Progress Toward Regional Measles Elimination — Worldwide, 2000–2016

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan,† with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals.

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals. * The coverage milestone is to be met by every country, whereas the incidence and mortality reduction milestones are to be met globally. † The Global Vaccine Action Plan is the implementation plan of the Decade of Vaccines, a collaboration between WHO; the United Nations Children's Fund (UNICEF); the Bill and Melinda Gates Foundation; the National Institute of Allergy and Infectious Diseases; the African Leaders Malaria Alliance; Gavi, the Vaccine Alliance; and others to extend the full benefit of immunization to all persons by 2020 and beyond. In addition to 2015 targets, it also set a target for measles and rubella elimination in five of the six WHO regions by 2020. http://www.who.int/immunization/global_vaccine_action_plan/en; http:// apps.who.int/gb/ebwha/pdf_files/wha65/a65_22-en.pdf.

Immunization Activities
To estimate coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) through routine immunization services, § WHO and the United Nations Children's Fund (UNICEF) use data from administrative records (administrative coverage is calculated by dividing the vaccine doses administered by the estimated target population) and immunization coverage surveys reported annually by 194 countries. During 2000-2016, estimated MCV1 coverage increased globally from 72% to 85% (Table 1)  Abbreviations: CI = confidence interval; MCV1 = first dose of measles-containing vaccine; MCV2 = second dose of measles-containing vaccine; NA = not applicable; UNICEF = United Nations Children's Fund. * Mortality estimates for 2000 might be different from previous reports. When the model used to generate estimated measles deaths is rerun each year using the new WHO/UNICEF Estimates of National Immunization Coverage data, as well as updated surveillance data, adjusted results for each year, including the baseline year, are also produced and updated. † Coverage data: WHO/UNICEF Estimates of National Immunization Coverage, July 15, 2017 update. http://www.who.int/immunization/monitoring_surveillance/data/en. § Reported case data: measles cases (2016) from World Health Organization, as of July 15, 2017 (http://apps.who.int/immunization_monitoring/globalsummary/ timeseries/tsincidencemeasles.html). Reported cases are a sizeable underestimate of the actual number of cases, accounting for the inconsistency between reported cases and estimated deaths. ¶ Cases per 1 million population; population data from United Nations, Department of Economic and Social Affairs, Population Division, 2016. Any country not reporting data on measles cases for that year was removed from both the numerator and denominator.
increased from 15% in 2000 to 60% in 2015 and 64% in 2016 (Table 1). During 2016, approximately 119 million persons received supplementary doses of measles-containing vaccine (MCV) during 33 mass immunization campaigns, known as supplementary immunization activities (SIAs), ¶ implemented in 31 countries ( Table 2). Based on doses administered, SIA coverage was ≥95% in 20 (61%) SIAs. Among the six countries that conducted post-SIA coverage surveys, estimated coverage was ≥95% in three, 90%-94% in two, and 84% in one. ¶ Supplemental immunization activities (SIAs) generally are carried out using two target age ranges. An initial, nationwide catch-up SIA focuses on all children aged 9 months-14 years, with the goal of eliminating susceptibility to measles in the general population. Periodic follow-up SIAs then focus on all children born since the last SIA. Follow-up SIAs generally are conducted nationwide every 2-4 years and focus on children aged 9-59 months; their goal is to eliminate any measles susceptibility that has developed in recent birth cohorts and to protect children who did not respond to MCV1.

Disease Incidence
Countries report the aggregate number of incident measles cases** , † † to WHO and UNICEF annually through the Joint Reporting Form. In 2016, 189 (97%) countries conducted ** http://apps.who.int/immunization_monitoring/globalsummary/timeseries/ tsincidencemeasles.html. † † Measles cases are defined differently in different countries. Some countries define measles cases as those that are laboratory-confirmed or epidemiologically linked; others define measles cases as those that are laboratory-confirmed, epidemiologically linked, or clinically compatible. Laboratory-confirmed cases are suspected measles cases with specimens that have detectable measles virusspecific immunoglobulin class M (IgM) antibodies, or specimens from which measles virus can be isolated or measles virus genome can be detected in appropriate clinical specimens by a proficient laboratory. Epidemiologically linked confirmed measles cases are suspected measles cases that have not been confirmed by a laboratory but are geographically and temporally related to a laboratory-confirmed case or, in the event of a chain of transmission, to another epidemiologically confirmed measles case, with dates of rash onset between cases occurring 7-21 days apart. Clinically compatible measles cases are suspected measles cases with fever and maculopapular rash and cough, coryza, or conjunctivitis, for which no adequate clinical specimen was collected and which have not been linked epidemiologically to a laboratory-confirmed case of measles or to a laboratory-confirmed case of another communicable disease. Abbreviations: IPV = inactivated polio vaccine; N = National; OPV = oral polio vaccine; SIA = supplementary immunization activity; SN = subnational. * SIAs generally are carried out using two approaches: 1) An initial, nationwide catch-up SIA targets all children aged 9 months to 14 years; it has the goal of eliminating susceptibility to measles in the general population. Periodic follow-up SIAs then target all children born since the last SIA. 2) Follow-up SIAs are generally conducted nationwide every 2-4 years and target children aged 9-59 months; their goal is to eliminate any measles susceptibility that has developed in recent birth cohorts and to protect children who did not respond to the first measles vaccination. The exact age range for follow-up SIAs depends on the age-specific incidence of measles, coverage with 1 dose of measles-containing vaccine, and the time since the last SIA. † Values >100% indicate that the intervention reached more persons than the estimated target population. § Rollover national campaigns started the previous year or will continue into the next year.
case-based surveillance in at least part of the country, and 191 (98%) had access to standardized quality-controlled testing through the WHO Global Measles and Rubella Laboratory Network. Nonetheless, surveillance was weak in many countries; fewer than half of countries (64 of 134; 48%) achieved the sensitivity indicator target of two or more discarded measles and rubella § § cases per 100,000 population in 2016 compared with 2015 (80 of 135; 59%). § § A discarded case is defined as a suspected case that has been investigated and discarded as nonmeasles and as nonrubella using 1) laboratory testing in a proficient laboratory or 2) epidemiological linkage to a laboratory-confirmed outbreak of a communicable disease that is not measles or rubella. The discarded case rate is used to measure the sensitivity of measles surveillance.
During 2000-2016, the number of measles cases reported annually worldwide decreased 85%, from 853,479 in 2000 to 214,812 in 2015 and then to 132,137 in 2016; measles incidence decreased 87%, from 145 to 19 cases per 1 million population (Table 1). Compared with 2015, 2016 incidence decreased from 29 to 19 cases per million, although three fewer countries (173 of 194; 89%) reported case data in 2016 than did in 2015 (176 of 194; 92%). ¶ ¶ The percentage of reporting countries with fewer than five measles cases per million population increased from 38% (64/169) in 2000 to 69% (119/173) in 2016. During 2000-2016, measles incidence of fewer than five cases per million was sustained in AMR (Table 1).
During 2015-2016, the number of reported measles cases declined globally and in all regions (AFR, 31%; AMR, 98%; EMR, 71%; EUR, 84%; SEAR, 44%, and WPR, 11%). In addition to aggregate reporting, countries report measles case-based data to WHO monthly. In some countries large discrepancies exist between the two reporting systems. During 2016, some countries either did not report or reported only a fraction of monthly reported measles cases through the Joint Reporting Form (e.g., India reported 70,798 measles cases through monthly reporting, but only 17,250 through the Joint Reporting Form).

Disease and Mortality Estimates
A previously described model for estimating measles disease and mortality was updated with new measles vaccination coverage data, case data, and United Nations population estimates for all countries during 2000-2016, enabling derivation of a new series of disease and mortality estimates (5). Based on the updated data, the estimated number of measles cases declined from 29,068,400 (95% confidence interval ¶ ¶ Twenty-one countries did not report measles case data in 2016: Antigua  (Figure).

Regional Verification of Measles Elimination
In 2016, four WHO regions had functioning regional verification commissions. In September 2016, the AMR regional verification commission declared the region free of endemic measles (6). In 2016, the EUR commission verified measles elimination in 24 countries (7). Two SEAR countries (Bhutan and Maldives) were verified as having eliminated measles in 2017 (8

Discussion
During 2000-2016, increased coverage with MCV administered through routine immunization programs worldwide, combined with SIAs, contributed to an 87% decrease in reported measles incidence and an 84% reduction in estimated measles mortality. Measles vaccination prevented an estimated 20.4 million deaths during this period, and during 2016, for the first time ever, estimated measles deaths declined to fewer than 100,000. Furthermore, the number of countries with measles incidence of fewer than five per million population has increased, although considerable underreporting occurred, and AMR has maintained an incidence of fewer than five cases per million population during 2000-2016. The decreasing number of circulating measles virus genotypes suggests interruption of some chains of transmission. However, the 2015 global control milestones were not met, global MCV1 coverage has stagnated, global MCV2 coverage has reached only 64%, and SIA quality was inadequate to achieve ≥95% coverage in several countries. With suboptimal MCV coverage, outbreaks continued to occur among unvaccinated persons, including school-aged children and young adults.
The 2016 Mid-term Review of the Global Measles and Rubella Strategic Plan 2012-2020 concluded that measles elimination strategies were sound, and the WHO Strategic Advisory Group of Experts on Immunization endorsed its findings. The review noted, however, that implementation of the strategies needs improvement. Measures should focus on strengthening immunization and surveillance systems. The Measles and Rubella Initiative should increase its emphasis on using surveillance data to drive programmatic actions. The findings in this report are subject to at least three limitations. First, SIA coverage data might be biased by inaccurate reports of the number of doses delivered, doses administered to children outside the target age group, and inaccurate estimates of the target population size. Second, large differences between the estimated and reported incidence indicate variable surveillance sensitivity, making comparisons between countries and regions difficult to interpret. Finally, the accuracy of the results from the measles mortality model is affected by biases in all model inputs, including country-specific measles vaccination coverage and measles case-based surveillance data.
The decrease in measles mortality to fewer than 100,000 deaths in 2016 is one of five main contributors (along with decreases in mortality from diarrhea, malaria, pneumonia, and neonatal intrapartum deaths) to the decline in overall child mortality worldwide and progress toward the fourth United Nations Millennium Development Goal, but continued work is needed to help achieve measles elimination goals (10). Of concern is the possibility that the gains made and future progress in measles elimination could be reversed when polio-funded resources supporting routine immunization services, measles SIAs, and measles surveillance diminish and disappear after polio eradication. Countries with the highest measles mortality rely most heavily on polio-funded resources and are at highest risk for reversal of progress after polio eradication is achieved. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage with substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals.

Conflict of interest
No conflicts of interest were reported.

Summary
What is already known about this topic?
The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage.
What is added by this report?
For the first time, annual estimated measles deaths were fewer than 100,000, in 2016. This achievement follows an increase in the number of countries providing the second dose of measlescontaining vaccine (MCV2) nationally through routine immunization services to 164 (85%) of 194 countries, and the vaccination of approximately 119 million persons against measles during supplementary immunization activities in 2016. During 2000-2016, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, annual estimated measles deaths decreased 84%, from 550,100 to 89,780, and an estimated 20.4 million deaths were prevented. However, the 2015 measles elimination milestones have not yet been met, and only one World Health Organization region has been verified as having eliminated measles.
What are the implications for public health practice?
To achieve measles elimination goals, countries and their partners need to act urgently to secure political commitment, raise the visibility of measles elimination, increase vaccination coverage, strengthen surveillance, and mitigate the threat of decreasing resources once polio eradication is achieved. Polio eradication resources have supported routine immunization services and surveillance activities.