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Altered reactivity to measles virus in previously vaccinated children.

In children vaccinated with killed measles vaccine, exposure to natural rubeola within two to four years can result in a clinical syndrome of altered measles reactivity.During a small epidemic of measles in Edmonton, Alberta, 51 children who had received their last killed measles vaccination 27 to 45 months before, were admitted to hospital with this syndrome.The syndrome consists of a prodromal cough and high fever followed by a maculopapular rash appearing on the extremities and progressing centrally. Pulmonary consolidations with or without pleural effusions were evident, but these cleared rapidly in four or five days. Initial WBC and ESR values suggested a bacterial etiology, but no pathogens could be isolated.Complement fixation titres for rubeola are present in acute and convalescent sera and indicate a definite measles infection.Previous killed measles vaccination excites a delayed hypersensitivity which is activated by the natural measles infection to account for this syndrome.It is recommended that killed measles vaccine be no longer used in routine vaccinations.

Child↗

Replication-incompetent adenoviruses as vectors for protective immunization against measles virus infection.

Despite the availability of an efficient live-attenuated measles virus vaccine about 1.5 million annual deaths from measles infections and their complications are recorded worldwide. Particularly in developing countries measles remains an unsolved problem and a new vaccine seems necessary. In our animal model of measles virus infection in rats we studied a candidate vaccine based on infectious replication incompetent (E1A-) adenovirus (RAd) where measles virus genes are expressed under the control of the cytomegalovirus immediate early promoter. The aim of the study was to characterize the cell mediated and humoral immunity after immunization with RAd and its protective effect. After challenge with a lethal dose of measles virus no signs of disease or histopathological changes were detected in RAd68-immunized rats. The elimination of measles virus was successful within a few days. The results demonstrate that defective recombinant adenovirus vectors can induce complete protection from experimental measles infection in rats.

Adenoviridae↗

Measles in infants: a review of studies on incidence, vaccine efficacy and mortality in east Africa.

Control of measles in developing countries is complicated by high incidence and mortality among infants. Hospital-based and community-based studies from East Africa were reviewed with respect to the reported incidence and mortality of measles and vaccine efficacy/seroconversion rates after the administration of measles vaccine to infants. The studies reviewed confirm that measles is particularly severe in infants, and some indicate that vaccination before 9 months with standard vaccine could be effective and have beneficial effects for children aged 6-9 months, while other studies refute this finding. Due to the high incidence and mortality of measles in infants, alternative control strategies are essential to reduce measles mortality. Further studies are needed on the effects of a two-dose schedule vaccinating at 6 and 9 months, which in mathematical modelling shows considerable benefit. Improved management of measles cases, including the administration of vitamin A could be considered as a complementary strategy for reducing measles mortality, especially in infants.

Age Distribution↗

IgG & IgM antibodies against measles virus in unvaccinated infants from Pune: evidence for subclinical infections.

IgG and IgM class of antibodies to measles virus were estimated in the plasma samples of 211 unvaccinated infants living under overcrowded conditions in Pune, Maharashtra. IgG antibodies to measles virus, in high titres, were detected in 52.1 per cent and IgM antibodies in 31.3 per cent of the infants studied. Most of the infants with IgM antibodies to measles virus had not suffered from an attack of measles. A history of contact with an older child with overt measles was available for 13.3 per cent of the 211 infants studied. Among these infants with such a contact history, 82.1 per cent had IgM antibodies to measles virus. These observations suggest that many infants studied by us, had experienced subclinical measles infections and many times older children with measles at home or in the neighbourhood might have transmitted such infections.

Antibodies, Viral↗

Measles immunity in Israeli young adults: effects of second immunization at 18 years of age.

Measles morbidity and mortality in Israel have declined since the introduction of routine vaccination, even though measles continues to occur in epidemic cycles. In this study we examined the antibody response to measles revaccination, and the effect of prior administration of immune serum globulin (ISG) on the antibody response to measles vaccine. A study group of 312 young adults in army service received the Schwartz strain measles vaccine. Serum antibody levels were studied prior to vaccination and 2 and 4 weeks after vaccination. The finding of this study show that: a) booster response occurs in those vaccinees shown to have low or undetectable prerevaccination titers of measles antibodies; b) there is no effect of administration of ISG, prior to vaccination, on the antibody response to measles vaccine; and c) at the present level of immunity to measles in the Israeli adolescent population, we still may witness periodic epidemics in populations at risk.

Adolescent↗

An evaluation of measles revaccination among school-entry-aged children.

BACKGROUND: A two dose measles vaccination schedule is recommended routinely for all school-entry-aged children. We evaluated this recommendation by determining both measles antibody seroprevalence and the response to revaccination in seronegative children in this age group. METHODS: Children 4 to 6 years of age who had received a single dose of measles vaccine between the ages of 15 to 17 months were tested for measles antibody by using enzyme-linked immunosorbent assay (ELISA) microneutralization technique. Seronegative children were revaccinated and again tested for measles antibody (immunoglobulin M [IgM] and neutralizing). RESULTS: Of 679 children tested, 37 (5.4%) were seronegative. Seronegativity was not significantly associated with age, sex, race, age at initial vaccination, time since vaccination, or maternal year of birth. However, children mothers with a college degree were 12 times more likely to be seronegative than children of mothers who never attended college (P < .01). Of the 37 seronegative children, 36 seroconverted after revaccination--33 producing IgM measles antibody, suggestive of a primary immune response. The cost per seroconversion would have been an estimated $415 if all 679 children had been revaccinated. CONCLUSIONS: Revaccination reduces the pool of children who are susceptible to measles. Although the cost per seroconversion is high, a two-dose schedule should reduce the substantial costs of controlling measles out breaks by reducing the number of outbreaks.

Antibodies, Viral↗

The influence of the HLA-DRB1*13 allele on measles vaccine response.

BACKGROUND: Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. METHODS: We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. RESULTS: The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different (p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%;p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). CONCLUSIONS: The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.

Alleles↗

Measles antibody response in vaccinated children.

The incidence of measles has declined in our country since the routine administration of measles vaccination was initiated. However, measles outbreaks have been observed even among previously vaccinated children. The objective of this study was to evaluated the measles antibody response of children vaccinated at nine months of age. Measles-specific IgG antibodies were determined by enzyme-linked immunosorbent assay. Of 345 children tested, 20.3 percent were immunologically measles-susceptible. When measles-specific antibody titers were analyzed with respect to the elapsed time since prior vaccination, the result was found to be insignificant (p > 0.05). These data suggest that the underestimated seropositivity rate of measles antibody may be related to both primary vaccine failure and inappropriate vaccination age.

Antibodies, Viral↗

[Clinical and serologic diagnosis of measles in children vaccinated against the disease].

At the period of mass immunization of children with live measles vaccine clinical symptoms of measles, their intensity and sequence apparently displayed some changes; therefore, serological diagnosis is more reliable in comparison with the clinical one. Result of serological study of 93 coupled blood sera of children who fell sick with the diagnosis of measles showed that only 54.3% of those vaccinated earlier and 49.2% of nonvaccinated children sustained measles, whereas the rest had had exanthematous disease of other etiology. All the children had fever (the majority not over 38.5 degrees C) and rash; other clinical signs of measles were of different intensity in the vaccinated and nonvaccinated children. Apparently such pathognomonic signs of measles as rash, Filatov's sports and conjunctivitis could not serve at present as a reliable criterion of clinical measles diagnosis. The majority of children vaccinated before who contracted the disease responded to the infection by an earlier and more intensive production of antibodies than nonvaccinated children who contracted the disease, this pointing to the possibility of manifestation in them of the clinically expressed booster-effect. The data obtained indicated a marked difficulty of clinical differential diagnosis of measles.

Adolescent↗

A measles epidemic controlled by immunisation.

AIM: In 1997, an immunisation campaign, using measles-mumps-rubella vaccine, was planned for children aged 2-10 years to prevent a measles epidemic predicted by mathematical modelling. The epidemic started before the campaign and is described here. METHOD: Measles hospitalisation, notification and laboratory data were combined. RESULTS: The epidemic started in April 1997 and was largely over by January 1998. No deaths were identified and only one hospitalisation was coded as measles encephalitis, compared to seven deaths and ten cases of measles encephalitis in the 1991 epidemic. For the 12 months from 1 March 1997 there were 2,169 (60 per 100,000) measles cases identified, 314 (9 per 100,000) of whom were hospitalised. Two-thirds of hospitalised cases were notified. The age-standardised measles incidence rates were 33, 34, and 174 per 100,000 for Europeans, Maori and Pacific people, respectively. The respective age-standardised hospitalisation rates were 4, 9 and 32 per 100,000. Measles incidence was highest for under one-year-olds (904 per 100,000) and low for 11-16 year-olds (27 per 100,000)--the cohort previously offered a second vaccine dose. Most cases were aged 10 years and under, and this group were the main drivers of virus transmission. CONCLUSIONS: The immunisation campaign prevented 90-95% of predicted cases. The campaign was appropriately targeted at children aged 10 years and under.

Adult↗

Present anti-measles immunity in Jordan.

The immunity of adults and the prevalence of measles was determined in order to evaluate the adequacy of current measles vaccination policy in Jordan. A total of 307 sera, collected from adults aged 18--40 years, were tested for anti-measles antibodies by ELISA technique. The overall prevalence of anti-measles antibodies was 94.8% and there was no significant difference in the seropositivity rate between males (95.7%) and females (94%). Of the tested adults, 71% were vaccinated and 29% escaped vaccination. In Jordan, measles outbreaks occur periodically and predominantly attack children aged 5--14 years. Our data support introducing the compulsory MMR vaccine in the year 2000 to improve the vaccination coverage of measles; since the optional single dose vaccination has not interrupted the circulation of the measles virus. A second dose of MMR vaccine could be offered to Jordanians either at school entry or at the age of 11--12 years, based on the outcome of the compulsory single dose of MMR vaccine.

Adolescent↗

Predicting the impact of measles vaccination in England and Wales: model validation and analysis of policy options.

Measles incidence in England and Wales has fallen to an all-time low. Attention is now focused on preventing local outbreaks, and, in the long run, on the elimination of indigenous measles. A realistic age-structured (RAS) mathematical model of measles transmission is used to reconstruct the impact of measles vaccination in England and Wales from 1968 to the present and to evaluate the merits of future policy options. In general, the predictions of the model show good agreement with long-term age stratified case reports and seroprevalence surveys. The model underestimates the proportion of cases that are notified in 0-2-year-old children. However, recent work suggests a high degree of misdiagnosis in this age group. Projections on the basis of the existing vaccination strategy in the UK suggest that the present level of measles vaccine coverage will be insufficient to eliminate small seasonal outbreaks of measles. This result is, however, sensitive to the assumed level of vaccine efficacy. Explorations of a variety of changes to current vaccination strategy favour a 2-dose schedule with the second dose administered at age 4 years irrespective of vaccination history. A vaccination campaign in school-age children, to reduce deficits in herd immunity, would accelerate progress towards measles elimination.

Adolescent↗

Measles.

PURPOSE OF REVIEW: The purpose of this review is to summarize important papers concerning measles disease and measles-containing vaccines published in 2004. RECENT FINDINGS: Endemic measles has been successfully controlled in the Americas and, to a lesser extent, in Europe. This has been achieved with a high uptake of two doses of a measles-containing vaccine. Even in industrialized countries, where vaccine uptake is poor, for example Japan, the disease is still a significant cause of morbidity and mortality. Vaccine failure is predominantly due to primary vaccine failure, which may, in part, be genetic in origin and related to HLA type. Measles-containing vaccines have been shown to be associated with febrile convulsions, but there is no strong evidence of a link with atopy. There is considerable evidence that there is no causal relationship with autistic disorders. In spite of this, many parents and some professionals have concerns about the safety of the vaccines, which may lead to their underuse. SUMMARY: It is possible to eliminate measles with a high uptake of two doses of measles-containing vaccine, but concerns about safety persist and need to be tackled. More research is required into how to do this effectively and also to elucidate the causes of vaccine failure.

Child, Preschool↗

Abnormalities of measles antibody response in human immunodeficiency virus type 1 (HIV-1) infection.

The finding that severe measles occurs in immunized as well as nonimmunized human immunodeficiency virus (HIV)-infected individuals suggests that both immunologic memory and the initial response to measles may be impaired by HIV infection. That the initial response is affected was supported by the finding that post-measles immunization titers of HIV-infected babies were significantly lower (p = 0.01) than those of normal babies. Poor immunologic memory was evidenced in HIV-infected children by lower titers than in normal children (p < 0.001) and by a continuing decline in measles antibody that was not arrested by reimmunization. Impaired memory appeared to be associated with defective avidity maturation. HIV-infected babies and infants or children had a significantly lower avidity index (AI) than age-matched normal children (p < 0.01). HIV-infected adults, who were infected with HIV following infection with measles, did not have AI values significantly different from normal adults (p = 0.18) but had significantly greater values than did HIV-infected babies and children (p < 0.01). Thus, in contrast to infants and children who were infected with HIV before measles immunization, the adult immune response to measles was less affected.

Adult↗

Clinical outcome in children hospitalized with complicated measles.

OBJECTIVE: To determine the association of clinical outcome of measles in children with demographic profile and complications. DESIGN: A cross-sectional analytical study. PLACE AND DURATION OF STUDY: Isolation ward, The Children's Hospital, Pakistan Institute of Medical Sciences (PIMS), from January 2003 to August 2004. PATIENTS AND METHODS: Detailed history and physical examination of all the hospitalized patients with complications of measles was filled in case report form. Immunization cards were assessed for measles vaccination status. Data was analyzed by using SPSS version 10 software. The clinical outcome of measles was compared with demographic profile and complications by using Chi-square test and p-values were obtained. RESULTS: Two hundred and five hospitalized patients with complications of measles were studied. There were 61.5% males. Mean age was 46.1 months and 57% patients were vaccinated against measles. Malnourished patients were 71.2% and had a longer hospital stay (p=0.010). Pneumonia (40.0%) and diarrhoea (38.5%) were the commonest complications. Seven children died. Mortality was significantly associated with younger age (p=0.04), unvaccinated status (p=0.04) and presence of encephalitis (p=0.00001). CONCLUSION: The most common complications of measles are pneumonia and diarrhoea with dehydration requiring hospitalization. Malnourished children experience more complications and have longer hospital stay. Mortality is significantly associated with infancy, unvaccinated status and encephalitis. A second dose of measles should be introduced at 15 months of age.

Child↗

Individual and community risks of measles and pertussis associated with personal exemptions to immunization.

CONTEXT: The risk of vaccine-preventable diseases among children who have philosophical and religious exemptions from immunization has been understudied. OBJECTIVES: To evaluate whether personal exemption from immunization is associated with risk of measles and pertussis at individual and community levels. DESIGN, SETTING, AND PARTICIPANTS: Population-based, retrospective cohort study using data collected on standardized forms regarding all reported measles and pertussis cases among children aged 3 to 18 years in Colorado during 1987-1998. MAIN OUTCOME MEASURES: Relative risk of measles and pertussis among exemptors and vaccinated children; association between incidence rates among vaccinated children and frequency of exemptors in Colorado counties; association between school outbreaks and frequency of exemptors in schools; and risk associated with exposure to an exemptor in measles outbreaks. RESULTS: Exemptors were 22.2 times (95% confidence interval [CI], 15.9-31.1) more likely to acquire measles and 5.9 times (95% CI, 4.2-8.2) more likely to acquire pertussis than vaccinated children. After adjusting for confounders, the frequency of exemptors in a county was associated with the incidence rate of measles (relative risk [RR], 1.6; 95% CI, 1.0-2.4) and pertussis (RR, 1.9; 95% CI, 1.7-2.1) in vaccinated children. Schools with pertussis outbreaks had more exemptors (mean, 4.3% of students) than schools without outbreaks (1. 5% of students; P =.001). At least 11% of vaccinated children in measles outbreaks acquired infection through contact with an exemptor. CONCLUSIONS: The risk of measles and pertussis is elevated in personal exemptors. Public health personnel should recognize the potential effect of exemptors in outbreaks in their communities, and parents should be made aware of the risks involved in not vaccinating their children.

Adolescent↗

Measles virus nucleic acid sequences in human brain.

We constructed a measles virus genomic recombinant DNA library, and used clones coding for portions of the viral P, M and H proteins to probe for measles virus nucleic acid sequences in post-mortem multiple sclerosis, SSPE and control brains. By dot blot hybridization, the probes detected measles virus nucleic acid sequences in as little as 3 nanograms of total RNA extracted from measles virus-infected cells and also in highly diluted RNA extracted from SSPE brain, but did not detect measles virus sequences in RNA extracted from 11 multiple sclerosis or 8 control brains, even at a 1 000-fold higher concentration of RNA. By in situ hybridization, these probes detected measles virus nucleic acid sequences in virtually every cell and the surrounding neuropile of SSPE brain, but again did not detect such sequences in multiple sclerosis or control brains. Our findings using these highly specific probes confirm that measles virus is found in SSPE brains and indicate that measles virus genome is unlikely to be present in multiple sclerosis or normal brains.

Base Sequence↗

Metabolic effects of acute measles in chronically malnourished Nigerian children.

We hypothesized that acute measles infection imposes severe metabolic demands on malnourished children. Nigerian rural communities, characterized by severe poverty and extensive malnutrition, served as site for this study. Sixty-five children (mean [+/-SD] age 2.67 +/- 1.96 years) with measles and a randomly selected equal number of children (age 2.83 +/- 1.23 years) from the same communities but measles-free were studied. Both groups were serologically negative for human immunodeficiency virus. The percentages of nonmeasles group who were underweight and wasted as exemplified by weight for age (WAZ) and weight for height (WHZ) scores less than -2.0 SD were 43% and 23%, respectively. Comparative values for the measles group (66% and 54% respectively) were significantly (P < 0.01 or 0.001) different. Compared to the controls, measles-infected children had significantly (P < 0.001) higher plasma cortisol level, marked hyporetinemia (plasma retinol 0.62 +/- 0.24 micromol/L) and prominent reduction (P < 0.002) in the sum of serum essential amino acids. Measles promoted a TH(1) to TH(2) cytokine shift, with severe depletion of plasma interleukin (IL)-12, a key cytokine in the development of cell mediated immunity. IL-6, a key stimulator of hepatic acute phase protein response, was prominently (P < 0.002) increased in plasma in measles-infected children. Glucocorticoids exert effects on cytokine expression, as well as on cytokine receptor expression and cytokine-regulated biological responses. They enhance synergistically, the effects of IL-1 and IL-6 type cytokines on many acute phase proteins. Because of the prominent increase in circulating level of cortisol in acute measles, glucocorticoid treatment for associated sepsis may pose serious problems. Additionally, glucocorticoids antagonize several effects of retinoids at cellular and transcriptional levels, thus suggesting that hypercortisolemia may increase the requirement for retinoids.

Amino Acids, Essential↗