Evidence to date has shown that inequality in health, and vaccination coverage in particular, can have ramifications to wider society. However, whilst individual studies have sought to characterise ...these heterogeneities in immunisation coverage at national level, few have taken a broad and quantitative view of the contributing factors to heterogeneity in immunisation coverage and impact, i.e. the number of cases, deaths, and disability-adjusted life years averted. This systematic review aims to highlight these geographic, demographic, and sociodemographic characteristics through a qualitative and quantitative approach, vital to prioritise and optimise vaccination policies.
A systematic review of two databases (PubMed and Web of Science) was undertaken using search terms and keywords to identify studies examining factors on immunisation inequality and heterogeneity in vaccination coverage. Inclusion criteria were applied independently by two researchers. Studies including data on key characteristics of interest were further analysed through a meta-analysis to produce a pooled estimate of the risk ratio using a random effects model for that characteristic.
One hundred and eight studies were included in this review. We found that inequalities in wealth, education, and geographic access can affect vaccine impact and vaccination dropout. We estimated those living in rural areas were not significantly different in terms of full vaccination status compared to urban areas but noted considerable heterogeneity between countries. We found that females were 3% (95%CI1%, 5%) less likely to be fully vaccinated than males. Additionally, we estimated that children whose mothers had no formal education were 28% (95%CI18%,47%) less likely to be fully vaccinated than those whose mother had primary level, or above, education. Finally, we found that individuals in the poorest wealth quintile were 27% (95%CI 16%,37%) less likely to be fully vaccinated than those in the richest.
We found a nuanced picture of inequality in vaccination coverage and access with wealth disparity dominating, and likely driving, other disparities. This review highlights the complex landscape of inequity and further need to design vaccination strategies targeting missed subgroups to improve and recover vaccination coverage following the COVID-19 pandemic.
Prospero, CRD42021261927.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive ...vaccination campaigns during the pandemic.
We used two to three models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption).
Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (SIAs) planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people per year until the campaigns are implemented. For meningococcal A vaccination, short-term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1- to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns.
The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination.
Bill and Melinda Gates Foundation and Gavi, the Vaccine Alliance.
The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the ...deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030.
16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort.
We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction 52–66), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in the 2019 birth cohort.
Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained.
Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for
type b, hepatitis B, human papillomavirus, Japanese encephalitis, ...measles,
serogroup A, rotavirus, rubella,
, and yellow fever over the years 2000-2030 across 112 countries.
Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.
We estimate 97 (95%CrI80, 120) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI41, 62) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI41, 69) million more deaths would occur over their lifetimes without vaccination against these diseases.
This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.
VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and ...interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered.
For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus HPV, meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO–UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up.
We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval CrI 17 248–134 941) during calendar years 2020–30, largely due to measles. For years of vaccination 2020–30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52–2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249–40 241 202) to 36 410 559 deaths averted (33 515 397–39 241 799). We estimated that catch-up activities could avert 78·9% (40·4–151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 7037–60 223 of 25 356 9859–75 073).
Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption.
The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.
For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the mammal, anaesthetics are known to act via two distinct mechanisms, either increasing inhibition via GABAA receptors (eg. Na-thiopentone) or decreasing excitation via NIvIDA receptors (eg. ...ketamine). The aim of this thesis is to investigate the effects of both increased inhibition and decreased excitation at the synaptic level within an invertebrate model system, something which cannot readily be done in vertebrate systems. This was achieved by carrying out experiments using both the above mentioned anaesthetics on the whole animal, isolated brain and cultured neurons. In invertebrates it has been shown that GABA and Glutamate can be both excitatory and inhibitory, and injection of GABA into Lymnaea has been shown to result in behavioural changes in feeding, locomotion, escape reactions, male mating and respiration. Injection of Na-thiopentone into the whole animal was carried out in this investigation, in order to establish the anaesthetic response of the animal model to this barbiturate. The presence of gamma-aminobutyric acid (GABA) receptors has been demonstrated in a respiratory interneuron (RPeD1) both electrophysiologically and via molecular techniques, however inmiunostaining has proved negative in RPeD1 and follower cells VD2/3 (unidirectional excitatory synapse) and VD4 (mutual inhibitory synapse). This suggests that these neurons are not themselves GABAergic, although this investigation shows the responses of these neurons to bath and direct application of GABA. Na-thiopentone did not reliably anaesthetise Lymnaea upon injection into the sole of the foot, suggesting that Na-thiopentone binds to proteins within the snail, andlor has a low affininty for the GABAA receptor in Lymnaea. Other anaesthetic studies using propofol and ketaniine have also demonstrated a lack of anaesthetic response. RPeD1 hyperpolarised and became quiescent in response to the application of high concentrations of GABA (10 3-104M), however at lower doses (1O 8-1O 5M), no effect was observed (p < 0.05). Under these conditions simultaneous recordings from VD4 showed hyperpolarisation in response to the application of GABA, whereas VD2 and VD3 exhibited excitatory responses. Presynaptic picoinjection of GABA also resulted in hyperpolarisation and quiescence in RJeD1, but the simultaneous response in VD3 was not observed. Postsynaptic application of GABA directly to 'VD2, and VD4 however, resulted in responses similar to those seen in the whole brain. VD2 and 3 also receive input 2, which hyperpolarises RPeD1 and elicits an excitatory EPSP in VD2 and 3 as this is similar to the response observed in this experiment it is possible that the effects of input 2 on RPeD1 and VD2 & 3 are mediated by GABA. As RPeDI does not stain positively for GABA and hyperpolarises in response to the drug, it seems unlikely that the postsynaptie effects are due to presynaptic release of GABA. RPeD1 has been shown to form reciprocal synapses with VD4 both in vivo and in vitro. When perfused with GABA (lmJ'i4), both cells hyperpolarised reversibly. The postsynaptic response could be due to the action of GABA presynaptically inhibiting RPeDI, or directly on postsynaptic GABA receptors. However VD4 forms connections with other cells in the brain such as input 3 which may also have resulted in this inhibitory response. RPeD1 would however have received a simultaneous excitatory input from this interneuron. Attempts were made to establish the nature of the RPeD1JVD4 synapse in these experiments, but no synapses were evident. These experiments therefore confirm the presence of GABA receptors in RPeD1 and suggest theft presence in VD2, and VD4. This investigation confirms the findings of previous studies, that injection and bath perfusion of barbiturates does not lead to responses in Lymnaea comparable to that of the mammal. In addition to it's main target site, ketamine (a frequently used intravenous anaesthetic) has also been shown to act at cholinergic receptors. The effects of ketamine on learning and memory and apoptosis in the mammalian CNS are well recognised. Within the Lymnaea CNS, VD4 and LPeD1 form a unidirectional excitatory cholinergic synapse, and this was chosen to investigate the effects of ketamine on excitatory synaptic transmission, short term potentiation and synapse formation in the invertebrate animal model. Ketamine decreased synaptic transmission between VD4 and LPeD1 in a concentration dependent manner, but did not significantly affect short term synaptic plasticity (pc0.05). While neurite outgrowth remained extensive, actual sprouting was diminished by all doses of ketamine. Cells exhibited extensive veiling, which was not present in control cells. Percentage chemical synapse formation was reduced by all doses of ketamine, and in some cases inappropriate inhibitory chemical synapses were formed. Furthermore acute, clinically relevant levels of ketamine reduce excitatory cholinergic transmission between VD4 and LPeD1, but short term plasticity is unaffected. Nerve regeneration was seriously compromised, and formation of appropriate chemical synapses greatly reduced. This data has serious implications for the clinical - use of ketamine, particularly in pregnant women, children or critical care patients where nerve regeneration and synapse formation are of great importance and long term exposure common practice. In conclusion, this work supports that of other studies which have showed that invertebrates appear to be relatively insensitive to barbiturates, whereas ketamine appears to effect excitation in a manner similar to that in the mammal.
In the mammal, anaesthetics are known to act via two distinct mechanisms, either increasing inhibition via GABAA receptors (eg. Na-thiopentone) or decreasing excitation via NIvIDA receptors (eg. ...ketamine). The aim of this thesis is to investigate the effects of both increased inhibition and decreased excitation at the synaptic level within an invertebrate model system, something which cannot readily be done in vertebrate systems. This was achieved by carrying out experiments using both the above mentioned anaesthetics on the whole animal, isolated brain and cultured neurons. In invertebrates it has been shown that GABA and Glutamate can be both excitatory and inhibitory, and injection of GABA into Lymnaea has been shown to result in behavioural changes in feeding, locomotion, escape reactions, male mating and respiration. Injection of Na-thiopentone into the whole animal was carried out in this investigation, in order to establish the anaesthetic response of the animal model to this barbiturate. The presence of gamma-aminobutyric acid (GABA) receptors has been demonstrated in a respiratory interneuron (RPeD1) both electrophysiologically and via molecular techniques, however inmiunostaining has proved negative in RPeD1 and follower cells VD2/3 (unidirectional excitatory synapse) and VD4 (mutual inhibitory synapse). This suggests that these neurons are not themselves GABAergic, although this investigation shows the responses of these neurons to bath and direct application of GABA. Na-thiopentone did not reliably anaesthetise Lymnaea upon injection into the sole of the foot, suggesting that Na-thiopentone binds to proteins within the snail, andlor has a low affininty for the GABAA receptor in Lymnaea. Other anaesthetic studies using propofol and ketaniine have also demonstrated a lack of anaesthetic response. RPeD1 hyperpolarised and became quiescent in response to the application of high concentrations of GABA (10 3-104M), however at lower doses (1O 8-1O 5M), no effect was observed (p < 0.05). Under these conditions simultaneous recordings from VD4 showed hyperpolarisation in response to the application of GABA, whereas VD2 and VD3 exhibited excitatory responses. Presynaptic picoinjection of GABA also resulted in hyperpolarisation and quiescence in RJeD1, but the simultaneous response in VD3 was not observed. Postsynaptic application of GABA directly to 'VD2, and VD4 however, resulted in responses similar to those seen in the whole brain. VD2 and 3 also receive input 2, which hyperpolarises RPeD1 and elicits an excitatory EPSP in VD2 and 3 as this is similar to the response observed in this experiment it is possible that the effects of input 2 on RPeD1 and VD2 & 3 are mediated by GABA. As RPeDI does not stain positively for GABA and hyperpolarises in response to the drug, it seems unlikely that the postsynaptie effects are due to presynaptic release of GABA. RPeD1 has been shown to form reciprocal synapses with VD4 both in vivo and in vitro. When perfused with GABA (lmJ'i4), both cells hyperpolarised reversibly. The postsynaptic response could be due to the action of GABA presynaptically inhibiting RPeDI, or directly on postsynaptic GABA receptors. However VD4 forms connections with other cells in the brain such as input 3 which may also have resulted in this inhibitory response. RPeD1 would however have received a simultaneous excitatory input from this interneuron. Attempts were made to establish the nature of the RPeD1JVD4 synapse in these experiments, but no synapses were evident. These experiments therefore confirm the presence of GABA receptors in RPeD1 and suggest theft presence in VD2, and VD4. This investigation confirms the findings of previous studies, that injection and bath perfusion of barbiturates does not lead to responses in Lymnaea comparable to that of the mammal. In addition to it's main target site, ketamine (a frequently used intravenous anaesthetic) has also been shown to act at cholinergic receptors. The effects of ketamine on learning and memory and apoptosis in the mammalian CNS are well recognised. Within the Lymnaea CNS, VD4 and LPeD1 form a unidirectional excitatory cholinergic synapse, and this was chosen to investigate the effects of ketamine on excitatory synaptic transmission, short term potentiation and synapse formation in the invertebrate animal model. Ketamine decreased synaptic transmission between VD4 and LPeD1 in a concentration dependent manner, but did not significantly affect short term synaptic plasticity (pc0.05). While neurite outgrowth remained extensive, actual sprouting was diminished by all doses of ketamine. Cells exhibited extensive veiling, which was not present in control cells. Percentage chemical synapse formation was reduced by all doses of ketamine, and in some cases inappropriate inhibitory chemical synapses were formed. Furthermore acute, clinically relevant levels of ketamine reduce excitatory cholinergic transmission between VD4 and LPeD1, but short term plasticity is unaffected. Nerve regeneration was seriously compromised, and formation of appropriate chemical synapses greatly reduced. This data has serious implications for the clinical - use of ketamine, particularly in pregnant women, children or critical care patients where nerve regeneration and synapse formation are of great importance and long term exposure common practice. In conclusion, this work supports that of other studies which have showed that invertebrates appear to be relatively insensitive to barbiturates, whereas ketamine appears to effect excitation in a manner similar to that in the mammal.
PDF
