Preventing maternal morbidity and mortality from preeclampsia and eclampsia particularly in low- and middle-income countries.

Preeclampsia (PE) is a complex heterogeneous disorder with overlapping clinical phenotypes that complicate diagnosis and management. Although several pathophysiological mechanisms have been proposed, placental dysfunction due to inadequate remodelling of uterine spiral arteries leading to mal-perfusion and syncytiotrophoblast stress is recognized as the unifying characteristic of early-onset PE. Placental overgrowth and or premature senescence are probably the causes of late-onset PE. The frequency of PE has increased over the last few decades due to population-wide increases in risk factors viz. obesity, diabetes, multifetal pregnancies and pregnancies at an advanced maternal age. Whilst multimodal tools with components comprising risk factors, biomarkers and sonography are used for predicting PE, aspirin is most effective in preventing early-onset PE. The incidence and clinical consequences of PE and eclampsia are influenced by socioeconomic and cultural factors, therefore management strategies should involve multi-sector partnerships to mitigate the adverse outcomes.

Identification of gene signature markers in gestational hypertension and early-onset pre-eclampsia.

INTRODUCTION: Hypertensive disorders in pregnancy (HDP) are the leading cause of perinatal mortality worldwide. Inflammatory responses induced by insufficient placental perfusion have become a focal point in understanding the pathogenesis and aetiology of HDP and developing reliable and consistent biomarkers. Therefore, this study aims to identify gene signatures linked to the pathophysiology of HDP (gestational hypertension and early and late-onset pre-eclampsia). METHODS: RNA was extracted from the maternal serum from the blood samples collected from different groups of HDP patients. A multiplex inflammation panel (255 inflammatory and housekeeping genes) and further gene expression analysis using NanoString Digital Direct Detection were done. The prominent expressions of these genes were further validated through qPCR techniques. RESULTS: NanoString analysis identified nine unique, significantly expressed genes (MAPK1, MAPK3, MAFF, HLA-DRA, IL12B, RHOA, MASP2, MEF2A and NR3C1) between specific group comparisons of different HPD classes and the normotensive groups. The qPCR showed that the HLA-DRA gene was significantly upregulated in the early-onset pre-eclamptic and gestational hypertensive group compared to its respective normotensive group. In contrast, MAFF and MEF2A were significantly downregulated in both HDPs compared to their controls. The MAPK1 gene was significantly higher in the early-onset group compared to the gestational hypertensive and normotensive groups. DISCUSSION: The upregulation of these distinctive genes in hypertensive groups compared to normotensives confirmed their diagnostic potential. Therefore, HLA-DRA, MAFF and MEF2A could be candidate markers of HDP, while the MAPK1 gene could be a differentiating marker between early-onset pre-eclampsia and gestational hypertension.

COVID-19 vaccine hesitancy among pregnant women in an antenatal clinic in Durban, South Africa.

Background: Mass administration of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most efficient intervention against the coronavirus disease 2019 (COVID-19) pandemic. Recently, vaccinations were shown to be safe and effective during pregnancy. However, vaccination rates are low in low- and middle-income countries, and vaccine hesitancy is a major limiting factor. Objectives: To investigate the rate of COVID-19 vaccine hesitancy among pregnant women. Method: A cross-sectional questionnaire-based investigation of 313 unvaccinated pregnant women attending an antenatal clinic in Durban, South Africa (SA). The questionnaire included clinical and socio-demographic data, and reasons for vaccine hesitancy were recorded and evaluated. Results: Of 313 women participating, 126 (40.3%) were vaccinated against COVID-19, 21/313 = 6.7%; for those unvaccinated, 21/187 (13.9%) were planning to be vaccinated. However, most unvaccinated women, 174 of 187 (93%), showed COVID-19 vaccine hesitancy. Conclusion: The COVID-19 vaccination hesitancy among pregnant women in Durban, SA, is exceptionally high. This requires urgent attention by the relevant health authorities (both professional health organisations and the SA Department of Health) as many countries experience different waves of the variants of SARS-CoV-2 and herd immunity may not have been achieved. Contribution: This study showed a high vaccine acceptance hesitancy rate among pregnant women in SA.

The role and expression of pro/antiangiogenic factors and microRNAs in gestational hypertension and pre-eclampsia.

OBJECTIVE: Pre-eclampsia and gestational hypertension are two common hypertensive disorders of pregnancy with pre-eclampsia accounting for high foetal and maternal morbidity and mortality rate. These disorders have an unknown aetiology and their hypertensive and end-organ pathophysiology may present too late in pregnancy. This makes the identification of early detection and differentiation markers vital. MicroRNAs have strongly been associated with pregnancy and their imbalance has been associated with the angiogenic dysregulation seen in pre-eclampsia. This study assesses the expression of pro- and antiangiogenic factors and their corresponding microRNAs in the maternal circulation of patients with pre-eclampsia and gestational hypertension. STUDY DESIGN: We analyzed angiogenic factors expression (sEng, TGF-ß, VEGF) normalized against housekeeping gene ß-actin and microRNAs (miRs: 210, 29B, 126) normalized against miR U6, potentially associated with pre-eclampsia and gestational hypertension using the targeted qPCR technique. These analytes were examined from early-onset (<34 weeks) (EOPE) (n = 12), late-onset (>34 weeks) (LOPE) (n = 12) pre-eclampsia, gestational hypertension (GH) (n = 12) and two gestationally matched normotensive groups (NG1 and 2) (n = 12) each in South African women of African ancestry. Group comparisons of experimental vs. control groups were assessed using t-test analysis for significance and represented as fold change expression. RESULTS: The relative expression in group comparisons showed significant (p < 0.05) fold change of VEGF, TGF-ß, sEng and miR126 in the EOPE vs. NG1. The GH vs. NG1 exhibited significant changes in VEGF, TGF-ß, miR126, miR210 and miR29B. The LOPE vs. NG2 showed significant relative expression in all the angiogenic factors (VEGF, TGF-ß and sEng). The GH vs. NG2 showed significant expression in VEGF and miR29B. The LOPE vs. EOPE showed significant fold changes in VEGF and miR210. Finally, only the GH vs. EOPE showed significant differences in miR210 and miR29B (p < 0.05). CONCLUSION: This study provides better insights into angiogenic factors and microRNAs specificity to the subtypes of gestational hypertensive disorders in pregnancy. Relative expression analysis of angiogenic factors and microRNAs showed possible novel characteristics of gestational hypertension, and potential common molecular and pathological profiles with pre-eclampsia. Furthermore, we postulate that sEng and miR29B could be early detection markers for pre-eclampsia and gestational hypertension, respectively.

Prevention of surgical site infection and sepsis in pregnant obese women.

Obesity is a major determinant of health outcomes and is on the increase in women worldwide. It predisposes to surgical site infection (SSI). Risk factors for the SSI include extremes of age, smoking, comorbidities such as hypertension and diabetes, inappropriate vertical abdominal and or uterine wall incisions, increased operating time, subcutaneous layer of 3 cm or more, and unnecessary use of subcutaneous drain. Most bacteria that cause SSIs are human commensals. Common organisms responsible for SSI include Staphylococcus aureus and coliforms such as Proteus mirabilis, and Escherichia coli. A surgeon's gloves post caesarean section in the obese has a preponderance of Firmicutes and Bacteroidetes, which increases SSI risk. The interaction of skin commensals and vaginal microbiome at the surgical incision site increases the risk of SSI in the obese compared to non-obese. Minimizing the risk of SSI involves modification of risk factors, timely treatment of SSI to prevent sepsis and compliance with the recommended care bundles.

Inequality in health care services in urban and rural settings in South Africa.

In low- and middle-income countries, urban and rural settings are distinct communities with the latter being more likely to have limited resources, particularly in health care services. We assessed the inequality in health care services in urban and rural settings in South Africa, highlighting the disparities between public and private health services, given that the latter are located mainly in urban settings. Rural settings suffer the highest inequality in the availability of drugs and supplies, overcrowding of health care facilities, delays in transporting patients, inadequate emergency medical services, and lack of experienced health care professionals. Rural settings also preferentially have a shortage of various levels of health care services, and increased security threats by criminals. In addition to specific remedies, the overarching key to solving these challenges is socio-economic growth, as well as visionary and compassionate leadership with integrity and accountability, which ensures policy development, implementation, monitoring, and evaluation.

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.

Pre-eclampsia: does cardiac function differ in HIV-positive and -negative women?

This review aimed to establish the impact of pre-eclampsia and HIV infection on cardiac function. Cardiovascular diseases have been reported to affect pregnancies complicated by both HIV and pre-eclampsia. Pre-eclampsia has been found to be associated with both systolic and diastolic dysfunction. Currently it has been found that there may be a dual, bidirectional pathophysiology, where placenta-mediated factors can influence cardiac function, or pre-existing cardiovascular disease can predispose to pre-eclampsia. Cardiovascular disease, HIV and pre-eclampsia are major health challenges individually and are interrelated with regard to pathophysiology. It has been found that both pre-eclampsia and HIV contribute to cardiac dysfunction as does the impact of antiretroviral therapy. Further research is needed to investigate the link between these diseases for the development of novel therapeutic interventions.

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.

COVID-19 vaccine hesitancy among pregnant women in an antenatal clinic in Durban, South Africa

Background: Mass administration of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most efficient intervention against the coronavirus disease 2019 (COVID-19) pandemic. Recently, vaccinations were shown to be safe and effective during pregnancy. However, vaccination rates are low in low- and middle-income countries, and vaccine hesitancy is a major limiting factor. Objectives: To investigate the rate of COVID-19 vaccine hesitancy among pregnant women. Method: A cross-sectional questionnaire-based investigation of 313 unvaccinated pregnant women attending an antenatal clinic in Durban, South Africa (SA). The questionnaire included clinical and socio-demographic data, and reasons for vaccine hesitancy were recorded and evaluated. Results: Of 313 women participating, 126 (40.3%) were vaccinated against COVID-19, 21/313 = 6.7%; for those unvaccinated, 21/187 (13.9%) were planning to be vaccinated. However, most unvaccinated women, 174 of 187 (93%), showed COVID-19 vaccine hesitancy. Conclusion: The COVID-19 vaccination hesitancy among pregnant women in Durban, SA, is exceptionally high. This requires urgent attention by the relevant health authorities (both professional health organisations and the SA Department of Health) as many countries experience different waves of the variants of SARS-CoV-2 and herd immunity may not have been achieved. Contribution: This study showed a high vaccine acceptance hesitancy rate among pregnant women in SA.

Unravelling the Mechanistic Role of ACE2 and TMPRSS2 in Hypertension: A Risk Factor for COVID-19.

BACKGROUND: This review explores the mechanistic action of angiotensin-converting enzyme- 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the renin-angiotensinaldosterone system (RAAS) that predisposes hypertensive patients to the adverse outcome of severe COVID-19. METHODS AND RESULTS: Entry of SARS-CoV-2 into the host cell via ACE2 disrupts the RAAS system, creating an imbalance between ACE and ACE2, with an increased inflammatory response, leading to hypertension (HTN), pulmonary vasoconstriction and acute respiratory distress. SARSCoV- 2 may also predispose infected individuals with existing HTN to a greater risk of severe COVID-19 complications. In the duality of COVID-19 and HTN, the imbalance of ACE and ACE2 results in an elevation of AngII and a decrease in Ang (1-7), a hyperinflammatory response and endothelial dysfunction. Endothelial dysfunction is the main factor predisposing hypertensive patients to severe COVID-19 and vice-versa. CONCLUSION: Despite the increase in ACE2 expression in hypertensive SARS-CoV-2 infected patients, ARBs/ACE inhibitors do not influence their severity and clinical outcomes, implicating continued usage. Future large-scale clinical trials are warranted to further elucidate the association between HTN and SARS-CoV-2 infection and the use of ARBs/ACEIs in SARS-CoV-2 hypertensive patients.

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

Maternal vaccination: A narrative review.

Background: Vaccinations in general are considered to be one of the greatest achievements in medicine, saving millions of lives globally. Aim: This narrative review highlights issues related to vaccination in pregnancy and provides information on those vaccines registered for use in pregnancy. Method: Published articles on vaccinations in pregnancy are included in this review. The search engines used included PubMed, Medline, Google Scholar, and ScienceDirect. Results: Vaccinations during pregnancy are more likely to be administered in high income countries (HICs) compared to low-income countries (LICs) due to easier access to healthcare services and better communicable disease awareness. Maternal and perinatal morbidity and mortality rates associated with infectious diseases are higher in LICs with access to maternal care services, infrastructure and hospital equipment lacking in these settings. Conclusion: Suitable vaccinations are recommended for use in pregnancy to prevent harm to women, their foetuses and newborns from some communicable diseases, and they have resulted in declines in maternal and infant morbidity and mortality. Furthermore, this review has shown that vaccination during pregnancy is not only safe for both the woman and her foetus but also effective. Therefore, health professionals and national governments should strongly consider approved vaccinations prior to or during pregnancy. Contribution: This review provides insight on the necessity of vaccination during pregnancy. In addition, it urges health professionals to inform patients of the importance of regular antenatal visits, and to receive the required vaccinations for a better health outcome.

Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review.

This review explores the role of transmembrane neuropilin-1 (NRP-1) in pregnancy, preeclampsia (PE), human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Since these conditions are assessed independently, this review attempts to predict their comorbid clinical manifestations. Dysregulation of NRP-1 contributes to the pathogenesis of PE by (a) impairing vascular endothelial growth factor (VEGF) signaling for adequate spiral artery remodeling and placentation, (b) inducing syncytiotrophoblast (ST) cell apoptosis and increasing ST-derived microparticle circulation and (c) by decreasing regulatory T cell activity predisposing maternal immune intolerance. Although NRP-1 is upregulated in SARS-CoV-2 placentae, its exploitation for SARS-CoV-2 internalization and increased infectivity may alter angiogenesis through the competitive inhibition of VEGF. The anti-inflammatory nature of NRP-1 may aid its upregulation in HIV-1 infection; however, the HIV-accessory protein, tat, reduces NRP-1 expression. Upregulated NRP-1 in macrophages and dendritic cells also demonstrated HIV-1 resistance/reduced infectivity. Notably, HIV-1-infected pregnant women receiving antiretroviral therapy (ART) to prevent vertical transmission may experience immune reconstitution, impaired decidualization, and elevated markers of endothelial injury. Since endothelial dysfunction and altered immune responses are central to PE, HIV-1 infection, ART usage and SARS-CoV-2 infection, it is plausible that an exacerbation of both features may prevail in the synergy of these events. Additionally, this review identifies microRNAs (miRNAs) mediating NRP-1 expression. MiR-320 and miR-141 are overexpressed in PE, while miR-206 and miR-124-3p showed increased expression in PE and HIV-1 infection. Additionally, miR-214 is overexpressed in PE, HIV-1 and SARS-CoV-2 infection, implicating treatment strategies to reduce these miRNAs to upregulate and normalize NRP-1 expression. However, inconsistencies in the data of the role and regulation of miRNAs in PE, HIV-1 and SARS-CoV-2 infections require clarification. This review provides a platform for early diagnosis and potential therapeutic intervention of PE, HIV-1, and SARS-CoV-2 infections independently and as comorbidities.

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry.

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-ß1 in maternal serum samples using ELISA technique. Serum protein markers TGF-ß1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-ß1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted.Impact statementWhat is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders.What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension.What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

South African medicinal plants displaying angiotensin-converting enzyme inhibition: Potential use in the management of preeclampsia.

In resource-limited settings, such as South Africa, hypertensive disorders of pregnancy such as preeclampsia, is the most common direct cause of maternal deaths. Current management strategies of preeclampsia primarily involve the use of pharmaceutical drugs, which are frequently associated with undesirable side-effects. Moreover, these drugs are often not easily accessible due to financial and economic constraints. Consequently, many patients rely on traditional medicine obtained from medicinal plants to manage health-related conditions. Angiotensin-converting enzyme inhibitors are widely used drugs for the management of preeclampsia. This narrative review aims to highlight the use of indigenous medicinal plants from South Africa with Angiotensin-converting enzyme inhibitory activity whilst also evaluating their potential use in the treatment of hypertension in pregnancy. This information will influence traditional healers and sangomas in their patient management. Furthermore, the antihypertensive potential of these plants will be unraveled thus facilitating the development of new naturally occurring pharmaceutical products to reduce maternal and neonatal mortality and morbidity.

COVID-19 death: A novel method of improving its identification when a patient has multiple diagnoses.

Assigning a primary cause of death to a deceased patient who had multiple principal diagnoses including coronavirus disease 2019 (COVID-19) is challenging because of the difficulty in selecting the most appropriate cause. To proffer a solution, the authors reviewed the literature on assigning a primary cause of death. In 2015, the Nnabuike-Jagidesa (NJ) model II was devised to improve the International Classification of Diseases and related health problems, 10th revision (ICD-10) guideline on how to assign a primary cause of death. The NJ model II stipulates that when there are multiple diagnoses with no plausible explanation that one of the illnesses could have resulted in the other clinical conditions, the single most appropriate primary cause of death is the condition with the highest case fatality ratio in that setting. In the index report, the authors opine that if the case fatality ratios are similar, the following objective criteria (listed in the order of priority) should be used to assign a primary cause of death: condition with the highest infection fatality ratio, condition that was the main indication for the last acute surgical or invasive procedure performed (during the course of the same ill-health) before the death and the disease that theoretically affects the highest number of body organs. Additionally, a clinical descriptor should be used when none of the objective criteria are satisfied. This novel approach, termed the modified NJ model II, is expected to improve the objectivity and reproducibility of the assigned primary cause of death in a deceased who had multiple diagnoses, which may include COVID-19.

Prevalance of abnormal vault cytology after hysterectomy for cervical intraepithelial neoplasia, Pietermaritzburg.

BACKGROUND: A simple hysterectomy is considered the definitive treatment modality for cervical intraepithelial neoplasia (CIN). However, it is associated with recurrence of vaginal intraepithelial neoplasia (VAIN) of up to 7.4%. We sought to determine recurrence rates of VAIN, in women living with HIV (WLWH) and non-infected women. METHODS: This was a descriptive retrospective review of patients who received a simple hysterectomy for CIN between January 2015 and December 2017 in Pietermaritzburg. RESULTS: Fifty-eight files were reviewed. Forty-two (72.4%) WLWH were seen; amongst those, 76.2% were virally suppressed. Abnormal vault cytology was only seen in patients with CIN grades 2 and 3. The recurrence rates for high-grade squamous intraepithelial lesion (HSIL) were 6.1% and 5.0% at 6 and 12 months, respectively. Human immunodeficiency virus co-infection was associated with 26.2% versus 13.3% of abnormal vault cytology compared to the HIV-negative counterparts (p = 0.164). Virologically suppressed patients had more abnormal cytology (28.1% vs. 0%) compared to the unsuppressed patients. There was a 17.2% and 65.5% loss- to follow-up rates at 6 and 12 months, respectively. Recurrence of premalignant lesions was noted amongst those who had the abdominal approach. CONCLUSION: The recurrence rates were comparable to the previous literature. A 6-month cytology follow-up showed no added benefit. Human immunodeficiency virus co-infection didn't show a statistical significance on the recurrence rates; however, more structured studies are required to address this. Primary health care-based post operative surveillance can be a solution to address high loss to follow-up.