Assessment of urine metabolite biomarkers for the detection of S. haematobium infection in pre-school aged children in a rural community in Zimbabwe.

BACKGROUND: Early diagnosis of urogenital schistosomiasis is key to its control and elimination. The current gold standard microscopic examination techniques lack sensitivity in detecting light Schistosomiasis infections in pre-school aged children thus it is urgent to develop diagnostic tools that may be integrated into control programs. In this study, we evaluated the diagnostic performance of urine metabolite biomarkers using a chemical reagent strip in the detection of S. haematobium infection in pre-school aged children. METHODS: A case-control study was conducted involving 82 pre-school aged children that were age and sex matched. Urine samples were collected for 3 consecutive days and were evaluated using urine filtration gold techniques as the gold standard method. The samples were simultaneously measured for metabolite biomarkers specifically haematuria, proteins, ketones, nitrites, glucose, bilirubin and urobilinogen using chemical reagent strips. Pearson correlation test was used to measure the relationship between S. haematobium infection and the urine metabolite biomarkers. RESULTS: The diagnostic performance of urine biomarkers were correlated with the microscopic examination urine filtration technique. Haematuria (r = 0.592, p = 0.0001) and proteinuria (r = 0.448, p = 0.0001) were correlated to S. haematobium infection. Negative correlations with p > 0.05 were recorded for ketones and urobilinogen. Highest sensitivity was 65.9% (CI, 49.4 - 79.9) for haematuria whilst protein (albumin) biomarker had a lower specificity value of 43.9% (28.5 - 60.3). Inversely, highest sensitivity was 87.8% (73.8 - 95.9) for proteinuria whilst haematuria had a lower sensitivity value of 82.9% (67.9 - 92.8). The positive predictive values ranged from 57.7% (41.6 - 72.2) to 79.4% (65.5 - 88.7) whereas negative predictive values ranged from 70.8% (60.8 - 79.2) to 52.0% (48.7 - 55.3). With respect to diagnostic efficiency, haematuria had a fair diagnostic performance with an area under the curve of 0.76 followed by proteinuria with proteinuria whilst the remaining metabolites fail discriminating ability with an area under the curve of less than 0.5. CONCLUSION: Although haematuria and protein biomarkers in urine are moderately sensitive and specific, they are important morbidity indicators of urogenital schistosomiasis in pre-school aged that may be utilised during screening in schistosomiasis control programs. We recommend comprehensive analysis of biomarkers using metabolomics techniques to identify novel urine biomarkers.

Is the Complement System Dysregulated in Preeclampsia Comorbid with HIV Infection?

South Africa is the epicentre of the global HIV pandemic, with 13.9% of its population infected. Preeclampsia (PE), a hypertensive disorder of pregnancy, is often comorbid with HIV infection, leading to multi-organ dysfunction and convulsions. The exact pathophysiology of preeclampsia is triggered by an altered maternal immune response or defective development of maternal tolerance to the semi-allogenic foetus via the complement system. The complement system plays a vital role in the innate immune system, generating inflammation, mediating the clearance of microbes and injured tissue materials, and a mediator of adaptive immunity. Moreover, the complement system has a dual effect, of protecting the host against HIV infection and enhancing HIV infectivity. An upregulation of regulatory proteins has been implicated as an adaptive phenomenon in response to elevated complement-mediated cell lysis in HIV infection, further aggravated by preeclamptic complement activation. In light of the high prevalence of HIV infection and preeclampsia in South Africa, this review discusses the association of complement proteins and their role in the synergy of HIV infection and preeclampsia in South Africa. It aims to identify women at elevated risk, leading to early diagnosis and better management with targeted drug therapy, thereby improving the understanding of immunological dysregulation.

Association of angiogenic factors (placental growth factor and soluble FMS-like tyrosine kinase-1) in preeclamptic women of African ancestry comorbid with HIV infection.

BACKGROUND: Preeclampsia is a significant cause of maternal and fetal morbidity and mortality, particularly in low- and middle-income countries like South Africa. AIM: The aim of our study was to investigate the association between placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) in South African preeclamptic women of African ancestry, comorbid with HIV infection. METHODS: The study population consisted of women attending a regional hospital in Durban, South Africa, stratified by pregnancy type (normotensive pregnant and preeclampsia) and HIV status. Preeclampsia was defined as new-onset hypertension and proteinuria. DNA was obtained from whole blood. The SNPs of interest were rs722503 in sFlt-1 and rs4903273 in PlGF. RESULTS: Our findings suggest that single nucleotide polymorphisms of rs722503 analysis show no significant associations between the genotypic frequencies of rs722503 variants and preeclampsia risk in either HIV-negative or HIV-positive groups of women of African ancestry. Similarly, the rs493273 polymorphism showed no significant association with preeclampsia risk in either HIV-negative or HIV-positive pregnant women. Additionally, comparisons of dominant, recessive, and over-dominant allele models did not reveal significant associations. These findings suggest that these genetic variants may not significantly contribute to preeclampsia development in this African ancestry population. However, significant differences were observed in the rs4903273 genotype frequencies between normotensive and preeclamptic women, regardless of HIV status, over dominant alleles AA + GG vs AG showed a significant difference [OR = 2.706; 95% Cl (1.199-5.979); adjusted p = 0.0234*], also in normotensive compared to EOPE (OR = 2.804; 95% Cl (1.151-6.89) p = 0.0326* and LOPE (OR = 2.601; 95% Cl (1.0310-6.539) p = 0.0492*), suggesting that they may be the potential role of this variant in preeclampsia susceptibility. CONCLUSION: The findings suggest that the rs722503 and rs493273 polymorphisms do not significantly contribute to preeclampsia susceptibility in HIV-negative or HIV-positive pregnant women. However, the rs4903273 genotype frequencies showed notable differences between normotensive and preeclamptic women, indicating a potential association with preeclampsia development in the African ancestry population irrespective of HIV status.

Is renal dysfunction amplified in an arginine vasopressin induced rat model of preeclampsia?

Renal dysfunction is important in preeclampsia (PE) pathophysiology and has not been fully explored in the arginine vasopressin (AVP) rat model of PE. This study aimed to determine kidney toxicity associated with this model. Female Sprague Dawley rats (n = 24) were subcutaneously infused with AVP or saline for 18 days. Urine samples (GD8, 14 and 18) were used to determine the levels of albumin, VEGF-A, clusterin, NGAL/Lipocalin-2, KIM-1, cystatin C, TIMP-1, ß2M and OPN via Multiplex ELISAs. Albumin, and NGAL/lipocalin-2 were significantly elevated in the PAVP vs PS group on GD14 and GD18 (p < 0.001) respectively. VEGF-A significantly decreased in the pregnant vs non-pregnant groups on GD14 and 18 (p < 0.001). Clusterin (p < 0.001) and OPN (p < 0.05) were significantly higher in the PAVP vs PS group on GD18. Cystatin C and KIM-1 are significantly upregulated in the PAVP vs PS groups throughout gestation (p < 0.05). ß2M is significantly elevated in the PAVP vs PS group on GD14 and 18 (p < 0.05). AVP elevated the urinary levels of the kidney injury biomarkers and replicated the renal dysfunction associated with PE development. Our findings confirm the potential applications of this model in studying the mechanisms underlying renal damage in PE.

Placental neutrophil reverse trans-migration and maternal serum neutrophil extracellular trap expression in HIV infection co-morbid pre-eclampsia in women of African ancestry.

Neutrophil extracellular traps (NETs) and placental neutrophil reverse transmigration (r-TM) are implicated in the pathogenesis of pre-eclampsia (PE). However, the role of the comorbidity of PE and human immunodeficiency virus (HIV) infection in placental neutrophil r-TM and serum NETs remains unknown. Human placental tissue (n = 160) and serum (n = 80) samples were obtained post-ethical approval and divided by pregnancy type and HIV status and across the study population. Immunohistochemistry and morphometry were performed to localize and quantify junctional adhesion molecule-C (JAM-C) expression as an inverse marker of neutrophil r-TM within placental villi. An enzyme-linked immunosorbent assay (ELISA) was performed to quantify the concentration of citrullinated histone H3 (cit-H3) as a marker of NETs. GraphPad Prism (version 8.0.2) was used to compare the results, and a p value of p < 0.05 was considered statistically significant. The localization of JAM-C was observed on the syncytiotrophoblasts (STBs) and endothelial cells of placental villi. The immunoexpression of JAM-C was elevated in PE vs. normotensive (N) placentae. In the exchange villi, JAM-C immunoexpression was higher in the N+ve vs. N-ve group. However, in PE comorbid HIV infection, JAM-C expression was lower in the PE+ve vs. PE-ve group. Citrullinated histone-H3 concentration was lower in the N+ve vs. N-ve group but elevated in early-onset PE (EOPE)+ve vs. late-onset PE (LOPE)+ve group. These results indicate that PE and HIV-infected placentae individually express elevated JAM-C, manifesting in less neutrophil r-TM. However, in exchange villi of PE comorbid with HIV infection reduced JAM-C enhances neutrophil r-TM, thus supporting the synergistic effect of PE comorbid with HIV.

Genetic Appraisal of RAAS-Associated SNPs: REN (rs16853055), AGT (rs3789678) and ACE (rs4305) in Preeclamptic Women Living with HIV Infection.

PURPOSE OF REVIEW: The primary goal of this review article was to determine whether the three RAAS-associated SNPs, Renin-rs16853055, AGT-rs3789678 and ACE-rs4305 are genetically linked to the development of hypertension in preeclampsia. The secondary goal was to establish if there was a link between these SNPs and HIV infection. RECENT FINDINGS: There is a paucity of findings related to the aforementioned SNPs and preeclampsia. There are no recent findings on the rs16853055 renin polymorphism. The rs3789678 angiotensinogen polymorphism correlated significantly with gestational hypertension. The rs4305 ACE polymorphism showed no significant association with the development of pregnancy-induced hypertension. There are conflicting findings when determining the relationship between ethnicity and the predisposition of preeclampsia and hypertension in relation to the discussed RAAS-associated SNPs. To date, the association between RAAS-associated SNPs and preeclamptic women co-morbid with HIV in South Africa has revealed that certain alleles of the AGT gene are more prominent in HIV-infected PE compared to normotensive pregnant HIV-infected women.

Placental progesterone and its receptor in HIV-infected pre-eclamptic women.

Given the high prevalence of HIV infection and pre-eclampsia (PE) in South Africa, this study evaluated and compared the placental immunostaining of progesterone (P) and progesterone receptors (PR) in the synergy of HIV-infected PE compared to normotensive pregnant women using immunohistochemistry interfaced with morphometric image analysis. Progesterone immunostaining was expressed widely across exchange and conducting villi within mesenchymal, endothelial, and trophoblast cells. In contrast, PR was expressed within syncytiotrophoblasts and was absent within endothelial cells. In exchange villi, P and PR immuno-expression was significantly lower in PE compared to the normotensive group (p = < 0.0001 and p = < 0.0001, respectively) and within the early-onset pre-eclampsia (EOPE) compared to the late-onset pre-eclampsia (LOPE) group (p = < 0.0001 and p = < 0.0001, respectively). Progesterone immuno-expression was significantly lower in the HIV+ compared to the HIV- group (p = < 0.0001), whilst PR was non-significant. In conducting villi, P and PR immuno-expression was significantly lower in the EOPE compared to the LOPE group (p = < 0.0001 and p = < 0.0001, respectively) and in the HIV+ compared to the HIV- group (p = < 0.0001 and p = 0.0009, respectively). Progesterone immuno-expression was slightly higher in the PE compared to normotensive group, and PR immuno-expression was non-significant. There was a significant difference between P and PR within exchange versus conducting villi regardless of pregnancy type, with villi type accounting for 34.47% and 15.28% of total variance for P and PR, respectively. Placental P and PR immuno-expression is downregulated in the duality of PE and HIV+ infection. The use of combined antiretroviral therapy (cART) may result in defective P synthesis, which causes insufficient binding to its receptors. Consequently, PI3K/AKT, JAK-STAT, and MAPK signalling pathways are affected, impairing trophoblast invasion and leading to pre-eclampsia development. Notably, the decrease in P and PR immuno-expression in EOPE validates their effect on placentation.

Hesperidin improves physiological outcomes in an arginine vasopressin rat model of pre-eclampsia.

BACKGROUND: Hesperidin, a flavanone commonly found in citrus fruits and herbal formulations, has emerged as a potential new therapeutic agent for modulating several diseases. Since pre-eclampsia is a growing public health threat, it may negatively impact the economy and increase the disease burden of South Africa. Phytocompounds are easily accessible, demonstrate minimal side effects, and may confer novel medicinal options as a treatment and preventive preference. OBJECTIVE: To investigate the physiological, biochemical, and hematological outcomes of hesperidin in an arginine vasopressin (AVP)-induced rodent model of pre-eclampsia. METHODS: Female Sprague-Dawley rats were surgically implanted with mini-osmotic pumps to deliver AVP (200 ng/h) subcutaneously. Animals were treated with hesperidin at 200 mg/kg.b.w via oral gavage for 14 days. Systolic and diastolic blood pressures were measured on GD 7, 14, and 18 using a non-invasive tail-cuff method and were euthanized on GD 21. RESULTS: The findings showed that hesperidin administration significantly decreased blood pressure (P < 0.05) and urinary protein levels in pregnant rats (P < 0.001). Placental and individual pup weight also increased significantly in the pregnant hesperidin-treated groups compared to AVP untreated groups (P < 0.001). Biochemical and hematological markers such as white blood cell count and lymphocyte levels differed significantly (P < 0.05) in AVP groups treated with and without hesperidin. CONCLUSION: Our results suggest that hesperidin is an antihypertensive agent with modes of action associated with its diuretic and blood pressure lowering effects and reduction of proteinuria in AVP-induced pre-eclamptic rats.

Is the central complement component C3 altered in the synergy of HIV infection and preeclampsia?

Objective: In light of complement activation in preeclampsia and HIV infection, this study evaluates the concentration of complement component 3 (C3) in HIV-associated preeclampsia. Method: The study population (n = 76) was equally stratified by pregnancy type (normotensive pregnant and preeclampsia) and by HIV status (HIV positive and HIV negative). The plasma concentration of C3 was determined using a Bioplex immunoassay procedure. Results: We report a significant increase in C3 concentration in the HIV-negative versus the HIV-positive groups (p < 0.05), regardless of pregnancy type. However, based on pregnancy type and irrespective of HIV status, C3 concentration was similar between normotensive versus preeclampsia. Concentration of C3 was significantly increased in the HIV-positive preeclamptic compared HIV-negative preeclamptic groups (p = 0.04). The correlation of C3 with all study groups was non-significant. Conclusion: This study demonstrates that C3 was upregulated in HIV-associated PE compared to HIV- associated normotensive pregnancies. The dysregulation of C3 expression by HIV infection may be attributed to antiretroviral therapy.

Differential expression of the angiotensin receptors (AT1, AT2, and AT4) in the placental bed of HIV-infected preeclamptic women of African ancestry.

The Renin-Angiotensin-Aldosterone System (RAAS) is implicated in the pathophysiology of preeclampsia (PE). There is a paucity of data on uteroplacental angiotensin receptors AT1-2 and 4. We evaluated the immunoexpression of AT1R, AT2R, and AT4R within the placental bed of PE vs. normotensive (N) pregnancies stratified by HIV status. Placental bed (PB) biopsies (n = 180) were obtained from N and PE women. Both groups were stratified by HIV status and gestational age into early-and late onset-PE. Immuno-labeling of AT1R, AT2R, and AT4R was quantified using morphometric image analysis. Immunostaining of PB endothelial cells (EC) and smooth muscle cells of spiral arteries (VSMC) displayed an upregulation of AT1R expression compared to the N group (p < 0.0001). Downregulation of AT2R and AT4R expression was observed in PE vs. N group (p = 0.0042 and p < 0.0001), respectively. AT2R immunoexpression declined between HIV+ve and HIV-ve groups, while AT1R and AT4R displayed an increase. An increase in AT1R expression was noted in the EOPE-ve/+ve and LOPE-ve/+ve compared to N-ve/N+ve. In contrast, AT2R and AT4R expression decreased in EOPE-ve/+ve and LOPE-ve/+ve compared to N-ve/N+ve. We demonstrate a significant downregulation of AT2R and AT4R with a concomitant elevated AT1R immunoexpression within PB of HIV-infected PE women. In addition, a decline in AT2R and AT4R with an increase in AT1R immunoexpression in PE, EOPE, and LOPE vs. normotensive pregnancies, irrespective of HIV status. Thus highlighting differential immunoexpression of uteroplacental RAAS receptors based on pregnancy type, HIV status, and gestational age.

Immunoexpression of neuropilin-1 in the chorionic villi of HIV-infected preeclamptic South African women of African ancestry.

Neuropilin-1 (NRP-1) is an essential regulator of maternal immune tolerance, placentation, and angiogenesis. Its dysregulation in preeclampsia (PE) and human immunodeficiency virus (HIV) infection implicates NRP-1 in disease susceptibility and progression. Therefore, this study investigates placental NRP-1 immunoexpression in HIV-complicated preeclamptic pregnancies in South African women of African ancestry receiving antiretroviral therapy. Immunohistochemistry of recombinant anti-neuropilin-1 antibody was performed on placental tissue from 30 normotensive and 60 early onset (EOPE) and late-onset (LOPE) preeclamptic women stratified by HIV status. Qualitative analysis of NRP-1 immunostaining within the chorionic villi revealed a predominant localization in trophoblasts and syncytial knots as well as endothelial, fibroblast-like, and Hofbauer cells. Following morphometric evaluation, we report that PE and HIV infection and/or antiretroviral usage independently downregulate placental NRP-1 immunoexpression; however, as a comorbidity, this decline is further augmented within the conducting and exchange villi. Furthermore, reduced immunoexpression of NRP-1 in EOPE compared with LOPE villi may be due to maternal-fetal maladaptation. It is plausible that the decreased NRP-1 immunoexpression in PE placentae facilitates syncytiotrophoblast apoptosis and subsequent deportation of NRP-1 into the maternal circulation, contributing to the anti-angiogenic milieu of PE. We hypothesize that the intense NRP-1 immunoreactivity observed in Hofbauer cells at the maternal-fetal interface may contribute to the natural prevention mechanism of HIV vertical transmission.

The Clinical Value of Rodent Models in Understanding Preeclampsia Development and Progression.

PURPOSE OF REVIEW: Preeclampsia (PE) is a leading global cause of maternal and fetal morbidity and mortality. The heterogeneity of this disorder contributes to its elusive etiology. Due to the ethical constraints surrounding human studies, animal models provide a suitable alternative for investigation into PE pathogenesis and novel therapeutic strategies. The purpose of this review is to compare and contrast the various rodent models used to study PE, in order to demonstrate their value in investigating and identifying different characteristics of this disorder. RECENT FINDINGS: Several approaches have been employed to create an appropriate animal model of PE, including surgical, genetic manipulation, and pharmacological methods in an attempt to mimic the maternal syndrome. Despite the absence of a model to completely model PE, these models have provided valuable information concerning various aspects of PE pathogenesis and novel therapeutic strategies and have led to the discovery of potential predictive markers of PE. Rodent and murine models have contributed significantly to the study of the pathology associated with specific aspects of the disorder. As a single fully encompassing animal model of PE remains absent, the use of a combination of models has potential value in understanding its etiology as well as in new treatment and management strategies.

Kidney injury molecule-1 and podocalyxin dysregulation in an arginine vasopressin induced rodent model of preeclampsia.

OBJECTIVE: To assess renal injury in an arginine vasopressin (AVP) rodent model of preeclampsia. STUDY DESIGN: Urinary expression of kidney injury molecule-1 (KIM-1), urinary protein and creatinine was determined in rodents (n = 24; pregnant AVP, pregnant saline, non-pregnant AVP and non-pregnant saline), which received a continuous dose of either AVP or saline via subcutaneous mini osmotic pumps for 18 days, using a Multiplex kidney toxicity immunoassay. Renal morphology was assessed using haematoxylin and eosin staining and transmission electron microscopy. The immunolocalization of KIM-1 and podocalyxin was qualitatively evaluated using immunohistochemistry. RESULTS: Urinary KIM-1 and urinary protein levels were significantly increased in treated vs. untreated rats on gestational days 8 (p < 0.05), 14 (p < 0.001) and 18 (p < 0.001). The pregnant rats displayed a lower trend of creatinine compared to the non-pregnant groups, albeit non-significantly. KIM-1 was immunolocalized in the proximal convoluted tubules in AVP treated vs. untreated groups. In contrast, podocalyxin was weakly immunostained within glomeruli of pregnant AVP treated vs. pregnant untreated rats. Histological evaluation revealed reduced Bowman's space, with some tubular and blood vessel necrosis in the pregnant treated group. Ultrastructural observations included effacement and fusion of podocyte foot processes, glomerular basement membrane abnormalities, podocyte nuclear crenations, mitochondrial oedema and cristae degeneration with cytoplasmic lysis within treated tissue. CONCLUSION: Our findings demonstrate region-specific kidney injury particularly glomerular impairment and endothelial injury in AVP-treated rats. The findings highlight the utility of this model in studying the mechanisms driving renal damage in a rodent model of preeclampsia.

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.

The complement system in preeclampsia: a review of its activation and endothelial injury in the triad of COVID-19 infection and HIV-associated preeclampsia.

This review assesses the complement system and its activation, with the pathological features of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus (HIV) infection and preeclampsia (PE). The complement system is the first defensive response by the host innate immune system to viral pathogens, including SARS-CoV-2. SARS-CoV-2 entry results in the release of pro-inflammatory cytokines and chemical mediators to create a "cytokine storm". Endothelial cell (EC) dysfunction and cell-mediated injury are also present. These factors cause an exacerbated inflammatory state. During HIV infection and PE, various complement components are elevated, causing a hyper-inflammatory state. Furthermore, EC dysfunction and cell-mediated injury are also present. The similarities in pathological aspects of these three disorders may emanate from excessive complement activation. This review serves as a platform for further research on the complement system, coronavirus disease 2019, HIV infection and PE.

Stress-Sensitive Regulators of Fetal Neurodevelopment in HIV and Preeclampsia: An Immunocytochemical Appraisal of Placental OGT and T4 Levels.

Preeclampsia and HIV are a significant burden to maternal health globally, especially in low-middle income countries such as South Africa. In the KwaZulu-Natal province, SA antenatal HIV prevalence is 41.1%, while PE is 12%. PE and HIV infections are maternal stress and inflammation that impact placental function and fetal development. Therefore, this study investigated the impact of the comorbidity of PE and HIV on placental stress and neurodevelopment. Placentae were obtained from four cohorts of pregnant women: normotensive HIV negative, normotensive HIV positive, preeclamptic HIV negative, and preeclamptic HIV positive. The placental tissue sections were immunostained for OGT and T4. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were higher in PE vs. the normotensive groups, irrespective of HIV status. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental efficiency coefficient. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were statistically higher in the PE compared to the normotensive. No significant differences were observed between HIV positive and HIV negative groups. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental coefficient. Furthermore, considerable upregulation in the placental expression of OGT in both the conducting and exchange villi of PE and concomitant downregulation in HIV-positive patients compared with Normotensive and HIV-negative individuals, respectively. Our results provide inferential evidence on the dysregulation of OGT in the comorbidity of PE and HIV. This may mediate a compromised programmed outcome of an adverse maternal environment during pregnancy and consequently affect fetal development.

Gene polymorphisms within regions of complement component C1q in HIV associated preeclampsia.

OBJECTIVE: This study investigates the association of C1q gene (rs292001 and rs294183) polymorphisms in HIV infected and uninfected preeclamptic women of African ancestry. MATERIALS AND METHODS: The study population consisted of 325 pregnant women of African ancestry grouped into 145 normotensive pregnant women (72 HIV uninfected normotensive, 73 HIV infected normotensive) and 180 preeclamptic pregnant women (103 HIV uninfected preeclamptics, 77 HIV infected preeclamptics). Preeclamptic pregnant women were further sub-grouped into 79 early-onset preeclampsia (EOPE) (40 HIV uninfected EOPE, 39 HIV infected EOPE) and 101 late-onset preeclampsia (LOPE) (63 HIV uninfected LOPE, 38 HIV infected LOPE). Genotyping of complement C1q gene polymorphisms (rs292001 and rs294183) was detected using a TaqMan® SNP Genotyping assay from purified DNA. RESULTS: No significant differences in allelic and genotype frequencies of rs292001 and rs294183 between preeclamptic and normotensive women were observed. Likewise, there were no significant differences in allelic and genotype frequencies between HIV infected normotensive vs HIV infected preeclampsia and HIV uninfected normotensive vs HIV uninfected preeclampsia for both SNPs. However, the odds ratio of preeclamptic women having the GA genotype was 1:2. CONCLUSION: We demonstrate that SNPs of the C1q gene (rs292001 and rs294183) are not associated with the pathogenesis of PE development in women of African ancestry. The role ofC1qrs292001 heterozygous GA is highlighted (with and without HIV infection) may affect susceptibility to PE development. Notably, this dysregulation may affect C1q translation and protein output thus influencing the downstream role of the complement system and functional immunology in HIV infection comorbid with PE.

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.

Circulatory and Placental Expression of Soluble Fms-like Tyrosine Kinase- 1 and Placental Growth Factor in HIV-infected Preeclampsia.

An imbalance between angiogenic and anti-angiogenic factors plays a fundamental role in the pathogenesis of preeclampsia (PE). Studies have shown a dysregulation of sFlt-1 and placental growth factor (PlGF) in PE. However, there are differing reports on the levels of these pro-/antiangiogenic factors in HIV-infected preeclamptic and normotensive pregnancies, possibly due to highly active antiretroviral therapy (HAART) and its immune reconstitution effect. The study aimed to investigate the effect of hypertension and ARVs on circulating and placental pro- and antiangiogenic factors in HIV-infected PE. The level of sFlt-1 expression is elevated in PE compared to normal pregnancies. PlGF was altered by placental dysfunction. Antiretroviral therapy does not impact the angiogenic shift in PE development. The angiogenic imbalance evident in the circulatory system by higher sFlt-1 compared to PlGF levels is replicated in the placenta by reduced expression of PlGF receptors in comparison to sFlt-1 receptors. However, there is a lack of data that explore the relationship between HAART and anti-angiogenic factors in the placenta and the circulation of PE comorbid with HIV infection.

Placental Morphology and Morphometry: Is It a Prerequisite for Future Pathological Investigations?

Successful pregnancy is dependent on implantation, nutrient and gas exchange, as well as fetal protection from the immunologic attack. Placental pathologies and preterm delivery closely correlate with the size and shape of the placenta. Additionally, normal vaginal microbiota is disturbed during viral insults such as SARS-CoV-2 and HIV, with consequent placental anomalies. This chapter focuses on placental development, morphology, and pathology while also investigating placental bed structure and function. Placental anomalies with regard to HIV-1 and SARS-CoV-2 infection and placental morphometric image analysis and its relevance for verification of placental pathology are explored. Since image analysis remains optional for routine diagnostic purposes, authentication of placental appraisal warrants the use of measurable predefined definitions. Immunohistochemical analyses of placental morphology and angiogenic, epithelial, and apoptotic mechanisms facilitate research into etiopathogenetic pathways involved in placental anomalies with a focus on discovering novel diagnostic foci. Thus, image analyses as an adjunct to complement pathological investigations are recommended.