A Praziquantel Treatment Study of Immune and Transcriptome Profiles in Schistosoma haematobium-Infected Gabonese Schoolchildren.

BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms. METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed. RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness. CONCLUSIONS: Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription factors involved in anergy

First experiences in the implementation of biometric technology to link data from Health and Demographic Surveillance Systems with health facility data

BACKGROUND: In developing countries, Health and Demographic Surveillance Systems (HDSSs) provide a framework for tracking demographic and health dynamics over time in a defined geographical area. Many HDSSs co-exist with facility-based data sources in the form of Health Management Information Systems (HMIS). Integrating both data sources through reliable record linkage could provide both numerator and denominator populations to estimate disease prevalence and incidence rates in the population and enable determination of accurate health service coverage. OBJECTIVE: To measure the acceptability and performance of fingerprint biometrics to identify individuals in demographic surveillance populations and those attending health care facilities serving the surveillance populations. METHODOLOGY: Two HDSS sites used fingerprint biometrics for patient and/or surveillance population participant identification. The proportion of individuals for whom a fingerprint could be successfully enrolled were characterised in terms of age and sex. RESULTS: Adult (18-65 years) fingerprint enrolment rates varied between 94.1% (95% CI 93.6-94.5) for facility-based fingerprint data collection at the Africa Centre site to 96.7% (95% CI 95.9-97.6) for population-based fingerprint data collection at the Agincourt site. Fingerprint enrolment rates in children under 1 year old (Africa Centre site) were only 55.1% (95% CI 52.7-57.4). By age 5, child fingerprint enrolment rates were comparable to those of adults. CONCLUSION: This work demonstrates the feasibility of fingerprint-based individual identification for population-based research in developing countries. Record linkage between demographic surveillance population databases and health care facility data based on biometric identification systems would allow for a more comprehensive evaluation of population health, including the ability to study health service utilisation from a population perspective, rather than the more restrictive health service perspective

Enhanced Pro-Inflammatory Cytokine Responses following Toll-Like-Receptor Ligation in Schistosoma haematobium-Infected Schoolchildren from Rural Gabon

BACKGROUND: Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. PRINCIPAL FINDINGS: Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-alpha responses than uninfected children and significantly higher TNF-alpha to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). CONCLUSIONS: This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host's innate immune system in the context of single TLR ligation

Circulating Naturally-Occurring Anticoagulants before Treatment and after Recovery from SARS-CoV-2 Infection in Ghana

Background: Disturbance in naturally-occurring anticoagulants may contribute to the hypercoagulable state in COVID-19. This study determined the plasma antigen levels of protein C (PC), protein S (PS), antithrombin-III (AT-III), and thrombomodulin (TM) before treatment and after recovery from COVID-19. Materials and Methods: This cross-sectional study, conducted from February to August 2022 at Kumasi South Hospital, recruited sixty-five RT-PCR-confirmed COVID-19 participants. A venous blood sample was taken for full blood count (FBC) analysis using a 3-part fully automated haematology analyzer, and PC, PS, AT-III, and TM antigen levels measured using ELISA. The data were analyzed using SPSS version 26.0. P<0.05 was considered statistically significant. Results: Severe COVID-19 participants had relatively lower haemoglobin (p<0.001), RBC (p<0.001), HCT% (p<0.001) and platelets (p<0.001), but higher RDW-CV% (p=0.013), WBC (p<0.001), and absolute lymphocyte counts (p<0.001) compared to those with the non-severe form of the disease. The overall prevalence of anaemia among the participants was 58.5%, and 32 (84.2%) and 6 (15.8%) of the anaemic participants had mild and moderate anaemia respectively. Protein C (p<0.001), PS (p<0.001) and ATIII (p<0.001) levels were lower among the severe COVID-19 participants than in the non-severe group. But severe COVID-19 group had higher TM levels (p<0.001) than the non-severe group. Again, participants had higher haemoglobin (p<0.001), RBC (p<0.001), HCT% (p=0.049), absolute neutrophil count (p<0.001) and platelets (p<0.001) after recovery from COVID-19 than the values on admission. Additionally, after recovery, participants had higher levels of PC (p<0.001), PS (p<0.001), and ATIII (p<0.001), but reduced TM (p<0.001). Conclusion: Severe COVID-19 patients had higher PC, PS, and AT-III, but lower TM levels. The changes in circulating anticoagulants may contribute to the hypercoagulable state of COVID-19. Blood cell indices are negatively affected during COVID-19. Complete recovery from the SARS-CoV-2 infection normalised the haematological indices. Assessment of naturally-occurring anticoagulants and the provision of anticoagulants are recommended in the management of COVID-19.   Doi: 10.28991/SciMedJ-2022-04-04-01 Full Text: PD

Reproductive Toxicity Potentials of Methanolic Extract of Portulaca Oleracea in Male Rats: an Experimental Study

Background: Purslane is an edible widely distributed shrub and one of the herbs used in decoctions for the treatment of different ailments including infertility. However, there is a shortage of evidence to validate its reproductive effects. Objective: To investigate the effect of methanolic extract of Portulaca oleracea (MEPO) on the reproductive system of male rats. Materials and Methods: Fifteen 10-wk old male Wistar rats with an average weight of 183 gr were randomly divided into three groups (n = 5/each). Group A (the control group) received distilled water only; group B received 400 mg/kg MEPO; and group C received 800 mg/kg MEPO for 14 days. The animals Fasted overnight after the 14th day of administration and euthanized by cervical dislocation. Blood samples, sperm, testes, and epididymis were collected for serum hormones, sperm, and histological analyses. Results: There was no significant change in the serum luteinizing hormone and testosterone levels across all groups when compared to the control. However, group C showed a significant increase (p = 0.020) in follicle-stimulating hormone levels when compared to the control. There was a significant reduction (p = 0.006) in the sperm count in group C when compared with the control group. There was also a significantly reduced (p = 0.003) sperm motility in MEPO-treated groups compared to the control. While the testis showed no abnormalities in its histoarchitecture across groups, the epididymis showed some blood congestion in MEPO-treated groups. Conclusion: Portulaca oleracea showed the ability to reduce sperm count and motility at higher doses. Key words: Portulaca oleracea, Purslane, Testis, Epididymis, Rat, Sperm motility

Trends in Stress Throughout Pregnancy and Postpartum Period During the COVID-19 Pandemic: Longitudinal Study Using Ecological Momentary Assessment and Data From the Postpartum Mothers Mobile Study

BackgroundStress is associated with adverse birth and postpartum health outcomes. Few studies have longitudinally explored racial differences in maternal stress in a birthing population in the United States during the ongoing COVID-19 pandemic. ObjectiveThis study aimed to do the following: (1) assess changes in reported stress before, during, and after initial emergency declarations (eg, stay-at-home orders) were in place due to the COVID-19 pandemic, and (2) assess Black-White differences in reported stress in a pregnant and postpartum population from Southwestern Pennsylvania. MethodsWe leveraged data from the ongoing Postpartum Mothers Mobile Study (PMOMS), which surveys participants in real time throughout the pregnancy and postpartum periods via ecological momentary assessment (EMA) and smartphone technology. We analyzed data from a subset of PMOMS participants (n=85) who were either Black or White, and who submitted EMA responses regarding stress between November 1, 2019, and August 31, 2020, the time frame of this study. We divided data into four phases based on significant events during the COVID-19 pandemic: “pre” phase (baseline), “early” phase (first case of COVID-19 reported in United States), “during” phase (stay-at-home orders), and “post” phase (stay-at-home orders eased). We assessed mean stress levels at each phase using linear mixed-effects models and post hoc contrasts based on the models. ResultsOverall mean stress (0=not at all to 4=a lot) during the pre phase was 0.8 for Black and White participants (range for Black participants: 0-3.9; range for White participants: 0-2.8). There was an increase of 0.3 points (t5649=5.2, P<.001) in the during phase as compared with the pre phase, and an increase of 0.2 points (t5649=3.1, P=.002) in the post phase compared with the pre phase (n=85). No difference was found between Black and White participants in the change in mean stress from the pre phase to the during phase (overall change predicted for the regression coefficient=–0.02, P=.87). There was a significant difference between Black and White participants in the change in mean stress from the during phase to the post phase (overall change predicted for the regression coefficient=0.4, P<.001). ConclusionsThere was an overall increase in mean stress levels in this subset of pregnant and postpartum participants during the same time as the emergency declarations/stay-at-home orders in the United States. Compared to baseline, mean stress levels remained elevated when stay-at-home orders eased. We found no significant difference in the mean stress levels by race. Given that stress is associated with adverse birth outcomes and postpartum health, stress induced by the ongoing COVID-19 pandemic may have adverse implications for birthing populations in the United States. International Registered Report Identifier (IRRID)RR2-10.2196/1356

Cytokine production in response to schistosomal products in PBMC cultures.

<p>PBMCs were stimulated with schistosomal egg antigen (SEA) or adult worm antigen (AWA). White and grey boxes correspond to <i>S. haematobium</i>-free and infected children respectively with the whiskers indicating minimal and maximal concentrations. * <i>p</i><0.05; ** <i>p</i><0.01. <b>Panel A</b>: Cytokine production did not differ between groups at 24 h (mainly innate response) but the adaptive IL-10 response after 72 h of incubation to both schistosomal products was significantly higher in infected children than in <i>S. haematobium</i>-free children. Furthermore, only infected children produced a significant innate TNF-α response to schistosomal products at 24 h. These plots are not adjusted for spontaneous cytokine production. <b>Panel B</b>: After 24 h (predominantly innate), most cytokine ratios induced by schistosomal products were more anti-inflammatory than the ratios induced by medium alone. When the adaptive response had developed after 72 h however, only infected children produced significant anti-inflammatory cytokine balances while pro-inflammatory indices were lower in infected children than in uninfected children (AWA; <i>p</i><0.05).</p

General characteristics of the study population.

<p>Thick smears (n = 1) for the diagnosis of blood parasites as well as stool samples (n = 6 for Kato-Katz and n = 5 for coproculture) for the diagnosis of intestinal helminths were missing at random.</p><p>* Including one child with a <i>T. trichiura</i> - <i>N. americanus</i> co-infection.</p><p>** Including one child with a <i>T. trichiura</i> - <i>A. lumbricoides</i> co-infection.</p><p>*** Including one child with a <i>T. trichiura</i> - <i>N. americanus</i> co-infection and another one with a <i>T. trichiura</i> - <i>A. lumbricoides</i> co-infection.</p

Cytokine production in response to TLR ligands in PBMC cultures.

<p>White and grey boxes correspond to <i>S. haematobium</i>-free and infected children respectively with the whiskers indicating minimal and maximal concentrations. * <i>p</i><0.05; ** <i>p</i><0.01. <b>Panel A</b>: At 24 h, the ‘innate’ time-point, infected children produced significantly more TNF-α in response to the TLR2/1 ligand Pam3CSK4 (Pam3) compared with uninfected children. TLR-mediated IL-10 production did not significantly deviate between infection groups. When innate cytokine responses faded at 72 h, similar trends were observed. These plots were not adjusted for spontaneous cytokine production. <b>Panel B</b>: At both time points, pro-inflammatory indices (i.e. cytokine ratio induced by one of the stimuli relative to the spontaneously produced ratio) induced by the TLR2 ligands, Pam3 and FSL-1, were significantly higher in infected <i>versus</i> uninfected children.</p