Planned delivery or expectant management for late preterm pre-eclampsia in low-income and middle-income countries (CRADLE-4): a multicentre, open-label, randomised controlled trial

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to evaluate whether planned delivery between 34+ 0 and 36+ 6 weeks’ gestation can reduce maternal mortality and morbidity without increasing perinatal complications in India and Zambia. / Methods: In this parallel-group, multicentre, open-label, randomised controlled trial, we compared planned delivery versus expectant management in women with pre-eclampsia from 34+ 0 to 36+ 6 weeks’ gestation. Participants were recruited from nine hospitals and referral facilities in India and Zambia and randomly assigned to planned delivery or expectant management in a 1:1 ratio by a secure web-based randomisation facility hosted by MedSciNet. Randomisation was stratified by centre and minimised by parity, single-fetus pregnancy or multi-fetal pregnancy, and gestational age. The primary maternal outcome was a composite of maternal mortality or morbidity with a superiority hypothesis. The primary perinatal outcome was a composite of one or more of: stillbirth, neonatal death, or neonatal unit admission of more than 48 h with a non-inferiority hypothesis (margin of 10% difference). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The trial was prospectively registered with ISRCTN, 10672137. The trial is closed to recruitment and all follow-up has been completed. / Findings: Between Dec 19, 2019, and March 31, 2022, 565 women were enrolled. 284 women (282 women and 301 babies analysed) were allocated to planned delivery and 281 women (280 women and 300 babies analysed) were allocated to expectant management. The incidence of the primary maternal outcome was not significantly different in the planned delivery group (154 [55%]) compared with the expectant management group (168 [60%]; adjusted risk ratio [RR] 0·91, 95% CI 0·79 to 1·05). The incidence of the primary perinatal outcome by intention to treat was non-inferior in the planned delivery group (58 [19%]) compared with the expectant management group (67 [22%]; adjusted risk difference –3·39%, 90% CI –8·67 to 1·90; non-inferiority p<0·0001). The results from the per-protocol analysis were similar. There was a significant reduction in severe maternal hypertension (adjusted RR 0·83, 95% CI 0·70 to 0·99) and stillbirth (0·25, 0·07 to 0·87) associated with planned delivery. There were 12 serious adverse events in the planned delivery group and 21 in the expectant management group. / Interpretation: Clinicians can safely offer planned delivery to women with late preterm pre-eclampsia, in a low-income or middle-income country. Planned delivery reduces stillbirth, with no increase in neonatal unit admissions or neonatal morbidity and reduces the risk of severe maternal hypertension. Planned delivery from 34 weeks’ gestation should therefore be considered as an intervention to reduce pre-eclampsia associated mortality and morbidity in these settings. / Funding: UK Medical Research Council and Indian Department of Biotechnology

Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation

Background Pneumococcal carriage is the primary reservoir for transmission and a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage. Methods We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA). Results PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not. Conclusion This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection

Prevalence of Hepatitis B Virus, HIV and HBV coinfection and associated factors in pregnant women attending antenatal care at the University Teaching Hospital, Lusaka, Zambia

Objectives: To explore the prevalence and associated socio-demographic factors of hepatitis B in HIV positive and HIV negative pregnant women attending antenatal care at the University Teaching Hospital, Lusaka, Zambia.Methods: This was a comparative cross-sectional study with a total of 316 (158 HIV negative and 158 HIV positive) pregnant women, aged 16-46years. Participants were recruited from the antenatal ward using convenient sampling method from women with a known and documented HIV status. A structured questionnaire was administered for sociodemographic data and bloods for HBsAg screening were collected. Data collection was done between 15th Dec 2016 and 30th May, 2017. The relationship between study variables and presence of HBV and HBV/HIV coinfection was examined using logistic regression. The selection for entry into the logistic regression model was considered at level p&lt;0.05.Results: Of the 316 study participants 11(3.5%) tested positive for HBsAg. There was no statistical difference in the prevalence of HBV in the HIV negative and HIV positive pregnant women (3.8% and 3.2% respectively, P=0.76). Similarly, there was no association between the age, marital status, parity, residence, religion, education level or form of employment with HBV infection. Being on combined anti-retroviral therapy (cART) had a 91% reduced odds for HBV co-infection[OR = 0.09, CI = 0.01 – 0.63, P = 0.02]Conclusion: There was no significant difference in the prevalence of HBV between the HIV positive and HIV negative pregnant women. However, HIV antiretroviral treatment seems to have a protective effect on acquisition of HBV infection. Therefore, regardless of their HIV status or socio-demographic characteristics, all pregnant women should routinely be screened for HBV so that babies born to high risk mothers can receive the birth doses of HBV vaccine and immunoglobulins to prevent transmission to newborns.Keywords: Hepatitis B virus, HBV and HIV Coinfectio

Disrupting the Systems: Opportunities to Enhance Methodological Approaches to Address Socio-Structural Determinants of HIV and End the Epidemic Through Effective Community Engagement

A world without HIV is only possible by addressing the socio-structural determinants of health. Our understanding of socio-structural determinants is constantly changing, and parallel changes must occur with the methodologies used to explain the drivers of the HIV epidemic. We argue for the need to engage communities in the planning, implementation, and dissemination of research on the socio-structural determinants of HIV. Community engagement should cross-cut various types of research including rigorous measurement development of socio-structural determinants and novel analytic techniques to model their role in the trajectory of the epidemic and the impact of interventions. Considering the role of place, we recommend collaboration between scientists and communities in the interpretation of results from studies that map HIV-related behaviors and movement. As we collectively delve into historically oppressive systems with colonial antecedents, we must be ready to challenge these systems and replace them with collaborative models. The success of research-driven HIV policy and programming will best be evaluated with methodologies derived from the insights of the very individuals that these policies and programs aim to serve

Vernacular discourse, emergent political languages and belonging in Southern Africa

Although academic debates and conversations on the subject of identity formation are numerous and too well known to rehearse, much of their focus has generally been on the discourse of the empowered; that is the discourse of those who control, design and create the public space. Such a focus overlooks the fact that identities are multi-layered, self-imposed and contested just as they are ascribed by others and, therefore, require a critical analysis to avoid essentialism that has bedevilled most mainstream academic debates and conversations on belonging and identity formation. This article uses the concept of vernacular discourse to examine emergent political languages that have shaped and continue to mediate everyday narratives about identity and belonging in southern Africa. The specific focus is on the post-apartheid South African context with some passing remarks on Zimbabwe and Botswana