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OBJECTIVE: To evaluate vaccine effectiveness and to assess risk factors for measles in Dhaka, Bangladesh. METHOD: A case-control study, involving 198 cases with 783 age-matched neighbourhood controls and 120 measles cases with 365 age-matched hospital controls, was conducted in 1995-96 in three large hospitals in Dhaka. FINDINGS: Measles vaccine effectiveness was estimated at 80% (95% confidence interval (CI) = 60-90%) using neighbourhood controls; very similar results were obtained using hospital controls. Visits to a health facility 7-21 days before onset of any symptoms were associated with increased risk of measles compared with neighbourhood (adjusted odds ratio (OR) = 7.0, 95% CI = 4.2-11.6) or hospital (adjusted OR = 1.7, 95% CI = 1.01-2.8) controls. Cases were more likely than controls to come from a household where more than one child lived (adjusted OR = 1.6, 95% CI = 1.1-2.5 versus neighbourhood controls; adjusted OR = 1.8, 95% CI = 1.02-3.0 versus hospital controls). CONCLUSIONS: To improve measles control in urban Dhaka missed immunization opportunities must be reduced in all health care facilities by following WHO guidelines. For measles elimination, more than one dose of vaccine would be required. Copyright © 2002 World Health Organization [ABSTRACT FROM AUTHOR]

Background: More than one dose of measles vaccine is necessary for the sustained control of measles. The aerosol route is thought to be more immunogenic for booster doses than traditional subcutaneous injections, so we did a randomised comparative trial of aerosol and subcutaneous measles vaccines in South African schoolchildren.Methods: 4327 schoolchildren (aged 5-14 years), assigned by block randomisation of classrooms, received standard titre doses of either Schwarz or Edmonston-Zagreb measles vaccines subcutaneously or by aerosol. Blood samples for antibody assay were collected before vaccination, at 1 month, and 1 year after vaccination. The main endpoints (antibody titres at 1 month and 1 year) were compared between groups.Findings: 992 children had antibody titre data available for all timepoints. 14 (3.6%) of 385 children who received Edmonston-Zagreb vaccine by aerosol were seronegative 1 year after vaccination, compared with 28 (8.6%) of 326 children who received Edmonston-Zagreb subcutaneous vaccine and 39 (13.9%) of 281 children who received Schwarz subcutaneous vaccine. At 1 month, 326 (84.7%) children who received aerosol Edmonston-Zagreb vaccine had seroconverted, compared with 257 (78.8%) who received subcutaneous Edmonston-Zagreb vaccine and 176 (62.6%) who received subcutaneous Schwarz vaccine. At 1 month, only 116 (22.7%) of 511 children in the Schwarz aerosol group had seroconverted; this aerosol vaccine had no detectable potency after 2 min of nebulisation. There were no serious side-effects: about 5% of children in each group had a rash within 2 weeks of vaccination.Interpretation: An aerosol vaccination method that uses currently available devices and a suitably stable vaccine is effective and acceptable. This form of delivery is adaptable to mass campaigns, avoids the risks associated with injections, and could help measles eradication. [ABSTRACT FROM AUTHOR]

Background: As of 1997, less than one-third of developing countries included rubella vaccine in their national immunization programme. In countries that have achieved high coverage of measles vaccine, an ideal opportunity exists to include control of rubella and congenital rubella syndrome (CRS) in enhanced measles control activities. Data on the burden of congenital rubella syndrome are important to guide rubella vaccination policies.Methods: We reviewed the literature to identify studies of rubella antibody prevalence in developing countries that were conducted on populations with no major selection bias, prior to wide-scale rubella vaccination in the country. We used a simple catalytic model to describe the age-specific prevalence of susceptibility to rubella virus infection in given populations. Estimates of the incidence of infection among pregnant women were calculated using expressions for the average prevalence of susceptibility to infection and the incidence of infection during gestation. To estimate the number of cases of CRS, we assumed an overall risk of 65% after infection in the first 16 weeks of pregnancy and zero risk thereafter. These estimates were derived for each country for which data were available, then for each World Health Organization region, excluding Europe.Results: The estimated mean incidence of CRS per 100,000 live births was lowest in the Eastern Mediterranean region (77.4, range 0-212) and highest in the Americas (175, range 0-598). The mean of the estimates of the total number of cases of CRS in developing countries in 1996 was approximately 110,000. The range was, however, very wide, from as few as 14,000 to as many as 308,000 cases.Conclusions: Congenital rubella syndrome is an under-recognized public health problem in many developing countries. There is an urgent need for collection of appropriate data to estimate the cost-effectiveness of a potential global rubella control programme. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. METHODS: Paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural Ethiopian community. Oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced IgG antibody capture (GAC) enzyme-linked immunosorbent assays (ELISAs), and for anti-HBc antibodies using a prototype GACELISA. IgG antibodies in serum to measles, rubella and HBc were determined using commercial ELISAs. FINDINGS: Relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-HBc. These assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages < 20 years). CONCLUSION: Our results suggest that oral fluid could have the potential to replace serum in IgG antibody prevalence surveys. Further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays. [ABSTRACT FROM AUTHOR]

Background: Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematized review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries (as defined by World Bank 2021 income classifications) published from 1962 to 2021., Methods: On 9 March 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health-care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075)., Results: We identified 221 relevant studies across all World Health Organization regions, decades, and unique age ranges. The overall crude mean seroprevalence across all studies was 78.0% (SD: 19.3%), and the median seroprevalence was 84.0% (IQR: 72.8-91.7%). We classified 80 (36.2%) studies as having severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias., Conclusions: While many studies have substantial underlying bias, many studies still provide some insights or data that could be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility.

Objectives: Many countries introduced rubella-containing vaccination (RCV) after 2011, following changes in recommended World Health Organization (WHO) vaccination strategies and external support. We evaluated the impact of these introductions., Methods: We estimated the country-specific, region-specific, and global Congenital Rubella Syndrome (CRS) incidence during 1996-2019 using mathematical modeling, including routine and campaign vaccination coverage and seroprevalence data., Results: In 2019, WHO African and Eastern Mediterranean regions had the highest estimated CRS incidence (64 [95% confidence intervals (CI): 24-123] and 27 [95% CI: 4-67] per 100,000 live births respectively), where nearly half of births occur in countries that have introduced RCV. Other regions, where >95% of births occurred in countries that had introduced RCV, had a low estimated CRS incidence (<1 [95% CI: <1 to 8] and <1 [95% CI: <1 to 12] per 100,000 live births in South-East Asia [SEAR] and the Western Pacific [WPR] respectively, and similarly in Europe and the Americas). The estimated number of CRS births globally declined by approximately two-thirds during 2010-2019, from 100,000 (95% CI: 54,000-166,000) to 32,000 (95% CI: 13,000-60,000), representing a 73% reduction since 1996, largely following RCV introductions in WPR and SEAR, where the greatest reductions occurred., Conclusions: Further reductions can occur by introducing RCV in remaining countries and maintaining high RCV coverage., Competing Interests: Declaration of competing interests The authors have no competing interests to declare., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Pilot testing is crucial when preparing any community-based vaccination coverage survey. In this paper, we use the term pilot test to mean informative work conducted before a survey protocol has been finalized for the purpose of guiding decisions about how the work will be conducted. We summarize findings from seven pilot tests and provide practical guidance for piloting similar studies. We selected these particular pilots because they are excellent models of preliminary efforts that informed the refinement of data collection protocols and instruments. We recommend survey coordinators devote time and budget to identify aspects of the protocol where testing could mitigate project risk and ensure timely assessment yields, credible estimates of vaccination coverage and related indicators. We list specific items that may benefit from pilot work and provide guidance on how to prioritize what to pilot test when resources are limited.

Background: WHO recommends at least 95% population coverage with two doses of measles-containing vaccine (MCV). Most countries worldwide use routine services to offer a first dose of measles-containing vaccine (MCV1) and later, a second dose of measles-containing vaccine (MCV2). Many countries worldwide conduct supplementary immunisation activities (SIAs), offering vaccination to all people in a specific age range irrespective of previous vaccination history. We aimed to estimate the relative effects of each dose and delivery route in 14 countries with high measles burden., Methods: We used an age-structured compartmental dynamic model, the Dynamic Measles Immunization Calculation Engine (DynaMICE), to assess the effects of different vaccination strategies on measles susceptibility and burden during 2000-20 in 14 countries with high measles incidence (containing 53% of the global birth cohort and 78% of the global measles burden). Country-specific routine MCV1 and MCV2 coverage data during 1980-2020 were obtained from the WHO and UNICEF Estimates of National Immunization Coverage database for all modelled countries and SIA data were obtained from the WHO summary of measles and rubella SIAs. We estimated the incremental health effects of different vaccination strategies using prevented cases of measles and deaths from measles and their efficiency using the incremental number needed to vaccinate (NNV) to prevent an additional measles case., Findings: Compared with no vaccination, MCV1 implementation was estimated to have prevented 824 million cases of measles and 9·6 million deaths from measles, with a median NNV of 1·41 (IQR 1·35-1·44). Adding routine MCV2 to MCV1 was estimated to have prevented 108 million cases and 404 270 deaths, whereas adding SIAs to MCV1 was estimated to have prevented 256 million cases and 4·4 million deaths. Despite larger incremental effects, adding SIAs to MCV1 (median incremental NNV 6·02, 5·30-7·68) showed reduced efficiency compared with adding routine MCV2 (5·41, 4·76-6·11)., Interpretation: Vaccination strategies, including non-selective SIAs, reach a greater proportion of children who are unvaccinated and reduce measles burden more than MCV2 alone, but efficiency is lower because of the wide age range targeted by SIAs. This analysis provides information to help improve the health effects and efficiency of measles vaccination strategies. The interplay between MCV1, MCV2, and SIAs should be considered when planning future measles vaccination strategies., Funding: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and - to the extent possible - quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT)., Methods: We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported., Results: We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0]., Conclusions: Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups)., (© 2023. The Author(s).)

Introduction: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs., Methods: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children., Results: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%)., Discussion: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Geographically precise identification and targeting of populations at risk of vaccine-preventable diseases has gained renewed attention within the global health community over the last few years. District level estimates of vaccination coverage and corresponding zero-dose prevalence constitute a potentially useful evidence base to evaluate the performance of vaccination strategies. These estimates are also valuable for identifying missed communities, hence enabling targeted interventions and better resource allocation. Here, we fit Bayesian geostatistical models to map the routine coverage of the first doses of diphtheria-tetanus-pertussis vaccine (DTP1) and measles-containing vaccine (MCV1) and corresponding zero-dose estimates in Nigeria at 1x1 km resolution and the district level using geospatial data sets. We also map MCV1 coverage before and after the 2019 measles vaccination campaign in the northern states to further explore variations in routine vaccine coverage and to evaluate the effectiveness of both routine immunization (RI) and campaigns in reaching zero-dose children. Additionally, we map the spatial distributions of reported measles cases during 2018 to 2020 and explore their relationships with MCV zero-dose prevalence to highlight the public health implications of varying performance of vaccination strategies across the country. Our analysis revealed strong similarities between the spatial distributions of DTP and MCV zero dose prevalence, with districts with the highest prevalence concentrated mostly in the northwest and the northeast, but also in other areas such as Lagos state and the Federal Capital Territory. Although the 2019 campaign reduced MCV zero-dose prevalence substantially in the north, pockets of vulnerabilities remained in areas that had among the highest prevalence prior to the campaign. Importantly, we found strong correlations between measles case counts and MCV RI zero-dose estimates, which provides a strong indication that measles incidence in the country is mostly affected by RI coverage. Our analyses reveal an urgent and highly significant need to strengthen the country's RI program as a longer-term measure for disease control, whilst ensuring effective campaigns in the short term., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Substantial inequalities exist in childhood vaccination coverage levels. To increase vaccine uptake, factors that predict vaccination coverage in children should be identified and addressed., Methods: Using data from the 2018 Nigeria Demographic and Health Survey and geospatial data sets, we fitted Bayesian multilevel binomial and multinomial logistic regression models to analyse independent predictors of three vaccination outcomes: receipt of the first dose of Pentavalent vaccine (containing diphtheria-tetanus-pertussis, Hemophilus influenzae type B and Hepatitis B vaccines) (PENTA1) (n = 6059) and receipt of the third dose having received the first (PENTA3/1) (n = 3937) in children aged 12-23 months, and receipt of measles vaccine (MV) (n = 11839) among children aged 12-35 months., Results: Factors associated with vaccination were broadly similar for documented versus recall evidence of vaccination. Based on any evidence of vaccination, we found that health card/document ownership, receipt of vitamin A and maternal educational level were significantly associated with each outcome. Although the coverage of each vaccine dose was higher in urban than rural areas, urban residence was not significant in multivariable analyses that included travel time. Indicators relating to socio-economic status, as well as ethnic group, skilled birth attendance, lower travel time to the nearest health facility and problems seeking health care were significantly associated with both PENTA1 and MV. Maternal religion was related to PENTA1 and PENTA3/1 and maternal age related to MV and PENTA3/1; other significant variables were associated with one outcome each. Substantial residual community level variances in different strata were observed in the fitted models for each outcome., Conclusion: Our analysis has highlighted socio-demographic and health care access factors that affect not only beginning but completing the vaccination series in Nigeria. Other factors not measured by the DHS such as health service quality and community attitudes should also be investigated and addressed to tackle inequities in coverage., Competing Interests: The authors have declared that no competing interests exist.

One important strategy to increase vaccination coverage is to minimize missed opportunities for vaccination. Missed opportunities for simultaneous vaccination (MOSV) occur when a child receives one or more vaccines but not all those for which they are eligible at a given visit. Household surveys that record children's vaccination dates can be used to quantify occurrence of MOSVs and their impact on achievable vaccination coverage. We recently automated some MOSV analyses in the World Health Organization's freely available software: Vaccination Coverage Quality Indicators (VCQI) making it straightforward to study MOSVs for any Demographic & Health Survey (DHS), Multi-Indicator Cluster Survey (MICS), or Expanded Programme on Immunization (EPI) survey. This paper uses VCQI to analyze MOSVs for basic vaccine doses among children aged 12-23 months in four rounds of DHS in Colombia (1995, 2000, 2005, and 2010) and five rounds of DHS in Nigeria (1999, 2003, 2008, 2013, and 2018). Outcomes include percent of vaccination visits MOSVs occurred, percent of children who experienced MOSVs, percent of MOSVs that remained uncorrected (that is, the missed vaccine had still not been received at the time of the survey), and the distribution of time-to-correction for children who received the MOSV dose at a later visit.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Through a combination of strong routine immunization (RI), strategic supplemental immunization activities (SIA) and robust surveillance, numerous countries have been able to approach or achieve measles elimination. The fragility of these achievements has been shown, however, by the resurgence of measles since 2016. We describe trends in routine measles vaccine coverage at national and district level, SIA performance and demographic changes in the three regions with the highest measles burden., Findings: WHO-UNICEF estimates of immunization coverage show that global coverage of the first dose of measles vaccine has stabilized at 85% from 2015 to 19. In 2000, 17 countries in the WHO African and Eastern Mediterranean regions had measles vaccine coverage below 50%, and although all increased coverage by 2019, at a median of 60%, it remained far below levels needed for elimination. Geospatial estimates show many low coverage districts across Africa and much of the Eastern Mediterranean and southeast Asian regions. A large proportion of children unvaccinated for MCV live in conflict-affected areas with remote rural areas and some urban areas also at risk. Countries with low RI coverage use SIAs frequently, yet the ideal timing and target age range for SIAs vary within countries, and the impact of SIAs has often been mitigated by delays or disruptions. SIAs have not been sufficient to achieve or sustain measles elimination in the countries with weakest routine systems. Demographic changes also affect measles transmission, and their variation between and within countries should be incorporated into strategic planning., Conclusions: Rebuilding services after the COVID-19 pandemic provides a need and an opportunity to increase community engagement in planning and monitoring services. A broader suite of interventions is needed beyond SIAs. Improved methods for tracking coverage at the individual and community level are needed together with enhanced surveillance. Decision-making needs to be decentralized to develop locally-driven, sustainable strategies for measles control and elimination.

Measles vaccination campaigns are conducted regularly in many low- and middle-income countries to boost measles control efforts and accelerate progress towards elimination. National and sometimes first-level administrative division campaign coverage may be estimated through post-campaign coverage surveys (PCCS). However, these large-area estimates mask significant geographic inequities in coverage at more granular levels. Here, we undertake a geospatial analysis of the Nigeria 2017-18 PCCS data to produce coverage estimates at 1 × 1 km resolution and the district level using binomial spatial regression models built on a suite of geospatial covariates and implemented in a Bayesian framework via the INLA-SPDE approach. We investigate the individual and combined performance of the campaign and routine immunization (RI) by mapping various indicators of coverage for children aged 9-59 months. Additionally, we compare estimated coverage before the campaign at 1 × 1 km and the district level with predicted coverage maps produced using other surveys conducted in 2013 and 2016-17. Coverage during the campaign was generally higher and more homogeneous than RI coverage but geospatial differences in the campaign's reach of previously unvaccinated children are shown. Persistent areas of low coverage highlight the need for improved RI performance. The results can help to guide the conduct of future campaigns, improve vaccination monitoring and measles elimination efforts. Moreover, the approaches used here can be readily extended to other countries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. MCD-H works at the Wold Health Organisation. The comments on this article reflect those of the authors alone and do not necessarily reflect those of the World Health Organization., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct regular situation analyses and to leverage models to adapt interventions to local needs. Here, we review applications of models to develop locally tailored interventions to support control and elimination efforts. In general, statistical and semi-mechanistic transmission models can be used to synthesize information from vaccination coverage, measles incidence, demographic, and/or serological data, offering a means to estimate the spatial and age-specific distribution of measles susceptibility. These estimates complete the picture provided by vaccination coverage alone, by accounting for natural immunity. Dynamic transmission models can then be used to evaluate the relative impact of candidate interventions for measles control and elimination and the expected future epidemiology. In most countries, models predict substantial numbers of susceptible individuals outside the age range of routine vaccination, which affects outbreak risk and necessitates additional intervention to achieve elimination. More effective use of models to inform both vaccination program planning and evaluation requires the development of training to enhance broader understanding of models and where feasible, building capacity for modelling in-country, pipelines for rapid evaluation of model predictions using surveillance data, and clear protocols for incorporating model results into decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. National immunization programs offer childhood vaccines through fixed and outreach services within the health system and often, additional supplementary immunization activities (SIAs) are undertaken to fill gaps and boost coverage. Here, we map predicted coverage at 1 × 1 km spatial resolution in five low- and middle-income countries to identify areas that are under-vaccinated via each delivery method using Demographic and Health Surveys data. We compare estimates of the coverage of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTP3), which is typically delivered through routine immunization (RI), with those of measles-containing vaccine (MCV) for which SIAs are also undertaken. We find that SIAs have boosted MCV coverage in some places, but not in others, particularly where RI had been deficient, as depicted by DTP coverage. The modelling approaches outlined here can help to guide geographical prioritization and strategy design.

Background: Control efforts for measles and rubella are intensifying globally. It becomes increasingly important to identify and reach remaining susceptible populations as elimination is approached., Methods: Serological surveys for measles and rubella can potentially measure susceptibility directly, but their use remains rare. In this study, using simulations, we outline key subtleties in interpretation associated with the dynamic context of age-specific immunity, highlighting how the patterns of immunity predicted from disease surveillance and vaccination coverage data may be misleading., Results: High-quality representative serosurveys could provide a more accurate assessment of immunity if challenges of conducting, analyzing, and interpreting them are overcome. We frame the core disease control and elimination questions that could be addressed by improved serological tools, discussing challenges and suggesting approaches to increase the feasibility and sustainability of the tool., Conclusions: Accounting for the dynamical context, serosurveys could play a key role in efforts to achieve and sustain elimination.

Background: Routine vaccination supplemented by planned campaigns occurring at 2-5 y intervals is the core of current measles control and elimination efforts. Yet, large, unexpected outbreaks still occur, even when control measures appear effective. Supplementing these activities with mass vaccination campaigns triggered when low levels of measles immunity are observed in a sample of the population (i.e., serosurveys) or incident measles cases occur may provide a way to limit the size of outbreaks., Methods and Findings: Measles incidence was simulated using stochastic age-structured epidemic models in settings conducive to high or low measles incidence, roughly reflecting demographic contexts and measles vaccination coverage of four heterogeneous countries: Nepal, Niger, Yemen, and Zambia. Uncertainty in underlying vaccination rates was modeled. Scenarios with case- or serosurvey-triggered campaigns reaching 20% of the susceptible population were compared to scenarios without triggered campaigns. The best performing of the tested case-triggered campaigns prevent an average of 28,613 (95% CI 25,722-31,505) cases over 15 y in our highest incidence setting and 599 (95% CI 464-735) cases in the lowest incidence setting. Serosurvey-triggered campaigns can prevent 89,173 (95% CI, 86,768-91,577) and 744 (612-876) cases, respectively, but are triggered yearly in high-incidence settings. Triggered campaigns reduce the highest cumulative incidence seen in simulations by up to 80%. While the scenarios considered in this strategic modeling exercise are reflective of real populations, the exact quantitative interpretation of the results is limited by the simplifications in country structure, vaccination policy, and surveillance system performance. Careful investigation into the cost-effectiveness in different contexts would be essential before moving forward with implementation., Conclusions: Serologically triggered campaigns could help prevent severe epidemics in the face of epidemiological and vaccination uncertainty. Hence, small-scale serology may serve as the basis for effective adaptive public health strategies, although, in high-incidence settings, case-triggered approaches are likely more efficient., Competing Interests: The authors have declared that no competing interests exist.

Seroepidemiology, the use of data on the prevalence of bio-markers of infection or vaccination, is a potentially powerful tool to understand the epidemiology of infection before vaccination and to monitor the effectiveness of vaccination programmes. Global and national burden of disease estimates for hepatitis B and rubella are based almost exclusively on serological data. Seroepidemiology has helped in the design of measles, poliomyelitis and rubella elimination programmes, by informing estimates of the required population immunity thresholds for elimination. It contributes to monitoring of these programmes by identifying population immunity gaps and evaluating the effectiveness of vaccination campaigns. Seroepidemiological data have also helped to identify contributing factors to resurgences of diphtheria, Haemophilus Influenzae type B and pertussis. When there is no confounding by antibodies induced by natural infection (as is the case for tetanus and hepatitis B vaccines), seroprevalence data provide a composite picture of vaccination coverage and effectiveness, although they cannot reliably indicate the number of doses of vaccine received. Despite these potential uses, technological, time and cost constraints have limited the widespread application of this tool in low-income countries. The use of venous blood samples makes it difficult to obtain high participation rates in surveys, but the performance of assays based on less invasive samples such as dried blood spots or oral fluid has varied greatly. Waning antibody levels after vaccination may mean that seroprevalence underestimates immunity. This, together with variation in assay sensitivity and specificity and the common need to take account of antibody induced by natural infection, means that relatively sophisticated statistical analysis of data is required. Nonetheless, advances in assays on minimally invasive samples may enhance the feasibility of including serology in large survey programmes in low-income countries. In this paper, we review the potential uses of seroepidemiology to improve vaccination policymaking and programme monitoring and discuss what is needed to broaden the use of this tool in low- and middle-income countries., (© 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Vaccination coverage is a widely used indicator of programme performance, measured by registries, routine administrative reports or household surveys. Because the population denominator and the reported number of vaccinations used in administrative estimates are often inaccurate, survey data are often considered to be more reliable. Many countries obtain survey data on vaccination coverage every 3-5years from large-scale multi-purpose survey programs. Additional surveys may be needed to evaluate coverage in Supplemental Immunization Activities such as measles or polio campaigns, or after major changes have occurred in the vaccination programme or its context. When a coverage survey is undertaken, rigorous statistical principles and field protocols should be followed to avoid selection bias and information bias. This requires substantial time, expertise and resources hence the role of vaccination coverage surveys in programme monitoring needs to be carefully defined. At times, programmatic monitoring may be more appropriate and provides data to guide program improvement. Practical field methods such as health facility-based assessments can evaluate multiple aspects of service provision, costs, coverage (among clinic attendees) and data quality. Similarly, purposeful sampling or censuses of specific populations can help local health workers evaluate their own performance and understand community attitudes, without trying to claim that the results are representative of the entire population. Administrative reports enable programme managers to do real-time monitoring, investigate potential problems and take timely remedial action, thus improvement of administrative estimates is of high priority. Most importantly, investment in collecting data needs to be complemented by investment in acting on results to improve performance., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries., Methods: We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000-2010 for each country, region and globally., Results: The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4-61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46-195) in the Western Pacific, excluding China, to 116 (95% CI: 56-235) and 121 (95% CI: 31-238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000-80,000) and SE Asia (49,000, 95% CI: 11,000-97,000). In 2010, 105,000 (95% CI: 54,000-158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000-169,000) in 1996., Conclusions: Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.

We investigated whether straight-line distance from residential compounds to healthcare facilities influenced mortality, the incidence of pneumonia and vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for pneumonia was conducted on 6938 children living in the catchment areas of the two largest healthcare facilities. Deaths were monitored by three-monthly home visits. Children living >5 km from the two largest healthcare facilities had a 2·78 [95% confidence interval (CI) 1·74-4·43] times higher risk of all-cause mortality compared to children living within 2 km of these facilities. The observed rate of clinical and radiological pneumonia was lower in children living >5 km from these facilities compared to those living within 2 km [rate ratios 0·65 (95% CI 0·57-0·73) and 0·74 (95% CI 0·55-0·98), respectively]. There was no association between distance and estimated pneumococcal vaccine efficacy. Geographical access to healthcare services is an important determinant of survival and pneumonia in children in rural Gambia.

Measles and rubella are major vaccine-preventable causes of child mortality and disability. They have been eliminated from the Americas and some other regions have also come close to elimination. In this paper, we review regional progress toward measles and rubella control/elimination goals, describe the recent epidemiology of these infections and discuss challenges to achieving the goals. Globally, measles vaccination is estimated to prevent nearly 2 million deaths each year. Despite this remarkable progress, large measles outbreaks have occurred in recent years, often involving older persons who were not vaccinated in earlier years. Such an occurrence would be particularly damaging for rubella control programmes as it could lead to peaks in congenital rubella syndrome. Challenges to achieving and sustaining high vaccination coverage include civil conflict, weak health systems, geographic, cultural and economic barriers to reaching certain population groups and inadequate monitoring and use of data for action. Countries and regions aiming to eliminate measles and control rubella urgently need to improve the implementation and monitoring of both routine and mass vaccination campaign strategies.

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.

Nationally representative household surveys are increasingly relied upon to measure maternal, newborn, and child health (MNCH) intervention coverage at the population level in low- and middle-income countries. Surveys are the best tool we have for this purpose and are central to national and global decision making. However, all survey point estimates have a certain level of error (total survey error) comprising sampling and non-sampling error, both of which must be considered when interpreting survey results for decision making. In this review, we discuss the importance of considering these errors when interpreting MNCH intervention coverage estimates derived from household surveys, using relevant examples from national surveys to provide context. Sampling error is usually thought of as the precision of a point estimate and is represented by 95% confidence intervals, which are measurable. Confidence intervals can inform judgments about whether estimated parameters are likely to be different from the real value of a parameter. We recommend, therefore, that confidence intervals for key coverage indicators should always be provided in survey reports. By contrast, the direction and magnitude of non-sampling error is almost always unmeasurable, and therefore unknown. Information error and bias are the most common sources of non-sampling error in household survey estimates and we recommend that they should always be carefully considered when interpreting MNCH intervention coverage based on survey data. Overall, we recommend that future research on measuring MNCH intervention coverage should focus on refining and improving survey-based coverage estimates to develop a better understanding of how results should be interpreted and used.

Background: A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3-4 years after primary vaccination., Methodology/principal Findings: We recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9 serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a median age of 45 months (range, 38-52 months); 138 had received 3 doses of PCV-9 in infancy and 144 were controls. Before receiving PCV-7, a high proportion of children had antibody concentrations >0.35 µg/mL to most of the serotypes in PCV-9 (average of 75% in the PCV-9 and 66% in the control group respectively). The geometric mean antibody concentrations in the vaccinated group were significantly higher compared to controls for serotypes 6B, 14, and 23F. Antibody concentrations were significantly increased to serotypes in the PCV-7 vaccine both 6-8 weeks and 16-18 months after PCV-7. Antibodies to serotypes 6B, 9V and 23F were higher in the PCV-9 group than in the control group 6-8 weeks after PCV-7, but only the 6B difference was sustained at 16-18 months. There was no significant difference in nasopharyngeal carriage between the two groups., Conclusions/significance: Pneumococcal antibody concentrations in Gambian children were high 34-48 months after a 3-dose primary infant vaccination series of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly higher than in control children for 3 of the 9 serotypes. Antibody concentrations increased after PCV-7 and remained raised for at least 18 months.

Background: Nasopharyngeal carriage of Streptococcus pneumoniae is extremely prevalent in The Gambia. We studied the effects of vaccination with pneumococcal conjugate vaccines on the carriage of individual serotypes and on antimicrobial resistance in vaccinated children and their younger siblings., Methods: A longitudinal study of a subsample of children (n=2342) who participated in a randomized, placebo controlled trial of a 9-valent pneumococcal conjugate vaccines (PCV-9) in The Gambia, and a cross-sectional study of non-PCV-9-vaccinated younger siblings (n=675)., Results: Recipients of PCV-9 were less likely to carry vaccine serotypes 4, 6B, 9V, 14, 19F, and 23F but more likely to carry vaccine-associated 19A and 9 nonvaccine serotypes at approximately 6 months postvaccination (age, 12 months) than were controls (each P<0.05). At approximately 16 months postvaccination, carriage of vaccine-associated-serotype 6A was also significantly reduced (P<0.01) while 3 other nonvaccine serotypes were more prevalent in the PCV-9 recipients (each P<0.05). At 16 months, but not 6 months, postvaccination PCV-9 recipients had lower rate of carrying isolates resistant to tetracycline and trimethoprim-sulfamethoxazole (TMP-SMZ) than controls (risk ratio: 0.90 and 0.95, respectively; each P<0.05). There was no difference in patterns of carriage of pneumococci in younger siblings of PCV-9 or placebo recipients., Conclusions: The effects of 9-valent pneumococcal conjugate vaccines on carriage of pneumococci persisted for at least 16 months postvaccination in Gambian children. Vaccination had no indirect effect on carriage in younger siblings and there was limited impact on antibiotic resistance.

Acute measles virus infection can result in a transient decrease in plasma human immunodeficiency virus type 1 (HIV-1) RNA loads. We report the kinetics of plasma HIV-1 RNA loads in 2 Zambian children with confirmed and probable measles, and show that the decline in viral load is of similar magnitude to the first-phase decay rate after initiation of antiretroviral therapy.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo. IgG antibodies to pneumococcal serotype 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F polysaccharides were measured by ELISA. The proportions of infants with antibody concentrations above 0.2, 0.35 and 1.0 microg/ml, and the geometric mean concentrations (GMCs) of anti-pneumococcal polysaccharide antibodies were substantially higher for each serotype in children who received three doses of PCV-9 than those in the placebo group. Among PCV-9 recipients, GMCs ranged between 2.61 and 11.09 microg/ml with the highest being against serotype 14 and the lowest against 9V polysaccharide. The estimated overall protective antibody level for all nine serotypes, based on the vaccine efficacy against vaccine-type invasive pneumococcal disease (IPD) of 77% (95% CI: 51, 90) observed in the trial, was 2.3 microg/ml (95% CI: 1.0, 5.0). The PCV-9 studied was immunogenic in a Gambian population where it was also found to be efficacious.