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Immune responses to measles and measles vaccine: challenges
for measles control.
Moss WJ, Polack FP.
W. Harry Feinstone Department of Molecular Microbiology and Immunology,
Bloomberg School of Public Health, Johns Hopkins University, Baltimore,
Maryland,USA.
Most strategies for reducing global measles morbidity and mortality and
eliminating measles are based on the ability to enhance immune responses to
measles virus. Challenges to measles elimination and eradication are based in
part on the need to sustain high levels of population immunity to interrupt
transmission of measles virus. We review aspects of the immunology of measles
and measles vaccination with the aim of demonstrating how knowledge of the
immune responses is essential to furthering the goals of reducing measles
morbidity and mortality and the elimination of measles.
Better understanding of the mechanisms
of immune suppression after measles, the potential for alternative vaccination
strategies to induce immunity in young infants, and the immunologic basis of
atypical measles, increased mortality after high-titer measles vaccine, and
waning immunity will lead to improved strategies for measles control and
elimination.
Successful boosting of a DNA measles immunization with an
oral plant-derived measles virus vaccine.
Webster DE, Cooney ML, Huang Z, Drew DR, Ramshaw IA, Dry IB, Strugnell RA,
Martin JL, Wesselingh SL.
Department of Medicine, Monash University Medical School, Alfred Hospital,
Prahran, Victoria 3181, Australia.
Despite eradication attempts, measles
remains a global health concern. Here we report results that
demonstrate that a single-dose DNA immunization followed by multiple boosters,
delivered orally as a plant-derived vaccine, can induce significantly greater
quantities of measles virus-neutralizing antibodies than immunization with
either DNA or plant-derived vaccines alone. This represents the first
demonstration of an enhanced immune response to a prime-boost vaccination
strategy combining a DNA vaccine with edible plant technology.
Current overview of the pathogenesis and prophylaxis of
measles with focus on practical implications.
Hilleman MR.
Merck Institute for Vaccinology, 770 Sumneytown Pike, West Point, PA 19486,
USA. lorraine_cox@merck.com
Measles is one of the most important diseases of mankind, which is so highly
contagious and evokes such persistent immunity that the virus cannot be
sustained in a population of less than about 500,000 persons. The first of the
licensed live virus vaccines against measles was developed empirically and was
approved in 1963. It provides high
level and lasting immunity and is a paradigm for solving major medical
problems without really understanding them. In spite of means for
control by prophylactic immunization, research on measles infection continues
to be part of the effort to understand the pathogenesis of many different
viruses, which may have important similarities and differences and provide
important insights. Measles, usually, is spontaneously reversible and is a
prime model for understanding virus-induced immunodeficiency disease (AIDS)
which is rarely reversible. Much has been learned of basic immunology and
vaccinology in measles through observation of the inappropriate use of
vaccines of appropriate composition, and through inappropriate host response
to measles vaccines of inappropriate composition. This review provides a
current overview of selected highlights of measles, the virus, its
immunopathogenesis, and its control by use of live virus vaccine
which may lead to elimination of the
disease and eventually to eradication of the virus.
[Eradication of infectious diseases and vaccination]
[Article in French]
Begue P.
Service de Pediatrie Generale, Pathologie Infectieuse et Tropicale-Hopital
Armand Trousseau, 26 avenue du docteur Arnold Netter-75012 Paris.
Immunizations in man may act upon the infectious diseases development in three
evolutive patterns: eradication, elimination, or disease control.
Since the eradication of smallpox,
very few diseases are at present candidates for a next eradication;
poliomyelitis will be the first, perhaps followed by measles in many years.
In spite of efficacious vaccines and a solely human reservoir, the eradication
requires very strict conditions. However some diseases have been recently
successfully eliminated: poliomyelitis (Americas, Europe, West Pacific
regions), measles (i.e. Finland, United States), rubella (i.e. Finland). In
spite of some limits, diphtheria, pertussis, hepatitis B are well controlled
providing to get a sufficient vaccine coverage and to improve a sustained
surveillance of those diseases. Regarding Haemophilus influenzae b, infections
it is premature to predict a near elimination and the control is not yet well
defined. National and regional programs have often to improve immunisation
coverage and a better surveillance.
[Measles: prospects of vaccine prophylaxis and decrease of
morbidity in Moscow]
[Article in Russian]
Lytkina IN, Filatov NN, Mironova VF, Solodovnikov IuP.
Center of State Sanitary and Epidemiological Surveillance in Moscow, Russia.
The results of the prolonged epidemiological surveillance on measles in Moscow
are presented. The detailed analysis of the influence of immunization on the
level of measles morbidity has been made.
Changes in the age structure of
measles patients with an essential increase in the proportion of adolescents
and adults due to mass vaccination of the child population are shown.
High risk groups have been determined according to the data of serological
screening and epidemiological surveillance. The prospects of the vaccinal
prophylaxis of measles under present conditions, as the basic intervention for
achieving sporadic level of morbidity in this infection and further
eradication are evaluated.
Global health strategies versus local primary health care
priorities--a case study of national immunisation days in Southern Africa.
Schreuder B, Kostermans C.
Royal Tropical Institute, Amsterdam.
Building on the successful eradication of smallpox, the World Health
Organisation, together with other agencies, is now moving quickly to the
eradication of poliomyelitis, originally aimed for the year 2000.
Plans for the subsequent global eradication of measles are in an advanced
stage. Eradication of both polio and measles incorporate as a
fundamental strategy high routine coverage, surveillance and special national
immunisation days (NIDs), which are supplementary to routine vaccination
services. There has been a lively debate on whether poor countries, with many
health problems that could be controlled, should divert their limited
resources for a global goal of eradication that may have low priority for
their children. From a cost-effectiveness perspective, NIDs are fully
justifiable. However, field observations in sub-saharan Africa show that NIDs
divert resources and, to a certain extent, attention from the development of
comprehensive primary health care (PHC). The routine immunisation coverage
rates dropped on average since the introduction of NIDs in 1996, which is
contrary to what was observed in the western Pacific and other regions. The
additional investment to be made when moving from disease control to
eradication may exceed the financial capacity of an individual country. Since
the industrialised countries benefit most from eradication, they should take
responsibility for covering the needs of those countries that cannot afford
the investment. The WHO's frequent argument that NIDs are promotive to PHC is
not confirmed in the southern African region. The authors think that the WHO
should, therefore, focus its attention on diminishing the negative
side-effects of NIDs and on getting the positive side-effects incorporated in
the integrated health services in a sustainable way.
[The expanded program of vaccination: 25 years tomorrow]
[Article in French]
Santoni F.
Ecole du Service de sante des armees, BP 43, 69998 Lyon Armees, France.
The expanded program on immunization will soon celebrate its 25th anniversary.
The original program included vaccination against diphtheria, tetanus,
pertussis, poliomyelitis, measles, and tuberculoses. It was expanded to
include first yellow fever and hepatitis B and later haemophilus. Results are
mixed. Diphtheria was under control but has made a major comeback since
vaccination was halted in eastern Europe. Tetanus in newborns should no longer
be a public health problem by 2005. Control of pertussis has not been achieved
because the vaccine has been unsuccessful in interrupting transmission.
Poliomyelitis is no longer reported in the Americas. Hopefully transmission of
the wild virus will be stopped by 2003 and total eradication of poliomyelitis
will be achieved by 2005. For several reasons, there has been an alarming
increase in tuberculosis with an estimated annual incidence of 5 million cases
worldwide. Eradication of measles was
achieved in the Americas in 2000 and is expected in the European region
by 2007 and in the east Mediterranean area by 2010. Current data on yellow
fever and hepatitis B is inadequate, these vaccination being still poorly
implemented in endemic areas. A more widespread use of the vaccine will be
needed. However spending cutbacks and changing priorities in the Health
Ministries will require a renewal of commitment to this immunization policy.
Publication Types:
Review
Review, Tutorial
PMID: 11582877 [PubMed - indexed for MEDLINE]
AN: 21467462
Eradication of measles was achieved in the Americas?
- SM
In 1994, countries in the Region of the
Americas set a goal of interrupting indigenous measles transmission by the end
of 2000 (1).
During 1990--2000, measles cases declined 99.3%, from approximately 250,000 to
1,754 (Figure 1).
During 2000, transmission occurred in five of 41 countries that report to the
Pan American Health Organization (PAHO)
(Argentina, Bolivia, Brazil, the Dominican Republic, and Haiti), and confirmed
cases were reported in 16 (<1%) of 12,010 municipalities (2--4).
Introducing a novel model to estimate national and global
measles disease burden.
Miller MA.
Children's Vaccine Initiative, World Health Organization, Geneva, Switzerland.
millermark@nih.gov
OBJECTIVES: In discussions of expanded
measles control, elimination, and possible eradication, better estimates of
disease burden are increasingly important to target vaccination control
measures. Because global surveillance for measles is inadequate, a model to quantify country-specific estimates of
measles disease burden was formulated to help policy-makers consider control
options. METHODS: Country-specific demographics, developmental status,
historic vaccine coverage rates, and age-specific vaccine efficacy and attack
rates were used to determine the number of measles cases and deaths for 5-year
periods. RESULTS: The model estimates an annual global incidence of 32 million
measles-susceptible persons ( approximately 25% of the global birth cohort),
resulting in 28 million cases and 691 thousand deaths. Eighty-four percent
(578,000) of the global deaths occur in the World Health Organization African
and Southeast Asian regions. Twenty countries account for 82% of deaths
attributable to measles. In nine countries, over 2% of the birth-cohort are
estimated to die from measles. CONCLUSIONS: This methodology quantifies
country- and age-specific measles disease burden and establishes regional and
global disease patterns, allowing aggregations by income groups and regions,
which aids policy formulation. The data may be continuously updated, based on
dynamic changes in vaccine coverage rates and the incorporation of national
vaccination campaigns.
Review of regional measles surveillance data in the
Americas, 1996-99.
Hersh BS, Tambini G, Nogueira AC, Carrasco P, de Quadros CA.
Division of Vaccines and Immunization, Pan American Health Organization,
Washington, DC, USA.
BACKGROUND: In 1994, ministers of
health of countries of North and South America established the goal of measles
eradication from the western hemisphere by 2000. To accomplish this
goal, the Pan American Health Organization (PAHO) developed an enhanced
measles vaccination strategy. METHODS: PAHO's measles eradication vaccination
strategy has evolved into three principal components; a catch-up measles
vaccination campaign, maintenance of high vaccination coverage (keep-up), and
periodic follow-up measles vaccination campaigns. To monitor progress towards
measles eradication, measles surveillance has been strengthened, including the
laboratory investigation of suspected measles cases. FINDINGS: Both the
catch-up and follow-up mass campaigns achieved high vaccination coverages in
the respective targeted age groups. In 1996, only 2109 confirmed measles cases
were reported in the Americas. In
1997, there was a resurgence of measles in the Americas, mostly as a result of
a large measles outbreak with over 42000 cases, which occurred mainly among
unvaccinated young adults in Sao Paulo State, Brazil. By 1998, there was a
reduction in the number of reported confirmed measles cases, with a total of
14474 cases. Reduction of cases continued to the end of 1999, with a total of
only 2828 confirmed cases. INTERPRETATION: PAHO's measles eradication
strategy has been effective in interrupting transmission and maintaining the
absence of measles virus circulation in most parts of the Americas. The PAHO
experience provides strong evidence that with full implementation of an
appropriate vaccination strategy, measles transmission can be effectively
interrupted.
Orenstein WA, Strebel PM, Papania M, Sutter RW, Bellini WJ, Cochi SL.
National Immunization Program, Centers for Disease Control and Prevention,
Atlanta, Ga. 30333, USA.
Measles eradication would avert the current annual 1 million deaths and save
the $1.5 billion in treatment and prevention costs due to measles in
perpetuity. The authors evaluate the biological feasibility of eradicating
measles according to 4 criteria: (1) the role of humans in maintaining
transmission, (2) the availability of accurate diagnostic tests, (3) the
existence of effective vaccines, and (4) the need to demonstrate elimination
of measles from a large geographic area. Recent successes in interrupting
measles transmission in the United States, most other countries in the Western
Hemisphere, and selected countries in other regions provide evidence for the
feasibility of global eradication.
Potential impediments to eradication include (1) lack of political will in
some industrialized countries, (2) transmission among adults, (3) increasing
urbanization and population density, (4) the HIV epidemic, (5) waning immunity
and the possibility of transmission from subclinical cases, and (6) risk of
unsafe injections. Despite these challenges, a compelling case can be made in
favor of measles eradication, and the authors believe that it is in our
future. The question is when.
In 1994, the Ministers of Health from the Region of the Americas targeted
measles for eradication from the Western Hemisphere by the year 2000. To achieve
this goal, the Pan American Health Organization (PAHO) developed an enhanced
measles eradication strategy. First, a one-time-only "catch-up" measles
vaccination campaign is conducted among children aged 9 months to 14 years.
Efforts are then made to vaccinate through routine health services ("keep-up")
at least 95% of each newborn cohort at 12 months of age. Finally, to assure high
population immunity among preschool-aged children, indiscriminate "follow-up"
measles vaccination campaigns are conducted approximately every 4 years. These
vaccination activities are accompanied by improvements in measles surveillance,
including the laboratory testing of suspected measles cases.
The implementation of the PAHO
strategy has resulted in a marked reduction in measles incidence in all
countries of the Americas. Indeed, in 1996 the all-time regional record low of
2109 measles cases was reported. There was a relative resurgence of measles in
1997 with over 20,000 cases, due to a large measles outbreak among infants,
preschool-aged children and young adults in Sao Paulo, Brazil.
Contributing factors for this outbreak included: low routine infant vaccination
coverage, failure to conduct a "follow-up" campaign, presence of susceptible
young adults, and the importation of measles virus, apparently from Europe.
In 1989, the World Health Assembly adopted the goal of reducing measles
morbidity and mortality by 90% and 95%, respectively, by 1995, compared with
estimates of the disease burden in the prevaccine era (1). In 1990, the World
Summit for Children adopted a goal of vaccinating 90% of children against
measles by 2000. Three regions of the World Health Organization (WHO) have
targeted elimination: in 1994, the American Region (AMR) targeted elimination by
2000; in 1997, the Eastern Mediterranean Region (EMR) targeted elimination by
2010; and in 1998, the European Region (EUR) targeted elimination by 2007. This
report updates progress since 1997 (2) toward global measles control and
regional elimination of measles, and includes vaccination coverage and disease
surveillance data received by WHO as of August 14, 1999. Data for 1998 suggest
that routine measles vaccination coverage has declined in some regions, the
number of countries reporting cases and coverage to WHO has decreased, and
measles continues to be an important cause of morbidity and mortality.
During August 10-November 23, 1998,
33 confirmed * measles cases were reported to the Anchorage Department of Health
and Human Services and the Alaska Department of Health and Social Services (ADHSS).
Of these, 26 cases were confirmed by positive rubeolaIgM
antibody test, and seven met the clinical case definition. This was the largest
outbreak of measles in the United States since 1996 (1,2). This report
summarizes results of the epidemiologic investigation conducted by ADHSS and
underscores the importance of second-dose requirements for measles vaccine.
During the early 1980s, in the
aftermath of smallpox eradication, some scientists and public health officials
urged consideration of a global effort to eradicate measles (1). During the
mid-1980s, however, the high level of population immunity required to interrupt
measles virus transmission became clear, and the prospect of measles eradication
seemed to recede (2). As recently as 1993, a task force on disease eradication
declared measles "not now eradicable"(3). The major obstacles to eradication
cited by the task force were the contagiousness of measles, the lack of a
vaccine that is effective among children aged less than 9 months (most of whom
have maternal antibody to measles that protects them from disease but which also
inhibits the immune response to the vaccine virus), and the incorrect perception
that measles is a mild illness.
Other presentations addressed surveillance for clinical disease and
laboratory tools for virus identification and antibody detection.
Information was presented concerning
other factors that could potentially affect the feasibility of measles
eradication (i.e., the possible existence of nonhuman reservoirs for the virus,
the possibility of transmission of measles from persons with asymptomatic
measles infection, and the possibility that vaccination-induced immunity to
measles might wane with the passage of time).
Department of Infectious and Tropical Diseases, London School of Hygiene and
Tropical Medicine, Keppel Street, London, UK. f.cutts@lshtm.ac.uk
The accelerating progress in reducing measles incidence and mortality in many
parts of the world has led to calls for its global eradication during the next
10-15 years. Three regions have established goals of elimination of indigenous
transmission of measles. The strategy used in the Americas of a mass 'catchup'
campaign of children 9 months to 15 years of age, high coverage through
routine vaccination of infants, intensive surveillance and follow-up campaigns
to prevent excessive build-up of susceptibles has had great success in
reducing measles transmission close to zero. However, while these developments
are impressive, much remains to be done to reduce measles-associated mortality
in western and central Africa, where less than half of children are currently
receiving measles vaccine and half a million children die from measles each
year. The obstacles to global measles eradication are perceived to be
predominantly political and financial. There are also technical questions,
however. These include the refinement of measles elimination strategies in the
light of recent outbreaks in the Americas; the implications of the HIV
epidemic for measles elimination, issues around injection safety, and concerns
about the possibility that secondary vaccine failures will contribute in
sustaining transmission in highly vaccinated populations. The global
priorities are to improve measles control in low income countries, increase
awareness among industrialized countries of the importance of measles, and
conduct studies to answer the technical questions about measles elimination
strategies.
Advances in global measles control and elimination: summary
of the 1997 international meeting.
A meeting concerning advances in measles control and elimination, the third in
a series, was held in Atlanta during August 1997. The meeting was cosponsored
by CDC, the Pan American Health Organization, the World Health Organization,
and the United Nations Children's Fund. Meeting participants concluded that
substantial progress has been made toward controlling measles.
Measles transmission has been
interrupted in several countries, reinforcing the view that measles
eradication is technically feasible using existing vaccines and intervention
strategies. However, measles still accounts for 10% of global mortality from
all causes among children aged <5 years (i.e., approximately 1 million deaths
annually). Progress toward measles control varies substantially among
countries and regions. Intensified efforts are necessary to implement
appropriate control and elimination strategies, including supplementary
vaccination campaigns, expansion of routine vaccination services, and
surveillance. These strategies and estimates of the resources required to
implement them will require adjustment based on accumulating experience.
Programmatic and financial obstacles must be overcome if the final goal of
measles eradication is to be achieved.
[Expanded program of vaccination. Results and prospects]
[Article in French]
Guerin N, Antona D.
Centre International de l'Enfance et de la Famille, Bois de Boulogne, Paris.
The expanded program on immunization, jointly launched by WHO and UNICEF in
1974 aimed in the beginning at immunizing 80% of the children of the world
against measles, tetanus, pertussis, poliomyelitis, diphtheria and
tuberculosis. After reaching the objectives in 1990, countries have been urged
towards eradication of poliomyelitis, elimination of neonatal tetanus, and
measles control. Immunization against hepatitis B and yellow fever were also
proposed according to local epidemiology.
Tremendous results have been already
delivered: the American continent has eliminated poliomyelitis since August
1991, it has reduced dramatically the incidence of measles. All the countries,
including those from Africa, are organizing campaigns aiming at polio
eradication. Active surveillance systems have been implemented. But financial
and operational constraints persist, linked to vaccines prices, their heat
sensitivity, injection techniques, and to the sterilisation
and waste disposal. Major efforts are still needed.
The progress of the Polio Eradication Initiative: what
prospects for eradicating measles?
Gounder C.
Johns Hopkins School of Hygiene and Public Health, Baltimore, USA.
Although various attempts have been made to eradicate infectious diseases,
only smallpox has been eradicated to date. Polio is targeted for eradication
in 2000 and already planning has begun for the eradication of measles.
However, before we commit to a measles
eradication effort, we must examine the lessons to be learned from polio
eradication. Of particular importance is the debate over whether resources
should be invested in 'horizontal' or 'vertical' programmes.
The outcome of these debates will have a very deep and lasting impact on
global health development in years to come. Collaboration between
targeted programmes and the primary health care sector through polio and
measles eradication efforts will help bring about the necessary balance
between goal-oriented programmes, which are subject to quality control and can
be evaluated by measurable outcomes, and broader efforts to build up
sustainable health infrastructure.
de Quadros CA, Hersh BS, Nogueira AC, Carrasco PA, da Silveira CM.
Pan American Health Organization, Washington, DC, USA.
In 1994, the Ministers of Health from the Region of the Americas targeted
measles for eradication from the Western Hemisphere by the year 2000. To
achieve this goal, the Pan American Health Organization (PAHO) developed an
enhanced measles eradication strategy. First, a one-time-only "catch-up"
measles vaccination campaign is conducted among children aged 9 months to 14
years. Efforts are then made to vaccinate through routine health services
("keep-up") at least 95% of each newborn cohort at 12 months of age. Finally,
to assure high population immunity among preschool-aged children,
indiscriminate "follow-up" measles vaccination campaigns are conducted
approximately every 4 years. These vaccination activities are accompanied by
improvements in measles surveillance, including the laboratory testing of
suspected measles cases. The implementation of the PAHO strategy has resulted
in a marked reduction in measles incidence in all countries of the Americas.
Indeed, in 1996 the all-time regional
record low of 2109 measles cases was reported. There was a relative resurgence
of measles in 1997 with over 20,000 cases, due to a large measles outbreak
among infants, preschool-aged children and young adults in Sao Paulo, Brazil.
Contributing factors for this outbreak included: low routine infant
vaccination coverage, failure to conduct a "follow-up" campaign, presence of
susceptible young adults, and the importation of measles virus, apparently
from Europe. PAHO's
strategy has been effective in interrupting measles virus circulation. This
experience demonstrates that global measles eradication is an achievable goal
using currently available measles vaccines.
Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Mexico, D.F.,
Mexico.
Infecto-contagious diseases in the twenty-first century with respect to
precedent will see themselves deprived of smallpox, dracunculiasis and very
probably of paralyzing poliomyelitis. Vaccination-preventable diseases, such
as measles, whooping cough, diphtheria, tetanus, rabies, some forms of
meningitis, yellow fever and episodes of disseminated tuberculosis will
greatly diminish in their rates of morbi-lethality;
the elimination of some, and the
eradication of measles, are expected. Other diseases such as diarrhea
(including cholera), geo-helminthiasis, some severe respiratory tract
infections and the majority of vector-transmitted infectious diseases will
decrease due to improvements in potable water services, drainage, sanitary
food control, living quarters, and individual and community anti-vector
action. Leprosy, onchocerciasis and several parasitoses will be controlled by
the available antimicrobial drugs. Infectious diseases will continue to be an
important health problem due to: Reduction in the immunocompetence resulting
from the aging of the population, chemotherapies necessary for neoplasms, and
autoimmune pathology and the survival of persons with primary
immunodeficiencies; lifestyles prone to infectious pathology, such as
mega-city urbanization, children in day care centers, industrialized foods,
intravenous drug addiction, sexual liberation, global commerce, and tourism;
antibiotic-multiresistant microbial flora; environmental disturbances as a
result of global warming, deforestation, the settling of virgin areas, dams,
the large-scale use of pesticides, fertilizers and antimicrobials, and
natural/social disasters generators of poverty, violence and deprivation will
result in emergence or re-emergence of infectious diseases already controlled
in the past.
Division of Immunology and Cell Biology, John Curtin School of Medical
Research, Australian National University.
This article lists the vaccines current available for the control of both
viral and bacterial infections. They may be attenuated live or inactivated
whole microorganisms, or subunit preparations. Many more are in the pipeline
and increasing attention is being given to establishing their safety before
registration. Following the earlier eradication of smallpox, good progress is
now being made toward the global eradication of poliomyelitis and
a new program to eliminate measles
from the Americas has begun. A variety of new approaches to vaccine
development is now available. The hepatitis B virus surface antigen, made by
DNA-transfected yeast or mammalian cells, is the basis of the first
genetically engineered vaccine. Early in the 21st century, new vaccines based
on oligopeptides, recombinant live viral or bacterial vectors (often existing
live vaccines), or recombinant DNA plasmids are likely to be registered for
human use. The efficacy of vaccines depends on the immune responses generated,
and the recent substantial increase in our understanding of the mammalian
immune system now offers great opportunities for manipulation to best obtain
desired responses. These include mixing vaccine formulations to maximize
immune responses, and combining vaccines to simplify their administration.
Despite these advances, some persisting infections, such as those caused by
HIV, plasmodia, and mycobacteria, still pose a great challenge to vaccine
developers.
Following the failure of disease eradication efforts in the
first half of this century, the success of smallpox eradication and
the ongoing initiatives against poliomyelitis and dracunculiasis are
re-establishing eradication as a viable disease control
strategy. The perpetual benefits of eradication, together with the
positive impact that such initiatives can have on health services in
general, are changing the world's perception of these endeavours. Among
the most obvious examples of this changing trend is the recent enthusiasm
in both industrialized and developing countries for
re-exploring the eradicability of measles.
Increasingly, it appears that measles,
the single leading cause of vaccine-preventable childhood morbidity and
mortality worldwide, may be the next major organism targeted for global
eradication.
AN: 98138034
[Discussion on the elimination of measles based on the
45-year-incidence data in Inner Mongolia]
[Article in Chinese]
Zhang LZ, Yan SH, Meng XK.
Inner Mongolia Autonomous Region Antiepidemic station, Huhhot.
Measles incidence data collected since
1950 in Inner Mongolia is analyzed in this paper. The following
characteristics have been noticed after measles vaccine was widely used: (1)
the incidence and the mortality of measles kept decreasing, (2) The epidemic
still occasionally appeared at low incidence level; (3) the proportion of
cases in older children increased; (4) the peak month of the disease
occurrence postponed; (5) the differences of incidence among districts
depending on the implementation of vaccine and immunization. Since the goal of
poliomyolitis
eradication is given priority to and should be achieved, measles eradication
program should not be overemphasized.
Towards eradication of measles virus: global progress and
strategy evaluation.
Nokes DJ, Williams JR, Butler AR.
Wellcome Centre for the Epidemiology of Infectious Disease, Department of
Zoology, University of Oxford, UK.
Despite an increase in global measles
vaccine coverage from under 20% in 1980 to around 80% in 1990, measles remains
a major cause of morbidity and mortality world-wide. This paper
addresses a number of issues relating to efforts to control measles, namely, (i)
at the global level, how might we assess the impact of measles vaccination on
the incidence of infection and associated disease, and, (ii), at the strategic
level, how can we utilise an understanding of the transmission dynamics of
childhood viral infections to aid the design of optimal immunisation
programmes? Based on WHO vaccine coverage data, and organising countries
according to similarities in demographic and epidemiological parameters, an
age-structured model of measles transmission is used to capture the non-linear
dynamics of infection and mass vaccination and to generate projections of the
impact of measles immunization world-wide.
The results provide a crude indication
of the percentage reduction in measles cases by year 2000 (compared with no
immunization) and suggest an approximately 70% reduction in cases over all
ages, and 77% reduction in cases under 5 years (where there is the greatest
risk of case fatality); these suggest that WHO targets for 1995 are unlikely
to be achieved. In the second part of the paper, examples are given to
illustrate the usefulness of a modelling approach in evaluating measles
immunization policy. The introduction of MMR vaccine in the UK in 1988 has
resulted in measles incidence falling to an all time low and attention has
turned to the requirements of elimination. A realistic age structured model,
validated using extensive serological data, is used to compare the merits of
single or two dose strategies. Based upon recent estimates of vaccine efficacy
(90%) and coverage (92% by end of second year of life) it is suggested that a
two-dose policy with a pre-school second dose given irrespective of vaccine
history is required to prevent the build up of susceptibles to epidemic
proportions in the longer term. In a second example, prompted by the success
of the campaign approach to polio and measles elimination in Central and South
America, simple models are used to explore and quantify the process by which
pulse vaccination programmes (i.e. repeated application across a wide age
range) act to control transmission.
Measles Virus Section, Centers for Disease Control and Prevention, Atlanta, GA
30333.
Measles virus is the prototypic member of the Morbillivirus genus of the
family Paramyxoviridae. The viral genomic RNA is single-stranded, nonsegmented,
and of negative polarity and encodes six major structural proteins. The two
viral transmembrane glycoproteins, the hemagglutinin and fusion proteins, are
both required for virus-host cell membrane fusion, while attachment to host
cells is mediated by the hemagglutinin. The human CD46 molecule has been
identified as a cellular receptor for measles virus. Antibodies raised against
either viral glycoprotein neutralize measles virus in vitro and protect
against infection. Although measles virus remains a single serotype
(monotypic), nucleotide sequence analyses have identified distinct lineages
among recent wild type isolates. These
genetic changes were manifested by detectable antigenic variation between
vaccine and wild type viruses and at some point may influence strategies for
control, elimination, and eventual eradication of measles virus.
Pulse mass measles vaccination across age cohorts.
Agur Z, Cojocaru L, Mazor G, Anderson RM, Danon YL.
Department of Applied Mathematics and Computer Science, Weizmann Institute of
Science, Rehovot, Israel.
Although vaccines against measles have
been routinely applied over a quarter of a century, measles is still
persistent in Israel, with major epidemics roughly every 5 years. Recent
serological analyses have shown that only 85% of Israelis aged 18 years have
anti-measles IgG
antibodies. Considering the high transmissibility of the virus and the
high level of herd immunity required for disease eradication, the Israeli
vaccination policy against measles is now being reevaluated. Motivated by
theoretical studies of populations in perturbed environments, we examined the
possibility of replacing the conventional cohort vaccination strategy by a
pulse strategy--i.e., periodic vaccination of several age cohorts at the same
time. Numerical studies of a deterministic age-structured model suggest that
vaccination, which renders immunity to no more than 85% of the susceptible
children aged 1-7 years, once every 5 years will suffice to prevent epidemics
in Israel, where infection rate is highest amongst schoolchildren. The model
suggests that by using such a strategy the density of susceptible individuals
is always kept below the threshold above which recurrent epidemics will be
maintained. Analysis of simpler, non-age-structured, models serves to clarify
the basic properties of the proposed strategy. Our theoretical results
indicate that the advantages and disadvantages of a pulse strategy should be
seriously examined in Israel and in countries with similar patterns of measles
virus transmission.
"Just one shot" is not enough--measles control and
eradication.
Levy MH, Bridges-Webb C.
Department of Community Medicine, University of Sydney, Croydon, NSW.
The epidemiology of measles in
Australia has changed in the last decade due to control of the disease by
increased immunization rates. Elimination of endemic measles is possible, but
has still to be attempted. A partially immunized population results in disease
in an older population, with the possibility of contracting measles in the
childbearing years. For elimination of measles to occur, a second dose of
measles-mumps-rubella vaccine should be introduced. Changes in the
immunization protocol would need to be monitored with reliable
population-based data on seroconversion rates and disease incidence. Reliable
documentation of immunization is a prerequisite for any legislative initiative
in the field of immunization. In order to maximize the impact of immunization
programmes, the social and cultural contexts within which immunization occurs
should receive greater consideration.
[Vaccination against measles. The situation in Mexico and
America. Advances in the method of aerosol immunization]
[Article in Spanish]
Fernandez de Castro J, Kumate J.
Direccion General de Medicina Preventiva, Mexico, D.F.
We present general comments on the
epidemiology of measles considering the pre-vaccine era as well as the
post-vaccine period in which some changes can be observed: the decrease in
morbidity and mortality, the extension of the inter-epidemic interval, the
increase in the mean age of infection, etc. We make some estimations about the
vaccine coverage and the ideal age of immunization for the goal of eradication
(assuming a lifelong immunity for the vaccinees).
The technical problems in measles immunization are also revised explaining why
no continental country has been able to eliminate the disease. We
describe the epidemiological situation in North America, Mexico and Latin
American countries. Lastly we present the Mexican experience with the inhaled
aerosolised vaccine: the studies in Monterrey (Sabin et al, 1982), other
investigation in Mexico, D.F. and in the State of Jalisco, as well as the mass
campaigns in Aguascalientes in 1988 and in Coahuila and Nuevo Leon in 1989. We
propose it as an effective, harmless, simple, inexpensive and practical
method.
Modelling forces of infection for measles, mumps and
rubella.
Farrington CP.
Communicable Disease Surveillance Centre, London, U.K.
Serological data from 8870 persons
collected prior to the introduction of measles, mumps and rubella (MMR)
vaccine in the UK are used to describe the rate at which individuals acquire
infection by these diseases at different ages. A parsimonious model is
developed and fitted under various interpretations of the data, particularly
concerning the probability of lifelong susceptibility to infection. It is
shown that, while the force of infection curves are relatively robust in their
general features, they exhibit considerable sensitivity in matters of
important detail. This is true in particular of the values taken by the force
of infection in older age groups. As a result, estimates of the average age at
infection are highly sensitive to these interpretations. This in turn may
limit the accuracy of predictions from mathematical models based on these
parameters, in particular regarding the level of immunization required for
eradication of disease.
Perspectives and limits in the eradication of infectious
diseases.
Stuart-Harris C.
Department of Virology, University of Sheffield.
Eradication of an infectious disease on a global scale means that transmission
of the disease has been completely vanished and the disease caused by the
infection has totally disappeared. Regional eradication represents
disappearance of an infection from a certain area or region whereas elsewhere
it continues to be transmitted. Smallpox which was finally eradicated in 1977
had been progressively eliminated from one continent after another in the
preceding years. At the present time regional elimination of paralytic
poliomyelitis has almost succeeded in the USA, the United Kingdom, Europe and
Asia through routine use of Sabin live oral vaccine. Paralysis associated with
the use of this vaccine has continued with an extremely low incidence-rate.
Contact-infection and spread of virus excreted by recently-vaccinated persons
occur to a significant extent and fortunately with polioviruses mostly
unchanged in virulence. The second
disease with attempted regional elimination is measles. In the USA county-wide
elimination was successful in 1985 in all but a minority of counties. There
followed two years with many more cases before a decline in incidence resumed
once again. Elsewhere the general sponsoring of immunization under the
expanded programme (EPI) of WHO is slowly taking effect.
Department of Epidemiology, Ministry of Health, Jerusalem, Israel.
Measles continues to occur in epidemic
waves in Israel, Gaza, and the West Bank, causing morbidity and mortality. In
Israel, immunization of infants against measles began in 1967, and 90% had
been immunized by the mid-1980s. In Gaza and the West Bank, where immunization
of infants against measles began in 1973 and 1976, respectively, the
immunization rate reached 75% in the late 1970s and increased to greater than
90% in the 1980s. Measles epidemics, which previously had occurred in 5- to
7-year cycles, occurred every 2-4 years in the 1980s and affected individuals
who were older than those affected in previous years. Israel's
commitment to eradicating measles by 1992 will require a substantially
expanded immunization program in comparison with the traditional program that
requires immunization of infants alone. The benefits of several alternative
immunization strategies considerably exceed their costs. A new, two-dose
immunization will be needed as a minimal strategy, and a campaign for
administering booster doses to school-aged children may be required as well to
achieve control and eradication of measles. Measles is a serious but
preventable public health problem; appropriate strategies must be devised by
national and international public health officials to control the disease in
developing and developed countries.
Measles and mathematics: "control or eradication?".
Kenya PR.
Kenya Medical Research Institute, Medical Research Centre, Nairobi.
A measles outbreak occurred in the Kirinyaga District in February, 1985.
Immunization coverage against measles was above 80% in the district and
increased by age. The immunization against measles was lowest (46%) in the age
group (8-11) months and highest (90%) in the (36-59) months age group.
However, the overall vaccine effectiveness in the childhood population (8-59)
months was only 43.5% and peaked (91.5%) in the (24-35) months age group.
Based on these and similar findings in
some developed and developing countries the proposal for global measles
eradication is suggestively premature and particularly so for the tropics. The
eradication of measles poses far more substantial obstacles than did smallpox
eradication. That transmission continues to occur in communities with very
high measles vaccination coverage and high vaccine effectiveness (vaccine
efficacy) is a true testimony to the difficulty involved.
Prospects for the eradication of infectious diseases.
Stuart-Harris C.
The meaning of eradication, which is an irreversible conclusion, is considered
primarily to distinguish it from elimination, which is reversible from outside
the area. Poliomyelitis and measles are at present the diseases for which
conditions most favor an attempt to produce eradication. Poliomyelitis has now
reached a frequency in the developing world as high as it was in the
prevaccine era of the United States. The use of oral vaccine is a deliberate
attempt to substitute the wild-type polioviruses in the community with the
vaccine-like viruses derived from the vaccine itself. Mass use of vaccine in
all children less than five years of age on a single day twice in a year has
produced a critical decrease in the incidence of the disease in Brazil.
Following determined efforts to
achieve immunization of at least 95% of the population, the United States is
now nearing the state of complete freedom from the transmission of measles
virus. The use of diploid cells for making vaccine has enabled the
virus to be given as an aerosol to babies less than six months of age and
would be of particular value in developing countries. The high
transmissibility of measles makes a severe demand for vaccine, but so long as
the uptake of vaccine reaches at least 90%, the successful elimination of
measles is extremely probable.
Advances in immunology, microbial genetics, molecular biology and biochemistry
are opening prospects for new purified and synthetic antigens against
infectious diseases, cancers of viral origin and some immunodeficiencies.
Immunization programmes against major childhood diseases with commonly used
vaccines gave excellent results and are leading to their virtual eradication
in developed countries. However some vaccines like the one against pertussis
proved to be of considerably lower effectiveness. Results achieved in
developing countries are in general lagging behind due to lower immunization
coverage. While in some countries immunization strategies for eradication of
measles are discussed, in others it is questionable whether immunization
should continue due to failures of immunization programmes.
Evaluation of the effectiveness of
national immunization
programmes by surveillance and
various other methods including the use of epidemiological models point ot
the deficiencies of vaccine potency and/or stability and the inadequacy of
vaccination schemes and
coverages. There is a
need to determine optimal immunization programmes for control and possible
eradication with currently available antigens and new ones. For newly
developed vaccines, ever increasing in number, but with the uncertainty of
their appropriate public health use, it is essential to study their optimal
and most cost-effective uses e.g., pertussis vaccination is an old unsolved
problem and that against hepatitis B a new one. Better results can be obtained
with current vaccines by appropriate modification of immunization programmes.
Some of the proposed strategies for using recently developed vaccines are
questionable and need critical examination.(ABSTRACT TRUNCATED AT 250 WORDS)
Mass vaccination programme aimed at eradicating measles,
mumps, and rubella in Sweden: first experience.
Christenson B, Bottiger M, Heller L.
General vaccination with a combined measles, mumps, and rubella vaccine was
introduced in Sweden in 1982. The immunisation schedule comprises two vaccine
injections, given at 18 months and 12 years of age, respectively. A controlled
field study was carried out in 150 children aged 18 months using two different
batches of the vaccine. Seroconversion was seen in 96% against measles, 93%
against mumps, and 99% against rubella--the same rates with both vaccine lots.
Nevertheless, a difference was noted between the two batches with respect to
postvaccination reactions. Fever and rash were recorded mainly five to 12 days
after vaccination. Moderate fever (38.5-39.4 degrees C) was observed in 22
children, high fever (greater than or equal to 39.5 degrees C) in 33, and rash
in 35. Preliminary results obtained by follow up of routinely vaccinated
schoolchildren aged 12 indicated considerably lower rates of fever and rash
during the postvaccination period, occurring in 3-10% of cases only.
These findings show that complete
eradication of measles, mumps, and rubella in Sweden is entirely practicable
by the mass vaccination
programme and that side effects
of vaccination are likely to be few and mild.
Comparison of the figures for measles morbidity in Mexico over the years is
difficult because of the different rates of reporting of cases. In the 1960s,
approximately 3% of the true number of cases of measles was reported, whereas
in 1980 this percentage increased to approximately 20%. A more representative
time curve can be drawn for mortality, which dropped sharply in 1973-1980 as a
result of the extensive use of measles vaccine. The relationship between
measles and immunization is close, and morbidity for the above period is a
mathematical function of the number of doses of vaccine distributed. During
1981, about four million doses of vaccine were administered, and in 1982
another four million children will be immunized, with a coverage of 70% of the
susceptible population. It is hoped
that in 1982 the incidence of measles will decrease to the low levels obtained
in 1974-1975, although eradication in the near future seems unlikely.
Measles is one of the major public health problems in Tanzania and is
recognized as such by the population. Since 1975 measles vaccination has been
given as part of the national expanded immunization program. On the basis of
the findings of measles surveys and a vaccination trial, the policy of
vaccination at six months of age has been changed to that of vaccination at
nine months of age, and malnourished children are now vaccinated. Vaccination
coverage is unsatisfactory because many villages are too far from health units
and because measles vaccination has low credibility. The epidemiology of
measles appears to be changing as a result of vaccination, and the age of
vaccination may have to be modified in the future. A policy of vaccinating
each child twice is being considered as well as one of vaccinating sick
children who are attending maternal and child health clinics.
At present eradication of measles is
not a realistic target for countries such as Tanzania.
Edmonston-Zagreb strain of measles vaccine: epidemiologic
evaluation in Yugoslavia.
Ikic DM.
According to epidemiologic data in
Yugoslavia, a high level of immunity (95%) must be attained in the susceptible
population between eight months and 30 years of age for the eventual
eradication of measles (to cut off the seasonal peak and to prevent the
epidemiologic wave). Where the vaccination rate produced a lower level of
immunity (e.g., 85% and 67%), the cyclic wave did not disappear completely but
was greatly reduced. Live measles vaccine prepared from a
further-attenuated Edmonston-Zagreb strain was used for vaccination in
Yugoslavia.
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.
Seasonality and the requirements for perpetuation and
eradication of viruses in populations.
Yorke JA, Nathanson N, Pianigiani G, Martin J.
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.
[A few viral infections in the recent epidemiological
evolution (author's transl)]
[Article in Italian]
Squeri L, Ioli A.
In the study we presented a few infections of viral etiology that showed
evident epidemiological evolutions during the last ten years.
We refered
of a disease nearly eradicated, of one that can be eradicated, and of a group
of infections that at present cannot be eradicated. The first is
poliomyelitis, the second is measles, the third is represented by viral
infections connected with the respiratory tract. As for the first
disease, the sistematic immunoprophilaxis applyed in different countries of
the world on one hand stopped the transmission of wild polioviruses and on the
other created an immunological barrier in those countries where polio
vaccination is maintained, as demonstrated by statistics revealing the absence
or low incidence of this disease. As for the epidemiological evolution of
measles, after considering the incidence due to age, environment,
social-hygienic conditions, mortality etc..., we refered in particular of a
vaccination that took place in USA where the disease decreased with 1968 then
rised next year a pause of the vaccination program. A second cycle of
vaccinations against measles revealed in 1972 a decrease of the disease this
signifying the importance of the vaccination in stopping, reducing or
modifying the epidemiology of measles. The epidemiological conditions of
respiratory infections are completely different due to the variety of the
etiological factors, the difficulty in preparing aspecific vaccines, and the
impossibility in recognising clinical forms caused by these viruses. All these
factors, impede, actually, a complete eradication.
The Alaska Department of Health and Social Services has instituted a special
surveillance program to investigate every suspected case of measles and
rubella. Clinical and epidemiologic information is obtained, and serologic
testing is performed to confirm all tentative diagnoses. In 1974, forty-one
cases were investigated, and none were confirmed as measles or rubella. This
record is attributed to high immunization levels and rapid epidemiologic
follow-up of all suspected cases. We believe that this program can be easily
instituted in other states, particularly those with a limited number of
reported cases.
PMID: 946025 [PubMed - indexed for MEDLINE]
Click here:
Measles
- Alaska to find out what happened after this
"eradication" of measles in Alaska. - SM
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MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS
OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
"A foolish faith in authority is the worst enemy of truth."
-- Albert Einstein, letter to a friend, 1901
"I know of no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."
-- Thomas Jefferson, letter to William C. Jarvis, September 28, 1820
"What's the point of vaccination if it doesn't protect you from the unvaccinated?"
-- Sandy Gottstein
"Who gets to decide what the greater good is and how many will be sacrificed to it?"
