Antenatal care service delivery and factors affecting effective tetanus vaccine coverage in low- and middle-income countries: results of the Maternal Immunisation and Antenatal Care Situational Analysis (MIACSA) project

Objectives:To map the integration of existing maternal tetanus immunization programmes within ante-natal care (ANC) services for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with high performance maternal vaccine service delivery.Design:A mixed methods, cross sectional study with four data collection phases including a desk review,online survey, telephone and face-to-face interviews and in country visits was undertaken between 2016 and 2018. Associations of different service delivery process components with protection at birth (PAB) andwithcountrygroupswereestablished.PABwasdefinedastheproportionofneonatesprotectedatbirthagainstneonataltetanus. Regression analysis and structural equation modelling was used to assess associations of different variables with maternal tetanus immunization coverage. Latent class analysis (LCA), was used to group country performance for maternal immunization, and to address the problem of multicollinearity.Setting:LMICs.Results: The majority of LMICs had a policy on recommended number of ANC visits, however most were yet toimplementtheWHOguidelinesrecommendingeightANCcontacts.Countriesthatrecommended>4ANC contacts were more likely to have high PAB > 90%. Passive disease surveillance was the most common form of dis-ease surveillance performed but the maternal and neonatal morbidity and mortality indicators recorded differed between countries. The presence of user fees for antenatal care and maternal immunization was significantly associated with lower PAB (<90%).Conclusions:Recommendations include implementing the current WHO ANC guideline to facilitate increased opportunities for vaccination during each pregnancy. Improved utilisation of ANC services by increasing the demand side by increasing the quality of services, reducing any associated costs and supporting user fee exemptions, or the supply side can also enhance utilisation of ANC services which are positioned as an ideal platform for delivery of maternal vaccine

Vaccine value profile for Group B streptococcus.

Group B streptococcus (GBS) is a major global cause of neonatal meningitis, sepsis and pneumonia, with an estimated 91,000 infant deaths per year and an additional 46,000 stillbirths. GBS infection in pregnancy is also associated with adverse maternal outcomes and preterm births. As such, the World Health Organization (WHO) prioritised the development of a GBS vaccine suitable for use in pregnant women and use in LMICs, where the burden of disease is highest. Several GBS vaccines are in clinical development. The WHO Defeating Meningitis by 2030 has set a target of 2026 for vaccine licensure. This 'Vaccine Value Profile' (VVP) for GBS is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO regions of AFR, AMR, EUR, WPR. All contributors have extensive expertise on various elements of the GBS VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information

A review of the costs of delivering maternal immunisation during pregnancy.

BACKGROUND: Routine maternal immunisation against influenza and pertussis are recommended by the WHO to protect mother and child, and new vaccines are under development. Introducing maternal vaccines into national programmes requires an understanding of vaccine delivery costs - particularly in low resource settings. METHODS: We searched Medline, Embase, Econlit, and Global Health for studies reporting costs of delivering vaccination during pregnancy but excluded studies that did not separate the vaccine purchase price. Extracted costs were inflated and converted to 2018 US dollars. RESULTS: Sixteen studies were included, of which two used primary data to estimate vaccine delivery costs. Costs per dose ranged from $0.55 to$0.64 in low-income countries, from $1.25 to$6.55 for middle-income countries, and from $5.76 to$39.87 in high-income countries. CONCLUSIONS: More research is needed on the costs of delivering maternal immunisation during pregnancy, and of integrating vaccine delivery into existing programmes of antenatal care especially in low and middle-income countries

Defining and reporting adverse events of special interest in comparative maternal vaccine studies: a systematic review

Introduction The GAIA (Global Alignment on Immunisation Safety Assessment in Pregnancy) consortium was established in 2014 with the aim of creating a standardised, globally coordinated approach to monitoring the safety of vaccines administered in pregnancy. The consortium developed twenty-six standardised definitions for classifying obstetric and infant adverse events. This systematic review sought to evaluate the current state of adverse event reporting in maternal vaccine trials following the publication of the case definitions by GAIA, and the extent to which these case definitions have been adopted in maternal vaccine safety research. Methods A comprehensive search of published literature was undertaken to identify maternal vaccine research studies. PubMed, EMBASE, Web of Science, and Cochrane were searched using a combination of MeSH terms and keyword searches to identify observational or interventional studies that examined vaccine safety in pregnant women with a comparator group. A two-reviewer screening process was undertaken, and a narrative synthesis of the results presented. Results 14,737 titles were identified from database searches, 435 titles were selected as potentially relevant, 256 were excluded, the remaining 116 papers were included. Influenza vaccine was the most studied (25.0%), followed by TDaP (20.7%) and SARS-CoV-2 (12.9%). Ninety-one studies (78.4%) were conducted in high-income settings. Forty-eight (41.4%) utilised electronic health-records. The majority focused on reporting adverse events of special interest (AESI) in pregnancy (65.0%) alone or in addition to reactogenicity (27.6%). The most frequently reported AESI were preterm birth, small for gestational age and hypertensive disorders. Fewer than 10 studies reported use of GAIA definitions. Gestational age assessment was poorly described; of 39 studies reporting stillbirths 30.8% provided no description of the gestational age threshold. Conclusions Low-income settings remain under-represented in comparative maternal vaccine safety research. There has been poor uptake of GAIA case definitions. A lack of harmonisation and standardisation persists limiting comparability of the generated safety data

Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa.

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa.  The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization

Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.

BACKGROUND: Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets. METHODS: We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates. FINDINGS: Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births. INTERPRETATION: Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies. FUNDING: Bill & Melinda Gates Foundation

Seasonal influenza vaccine policy, use and effectiveness in the tropics and subtropics - a systematic literature review

AIM: The evidence needed for tropical countries to take informed decisions on influenza vaccination is scarce. This article reviews policy, availability, use and effectiveness of seasonal influenza vaccine in tropical and subtropical countries. METHOD: Global health databases were searched in three thematic areas - policy, availability and protective benefits in the context of human seasonal influenza vaccine in the tropics and subtropics. We excluded studies on monovalent pandemic influenza vaccine, vaccine safety, immunogenicity and uptake, and disease burden. RESULTS: Seventy-four countries in the tropics and subtropics representing 60% of the world's population did not have a national vaccination policy against seasonal influenza. Thirty-eight countries used the Northern Hemisphere and 21 countries the Southern Hemisphere formulation. Forty-six countries targeted children and 57 targeted the elderly; though, the age cut-offs varied. Influenza vaccine supply increased twofold in recent years. However, coverage remained lower than five per 1000 population. Vaccine protection against laboratory-confirmed influenza in the tropics ranged from 0% to 42% in the elderly, 20-77% in children and 50-59% in healthy adults. Vaccinating pregnant women against seasonal influenza prevented laboratory-confirmed influenza in both mothers (50%) and their infants <6 months (49-63%). CONCLUSION: Guidelines on vaccine composition, priority risk groups and vaccine availability varied widely. The evidence on vaccine protection was scarce. Countries in the tropics and subtropics need to strengthen and expand their evidence-base required for making informed decisions on influenza vaccine introduction and expansion, and how much benefit to expect

Influenza vaccination policies for health workers in low-income and middle-income countries: A cross-sectional survey, January-March 2020

Introduction: The World Health Organization (WHO) recommends vaccination of health workers against influenza, but uptake in low-resource settings remains low. To complement routine global data collection efforts we conducted a detailed survey on influenza vaccination policies for health workers in low-income and middle-income countries (LMICs) in early 2020. Methods: Health worker vaccination policy data were collected via a web-based survey tool sent to Expanded Programme on Immunization managers or equivalent managers of all eligible countries. High-income countries and countries with active civil war were excluded from the participation. The survey was sent by email to 109 LMICs in all WHO Regions to invite participation. Data were analyzed by World Bank income category and WHO Region. Statistical methods were applied to assess mean vaccination rates across countries. Results: Sixty-eight (62%) out of 109 invited LMICs were studied. Thirty-five (51.5%) reported to have a policy for influenza vaccination of health workers. Vaccinations were voluntary in 23 countries (66%), mandatory in 4 (11%), while in 8 countries (23%) mixed vaccination policies existed. A mechanism to estimate vaccine uptake existed in 26 countries (74%). Low-income and African Region countries were less likely to have influenza vaccination policies for health workers (p-values &lt; 0.001 and 0.009, respectively). The most common reason for not having a vaccination policy for health workers was influenza not being a priority (48.5%). Conclusions: Despite policies being in place in more than half LMICs studied, gaps remain in translating vaccination policies to action, particularly in low-income and African Region countries. To optimize the operationalization of policies, further research is needed within countries, to enable evidence-based introduction decisions, categorization of health workers for vaccination, identification of factors impacting effective service delivery, strengthening monitoring and estimation of vaccination uptake rates and ensure sustainability of funding. © 2020 Elsevier Lt