Eradicating Measles: A Call for an Exceptional Coordinated Global Effort.

There are compelling epidemiological, economic, and ethical arguments for setting a global measles eradication goal. The 6 chairpersons of Regional Verification Commissions for Measles and Rubella elimination advocate that the time for courageously accelerating efforts to ensure a world where no child dies of measles, is NOW!

Emerging and Reemerging Aedes-Transmitted Arbovirus Infections in the Region of the Americas: Implications for Health Policy.

The increasing geographical spread and disease incidence of arboviral infections are among the greatest public health concerns in the Americas. The region has observed an increasing trend in dengue incidence in the last decades, evolving from low to hyperendemicity. Yellow fever incidence has also intensified in this period, expanding from sylvatic-restricted activity to urban outbreaks. Chikungunya started spreading pandemically in 2005 at an unprecedented pace, reaching the Americas in 2013. The following year, Zika also emerged in the region with an explosive outbreak, carrying devastating congenital abnormalities and neurologic disorders and becoming one of the greatest global health crises in years. The inadequate arbovirus surveillance in the region and the lack of serologic tests to differentiate among viruses poses substantial challenges. The evidence for vector control interventions remains weak. Clinical management remains the mainstay of arboviral disease control. Currently, only yellow fever and dengue vaccines are licensed in the Americas, with several candidate vaccines in clinical trials. The Global Arbovirus Group of Experts provides in this article an overview of progress, challenges, and recommendations on arboviral prevention and control for countries of the Americas.

Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome.

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs.

Accelerating Global Measles and Rubella Eradication-Saving Millions of Lives, Preventing Disability, and Averting the Next Pandemic.

No vaccine has been more effective in reducing disease burden, especially in preventing child deaths, than measles-containing vaccine. The return on investment makes measles-containing vaccine one of the most cost-effective public health measures available. Exhaustive reviews of biological, technical, economic and programmatic evidence have concluded that measles can and should be eradicated, and by including rubella antigen in measles-containing vaccine, congenital rubella syndrome will also be eradicated. All World Health Organisation Regions have pledged to achieve measles elimination. Unfortunately, not all countries and global partners have demonstrated an appropriate commitment to these laudable public health goals, and the negative impact of the COVID-19 pandemic on coverage rates has been profound. Unsurprisingly, large disruptive outbreaks are already occurring in many countries with a global epidemic curve ominously similar to that of 2018/2019 emerging. The Immunization Agenda 2030 will fail dismally unless measles and rubella eradication efforts are accelerated. Over half of all member states have been verified to have eliminated rubella and endemic rubella transmission has not been re-established in any country to date. In 2023, 84 countries and areas were verified to have sustained elimination of measles. However, without a global target, this success will be difficult to sustain. Now is the time for a global eradication goal and commitment by the World Health Assembly. Having a galvanising goal, with a shared call for action, will demand adequate resourcing from every country government and global partners. Greater coordination across countries and regions will be necessary. Measles, rubella and congenital rubella syndrome eradication should not remain just a technically feasible possibility but rather be completed to ensure that future generations of children do not live under the shadow of preventable childhood death and lifelong disability.

Potential intussusception risk versus health benefits from rotavirus vaccination in Latin America.

BACKGROUND: With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine, the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination. To inform policy considerations, we estimated excess intussusception cases and mortality potentially caused by rotavirus vaccine for each of the 14 countries and compared these estimates to hospitalizations and deaths expected to be averted through vaccination. METHODS: We used regional rotavirus disease burden and rotavirus vaccine efficacy data, global natural intussusception and regional rotavirus vaccine-related risk estimates, and country-specific diphtheria, tetanus, and pertussus vaccination coverage rates to estimate rotavirus vaccine coverage rates. We performed a probabilistic sensitivity analysis to account for uncertainty in these parameters. RESULTS: For an aggregate hypothetical birth cohort of 9.5 million infants in these 14 countries, rotavirus vaccine would annually prevent 144 746 (90% confidence interval [CI], 128 821-156 707) hospitalizations and 4124 deaths (90% CI, 3740-4239) due to rotavirus in their first 5 years of life but could cause an additional 172 hospitalizations (90% CI, 126-293) and 10 deaths (90% CI, 6-17) due to intussusception, yielding benefit-risk ratios for hospitalization and death of 841:1 (90% CI, 479:1 to 1142:1) and 395:1 (90% CI, 207:1 to 526:1), respectively. In an uncertainty analysis using 10 000 simulations of our probabilistic parameters, in comparing rotavirus disease averted to intussusception events caused, the hospitalization ratio was never below 100:1, and our death ratio fell below 100:1 only once. CONCLUSIONS: The health benefits of vaccination far outweigh the short-term risks and support continued rotavirus vaccination in Latin America.

Seasonal Influenza Prevention and Control Progress in Latin America and the Caribbean in the Context of the Global Influenza Strategy and the COVID-19 Pandemic.

Each year in Latin America and the Caribbean, seasonal influenza is associated with an estimated 36,500 respiratory deaths and 400,000 hospitalizations. Since the 2009 influenza A(H1N1) pandemic, the Region has made significant advances in the prevention and control of seasonal influenza, including improved surveillance systems, burden estimates, and vaccination of at-risk groups. The Global Influenza Strategy 2019-2030 provides a framework to strengthen these advances. Against the backdrop of this new framework, the University of Colorado convened in October 2020 its Immunization Advisory Group of Experts to review and discuss current surveillance, prevention, and control strategies for seasonal influenza in Latin America and the Caribbean, also in the context of the COVID-19 pandemic. This review identified five areas for action and made recommendations specific to each area. The Region should continue its efforts to strengthen surveillance and impact evaluations. Existing data on disease burden, seasonality patterns, and vaccination effectiveness should be used to inform decision-making at the country level as well as advocacy efforts for programmatic resources. Regional and country strategic plans should be prepared and include specific targets for 2030. Existing investments in influenza prevention and control, including for immunization programs, should be optimized. Finally, regional partnerships, such as the regional networks for syndromic surveillance and vaccine effectiveness evaluation (SARInet and REVELAC-i), should continue to play a critical role in continuous learning and standardization by sharing experiences and best practices among countries.

The ethical case for global measles eradication-justice and the Rule of Rescue.

Measles causes a substantial disease burden for all countries, while mortality is greatest in underserved, marginalized populations. Global measles eradication is feasible and the strategies critically rely upon well-functioning national immunisation programs and surveillance systems. All six regions of the World Health Organisation have adopted measles elimination targets. The Rule of Rescue and the principle of justice leave no ethical place for health programs, governments, global public health bodies or donors to hide if they impede efforts to eradicate measles globally by not taking all necessary actions to establish a global eradication target and committing the resources essential to achieve this goal.

Confirmation of rubella within 4 days of rash onset: comparison of rubella virus RNA detection in oral fluid with immunoglobulin M detection in serum or oral fluid.

Rubella virus infection is typically diagnosed by the identification of rubella virus-specific immunoglobulin M (IgM) antibodies in serum, but approximately 50% of serum samples from rubella cases collected on the day of rash onset are negative for rubella virus-specific IgM. The ability to detect IgM in sera and oral fluids was compared with the ability to detect rubella virus RNA in oral fluids by reverse transcription-PCR (RT-PCR) by using paired samples taken within the first 4 days after rash onset from suspected rubella cases during an outbreak in Perú. Sera were tested for IgM by both indirect and capture enzyme immunoassays (EIAs), and oral fluids were tested for IgM by a capture EIA. Tests for IgM in serum were more sensitive for the confirmation of rubella than the test for IgM in oral fluid during the 4 days after rash onset. RT-PCR confirmed more suspected cases than serum IgM tests on days 1 and 2 after rash onset. The methods confirmed approximately the same number of cases on days 3 and 4 after rash onset. However, a few cases were detected by serum IgM tests but not by RT-PCR even on the day of rash onset. Nine RT-PCR-positive oral fluid specimens were shown to contain rubella virus sequences of genotype 1C. In summary, RT-PCR testing of oral fluid confirmed more rubella cases than IgM testing of either serum or oral fluid samples collected in the first 2 days after rash onset; the maximum number of confirmations of rubella cases was obtained by combining RT-PCR and serology testing.

Expansion of seasonal influenza vaccination in the Americas.

BACKGROUND: Seasonal influenza is a viral disease whose annual epidemics are estimated to cause three to five million cases of severe illness and 250,000 to 500,000 deaths worldwide. Vaccination is the main strategy for primary prevention. METHODS: To assess the status of influenza vaccination in the Americas, influenza vaccination data reported to the Pan American Health Organization (PAHO) through 2008 were analyzed. RESULTS: Thirty-five countries and territories administered influenza vaccine in their public health sector, compared to 13 countries in 2004. Targeted risk groups varied. Sixteen countries reported coverage among older adults, ranging from 21% to 100%; coverage data were not available for most countries and targeted populations. Some tropical countries used the Northern Hemisphere vaccine formulation and others used the Southern Hemisphere vaccine formulation. In 2008, approximately 166.3 million doses of seasonal influenza vaccine were purchased in the Americas; 30 of 35 countries procured their vaccine through PAHO's Revolving Fund. CONCLUSION: Since 2004 there has been rapid uptake of seasonal influenza vaccine in the Americas. Challenges to fully implement influenza vaccination remain, including difficulties measuring coverage rates, variable vaccine uptake, and limited surveillance and effectiveness data to guide decisions regarding vaccine formulation and timing, especially in tropical countries.

Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated. After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

Progress in vaccination against hepatitis B in the Americas.

Hepatitis B is a serious public health problem leading to chronic infection, liver cirrhosis, and hepatocellular carcinoma. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) recommend routine universal infant vaccination against hepatitis B as the main strategy for the control hepatitis B and its severe consequences. PAHO additionally recommends routinely vaccinating healthcare workers. As of 2005, all countries in the Americas, except Haiti and Dominica, have hepatitis B vaccine in their childhood immunization schedule; 13 countries/territories include a hepatitis B dose given at birth. Hepatitis B vaccine has been incorporated into national schedules using different modalities; notably, 28 countries use it as a combination vaccine diphtheria tetanus pertussis + Haemophilus influenzae type b + hepatitis B (DTP+Hib+Hep B) for infants. Coverage levels for the third dose of hepatitis B are usually over 80%; however, hepatitis B vaccine coverage overall is lower than for the third dose of DTP. Insufficient information is available at this time to assess the use of hepatitis B vaccine in healthcare workers in the Americas. The most important factor associated with the success in the implementation of hepatitis B vaccination has been the strong commitment of country governments. This experience can be used as a model when implementing new technologies in health as they become available. However, much still needs to be done to improve hepatitis B coverage.

Development of a cholera vaccination policy on the Island of Hispaniola, 2010-2013.

Deployment of oral cholera vaccine (OCV) on the Island of Hispaniola has been considered since the emergence of the disease in October of 2010. At that time, emergency response focused on the time-tested measures of treatment to prevent deaths and sanitation to diminish transmission. Use of the limited amount of vaccine available in the global market was recommended for demonstration activities, which were carried out in 2012. As transmission continues, vaccination was recommended in Haiti as one component of a comprehensive initiative supported by an international coalition to eliminate cholera on the Island of Hispaniola. Leveraging its delivery to strengthen other cholera prevention measures and immunization services, a phased OCV introduction is pursued in accordance with global vaccine supply. Not mutually exclusive or sequential deployment options include routine immunization for children over the age of 1 year and campaigns in vulnerable metropolitan areas or rural areas with limited access to health services.

Critical issues in implementing a national integrated all-vaccine preventable disease surveillance system.

In 2007, the World Health Organization published the Global Framework for Immunization Monitoring and Surveillance (GFIMS) outlining measures to enhance national surveillance for vaccine preventable diseases (VPDs). The GFIMS emphasized that VPD surveillance should be integrated and placed in a 'unified framework' building upon the strengths of existing surveillance systems to prevent duplication of activities common to all surveillance systems and to minimize human resource and supply expenditures. Unfortunately, there was little experience in actually developing integrated VPD surveillance. We describe the process of developing operational guidance for ministries of health to implement such an integrated surveillance system for multiple VPDs.

Vaccination legislation in Latin America and the Caribbean.

Governments have the authority and responsibility to ensure vaccination for all citizens. The development of vaccination legislation in Latin America and the Caribbean (LAC) parallels the emergence of sustainable, relatively autonomous, and effective national immunization programs. We reviewed vaccination legislation and related legal documents from LAC countries (excluding Canada, Puerto Rico, the United States, and the US Virgin Islands), and described and assessed vaccination legislation provisions. Twenty-seven of the 44 countries and territories in the Region have proposed or enacted vaccination legislation. Provisions vary substantially, but legal frameworks generally protect the sustainability of the immunization program, the individual's right to immunization, and the state's responsibility to provide it as a public good. Of the legislation from countries and territories included in the analysis, 44 per cent protects a budget line for vaccines, 96 per cent mandates immunization, 63 per cent declares immunization a public good, and 78 per cent explicitly defines the national vaccine schedule. We looked for associations between vaccination legislation in LAC and national immunization program performance and financing, and conclude with lessons for governments seeking to craft or enhance vaccination legislation.

Systematic documentation of new vaccine introduction in selected countries of the Latin American Region.

BACKGROUND: Countries in Latin America were among the first developing countries to introduce new vaccines, particularly rotavirus (RV) and pneumococcal conjugate vaccines (PCVs), into their national immunization schedules. Experiences and lessons learned from these countries are valuable to donors, immunization partners, and policy makers in other countries wishing to make informed decisions on vaccine introduction. OBJECTIVES: In order to enhance knowledge and promote understanding of the process of new vaccine introduction in the Latin American Region, with particular focus on RV and PCV, we conducted a systematic qualitative assessment. We evaluated the decision-making process, documented the structure in place, and reviewed key factors pertaining to new vaccine introduction. These include country morbidity and mortality data available prior to vaccine introduction, funding sources and mechanisms for vaccine introduction, challenges of implementation, and assessment of vaccine impact. METHODS: From March 2010 to April 2011, we evaluated a subset of countries that had introduced RV and/or PCV in the past five years through interviews with key informants at the country level and through a systematic review of published data, gray literature, official technical documents, and country-specific health indicators. Countries evaluated were Bolivia, Brazil, Nicaragua, Peru, and Venezuela. RESULTS: In all countries, the potential of new vaccines to reduce mortality, as established by Millennium Development Goal 4, was an important consideration leading to vaccine introduction. Several factors-the availability of funds, the existence of sufficient evidence for vaccine introduction, and the feasibility of sustainable financing-were identified as crucial components of the decision-making process in the countries evaluated. CONCLUSIONS: The decision making process regarding new vaccine introduction in the countries evaluated does not follow a systematic approach. Nonetheless, existing evidence on efficacy, potential impact, and cost-effectiveness of vaccine introduction, even if not local data, was important in the decision making process for vaccine introduction.