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.

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 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.

Association of Schistosoma haematobium infection morbidity and severity on co-infections in pre-school age children living in a rural endemic area in Zimbabwe.

BACKGROUND: Individuals living in Schistosoma haematobium endemic areas are often at risk of having other communicable diseases simultaneously. This usually creates diagnostic difficulties leading to misdiagnosis and overlooking of schistosomiasis infection. In this study we investigated the prevalence and severity of coinfections in pre-school age children and further investigated associations between S. haematobium prevalence and under 5 mortality. METHODS: A community based cross-sectional survey was conducted in Shamva District, Zimbabwe. Using random selection, 465 preschool age children (1-5 years of age) were enrolled through clinical examination by two independent clinicians for the following top morbidity causing conditions: respiratory tract infections, dermatophytosis, malaria and fever of unknown origin. The conditions and their severe sequels were diagnosed as per approved WHO standards. S. haematobium infection was diagnosed by urine filtration and the children were screened for conditions common in the study area which included HIV, tuberculosis, malnutrition and typhoid. Data was analysed using univariate and multinomial regression analysis and relative risk (RR) calculated. RESULTS: Prevalence of S. haematobium was 35% (145). The clinical conditions assessed had the following prevalence in the study population: upper respiratory tract infection 40% (229), fever of unknown origin 45% (189), dermatophytosis 18% and malaria 18% (75). The odds of co-infections observed with S. haematobium infection were: upper respiratory tract infection aOR = 1.22 (95% CI 0.80 to 1.87), dermatophytosis aOR = 4.79 (95% CI 2.78 to 8.25), fever of unknown origin aOR = 10.63 (95% CI 6.48-17.45) and malaria aOR = 0.91 (95% CI 0.51 to1.58). Effect of schistosomiasis coinfection on disease progression based on the odds of the diseases progressing to severe sequalae were: Severe pneumonia aOR = 8.41 (95% CI 3.09-22.93), p < 0.0001, complicated malaria aOR = 7.09 (95% CI 1.51-33.39), p = 0.02, severe dermatophytosis aOR = 20.3 (95% CI 4.78-83.20):p = 0.03, and fever of unknown origin aOR = 1.62 (95%CI 1.56-4.73), p = 0.02. CONCLUSION: This study revealed an association between schistosomiasis and the comorbidity conditions of URTI, dermatophytosis, malaria and FUO in PSAC living in a schistosomiasis endemic area. A possible detrimental effect where coinfection led to severe sequels of the comorbidity conditions was demonstrated. Appropriate clinical diagnostic methods are required to identify associated infectious diseases and initiate early treatment of schistosomiasis and co-infections in PSAC.

Clinical morbidity associated with Schistosoma haematobium infection in pre-school age children from an endemic district in Zimbabwe.

OBJECTIVE: To investigate Schistosoma haematobium morbidity in infected pre-school age children and establish their disease burden. METHODOLOGY: Pre-school age children (1-5 years) who were lifelong residents of the study area and had no other infections were included in the study. Participants underwent a physical examination with clinicians blinded to their infection status. Diagnosis of S. haematobium was by urine filtration. RESULTS: The prevalence of S. haematobium was 35.1% (146/416). The clinical features observed in patients with Schistosoma haematobium were as follows: wheezes (morbidity attributable factor (AF = 93.9%), haematuria (AF = 92.6%), ascites (AF = 91.5%), atopy (AF = 76.9%), inguinal lymphadenopathy (AF = 68.4%), stunting (AF = 38.2), malnutrition (MUAC)(AF = 20%) and weight for height scales (AF = 5%). Schistosoma. haematobium infected children were at greater odds ratio of presenting with inguinal lymphadenopathy (AOR)=99.2(95% CI 24.2 to 854.5), wheezes in the chest (AOR = 35.4 95% CI 15.3 to 94.2), Distended abdomen with ascites (AOR = 23.9 95% CI 11.4 to 54), haematuria (AOR = 12.6 95% CI 11.6 to 14.1), atopy history (AOR = 5.6 95% CI 1.85 to 20.2), malnutrition (AOR = 2.3 95% CI 1.4 to 3.2) and stunting (AOR = 1.9 95% CI 1.1 to2.7). CONCLUSION: The study is novel as it demonstrates for the first time clinical morbidity markers associated with S. haematobium infection in pre-school age children. Furthermore the study adds scientific evidence to the call for inclusion of pre-school age children in schistosomiasis control programmes. These morbidity markers highlight the need for early diagnosis and screening for S. haematobium in pre-school age children.

OBJECTIF: Etudier la morbidité de Schistosoma haematobium chez les enfants d'âge préscolaire infectés et établir sa charge de morbidité. MÉTHODOLOGIE: Les enfants d'âge préscolaire (1 à 5 ans) qui avaient toujours résidents de la zone d'étude et qui n'avaient pas d'autres infections ont été inclus dans l'étude. Les participants ont subi un examen physique avec des cliniciens en aveugle sur leur état d'infection. Le diagnostic de S. haematobium a été effectué par filtration d'urine. RÉSULTATS: La prévalence de S. haematobium était de 35,1% (146/416). Les caractéristiques cliniques observées chez les patients infectés par S. haematobium étaient: respiration sifflante (facteur attribuable à la morbidité (FA = 93,9%), hématurie (FA = 92,6%), ascite (FA = 91,5%), atopie (FA = 76,9%), lymphadénopathie inguinale (FA = 68,4%), retard de croissance ( AF = 38,2), malnutrition (MUAC) (AF = 20%) et poids pour les échelles de taille (AF = 5%). Les enfants infectés par S. haematobium présentaient un rapport de cotes plus élevé de présenter une lymphadénopathie inguinale (AOR) = 99,2 ; (IC95%: 24,2 à 854,5), respiration sifflante dans la poitrine (AOR = 35,4 ; IC95%: 15,3 à 94,2), abdomen distendu avec ascite (AOR = 23,9 ; IC95%: 11,4 à 54), hématurie (AOR = 12,6 ; IC95%: 11,6 à 14,1), antécédents d'atopie (AOR = 5,6 ; IC95%: 1,85 à 20,2), malnutrition (AOR = 2,3 ; IC95%: 1,4 à 3,2) et retard de croissance (AOR = 1,9 ; IC95%: 1,1 à 2,7). CONCLUSION: L'étude est nouvelle car elle démontre pour la première fois des marqueurs cliniques de morbidité associés à une infection à S. haematobium chez des enfants d'âge préscolaire. En outre, l'étude ajoute des données scientifiques à l'appel à l'inclusion des enfants d'âge préscolaire dans les programmes de lutte contre la schistosomiase. Ces marqueurs de morbidité mettent en évidence la nécessité d'un diagnostic précoce et d'un dépistage de S. haematobium chez les enfants d'âge préscolaire.

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.