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Patterns of Transmission in Measles Outbreaks in the United States, 1985–1986
Abstract
Since the licensing of measles vaccine in 1963, the incidence of reported measles in the United States has declined to less than 2 percent of previous levels. To characterize the current epidemiology of measles in the United States, we analyzed measles outbreaks that occurred during 1985 and 1986. There were 152 outbreaks (defined as five or more cases related epidemiologically), which accounted for 88 percent of the cases reported during those two years. There were two major types of outbreaks: those in which most of the cases occurred among preschool-age children (those under 5 years of age) (26 percent) and those in which most of the cases occurred among school-age persons (those 5 to 19 years of age) (67 percent). The outbreaks among preschool-age children ranged in size from 5 to 945 cases (median, 13); a median of only 14 percent of the cases occurred in vaccinated persons, and a median of 45 percent of the cases were classified as preventable according to the current strategy. Outbreaks among school-age persons ranged in size from 5 to 363 cases (median, 25); a median of 60 percent of the cases occurred in vaccinated persons, and a median of only 27 percent of the cases were preventable. The outbreaks among preschool-age children indicate deficiencies in the implementation of the national measles-elimination strategy. However, the extent of measles transmission among highly vaccinated school-age populations suggests that additional strategies, such as selective or mass revaccination, may be necessary to prevent such outbreaks.
... Due to high immunization coverage of the population with measles vaccines-both live and inactivated-the incidence of measles had fallen by 1968 to 5% of pre-vaccine levels. Measles disease incidence was further reduced throughout the next decade and a half [24]. ...
... In the mid-1980s, a trend in measles outbreaks was observed by CDC epidemiologists, showing that infections were occurring within two population groups: (1) preschool children in whom cases occurred predominantly in unvaccinated children less than 5 years of age, and (2) school-age children affecting primarily children who previously had been appropriately vaccinated with a single dose of a measles containing vaccine. The preschool outbreaks were a result of failure to vaccinate and the school-age outbreaks were the result of vaccine failures due to insufficient protection induced by a single dose of measles-containing vaccine [24,25]. ...
... Although the major cause of the resurgence was failure to vaccinate preschool-age children with a single dose of measles containing vaccine, the epidemic was characterized by college outbreaks affecting students who had received a single dose of vaccine as well as outbreaks in high schools and middle schools. These outbreaks resulted in emergency revaccination efforts among affected populations [24]. ...
... The USA established its first measles elimination goal in 1966 [63]. Measles elimination appeared close in 1983, but subsequently outbreaks occurred among highly vaccinated school-age populations [64], leading to expensive outbreak control activities [65,66]. In 1989, a two-dose measles vaccination strategy was recommended [67]. ...
... From 1989-1991 there was a large measles resurgence in the USA (rubella and CRS also increased at that time) [68]. Almost one half of all measles cases and 90% of deaths occurred in unvaccinated preschool children [65,69,70]. Control required immense efforts to deliver the first dose on time [71], demonstrating the critical importance of achieving and sustaining high and timely routine coverage. ...
Measles and rubella are major vaccine-preventable causes of child mortality and disability. They have been eliminated from the Americas and some other regions have also come close to elimination. In this paper, we review regional progress toward measles and rubella control/elimination goals, describe the recent epidemiology of these infections and discuss challenges to achieving the goals. Globally, measles vaccination is estimated to prevent nearly 2 million deaths each year. Despite this remarkable progress, large measles outbreaks have occurred in recent years, often involving older persons who were not vaccinated in earlier years. Such an occurrence would be particularly damaging for rubella control programmes as it could lead to peaks in congenital rubella syndrome. Challenges to achieving and sustaining high vaccination coverage include civil conflict, weak health systems, geographic, cultural and economic barriers to reaching certain population groups and inadequate monitoring and use of data for action. Countries and regions aiming to eliminate measles and control rubella urgently need to improve the implementation and monitoring of both routine and mass vaccination campaign strategies.
... VE of a single dose of measles vaccine in this outbreak was below the recommended ≥ 93% ( CDC, 2021a ). While studies have shown that measles outbreaks can occur in communities with > 95% VC and with documented VE > 85% ( Markowitz et al., 1989 ;Marin et al., 2006 ), most measles outbreaks occur in settings with VC < 95%, VE < 85% or both ( Belda et al., 2017 ;Mohammed and Alemu, 2017 ;Majwala et al., 2018 ;Nsubuga et al., 2018 ). The relatively high VC and VE in this investigation could explain the small size and limited spread of this outbreak ( Yeung et al., 2005 ). ...
Background: Semuto Subcounty reported rubella/measles outbreaks in January 2020 and June-August 2021. We investigated the measles outbreak in 2021 to determine the scope, and factors associated with the transmission.
Methods: A probable case had acute onset of fever and a generalized maculopapular rash with ≥1 of: cough/cold, or red eyes in a resident of Semuto Subcounty, from June 1-August 31, 2021. A confirmed case was a probable case with a blood sample positive for measles-specific IgM. We conducted a 1(30):4(122) village-matched case-control study. A control was a randomly-sampled person 6 months-9 years without signs/symptoms of measles from June 1-August 31, 2021, residing in the same village as the case. We obtained Adjusted Mantel-Haenszel odds ratios (ORMH) and confidence intervals (CIs).
Results: We identified 30 case-persons (3 confirmed); 16 (53%) were male. The subcounty attack rate (AR) was 3.2/1000. Children 5-9 years were the most affected (AR=5.0/1,000). Twenty-two (79%) case-persons and 116 (97%) control-persons had ever received measles vaccine (ORMH=0.13, 95% CI=0.03-0.52). Interaction with symptomatic persons at water collection points (ORMH=4.4, 95% CI=1.6-12) and playing at community playgrounds (ORMH=4.2, 95% CI=1.7-11) increased the odds of infection.
Conclusions: Socializing/congregating at water collection points and community playgrounds facilitated measles transmission in this outbreak.
... We, right now, focus so much on the concept of herd all faiths that were placed on herd immunity [15,47]. This incident highlights the fact that heterogenicity within a population does play an important role and is an obstacle in achieving herd immunity. ...
The world today mourns every day for the people who
have succumbed to the pandemic caused by Severe Acute
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
After a strict restriction of movement of the population to
hold off further spread of the virus, while experts figure
out a solution to this infection, economy deteriorated in
various countries. While looking for a new strategy to
hold off the virus and also avoid succumbing to further
economic crisis, an idea started running around in every
corner of the world which is HERD IMMUNITY. Even
though Herd Immunity is an old topic, the risks of it have
not been accessed fully while trying to achieve it today.
Till now, vaccination was the only way it was obtained,
but with this pandemic, the alternate strategy of obtaining
it by natural infection and recovery of the healthy
individuals is now a burning debate across the world
... Examination of reasons for the resurgence identified two kinds of outbreaks: (1) large outbreaks among unvaccinated preschoolaged children, mainly in large urban centers, and (2) smaller outbreaks among vaccinated children who, we know retrospectively, needed a second dose of a measles-containing vaccine. 64,65 Additional analyses showed that unvaccinated preschool-aged outbreaks affected mostly young minority children in urban areas, with African American, Latino, and American Indian/Alaska Native children who contracted measles at rates three to 16 times higher than white children did. 2 The NVAC examined evidence that pointed to challenges in the United States immunization system that likely contributed to the measles resurgence and to low immunization coverage rates that were well below Healthy People 2000 objectives for preschool children. Low vaccination coverage was primarily attributed to barriers in access to vaccination services or to missed opportunities to vaccinate by health care providers. ...
One of the ten greatest public health achievements is childhood vaccination because of its impact controlling and eliminating vaccine-preventable diseases (VPDs). Evidence-based immunization policies and practices are responsible for this success and are supported by epidemiology that has generated scientific evidence for informing policy and practice. The purpose of this report is to highlight the role of epidemiology in the development of immunization policy and successful intervention in public health practice that has resulted in a measurable public health impact: the control and elimination of VPDs in the United States. Examples in which epidemiology informed immunization policy were collected from a literature review and consultation with experts who have been working in this field for the past 30 years. Epidemiologic examples (e.g., thimerosal-containing vaccines and the alleged association between the measles, mumps, and rubella (MMR) vaccine and autism) are presented to describe challenges that epidemiologists have addressed.
Finally, we describe ongoing challenges to the nation’s ability to sustain high vaccination coverage, particularly with concerns about vaccine safety and effectiveness, increasing use of religious and philosophical belief exemptions to vaccination, and vaccine hesitancy. Learning from past and current experiences may help epidemiologists anticipate and address current and future challenges to respond to emerging infectious diseases, such as COVID-19, with new vaccines and enhance public health impact of immunization programs for years to come.
... Measles, which is caused by measles virus (MeV), is a highly contagious disease characterized by fever, maculopapular rash, conjunctivitis, cough and Koplik spots, and other complications include pneumonia, encephalitis, and death [1,2]. The measles vaccine is a highly safe and effective vaccine for controlling and interrupting MeV infection; however, cases of measles have risen to high levels globally in recent years [3][4][5][6][7]. ...
Background:
Measles outbreaks have threatened the global elimination and eradication of measles in recent years. Measles virus (MeV)-specific antibodies are successful in clearing MeV infection. Follicular helper T (Tfh) cells play a crucial role in promoting antibody production. This study investigated the potential role of Tfh cells in peripheral blood mononuclear cells (PBMCs) from children with acute MeV infection.
Results:
The frequencies of CXCR5+CD4+ Tfh, ICOShigh Tfh, and PD-1high Tfh cells in PBMCs and levels of IL-6 and IL-21 in plasma were significantly elevated in patients with acute MeV infection. Moreover, a positive correlation was discovered among the frequency of ICOShigh Tfh cells, plasma levels of IL-21 and optical density (OD) values of MeV-specific IgM antibodies in the patients with acute MeV infection. However, elevated plasma MeV-specific NAb titres were not associated with the frequency of Tfh, ICOShigh Tfh, or PD-1high Tfh cells in the patients with acute MeV infection.
Conclusion:
These results suggest that an elevated Tfh cell frequency and associated molecules possibly play a key role in children with acute MeV infection, which contributes to the prevention and treatment of MeV infection in children.
... Based on my experience in baseball as a child, we called this programmatic failures (i.e., strategy implementation failures or "preventable cases"in other words "unearned runs"). 6 In contrast, when outbreaks primarily involved school-aged children, the greatest proportion of cases was in persons who had had the recommended one dose of vaccine but still got measles. These were "strategy failures" since only one dose was recommended at the time and we called them "non-preventable" (in other words "earned runs"). ...
... Where there were less stringent vaccination requirements at school entry, more cases of measles were observed [46]. Analyses of pre-elimination measles outbreaks in the USA indicated that transmission occurred among highly vaccinated school-aged populations, suggesting that higher population immunity levels were needed among school-aged children compared to preschool-aged children [47]. It has been proposed that minimum coverage levels as low as 80% at the second birthday of children may be sufficient to prevent transmission among preschool-aged children in the USA if population immunity is at least 93% among over-5-year-olds [48]. ...
Background:
Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns.
Methods:
We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination.
Results:
We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5-9-year-olds than established previously.
Conclusions:
The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5-9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.
... 26 Analyses of pre-elimination measles outbreaks in the US indicated that transmission occurred among highly vaccinated school-aged populations, indicating that higher population immunity 200 levels are needed among school-aged children compared to preschool-aged chil- dren. 27 It has been suggested that minimum coverage levels as low as 80% at the second birthday of children may be sufficient to prevent transmission among preschool-aged children in the United States if population immunity is at least 93% among over-5 year olds. 28 ...
Vaccination has reduced the global incidence of measles to the lowest rates in history. Local interruption of measles transmission, however, requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure, however, does not easily translate into required immunity levels across all age groups that would be sufficient to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles using observed contact patterns from a broad range of settings. We combined recent observations on age-specific mixing patterns with scenarios for the distribution of immunity to estimate transmission potential. We validated these models by deriving predictions based on serological studies and comparing them to observed case data. We found that 95% immunity needs to be achieved at the time of school entry to guarantee elimination. The level of immunity found in the 5-to-9 year old age group in serological studies was the strongest predictor of future case load. Higher levels of immunity in 5-to-9 year olds are required than the previously derived target of 90% to interrupt transmission. While such high levels can be difficult to achieve, school entry provides a clear opportunity to ensure sufficient levels of immunity.
... 10 In contrast, individuals with T-cell deficiencies, such as, leukemia and human immunodeficiency virus (HIV) infection experience a progressive illness with 50-100% mortality. [11][12] These findings clearly suggest that the cellular immune response plays a central role in immunity to measles infection and in protection against reinfection. ...
Gamma interferon (IFN-γ) plays an important role in the immune response to live measles virus vaccination. To study the immune response to measles vaccination, IFN-γ level was estimated in 30 children. Of these, 24 children vaccinated with a single dose of measles vaccine at nine months of age and 06 children vaccinated with a second dose during the Measles Catch-up Immunization campaign. Measles vaccine strain was cultured in Vero cell line and the Tissue Culture Infective Dose (TCID)50 was used as standard live virus. Peripheral blood Mononuclear cells (PBMCs) was separated by Ficoll- Hypaque density gradient centrifugation and stimulated with measles virus antigens and mitogens (lectin), cultured in CO2 and IFN-γ level was measured from culture supernatant by ELISA. On stimulation with measles antigen and lectin respectively, IFN-γ level was highest (105 pg/ml and 226.54 pg/ml) in the 109-120 months age group while it was lowest (12.97±8.16 pg/ml and 13.16±8.0 pg/ml) in the 61-72 months age group. No significant difference was observed in IFN-γ level after stimulation with either measles antigen or lectin among well-nourished (p<0.8) and mal-nourished (p<0.7) children suggesting that nutritional status did not have any effect on IFN-γ level. However, IFN-γ level was higher in children who received two dose of measles vaccine than those who received a single dose (p<0.001).Bangladesh Med Res Counc Bull 2014; 40 (3): 118-121
... Prior to 1989, ACIP recommended only one dose of measles vaccine routinely, to be given during a scheduled preschool visit. 35 A second dose had been discussed and rejected by ACIP owing to cost considerations. In 1989, there was a resurgence of measles, which initially included outbreaks among college students who had been vaccinated at preschool age. ...
After publication of certain vaccine recommendations made by the Advisory Committee on Immunization Practices, several unexpected events have occurred during implementation of these recommendations. These have included changes in recommendations following adverse events involved with a particular vaccine and the conferral of community protection as an offshoot of vaccination of a specific population. Vaccine shortages and hesitancy have also been proven impediments to full implementation, and vaccine recommendations have not gone unaffected by either public perception of a vaccine or by cost considerations.
Copyright © 2015 American Journal of Preventive Medicine and Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
... The Centers for Disease Control (CDC) re- 12 In 101 of these outbreaks, 67% of the cases occurred in schoolaged children, of whom 27% were unvaccinated and therefore considered to have preventable disease. 13 Measles outbreaks during this period developed in schools with immunization rates usually ≥96%. ...
Outbreaks of measles have been reported over the past 5 years, particularly affecting children between the ages of 1 and 5 years. Most of these children are younger than the age recommended by the Advisory Committee on Immunization Practices for the second dose of measles-mumps-rubella (MMR) vaccine. Question may arise as to whether strict adherence to the scheduled second dose is required or whether there is opportunity for earlier immunization under special circumstances (e.g., traveling abroad, poor response as evidenced by titer levels). The history of measles, its characteristics, and its evolving past and current immunization policies will be reviewed, focusing on the original intent of the recommended schedule and presenting a case in which deviating from current practice could be justified.
... [272], [273], [274], [275], [276], [277], [278], [279], [280], [281], [282], [283] According to The New England Journal of Medicine, 60 percent of all measles cases among American schoolchildren between 1985 and 1986 occurred in those who were vaccinated. [284] Scientist Trevor Gunn also points out that for several reasons, there is underreporting of illness caused by vaccination. These include: financial backlash from vaccination producers, and the restricted length of time for which adverse symptoms must occur-In England "72 hours for whooping cough and 8-20 hours for the MMRP" vaccines. ...
Today we have a major controversy brewing in the U.S. healthcare field. The question is being asked if the vaccinations that we are giving our children are safe and effective. What is the proof that vaccinations are safe? We have undertaken an enormous job of reviewing the world literature to examine whether vaccinations are safe, and whether they are effective. We have taken an in depth look at the politics, the economic incentives, and the conflicts of interest involved in the politics of vaccinations. We have reviewed the scientific literature and we have examined the results on the people who have received vaccinations and the health effects of these (often mandated) medical procedures. We have examined here the myths versus the facts in the science of vaccines, and whether the procedures themselves represent good science or whether the manufacturers and physicians who provide them support conjecture or good scientific practice. We have examined the lobbying on behalf of the vaccine makers, and we have examined the safety and efficacy of the dozens of vaccinations that children are receiving in the first months of life. Our society rarely looks at the safety and efficacy of medical manufactures which have enormous power to influence the decisions of the CDC, the FDA, and the Institutes of Allergy and Infectious Disease [] , but the media rarely hears of the trajedies and the side effects. We do, however, hear that vaccines promise to prevent some new condition, (such as genital warts. [11] [12] [13]) However, we have innundated the developing baby's body with dozens of vaccines [14] , but no industry advisor or anyone in the FDA has ever suggested that this is too much. We are overwhelming the child's system with adverse effects, and all this has happened in the last 40 years.
... Despite optimism that vaccination programs would eventually eradicate measles, reduced vaccination coverage against measles resulted in outbreaks of measles in many western countries. In the US, two major types of outbreaks have been described: those in which most of the cases occurred among preschool-age children (those under 5 years of age), and those in which most of the cases occurred among school-age persons (those 5 to 19 years of age) [27]. Most outbreaks occurred within small clusters, were acquired outside of the United States, and involved individuals who had not been vaccinated [28]. ...
Citation: Ariad S, Lazarev I, Benharroch D (2011) Measles Virus: Association with Cancer. J Clin Cell Immunol S5:002. Abstract Measles virus (MV) is a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified. Despite initial optimism that vaccination programs would eventually eradicate measles, reduced vaccination coverage against measles continues to result in outbreaks of measles. Mild or asymptomatic measles infections are common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations. Persistent, asymptomatic MV infections commonly persist in apparently healthy individuals. MV has been detected in several malignancies, including lung, breast, and endometrial cancers, as well as Hodgkin's lymphoma. The presence of MV in these tumors was associated with distinct clinico-pathological characteristics: in lung cancer, older ages of patients and over expression of Pirh2, and in breast cancer, age less than 50 years, lower histological grade, and over expression of p53. Nectin-4 is the MV receptor in epithelial cells and is highly expressed in certain epithelial tumors. MV-associated tumorigenesis may be linked to the effect of MV-phosphoprotein on Pirh2, an E3 ubiquitin ligase of p53. By way of MV interaction with Nectin-4 and Pirh2, persistent MV infection may co-act with other factors in transforming cells to become malignant.
... The licensed vaccine has a 95% seroconversion rate when given at the age of 12 months [16] and immunity in the population has to be over 95% to prevent endemic measles transmission [22]. If crowding is a factor, susceptible individuals can become infected even if vaccine coverage is high [23]. In urban districts of Guinea-Bissau, an increase in vaccine coverage from 61% to 80% did not reduce measles incidence among infants < 9 months of age, presumably due to the virus' extreme contagiousness [24]. ...
Despite the overall progress achieved with mass immunization campaigns in sub-Saharan Africa, measles mortality in young children remains a significant public health problem. Investigators at the Center for Vaccine Development (CVD) developed two Sindbis replicon-based measles DNA vaccine candidates encoding the measles virus (MV) hemagglutinin (H) or H and fusion (F) proteins to specifically target infants who are too young to receive the currently licensed measles vaccines. The Sindbis DNA replicons were well tolerated and highly immunogenic, eliciting plaque reduction neutralizing antibodies and measles-specific IFN-secreting T cells when administered to cotton rats, newborn and adult mice, and to juvenile and very young infant rhesus monkeys. A heterologous prime-boost regimen consisting of parenteral priming with DNA vaccine encoding H (pMSIN-H) and boosting with aerosolized attenuated MV vaccine was well tolerated by very young infant rhesus macaque monkeys and protected against viremia following respiratory challenge with wild type MV. A randomized, double-blind, placebo-controlled, Phase 1 clinical trial was conducted to evaluate the safety of these DNA vaccines in healthy adults living in the U. S. A. Three dosage levels of similar to 200, 400 and 800 g of each DNA vaccine administered in a 2-dose regimen were found to be safe and well tolerated. Among the various candidate DNA vaccine strategies for young infants, this is the most advanced, having been tested in a Phase 1 clinical study. If successful, the proposed strategy would allow to prevent the "window of vulnerability" that otherwise opens at similar to 16 weeks of age as maternal antibodies wane. (C) 2010 Published by Elsevier Ltd.
Au tournant des années 1990, la rougeole a balayé le monde. Évitable par la vaccination depuis 1963, la « première maladie » est pourtant une des grandes absentes d’un siècle pandémique qui tarde à s’achever, si ce n’est pour en faire l’incarnation d’un anti-vaccinationisme rampant. Au travers d’une chronique de la « crise » de 1988-1992, nous reviendrons sur le processus de coproduction entre l’infection et les technologies qui en protègent. Nous aborderons plus particulièrement la dimension sociale de l’infection virale pour comprendre pourquoi la vaccination de masse, au coeur d’une entreprise d’éradication appuyée, ne suffit pas à éviter la rougeole et participe même à accroître certaines inégalités en santé qui influent sur son épidémiologie. L’expérience de la COVID‑19 nous exhorte à mener ce genre de travail rétrospectif et à mobiliser l’Histoire en discipline de santé publique pour mieux saisir la place de la vaccination dans le passé et le présent viraux et contagieux . Documentation de l’OMS, littérature scientifique et terrain ethnographique forceront ensemble une approche « à parts égales » des espaces et des acteurs concernés, faisant dialoguer les expériences très locales et les politiques internationales pour révéler les écueils d’une santé (publique) globale ultra-technologisée et très verticale.
Alerts,~~~~Ñ oIcs anIaeReot3 measles is not required for matriculation. Students requesting religious, philosophical, or medical exemption are informed that they may be excluded from classes and other campus activities in the event of a measles outbreak. With current policies and enforcement procedures in place, a vaccination level of more than 95% can be maintained and future outbreaks prevented or limited. If such policies were widely adopted, college students might be eliminated as an important source of measles transmission. This would contribute to the support of global measles eradication recently explored by the World Health Organization, the Pan American Health Organization, and the CDC.8 In that report the participants concluded: Preventing measles outbreaks is more effective than trying to contain them. Mass vaccination campaigns under-taken in response to outbreaks are of limited usefulness. .. because such efforts are costly, disruptive and often ineffective by the time they are instituted.8(Pl7S We concur with this statement. With the recent agreement by the CDC's immunization committee and the American Academy of Pedi-atrics' Committee on Infectious Diseases to recommend a second dose of measles vaccine any time longer than one month after the first, a recent editorial points out that the question of the optimal timing for the second dose may become moot as the goal of measles eradication is attained in the 21st century.9 In the meantime, although measles outbreaks are still a possibility, we support the use of PIRs to help prevent them and to lessen the costly effects of measles outbreaks in a college setting. ACKNOWLEDGMENT
Introduction:
measles is the leading vaccine preventable childhood disease designated for elimination by WHO. More than 20 million people are affected by measles each year, particularly in Africa and Asia. With annual outbreaks reported from Ethiopia´s Oromia region. We analyzed measles containing vaccine coverage (MCV), measles cases and measles deaths over a 10-year period (2007-2016).
Methods:
we reviewed Oromia measles surveillance data and first-dose measles containing vaccine (MCV1) administrative coverage. Descriptive statistics and multivariable logistic regression were performed to assess variables associated with measles death. Additional spatial mapping was performed to visually display key areas of measles case distribution in Oromia.
Results:
a total of 26,908 measles suspect cases were identified, of which 18,223 (68%) were confirmed. A median age of 6 years (IQ range 0.5-71 years) and 288 deaths were observed. Among the total cases, 29% were unvaccinated and 46% had unknown vaccination status. The highest IR was seen in Guji zone (IR=190/100,000 population) among 1-4 years, with a majority from rural areas. Risk factors associated with death include age <5 years (AOR=1.82, CI: 1.42-2.33), unvaccinated status (AOR=1.44, CI: 1.06-1.95) and inpatient treatment (AOR=2.12, CI: 1.58-2.85). Of 8,732 measles IgM negative/indeterminate specimens, 10.5% tested positive for rubella specific IgM.
Conclusion:
outbreaks of measles are an ongoing public health concern in the Oromia region. Children aged 1-15 years remain at high risk for contracting measles in the region. We recommend strengthening routine immunization to reach all children, especially in rural areas and that the measles-rubella (MR) vaccine be considered.
Background
Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90–95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns.
Methods
We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination.
Results
We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5–9 year olds than established previously.
Conclusions
The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5–9 year olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.
Background:
Despite improvements in reported coverage of measles-containing vaccine (MCV) and progress towards elimination of measles, 172 939 measles cases were reported worldwide in 2017. Questions have been raised about whether measles cases are due to failure of immunisation programmes or vaccine policy failure, which might require changes to vaccination schedules or number of doses.
Methods:
This retrospective review of global surveillance data analysed case-based data for cases of measles occurring during 2013-17 submitted to WHO by its member states. Cases were classified as programmatically preventable (ie, did not receive the age-appropriate number of doses for that country) or programmatically non-preventable (ie, appropriately vaccinated as per national programme) on the basis of age at onset, year of birth, vaccination status, and eligibility for MCV doses in the country reporting the case. We grouped reasons why cases were non-preventable into four categories as follows: (1) received at least two doses of MCV; (2) too young for first dose; (3) received one dose but was too young to receive the second; or (4) was only eligible for one dose according to the national schedule. We analysed numbers and proportions of preventable and non-preventable cases of measles by region and year, reasons for non-preventable cases by year, preventable cases by age group, and preventable and non-preventable cases, including reasons for non-preventable cases, by measles elimination status of countries.
Findings:
Between Jan 1, 2013, and Dec 31, 2017, 634 139 measles cases were reported; 7850 (1%) cases were excluded because they did not provide age at onset, so 626 289 were included in our analysis. 191 333 (31%) of these cases had unknown vaccination status. 275 754 (63%) of the 434 956 cases with available vaccination data were categorised as programmatically preventable, 213 461 (77%) of whom were aged 1 year to less than 15 years. 156 384 (36%) cases were categorised as non-preventable, of whom 38 677 (25%) were two-dose vaccine recipients, 74 438 (48%) were too young to receive their first MCV dose, 11 914 (8%) received their first dose and were too young to receive their second dose, and 31 355 (20%), mostly in the Africa region, were non-preventable because they were only eligible for one dose on the basis of the national immunisation programme.
Interpretation:
Most measles cases during 2013-17 were programmatically preventable, highlighting the need for improving the effectiveness of immunisation programmes that already exist. Individual countries should do similar analyses to establish the changes needed in their country to decrease numbers of measles cases.
Funding:
None.
Macartney et al¹ report in this issue of JAMA Pediatrics on the safety of using combination measles-mumps-rubella-varicella (MMRV) vaccine as the second dose of measles-mumps-rubella (MMR) vaccine and sole dose of varicella vaccine in Australia, and the effect of this policy on national vaccine coverage. They found that there was no increase in febrile seizures when MMRV is administered in the second year of life approximately 6 months after a first dose of MMR and that on-time vaccination increased with use of MMRV. Are these findings an indication that the timing and use of combination MMRV vaccine should be reconsidered for the United States?
Vaccination has greatly reduced the incidence of measles in the United States. Yet, because of the highly infectious nature and potentially fatal complications of the disease, primary care physicians need to remain alert to possible cases and to react aggressively during an outbreak. Dr Holtan discusses why measles persists, who is at risk, and how immunity is achieved.
Prior to measles vaccine licensure, virtually every child in the United States suffered from measles. While the reported number of cases averaged approximately 525,000 annually, an incidence rate of 315 per 100,000 total population, the actual yearly number of cases approached 4 million [1–4]. Measles vaccine offered the opportunity to prevent this substantial health burden. This report will describe the results achieved using a single dose measles vaccine schedule, recent recommendations for a two-dose schedule, and the efforts to control a resurgence of measles in the United States.
In 1982, a two-dose vaccination programme with the combined vaccine against measles, mumps and rubella (MMR) was introduced in Sweden [20]. The vaccination coverage was sufficiently high to reduce transmission of these viral infections [1, 2, 4, 5, 7]. The reported incidence of measles decreased from 76 per 10 000 individuals in 1982 to 1.2 per 100 000 in 1988[7]. Vaccination against measles had been introduced in Sweden in 1971 and was offered to children from the age of 18 months. In 1981, reports from child-health centres showed that 56% of all the pre-school children had been vaccinated against measles. In 1982, 88% of the 12-year-olds born in 1970 received the trivalent MMR vaccine. The coverage continued to increase and during 1989 an average of 95% of the children received the trivalent vaccine at both occasions. The vaccination coverage has been sufficiently high to reduce transmission of measles in Sweden. Evaluation of the immune status before and after vaccination is essential for the prevention of infections. At the same time as the vaccination schedule was introduced a vaccination study was started. Each year between 400 and 800 12-year-old school-children were tested on serum samples obtained prior to and after vaccination.
Only minor variations of the prevaccination immunity to measles were seen during the period 3–7 years after introduction of the programme. The age groups studied had partly been vaccinated against measles earlier. Between 12 and 16% lacked prevaccination or natural immunity. The seroconversion rate of children seronegative for measles was high, i.e. 100% in 1985 and later varied between 96 and 97%. During the follow-up period there was a declining incidence of measles, mumps and rubella. The relationship between the vaccination and reduction of disease and natural immunity strongly suggests that the association is causal and that this vaccination policy reduced the transmission of infection.
The decision to choose a two-dose measles vaccination schedule depends on whether elimination rather then control is the goal. Both mathematical models and epidemiologic observations suggest that elimination is not possible with only one dose of current measles vaccines. A two-dose schedule is clearly a minimum requirement for elimination. The decision to implement a second dose requires social and governmental acceptance of the need for elimination. The country must have both the desire to commit economic resources and the health care infrastructure to deliver the second dose. Decision makers must realize that it may require ten or more years to achieve elimination. A two-dose schedule will not prevent outbreaks, unless programs are in place to ensure high coverage with both doses. Poorly implemented programs will result in continued outbreaks and loss of public confidence in the strategy. It may be better to identify and vaccinate high-risk groups and thus ensure high first-dose coverage at an appropriate age, rather than to give 90% of the population two doses and 10% of the population no doses.
The traditional emphasis on single-dose immunization against measles has failed to meet control or eradication requirements even in the most developed parts of the world. A single dose strategy is limited because of insufficient coverage rates in infancy, schoolage epidemics and primary and secondary vaccination failure. A second measles booster dose in required in order to reduce population susceptibility to sufficiently low levels to allow the goal of measles elimination to be achieved. This paper estimates the costs and benefits of a decision taken in Israel in 1988 to add school age measles immunization to the present 15 month old use of measles vaccine in Israel. The second dose policy of immunizing all Israeli children aged 6 for the years 1988–2008, costs around 14.15 million, yielding a benefit-to-cost ratio of 7.86/1. The vaccination programme was estimated to prevent over a 20 year period, approximately 80 300 simple cases, 9162 hospitalized cases, 21 non-fatal cases of encephalitis, 18 cases of SSPE and to save 85 lives. The break-even point for benefits to the health services alone, occurs if vaccine costs were to rise from 2.59 per dose. Therefore the decision to introduce a second measles dose in Israel seems to be fully justifiable on monetary grounds alone. Extremely high benefit-to-cost ratios for the adoption of a two dose policy, were also estimated for the UK (86.3/1), Spain (76.1/1) and Italy (53.0/1). For the Philippines and Nigeria the benefit to cost ratios were 11.4/1 and 20.6/1 respectively, though in the Philippines the benefit-to-cost ratio to the health services alone was less than unity. Limitations in resources for preventive health care remains a serious problem, even in developed countries. However, our cost-benefit calculations show the two-dose approach to be economically justifiable for many developing and developed countries.
Viral infections are among the most common afflictions of man. It has been estimated that children experience two to seven respiratory infections each year; adults are afflicted with one to three such episodes.1
Edward Jenner, an 18th century English physician, observed that milkmaids who had recovered from cowpox, did not have the facial scars of smallpox. In 1796, he demonstrated that inoculation of a susceptible individual with material from a cowpox lesion protected against smallpox. The next vaccination (against rabies) was introduced 100 years later. The pace of vaccine introduction then increased with a marked acceleration in the introduction of new vaccines in the last years of the 20th century. The widespread use of vaccines has had a dramatic impact on the occurrence of infectious diseases in the United States. This chapter describes the progress made as a result of immunization as well as the challenges remaining to realize the full current and future potential of immunizations. It focuses on smallpox, poliomyelitis, and measles, and briefly addresses other vaccine-preventable diseases of childhood.
This report is a compendium of all current recommendations for the prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps. The report presents the recent revisions adopted by the Advisory Committee on Immunization Practices (ACIP) on October 24, 2012, and also summarizes all existing ACIP recommendations that have been published previously during 1998-2011 (CDC. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1998;47[No. RR-8]; CDC. Revised ACIP recommendation for avoiding pregnancy after receiving a rubellacontaining vaccine. MMWR 2001;50:1117; CDC. Updated recommendations of the Advisory Committee on Immunization Practices [ACIP] for the control and elimination of mumps. MMWR 2006;55:629-30; and, CDC. Immunization of healthcare personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60[No. RR-7]). Currently, ACIP recommends 2 doses of MMR vaccine routinely for children with the first dose administered at age 12 through 15 months and the second dose administered at age 4 through 6 years before school entry. Two doses are recommended for adults at high risk for exposure and transmission (e.g., students attending colleges or other post-high school educational institutions, healthcare personnel, and international travelers) and 1 dose for other adults aged >/=18 years. For prevention of rubella, 1 dose of MMR vaccine is recommended for persons aged >/=12 months. At the October 24, 2012 meeting, ACIP adopted the following revisions, which are published here for the first time. These included: * For acceptable evidence of immunity, removing documentation of physician diagnosed disease as an acceptable criterion for evidence of immunity for measles and mumps, and including laboratory confirmation of disease as a criterion for acceptable evidence of immunity for measles, rubella, and mumps. * For persons with human immunodeficiency virus (HIV) infection, expanding recommendations for vaccination to all persons aged >/=12 months with HIV infection who do not have evidence of current severe immunosuppression; recommending revaccination of persons with perinatal HIV infection who were vaccinated before establishment of effective antiretroviral therapy (ART) with 2 appropriately spaced doses of MMR vaccine once effective ART has been established; and changing the recommended timing of the 2 doses of MMR vaccine for HIV-infected persons to age 12 through 15 months and 4 through 6 years. * For measles postexposure prophylaxis, expanding recommendations for use of immune globulin administered intramuscularly (IGIM) to include infants aged birth to 6 months exposed to measles; increasing the recommended dose of IGIM for immunocompetent persons; and recommending use of immune globulin administered intravenously (IGIV) for severely immunocompromised persons and pregnant women without evidence of measles immunity who are exposed to measles. As a compendium of all current recommendations for the prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps, the information in this report is intended for use by clinicians as baseline guidance for scheduling of vaccinations for these conditions and considerations regarding vaccination of special populations. ACIP recommendations are reviewed periodically and are revised as indicated when new information becomes available.
Background: The aim of this study was to determine measles
antibody titer in children who received two doses of vaccine and
were reimmunized at 7 years of age.
Methods: The school children were randomly choosen from
various areas of Tehran who had received two doses of measles
vaccine at 9 and 15 months of age and reimmunized at 7 years of
age. Measles antibody was measured in children aged 7 years and
4-6 weeks after reimmunization by Enzyme-linked immunosorbent
assay (ELISA).
Findings: A total of 339 children were evaluated. Antibody titers
in 132 (38.9%) children were more than 10 IU/ml (mean 68.3
IU/ml) and 207 (61.1%) less than 10 IU/ml. Antibody titers in 32 of
42 children who had been reimmunized were less than 10 IU/ml. In
two (6.3%) of 32 children antibody titers did not rise after
reimmunization and the mean antibody titer in remainder (30) of
the children was 71.3 IU/ml. Antibody titers in 10 (23.8%) of 42
children before and after reimmunization were 58 and 168.5 IU/ml
respectively. After reimmunization, the mean antibody titer in
children with high titer before reimmunization was higher than
those with low antibody titer.
Conclusion:
This study indicates that children with two dose measles
immunization before and after the first year of age are still
immunologically resistant against measles at 7 years of age.
Immunization is the most efficacious and cost effective intervention
available to improve the health and wellbeing of children and
prevention of the infectious disease.
Health care personnel are required to be immune against vaccine-preventable diseases, such as measles, mumps, rubella, and varicella. The aim of this study is to evaluate the accuracy of self-reported histories of disease and vaccination against measles, mumps, rubella, and varicella in order to determine the immune status of health care personnel. A self-reported questionnaire of history of previous disease and vaccination against these diseases was administered to a total of 910 health care personnel in Shimane university hospital in Japan, whose results were compared with serological evidences. There were numerous subjects who did not remember a history of disease (greater than 33% each) and of vaccination (greater than 58% each). Self-reported history of disease and vaccination had high positive predictive value against either disease for testing positive for antiviral antibodies. However, a considerable number of false-negative subjects could be found; 88.9% of subjects for measles, 89.3% for mumps, 62.2% for rubella and 96.3% for varicella in the population who had neither a self-reported history of disease nor a vaccination against each disease. In addition, regardless of the disease in question, a negative predictive value in self-reported history of disease and vaccination was remarkably low. These results suggest that self-reported history of disease and vaccination was not predictive to determine the accurate immune status of health care personnel against measles, mumps, rubella, and varicella. A seroprevalence survey, followed by an adequate immunization program for susceptible subjects, is crucial to prevent and control infection in hospital settings.
There are several viral infectious diseases with a high impact on developing countries which can be prevented by immunization with existing vaccines. The most important are poliomyelitis, measles, hepatitis B and yellow fever. Vaccines against poliomyelitis and measles used within the framework of the WHO/Expanded Programme on Immunization prevent about 1.4 million deaths from measles and 360,000 cases of paralytic polio per year in developing countries, but about 1.5 million measles' deaths and 200,000 cases of paralytic polio still occur. Hepatitis B infection and its sequelae are responsible for over 50 million infections and one million deaths annually. Highly effective hepatitis B vaccines are now available and the price of these vaccines for the developing world has fallen dramatically. Despite the availability of a safe and efficacious yellow fever vaccine since 1937, 5400 cases of this disease with 3200 deaths were reported in Africa and South America from 1986 to 1988. Because of the efficacy of existing vaccines and the lack of animal reservoirs or vectors, systematic vaccination programmes within the framework of the Expanded Programme on Immunization (EPI) could theoretically eliminate and even eradicate poliomyelltis, measles and hepatitis B. Many different obstacles need to be overcome before these goals are realized.
State immunization laws which exempt religious groups present difficult problems in disease control in measles epidemics. Two outbreaks are described, 136 cases in a college for Christian Scientists, and 51 cases associated with a camp attended by Christian Scientists. Control measures at the college included immunization and quarantine. An alternative strategy at the camp consisted of dispersal of exposed persons from the camp and their being quarantined in their home States. Three deaths (case-fatality ratio = 2.2 percent) were reported at the college; no serious complications were reported from the camp-associated epidemic. No transmission into the general community occurred in either epidemic. Public health officials are encouraged to be aware of the legal rights and obligations of religiously exempt groups so that outbreaks in these groups can be effectively controlled, even if standard immunization strategies are not possible. Early reporting and rapid case identification, investigation, and quarantine or vaccination procedures by public health workers are necessary for disease control in these settings.
The appropriate age for measles vaccination is determined by weighing the risk of measles disease and complications at a given age with vaccine efficacy at that age. In the United States, measles vaccine was initially used in children as young as 9 months of age because the disease was common and complications were greatest in persons less than 1 year of age. In 1965, when it became apparent that vaccine failure was unacceptably high in children less than 1 year and when epidemiologic analysis indicated that children greater than or equal to 1 year, particularly schoolchildren, were the primary focus of measles transmission, the vaccination age was raised to 12 months. In 1976, further studies showed efficacy was slightly higher at 15 months of age versus 12 months or 12-14 months of age. Because the risk of acquiring measles in children less than 15 months was low, the age for routine vaccination was increased to 15 months. This age recommendation may be appropriate for developed countries where the epidemiology of measles may be similar to the epidemiology in the United States. However, this age is inappropriate for many countries in the developing world where the risks of measles and complications from measles are high in young preschool children. In those countries, the recommended age for routine vaccination against measles is generally 9 months.
An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent. Nineteen (70 per cent) of the cases were students who had histories of measles vaccination at 12 months of age or older and are therefore considered vaccine failures. Persons who were unimmunized or immunized at less than 12 months of age had substantially higher attack rates compared to those immunized on or after 12 months of age. Vaccine failures among apparently adequately vaccinated individuals were sources of infection for at least 48 per cent of the cases in the outbreak. There was no evidence to suggest that waning immunity was a contributing factor among the vaccine failures. Close contact with cases of measles in the high school, source or provider of vaccine, sharing common activities or classes with cases, and verification of the vaccination history were not significant risk factors in the outbreak. The outbreak subsided spontaneously after four generations of illness in the school and demonstrates that when measles is introduced in a highly vaccinated population, vaccine failures may play some role in transmission but that such transmission is not usually sustained.
Great success has been achieved in controlling measles in the United States with a greater than 99% reduction in incidence rate from the prevaccine era. However, since 1981, the incidence rate of measles in the United States has been relatively stable at approximately 1,500 to 3,000 reported cases annually. We reviewed available information to determine the remaining impediments to elimination of measles. The potential impediments can be divided into two categories: (1) implementation of the current strategy and (2) whether the current strategy needs modification. The major reason for the failure to achieve elimination appears to be the fact that some persons for whom vaccine is indicated have not been vaccinated. While vaccine failures and importations play a role in transmission, sustained transmission in a totally vaccinated community has not been demonstrated. All chains of transmission have involved some unvaccinated persons. Measles elimination will require complete implementation of current strategies and careful monitoring of epidemiologic trends to determine whether future modifications in strategy are needed.
Mathematical models for the dynamics of directly transmitted viral and bacterial infections are guides to the understanding
of observed patterns in the age specific incidence of some common childhood diseases of humans, before and after the advent
of vaccination programs. For those infections that show recurrent epidemic behavior, the interepidemic period can be related
to parameters characterizing the infection (such as latent and infectious periods and the average age of first infection);
this relation agrees with the data of a variety of childhood diseases. Criteria for the eradication of a disease are given,
in terms of the proportion of the population to be vaccinated and the age-specific vaccination schedule. These criteria are
compared with a detailed analysis of the vaccination programs against measles and whooping cough in Britain, and estimates
are made of the levels of protection that would be needed to eradicate these diseases.
ON OCT 4, 1978, the Secretary of the Department of Health, Education, and Welfare, Joseph A. Califano, Jr, announced, "We are launching an effort that seeks to free the United States from measles by October 1, 1982" (statement made in Washington, DC, Oct 4, 1978). In announcing this initiative, the secretary noted the "remarkable progress made in controlling measles in the past 15 years" that made possible such an attempt to "eliminate indigenous cases of measles in this country." The purpose of this article is to describe the epidemiologic and operational history behind this initiative, to present its scientific rationale, and to summarize the major tactics viewed as essential to its successful execution.Background
Measles has had severe impact in the United States. Outbreaks were reported as early as 1635; a major epidemic occurred in the colonies in the period 1713 to 1715. In 1772, it was reported that 800
• Great success has been achieved in controlling measles In the United States with a greater than 99% reduction in incidence rate from the prevaccine era. However, since 1981, the incidence rate of measles in the United States has been relatively stable at approximately 1,500 to 3,000 reported cases annually. We reviewed available information to determine the remaining impediments to elimination of measles. The potential impediments can be divided into two categories: (1) implementation of the current strategy and (2) whether the current strategy needs modification. The major reason for the failure to achieve elimination appears to be the fact that some persons for whom vaccine is indicated have not been vaccinated. While vaccine failures and importations play a role in transmission, sustained transmission in a totally vaccinated community has not been demonstrated. All chains of transmission have involved some unvaccinated persons. Measles elimination will require complete implementation of current strategies and careful monitoring of epidemiologic trends to determine whether future modifications in strategy are needed.
(AJDC 1985;139:881-888)
During November, 1975, to May, 1976, measles occurred at a rate of 20.3 cases per 1000 in a purported immunized population, of whom historical and serologic survey revealed that 9 per cent had no history of either measles illness or vaccination and 18 per cent did not have detectable measles antibody. Antibody was detectable in 92 per cent of those vaccinated at greater than or equal to 13 months, 80 per cent at 12 months and 67 per cent of those vaccinated when less than one year old (P less than 0.001), but no significant differences existed with increasing years since vaccination (P greater than 0.1). A second vaccination increased detectable antibody prevalence only in those originally vaccinated when less than nine months old (42 to 80 per cent, P less than 0.02). During a measles outbreak, more cases occurred in those receiving vaccine when less than 12 months old than in those vaccinated at greater than or equal to 12 months (37 per cent vs. 9 per cent, P less than 0.001). A second vaccination protected those originally vaccinated at less than 12 months (35 per cent ill without a second vaccination vs. 2 per cent with, P less than 0.001). Thus, a single measles vaccination of children less than 12 months old does not protect; a second vaccination will protect this group.
Perpetuation of a virus in a population is distinct from the ability to persist in a cell culture or individual host. Parameters which determine perpetuation include: 1) the size of the population; 2) the turnover of the population; 3) the proportion of immunes in the population; 4) the transmissibility of the infection; and 5) the generation time between sequential infections. These parameters may be grouped into two composite factors which most directly affect transmission dynamics and perpetuation: (a) population turnover per generation period, and (b) transmissibility or the fraction of susceptibles infected per existing infection. Perpetuation in small populations usually requires either the ability to persist in individuals or rapid population turnover. Conversely, human viruses which initiate only acute infections require larger populations to persist. Seasonal variation in transmissibility can greatly increase the minimum population size in which persistence is possible, and we argue that the population size of 500,000 for measles persistence (described by Bartlett) is primarily a consequence of seasonal variation. Computer modelling can be used to examine the effect of changes in parameters which determine the seasonal cycle of virus perpetuation and fadeout. Finally, human infections are reviewed to indicate those which have been eradicated (smallpox), are on the threshold of eradication (poliomyelitis), are possibly eradicable (measles), or could be candidates for future efforts (hepatitis A and hepatitis B). In developing a strategy for eradication two points are of great potential utility: first, the seasonal trough should be exploited as a time for effective intervention; and, second, containment efforts should be directed at epidemiologically important population groupings such as schools.
In a randomized clinical trial designed to evaluate the effect of diuresis on infants with hyaline membrane disease, seven infants were treated with furosemide (2 mg/kg intravenously) and five received 5% dextrose water in 0.225% sodium chloride (control group). Arterial blood gas analyses performed before and during the six hours after treatment showed no significant difference between control and treated infants. Urine output and urine sodium and calcium loss were significantly increased (P less than .05) in the infants receiving furosemide. The diuresis seemed to have no effect on left atrial size determined echocardiographically, whereas measurements of dynamic skinfold thickness suggested mobilization of subcutaneous water. One infant became seriously dehydrated and hypotensive secondary to a massive diuresis. We concluded that furosemide had a potent diuretic effect in infants with hyaline membrane disease but does not improve cardiorespiratory function acutely. This may be because of failure to mobilize pulmonary interstitial fluid in the time period tested. It may also be possible that the presence of pulmonary interstitial fluid does not play an important role in the impairment of gas exchange in the acute stage of hyaline membrane disease.
Despite the uncertainties, the present situation in the United States seems the most favorable ever for the elimination of indigenous measles. The incidence rate of the disease is low, and immunization levels are high. Measles remains a substantive cause of childhood morbidity and occasional mortality in the United States. Given a vaccine of high effectiveness with low risk, effective strategies for control, and the present epidemiologic and programmatic situation, a serious attempt to eliminate measles from the United States seems not only rational and desirable but virtually obligatory.
A measles epidemic in a modern suburban elementary school in upstate New York in spring, 1974, is analyzed in terms of a model which provides a basis for apportioning the chance of infection from classmates sharing the same home room, from airborne organisms recirculated by the ventilating system, and from exposure in school buses. The epidemic was notable because of its explosive nature and its occurrence in a school where 97% of the children had been vaccinated. Many had been vaccinated at less than one year of age. The index case was a girl in second grade who produced 28 secondary cases in 14 different classrooms. Organisms recirculated by the ventilating system were strongly implicated. After two subsequent generations, 60 children had been infected, and the epidemic subsided. From estimates of major physical and biologic factors, it was possible to calculate that the index case produced approximately 93 units of airborne infection (quanta) per minute. The epidemic pattern suggested that the secondaries were less infectious by an order of magnitude. The exceptional infectiousness of the index case, inadequate immunization of many of the children, and the high percentage of air recirculated throughout the school, are believed to account for the extent and sharpness of the outbreak.
During a large outbreak of measles in Ohio in 1976 it was possible to measure measles vaccine efficacy by age at time of vaccination and number of years since vaccination. Using a summed incidence method to control for the confounding variable introduced by mass immunization clinics held during the outbreak, vaccine efficacy was greater than 95% for children vaccinated at 12, 13, and 14 or more months of age. Vaccine efficacy for those vaccinated at 12 months of age was notably better than for those vaccinated at younger ages but not different from those vaccinated at older ages. Although recently administered vaccine appeared more efficacious than vaccine administered in the past, this difference was not significant when controlled for age at vaccination. Evaluation of the mass clinics held during the outbreak demonstrated that 59.6% of the inadequately immunized children attended the clinics, but this was not substantially different from the proportion of adequately immunized who attended (52.4%). Recommendations for measles revaccination need not include children previously vaccinated at 12 months of age or greater.
A model for the spread of an infectious disease for which recovery gives temporary or permanent immunity is analysed. A heterogeneous population is divided into homogeneous groups in which immunization of newborns and of susceptibles of all ages is possible. Births and deaths occur at equal rates in each group and all newborns are susceptible. The threshold criterion obtained for the nonlinear differential equation model can be used to determine the immunization rates which will cause the disease to die out.
A serologic study was made in 34 children immunized against measles at the age of 12 months. Using a sensitive virus neutralization test, it was found that many of the children had pre-existing maternal antibody to measles virus. Children with high pre-existing antibody titers failed to seroconvert. Children with lower pre-existing antibody titers seroconverted, but the resulting antibody titer was significantly lower than in children without pre-existing antibody titer. The results of this study demonstrate a probably mechanism for measles vaccine failure in 12-month-old children and support the recommendation of the Public Health Service Advisory Committee on Immunization Practices to postpone measles vaccination to 15 months of age.
Chen, R. T. (CDC, Atlanta, GA 30333), G. M. Goldbaum, S. G. F. Wassilak, L. E. Markowitz, and W. A. Orenstein. An explosive point-source measles outbreak in a highly vaccinated population: modes of transmission and risk factors for disease. Am J Epidemiol 1989;129:173–82.
In 1985, 69 secondary cases, all in one generation, occurred in an Illinois high school after exposure to a vigorously coughing Index case. The school's 1,873 students had a pre-outbreak vaccination level of 99.7% by school records. The authors studied the mode of transmission and the risk factors for disease in this unusual outbreak. There were no school assemblies and little or no air recircu latlon during the schooldays that exposure occurred. Contact interviews were completed with 58 secondary cases (84%); only 11 secondary cases (19%) of these may have had exposure to the index case in the classrooms, buses, or out of school. With the use of the Reed-Frost epidemic model, only 22–65% of the secondary cases were likely to have had at least one person-to-person contact with the index case during class exchanges, suggesting that this mode of transmission alone could not explain this outbreak. A comparison of the first 45 cases and 90 matched controls suggested that cases were less likely than controls to have provider-verifiable school vaccination records (odds ratio (OR) = 8.1) and more likely to have been vaccinated at less than age 12 months (OR = 8.6) or at age 12–14 months (OR = 7.0). Despite high vaccination levels, explosive measles outbreaks may occur in secondary schools due to 1) airborne measles transmission, 2) high contact rates, 3) inaccurate school vaccination records, or 4) Inadequate immunity from vaccinations at younger ages.
Davis, R. M. (CDC, Atlanta, GA 30333), E. D. Whitman, W. A. Orenstein, S. R. Preblud, L. E. Markowitz, and A. R. Hinman. A persistent outbreak of measles despite appropriate prevention and control measures. Am J Epidemiol 1987; 126:438-49.
From January 4 to May 13, 1985, an outbreak of 137 cases of measles occurred in Montana and persisted for 12 generations of spread. A total of 114 cases occurred on the Blackfeet Indian reservation in northwest Montana. Of the 137 cases, 82 (59.9%) were in school-aged children (aged 5-19 years). Of the 114 cases on the reservation, 108 (94.7%) were classified as programmatically nonpreventable. A total of 64 (82.1%) of the 78 patients on the reservation who were born after 1956 and were above the recommended age at vaccination had a history of adequate measles vaccination. Additionally, an audit of immunization records at the schools in Browning, Montana, where most of the cases occurred, showed that 98.7% of students were appropriately vaccinated. A retrospective cohort study in the Browning schools failed to identify age at vaccination or time since vaccination as significant risk factors for vaccine failure. Overall vaccine efficacy was 96.9% (95% confidence interval = 89.5-98.2%). None of 80 Browning students who were vaccinated at less than 12 months of age and revaccinated at 15 months of age or older became infected. A case-control study showed a significant association between attendance at Browning basketball games and infection early in the outbreak. This outbreak suggests that measles transmission may persist in some settings despite appropriate implementation of the current measles elimination strategy.
An outbreak of measles occurred in Tucson, AZ, in 1985; 112 of the 225 cases were among students at two large high schools. A review of the immunization records of all students at both schools was undertaken in order to assess the risk of a person contracting measles in relation to that person's immunization status. Two factors, the lack of an immunization record and immunization prior to 12 months of age, showed a positive association with contracting measles. The association was statistically significant at one high school but not the other. At the first high school, students who were immunized at 12 to 14 months of age had a greater risk of infection than those immunized at 15 months or older. However, age at immunization of 12 to 14 months was not associated with a significantly higher risk when persons with multiple doses of vaccine were excluded from the analysis. Students of both schools showed a lower attack rate for those who had received multiple doses of vaccine, but the difference was not statistically significant.
A statewide serosurvey was conducted among 6th, 10th and 12th grade Massachusetts schoolchildren in 1982. Sera were screened using a standard measles hemagglutination inhibition (HI) assay, a sensitive measles plaque neutralization assay, and four rubella assays with corresponding sensitivity limits of approximately 15, 10, 7.5, and 5 international units (IU) of rubella antibody/ml respectively. Using the most sensitive assays, seroprevalence was 98.6% for measles antibodies and 93.1% for any rubella antibodies. For persons who received single doses of either combined measles and rubella vaccines or separate single vaccinations at different times, there were no significant differences in seroprevalence using sensitive assays. Of persons who received combined vaccines, 99.3% had antibody against measles compared to 98.4% of single antigen recipients. For rubella, 98.6% of combined vaccine recipients had antibody compared to 95.7% of single antigen recipients. These seroprevalence data indicate the effectiveness of a combined vaccination program and support epidemiologic data indicating virtual elimination of these diseases in Massachusetts schoolchildren.
A target has been set to eliminate measles, poliomyelitis, congenital rubella (as well as diphtheria and neonatal tetanus) from the 32 countries of the European Region of WHO by the year 2000. Achievement of this target will require achievement and maintenance of high levels of immunization coverage as well as strengthened surveillance and outbreak control. Use of combined vaccines and simultaneous administration of vaccines is a key component of achieving the goal.
Davis, R. M. (CDC, Atlanta, GA 30333), E. D. Whitman, W. A. Orenstein, S. R. Preblud, L. E. Markowitz, and A. R. Hinman. A persistent outbreak of measles despite appropriate prevention and control measures. Am J Epidemiol 1987; 126:438-49.
From January 4 to May 13, 1985, an outbreak of 137 cases of measles occurred in Montana and persisted for 12 generations of spread. A total of 114 cases occurred on the Blackfeet Indian reservation in northwest Montana. Of the 137 cases, 82 (59.9%) were in school-aged children (aged 5-19 years). Of the 114 cases on the reservation, 108 (94.7%) were classified as programmatically nonpreventable. A total of 64 (82.1%) of the 78 patients on the reservation who were born after 1956 and were above the recommended age at vaccination had a history of adequate measles vaccination. Additionally, an audit of immunization records at the schools in Browning, Montana, where most of the cases occurred, showed that 98.7% of students were appropriately vaccinated. A retrospective cohort study in the Browning schools failed to identify age at vaccination or time since vaccination as significant risk factors for vaccine failure. Overall vaccine efficacy was 96.9% (95% confidence interval = 89.5-98.2%). None of 80 Browning students who were vaccinated at less than 12 months of age and revaccinated at 15 months of age or older became infected. A case-control study showed a significant association between attendance at Browning basketball games and infection early in the outbreak. This outbreak suggests that measles transmission may persist in some settings despite appropriate implementation of the current measles elimination strategy.
An outbreak of measles occurred among adolescents in Corpus Christi, Texas, in the spring of 1985, even though vaccination requirements for school attendance had been thoroughly enforced. Serum samples from 1806 students at two secondary schools were obtained eight days after the onset of the first case. Only 4.1 percent of these students (74 of 1806) lacked detectable antibody to measles according to enzyme-linked immunosorbent assay, and more than 99 percent had records of vaccination with live measles vaccine. Stratified analysis showed that the number of doses of vaccine received was the most important predictor of antibody response. Ninety-five percent confidence intervals of seronegative rates were 0 to 3.3 percent for students who had received two prior doses of vaccine, as compared with 3.6 to 6.8 percent for students who had received only a single dose. After the survey, none of the 1732 seropositive students contracted measles. Fourteen of 74 seronegative students, all of whom had been vaccinated, contracted measles. In addition, three seronegative students seroconverted without experiencing any symptoms. We conclude that outbreaks of measles can occur in secondary schools, even when more than 99 percent of the students have been vaccinated and more than 95 percent are immune.
FRom September 9, 1981 to January 5, 1982, a measles outbreak occurred in Warren County, Pennsylvania. The outbreak persisted for nine weeks following the implementation of a county-wide outbreak control program primarily consisting of identifying and vaccinating susceptible schoolchildren. Forty-six cases occurred among students more than two weeks after control program implementation. All 46 had a school record indicating adequate measles vaccination; 13 had been vaccinated at control program clinics by one jet-injector team (Team A). A seroprevalence survey demonstrated that persons vaccinated by Team a had a significantly higher rate of vaccination failure than children vaccinated by other teams (37.0% vs. 5.9%, p = 5.7 X 10(-7). A case-control study was undertaken to assess possible additional risk factors for developing measles. Individuals with measles were nine times more likely than control individuals to have records of measles immunization that could not be verified with providers or to have been vaccinated at 12 months of age. The most likely reasons that this outbreak was sustained among persons with adequate vaccination histories were: 1) impotent vaccines and/or improper vaccine administration techniques were used by one jet-injector team; 2) several persons with histories of adequate vaccination were really not adequately vaccinated; adn 3) a substantial number of persons had been vaccinated at 12 months of age. There is no evidence from this outbreak that transmission of measles can be sustained among the 2-10% of individuals expected to remain susceptible following a single appropriate measles vaccination.
An outbreak of measles occurred in a municipal school system which had reported 98% of students immunized against measles. A case-control study was conducted to determine reasons for vaccine failure. Vaccine failure was associated with immunizations that could not be documented in the provider's records. Among children with provider-documented immunization, vaccine failure was associated with vaccination at 12 to 14 months of age with an odds ratio of 4.73. Among children vaccinated at 15 months or older, vaccine failure was not associated with time elapsed since vaccination. Studies should be conducted to determine whether unreliable immunization records are a more widespread problem. Further consideration should be given to routine revaccination of children previously vaccinated at 12 to 14 months of age.
The immune status of children vaccinated before 1 year of age was investigated during a measles epidemic in an industrial section of Connecticut. Of the 61 documented cases which occurred in former recipients of live vaccine, 46% were children vaccinated before age 1; children vaccinated before 1 year of age comprised one third of the total vaccinated population under study. The disproportionately increased number of cases in children vaccinated before their first birthday was not statistically significant. Of children vaccinated before age 1, 80% had demonstrable measles antibody. The geometric mean antibody titer of those vaccinated in infancy was lower that that of children vaccinated after 1 year of age (p< 0.01). Following revaccination, 20 of 21 seronegative children who had been vaccinated before age 1 year showed an IgG response without IgM; both IgM and IgG appeared following primary vaccination in 7 previously unvaccinated children. A child with measles encephalitis who had previously received live vaccine at 10 months of age also showed a secondary antibody response. The study suggests that infancy is only a relative contraindication of live measles virus vaccination; it further suggests that capacity for anamnestic response is not necessarily protective against measles.
A measles epidemic, during which 130 children were hospitalized and six died, occurred in St. Louis City and County during 1970 to 1971. A survey revealed an attack rate of 8.5 per cent in unvaccinated children who had not had natural measles, a rate of 1.7 per cent in children vaccinated after one year of age, but 6.3 per cent for children immunized before age one year. Measles attack rates in vaccinees were independent of time elapsed since immunization. Serum from 8 of 15 children with modified measles had no reduction in acute measles hemagglutination-inhibiting antibody titer after treatment with 2-mercaptoethanol. Twelve children had "atypical measles-rd but six of them had received only live vaccine. Ten per cent of 248 immunized children had hemagglutination-inhibiting titers of <5. Twenty-four cases of measles occurred in a school in which 89 per cent of the children were immunized or had had natural disease; 19 of these cases were vaccine failures. Vaccine failure contributed significantly to the propagation of this epidemic.
The global eradication of measles is desirable because the disease occurs almost universally, affects large numbers of children, can cause serious complications, and is responsible for about 900 000 deaths a year in developing countries. The feasibility of a measles eradication programme is suggested by the success of smallpox eradication, the availability of a heat-stable, cheap, and effective vaccine, and the fact that interruption of measles transmission has been achieved in some places. Eradication of measles globally would also result in the saving of the large sums of money being spent on measles treatment, vaccination, and surveillance.
From a theoretical and technical point of view, measles can be eradicated from the world. This disease has been eliminated
for a period of years from at least one country in the developing world (The Gambia). Experience in the United States indicates
that it will be eliminated from that country in the near future. Whether the necessary financial, political, and personnel
resources to achieve global eradication can be mobilized in the next several years remains in doubt.
The foregoing data clearly indicate that measles is not presently indigenous in most of the United States; it is focal both in time and in place. Large areas of the country are free of measles except for periodic introductions, many of which result in no further transmission, and most of which result in limited transmission. A high proportion of the young children in the country have been vaccinated, and a mechanism exists to maintain this standard by enforcing school laws, by providing parental education, and by tracking children felt to be at greatest risk of missing immunizations. Efforts are being made to improve immunization levels in preschool children and in susceptible adolescents and young adults. Suspected cases of measles are being investigated promptly at the local level, and appropriate responses are being made to identify and vaccinate susceptible persons in the area in which the case occurs. These factors combine to indicate that, if current efforts are sustained, the elimination of measles transmission in the United States is both feasible and imminent.
- Krugman
Assessment and validation of immunization status in the US
- D L Eddins
- B I Sirotkin
- P Holmgreen
- S Russell