Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

Who is missed in a community-based survey: Assessment and implications of biases due to incomplete sampling frame in a community-based serosurvey, Choma and Ndola Districts, Zambia, 2022.

Community-based serological studies are increasingly relied upon to measure disease burden, identify population immunity gaps, and guide control and elimination strategies; however, there is little understanding of the potential for and impact of sampling biases on outcomes of interest. As part of efforts to quantify measles immunity gaps in Zambia, a community-based serological survey using stratified multi-stage cluster sampling approach was conducted in Ndola and Choma districts in May-June 2022, enrolling 1245 individuals. We carried out a follow-up study among individuals missed from the sampling frame of the serosurvey in July-August 2022, enrolling 672 individuals. We assessed the potential for and impact of biases in the community-based serosurvey by i) estimating differences in characteristics of households and individuals included and excluded (77% vs 23% of households) from the sampling frame of the serosurvey and ii) evaluating the magnitude these differences make on healthcare-seeking behavior, vaccination coverage, and measles seroprevalence. We found that missed households were 20% smaller and 25% less likely to have children. Missed individuals resided in less wealthy households, had different distributions of sex and occupation, and were more likely to seek care at health facilities. Despite these differences, simulating a survey in which missed households were included in the sampling frame resulted in less than a 5% estimated bias in these outcomes. Although community-based studies are upheld as the gold standard study design in assessing immunity gaps and underlying community health characteristics, these findings underscore the fact that sampling biases can impact the results of even well-conducted community-based surveys. Results from these studies should be interpreted in the context of the study methodology and challenges faced during implementation, which include shortcomings in establishing accurate and up-to-date sampling frames. Failure to account for these shortcomings may result in biased estimates and detrimental effects on decision-making.

The 2020 immunization programme landscape: Piloting an assessment metric to evaluate the maturity of national immunization programmes across the life course.

BACKGROUND: The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity. METHODS: Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group. RESULTS: More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16). DISCUSSION: The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead.

An Estimate Of The Return On Investment Of A Malaria Vaccine In 20 Sub-Saharan African Countries, 2021-30.

Malaria is a leading global health problem that was responsible for an estimated 619,000 deaths worldwide in 2021. We modeled the return on investment (ROI) for the introduction and continuation of a four-dose malaria vaccine, RTS,S/AS01, from 2021 to 2030 in twenty sub-Saharan African countries supported by Gavi, the Vaccine Alliance. We used the Decade of Vaccine Economics benefits and costing outputs to calculate an ROI using health impact data modeled by the Swiss Tropical and Public Health Institute (hereafter "Swiss") and Imperial College London (hereafter "Imperial"). The Swiss estimates with a base vaccine price of US$7.00 resulted in an ROI of 0.42, and the Imperial impact estimates with the same base vaccine price resulted in an ROI of 2.30. Inclusion of the fifth seasonal dose for ten countries exhibiting high seasonal disease burden increased the Swiss ROI by 143 percent, to 1.02, and the Imperial ROI by 23.5 percent, to 2.84. To improve ROI, decision makers should continue to improve delivery platforms, decrease vaccine delivery costs, deliver the malaria vaccine in fewer doses, and provide access to vaccine resources.

Challenges Addressing Inequalities in Measles Vaccine Coverage in Zambia through a Measles-Rubella Supplementary Immunization Activity during the COVID-19 Pandemic.

BACKGROUND: Measles-rubella supplementary immunization activities (MR-SIAs) are conducted to address inequalities in coverage and fill population immunity gaps when routine immunization services fail to reach all children with two doses of a measles-containing vaccine (MCV). We used data from a post-campaign coverage survey in Zambia to measure the proportion of measles zero-dose and under-immunized children who were reached by the 2020 MR-SIA and identified reasons associated with persistent inequalities following the MR-SIA. METHODS: Children between 9 and 59 months were enrolled in a nationally representative, cross-sectional, multistage stratified cluster survey in October 2021 to estimate vaccination coverage during the November 2020 MR-SIA. Vaccination status was determined by immunization card or through caregivers' recall. MR-SIA coverage and the proportion of measles zero-dose and under-immunized children reached by MR-SIA were estimated. Log-binomial models were used to assess risk factors for missing the MR-SIA dose. RESULTS: Overall, 4640 children were enrolled in the nationwide coverage survey. Only 68.6% (95% CI: 66.7%, 70.6%) received MCV during the MR-SIA. The MR-SIA provided MCV1 to 4.2% (95% CI: 0.9%, 4.6%) and MCV2 to 6.3% (95% CI: 5.6%, 7.1%) of enrolled children, but 58.1% (95% CI: 59.8%, 62.8%) of children receiving the MR-SIA dose had received at least two prior MCV doses. Furthermore, 27.8% of measles zero-dose children were vaccinated through the MR-SIA. The MR-SIA reduced the proportion of measles zero-dose children from 15.1% (95% CI: 13.6%, 16.7%) to 10.9% (95% CI: 9.7%, 12.3%). Zero-dose and under-immunized children were more likely to miss MR-SIA doses (prevalence ratio (PR): 2.81; 95% CI: 1.80, 4.41 and 2.22; 95% CI: 1.21 and 4.07) compared to fully vaccinated children. CONCLUSIONS: The MR-SIA reached more under-immunized children with MCV2 than measles zero-dose children with MCV1. However, improvement is needed to reach the remaining measles zero-dose children after SIA. One possible solution to address the inequalities in vaccination is to transition from nationwide non-selective SIAs to more targeted and selective strategies.

Feasibility assessment of measles and rubella eradication.

This report addresses the epidemiological aspects and feasibility of measles and rubella eradication and the potential resource requirements in response to the request of the Director-General at the Seventieth World Health Assembly held on May 31, 2017. A guiding principle is that the path toward measles and rubella eradication should serve to strengthen primary health care, promote universal health coverage, and be a pathfinder for new vision and strategy for immunization over the next decade as laid out in the Immunization Agenda 2030. Specifically, this report: 1) highlights the importance of measles and rubella as global health priorities; 2) reviews the current global measles and rubella situation; 3) summarizes prior assessments of the feasibility of measles and rubella eradication; 4) assesses the progress and challenges in achieving regional measles and rubella elimination; 5) assesses additional considerations for measles and rubella eradication, including the results of modelling and economic analyses; 6) assesses the implications of establishing a measles and rubella eradication goal and the process for setting an eradication target date; 7) proposes a framework for determining preconditions for setting a target date for measles and rubella eradication and how these preconditions should be understood and used; and 8) concludes with recommendations endorsed by SAGE.

The cost-effectiveness of scaling-up rapid point-of-care testing for early infant diagnosis of HIV in southern Zambia.

INTRODUCTION: Early infant diagnosis (EID) and treatment can prevent much of the HIV-related morbidity and mortality experienced by children but is challenging to implement in sub-Saharan Africa. Point-of-care (PoC) testing would decentralize testing and increase access to rapid diagnosis. The objective of this study was to determine the cost-effectiveness of PoC testing in Southern Province, Zambia. METHODS: A decision tree model was developed to compare health outcomes and costs between the standard of care (SoC) and PoC testing using GeneXpert and m-PIMA platforms. The primary health outcome was antiretroviral treatment (ART) initiation within 60 days of sample collection. Additional outcomes included ART initiation by 12 months of age and death prior to ART initiation. Costs included both capital and recurrent costs. Health outcomes and costs were combined to create incremental cost effectiveness ratios (ICERs). RESULTS: The proportion of children initiating ART within 60 days increased from 27.8% with SoC to 79.8-82.8% with PoC testing depending on the algorithm and platform. The proportion of children initiating ART by 12 months of age increased from 50.9% with SoC to 84.0-86.5% with PoC testing. The proportion of HIV-infected children dying prior to ART initiation decreased from 18.1% with SoC to 3.8-4.6% with PoC testing. Total program costs were similar for the SoC and GeneXpert but higher for m-PIMA. ICERs for PoC testing were favorable, ranging from $23-1,609 for ART initiation within 60 days, $37-2,491 for ART initiation by 12 months of age, and $90-6,188 for deaths prior to ART initiation. Factors impacting the costs of PoC testing, including the lifespan of the testing instruments and integrated utilization of PoC platforms, had the biggest impact on the ICERs. Integrating utilization across programs decreased costs for the EID program, such that PoC testing was cost-saving in some situations. CONCLUSION: PoC testing has the potential to improve linkage to care and ART initiation for HIV-infected infants and should be considered for implementation within EID programs to achieve equity in access to HIV services and reduce HIV-related pediatric morbidity and mortality.

Modeling the cost-effectiveness of point-of-care platforms for infant diagnosis of HIV in sub-Saharan African countries.

BACKGROUND: Early infant diagnosis of HIV (EID) improves child survival through earlier initiation of antiretroviral therapy (ART). In many settings, ART initiation is hindered by delays in testing performed in centralized labs. Point-of-care (PoC) platforms offer opportunities to improve the timeliness of ART initiation. METHODS: We used a mathematical model to estimate the costs and performance of on-site PoC testing using three platforms (m-PIMA, GeneXpert IV, and GeneXpert Edge) compared with the standard of care (SoC). Primary outcomes included ART initiation within 60 days of sample collection, HIV-related mortality before ART initiation, and incremental cost-effectiveness ratios (ICERs). RESULTS: PoC testing significantly increased ART initiation within 60 days (from 19% with SoC to 82-84% with PoC) and decreased HIV-related mortality (from 23% with SoC to 5% with PoC). ART initiation and mortality were similar across PoC platforms. When only used for EID and with high coverage of prevention of mother-to-child transmission (PMTCT) programs, ICERs for PoC testing compared with the SoC ranged from $430 to $1097 per additional infant on ART within 60 days and from $1527 to $3888 per death averted. PoC-based testing was more cost-effective in settings with lower PMTCT coverage, greater delays in the SoC, and when PoC instruments could be integrated with other disease programs. CONCLUSION: Our findings illustrate that PoC platforms can dramatically improve the timeliness of EID and linkage to HIV care. The cost-effectiveness of PoC platforms depends on the cost of PoC testing, existing access to diagnostic testing, and the ability to integrate PoC testing with non-EID programs.

How much does it cost to measure immunity? A costing analysis of a measles and rubella serosurvey in southern Zambia.

BACKGROUND: Serosurveys are a valuable surveillance tool because they provide a more direct measure of population immunity to infectious diseases, such as measles and rubella, than vaccination coverage estimates. However, there is concern that serological surveys are costly. We adapted a framework to capture the costs associated with conducting a serosurvey in Zambia. METHODS: We costed a nested serosurvey in Southern Province, Zambia that collected dried blood spots from household residents in a post-campaign vaccine coverage survey. The financial costs were estimated using an ingredients-based costing approach. Inputs included personnel, transportation, field consumable items, social mobilization, laboratory supplies, and capital items, and were classified by serosurvey function (survey preparation, data collection, biospecimen collection, laboratory testing, and coordination). Inputs were stratified by whether they were applicable to surveys in general or attributable specifically to serosurveys. Finally, we calculated the average cost per cluster and participant. RESULTS: We estimated the total nested serosurvey cost was US $68,558 to collect dried blood spots from 658 participants in one province in Zambia. A breakdown of the cost by serosurvey phase showed data collection accounted for almost one third of the total serosurvey cost (32%), followed by survey preparation (25%) and biospecimen collection (20%). Analysis by input categories indicated personnel costs were the largest contributing input to overall serosurvey costs (51%), transportation was second (23%), and field consumables were third (9%). By combining the serosurvey with a vaccination coverage survey, there was a savings of $43,957. We estimated it cost $4,285 per average cluster and $104 per average participant sampled. CONCLUSIONS: Adding serological specimen collection to a planned vaccination coverage survey provided a more direct measurement of population immunity among a wide age group but increased the cost by approximately one-third. Future serosurveys could consider ways to leverage existing surveys conducted for other purposes to minimize costs.

Relative Contributions of Malaria, Inflammation, and Deficiencies of Iron and Vitamin A to the Burden of Anemia during Low and High Malaria Seasons in Rural Zambian Children.

OBJECTIVE: To estimate the burden of anemia attributable to malaria, inflammation, and deficiency of iron or vitamin A during low and high malaria seasons among Zambian children. STUDY DESIGN: From a cohort of children (n = 820), 4-8 years of age participating in a randomized controlled trial of pro-vitamin A, we estimated attributable fractions for anemia (hemoglobin of <110 or 115 g/L, by age) owing to current malaria or inflammation (C-reactive protein of >5 mg/L, or α-1 acid glycoprotein of >1 g/L, or both), and current or prior iron deficiency (ID; defined as low ferritin [<12 or 15 µg/L for age <5 or >5 years] or functional ID [soluble transferrin receptor of >8.3 mg/L] or both) and vitamin A deficiency (retinol of <0.7 µmol/L), during low and high malaria seasons, using multivariate logistic regression. Serum ferritin, soluble transferrin receptor, and retinol were adjusted for inflammation. RESULTS: The burden of anemia independently associated with current malaria, inflammation, ID, and vitamin A deficiency in the low malaria season were 12% (P < .001), 6% (P = .005), 14% (P = .001), and 2% (P = .07), respectively, and 32% (P < .001), 15% (P < .001), 10% (P = .06), and 2% (P = .06), respectively, in the high malaria season. In both seasons, functional ID was independently associated with more anemia (approximately 11%) than low ferritin (approximately 4%). Anemia and ID in the low malaria season, accounted for 20% (P < .001) and 4% (P = .095) of the anemia in the subsequent high malaria season. CONCLUSIONS: Anemia in this population is strongly linked to malaria, inflammation, and functional ID, and to a lesser extent, low iron stores. Integrated control strategies are needed.

Distinct Antibody Signatures Associated with Different Malaria Transmission Intensities in Zambia and Zimbabwe.

Antibodies to Plasmodium falciparum are specific biomarkers that can be used to monitor parasite exposure over broader time frames than microscopy, rapid diagnostic tests, or molecular assays. Consequently, seroprevalence surveys can assist with monitoring the impact of malaria control interventions, particularly in the final stages of elimination, when parasite incidence is low. The protein array format to measure antibodies to diverse P. falciparum antigens requires only small sample volumes and is high throughput, permitting the monitoring of malaria transmission on large spatial and temporal scales. We expanded the use of a protein microarray to assess malaria transmission in settings beyond those with a low malaria incidence. Antibody responses in children and adults were profiled, using a P. falciparum protein microarray, through community-based surveys in three areas in Zambia and Zimbabwe at different stages of malaria control and elimination. These three epidemiological settings had distinct serological profiles reflective of their malaria transmission histories. While there was little correlation between transmission intensity and antibody signals (magnitude or breadth) in adults, there was a clear correlation in children younger than 5 years of age. Antibodies in adults appeared to be durable even in the absence of significant recent transmission, whereas antibodies in children provided a more accurate picture of recent levels of transmission intensity. Seroprevalence studies in children could provide a valuable marker of progress toward malaria elimination.IMPORTANCE As malaria approaches elimination in many areas of the world, monitoring the effect of control measures becomes more important but challenging. Low-level infections may go undetected by conventional tests that depend on parasitemia, particularly in immune individuals, who typically show no symptoms of malaria. In contrast, antibodies persist after parasitemia and may provide a more accurate picture of recent exposure. Only a few parasite antigens-mainly vaccine candidates-have been evaluated in seroepidemiological studies. We examined antibody responses to 500 different malaria proteins in blood samples collected through community-based surveillance from areas with low, medium, and high malaria transmission intensities. The breadth of the antibody responses in adults was broad in all three settings and was a poor correlate of recent exposure. In contrast, children represented a better sentinel population for monitoring recent malaria transmission. These data will help inform the use of multiplex serology for malaria surveillance.

Accelerating measles and rubella elimination through research and innovation - Findings from the Measles & Rubella Initiative research prioritization process, 2016.

The Measles & Rubella Initiative (M&RI) identified five key strategies to achieve measles and rubella elimination, including research and innovation to support cost-effective operations and improve vaccination and diagnostic tools. In 2016, the M&RI Research and Innovation Working Group (R&IWG) completed a research prioritization process to identify key research questions and update the global research agenda. The R&IWG reviewed meeting reports and strategic planning documents and solicited programmatic inputs from vaccination experts at the program operational level through a web survey, to identify previous research priorities and new research questions. The R&IWG then convened a meeting of experts to prioritize the identified research questions in four strategic areas: (1) epidemiology and economics, (2) surveillance and laboratory, (3) immunization strategies, and (4) demand creation and communications. The experts identified 19 priority research questions in the four strategic areas to address key areas of work necessary to further progress toward elimination. Future commitments from partners will be needed to develop a platform for improved coordination with adequate and predictable resources for research implementation and innovation to address these identified priorities.

Comparison of three rapid household survey sampling methods for vaccination coverage assessment in a peri-urban setting in Pakistan.

BACKGROUND: Household surveys are an essential tool for vaccine coverage monitoring in developing countries, and the World Health Organization (WHO) Expanded Program on Immunization (EPI) cluster survey design has been a default choice for decades. In response to methodological limitations of the traditional EPI sampling, alternative methods have been proposed, based on modern statistical and geographical techniques. This study compared the coverage estimates and the time efficiency of the EPI sampling design and two alternative methods: the compact segment sampling and innovative grid-based geographical information system (GIS) sampling. METHODS: We conducted a series of equal-sized concurrent prospective vaccine coverage surveys in Karachi, Pakistan, from January to December 2016, using traditional EPI, compact segment and grid-based GIS sampling methods. RESULTS: No differences in vaccine coverage estimates were identified across sampling methods in the peri-urban setting; however, due to stronger clustering effects and correct incorporation of sampling weights, the compact segment [design effect (DEFF) = 2.03] and the grid-based GIS surveys (DEFF = 1.72) had higher design effects and, therefore, appeared to have lower statistical precision than the traditional EPI surveys (DEFF = 1.57). To achieve the same level of apparent precision, data collection activities in the compact segment surveys would require more than twice the implementation time needed compared with the traditional EPI surveys. CONCLUSIONS: The precision of the EPI surveys appeared higher than that of the alternative methods because, under a questionable self-weighting assumption, the estimated design effect did not account for variable sampling weights. The compact segment and grid-based GIS methods were designed to improve randomness and representativeness of sampling households. Although these alternative methods did not result in coverage estimates that differed from the EPI survey results in the peri-urban setting, they have a lower risk of selection bias and therefore may be preferred.

Spatial and temporal changes in household structure locations using high-resolution satellite imagery for population assessment: an analysis in southern Zambia, 2006-2011.

Satellite imagery is increasingly available at high spatial resolution and can be used for various purposes in public health research and programme implementation. Comparing a census generated from two satellite images of the same region in rural southern Zambia obtained four and a half years apart identified patterns of household locations and change over time. The length of time that a satellite image-based census is accurate determines its utility. Households were enumerated manually from satellite images obtained in 2006 and 2011 of the same area. Spatial statistics were used to describe clustering, cluster detection, and spatial variation in the location of households. A total of 3821 household locations were enumerated in 2006 and 4256 in 2011, a net change of 435 houses (11.4% increase). Comparison of the images indicated that 971 (25.4%) structures were added and 536 (14.0%) removed. Further analysis suggested similar household clustering in the two images and no substantial difference in concentration of households across the study area. Cluster detection analysis identified a small area where significantly more household structures were removed than expected; however, the amount of change was of limited practical significance. These findings suggest that random sampling of households for study participation would not induce geographic bias if based on a 4.5-year-old image in this region. Application of spatial statistical methods provides insights into the population distribution changes between two time periods and can be helpful in assessing the accuracy of satellite imagery.

Predictive Malaria Risk and Uncertainty Mapping in Nchelenge District, Zambia: Evidence of Widespread, Persistent Risk and Implications for Targeted Interventions.

Malaria risk maps may be used to guide policy decisions on whether vector control interventions should be targeted and, if so, where. Active surveillance for malaria was conducted through household surveys in Nchelenge District, Zambia from April 2012 through December 2014. Households were enumerated based on satellite imagery and randomly selected for study enrollment. At each visit, participants were administered a questionnaire and a malaria rapid diagnostic test (RDT). Logistic regression models were used to construct spatial prediction risk maps and maps of risk uncertainty. A total of 461 households were visited, comprising 1,725 participants, of whom 48% were RDT positive. Several environmental features were associated with increased household malaria risk in a multivariable logistic regression model adjusting for seasonal variation. The model was validated using both internal and external evaluation measures to generate and assess root mean square error, as well as sensitivity and specificity for predicted risk. The final, validated model was used to predict and map malaria risk including a measure of risk uncertainty. Malaria risk in a high, perennial transmission setting is widespread but heterogeneous at a local scale, with seasonal variation. Targeting malaria control interventions may not be appropriate in this epidemiological setting.

Research priorities for global measles and rubella control and eradication.

In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibility of measles eradication concluded that (1) measles can and should be eradicated, (2) eradication by 2020 is feasible if measurable progress is made toward existing 2015 measles mortality reduction targets, (3) measles eradication activities should occur in the context of strengthening routine immunization services, and (4) measles eradication activities should be used to accelerate control and elimination of rubella and congenital rubella syndrome (CRS). The expert advisory panel also emphasized the critical role of research and innovation in any disease control or eradication program. In May 2011, a meeting was held to identify and prioritize research priorities to support measles and rubella/CRS control and potential eradication activities. This summary presents the questions identified by the meeting participants and their relative priority within the following categories: (1) measles epidemiology, (2) vaccine development and alternative vaccine delivery, (3) surveillance and laboratory methods, (4) immunization strategies, (5) mathematical modeling and economic analyses, and (6) rubella/CRS control and elimination.

Measles.

Measles is a highly contagious disease caused by measles virus and is one of the most devastating infectious diseases of man--measles was responsible for millions of deaths annually worldwide before the introduction of the measles vaccines. Remarkable progress in reducing the number of people dying from measles has been made through measles vaccination, with an estimated 164,000 deaths attributed to measles in 2008. This achievement attests to the enormous importance of measles vaccination to public health. However, this progress is threatened by failure to maintain high levels of measles vaccine coverage. Recent measles outbreaks in sub-Saharan Africa, Europe, and the USA show the ease with which measles virus can re-enter communities if high levels of population immunity are not sustained. The major challenges for continued measles control and eventual eradication will be logistical, financial, and the garnering of sufficient political will. These challenges need to be met to ensure that future generations of children do not die of measles.