Combined Measles Research Articles

Progress in Measles and Rubella Elimination in Iran

Measles is a leading cause of death worldwide because of vaccine preventable diseases. Prevention and control of measles and rubella is a high priority for the Islamic Republic of Iran. In 2002, the Ministry of Health and Medical Education in Iran developed a comprehensive strategy to eliminate measles and rubella. This strategy included recommendations for a mass immunization campaign for all persons between the ages of 5-25 years with measles-rubella (MR) vaccine. This report reviews the results of this campaign and progress in the elimination of measles and rubella in Iran. Measles vaccination coverage, supplemental immunization activities, surveillance data, and results from a nationwide serosurvey were reviewed. Between 1980 and 2005, vaccination coverage ranged from 38%-99% with sustained high coverage (> or =94-99%) for the past decade. Despite high coverage with the first dose of measles vaccine (MCV1) and the introduction of a second dose of measles in 1984, case counts remained high between 1980 and 2005 with a median case count of 4414. In December 2003, a nationwide immunization campaign was conducted targeting 33,579,082 people between the ages of 5 and 25 years with a combined measles and rubella vaccine; 98% of the target population was vaccinated. A postcampaign serosurvey conducted in 2004 revealed >97.4% of the population aged between 5 and 40 years had immunity to measles and rubella. Case-based surveillance for measles identified 3 children with laboratory confirmed disease in 2004, 35 in 2005, and 42 children in 2006. Most confirmed disease occurred in immigrant communities or communities with migrant populations from neighboring counties with ongoing measles outbreaks. Surveillance for rubella was established after the campaign and identified 37 patients with confirmed disease in the follow-up period. Implementation of a comprehensive strategy for measles elimination in Iran has remarkably reduced the incidence of measles and rubella to <1 case per 1,000,000. Sporadic transmission continues to occur, particularly in areas with immigrant and nomadic populations.

The contribution of single antigen measles, mumps and rubella vaccines to immunity to these infections in England and Wales

Objective:To obtain information on the use of single antigen measles, mumps and rubella vaccines to improve estimates of population immunity and help predict outbreaks.Design:We requested information from providers of single...

Current problems of measles control in Japan and Western Pacific Region

Measles is still the leading cause of childhood death and is a vaccine-preventable disease globally. Even countries in which measles had been eradicated still remain at risk of importation from countries that have not yet eliminated the disease. Although two dose of immunization program with combined measles and rubella (MR) vaccine has been started since April 2006, there are still estimated 5–10 thousands measles cases annually in Japan. We introduced the Vero/hSLAM cell line for routine isolation of wild measles viruses in the WHO laboratory network. Vero/hSLAM cells express both CD46 and SLAM receptors and are highly sensitive to both vaccine and wild measles virus strains. Although Vero/hSLAM cell lines require an expensive antibiotics (G418) to maintain the transfection necessary for expression of the human SLAM receptor, we are trying to establish more simple, rapid and reliable diagnostic assays for measles virus infection.

Bad science in the headlines

![][1] This year has seen an intensification in the debate on how scientific stories with societal relevance are reported in the media. One cause was the Korean stem‐cell scandal, in which Hwang Woo‐Suk and colleagues claimed to have cloned human embryos. Lambasting the media for their part in distorting or sensationalizing scientific findings is not new, but recent scandals—and some not so recent—highlight the role played by elements of the scientific community itself. Ultimately, each side must take an appropriate share of responsibility for the impact that controversial or dubious research has on the public. When it comes to distributing blame for misleading the public, most scientists are quick to point to the media. In an analysis of the public reporting of science in the UK, published earlier this year by the Social Market Foundation (SMF; London, UK), the press in particular come under fire for negative sensationalism that is often to the detriment of the public good (SMF, 2006). The report repeatedly cites the media frenzy that began in 1998 when Andrew Wakefield, a UK‐based doctor, suggested a link between the administration of the combined measles, mumps and rubella (MMR) vaccine and the development of autism in children. The news reached the media through press releases and a press conference. Relentless negative press coverage over the next five years eventually led to a significant fall in MMR vaccinations in the UK and elsewhere. Many newspapers conveniently ignored expert advice on the safety of the vaccine in favour of attacking the UK government, which defended the vaccine's safety. “This mistrust of the government and its motives coupled with a sensationalist tendency in some parts of the press … lie at the heart of the problem,” the SMF report states. “Particular difficulties arise when a scientific story becomes a political one and … [1]: /embed/graphic-1.gif

Safety and Immunogenicity of a Combination: Measles, Mumps, Rubella and Varicella Vaccine (ProQuad®)

Background: A combination measles, mumps, rubella, and varicella vaccine (ProQuad®, Merck & Co., Inc, West Point, PA) was evaluated in 5 clinical trials. Use of ProQuad® would result in fewer injections for children and would facilitate universal immunization against all 4 diseases. Objective: To describe the combined results obtained from the studies conducted during the clinical development program for ProQuad®. Methods: A total of 5833 healthy children, 12-23 months of age, and 399 healthy children, 4-6 years of age, received 1 or 2 doses of ProQuad® in 5 controlled clinical trials. M-M-R®II and VARIVAX® were used as the control for most studies. Safety was evaluated for 6 weeks postvaccination and immunogenicity was assessed 6 weeks after each dose by a sensitive assay (ELISA or gpELISA). Results: A single dose of ProQuad® in 12- to 23-month-old children was shown to be as immunogenic as a single dose of M-M-R®II and VARIVAX® and was generally well tolerated. ProQuad® can be used concomitantly with other vaccines (hepatitis B and Haemophilus influenzae b). A higher rate of fever was reported after 1 dose of ProQuad® compared to M-M-R®II and VARIVAX®, but fever episodes were transient without long-term sequelae. Both a 2-dose regimen of ProQuad® in 12- to 23-month-olds and use of ProQuad® in place of M-M-R®II at 4-6 years were shown to be immunogenic and well tolerated. The incidence of adverse experiences following a second dose of ProQuad® was lower than that following the initial dose. Conclusions: A single dose of ProQuad® is as immunogenic as M-M-R®II and VARIVAX® and is well tolerated in a 1- or 2-dose schedule. ProQuad® should easily fit into the routine immunization schedule.

The Safety and Immunogenicity of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children

This clinical trial was conducted to demonstrate that each of 3 consistency lots of a combined measles, mumps, rubella and varicella vaccine (MMRV) would be well tolerated, induce clinically acceptable and similar immune responses to each antigen and induce immune responses similar to measles, mumps and rubella vaccine (MMR) administered concomitantly with varicella vaccine (V). An additional objective was to evaluate the persistence of antibodies 1 year postvaccination. Study participants 12 to 23 months of age received a single injection of either one of 3 consistency lots of MMRV or MMR + V administered at separate injection sites. A total of 3,928 healthy children were enrolled at study sites in the United States and Canada. Immune responses to measles, mumps, rubella and varicella in children immunized with each of 3 lots of MMRV were similar and the combined response to all 3 lots was comparable to that of the control group. The 1-year antibody persistence rates for measles, mumps, rubella and varicella viruses were each greater than 95% and comparable among the recipients of the 3 consistency lots of MMRV and the control group. All vaccines were generally well tolerated during the 42 days after vaccination and the overall incidence of adverse experiences was comparable between recipients of MMRV and MMR + V. Rates of fever (temperature >or=38.9 degrees C oral equivalent or tactile) were greater in recipients of MMRV than in recipients of MMR + V (39.1% versus 33.1%, P = 0.001). Fevers were transient and there was no difference in the incidence of febrile seizures. MMRV was generally well tolerated and had comparable immunogenicity and overall safety profiles to MMR + V administered concomitantly. Long-term persistence of antibodies after receipt of MMRV is expected based on similar antibody titers against all 4 antigens 1 year postvaccination compared with recipients of MMR and V.

A Combination Measles, Mumps, Rubella, and Varicella Vaccine (ProQuad) Given to 4- to 6-Year-Old Healthy Children Vaccinated Previously With M-M-RII and Varivax

In the United States, children receive primary doses of M-M-RII (Merck & Co, Inc, West Point, PA) and Varivax (Merck & Co, Inc) beginning at 12 months, often at the same health care visit. Currently a second dose of M-M-RII is given to 4- to 6-year-old children, to increase vaccination rates and to reduce the number of individuals without detectable antibodies. A second dose of a varicella-containing vaccine may result in similar benefits. To demonstrate that ProQuad (measles, mumps, rubella, and varicella virus vaccine live; Merck & Co, Inc) may be given in place of a second dose of M-M-RII or second doses of M-M-RII and Varivax for 4- to 6-year-old children. Four- to 6-year-old children who had been immunized previously with M-M-RII and Varivax were assigned randomly to receive either ProQuad and placebo (N = 399), M-M-RII and placebo (N = 195), or M-M-RII and Varivax (N = 205) and were then monitored for safety and immunogenicity. ProQuad was generally well tolerated. Similarity (noninferiority) was demonstrated in postvaccination antibody responses to measles, mumps, and rubella between recipients of ProQuad and all recipients of M-M-RII and in responses to varicella between recipients of ProQuad and recipients of Varivax. Postvaccination seropositivity rates for antibodies against all 4 viruses were nearly 100% in all 3 groups. Small fold increases were observed for measles, mumps, and rubella antibody titers. In contrast, substantial boosts in varicella antibody titers were observed among recipients of a second dose of varicella vaccine, administered as ProQuad or Varivax. ProQuad may be used in place of a second dose of M-M-RII or second doses of M-M-RII and Varivax for 4- to 6-year-old children.

Dose-Response Study of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children

A combined measles, mumps, rubella and varicella (MMRV) vaccine would facilitate universal immunization against 4 diseases by decreasing the number of injections and thus enhancing compliance and coverage rates. If a second dose of varicella vaccine were to be recommended, MMRV could be used to administer a routine second dose of M-M-RII with the added advantage of boosting varicella-zoster virus (VZV) antibody titers. Subjects 12-23 months of age received a single injection of 1 of 3 lots of an MMRV vaccine (ProQuad) containing high, middle or low VZV potency, or VARIVAX given concomitantly with M-M-RII. Recipients of MMRV received a second injection of MMRV approximately 90 days later. We enrolled 1559 subjects in the study. Antibody response rates to VZV 6 weeks after 1 injection of high potency MMRV (88.6%) or 2 injections of MMRV of any varicella potency (99.7-100%) were similar to the response rates after concomitant administration of M-M-RII and VARIVAX (93.1%). The second injection of MMRV boosted VZV antibody titers. Antibody responses to measles, mumps and rubella were >or=98%, similar to the control, after 1 or 2 injections of MMRV. MMRV was generally well-tolerated during the 42 days after vaccination. One injection of high potency MMRV resulted in antibody responses to the 4 vaccine components equivalent to those found after concomitant administration of M-M-RII and VARIVAX. A second injection of MMRV resulted in a significant boost in VZV antibody. This boost may translate into enhanced immunogenicity against varicella, which is known to correlate with increased protection.

Evaluation of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children

A quadrivalent measles, mumps, rubella and varicella vaccine would facilitate universal immunization against all 4 diseases, improve compliance and immunization rates and decrease the number of injections given to children and visits to physicians' offices. To evaluate 1- and 2-dose regimens of a combined measles, mumps, rubella and varicella vaccine (ProQuad, referred to as MMRV) manufactured with a varicella component of increased potency. In this partially blind, multicenter study, 480 healthy 12- to 23-month-old children were randomized to receive either MMRV and placebo or M-M-RII and VARIVAX. Injections were given concomitantly at separate sites. Subjects randomized to receive MMRV and placebo received a second dose of MMRV 90 days later. Subjects were followed for 42 days after each vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after each vaccination. Measles-like rash and fever during days 5-12 were more common after the first dose of MMRV (rash, 5.9%; fever, 27.7%) than after M-M-RII and VARIVAX (rash, 1.9%; fever, 18.7%). The incidence of other adverse events were similar between groups. Response rates were >90% to all vaccine components in both groups. Geometric mean titers to measles and mumps were significantly higher after 1 dose of MMRV than after administration of M-M-RII and VARIVAX. The second dose of MMRV elicited slight to moderate increases in measles, mumps and rubella antibody titers and a substantial increase in varicella antibody titer (from 13.0 to 588.1 glycoprotein antigen-based enzyme-linked immunosorbent assay units/mL). A 1- or 2-dose regimen of MMRV is generally well-tolerated when administered to 12- to 23-month-old children and has a safety and immunogenicity profile similar to that of M-M-RII and VARIVAX administered concomitantly.

Mumps outbreaks across England and Wales in 2004: observational study

In October 1988, routine immunisation against mumps was introduced in the United Kingdom as a combined measles, mumps, and rubella (MMR) vaccine for children aged 12-15 months. Although the incidence...

THE ALCOHOL INDUSTRY HAS A CONFLICT OF INTEREST IN ALCOHOL RESEARCH AND POLICY

Sir—Can you imagine a situation where representatives of the tobacco industry are given a place at the table in deciding national policies on tobacco control, or in determining the research priorities for officially sponsored research on tobacco-related problems? This probably seems a little far-fetched in a policy environment such as the United Kingdom, where tobacco control measures include massively increasing tax on tobacco, and the government is considering a ban on tobacco advertising and smoking in public places. This would also be unthinkable for an industry which has been shown clearly to distort research evidence that would potentially damage tobacco sales. But that is analogous to the situation described in your recent editorial concerning the Portman Group and the Alcohol Education and Research Council (AERC) (Edwards et al. 2004). Unfortunately, the influence of the alcohol industry goes much further than just the research agenda. The alcohol industry now has unprecedented access to influencing the UK government's alcohol strategy. As a result it has managed to persuade the UK government to leave alcohol control largely to industry self-regulation, an approach which until now has not managed to stem the rising tide of alcohol-related problems in the United Kingdom (Prime Minister's Strategy Unit 2004), and has been shown to be ineffective in other countries (Babor et al. 2003). Alcohol control policies based on sound research evidence that were inconvenient to the alcohol industry have been excluded from the National Alcohol Harm Reduction Strategy for England (Drummond 2004). Instead we have a new Licensing Act (DCMS 2003) which paves the way for 24-hour opening hours for licensed premises in England, which may have harmful consequences in terms of public health, crime and disorder. Far from being a ‘little storm in a British beer mug’, as Edwards et al. (2004) suggest, tongues in cheeks, these developments should be of great concern to the international addiction research community. If properly conducted independent research is ignored or trashed in favour of commercially motivated advice from the alcohol industry, what is the point of commissioning or carrying out research? Public confidence in UK government-funded research, and advice based upon it, suffered in the wake of the bovine spongiform encephalopathy (BSE) crisis (BBC News 2000). As a result, when concerns were raised more recently about the safety of the combined measles, mumps and rubella (MMR) triple vaccine and a possible link to autism, many parents were sceptical of the Department of Health's advice, and vaccination levels dropped dramatically (BBC News 2004). We now know that the Lancet withdrew the research paper which started the MMR scare when it discovered that the principal author had an undeclared financial conflict of interest. Further, the Royal College of General Practitioners has raised concerns about the ‘unhealthy’ influence of the pharmaceutical industry in research and medical education, prompting the House of Commons Health Committee to hold a public inquiry on the influence of the industry over the health system (Moynihan 2004). If the government wants to restore confidence in publicly funded research, it needs to ensure that the commissioning of research, upon which policies are based, is free from any implication of conflict of interest. The government also needs to ensure that alcohol policy is based on independent research evidence rather than listening to the braying of alcohol industry lobbyists. As far as the AERC is concerned, its credibility as a publicly funded research sponsor has been seriously damaged by the appointment to its Board of a Portman Group representative with such a clear conflict of interest in relation to independent research on alcohol. The AERC needs to reverse its decision in relation to this appointment. Alcohol researchers also need to think carefully about their involvement with the AERC. To obtain funding from an organization with a clear conflict of interest undermines the independence and credibility of the research. This may cause some short-term pain for researchers, but there will be a longer-term gain of ridding publicly funded research of conflict of interest and alcohol industry lobbyists. In the interests of restoring public confidence in research, the government would be well advised to have this alcohol research funding administered by a research body that is free from industry lobby groups. The government has become too close to the alcohol industry in determining alcohol research and public policy priorities, a relationship which it may yet come to regret.

Childhood immunization: public health or parental choice?

Childhood immunization is a key tool in disease control and the main instrument in the government’s campaign to achieve the World Health Organization target for interrupting transmission of a range of indiginous diseases (Spika et al, 2003). However, rates of immunization have fallen over public concern about the safety of the combined measles, mumps and rubella (MMR) vaccine. Statistics show immunization uptake at around 85% (Department of Health (DH), 2004a) nationally, up from a low of 78%, and still much lower than the 95% rate required to achieve the population or herd immunity needed to effectively interrupt the transmission of the diseases (Carlowe 2003).

Estimation of infectious disease parameters from serological survey data: the impact of regular epidemics.

Serological surveys are a useful source of information about epidemiological parameters for infectious diseases. In particular they may be used to estimate contact rates, forces of infection, the reproduction number and the critical vaccination threshold. However, these estimation methods require the assumption that the infection is in endemic equilibrium. Such equilibria seldom exist in practice: for example, many common infections of childhood exhibit regular epidemic cycles. In this paper, we investigate whether ignoring such cycles produces biased estimates. We apply the methods to data on mumps and rubella in the U.K. prior to the introduction of the combined measles, mumps, rubella (MMR) vaccine. We conclude that past epidemics have only a marginal effect on estimates, and that standard methods that do not adjust for regular epidemics are valid.

Safety concerns regarding combination vaccines: the experience in Japan

This study explored the safety concerns associated with combination vaccines in Japan. The impact of Japan’s decision in 1975 to withdraw the combined diptheria, tetanus, and pertussis (DTP) vaccine, and then in 1993, the combined measles, mumps, and rubella (MMR) vaccine and provide only the single antigen vaccines was analyzed. Interviews with both governmental and non-governmental agency officials in Japan demonstrated that withdrawal of the DTP and MMR vaccines had significant impact on the rates of immunization and disease despite the availability of monovalent vaccines.

Safety concerns regarding combination vaccines: the experience in Japan

This study explored the safety concerns associated with combination vaccines in Japan. The impact of Japan’s decision in 1975 to withdraw the combined diptheria, tetanus, and pertussis (DTP) vaccine, and then in 1993, the combined measles, mumps, and rubella (MMR) vaccine and provide only the single antigen vaccines was analyzed. Interviews with both governmental and non-governmental agency officials in Japan demonstrated that withdrawal of the DTP and MMR vaccines had significant impact on the rates of immunization and disease despite the availability of monovalent vaccines.

Preventing congenital rubella infection in the European Region of WHO: 2010 target.

The World Health Organisation (WHO) Regional Office for Europe has recently published a strategic plan and surveillance guidelines for measles and congenital rubella infection. The strategy prioritises measles control activities but encourages the introduction of rubella vaccine when measles vaccine coverage has reached &gt;90 %; although, many western European countries with suboptimal measles vaccine coverage are already using the combined measles, mumps and rubella (MMR) vaccine. Women in these countries may have an especially high risk of having an infant with congenital rubella syndrome. WHO is seeking to improve the surveillance for rubella and congenital rubella syndrome as a means to obtain better information on the burden of these diseases and engage policy decision makers in the need to support the WHO European Region's strategies for rubella.

There is little evidence that combined vaccination against measles, mumps, and rubella is associated with autism

Madsen K, Hviid A, Vestergaard M et al. A population-based study if measles, mumps, and rubella vaccination and autism. N Eng J Med2002 Nov; 347 : 1477 –82 [OpenUrl][1][CrossRef][2][PubMed][3][Web of...

Comparison of social distribution of immunisation with measles, mumps, and rubella vaccine, England, 1991-2001

Since the late 1990s, the possible adverse effects of the combined measles, mumps, and rubella (MMR) vaccine have caused intense public debate. After the vaccine was introduced in 1988, coverage...

Reactogenicity and immunogenicity of a live attenuated tetravalent measles–mumps–rubella–varicella (MMRV) vaccine

In countries where routine varicella vaccination is implemented, it is usually given at the same age as that recommended for measles–mumps–rubella (MMR) vaccination. A combined multivalent measles–mumps–rubella–varicella (MMRV) vaccine would offer the convenience of a single injection and facilitate implementation of varicella vaccination into routine childhood immunisation schedules. We evaluated the immunogenicity and reactogenicity of a tetravalent MMRV candidate vaccine compared to an extemporaneous mix of a measles–mumps–rubella vaccine and varicella vaccine (MMR/V), and to a measles–mumps–rubella (MMR) vaccine alone. A multicentre study was conducted in which a total of 240 healthy children aged 12 months (80 per group) were randomised to receive MMRV, MMR/V, or MMR alone. Active surveillance for adverse events was undertaken for 43 days post-vaccination. Blood samples were taken prior to vaccination and at 60 days post-vaccination. There were no significant differences between groups in rates of pain, redness, or swelling at the site of vaccination. There was no significant difference in the rate of any fever (axillary temperature ≥37.5 °C) and grade 3 fever (axillary temperature >39.0 °C) between the groups receiving MMRV and MMR during the 43-day follow-up period. Although, a significant increase was found for fever of any cause with onset between days 0 and 14 for MMRV compared to the MMR group, there was no significant difference in grade 3 fever rates during the same period. With respect to immunogenicity, MMRV and MMR/V demonstrated similar seroconversion rates to each component compared to MMR alone, with at least 91.9% of subjects in all groups seroconverting to each vaccine component 60 days after vaccination. Decreased GMTs for varicella antibody at day 60 indicated that there may have been inhibition of this response compared to MMR/V. This tetravalent MMRV candidate vaccine showed promising results, although further examination of the possible increase in minor fever and decreased varicella immunogenicity should be assessed in future studies.

Parents found it difficult to obtain objective information and advice about the combined mumps, measles, and rubella vaccine

(2001) Br J Gen Pract 51, 904; Evans M, Stoddart H, Condon L, et al. . Parents’ perspectives on the MMR immunization: a focus group study. . Nov; . :...