P. Serrano - Academia.edu (original) (raw)

Papers by P. Serrano

Research paper thumbnail of Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy

Vaccine, 2016

Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC... more Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction.

Research paper thumbnail of Measles and rubella elimination in the WHO Region for Europe: progress and challenges

Clinical Microbiology and Infection, 2017

Globally measles remains one of the leading causes of death among young children even though a sa... more Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015e2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country's National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC's conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners.

Research paper thumbnail of National and Global Options for Managing the Risks of Measles and Rubella

Journal of Vaccines & Vaccination, 2012

Countries currently choose from several different measles and rubella containing vaccine options ... more Countries currently choose from several different measles and rubella containing vaccine options and use a wide range of vaccination schedules as they control the transmission of measles only or measles and rubella viruses within their borders and cooperate and coordinate to achieve regional and/or global goals. This paper discusses the current national options that countries use or could use for national measles and/or rubella control or elimination and existing associated regional goals to characterize the expected current global path and identify alternative paths. With highly effective, relatively inexpensive, and safe vaccines available we can potentially end indigenous measles and rubella virus transmission. The Pan American Health Organization eliminated endemic transmission of both measles and rubella, which demonstrated the possibility of global eradication, and four other regions of the World Health Organization are now pursuing targets for regional elimination. We discuss the choice of a global strategy of control compared to eradication to highlight the choices, opportunities, issues, and challenges that will ultimately determine the magnitude of human and financial costs of measles and rubella globally over the next several decades and beyond.

Research paper thumbnail of Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome

Journal of Infectious Diseases, 2014

Background. Congenital rubella syndrome (CRS) case identification is challenging in older childre... more 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.

Research paper thumbnail of Elimination of Endemic Measles, Rubella, and Congenital Rubella Syndrome From the Western Hemisphere

JAMA Pediatrics, 2014

IMPORTANCE To verify the elimination of endemic measles, rubella, and congenital rubella syndrome... more IMPORTANCE To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS Since 2001, US reported measles incidence has remained below 1 case per 1 000 000 population. Since 2004, rubella incidence has been below 1 case per 10 000 000 population, and CRS incidence has been below 1 case per 5 000 000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

Research paper thumbnail of Research priorities for global measles and rubella control and eradication

Vaccine, 2012

In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibi... more 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.

Research paper thumbnail of Reducing global disease burden of measles and rubella: Report of the WHO Steering Committee on research related to measles and rubella vaccines and vaccination, 2005

Vaccine, 2007

The WHO Steering Committee reviewed and evaluated the progress towards global control of measles ... more The WHO Steering Committee reviewed and evaluated the progress towards global control of measles and rubella and provided guidelines for future research activities concerning both diseases during its meeting in New Delhi, in April 2005. Global measles vaccination coverage increased from 71% in 1999 to 76% in 2004 and indigenous transmission was interrupted or kept at very low levels in many countries. However, Africa and Southeast Asia continue to experience endemic transmission and high mortality rates, despite a global mortality reduction of 39% between 1999 and 2003. On the basis of reports from countries with continued indigenous measles virus transmission, future control strategies as well as advantages and potential drawbacks of global measles eradication were discussed. Similarly the burden of rubella and congenital rubella syndrome (CRS) as well as the cost-effectiveness of rubella vaccination was assessed using different methods in several countries without vaccination programs. As measles and rubella viruses continue to circulate surveillance and control strategies need further optimization. RT-PCR was considered as an alternative method for laboratory diagnosis of CRS. The value of dried blood spots and oral fluid as alternative samples for measles and rubella IgG and IgM detection and genotype determination was evaluated. However further validation of these methods in different settings is required before their routine use can be recommended.

Research paper thumbnail of Measles Outbreak Associated With an International Youth Sporting Event in the United States, 2007

The Pediatric Infectious Disease Journal, 2010

Background: Despite elimination of endemic measles in the United States (US), outbreaks associate... more Background: Despite elimination of endemic measles in the United States (US), outbreaks associated with imported measles continue to occur. In 2007, the initiation of a multistate measles outbreak was associated with an imported case occurring in a participant at an international youth sporting event held in Pennsylvania. Methods: Case finding and contact tracing were conducted. Control measures included isolating ill persons and administering postexposure prophylaxis to exposed persons without documented measles immunity. Laboratory evaluation of suspected cases and contacts included measles serologic testing, viral culture, detection of viral RNA by reverse-transcription polymerase chain reaction, and viral genotyping. Results: The index case occurred in a child from Japan aged 12 years. Contact tracing among 1250 persons in 8 states identified 7 measles cases; 5 (71%) cases occurred among persons without documented measles vaccination. Epidemiologic and laboratory investigation supported a single chain of transmission, linking the outbreak to contemporaneous measles virus genotype D5 transmission in Japan. Of the 471 event participants, 193 (41%) lacked documentation of presumed measles immunity, 94 (49%) of 193 were US-resident adults, 19 (10%) were non-US-resident adults (aged Ͼ18 years), and 80 (41%) were non-US-resident children. Discussion: Measles outbreaks associated with imported disease are likely to continue in the US. Participants in international events, international travelers, and persons with routine exposure to such travelers might be at greater risk of measles. To reduce the impact of imported cases, high measles, mumps, and rubella vaccine coverage rates should be maintained throughout the US, and support should continue for global measles control and elimination.

Research paper thumbnail of Measles, Rubella, and Varicella Among the Crew of a Cruise Ship Sailing From Florida, United States, 2006

Journal of Travel Medicine, 2012

Background. Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varic... more Background. Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varicella have been previously associated with introduction and spread among susceptible crew members originating from countries with endemic transmission of these diseases. Methods. During February to April 2006, we investigated a cluster of rash illnesses due to measles, rubella, or varicella on a cruise ship sailing from Florida to the Caribbean. Case-finding measures included review of medical logs, active surveillance for rash illness among crew members, and passive surveillance for rash illness in the ship's infirmary lasting two incubation periods from the last case of measles. Passengers with potential exposure to these VPD were notified by letters. All susceptible crew members with potential exposure were administered the measles, mumps, and rubella vaccine after informed consent. Results. A total of 16 cases were identified only among crew members: 1 rubella, 3 measles (two-generation spread), 11 varicella (three-generation spread), and 1 unknown diagnosis. Of 1,197 crew members evaluated, 4 had proof of immunity to measles and rubella. Based on passive surveillance, no cases were identified among passengers, the majority of whom resided in the United States. Conclusion. The international makeup of the population aboard cruise ships combined with their semi-enclosed environment has the potential to facilitate introduction and spread of VPD such as measles, rubella, and varicella onboard and into communities. Cruise lines should ensure crew members have evidence of immunity to these diseases. Passengers should be up to date with all vaccinations, including those that are travel-specific, prior to embarking on cruise travel.

Research paper thumbnail of Evidence Used to Support the Achievement and Maintenance of Elimination of Rubella and Congenital Rubella Syndrome in the United States

The Journal of Infectious Diseases, 2011

Research paper thumbnail of Virologic Surveillance for Wild-type Rubella Viruses in the Americas

Journal of Infectious Diseases, 2011

The goal of eliminating rubella from the Americas by 2010 was established in 2003. Subsequently, ... more The goal of eliminating rubella from the Americas by 2010 was established in 2003. Subsequently, a systematic nomenclature for wild-type rubella viruses (wtRVs) was established, wtRVs circulating in the region were catalogued, and importations of wtRVs into a number of countries were documented. The geographic distribution of wtRVs of various genotypes in the Americas, interpreted in the context of the global distribution of these viruses, contributed to the documentation of rubella elimination from some countries. Data from virologic surveillance also contributed to the conclusion that viruses of genotype 2B began circulating endemically in the Americas during 2006-2007. Viruses of one genotype (1C), which are restricted to the Americas, will likely disappear completely from the world as they are eliminated from the Americas. Efforts to expand virologic surveillance for wtRVs in the Americas will also provide additional data aiding the elimination of rubella from the region. For example, identification of vaccine virus in specimens from rash and fever cases found during elimination can identify such cases as vaccine associated.

Research paper thumbnail of Guidelines for the Documentation and Verification of Measles, Rubella, and Congenital Rubella Syndrome Elimination in the Region of the Americas

Journal of Infectious Diseases, 2011

Research paper thumbnail of Persistence of Rubella Antibodies after 2 Doses of Measles‐Mumps‐Rubella Vaccine

The Journal of Infectious Diseases, 2009

Background. Since 1990, most schoolchildren in the United States have received a second dose of m... more Background. Since 1990, most schoolchildren in the United States have received a second dose of measlesmumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short-and long-term rubella immunogenicity of MMR2. Methods. At enrollment in 1994-1995, children () in a rural Wisconsin health maintenance organi-n p 307 zation received MMR2 at age 4-6 years. A comparison group of older children () was vaccinated at age n p 306 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10). Results. Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns. Conclusions. Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination. Rubella is an infectious viral disease, typically causing a mild fever, rash, and lymphadenopathy [1]. Infection of a pregnant woman, however, can have devastating effects on the fetus, including cataracts, hearing impairment, heart defects, and other disorders termed congenital rubella syndrome (CRS) [1]. Before the introduction of vaccine in the United States, CRS oc

Research paper thumbnail of An Economic Analysis of the Current Universal 2-dose measles-mumps-rubella Vaccination Program in the United States

The Journal of Infectious Diseases, 2004

To evaluate the economic impact of the current 2-dose measles-mumps-rubella (MMR) vaccination pro... more To evaluate the economic impact of the current 2-dose measles-mumps-rubella (MMR) vaccination program in the United States, a decision tree-based analysis was conducted with population-based vaccination coverage and disease incidence data. All costs were estimated for a hypothetical US birth cohort of 3,803,295 infants born in 2001. The 2-dose MMR vaccination program was cost-saving from both the direct cost and societal perspectives compared with the absence of MMR vaccination, with net savings (net present value) from the direct cost and societal perspectives of 3.5billionand3.5 billion and 3.5billionand7.6 billion, respectively. The direct and societal benefitcost ratios for the MMR vaccination program were 14.2 and 26.0. Analysis of the incremental benefit-cost of the second dose showed that direct and societal benefit-cost ratios were 0.31 and 0.49, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector had little effect on the results. From both perspectives under even the most conservative assumptions, the national 2-dose MMR vaccination program is highly cost-beneficial and results in substantial cost savings. Endemic measles has been eliminated from the United States [1], and rubella and mumps are reported at record low incidences. These significant public health achievements have been realized through a 2-dose measles-mumps-rubella (MMR) vaccination program. Two previous measles elimination programs in the United States, started in 1966 and 1978, relied on a 1-dose vaccination strategy and did not achieve elimination of endemic measles, although they did reduce the incidence of measles substantially. The successful elimination of endemic measles with the 2-dose MMR strategy prompted us to perform an economic analysis of the 2-dose MMR vaccination program. In the prevaccine era, ∼4 million persons-the size of 1 birth cohort-were infected with measles each year. These cases were associated with a reported 500 deaths, 48,000 hospitalizations, and 4000 cases of encephalitis

Research paper thumbnail of Changing Epidemiology of Congenital Rubella Syndrome in the United States

The Journal of Infectious Diseases, 1998

To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome... more To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome (CRS) and to identify missed opportunities for maternal vaccination, data from CRS cases reported to the National Congenital Rubella Syndrome Registry (NCRSR) from 1985 through 1996 were analyzed. Missed opportunities for maternal vaccination were defined as missed postpartum, premarital, and occupational opportunities, that is, times when rubella vaccination is recommended but was not given. From 1985 through 1996, 122 CRS cases were reported to the NCRSR. The most frequent CRS-related defect was congenital heart disease. Of the reported infants with CRS, 44% were Hispanic. Of 121 known missed opportunities for rubella vaccination among 94 mothers of infants with indigenous CRS, 98 (81%) were missed postpartum opportunities. CRS continues to occur in the United States. Hispanic infants have an increased risk of CRS. Missed opportunities for postpartum rubella vaccination were identified for 52% of indigenous CRS cases.

Research paper thumbnail of Reducing the Global Burden of Congenital Rubella Syndrome: Report of the World Health Organization Steering Committee on Research Related to Measles and Rubella Vaccines and Vaccination, June 2004

The Journal of Infectious Diseases, 2005

Research paper thumbnail of Rubella and measles seroprevalence among women of childbearing age, Argentina, 2002

Epidemiology and Infection, 2005

To assess rubella and measles susceptibility among women of childbearing age we conducted a cross... more To assess rubella and measles susceptibility among women of childbearing age we conducted a cross-sectional seroprevalence study in four cities and one rural area in Argentina. A convenience sample of women aged 15–49 years seeking care in public health-care institutions was selected (n=2804). Serum specimens were tested for rubella and measles IgG antibody titres. The overall susceptibility to rubella and measles was 8·8 and 12·5% respectively. Seroprevalence differences were found for both rubella…

Research paper thumbnail of The Epidemiological Profile of Rubella and Congenital Rubella Syndrome in the United States, 1998–2004: The Evidence for Absence of Endemic Transmission

Clinical Infectious Diseases, 2006

In 1969, the United States established its national rubella vaccination program. With the success... more In 1969, the United States established its national rubella vaccination program. With the success of the program, 32 years later, reports of rubella reached record low numbers. To assess the achievement of elimination of rubella and congenital rubella syndrome (CRS) in the United States, 7 epidemiological criteria were used.

Research paper thumbnail of Genetic Analysis of Rubella Viruses Found in the United States between 1966 and 2004: Evidence That Indigenous Rubella Viruses Have Been Eliminated

Clinical Infectious Diseases, 2006

Wild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, o... more Wild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, of which 3 are provisional. The genotypes of 118 viruses from the United States were determined by sequencing part of the E1 coding region of these viruses and comparing the resulting sequences with reference sequences for each genotype, using the Bayesian inference program MRBAYES. Three genotypes of rubella viruses were found in the United States too infrequently to be considered for indigenous transmission. A fourth genotype was found frequently until 1981, and a fifth genotype was found frequently until 1988, but neither was obtained from nonimported cases after 1988. A sixth genotype was found frequently during 1996-2000, likely because of multiple importations from neighboring countries. The results of the present genetic analysis of rubella viruses found in the United States are consistent with elimination of indigenous viruses by 2001, the year when rubella was considered to be eliminated on the basis of epidemiological evidence. Virus surveillance and the genetic characterization of circulating, wild-type viruses (molecular epidemiology) have contributed to global and regional control efforts for both polio and measles, including the discovery that vaccine-derived poliovirus recombinants can circulate and cause poliomyelitis and determinations of whether measles outbreaks were caused by imported or nonimported viruses [1-3]. Molecular epidemiological studies of measles viruses isolated in the United States determined that the transmission of a single genotype of measles virus present during the measles resurgent period of 1989-1992 was interrupted and that an endemic genotype of measles has not been present in the United States since 1994 [4, 5]. Sufficient sequence variability exists in known rubella viruses to allow investigations of their phylogeny and a Deceased.

Research paper thumbnail of The Evidence for the Elimination of Rubella and Congenital Rubella Syndrome in the United States: A Public Health Achievement

Clinical Infectious Diseases, 2006

Research paper thumbnail of Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy

Vaccine, 2016

Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC... more Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction.

Research paper thumbnail of Measles and rubella elimination in the WHO Region for Europe: progress and challenges

Clinical Microbiology and Infection, 2017

Globally measles remains one of the leading causes of death among young children even though a sa... more Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015e2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country's National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC's conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners.

Research paper thumbnail of National and Global Options for Managing the Risks of Measles and Rubella

Journal of Vaccines & Vaccination, 2012

Countries currently choose from several different measles and rubella containing vaccine options ... more Countries currently choose from several different measles and rubella containing vaccine options and use a wide range of vaccination schedules as they control the transmission of measles only or measles and rubella viruses within their borders and cooperate and coordinate to achieve regional and/or global goals. This paper discusses the current national options that countries use or could use for national measles and/or rubella control or elimination and existing associated regional goals to characterize the expected current global path and identify alternative paths. With highly effective, relatively inexpensive, and safe vaccines available we can potentially end indigenous measles and rubella virus transmission. The Pan American Health Organization eliminated endemic transmission of both measles and rubella, which demonstrated the possibility of global eradication, and four other regions of the World Health Organization are now pursuing targets for regional elimination. We discuss the choice of a global strategy of control compared to eradication to highlight the choices, opportunities, issues, and challenges that will ultimately determine the magnitude of human and financial costs of measles and rubella globally over the next several decades and beyond.

Research paper thumbnail of Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome

Journal of Infectious Diseases, 2014

Background. Congenital rubella syndrome (CRS) case identification is challenging in older childre... more 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.

Research paper thumbnail of Elimination of Endemic Measles, Rubella, and Congenital Rubella Syndrome From the Western Hemisphere

JAMA Pediatrics, 2014

IMPORTANCE To verify the elimination of endemic measles, rubella, and congenital rubella syndrome... more IMPORTANCE To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS Since 2001, US reported measles incidence has remained below 1 case per 1 000 000 population. Since 2004, rubella incidence has been below 1 case per 10 000 000 population, and CRS incidence has been below 1 case per 5 000 000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

Research paper thumbnail of Research priorities for global measles and rubella control and eradication

Vaccine, 2012

In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibi... more 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.

Research paper thumbnail of Reducing global disease burden of measles and rubella: Report of the WHO Steering Committee on research related to measles and rubella vaccines and vaccination, 2005

Vaccine, 2007

The WHO Steering Committee reviewed and evaluated the progress towards global control of measles ... more The WHO Steering Committee reviewed and evaluated the progress towards global control of measles and rubella and provided guidelines for future research activities concerning both diseases during its meeting in New Delhi, in April 2005. Global measles vaccination coverage increased from 71% in 1999 to 76% in 2004 and indigenous transmission was interrupted or kept at very low levels in many countries. However, Africa and Southeast Asia continue to experience endemic transmission and high mortality rates, despite a global mortality reduction of 39% between 1999 and 2003. On the basis of reports from countries with continued indigenous measles virus transmission, future control strategies as well as advantages and potential drawbacks of global measles eradication were discussed. Similarly the burden of rubella and congenital rubella syndrome (CRS) as well as the cost-effectiveness of rubella vaccination was assessed using different methods in several countries without vaccination programs. As measles and rubella viruses continue to circulate surveillance and control strategies need further optimization. RT-PCR was considered as an alternative method for laboratory diagnosis of CRS. The value of dried blood spots and oral fluid as alternative samples for measles and rubella IgG and IgM detection and genotype determination was evaluated. However further validation of these methods in different settings is required before their routine use can be recommended.

Research paper thumbnail of Measles Outbreak Associated With an International Youth Sporting Event in the United States, 2007

The Pediatric Infectious Disease Journal, 2010

Background: Despite elimination of endemic measles in the United States (US), outbreaks associate... more Background: Despite elimination of endemic measles in the United States (US), outbreaks associated with imported measles continue to occur. In 2007, the initiation of a multistate measles outbreak was associated with an imported case occurring in a participant at an international youth sporting event held in Pennsylvania. Methods: Case finding and contact tracing were conducted. Control measures included isolating ill persons and administering postexposure prophylaxis to exposed persons without documented measles immunity. Laboratory evaluation of suspected cases and contacts included measles serologic testing, viral culture, detection of viral RNA by reverse-transcription polymerase chain reaction, and viral genotyping. Results: The index case occurred in a child from Japan aged 12 years. Contact tracing among 1250 persons in 8 states identified 7 measles cases; 5 (71%) cases occurred among persons without documented measles vaccination. Epidemiologic and laboratory investigation supported a single chain of transmission, linking the outbreak to contemporaneous measles virus genotype D5 transmission in Japan. Of the 471 event participants, 193 (41%) lacked documentation of presumed measles immunity, 94 (49%) of 193 were US-resident adults, 19 (10%) were non-US-resident adults (aged Ͼ18 years), and 80 (41%) were non-US-resident children. Discussion: Measles outbreaks associated with imported disease are likely to continue in the US. Participants in international events, international travelers, and persons with routine exposure to such travelers might be at greater risk of measles. To reduce the impact of imported cases, high measles, mumps, and rubella vaccine coverage rates should be maintained throughout the US, and support should continue for global measles control and elimination.

Research paper thumbnail of Measles, Rubella, and Varicella Among the Crew of a Cruise Ship Sailing From Florida, United States, 2006

Journal of Travel Medicine, 2012

Background. Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varic... more Background. Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varicella have been previously associated with introduction and spread among susceptible crew members originating from countries with endemic transmission of these diseases. Methods. During February to April 2006, we investigated a cluster of rash illnesses due to measles, rubella, or varicella on a cruise ship sailing from Florida to the Caribbean. Case-finding measures included review of medical logs, active surveillance for rash illness among crew members, and passive surveillance for rash illness in the ship's infirmary lasting two incubation periods from the last case of measles. Passengers with potential exposure to these VPD were notified by letters. All susceptible crew members with potential exposure were administered the measles, mumps, and rubella vaccine after informed consent. Results. A total of 16 cases were identified only among crew members: 1 rubella, 3 measles (two-generation spread), 11 varicella (three-generation spread), and 1 unknown diagnosis. Of 1,197 crew members evaluated, 4 had proof of immunity to measles and rubella. Based on passive surveillance, no cases were identified among passengers, the majority of whom resided in the United States. Conclusion. The international makeup of the population aboard cruise ships combined with their semi-enclosed environment has the potential to facilitate introduction and spread of VPD such as measles, rubella, and varicella onboard and into communities. Cruise lines should ensure crew members have evidence of immunity to these diseases. Passengers should be up to date with all vaccinations, including those that are travel-specific, prior to embarking on cruise travel.

Research paper thumbnail of Evidence Used to Support the Achievement and Maintenance of Elimination of Rubella and Congenital Rubella Syndrome in the United States

The Journal of Infectious Diseases, 2011

Research paper thumbnail of Virologic Surveillance for Wild-type Rubella Viruses in the Americas

Journal of Infectious Diseases, 2011

The goal of eliminating rubella from the Americas by 2010 was established in 2003. Subsequently, ... more The goal of eliminating rubella from the Americas by 2010 was established in 2003. Subsequently, a systematic nomenclature for wild-type rubella viruses (wtRVs) was established, wtRVs circulating in the region were catalogued, and importations of wtRVs into a number of countries were documented. The geographic distribution of wtRVs of various genotypes in the Americas, interpreted in the context of the global distribution of these viruses, contributed to the documentation of rubella elimination from some countries. Data from virologic surveillance also contributed to the conclusion that viruses of genotype 2B began circulating endemically in the Americas during 2006-2007. Viruses of one genotype (1C), which are restricted to the Americas, will likely disappear completely from the world as they are eliminated from the Americas. Efforts to expand virologic surveillance for wtRVs in the Americas will also provide additional data aiding the elimination of rubella from the region. For example, identification of vaccine virus in specimens from rash and fever cases found during elimination can identify such cases as vaccine associated.

Research paper thumbnail of Guidelines for the Documentation and Verification of Measles, Rubella, and Congenital Rubella Syndrome Elimination in the Region of the Americas

Journal of Infectious Diseases, 2011

Research paper thumbnail of Persistence of Rubella Antibodies after 2 Doses of Measles‐Mumps‐Rubella Vaccine

The Journal of Infectious Diseases, 2009

Background. Since 1990, most schoolchildren in the United States have received a second dose of m... more Background. Since 1990, most schoolchildren in the United States have received a second dose of measlesmumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short-and long-term rubella immunogenicity of MMR2. Methods. At enrollment in 1994-1995, children () in a rural Wisconsin health maintenance organi-n p 307 zation received MMR2 at age 4-6 years. A comparison group of older children () was vaccinated at age n p 306 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10). Results. Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns. Conclusions. Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination. Rubella is an infectious viral disease, typically causing a mild fever, rash, and lymphadenopathy [1]. Infection of a pregnant woman, however, can have devastating effects on the fetus, including cataracts, hearing impairment, heart defects, and other disorders termed congenital rubella syndrome (CRS) [1]. Before the introduction of vaccine in the United States, CRS oc

Research paper thumbnail of An Economic Analysis of the Current Universal 2-dose measles-mumps-rubella Vaccination Program in the United States

The Journal of Infectious Diseases, 2004

To evaluate the economic impact of the current 2-dose measles-mumps-rubella (MMR) vaccination pro... more To evaluate the economic impact of the current 2-dose measles-mumps-rubella (MMR) vaccination program in the United States, a decision tree-based analysis was conducted with population-based vaccination coverage and disease incidence data. All costs were estimated for a hypothetical US birth cohort of 3,803,295 infants born in 2001. The 2-dose MMR vaccination program was cost-saving from both the direct cost and societal perspectives compared with the absence of MMR vaccination, with net savings (net present value) from the direct cost and societal perspectives of 3.5billionand3.5 billion and 3.5billionand7.6 billion, respectively. The direct and societal benefitcost ratios for the MMR vaccination program were 14.2 and 26.0. Analysis of the incremental benefit-cost of the second dose showed that direct and societal benefit-cost ratios were 0.31 and 0.49, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector had little effect on the results. From both perspectives under even the most conservative assumptions, the national 2-dose MMR vaccination program is highly cost-beneficial and results in substantial cost savings. Endemic measles has been eliminated from the United States [1], and rubella and mumps are reported at record low incidences. These significant public health achievements have been realized through a 2-dose measles-mumps-rubella (MMR) vaccination program. Two previous measles elimination programs in the United States, started in 1966 and 1978, relied on a 1-dose vaccination strategy and did not achieve elimination of endemic measles, although they did reduce the incidence of measles substantially. The successful elimination of endemic measles with the 2-dose MMR strategy prompted us to perform an economic analysis of the 2-dose MMR vaccination program. In the prevaccine era, ∼4 million persons-the size of 1 birth cohort-were infected with measles each year. These cases were associated with a reported 500 deaths, 48,000 hospitalizations, and 4000 cases of encephalitis

Research paper thumbnail of Changing Epidemiology of Congenital Rubella Syndrome in the United States

The Journal of Infectious Diseases, 1998

To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome... more To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome (CRS) and to identify missed opportunities for maternal vaccination, data from CRS cases reported to the National Congenital Rubella Syndrome Registry (NCRSR) from 1985 through 1996 were analyzed. Missed opportunities for maternal vaccination were defined as missed postpartum, premarital, and occupational opportunities, that is, times when rubella vaccination is recommended but was not given. From 1985 through 1996, 122 CRS cases were reported to the NCRSR. The most frequent CRS-related defect was congenital heart disease. Of the reported infants with CRS, 44% were Hispanic. Of 121 known missed opportunities for rubella vaccination among 94 mothers of infants with indigenous CRS, 98 (81%) were missed postpartum opportunities. CRS continues to occur in the United States. Hispanic infants have an increased risk of CRS. Missed opportunities for postpartum rubella vaccination were identified for 52% of indigenous CRS cases.

Research paper thumbnail of Reducing the Global Burden of Congenital Rubella Syndrome: Report of the World Health Organization Steering Committee on Research Related to Measles and Rubella Vaccines and Vaccination, June 2004

The Journal of Infectious Diseases, 2005

Research paper thumbnail of Rubella and measles seroprevalence among women of childbearing age, Argentina, 2002

Epidemiology and Infection, 2005

To assess rubella and measles susceptibility among women of childbearing age we conducted a cross... more To assess rubella and measles susceptibility among women of childbearing age we conducted a cross-sectional seroprevalence study in four cities and one rural area in Argentina. A convenience sample of women aged 15–49 years seeking care in public health-care institutions was selected (n=2804). Serum specimens were tested for rubella and measles IgG antibody titres. The overall susceptibility to rubella and measles was 8·8 and 12·5% respectively. Seroprevalence differences were found for both rubella…

Research paper thumbnail of The Epidemiological Profile of Rubella and Congenital Rubella Syndrome in the United States, 1998–2004: The Evidence for Absence of Endemic Transmission

Clinical Infectious Diseases, 2006

In 1969, the United States established its national rubella vaccination program. With the success... more In 1969, the United States established its national rubella vaccination program. With the success of the program, 32 years later, reports of rubella reached record low numbers. To assess the achievement of elimination of rubella and congenital rubella syndrome (CRS) in the United States, 7 epidemiological criteria were used.

Research paper thumbnail of Genetic Analysis of Rubella Viruses Found in the United States between 1966 and 2004: Evidence That Indigenous Rubella Viruses Have Been Eliminated

Clinical Infectious Diseases, 2006

Wild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, o... more Wild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, of which 3 are provisional. The genotypes of 118 viruses from the United States were determined by sequencing part of the E1 coding region of these viruses and comparing the resulting sequences with reference sequences for each genotype, using the Bayesian inference program MRBAYES. Three genotypes of rubella viruses were found in the United States too infrequently to be considered for indigenous transmission. A fourth genotype was found frequently until 1981, and a fifth genotype was found frequently until 1988, but neither was obtained from nonimported cases after 1988. A sixth genotype was found frequently during 1996-2000, likely because of multiple importations from neighboring countries. The results of the present genetic analysis of rubella viruses found in the United States are consistent with elimination of indigenous viruses by 2001, the year when rubella was considered to be eliminated on the basis of epidemiological evidence. Virus surveillance and the genetic characterization of circulating, wild-type viruses (molecular epidemiology) have contributed to global and regional control efforts for both polio and measles, including the discovery that vaccine-derived poliovirus recombinants can circulate and cause poliomyelitis and determinations of whether measles outbreaks were caused by imported or nonimported viruses [1-3]. Molecular epidemiological studies of measles viruses isolated in the United States determined that the transmission of a single genotype of measles virus present during the measles resurgent period of 1989-1992 was interrupted and that an endemic genotype of measles has not been present in the United States since 1994 [4, 5]. Sufficient sequence variability exists in known rubella viruses to allow investigations of their phylogeny and a Deceased.

Research paper thumbnail of The Evidence for the Elimination of Rubella and Congenital Rubella Syndrome in the United States: A Public Health Achievement

Clinical Infectious Diseases, 2006