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Measles mortality and vaccine efficacy in rural West Africa.

Measles mortality and measles vaccine efficacy were determined during outbreaks in three Gambian villages. There were 146 cases of measles among 1073 children younger than 11 years. 30% of the children had been vaccinated against measles. The attack rate in unvaccinated children aged 9-47 months was 43% compared with 6% for children of the same age with documented measles vaccination. Vaccine efficacy was 37% for children vaccinated at 6-8 months of age and 89% for children vaccinated at 9 months or older. 5% of measles cases died before the initial investigation of the outbreaks and a further 10% of cases died during the ensuing 9 months. Only 1% of children who did not contract measles died in the 9 months after the outbreaks. Case-fatality rates were highest for measles patients less than 1 year old (64%) and fell with age. Measles remains a significant source of acute and delayed mortality in unvaccinated African populations.

Africa, Western↗

A fourteen-year study to identify measles antigen in urine specimens by fluorescent-antibody methods.

Between 1965 and 1979 inclusive, 426 morning urine specimens from 410 patients admitted to hospital with the provisional diagnosis of measles were tested for measles antigen by fluorescent-antibody methods. One hundred and forty-two specimens (33.3 per cent) were positive. Of 74 patients who were clinically assessed not to have measles, 6/77 specimens (7.8 per cent) gave false positive results, and 71/77 (92.2 per cent) gave true negative results. Three hundred and forty-nine urine specimens were tested from 336 patients clinically judged to have had measles and 136 of these specimens (39 per cent) were positive. The positive rate was highest in a small number of specimens taken before the rash and next highest at the onset of the rash. The positive rate then fell; it rose again near the end of the first week, but the further increased positive rate after that time was associated with very small numbers of specimens. Of 12 child contacts of measles, 5/12 (41.67 per cent) had positive urine specimens and one of them developed measles two days after sampling. None of the seven patients with negative urine specimens developed measles. Measles antigen was detected in urine sediment by fluorescent-antibody tests in 39 per cent of the patients with measles studied.

Adolescent↗

Cost-effectiveness of measles elimination in Latin America and the Caribbean: a prospective analysis.

BACKGROUND: In 1994, the Americas set a goal of interrupting indigenous measles transmission from the Western Hemisphere by 2000. To accomplish this goal, the Pan American Health Organization (PAHO) developed an enhanced measles vaccination strategy. METHODS: Cost data was collected at PAHO for Latin American and Caribbean (LAC) countries covering 96% of the region's population on components of the routine programs, and the 'follow-up' activities from member countries. In order to interpret our findings we have compared the present scenario regarding measles with one that would have ensued if past trends continued. RESULTS: For the entire LAC population, estimated cost of elimination program will be US$ 571 million in present value terms. INTERPRETATION: The vaccination strategy toward achieving elimination of measles costs USD 244 million, incremental from the cost of vaccination before the elimination program. Within 2000-2020, the current program will have prevented the occurrence of 3.2 million cases of measles and 16,000 deaths. Thus, vaccination strategy prevents a single case of measles at the cost of USD 71.75 and prevents a death due to measles at the cost of USD 15,000. The case fatality rate depends on a well functioning treatment program for measles cases. The vaccination strategy saves a total of USD 208 million in treatments costs due to reduced incidence of measles.

Adolescent↗

Modelling measles re-emergence as a result of waning of immunity in vaccinated populations.

An age-structured mathematical model of measles transmission in a vaccinated population is used to simulate the shift from a population whose immunity is derived from natural infection to a population whose immunity is vaccine-induced. The model incorporates waning of immunity in a population of vaccinees that eventually will become susceptible to a milder form of vaccine-modified measles with a lower transmission potential than unvaccinated classical measles. Using current estimates of duration of vaccine-derived protection, measles would not be expected to re-emerge quickly in countries with sustained high routine vaccine coverage. However, re-emergence is possible to occur several decades after introduction of high levels of vaccination. Time until re-emergence depends primarily on the contagiousness of vaccine-modified measles cases in comparison to classical measles. Interestingly, in a population with a high proportion of vaccinees, vaccine-modified measles and classical measles would occur essentially in the same age groups. Although waning of humoral immunity in vaccinees is widely observed, re-emergence of measles in highly vaccinated populations depends on parameters for which better estimates are needed.

Adolescent↗

Secondary measles vaccine failures identified by measurement of IgG avidity: high occurrence among teenagers vaccinated at a young age.

Failure to seroconvert (primary vaccine failure) is believed to be the principal reason (approx. > 95%) why some vaccinees remain susceptible to measles and is often attributed to the persistence of maternal antibodies in children vaccinated at a young age. Avidity testing is able to separate primary from secondary vaccine failures (waning and/or incomplete immunity), but has not been utilized in measles epidemiology. Low-avidity (LA) and high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years, range 2-22 years) from an outbreak in 1988-9 in Finland were tested for measles-virus IgG avidity using a protein denaturating EIA. Severity of measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2 years, range 2-22 years). The patients with HA antibodies (n = 28) tended to have clinically mild measles and rapid IgG response. Among failures vaccinated at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA antibodies, respectively. When a single measles, mumps and rubella (MMR) vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14) showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15 months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of HA responses compared to MMR recipients. Apart from one municipality, where even re-vaccinees had high risk of primary infection, 89% (CI 69 to approximately 100) of the infected re-vaccinees had an HA response. Secondary measles-vaccine failures are more common than was more previously thought, particularly among individuals vaccinated in early life, long ago, and among re-vaccinees. Waning immunity even among individuals vaccinated after 15 months of age, without the boosting effect of natural infections should be considered a relevant possibility in future planning of vaccination against measles.

Adolescent↗

Measles virus infection in the placenta of monozygotic twins.

We report a case of monozygotic twins whose mother was infected with measles at 19 weeks' gestation. One of the twins died in utero at 32 weeks' gestation. The placenta of the stillbirth showed massive fibrin deposition, and some residual trophoblasts contained many inclusion bodies positive for measles virus antigen. Fetal organs and cells other than a few splenic lymphocytes showed no evidence of measles virus infection. The placenta of the surviving infant showed focal intervillous fibrin deposits, and only a few syncytiotrophoblasts were positive for measles virus antigen. At present, 7 months after the delivery, the surviving infant has not developed any sign of measles virus infection. Postpartum course of the mother has been uneventful, although high titers of serum anti-measles virus IgM persisted for 6 months after delivery. This case is informative in the following respects: the villous trophoblasts had diagnostic inclusion bodies and ultrastructural evidence of measles virus infection, the degree of viral involvement within the monochorionic placenta was uneven, both of the twins were virtually free from measles virus infection despite the marked involvement of the placenta, and measles virus infection had persisted in the monochorionic placenta for approximately 13 weeks.

Adult↗

Vaccine-modified measles in previously immunized children in Accra, Ghana: clinical, virological and serological parameters.

Despite rapidly increasing measles immunization coverage, epidemics of measles occurred from January to March 2000 in some parts of Accra, the capital of Ghana. 44 cases of acute measles were diagnosed at three health facilities during the outbreaks, which we examined clinically and serologically. The peak incidence occurred among 6-12-year-olds, clinical symptoms were milder than the typical symptoms of measles, and fever was significantly less common. None of the cases developed complications and all recovered completely. Thirty-eight (86.4%) were tested serologically; IgM antibodies were detected in 73.7% and IgG antibodies in 84.2% during the acute phase. Milder symptoms in a significant number of cases with measles IgG antibodies suggest that these are vaccine-modified measles, attributable to waning antibodies and low circulation of wild type virus in an area of high vaccine coverage. Serological confirmation will be required for accurate diagnosis, if measles is to be eradicated or kept under control. It also seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody levels and to protect children against measles in Ghana. This will eliminate the frequent outbreaks of measles involving immunized children.

Child↗

Prolonged measles virus shedding in human immunodeficiency virus-infected children, detected by reverse transcriptase-polymerase chain reaction.

A reverse transcriptase-polymerase chain reaction assay was used to detect measles virus RNA in peripheral blood mononuclear cells, urine, and nasopharyngeal specimens from Zambian children during hospitalization and approximately 1-2 months after discharge. Of 47 children, 29 (61.7%) had prolonged measles virus shedding, as defined by detection of measles virus RNA in > or =1 specimen obtained 30-61 days after rash onset. Ten (90.9%) of 11 human immunodeficiency virus (HIV)-infected children had prolonged measles virus shedding, compared with 19 (52.8%) of 36 HIV-uninfected children (P=.02). Prolonged measles virus shedding did not correlate with levels of measles virus-specific antibody. HIV-infected children with measles may have a prolonged infectious period that potentially enhances measles virus transmission and hinders measles control.

Adolescent↗

Evaluation of urban measles mass campaigns for children aged 9-59 months in Mali.

There are an estimated 234,000 cases of measles and 13,851 measles-related deaths per year in Mali. In 1998 and 1999, 548,309 children aged 9-59 months were vaccinated against measles during mass campaigns in urban centers across Mali. After the first campaign, measles incidence decreased by 95% in districts encompassing vaccinated urban centers and by 41% in nonvaccinated districts. There was no shift in the proportion of cases by age group in vaccinated centers. Measles in vaccinated districts after the campaign was likely related to persistent transmission in age groups not targeted for vaccination and among children living in nonvaccinated districts. The second campaign (1999) did not change the incidence of measles in vaccinated compared with nonvaccinated centers. Urban mass measles vaccination probably did not affect overall measles transmission in Mali. Mass vaccination of all children in Mali, targeting a larger age group, will be necessary to reach measles control objectives.

Antibodies, Viral↗

Progress in accelerated measles control in the People's Republic of China, 1991-2000.

Measles incidence decreased dramatically following widespread use of measles vaccine in China in 1965. To evaluate continued progress in accelerated measles control, data on measles cases reported to the National Notifiable Disease Reporting System during 1991 to 2000 were analyzed. From 1991-1995 to 1996-2000, average annual measles incidence decreased from 9.0 to 5.7 cases per 100,000 population, mortality rates fell from <0.3 to 0.1 deaths per million population, and the percentage of China's total population residing in provinces with a measles incidence of <2 cases per 100,000 population and having a measles elimination goal increased from 21% to 29%. Incidence rates were highest in western provinces and in infants and young children. Additional attention must be focused on western provinces and toward ensuring that all infants are immunized. Achieving high routine two-dose coverage with measles vaccine and enforcing school entry requirements may be highly effective strategies to support further gains in measles control.

Child↗

Progress toward interruption of endemic measles transmission in Tunisia.

Measles was the second leading cause of infant mortality in Tunisia prior to introduction of measles vaccination in 1979. The number of reported measles cases has decreased from 3007 in 1981 to 47 cases in 2000 due in part to the high coverage rates achieved after 1992. During 1998, a measles catch-up campaign vaccinated 1,846,657 children (95%) aged 6-16 years, and a follow-up campaign for children aged 9 months to 5 years in 2001 reached 547,766 (94%). During 1999-2001, 1717 cases of rash and fever illness were tested for measles; only 3 (0.2%) were positive for measles. From February to July 2002, an outbreak of measles involving 87 cases occurred in Tunisia in a health care setting and 56 (64%) patients were aged 15-30 years. The low number of laboratory-confirmed measles cases during 1999-2001 suggests endemic measles transmission may have been interrupted.

Adolescent↗

The unfinished measles immunization agenda.

Despite achieving and sustaining global measles vaccination coverage of about 80% over the past decade, worldwide measles remains the fifth leading cause of mortality among children aged <5 years. In May 2002, the United Nations Special Session on Children endorsed the goal of reducing measles deaths by half by 2005. Countries and World Health Organization (WHO) regions that adopted aggressive measles control or elimination strategies have shown excellent results. In 2001, countries in the Americas reported an all time low of 537 confirmed measles cases. Substantial progress in measles control has also been achieved in the WHO Western Pacific Region, in seven southern African countries, and in selected countries in WHO European, Eastern Mediterranean, and Southeast Asian regions. The ongoing measles disease burden and availability of safe and effective measles mortality reduction strategies make a compelling case to complete the unfinished agenda of measles immunization.

Child↗

Experience in global measles control, 1990-2001.

Worldwide during the 1980s remarkable progress was made in controlling measles through increasing routine measles vaccination to nearly 80%. In 2000, an estimated 777,000 measles deaths occurred, of which 452,000 were in the African Region of the World Health Organization (WHO). In 2001, WHO and the United Nations Children's Fund published a 5-year strategic plan to reduce measles mortality by half by 2005. Strategies include providing a second opportunity for measles immunization to all children through nationwide supplementary immunization activities, increasing routine vaccination coverage, and improving surveillance with laboratory confirmation of suspected measles cases. In 2000, over 100 million children received a dose of measles vaccine through supplementary immunization activities, a number projected to increase during 2002-2005. Current systems for monitoring measles vaccination coverage and disease burden must be improved to accurately assess progress toward measles control goals.

Child↗

Measles transmission and vaccine effectiveness during a large outbreak on a densely populated island: implications for vaccination policy.

BACKGROUND: The Republic of the Marshall Islands (RMI) is a South Pacific nation freely associated with the United States. In 2003, the RMI experienced the largest measles outbreak within the United States or its associated areas for more than a decade, although the reported coverage of 1-dose measles-mumps-rubella (MMR) vaccine was 80%-93%. The outbreak ended only after vaccination of >35,000 persons among a population of 51,000. Of outbreak cases, 41% were reported to have been previously vaccinated. We studied measles attack rates in RMI households to assess vaccine effectiveness and patterns of disease transmission. METHODS: For the household secondary attack rate study, households were selected by convenience sampling of outbreak measles cases. The primary case was defined as the first person with measles in a household. Secondary cases were household members with measles onset 7-18 days after the primary case's rash onset. Vaccine effectiveness analysis was limited to children aged 6 months to 14 years, with vaccination status verified against written records. RESULTS: Seventy-two households were included in the study. The median household size was 11 persons, and the median number of persons per room was 5.5. Secondary cases were more likely than primary cases to be infants (46% vs. 13%; P=.03). MMR vaccine effectiveness was 92% (95% confidence interval [CI], 67%-98%) for 1 dose and 95% (95% CI, 82%-98%) for 2 doses. CONCLUSIONS: Measles vaccine effectiveness was high; thus, diminished effectiveness was not the main cause of the outbreak. In communities with high population density and household crowding, very high population immunity is needed to prevent measles outbreaks and to protect infants below the age of vaccination. This may require excellent implementation of a routine 2-dose measles vaccination strategy.

Adolescent↗

No long-term excess mortality after measles infection: a community study from Senegal.

Because measles immunization has been found in all studies to reduce mortality with more than the share of deaths attributed to acute measles, the authors examined mortality after measles infection in a study in a rural area of Senegal that included 6,924 unimmunized children, whom 1,118 developed measles. Age-adjusted post-measles mortality was similar to the mortality of unvaccinated, uninfected children (mortality ratio (MR) = 1.04, 95% confidence interval (CI) 0.80-1.35). When controlling for source of infection, mortality rate was significantly different for children who contracted measles from a person outside the home (index cases vs. unvaccinated, uninfected MR = 0.27, 95% CI 0.09-0.85) and for children infected at home (secondary cases vs. unvaccinated, uninfected MR = 1.10, 95% CI 0.80-1.51). Hence, secondary cases had markedly higher long-term mortality than did index cases (MR = 4.13, 95% CI 1.26-13.58). These estimates were essentially unchanged when the effects of season, period, separation from mother, size of community, and size of compound were investigated using a multivariate Cox regression model. The authors conclude that measles infection was not associated with increased mortality after the acute phase of infection and that index cases had lower mortality than uninfected, unvaccinated children. The reduction in mortality after measles immunization can therefore not be explained by the prevention of post-measles mortality.

Age Factors↗

Evaluation of a measles-smallpox vaccination campaign by a sero-epidemiologic method.

An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign.

Age Factors↗

Measles immunization: early two-doses policy experience.

Before the implementation of the two-dose measles immunization policy in Saudi Arabia, 50 per cent of measles cases in children below the age of one year were reported for the age group 6-8 months. In 1991 two doses of measles vaccine, at 6 months and 12 months, the second dose incorporated with MMR, were integrated into the expanded programme of immunization (EPI). Since 1993, vaccination coverage for the second dose has been above 90 per cent. While measles incidence remains stable in infants below 6 months of age, the incidence in children 9-11 months of age dropped by 50 per cent. The greatest impact was seen in the 6-8-month age group where the incidence dropped by more than 75 per cent. Moreover this two-dose strategy resulted in a situation in which 80 per cent of the measles cases were in children above the age of 5 years, mostly those who had not had two doses of measles vaccine. Further control measures should include non-selective vaccination of school children against measles. The two-dose measles vaccination policy is visualized as a necessity if the goal of measles elimination is to be achieved. Routine monthly reports validated by surveys using the WHO standard 30 cluster technique was used for the study.

Adolescent↗

Cutaneous manifestations of measles in AIDS.

In immunocompetent patients, infection by the measles (rubeola) paramyxovirus produces fever, cough, coryza, Koplik's spots, and, on the skin, a macular erythema that can become confluent. The erythema has a striking cephalocaudal spread and clearing. The diagnosis of measles on a skin biopsy and the distinction from an erythema multiforme type of drug eruption can be difficult. We studied a skin biopsy from a patient with the acquired immunodeficiency syndrome (AIDS) who presented with measles. In contrast to erythema multiforme, the measles biopsy has necrosis of clusters of keratinocytes in the high spinous layer and granular layer of the epidermis, whereas erythema multiforme has necrosis of basal keratinocytes. Multinucleated keratinocytes may or may not be prominent in the measles biopsy. Cytoplasmic swelling of the keratinocytes in the granular layer may be present even when multinucleated cells are sparse. Immunoperoxidase reactivity for measles virus protein is present in intranuclear inclusions and in the cytoplasm of infected upper spinous keratinocytes. There were more cells with positive staining in the biopsy from the AIDS patient than in another biopsy from an immunocompetent patient with measles. The AIDS patient was seronegative for measles throughout the course of the illness. The examination of the skin biopsy can be very important in the diagnosis of measles in AIDS patients or immunocompromised patients who may not develop the usual diagnostic serology.

AIDS-Related Opportunistic Infections↗