Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial

Background Neonates born to women infected with HIV are at increased risk for invasive group B streptococcus (GBS) disease. We aimed to compare safety and immunogenicity of trivalent glycoconjugate GBS vaccine in pregnant women with and without HIV in Malawi and South Africa. Methods In our non-randomised phase 2, open-label, multicentre study, we recruited pregnant women attending two antenatal clinics, one in Blantyre, Malawi, and one in Soweto, Johannesburg, South Africa. Participants were divided into three groups on the basis of their HIV infection status (no infection, infection and high CD4 cell count [>350 cells per mu L], and infection and low CD4 cell count [>50 to <= 350 cells per mu L]) and received a 5 mu g dose of glycoconjugate GBS vaccine (serotypes Ia, Ib, and III, with CRM197 [Novartis Vaccines, Siena, Italy]) intramuscularly at 24-35 weeks' gestation. GBS serotype-specific antibody concentrations were measured before vaccination (day 1), day 15, day 31, and at delivery, and in infants at birth and day 42 of life. The primary outcomes were safety in mothers and infants and the amount of placental transfer of GBS serotype-specific antibodies from mothers to their infants. All immunogenicity and safety analyses were done on the full analysis set, including participants who, or whose mother, correctly received the vaccine and who provided at least one valid assessable serum sample. This study is registered with ClinicalTrials.gov, number NCT01412801. Findings 270 women and 266 infants were enrolled between Sept 26, 2011, and Dec 4, 2012 (90 women and 87 infants without HIV, 89 and 88 with HIV and high CD4 cell counts, and 91 and 91 with HIV and low CD4 cell counts, respectively). Seven women were lost to follow-up, six withdrew consent, one died, and two relocated. Eight infants died or were stillborn and two were lost to follow-up. Across serotypes, fold change in antibody concentrations were higher for the HIV-uninfected group than the HIV-infected groups. Transfer ratios were similar across all three groups (0.49-0.72; transfer ratio is infant geometric mean antibody concentration in blood collected within 72 h of birth divided by maternal geometric mean antibody concentration in blood collected at delivery); however, at birth, maternally derived serotype-specific antibody concentrations were lower for infants born to women infected with HIV (0.52-1.62 mu g/mL) than for those born to women not infected with HIV (2.67-3.91 mu g/mL). 151 (57%) of 265 women reported at least one solicited adverse reaction: 39 (45%) of 87 women with HIV and low CD4 cell counts, 52 (59%) of 88 women with HIV and high CD4 cell counts, and 60 (67%) of 90 women in the HIV-uninfected group. 49 (18%) of 269 women had at least one adverse event deemed possibly related to the vaccine (six [7%] in the HIV and low CD4 cell count group, 12 [13%] in the HIV and high CD4 cell count group, and 21 [23%] in the HIV-uninfected group), as did three (1%) of 266 neonates (zero, two [1%], and one [1%]); none of these events was regarded as serious. Interpretation The vaccine was less immunogenic in women infected with HIV than it was in those not infected, irrespective of CD4 cell count, resulting in lower levels of serotype-specific maternal antibody transferred to infants, which could reduce vaccine protection against invasive GBS disease. A validated assay and correlate of protection is needed to understand the potential protective value of this vaccine. Copyright (C) Heyderman et al. Open Access article distributed under the terms of CC BY

Midwife‐Led Ultrasound Scanning to Date Pregnancy in Malawi: Development of a Novel Training Program

The use of ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organization. However, this modality remains unavailable to many women in low-income countries where trained practitioners are scarce. Although previous initiatives have demonstrated efficacy in training midwives and technicians to perform antenatal ultrasound, these programs have often been too long and too complex to be realistic within the specific constraints of this context, highlighting the need for a novel and pragmatic approach. We describe the development and piloting of a bespoke course to teach midwives 3 fundamental components of early antenatal ultrasound scanning: (1) to identify the number of fetuses, (2) to confirm fetal viability, and (3) to determine gestational age. Having established that 5 days is insufficient, we propose that the minimum duration required to train ultrasound-naive midwives to competency is 10 days. Our completed program therefore consists of one and one-half days of didactic teaching, followed by 8 and one-half days of supervised hands-on practical training in which trainees are assessed on their skills. This package has subsequently been successfully implemented across 6 sites in Malawi, where 28 midwives have achieved competency. By describing the processes involved in our cross-continental collaboration, we explain how unexpected challenges helped shape and improve our program, demonstrating the value of preimplementation piloting and a pragmatic and adaptive approach

Training in Ultrasound to Determine Gestational Age (TUDA): Evaluation of a Novel Education Package to Teach Ultrasound-Naive Midwives Basic Obstetric Ultrasound in Malawi

IntroductionAlthough ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organisation, it remains unavailable to many women in low-income countries where trained practitioners are scarce. This study aimed to evaluate a novel, context-specific education package to teach midwives basic obstetric ultrasound, including the determination of gestational age by measurement of fetal femur length.MethodsThe study was conducted across six sites in Malawi in January 2021. Following a virtual “training of the trainers”, local teams delivered a 10-day programme encompassing both didactic and “hands on” components. Matched pre and post course tests assessed participants' knowledge of key concepts, with Objective Structured Clinical Examinations used to evaluate practical skills. To achieve a pass, trainees were required to establish the gestational age to within ±7 days of an experienced practitioner and achieve an overall score of &amp;gt;65% on five consecutive occasions. A matched pre and post course survey explored participants' attitudes and confidence in performing ultrasound examinations.ResultsOf the 29 midwives who participated, 28 finished the programme and met the criteria specified to pass. 22 midwives completed the matched knowledge tests, with the mean (SD) score increasing from 10.2 (3.3) to 18 (2.5) after training (P &amp;lt;0.0001). Mean difference 7.9, 95% CI 6.5–9.2. Midwives passed 87% of the Observed Structured Clinical Examinations, establishing the gestational age to within ±7 days of an experienced practitioner in 89% of assessments. Beliefs regarding the importance of antenatal ultrasound increased post course (p = 0.02), as did confidence in performing ultrasound examinations (p &amp;lt;0.0001).ConclusionThis study demonstrates not only that ultrasound-naive practitioners can be taught to perform basic obstetric ultrasound dating scans, confidently and competently, after 10 days of training, but also that local teams can be orientated to successfully deliver the programme virtually. Previous ultrasound training initiatives, while often more comprehensive in their syllabus, have been of considerably longer duration and this is likely to be a barrier to upscaling opportunities. We propose that this focused training increases the potential for widescale and sustainable implementation.</jats:sec

Informing prevention of stillbirth and preterm birth in Malawi:development of a minimum dataset for health facilities participating in the DIPLOMATIC collaboration

OBJECTIVE: The global research group, DIPLOMATIC (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries), aims to reduce stillbirths and preterm births and optimise outcomes for babies born preterm. Minimum datasets for routine data collection in healthcare facilities participating in DIPLOMATIC (initially in Malawi) were designed to assist understanding of baseline maternal and neonatal care processes and outcomes, and facilitate evaluation of improvement interventions and pragmatic clinical trials. DESIGN: Published and grey literature was reviewed alongside extensive in-country consultation to define relevant clinical best practice guidance, and the existing local data and reporting infrastructure, to identify requirements for the minimum datasets. Data elements were subjected to iterative rounds of consultation with topic experts in Malawi and Scotland, the relevant Malawian professional bodies and the Ministry of Health in Malawi to ensure relevance, validity and feasibility. SETTING: Antenatal, maternity and specialist neonatal care in Malawi. RESULTS: The resulting three minimum datasets cover the maternal and neonatal healthcare journey for antenatal, maternity and specialist neonatal care, with provision for effective linkage of records for mother/baby pairs. They can facilitate consistent, precise recording of relevant outcomes (stillbirths, preterm births, neonatal deaths), risk factors and key care processes. CONCLUSIONS: Poor quality routine data on care processes and outcomes constrain healthcare system improvement. The datasets developed for implementation in DIPLOMATIC partner facilities reflect, and hence support delivery of, internationally agreed best practice for maternal and newborn care in low-income settings. Informed by extensive consultation, they are designed to integrate with existing local data infrastructure and reporting as well as meeting research data needs. This work provides a transferable example of strengthening data infrastructure to underpin a learning healthcare system approach in low-income settings.DIPLOMATIC is funded by the UK National Institute for Health Research

Review of the contemporary use of transvaginal cervical cerclage for the prevention of preterm birth at Tygerberg Hospital

Thesis (MMed)--Stellenbosch University, 2017.ENGLISH SUMMARY: Aim: The main aim of this study was to review the contemporary use of transvaginal cervical cerclage. Methods: This retrospective observational study was done at Tygerberg Academic Hospital (TBH), a secondary and tertiary referral centre in the Western Cape Province. It included all pregnancies in whom a transvaginal cervical cerclage was placed from 1 Jan 2009 to 31 Dec 2014. Cervical cerclage was deemed successful if pregnancy was carried beyond 28 weeks of gestation. Results: 140 transvaginal cerclages were identified for analysis, which consisted of 80 history indicated (HI), 51 ultrasound indicated (UI) and 9 clinical indicated (CI) cerclages. An overall success rate of 74.3% was noted, with individual success rates of 81.3% and 76.5% in the HI and UI groups respectively. All CI cerclages delivered before 28 weeks. The overall live born rate after 24 weeks gestation was 78.6%; 85.0% in the HI group, 76.5% in the UI group and 22.2% in the CI group. The preterm birth (PTB) rate <34 weeks was 42.6% and 33.3% in the HI and UI groups. Cerclage related complications, specifically perioperative rupture of membranes (1.4%), cervical tears (2.1%) and suture displacement (5.0%) were infrequently seen, while preterm rupture of membranes at any gestation was encountered in 22.1% of all cases. Conclusion: Cervical cerclage remains one of the key preventative measures in prevention of PTB especially in high risk populations. Our data highlights the diversity of patients at risk of PTB and the complexities involved in their care. This study sheds light on the need for correct identification of suitable women for cervical cerclage insertion in a developing country setting.AFRIKAANS OPSOMMING: Doel: Die hoofdoel van hierdie studie was om die kontemporêre gebruik van transvaginale servikale steek te hersien. Metodes: Hierdie retrospektiewe waarnemingstudie is by Tygerberg Akademiese Hospitaal (TBH), 'n sekondêre en tersiêre verwysingsentrum in die Wes-Kaapprovinsie, gedoen. Alle swangerskappe is ingesluit in wie 'n transvaginale servikale steek van 1 Januarie 2009 tot 31 Desember 2014 geplaas was. ʼn Servikale steek is as suksesvol beskou as die swangerskap verby 28 weke volhou. Resultate: 140 transvaginale steke is geïdentifiseer vir analise, wat saamgestel is uit 80 geskiedenis aangeduide (HI), 51 ultraklank aangeduide (UI) en 9 klinies aangeduide (CI) steke. Die algehele sukseskoers van 74.3% was waargeneem, met individuele sukseskoerse van onderskeidelik 81,3% en 76,5% in die HI- en UI-groepe. Al die CI steke is voor 28 weke verlos. Die algehele lewendige geboortekoers, na 24 weke, was 78,6%, 85,0% in die HI-groep, 76,5% in die UI-groep en 22,2% in die CI-groep. Die voortydige kraam (PTB)-koers <34 weke, was 42,6% en 33,3% in die HI- en UI-groepe. Steek-verwante komplikasies, spesifiek peri-operatiewe ruptuur van membrane (1.4%), servikale skeure (2.1%) en steek verplasing (5.0%) was selde gesien terwyl premature ruptuur van membrane by enige swangerskapsduur voorkom in 22.1% van alle gevalle. Gevolgtrekking: Servikale steke bly een van die belangrikste voorkomende maatreëls in die voorkoming van PTB, veral in hoërisiko-bevolkings. Ons data beklemtoon die omvang van pasiënte wat ʼn risiko het vir PTB en die kompleksiteite wat by hul sorg betrokke is. Hierdie studie beklemtoon die behoefte aan korrekte identifisering van geskikte vroue vir servikale steke in 'n ontwikkelende land omgewing

DIPLOMATIC study documents

This archive comprises study documents including work packages 1 to 8, some of the materials include the following: - study protocol (an over-arching very detailed description of the experiment); - consent forms; - educational materials relating to ultrasound scanning and so on. ## Access ## Requests for a copy of the data are welcome. The data are held in the DataVault, which is directly accessible only to University of Edinburgh nominated users. To request a copy, please contact Lorraine Adamson.DIPLOMATIC is a clinical trial, a multidisciplinary international collaboration investigating interventions in pre-term birth and still-term birth in low and middle income countries. (DIPLOMATIC: using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries)