Is global measles eradication feasible?

Measles is one of most infectious diseases. Before the introduction of the measles vaccine, practically all children in the long run contracted measles. By the end of the 1980s most countries of the world had incorporated measles vaccine into their routine vaccination programs. Globally, some 800,000 deaths due to measles still occur every year, half of them in Africa. Eradication of measles would play an important role in improving child survival. The goal to eradicate measles from the Americas was set by the Pan American Sanitary Conference in 1994. Progress to date has been remarkable. Measles is no longer an endemic disease in the Americas and interruption of transmission has been documented in most countries. As of August 2005, 3 years have elapsed since the detection of the last indigenous case in Venezuela in September 2002. This experience shows that interruption of measles transmission can be achieved and sustained over a long period of time and that global eradication is feasible if appropriate strategy is implemented. Even in a new paradigm in which eradication is not followed by the discontinuation of vaccination, eradication of measles will be a good investment to avoid expensive epidemics and save the almost one million children that die every year to infection with the measles virus. It is not a dream to think that we will se a world free of measles by the year 2015.

Considerations for combination vaccine development and use in the developing world.

As more vaccines are developed and become available, combination vaccines will provide a way of delivering multiple antigens to avoid multiple injections and complications in the regular immunization schedules. The advantages of combination vaccines are that they decrease the discomfort of vaccine recipients and parents and also reduce the delivery cost of vaccines. We address some of the issues related to the use of combination vaccines in the developing world. Which vaccines are needed? Do developing countries have the appropriate infrastructure to deliver them? Can vaccines become affordable for countries with low incomes? And what is really needed to achieve the goal of providing developing countries with new vaccines of epidemiologic significance in a timely fashion?

Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

BACKGROUND: With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. METHODS: Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. RESULTS: All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. CONCLUSIONS: Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999. PAHO Sireva-Vigía Study Group. Pan American Health Organization.

BACKGROUND: Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. METHODS: The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. RESULTS: By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. CONCLUSION: These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

[Poliomyelitis outbreak caused by vaccine-derived virus in Haiti and the Dominican Republic]. / Brote de poliomielitis en Haití y la República Dominicana debido a un virus derivado de la vacuna antipoliomielítica oral.

In October 2000, the Ministries of Health of the Dominican Republic and Haiti notified two cases of acute flaccid paralysis (AFP) in rural areas, one of them in a 9-month-old female, and the other in a 2-year-old female, respectively. Stool samples that were obtained from these cases, which occurred in July and August 2000, after a 9-year interruption of wild poliovirus circulation in the Western Hemisphere, revealed the presence of type 1 poliovirus. Genetic sequencing, which was later performed at the Centers for Disease Control and Prevention, in Atlanta, Georgia, United States of America, revealed an atypical descendant of the virus used in the manufacture of the oral polio vaccine (OPV), but with 3% genetic divergence with respect to the parent strain. Normally, viral isolates that derive from vaccine components show 99.5% genetic agreement with the parent strain; in wild polioviruses, on the other hand, this agreement is usually less than 82.0%. Thus, the 3% genetic divergence detected in this study suggests that, in areas with low vaccine coverage, the virus used in the vaccine remained in circulation for at least two years, during which it recovered the neurovirulence and communicability of wild poliovirus type 1. This report describes the characteristics and results of the active search for cases of AFP that was sparked by the detection of the two index cases. It also looks at the public health implications of this outbreak for the entire Region of the Americas.

Strategies to eradicate rubella in the English-speaking Caribbean.

OBJECTIVE: This report presents the strategies used to eradicate rubella in the Caribbean region and the challenges faced by that effort. METHODS: Using the surveillance system for measles cases that was instituted in all countries in the Caribbean Community (CARICOM), 12 countries confirmed cases of rubella between 1992 and 1996. Rubella infections occurred in epidemic proportions in 6 countries during that period. RESULTS: On the basis of the rubella prevalence data, rubella-congenital rubella syndrome (CRS) cost-benefit analysis, and cost-effectiveness of the mass campaign, the Council for Human and Social Development of CARICOM resolved, on April 21, 1998, that every effort would be made to eradicate rubella, as well as to prevent the occurrence of new cases of CRS by the end of 2000. Using the Pan American Health Organization's template for measles eradication, CARICOM proposed and implemented the main strategies for rubella and CRS eradication, and rubella mass campaigns were conducted in 18 countries. The target population, which included males and females (aged 20-40 years), was approximately 2.2 million. CONCLUSION: The major challenges for rubella eradication are attaining high vaccine coverage in the adult population and maintaining an effective surveillance system able to detect rubella activity.

Review of regional measles surveillance data in the Americas, 1996-99.

BACKGROUND: In 1994, ministers of health of countries of North and South America established the goal of measles eradication from the western hemisphere by 2000. To accomplish this goal, the Pan American Health Organization (PAHO) developed an enhanced measles vaccination strategy. METHODS: PAHO's measles eradication vaccination strategy has evolved into three principal components; a catch-up measles vaccination campaign, maintenance of high vaccination coverage (keep-up), and periodic follow-up measles vaccination campaigns. To monitor progress towards measles eradication, measles surveillance has been strengthened, including the laboratory investigation of suspected measles cases. FINDINGS: Both the catch-up and follow-up mass campaigns achieved high vaccination coverages in the respective targeted age groups. In 1996, only 2109 confirmed measles cases were reported in the Americas. In 1997, there was a resurgence of measles in the Americas, mostly as a result of a large measles outbreak with over 42000 cases, which occurred mainly among unvaccinated young adults in Sao Paulo State, Brazil. By 1998, there was a reduction in the number of reported confirmed measles cases, with a total of 14474 cases. Reduction of cases continued to the end of 1999, with a total of only 2828 confirmed cases. INTERPRETATION: PAHO's measles eradication strategy has been effective in interrupting transmission and maintaining the absence of measles virus circulation in most parts of the Americas. The PAHO experience provides strong evidence that with full implementation of an appropriate vaccination strategy, measles transmission can be effectively interrupted.

State of immunization in the Americas.

Countries in the Americas have led the world in conquering infectious diseases preventable through vaccination. In 1971, the Western hemisphere achieved smallpox eradication. In 1991, the Americas were free of indigenous transmission of wild poliovirus. In 1998, overall regional vaccination coverage was 86% for diphtheria-pertussis-tetanus, 89% for oral poliovirus vaccine 3, 98% for bacille Calmette-Guérin vaccine, and 85% for measles. These figures confirm that most of the children in the Americas are protected against these diseases. The breakthroughs obtained in immunization have stimulated countries to promote new initiatives aimed at the control and eradication of other vaccine-preventable diseases and to introduce new vaccines into routine schedules. In the 21st century, vaccines will remain the most cost-effective means of preventing diseases and avoiding expensive treatment costs.

[Introduction of a conjugate vaccine against Hib in Chile and Uruguay]. / Introducción de la vacuna conjugada contra Hib en Chile y Uruguay.

In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib) has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with the support of scientific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future.

The immunisation programme in the Caribbean.

PIP: The Directing Council of Pan American Health Organization approved a resolution concerning the formal inauguration of the Expanded Programme on Immunization (EPI) in the Americas in October 1977. Subsequently, the EPI entered full implementation in those countries that were members of the Caribbean Epidemiology Center (CAREC) during 1978-80. All 19 CAREC Member Countries (CMC) were conducting routine immunization with diphtheria, pertussis, tetanus, poliomyelitis, measles and BCG vaccines by 1980. The establishment of the program in these countries resulted in focused activities, including training and the development of operational guidelines. Health education has been primarily used to encourage mothers to have their children vaccinated at optimum age, and to advise parents and guardians about adverse reaction to vaccines. Great efforts have been made in immunization coverage in all the CMCs for the six vaccine preventable diseases. The eradication of poliomyelitis, the interruption of measles transmission (8 years measles-free), and the implementation of strategies for the elimination of rubella and CRS have presented many challenges to public health practitioners in the region. The success of all these initiatives is a reflection of the deep commitment and strong partnerships, which have been developed between the governments, health practitioners, and people of the region. Moreover, technical and financial support from both international agencies and service clubs played a major role in the success of the program.^ieng

Rational use of rubella vaccine for prevention of congenital rubella syndrome in the Americas.

Rubella is a viral disease with minor morbidity and few complication unless it is contracted by a pregnant woman. Rubella infection during the first trimester of pregnancy often leads to fetal death or severe congenital defects (congenital rubella syndrome, CRS). Rubella remains endemic in many countries of Latin America and the Caribbean. It has been estimated that 20,000 or more infants are perhaps born with CRS each year in Latin American and Caribbean countries. While the inclusion of rubella vaccination into routine childhood immunization will decrease rubella virus circulation among young children, it will not have immediate impact on the transmission of rubella among adults or the occurrence of CRS. A one-time mass campaign targeting both males and females 5 to 39 years of age with measles-mumps-rubella or measles-rubella vaccine followed by the use of measles-mumps-rubella vaccine in routine early childhood vaccination will prevent and control both rubella and CRS promptly. In April 1988, the Ministers of Health of the English-speaking Caribbean targeted rubella for elimination by the end of the year 2000 using the vaccination strategy outlined above. The rubella elimination experience of these countries will provide useful information for the eventual elimination of rubella virus from the Americas.

[Eradication of measles in Cuba]. / La eliminación del sarampión en Cuba.

The vaccine against measles came into use in Cuba in 1971. During the seventies, a new early strategy for measles control was established, and it was followed by further efforts in the early eighties. Despite improvements to the control program, disease outbreaks continued to occur. In 1986, after examining the experience acquired through the control initiatives that were already in place, a new measles vaccination strategy was adopted. In time, the new vaccination strategy against measles came to have three main components: first, a single vaccination "catching-up" campaign targeting children 1 to 14 years of age. Second, efforts were made to achieve and maintain high vaccine coverage through mandatory vaccination services for 12-month-old children ("maintenance vaccination"). Finally, periodic "follow-up" campaigns were carried out for children 2 to 6 years of age. Steps were taken, for the purpose of monitoring the progress made so far toward eliminating measles, to strengthen disease surveillance systems, including the screening of suspected cases. The "catching-up" and "follow-up" campaigns both achieved greater than 98% coverage within targeted age groups. The routine vaccination program has also maintained high coverage. The high population immunity against measles that has been attained through these vaccination strategies has resulted in a rapid decrease in the incidence of the disease. From 1989 to 1992, less than 20 laboratory-confirmed cases were reported annually. In Cuba, the last case confirmed through serologic screening was reported in July 1993. Cuba's strategy for measles elimination has interrupted disease transmission and kept the causal virus from circulating on the island. Cuba's experience with measles elimination suggests that if an appropriate vaccination strategy is applied, measles can be globally eradicated.

Perspectives from the global poliomyelitis eradication initiative.

Ten years after the year 2000 target was set by the World Health Assembly, the global poliomyelitis eradication effort has made significant progress towards that goal. The success of the initiative is built on political commitment within the endemic countries. A partnership of international organizations and donor countries works to support the work of the countries. Interagency coordinating committees are used to ensure that all country needs are met and to avoid duplication of donor effort. Private sector support has greatly expanded the resources available at both the national and international level. At the programmatic level, rapid implementation of surveillance is the key to success, but the difficulty of building effective surveillance programmes is often underestimated. Mass immunization campaigns must be carefully planned with resources mobilized well in advance. Programme strategies should be simple, clear and concise. While improvements in strategy and technology should be continuously sought, changes should be introduced only after careful consideration. Careful consideration should be given in the planning phases of a disease control initiative on how the initiative can be used to support other health initiatives.

Measles eradication: experience in the Americas.

In 1994, the Ministers of Health from the Region of the Americas targeted measles for eradication from the Western Hemisphere by the year 2000. To achieve this goal, the Pan American Health Organization (PAHO) developed an enhanced measles eradication strategy. First, a one-time-only "catch-up" measles vaccination campaign is conducted among children aged 9 months to 14 years. Efforts are then made to vaccinate through routine health services ("keep-up") at least 95% of each newborn cohort at 12 months of age. Finally, to assure high population immunity among preschool-aged children, indiscriminate "follow-up" measles vaccination campaigns are conducted approximately every 4 years. These vaccination activities are accompanied by improvements in measles surveillance, including the laboratory testing of suspected measles cases. The implementation of the PAHO strategy has resulted in a marked reduction in measles incidence in all countries of the Americas. Indeed, in 1996 the all-time regional record low of 2109 measles cases was reported. There was a relative resurgence of measles in 1997 with over 20,000 cases, due to a large measles outbreak among infants, preschool-aged children and young adults in São Paulo, Brazil. Contributing factors for this outbreak included: low routine infant vaccination coverage, failure to conduct a "follow-up" campaign, presence of susceptible young adults, and the importation of measles virus, apparently from Europe. PAHO's strategy has been effective in interrupting measles virus circulation. This experience demonstrates that global measles eradication is an achievable goal using currently available measles vaccines.

[Public laboratories for vaccine production: a new paradigm]. / Los laboratorios públicos productores de vacunas: el nuevo paradigma.

In Latin America and the Caribbean, public laboratories that produce vaccines have contributed in varying degrees to the control and eradication of vaccine-preventable diseases, and several of them are manufacturing vaccines that are routinely applied in national immunization programs, such as the vaccine against tuberculosis (made with the bacillus of Calmette-Guérin, BCG), the triple vaccine against diphtheriatetanus-pertussis (DTP), tetanus toxoid (TT), the vaccine against measles and the oral vaccine against polio. Thanks to recent scientific strides, one can foresee an important increase in the number of safe and effective vaccines that will be available in the near future for use in routine vaccination programs. However, there are high costs involved in developing such vaccines and in protecting the intellectual property rights involved, and few laboratories in Latin America have the technical capacity to research and develop these vaccines. Such factors will affect the speed with which they are assimilated into vaccination programs in countries of the Region. Currently, public laboratories that manufacture vaccines in the Region are not equipped to compete in this new scenario and run the risk of being completely outmarketed. Thus, they must radically change their style of management and their scientific and technical capabilities, backed by a commitment from governments to improve and strengthen those political and financial aspects that can assure that national laboratories participate in the sustainable supply of vaccines to immunization programs, as well as in researching, developing, and producing new vaccines.