilot study to design and produce a peptide microarray for the integrated surveillance of neglected tropical diseases. The peptide microarray was evaluated against peptides derived from Ascaris lumbricoides, Necator americanus, Schistosoma haematobium, Schistosoma mansoni, Trichuris trichiura, Bacillus anthracis, Mycobacterium leprae, Wuchereria bancrofti, Rabies lyssavirus, Chlamydia trachomatis and Trypanosoma brucei. METHODS: S. haematobium was diagnosed using the urine filtration technique. S. mansoni, A. lumbricoides, N. americanus and T. trichiura were diagnosed using the Kato Katz and formal ether concentration techniques. Immunogenic peptides were retrieved from the Tackling Infection to Benefit Africa infectious diseases epitope microarray. Further peptides were predicted using ABCpred. IgG and IgM reactivity against the derived peptides were evaluated using peptide microarray multiplex immunoassays. Positive response was defined as fluorescence intensity ≥ 500 fluorescence units. Immunodominant peptides were identified using color-coded heat maps and bar graphs reflecting the obtained fluorescence signal intensities. Receiver Operating Characteristic analysis and Mann-Whitney-U test were performed to determine the diagnostic validity of the peptides. RESULTS: Species-specific responses with at least one peptide derived from each NTD pathogen were observed. The reactive peptides included; for S. haematobium, XP_035588858.1-206-220 and XP_035588858.1-206-220 immunodominant for IgG and IgM respectively, for S. mansoni, P20287.1-58-72 immunodominant for both antibodies and for T. trichiura, CDW52482.1-326-340 immunodominant for IgG and CDW57769.1-2017-2031 and CDW57769.1-1518-1532 immunodominant for IgM. According to ROC analysis most of the peptides selected were inaccurate; with AUC < 0.5. Some peptides had AUC values ranging from 0.5 to 0.5875 for both IgM and IgG suggesting no discrimination. CONCLUSION: Multiplex peptide microarrays are a valuable tool for integrated NTDs surveillance and for screening parasites exposure in endemic areas. Species sero-reactivity observed in the study maybe indicative of exposure to the different NTDs parasites. However, although peptides with the least cross reactivity were selected there is need to validate the sero-reactivity with recombinant antigens and immune-blotting techniques such as western blotting.

Scoping review of the applications of peptide microarrays on the fight against human infections.

INTRODUCTION: This scoping review explores the use of peptide microarrays in the fight against infectious diseases. The research domains explored included the use of peptide microarrays in the mapping of linear B-cell and T cell epitopes, antimicrobial peptide discovery, immunosignature characterisation and disease immunodiagnostics. This review also provides a short overview of peptide microarray synthesis. METHODS: Electronic databases were systematically searched to identify relevant studies. The review was conducted using the Joanna Briggs Institute methodology for scoping reviews and data charting was performed using a predefined form. The results were reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: Ninety-five articles from 103 studies were included in the final data charting process. The majority (92. 0%) of the articles were published during 2010-2020 and were mostly from Europe (44.2%) and North America (34.7%). The findings were from the investigation of viral (45.6%), bacterial (32. 0%), parasitic (23.3%) and fungal (2. 0%) infections. Out of the serological studies, IgG was the most reported antibody type followed by IgM. The largest portion of the studies (77.7%) were related to mapping B-cell linear epitopes, 5.8% were on diagnostics, 5.8% reported on immunosignature characterisation and 8.7% reported on viral and bacterial cell binding assays. Two studies reported on T-cell epitope profiling. CONCLUSION: The most important application of peptide microarrays was found to be B-cell epitope mapping or antibody profiling to identify diagnostic and vaccine targets. Immunosignatures identified by random peptide microarrays were found to be applied in the diagnosis of infections and interrogation of vaccine responses. The analysis of the interactions of random peptide microarrays with bacterial and viral cells using binding assays enabled the identification of antimicrobial peptides. Peptide microarray arrays were also used for T-cell linear epitope mapping which may provide more information for the design of peptide-based vaccines and for the development of diagnostic reagents.

Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers.

Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6 and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins.

Assessing early child development and its association with stunting and schistosome infections in rural Zimbabwean children using the Griffiths Scales of Child Development.

There is a paucity of reference early childhood development (ECD) data at community level in rural Africa. Our objective was to conduct a comprehensive assessment of ECD in rural Zimbabwe and determine the impact of stunting and schistosome infections on ECD. Using the Griffiths Scales of Child Development, we conducted a cross sectional assessment of Eye and Hand Coordination (EHC), Personal-Social-Emotional (PSE), Language and Communication (LC), Foundations of Learning (FL) and Gross Motor (GM) domains and the summary General Development (GD) in 166 children aged 6-72 months. The effects of stunting, malnutrition and Schistosoma haematobium infection on ECD was determined. The impact of praziquantel curative treatment of schistosome infection on the developmental scores was determined through a longitudinal follow up at 6 and 12 months. From an initial 166 children, 11 were found to have developmental deficits warranting further investigation. Of the remaining 155, 58.7% recorded a good (≥ average) score for the overall General Development (GD). Proportions of children scoring above the cut-off (≥ average) for each domain were GM (84.5%), PSE (80.6%), EHC (61.9%), FL (43.9%) and LC (44.5%). The prevalence of stunting was 26.8% (95% CI = 20.1%-34.8%) Scores for stunted children were significantly lower for EHC (p = 0.0042), GM (p = 0.0099), and GD (p = 0.0014) with the fraction of lower scores attributable to stunting being GM = 63.4%, GD = 46.6%, EHC = 45%, and LC = 21%. S. haematobium infection prevalence was 39.7% and mean infection intensity was 5.4 eggs/10 ml urine. Infected children had poorer cognitive performance scores for the FL (p = 0.0005) with 30.8% of poor FL attributable to the infection. Performance in all domains improved to the expected normal or above reference levels at 6 and 12 months post curative treatment of schistosome infections. Our study documented reference values for ECD in rural Zimbabwean children. The study detected deficiencies in the FL domain, which were more pronounced in children, infected with schistosomes, highlighting the need for provision of cognitive stimulation tools and access to early childhood foundation education. There is also need for improved child nutrition and treatment of schistosome infections to improve child development outcomes.

Landscape, Presentation, and Characteristics of Brain Gliomas in Zimbabwe.

INTRODUCTION: Gliomas are tumors of the supporting cells of the central nervous system. They have great heterogeneity in their clinical and pathological features as well as prognosis. There is paucity of glioma epidemiology data in Zimbabwe. We carried out a study to determine the landscape, presentation, and characteristics of brain gliomas in Zimbabwe. MATERIALS AND METHODS: A prospective cross-sectional study was conducted in Zimbabwe over a 2 years period to determine descriptive epidemiological data with regards to demographic distribution, presentation, and tumor characteristics. Consecutive patients from across the country with brain gliomas were recruited in the study. RESULTS: A total of 112 brain tumors were diagnosed histologically. Of these 43.8% (n = 49) were gliomas and hence recruited in the study. The mean age of study participants was 40.3 years (standard deviation = 23.1 years), range 3-83 years. Male to female ratio (M:F) was 1:1. The study population consisted of 14% caucasians (n = 7), 83.7% black (n = 41), and 2% (n = 1) were of mixed race. Eighty-six percent (n = 42) of participants were from urban areas. The most common presenting complaint was headache in 87.8% (n = 43). The majority (61.2%) presented with a Karnofsky score ≥70%. Astrocytomas were the most common gliomas constituting 57.1% (n = 28), followed by ependymomas and oligodendrogliomas being 8.1% (n = 4) each. There was no statistical difference in the hemisphere of the brain involved (P = 0.475). Eight percent of the population were HIV positive (n = 4). Age above 60 years has an adjusted odds ratio of 13 for presenting with high-grade tumors. CONCLUSION: There is a disproportionately high number of gliomas among Caucasians, urban dwellers, and those gainfully employed. The prevalence of HIV in glioma patients is less than that of the general population.

Clinical utility of peptide microarrays in the serodiagnosis of neglected tropical diseases in sub-Saharan Africa: protocol for a diagnostic test accuracy systematic review.

INTRODUCTION: Neglected tropical diseases tend to cluster in the same poor populations and, to make progress with their control, they will have to be dealt with in an integrated manner. Peptide microarrays may be a solution to these problems, where diagnosis for co-infection can be detected simultaneously using the one tool. A meta-analysis using hierarchical models will be performed to assess the diagnostic accuracy of peptide microarrays for detecting schistosomiasis (Schistosoma mansoni and S. haematobium), soil-transmitted helminths (Trichuris trichiura, Ascaris lumbricoides and Necator americanus), trachoma (Chlamydia trachomatis), lymphatic filariasis (Wuchereria bancrofti) and onchocerciasis (Onchocerca volvulus) in people residing in sub-Saharan Africa. METHODS AND ANALYSIS: A comprehensive search of the following databases will be performed: Cochrane Infectious Diseases Group Specialised Register, PubMed, EMBASE and The Web of Science. Studies comparing peptide microarrays with a reference standard from a random or consecutive series of patients will be included in the study. Two review authors will independently screen titles and abstracts for relevance, assess full-text articles for inclusion and carry out data extraction using a tailored data extraction form. The quality Assessment of Diagnostic Accuracy Studies-2 tool will be used to assess the quality of the selected studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model will be performed to evaluate the diagnostic accuracy of the peptide microarrays. Meta-regression analyses will be performed to investigate heterogeneity across studies. ETHICS AND DISSEMINATION: There is no requirement for ethical approval because the work will be carried out using previously published data, without human beings involvement. Findings will be disseminated through peer-reviewed publication and in conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020175145.

Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis.

Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis.

Effects of TNF-α and IL-10-819 T>C single nucleotide polymorphisms on urogenital schistosomiasis in preschool children in Zimbabwe.

BACKGROUND: Knowledge gaps exist between host genetic factors and susceptibility to schistosomiasis. OBJECTIVE: This study determined cytokine levels and single nucleotide polymorphisms of tumour necrosis factor (TNF)-α (rs1800629) and interleukin (IL)-10 (rs1800871) and their possible impact on susceptibility to schistosomiasis in preschool-age children in the Madziva area of Shamva district, Mashonaland Central province, Zimbabwe. METHODS: Urogenital schistosomiasis was diagnosed using the urine filtration method, while a sandwich enzyme-linked immunosorbent assay was used for cytokine level determination. The survey was done in August 2015 and reinfection levels post treatment were assessed at 3, 6 and 12 months. Amplification refractory mutation system polymerase chain reaction with visualisation on 2% agarose gel electrophoresis was used for genotyping. RESULTS: Schistosomiasis prevalence was found to be 10.5% (59/563). Reinfections were detected in only six children at 3 months and only one was reinfected at 12 months. There were no significant differences in TNF-α-308 G/A allele or genotype frequencies between the Schistosoma haematobium infected participants (p = 0.360) and uninfected participants (p = 0.279). However, no children with the IL-10-819 TT genotype had schistosomiasis. The TNF-α GG genotype corresponded with significantly lower TNF-α levels when compared with the GA or AA genotypes (p < 0.001), and TNF-α levels were significantly lower in infected children compared to uninfected children (p < 0.001). CONCLUSION: Higher TNF-α levels and lower IL-10 levels are potentially protective against schistosomiasis infection. The IL-10-819 TT genotype is potentially protective against infection through its association with lower IL-10 levels.

Interleukin-13 rs1800925/-1112C/T promoter single nucleotide polymorphism variant linked to anti-schistosomiasis in adult males in Murehwa District, Zimbabwe.

BACKGROUND: Chronic schistosomiasis is predominantly induced through up-regulation of inflammatory cytokines such as interleukin (IL)-13. IL-13 may contribute to the disease outcomes by increasing eosinophil infiltration thereby promoting fibrosis. IL-13 may act as an immunosuppressive inflammatory cytokine that may promote carcinogenesis and also may offer protection against schistosomiasis thereby reducing risk of schistosome infections. Our study evaluated the frequency of the IL-13 rs1800925/-1112 C/ T promoter single nucleotide polymorphisms (SNPs) among schistosomiasis infected individuals and assessed the association of the variants on IL-13 cytokine levels. We also investigated IL-13 rs1800925 polymorphisms on prostate-specific antigen levels as an indicator for risk of prostate cancer development. METHODOLOGY: The study was cross-sectional and included 50 schistosomiasis infected and 316 uninfected male participants residing in Murehwa District, Zimbabwe. IL-13 rs1800925 SNPs were genotyped by allele amplification refractory mutation system-polymerase chain reaction. Concentrations of serum prostate-specific antigens and plasma IL-13 were measured using enzyme-linked immunosorbent assay. RESULTS: Frequencies of the genotypes CC, CT and TT, were 20%, 58% and 22% in schistosomiasis infected, and 18.3%, 62.1% and 19.6% in uninfected participants with no statistical differences. There were significantly (p<0.05) higher IL-13 cytokine levels among both infected and uninfected participants with the genotypes CC and CT; median 92.25 pg/mL and 106.5 pg/mL, respectively, compared to TT variant individuals; 44.78 pg/mL. Within the schistosomiasis uninfected group, CC and CT variants had significantly (p<0.05) higher IL-13 levels; median 135.0 pg/mL and 113.6 pg/mL, respectively compared to TT variant individuals; 47.15 pg/mL. Within the schistosomiasis infected group, CC, CT and TT variant individuals had insignificant differences of IL-13 level. Using logistic regression, no association was observed between prostate-specific antigen levels, IL-13 cytokine levels and IL-13 rs1800925 variants (p>0.05). CONCLUSION: IL-13 rs1800925 C variant individuals had the highest IL-13 cytokine levels among the schistosomiasis uninfected suggesting that they may be protective against Schistosoma infections. There was no association between IL-13 concentrations or IL-13 rs1800925 variants and risk of prostate cancer indicating that IL-13 levels and IL-13 rs10800925 may not be utilised as biomarker for risk of prostate cancer in schistosome infections.

Association of TNF (rs1800629) promoter polymorphism and schistosomiasis with sub-microscopic asymptomatic Plasmodium falciparum infections in a schistosomiasis-endemic area in Zimbabwe.

OBJECTIVES: Infection with Plasmodium falciparum parasites may result in a wide spectrum of symptoms ranging from asymptomatic to mild or severe. A number of factors are associated with this heterogeneous response to P. falciparum infection. In the present study, associations of sub-microscopic asymptomatic P. falciparum with Schistosoma species and TNF (rs1800629) polymorphism were investigated. METHODS: 361 clinically healthy primary school children were microscopically screened for S. haematobium, S. mansoni and P. falciparum. Sub-microscopic asymptomatic P. falciparum infections were determined by PCR. Genotypic profiles were identified using ARMS-PCR. Logistic regression was used to assess the association of sub-microscopic asymptomatic P. falciparum with Schistosoma species and TNF (rs1800629) polymorphism. RESULTS: 17.2% of the children were infected with S. mansoni, and 27.4% were infected with S. haematobium. Microscopic examination of thick smears detected only one child infected with P. falciparum. Based on PCR results, 46.1% were infected with sub-microscopic asymptomatic P. falciparum. Children carrying heterozygous AG (OR: 16.964, 95% CI: 0.496-586.547) and homozygous GG (OR: 2.280, 95% CI: 0.111-46.796) genotypes of rs1800629 were associated with an increased likelihood of sub-microscopic asymptomatic P. falciparum infections compared with those carrying homozygous AA genotype. Children without S. haematobium infections (OR: 1.051, 95% CI: 0.146-8.985) and S. mansoni (OR: 2.658, 95% CI: 0.498-14.184) also had an increased likelihood (risk) of being infected with sub-microscopic asymptomatic P. falciparum compared with the Schistosoma-infected groups. However, all the associations observed were not statistical significant. CONCLUSION: No associations were observed between rs1800629 and schistosomiasis with sub-microscopic asymptomatic P. falciparum infections. This study also reports a high prevalence of sub-microscopic asymptomatic P. falciparum infection concomitant with low malaria transmission.

OBJECTIFS: L'infection par les parasites P. falciparum peut entraîner un large éventail de présentations allant d'asymptomatiques à bénignes ou sévères. Un certain nombre de facteurs sont associés à cette réaction hétérogène à l'infection à P. falciparum. Dans la présente étude, les associations entre la présentation asymptomatique sous-microscopique de P. falciparum avec les espèces de Schistosoma et le polymorphisme du TNF (rs1800629) ont été investiguées. MÉTHODES: 364 écoliers du primaire en bonne santé clinique ont subi microscopique pour S. haematobium, S. mansoni et P. falciparum. Les infections asymptomatiques sous-microscopiques à P. falciparum ont été déterminées par PCR. Les profils génotypiques ont été identifiés en utilisant ARMS-PCR. La régression logistique a été utilisée pour évaluer l'association entre la présentation asymptomatique sous-microscopique de P. falciparum avec les espèces de Schistosoma et le polymorphisme du TNF (rs1800629). RÉSULTATS: Parmi les enfants, 17,2% étaient infectés par S. mansoni et 27,4% étaient infectés par S. haematobium. L'examen microscopique de frottis épais n'a détecté qu'un seul enfant infecté par P. falciparum. D'après les résultats de la PCR, 46,1% étaient infectés par P. falciparum asymptomatique sous-microscopique. Les enfants porteurs des génotypes hétérozygotes AG (OR: 16,964 ; IC95%: 0,496-586,547) et homozygotes GG (OR: 2,280 ; IC95%: 0,111-46,796) de rs1800629 étaient associés à une probabilité accrue d'infections asymptomatiques sous-microscopiques à P. falciparum par rapport à ceux porteurs du génotype homozygote AA. Les enfants sans infection à S. haematobium (OR: 1,051 ; IC95%: 0,146-8,985) et S. mansoni (OR: 2,658 ; IC95%: 0,498 à 14,184) présentaient également une probabilité (risque) accrue d'être infectés par P. falciparum asymptomatique sous-microscopique par rapport à ceux infectés par Schistosoma. Cependant, toutes les associations observées n'étaient pas statistiquement significatives. CONCLUSION: Aucune association n'a été observée entre le rs1800629 et la schistosomiase avec des infections asymptomatiques sous-microscopiques à P. falciparum. Cette étude rapporte une prévalence élevée d' infection asymptomatique sous-microscopique à P. falciparum concomitante à une faible transmission du paludisme.

Schistosoma haematobium infection is associated with alterations in energy and purine-related metabolism in preschool-aged children.

Helminths are parasitic worms that infect over a billion people worldwide. The pathological consequences from infection are due in part, to parasite-induced changes in host metabolic pathways. Here, we analyse the changes in host metabolic profiles, in response to the first Schistosoma haematobium infection and treatment in Zimbabwean children. A cohort of 83 schistosome-negative children (2-5 years old) as determined by parasitological examination, guardian interviews and examination of medical records, was recruited at baseline. Children were followed up after three months for parasitological diagnosis of their first S. haematobium infection, by detection of parasite eggs excreted in urine. Children positive for infection were treated with the antihelminthic drug praziquantel, and treatment efficacy checked three months after treatment. Blood samples were taken at each time point, and capillary electrophoresis mass spectrometry in conjunction with multivariate analysis were used to compare the change in serum metabolite profiles in schistosome-infected versus uninfected children. Following baseline at the three-month follow up, 11 children had become infected with S. haematobium (incidence = 13.3%). Our results showed that infection with S. haematobium was associated with significant increases (>2-fold) in discriminatory metabolites, linked primarily with energy (G6P, 3-PG, AMP, ADP) and purine (AMP, ADP) metabolism. These observed changes were commensurate with schistosome infection intensity, and levels of the affected metabolites were reduced following treatment, albeit not significantly. This study demonstrates that early infection with S. haematobium is associated with alterations in host energy and purine metabolism. Taken together, these changes are consistent with parasite-related clinical manifestations of malnutrition, poor growth and poor physical and cognitive performance observed in schistosome-infected children.

Association of schistosomiasis and risk of prostate cancer development in residents of Murehwa rural community, Zimbabwe.

BACKGROUND: Prostatic male genital schistosomiasis and prostate cancer co-existence cases are uncommon however, some studies have indicated that schistosomiasis may trigger development of prostate cancer regardless of age. Schistosomiasis is a public health problem in sub-Saharan Africa and may account for some undocumented cases of schistosomiasis prostatic cancer in schistosome endemic rural communities. It is against this background that we investigated the association between schistosomiasis and risk of prostate cancer development in residents of Murehwa Community, a schistosomiasis endemic area. METHODOLOGY: We conducted a cross sectional study involving 366 men residing in Murehwa District, Zimbabwe. Schistosoma haematobium and S. mansoni infection was diagnosed using urine filtration and Kato Katz techniques, respectively. Haematuria was detected using urinalysis reagent strip test. A structured questionnaire was used to obtain history of schistosomiasis infection among study participants. Risk of prostate cancer development was assessed by measuring prostate-specific antigen levels in serum using the ELISA. RESULTS: Prevalence of S. haematobium and S. mansoni infection was 12.3% and 1.4%, respectively. Individuals with schistosomiasis had higher prostate-specific antigen levels (mean 1.208 ± SD 1.557 ng/mL) compared to those without schistosomiasis (mean 0.7721 ± SD 1.173 ng/mL; p < 0.05). Older individuals > 50 years had higher prostate specific antigen levels (mean 0.7212 ± SD 1.313 ng/mL) compared to individuals < 50 years old (mean 0.4159 ± SD 0.8622 ng/mL; p < 0.05). Prostate-specific antigen levels log10 (mean 0.2584 ± SD 0.2128 ng/mL) and were associated to S. haematobium infection intensity log10 (mean 1.121 ± SD 0.5371 eggs/10 mL), r(s) = - 0.3225, p < 0.05. There was a correlation between prostate-specific antigen levels log10 (mean 0.2246 ± SD 0.1858 ng/mL) and S. haematobium infection intensity log10 (mean 1.169 ± SD 0.5568 eggs/10 mL) among participants with a history of schistosomiasis infection (r(s) = - 0.3520; p < 0.05). There was no correlation between prostate-specific antigen levels of > 4 ng/mL (mean 5.324 ± SD1.568 ng/mL) and schistosome eggs log10 (mean 1.057 ± SD 0.6730 eggs/10 mL; p > 0.05). CONCLUSION: Urogenital schistosome infections and history of schistosome infections were associated with prostate specific antigen levels, an indicator for risk of prostate cancer. Therefore, S. haematobium schistosome egg burden was associated with the risk of prostate cancer development in adult males residing in Murehwa District, Zimbabwe.

Positive impact of preventative chemotherapy during a national helminth control program: Perception and KAP.

Helminth control at the national level is currently based on mass drug administration (MDA) programs. Perception of the MDA programs for helminth control by the affected populations influences compliance and future designs of the programs. We determined the perception of Zimbabwe's National Helminth Control Program (2012-2017) with a specific focus on schistosomiasis in the school children treated with praziquantel, schoolteachers and village health workers (VHW). The study enrolled 409 children from Grades 6 and 7 who had the full benefit of the 6 years of MDA from 2012 to 2017. Thirty-six schoolteachers and 22 VHW serving the schools were also recruited. A structured questionnaire developed in English, translated into the local language Shona, and validated prior to the study was administered to the children and the adults. The questions focused on the perceived impact on health, school attendance and performance and Knowledge Attitudes and Practice (KAP) among the school children. Data were captured electronically on android platforms using the Open Data Kit. Overall, 84% of the children responded that their awareness of schistosomiasis (transmission, disease, treatment and infection avoidance) had improved because of participating in the MDAs. Of the 151 children self-diagnosed with schistosomiasis, 74% reported that their health had improved following treatment with praziquantel. This included resolution of haematuria, painful urination, sore stomach, tiredness and falling asleep during class lessons. The children and teachers reported improvements in both pupil school attendance and performance at school while the VHW and teachers reported an increase in health-seeking behaviour amongst the school children for schistosomiasis treatment in-between MDAs. The majority of VHW (96%) reported improvement in handwashing behaviour, schistosomiasis awareness (96%) and treatment uptake (91%) within the communities where the school children belonged. However, only 59% of the VHW reported improvement in toilet use while only 50% of the VHW reported improvement in clean water use within their communities. This study indicated that the surveyed children perceived the MDA program had improved their health, school attendance, school performance and awareness of schistosomiasis. The VHW also perceived that the MDA program had improved the community KAP.

Antimicrobial effects of craniopharyngioma cystic fluid.

BACKGROUND: Tumours are known to increase the risk of infections, especially those occurring in the central nervous system where insertion of surgical hardware/shunts such as in craniopharyngiomas may be required. However, infections are surprisingly scarce in craniopharyngioma cases. In this study, we explored the possibility of antimicrobial effects of craniopharyngioma cystic fluid. METHODS: The antibacterial effect of craniopharyngioma cystic fluid samples against selected human pathogens: Escherichia. coli, S. aureus and S. pneumoniae were determined using the agar disc diffusion method. Streptomycin and ampicillin were used as controls. The test organisms were cultured in Mueller-Hinton broth overnight at 37 °C. McFarland standard was used as a reference to adjust the inoculum size of each test organism to a concentration of 1 × 106 CFU/ml using sterile broth. RESULTS: The craniopharyngioma cystic fluid inhibited growth of Gram-positive bacteria S. aureus and S. pneumoniae, but not the Gram-negative bacteria, E. coli. The samples showed the highest zones of S. pneumoniae growth inhibition of up to 20.0 ± 1.0 mm compared with 18.0 ± 1.0 mm of streptomycin and 9.0 ± 0.0 mm of ampicillin. CONCLUSION: Craniopharyngioma cystic fluid showed significant antibacterial properties against Gram-positive bacteria. This novel finding has implications in the way we view infections in craniopharyngioma patients. More studies need to be carried out to further elucidate this unique finding and possibly exploit these antimicrobial properties.

Six rounds of annual praziquantel treatment during a national helminth control program significantly reduced schistosome infection and morbidity levels in a cohort of schoolchildren in Zimbabwe.

BACKGROUND: The World Health Organization recommends that schistosomiasis be treated through Mass Drug Administration (MDA). In line with this recommendation, Zimbabwe commenced a national helminth control program in 2012 targeting schoolchildren throughout the country for 6 years. This study, part of a larger investigation of the impact of helminth treatment on the overall health of the children, determined the effect of annual praziquantel treatment on schistosome infection and morbidity in a cohort of children during Zimbabwe's 6-year national helminth control program. METHODOLOGY/PRINCIPAL FINDINGS: A school-based longitudinal study was carried out in 35 sentinel sites across Zimbabwe from September 2012 to November 2017. The sentinel sites were selected following a countrywide survey conducted in 280 primary schools. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni was diagnosed using both the Kato-Katz and formol-ether concentration techniques. S. haematobium morbidity was determined through detection of macro and microhaematuria. A cohort of children aged 6-15 years old was surveyed annually before MDA and 6 weeks post treatment. Maximum treatment coverage reached 90% over the 6 rounds of MDA. At baseline S. haematobium infection prevalence and intensity were 31.7% (95% CI = 31.1-32.2) and 28.75 eggs/10ml urine (SEM = 0.81) respectively, while S. mansoni prevalence and intensity were 4.6% (95% CI = 4.4-4.8) and 0.28 eggs/25mg (SEM = 0.02). Prior to the 6th round of MDA, S. haematobium infection prevalence had reduced to 1.56% (p<0.001) and infection intensity to 0.07 (SEM 0.02). Six weeks later after the 6th MDA, both were 0. Similarly the prevalence of S. haematobium morbidity as indicated by haematuria also fell significantly from 32.3% (95% CI = 29.9-34.6) to 0% (p< 0.0001) prior to the final MDA. For S.mansoni, both prevalence and intensity had decreased to 0 prior to the 6th MDA. After 6 rounds of annual MDA, prevalence and intensity of both schistosome species decreased significantly to 0% (p< 0.0001). CONCLUSION: Zimbabwe's helminth control program significantly reduced schistosome infection intensity and prevalence and urogenital schistosomiasis morbidity prevalence in a cohort of school-aged children, moving the schistosome prevalence in the children from moderate to low by WHO classification. These findings will inform the design of the country's next stage interventions for helminth control and eventual elimination.

Possible association and co-existence of schistosome infection and prostate cancer: A systematic review.

Male genital schistosomiasis (MGS) may result in eggs lodged in the prostate causing persistent inflammation that may play a major role in prostate carcinogenesis. Globally, prostate cancer (PCa) is one of the most common cancers and the global distribution of PCa overlaps with that of schistosomiasis infections, suggesting a probable causal relationship. Objectives of this review were to assess evidence of co-existence of schistosomiasis and PCa and possible causal association between the two diseases. Relevant literature published between 1950 and 2019 yielded 20 publications on schistosomiasis and PCa co-existence. Schistosoma (S.) haematobium and S. mansoni were associated with MGS manifestation and mostly prostate adenocarcinoma diagnosis. Effects of prostatic MGS infection progressed over time with high Schistosoma egg burden thought to contribute to the development of PCa. Causal association and mechanistic pathways of MGS on PCa development and the role of Schistosoma eggs on the development of PCa remains unestablished.