Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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]). INTERPRETATION: 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. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

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.

Seroprevalence and assessment of public awareness of Brucella spp., Toxoplasma gondii and Chlamydia abortus in small ruminants from selected smallholder commercial farms of Zimbabwe.

Brucella spp., Toxoplasma gondii, and Chlamydia abortus have long been recognized as zoonoses and significant causes of reproductive failure in small ruminants globally. A cross-sectional study was conducted in August 2020 to determine the seroprevalences of Brucella spp., Toxoplasma gondii and Chlamydia abortus in 398 small ruminants from four districts of Zimbabwe (Chivi, Makoni, Zvimba, and Goromonzi) using Indirect-ELISAs. A structured questionnaire was used to assess the knowledge, attitudes, and practices of 103 smallholder farmers towards small ruminant abortions, Brucella spp., T. gondii and C. abortus, and to obtain a general overview of the significance of small ruminant reproductive failure(s) on their livelihoods. The overall seroprevalences were: 9.1% (95% CI: 6.4-12.3) for Brucella spp., 6.8% (95% CI: 4.5-9.7) for T. gondii and 2.0% (95% CI: 0.9-3.9) for C. abortus. Location, age, parity, and abortion history were associated with Brucella spp. seropositivity. Location was also associated with both T. gondii and C. abortus seropositivity. The questionnaire survey established that 44% of respondents had recently faced reproductive disease challenges within their flocks, with 34% correctly identifying abortion causes and only 10%, 6% and 4% having specific knowledge of Brucella spp., C. abortus and T. gondii, respectively. This study provides the first serological evidence of Brucella spp. in small ruminants since 1996 and builds the evidence on small ruminant toxoplasmosis and chlamydiosis in Zimbabwe. Evidence of these zoonoses in small ruminants and the paucity of knowledge shows the need for a coordinated One Health approach to increase public awareness of these diseases, and to establish effective surveillance and control measures. Further studies are required to establish the role these diseases play in small ruminant reproductive failure(s), to identify the Brucella spp. detected here to species/subspecies level, and to assess the socio-economic impact of reproductive failure in livestock among marginalised rural communities.

COVID-19 impact on routine immunisations for vaccine-preventable diseases: Projecting the effect of different routes to recovery.

Over the past two decades, vaccination programmes for vaccine-preventable diseases (VPDs) have expanded across low- and middle-income countries (LMICs). However, the rise of COVID-19 resulted in global disruption to routine immunisation activities. Such disruptions could have a detrimental effect on public health, leading to more deaths from VPDs, particularly without mitigation efforts. Hence, as routine immunisation activities resume, it is important to estimate the effectiveness of different approaches for recovery. We apply an impact extrapolation method developed by the Vaccine Impact Modelling Consortium to estimate the impact of COVID-19-related disruptions with different recovery scenarios for ten VPDs across 112 LMICs. We focus on deaths averted due to routine immunisations occurring in the years 2020-2030 and investigate two recovery scenarios relative to a no-COVID-19 scenario. In the recovery scenarios, we assume a 10% COVID-19-related drop in routine immunisation coverage in the year 2020. We then linearly interpolate coverage to the year 2030 to investigate two routes to recovery, whereby the immunization agenda (IA2030) targets are reached by 2030 or fall short by 10%. We estimate that falling short of the IA2030 targets by 10% leads to 11.26% fewer fully vaccinated persons (FVPs) and 11.34% more deaths over the years 2020-2030 relative to the no-COVID-19 scenario, whereas, reaching the IA2030 targets reduces these proportions to 5% fewer FVPs and 5.22% more deaths. The impact of the disruption varies across the VPDs with diseases where coverage expands drastically in future years facing a smaller detrimental effect. Overall, our results show that drops in routine immunisation coverage could result in more deaths due to VPDs. As the impact of COVID-19-related disruptions is dependent on the vaccination coverage that is achieved over the coming years, the continued efforts of building up coverage and addressing gaps in immunity are vital in the road to recovery.

Combining rapid antigen testing and syndromic surveillance improves community-based COVID-19 detection in a low-income country.

Diagnostics for COVID-19 detection are limited in many settings. Syndromic surveillance is often the only means to identify cases but lacks specificity. Rapid antigen testing is inexpensive and easy-to-deploy but can lack sensitivity. We examine how combining these approaches can improve surveillance for guiding interventions in low-income communities in Dhaka, Bangladesh. Rapid-antigen-testing with PCR validation was performed on 1172 symptomatically-identified individuals in their homes. Statistical models were fitted to predict PCR-status using rapid-antigen-test results, syndromic data, and their combination. Under contrasting epidemiological scenarios, the models' predictive and classification performance was evaluated. Models combining rapid-antigen-testing and syndromic data yielded equal-to-better performance to rapid-antigen-test-only models across all scenarios with their best performance in the epidemic growth scenario. These results show that drawing on complementary strengths across rapid diagnostics, improves COVID-19 detection, and reduces false-positive and -negative diagnoses to match local requirements; improvements achievable without additional expense, or changes for patients or practitioners.

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries. Methods: 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. Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases. Conclusions: 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. Funding: 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.

Knowledge, beliefs and practices regarding prevention of bacterial meningitis in Burkina Faso, 5 years after MenAfriVac mass campaigns.

BACKGROUND: To adapt communications concerning vaccine prevention, we studied knowledge, beliefs and practices around meningitis risk and prevention in a young adult population in Burkina Faso in 2016, 5 years after the MenAfriVac® mass campaign and one year before the vaccine's inclusion in the infant immunization schedule. METHODS: In a representative sample of the population aged 15 to 33 years (N = 220) in Bobo-Dioulasso, Burkina Faso, study nurses administered a standardized paper questionnaire consisting of predominantly open questions, collecting information on meningitis risk factors and prevention, and on exposure to dry air and kitchen fire smoke. We identified themes and analyzed their frequency. We created a meningitis knowledge score (range 0 to 4) based on pre-defined best responses and analyzed the determinants of knowledge score levels ≥2 (basic score) and ≥3 (high score) using multivariate logistic regression. RESULTS: Biomedically supported facts and good practices were known by the majority of participants (eg vaccine prevention, 84.5%). Younger women aged 15-20 years had a higher frequency of low scores <2 (17.0%) compared to older women aged 21-33 years (6.3%) and men of both age groups (3.8%). Junior secondary School attendance explained the differences between the two groups of women, the gender gap for the older, but not the young women, and explained score differences among young women. Local understandings and practices for risk and prevention were commonly reported and used (risk from unripe mango consumption and prevention through nasal application of shea nut butter). DISCUSSION: This study shows a gender gap in knowledge of meningitis risk and prevention, largely due to education-level inequalities. Women below 21 years had particularly low levels of knowledge and may need interventions outside schools and perinatal care. Our study suggests a strong adherence to local understandings of and practices around meningitis risk and prevention, which should be taken into account by vaccination promotion.

Understanding the Role of Duration of Vaccine Protection with MenAfriVac: Simulating Alternative Vaccination Strategies.

We previously developed a transmission dynamic model of Neisseria meningitidis serogroup A (NmA) with the aim of forecasting the relative benefits of different immunisation strategies with MenAfriVac. Our findings suggested that the most effective strategy in maintaining disease control was the introduction of MenAfriVac into the Expanded Programme on Immunisation (EPI). This strategy is currently being followed by the countries of the meningitis belt. Since then, the persistence of vaccine-induced antibodies has been further studied and new data suggest that immune response is influenced by the age at vaccination. Here, we aim to investigate the influence of both the duration and age-specificity of vaccine-induced protection on our model predictions and explore how the optimal vaccination strategy may change in the long-term. We adapted our previous model and considered plausible alternative immunization strategies, including the addition of a booster dose to the current schedule, as well as the routine vaccination of school-aged children for a range of different assumptions regarding the duration of protection. To allow for a comparison between the different strategies, we use several metrics, including the median age of infection, the number of people needed to vaccinate (NNV) to prevent one case, the age distribution of cases for each strategy, as well as the time it takes for the number of cases to start increasing after the honeymoon period (resurgence). None of the strategies explored in this work is superior in all respects. This is especially true when vaccine-induced protection is the same regardless of the age at vaccination. Uncertainty in the duration of protection is important. For duration of protection lasting for an average of 18 years or longer, the model predicts elimination of NmA cases. Assuming that vaccine protection is more durable for individuals vaccinated after the age of 5 years, routine immunization of older children would be more efficient in reducing disease incidence and would also result in a fewer number of doses necessary to prevent one case. Assuming that elimination does not occur, adding a booster dose is likely to prevent most cases but the caveat will be a more costly intervention. These results can be used to understand important sources of uncertainty around MenAfriVac and support decisions by policymakers.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Group B Streptococcal Disease in England (1998 - 2017): A Population-based Observational Study.

BACKGROUND AND OBJECTIVES: Group B Streptococcus (GBS) is the leading cause of sepsis and meningitis in infants <90 days. In this study, the burden of GBS disease and mortality in young infants in England was assessed. METHODS: Using linked hospitalization records from every National Health Service (NHS) hospital from April 1, 1998 to March 31, 2017, we calculated annual GBS incidence in infants aged <90 days and, using regression models, compared their perinatal factors, rates of hospital-recorded disease outcomes, and all-cause infant mortality rates with those of the general infant population. RESULTS: 15 429 infants aged <90 days had a hospital-recorded diagnosis of GBS, giving an average annual incidence of 1.28 per 1000 live births (95% CI 1.26-1.30) with no significant trend over time. GBS-attributable mortality declined significantly from 0.044 (95% CI .029-.065) per 1000 live births in 2001 to 0.014 (95% CI .010-.026) in 2017 (annual percentage change -6.6, 95% CI -9.1 to -4.0). Infants with GBS had higher relative rates of visual impairment (HR 7.0 95% CI 4.1-12.1), cerebral palsy (HR 9.3 95% CI 6.6-13.3), hydrocephalus (HR 17.3 95% CI 13.8-21.6), and necrotizing enterocolitis (HR 18.8 95% CI 16.7-21.2) compared with those without GBS. CONCLUSIONS: Annual rates of GBS disease in infants have not changed over 19 years. The reduction in mortality is likely multifactorial and due to widespread implementation of antibiotics in at-risk mothers and babies, as well as advances in managing acutely unwell infants. New methods for prevention, such as maternal vaccination, must be prioritized.

Spatiotemporal Analysis of Serogroup C Meningococcal Meningitis Spread in Niger and Nigeria and Implications for Epidemic Response.

BACKGROUND: After the re-emergence of serogroup C meningococcal meningitis (MM) in Nigeria and Niger, we aimed to re-evaluate the vaccination policy used to respond to outbreaks of MM in the African meningitis belt by investigating alternative strategies using a lower incidence threshold and information about neighboring districts. METHODS: We used data on suspected and laboratory-confirmed cases in Niger and Nigeria from 2013 to 2017. We calculated global and local Moran's I-statistics to identify spatial clustering of districts with high MM incidence. We used a Pinner model to estimate the impact of vaccination campaigns occurring between 2015 and 2017 and to evaluate the impact of 3 alternative district-level vaccination strategies, compared with that currently used. RESULTS: We found significant clustering of high incidence districts in every year, with local clusters around Tambuwal, Nigeria in 2013 and 2014, Niamey, Niger in 2016, and in Sokoto and Zamfara States in Nigeria in 2017.We estimate that the vaccination campaigns implemented in 2015, 2016, and 2017 prevented 6% of MM cases. Using the current strategy but with high coverage (85%) and timely distribution (4 weeks), these campaigns could have prevented 10% of cases. This strategy required the fewest doses of vaccine to prevent a case. None of the alternative strategies we evaluated were more efficient, but they would have prevented the occurrence of more cases overall. CONCLUSIONS: Although we observed significant spatial clustering in MM in Nigeria and Niger between 2013 and 2017, there is no strong evidence to support a change in methods for epidemic response in terms of lowering the intervention threshold or targeting neighboring districts for reactive vaccination.

Health impact and cost-effectiveness of introducing the vaccine (Bexsero) against MenB disease into the Brazilian immunization programme.

Invasive meningococcal disease (IMD) is associated with a high mortality and severe sequelae. The aim of the present study was to evaluate the potential cost-effectiveness of the Bexsero vaccine in Brazil. We used a cohort model to compare routine vaccination against MenB disease with no vaccination. Epidemiological and cost estimates were obtained from the Brazilian Health Information System. The cost per disability-adjusted life year (DALY) averted and incremental cost-effectiveness ratio (ICER) was estimated assuming a 3-dose vaccination schedule, at R$90 (£ 20.50) per vaccine dose, 82.0% vaccine efficacy against MenB disease and a vaccine uptake of 90.0%. We estimated that 1,527 MenB cases would be prevented and 78 deaths averted. This strategy would cost R$ 762,381, 000 (£ 174,059,503) with a R$ 4,364,280 (£ 996,410) reduction in disease treatment costs. However, at an ICER of 372,256 (£ 84,990) per DALY averted, a vaccination programme is unlikely to be cost-effective.

Risk factors for acquisition of meningococcal carriage in the African meningitis belt.

OBJECTIVE: To investigate potential risk factors for acquisition in seven countries of the meningitis belt. METHODS: Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions. RESULTS: Over the course of the study, acquisition was higher in: (i) 5-to 14-year olds, as compared with those 30 years or older (OR 3.6, 95% CI 1.4-9.9); (ii) smokers (OR 3.6, 95% CI 0.98-13); and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3-5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season (OR 3.7, 95% CI 2.0-6.7) and lower in those reporting antibiotic use (OR 0.17, 95% CI 0.03-0.56). CONCLUSIONS: Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt.

OBJECTIF: Investiguer les facteurs de risque potentiels d'acquisition dans sept pays de la ceinture de la méningite. MÉTHODES: Des ménages ont été suivis toutes les deux semaines pendant deux mois, puis tous les mois pendant quatre mois. Des prélèvements pharyngés sur écouvillons ont été collectés auprès de tous les membres disponibles du ménage à chaque visite et des questionnaires ont été remplis. Les risques d'acquisition sur l'ensemble de la période d'étude et pour chaque visite ont été analysés par une série de régressions logistiques. RÉSULTATS: Au cours de l'étude, l'acquisition a été plus élevée chez: (i) les 5-14 ans, par rapport à ceux âgés de 30 ans ou plus (OR = 3,6; IC95%: 1,4-9,9); (ii) les fumeurs (OR = 3,6; IC95%: 0,98-13); et (iii) les personnes exposées à la fumée de bois à la maison (OR = 2,6; IC95%: 1,3-5,6). Le risque d'acquisition d'une visite à l'autre était plus élevé chez les personnes signalant un mal de gorge pendant la saison sèche (OR = 3,7; IC95%: 2,0-6,7) et plus faible chez celles signalant une utilisation d'antibiotique (OR = 0,17; IC95%: 0,03-0,56). CONCLUSIONS: L'acquisition du portage du méningocoque a culminé chez les enfants d'âge scolaire. Les symptômes récents de maux de gorge pendant la saison sèche, mais pas pendant la saison des pluies, étaient associés à un risque d'acquisition plus élevé. Les infections des voies respiratoires supérieures pourraient être un facteur important d'épidémies dans la ceinture de la méningite.

Narrative review of methods and findings of recent studies on the carriage of meningococci and other Neisseria species in the African Meningitis Belt.

OBJECTIVE: To review the findings of studies of pharyngeal carriage of Neisseria meningitidis and related species conducted in the African meningitis belt since a previous review published in 2007. METHODS: PubMed and Web of Science were searched in July 2018 using the terms 'meningococcal OR Neisseria meningitidis OR lactamica AND carriage AND Africa', with the search limited to papers published on or after 1st January 2007. We conducted a narrative review of these publications. RESULTS: One hundred and thirteen papers were identified using the search terms described above, 20 of which reported new data from surveys conducted in an African meningitis belt country. These papers described 40 surveys conducted before the introduction of the group A meningococcal conjugate vaccine (MenAfriVacR ) during which 66 707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from <1% to 24%. The mean pharyngeal carriage prevalence of N. meningitidis across all surveys was 4.5% [95% CI: 3.4%, 6.8%] and that of capsulated N. meningitidis was 2.8% [95% CI: 1.9%; 5.2%]. A study of households provided strong evidence for meningococcal transmission within and outside households. The introduction of MenAfriVac® led to marked reductions in carriage of the serogroup A meningococcus in Burkina Faso and Chad. CONCLUSIONS: Recent studies employing standardised methods confirm the findings of older studies that carriage of N. meningitidis in the African meningitis belt is highly variable over time and place, but generally occurs with a lower prevalence and shorter duration than reported from industrialised countries.

Reactive vaccination as a control strategy for pneumococcal meningitis outbreaks in the African meningitis belt: Analysis of outbreak data from Ghana.

Streptococcus pneumoniae is increasingly recognised as an important cause of bacterial meningitis in the African meningitis belt. The World Health Organization sets guidelines for response to outbreaks of meningococcal meningitis, but there are no current guidelines for outbreaks where S. pneumoniae is implicated. We aimed to evaluate the impact of using a similar response to target outbreaks of vaccine-preventable pneumococcal meningitis in the meningitis belt. Here, we adapt a previous model of reactive vaccination for meningococcal outbreaks to estimate the potential impact of reactive vaccination in a recent pneumococcal meningitis outbreak in the Brong-Ahafo region of central Ghana using weekly line list data on all suspected cases over a period of five months. We determine the sensitivity and specificity of various epidemic thresholds and model the cases and deaths averted by reactive vaccination. An epidemic threshold of 10 suspected cases per 100,000 population per week performed the best, predicting large outbreaks with 100% sensitivity and more than 85% specificity. In this outbreak, reactive vaccination would have prevented a lower number of cases per individual vaccinated (approximately 15,300 doses per case averted) than previously estimated for meningococcal outbreaks. Since the burden of death and disability from pneumococcal meningitis is higher than that from meningococcal meningitis, there may still be merit in considering reactive vaccination for outbreaks of pneumococcal meningitis. More outbreak data are needed to refine our model estimates. Whatever policy is followed, we emphasize the importance of timely laboratory confirmation of suspected cases to enable appropriate decisions about outbreak response.

The views of the general public on prioritising vaccination programmes against childhood diseases: A qualitative study.

BACKGROUND: Decisions regarding which vaccines are funded in the United Kingdom (UK) are increasingly informed by cost-effectiveness analyses. Such analyses use Quality Adjusted Life Years (QALYs) as a measure of effectiveness and assume that QALYs are equal regardless of where and in whom they occur in the population. However, there is increasing debate about whether this QALY approach is appropriate and whether societal preferences for childhood vaccinations should be used to help inform childhood immunisation policy. OBJECTIVE: To gauge the general public's preferences for prioritising certain characteristics of childhood vaccination, to help inform future policy making decisions in the UK. DESIGN: Qualitative design using individual face-to-face interviews, with data analysed using an inductive thematic framework approach. SETTING: Two counties in England, UK. POPULATION: Adult members of the general public were recruited using the Bristol and South Gloucestershire open electoral registers, using gender and deprivation quotas for each area. PARTICIPANTS: 21 members of the public participated in qualitative interviews. RESULTS: The qualitative research identified three major themes and several key attributes that influences participant's opinions about priority setting for childhood vaccinations: (1) population segment (i.e. age group, carer impact and social group), (2) vaccine preventable diseases preferences (i.e. disease severity, disease incidence and declining infection) and (3) risks and benefits associated with childhood vaccinations (i.e. vaccine associated side-effects, herd protection and peace of mind). CONCLUSION: Evidence from this qualitative study suggests that some members of the UK general public have more nuanced views than the health-maximisation approach when considering how childhood vaccines should be prioritised. This is not necessarily captured by the current economic approaches for assessing the benefits from childhood vaccinations in the UK, but is an important area for future research to ensure appropriate decision making.

Investigation of correlates of protection against pharyngeal carriage of Neisseria meningitidis genogroups W and Y in the African meningitis belt.

BACKGROUND: Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known. METHODS: Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional survey. Serum bactericidal antibody titres at baseline were compared between individuals in the household of the carrier who became a carrier of a meningococcus of the same genogroup during six months of subsequent follow-up and household members who did not become a carrier of a meningococcus of this genogroup during this period. RESULTS: Serum bacterial antibody titres were significantly higher in carriers of a serogroup W or Y meningococcus at the time of recruitment than in those who were not a carrier of N. meningitidis of the same genogroup. Serum bactericidal antibody titres to a strain of N. meningitis of the same genogroup as the index cases were no different in individuals who acquired carriage with a meningococcus of the same genogroup as the index case than in those who did not become a carrier during six months of follow-up. CONCLUSION: Serum bacterial antibody titres to N. meningitidis of genogroup W or Y in the range of those acquired by natural exposure to meningococci of these genogroups, or with cross-reactive bacteria, are not associated with protection against acquisition of carriage with meningococci of either of these genogroups.

Impact of MenAfriVac in nine countries of the African meningitis belt, 2010-15: an analysis of surveillance data.

BACKGROUND: In preparation for the introduction of MenAfriVac, a meningococcal group A conjugate vaccine developed for the African meningitis belt, an enhanced meningitis surveillance network was established. We analysed surveillance data on suspected and confirmed cases of meningitis to quantify vaccine impact. METHODS: We compiled and analysed surveillance data for nine countries in the meningitis belt (Benin, Burkina Faso, Chad, Côte d'Ivoire, Ghana, Mali, Niger, Nigeria, and Togo) collected and curated by the WHO Inter-country Support Team between 2005 and 2015. The incidence rate ratios (IRRs) of suspected and confirmed cases in vaccinated and unvaccinated populations were estimated with negative binomial regression models. The relative risk of districts reaching the epidemic threshold of ten per 100 000 per week was estimated according to district vaccination status. FINDINGS: The incidence of suspected meningitis cases declined by 57% (95% CI 55-59) in vaccinated compared with unvaccinated populations, with some heterogeneity observed by country. We observed a similar 59% decline in the risk of a district reaching the epidemic threshold. In fully vaccinated populations, the incidence of confirmed group A disease was reduced by more than 99%. The IRR for non-A serogroups was higher after completion of MenAfriVac campaigns (IRR 2·76, 95% CI 1·21-6·30). INTERPRETATION: MenAfriVac introduction has led to substantial reductions in the incidence of suspected meningitis and epidemic risk, and a substantial effect on confirmed group A meningococcal meningitis. It is important to continue strengthening surveillance to monitor vaccine performance and remain vigilant against threats from other meningococcal serogroups and other pathogens. FUNDING: World Health Organization.

Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad.

BACKGROUND: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an "accidental pathogen"; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates. RESULTS: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier. CONCLUSIONS: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium.