Preparing for Disease X: Ensuring Vaccine Equity for Pregnant Women in Future Pandemics.

Disease X represents a yet unknown human pathogen which has potential to cause a serious international epidemic or pandemic. The COVID-19 pandemic has illustrated that despite being at increased risk of severe disease compared with the general population, pregnant women were left behind in the development and implementation of vaccination, resulting in conflicting communications and changing guidance about vaccine receipt in pregnancy. Based on the COVID-19 experience, the COVAX Maternal Immunization Working Group have identified three key factors and five broad focus topics for consideration when proactively planning for a disease X pandemic, including 10 criteria for evaluating pandemic vaccines for potential use in pregnant women. Prior to any disease X pandemic, collaboration and coordination are needed to close the pregnancy data gap which is currently a barrier to gender equity in health innovation, which will aid in allowing timely access to life-saving interventions including vaccines for pregnant women and their infants.

Conducting clinical research in a resource-constrained setting: lessons from a longitudinal cohort study in The Gambia.

Clinical research conducted to Good Clinical Practice (GCP) standards is increasingly being undertaken in resource-constrained low-income and middle-income countries (LMICs) settings. This presents unique challenges that differ from those faced in high-income country (HIC) contexts, due to a dearth of infrastructure and unique socio-cultural contexts. Field experiences by research teams working in these LMIC contexts are thus critical to advancing knowledge on successful research conduct in these settings. The Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine has operated in The Gambia, a resource-constrained LMIC for over 70 years and has developed numerous research support platforms and systems. The unit was the lead clinical collaborator in a recently completed Expanded Program on Immunization Consortium (EPIC) study, involving a multicountry collaboration across five countries including the USA, Canada, Belgium, Papua New Guinea and The Gambia. The EPIC study recruited and completed follow-up of 720 newborn infants over 2 years. In this paper, we provide in-depth field experience covering challenges faced by the Gambian EPIC team in the conduct of this study. We also detail some reflections on these challenges. Our findings are relevant to the international research community as they highlight practical day-to-day challenges in conducting GCP standard clinical research in resource-constrained LMIC contexts. They also provide insights on how study processes can be adapted early during research planning to mitigate challenges.

Immunization: vital progress, unfinished agenda.

Vaccination against infectious diseases has changed the future of the human species, saving millions of lives every year, both children and adults, and providing major benefits to society as a whole. Here we show, however, that national and sub-national coverage of vaccination varies greatly and major unmet needs persist. Although scientific progress opens exciting perspectives in terms of new vaccines, the pathway from discovery to sustainable implementation can be long and difficult, from the financing, development and licensing to programme implementation and public acceptance. Immunization is one of the best investments in health and should remain a priority for research, industry, public health and society.

Tracking coverage, dropout and multidimensional equity gaps in immunisation systems in West Africa, 2000-2017.

BACKGROUND: Several West African countries are unlikely to achieve the recommended Global Vaccine Action Plan (GVAP) immunisation coverage and dropout targets in a landscape beset with entrenched intra-country equity gaps in immunisation. Our aim was to assess and compare the immunisation coverage, dropout and equity gaps across 15 West African countries between 2000 and 2017. METHODS: We compared Bacille Calmette Guerin (BCG) and the third dose of diphtheria-tetanus-pertussis (DTP3) containing vaccine coverage between 2000 and 2017 using the WHO and Unicef Estimates of National Immunisation Coverage for 15 West African countries. Estimated subregional median and weighted average coverages, and dropout (DTP1-DTP3) were tracked against the GVAP targets of ≥90% coverage (BCG and DTP3), and ≤10% dropouts. Equity gaps in immunisation were assessed using the latest disaggregated national health survey immunisation data. RESULTS: The weighted average subregional BCG coverage was 60.7% in 2000, peaked at 83.2% in 2009 and was 65.7% in 2017. The weighted average DTP3 coverage was 42.3% in 2000, peaked at 70.3% in 2009 and was 61.5% in 2017. As of 2017, 46.7% of countries (7/15) had met the GVAP targets on DTP3 coverage. Average weighted subregional immunisation dropouts consistently reduced from 16.4% in 2000 to 7.4% in 2017, meeting the GVAP target in 2008. In most countries, inequalities in BCG, and DTP3 coverage and dropouts were mainly related to equity gaps of more than 20% points between the wealthiest and the poorest, high coverage regions and low coverage regions, and between children of mothers with at least secondary education and those with no formal education. A child's sex and place of residence (urban or rural) minimally determined equity gaps. CONCLUSIONS: The West African subregion made progress between 2000 and 2017 in ensuring that its children utilised immunisation services, however, wide equity gaps persist.

Vaccine wastage in The Gambia: a prospective observational study.

BACKGROUND: Vaccination is a cost-effective and life-saving intervention. Recently several new, but more expensive vaccines have become part of immunization programmes in low and middle income countries (LMIC). Monitoring vaccine wastage helps to improve vaccine forecasting and minimise wastage. As the costs of vaccination increases better vaccine management is essential. Many LMIC however do not consistently monitor vaccine wastage. METHODS: We conducted two surveys in health facilities in rural and urban Gambia; 1) a prospective six months survey in two regions to estimate vaccine wastage rates and type of wastage for each of the vaccines administered by the Expanded programme on Immunization (EPI) and 2) a nationwide cross sectional survey of health workers from randomly selected facilities to assess knowledge, attitude and practice on vaccine waste management. We used WHO recommended forms and standard questionnaires. Wastage rates were compared to EPI targets. RESULTS: Wastage rates for the lyophilised vaccines BCG, Measles and Yellow Fever ranged from 18.5-79.0%, 0-30.9% and 0-55.0% respectively, mainly through unused doses at the end of an immunization session. Wastage from the liquid vaccines multi-dose/ single dose vials were minimal, with peaks due to expiry or breakage of the vaccine diluent. We interviewed 80 health workers and observed good knowledge. Batching children for BCG was uncommon (19%) whereas most health workers (73.4%) will open a vial as needed. CONCLUSION: National projected wastage targets were met for the multi-dose/single dose vials, but for lyophilised vaccines, the target was only met in the largest major health facility.

Why the Convention on the Rights of the Child must become a guiding framework for the realization of the rights of children affected by tuberculosis.

BACKGROUND: Until recently, paediatric tuberculosis (TB) has been relatively neglected by the broader TB and the maternal and child health communities. Human rights-based approaches to children affected by TB could be powerful; however, awareness and application of such strategies is not widespread. DISCUSSION: We summarize the current challenges faced by children affected by TB, including: consideration of their family context; the limitations of preventive, diagnostic and treatment options; paucity of paediatric-specific research; failure in implementation of interventions; and stigma. We examine the articles of the Convention on the Rights of the Child (CRC) and relate them to childhood TB. Specifically, we focus on the five core principles of the CRC: children's inherent right to life and States' duties towards their survival and development; children's right to enjoyment of the highest attainable standard of health; non-discrimination; best interests of the child; and respect for the views of the child. We highlight where children's rights are violated and how a human rights-based approach should be used as a tool to help children affected by TB, particularly in light of the Sustainable Development Goals and their focus on universality and leaving no one behind. The article aims to bridge the gap between those providing paediatric TB clinical care and conducting research, and those working in the fields of human rights policy and advocacy to promote a human rights-based approach for children affected by TB based upon the Convention on the Rights of the Child.

What determines uptake of pertussis vaccine in pregnancy? A cross sectional survey in an ethnically diverse population of pregnant women in London.

INTRODUCTION: Following the major outbreak of pertussis and 14 infant deaths across England in 2012, the Department of Health (DH) introduced the UK's first maternal pertussis vaccination programme. Data published by Public Health England (PHE) suggest uptake of the vaccine varies considerably across the country. The reasons for this heterogeneity need to be addressed to optimise the impact of the programme. OBJECTIVE: To assess uptake of antenatal pertussis and influenza vaccine in a leading NHS Trust in London and to explore awareness and attitudes of pregnant women towards the pertussis vaccination programme. DESIGN: A cross sectional survey was conducted in an ethnically diverse group of 200 pregnant women accessing antenatal care at Imperial Healthcare NHS Trust. Quantitative data was tabulated and content analysis was carried out on the free text. Qualitative data was divided into themes for accepting or declining the vaccine. RESULTS: Awareness of the programme was 63% (126/200) with actual uptake of the vaccine only 26.0% (52/200). Women had received information from multiple sources, primarily General Practitioners (GP) and midwives. 34.0% (68/200) of women were offered the vaccine at their GP practice, only 24% reported a meaningful discussion with their GP about it. Uptake differed by up to 15.0% between ethnicities. Qualitative data showed that uptake could be significantly enhanced if vaccination was recommended by a familiar healthcare professional. Feeling uninformed, lack of professional encouragement and uncertainties of risk and benefit of the vaccine were the greatest barriers to uptake. CONCLUSION: Vaccine uptake in this cohort of pregnant women was poor. Understanding the target audience and engaging with key groups who influence women's decision-making is essential. Knowledgeable health care professionals need to recommend the vaccine and provide accurate and timely information to increase success of this important programme.

Biological challenges to effective vaccines in the developing world.

The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy.

Ebola: a holistic approach is required to achieve effective management and control.

The current Ebola outbreak in West Africa has already caused substantial mortality and dire human and economic consequences. It continues to represent an alarming public health threat in the region and beyond and jeopardizes the provision of health care and other services in the affected countries. The scale of the epidemic has accelerated research efforts for diagnostics, treatment, and prevention galvanized through increased availability of funding. Our knowledge relating to the virus, disease pathogenesis, risk factors, dynamics of transmission, and epidemic control is increasing, and sociocultural factors have emerged as critical determinants for the success and failure of control efforts. However, there is a long way to go. In this review we summarize the current knowledge, examine the sociocultural context in West Africa, and outline priority areas for future research.

Non-tuberculous mycobacteria in children: muddying the waters of tuberculosis diagnosis.

Non-tuberculous mycobacteria (NTM) are a large family of acid-fast bacteria, widespread in the environment. In children, NTM cause lymphadenitis, skin and soft tissue infections, and occasionally also lung disease and disseminated infections. These manifestations can be indistinguishable from tuberculosis on the basis of clinical and radiological findings and tuberculin skin testing. A diagnostic and therapeutic problem for respiratory physicians and other clinicians is therefore evident, particularly in settings where childhood tuberculosis is common, and bacteriological confirmation of any mycobacterial disease is difficult because of low availability of laboratory services in low-resource settings and the inherent paucibacillary nature of mycobacterial disease in childhood. The epidemiology of NTM varies by world region, and attempts to understand the burden of NTM disease and to identify risk factors in the paediatric population are hampered by inadequate mandatory NTM reporting and the overlap of clinical presentation with tuberculosis. The immune response to both NTM and Mycobacterium tuberculosis is based on cellular immunity and relies on the type-1 cytokine pathway. The disruption of this immune response by genetic or acquired mechanisms, such as mendelian susceptibility to mycobacterial disease or HIV, might result in predisposition to mycobacterial infections. Published diagnostic and management guidelines do not provide specific advice for diagnosis of NTM in children, from whom the quantity and quality of diagnostic samples are often suboptimum. Treatment of NTM infections is very different from the treatment of tuberculosis, depends on the strain and anatomical site of infection, and often involves antibiotic combinations, surgery, or both. In this Review, we summarise the epidemiological and clinical features of NTM infection in children, with a specific focus on the implications for public health in settings with a high endemic burden of childhood tuberculosis.