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At least 19 recordsLinked to original sources
PubMed1995

Assumptions and contradictions in measles and measles immunization research: is measles good for something?

Measles infection, the major cause of childhood mortality among infections preventable by immunization, has been considered to kill mainly young and malnourished children. Assuming that mainly 'weak' children are saved by immunizations, it has been speculated that the impact on survival of immunization is likely to be limited because the malnourished children are more prone to die of other infections. However, recent studies from developing countries have suggested that host factors may not be the most important determinants of acute and long-term mortality after measles infection. Instead, it was found that infection contracted after exposure at home infection contracted from someone outside the home. Furthermore, measles is particularly severe if contracted from someone of the opposite sex. Hence transmission factors, in particularly intensity of exposure and cross-sex transmission, may be more important determinants of measles mortality than the determinants of measles mortality than the host factors usually emphasized. Consistent with these observations and in contrast to assumptions about 'weak' children dying, immunization is associated with a major reduction in mortality. Since measles immunization is associated with a 30% reduction in mortality or more, the impact is much larger than should be expected from the proportion of all deaths attributed to measles. It has therefore been suggested that measles immunization may prevent the persistent immunosuppression and delayed mortality assumed to be associated with measles. However, several observations contradict the common understanding that the function of measles immunization is only to prevent the acute and long-term mortality associated with measles infection. Recently, the high-titre measles immunization recommended by WHO was found to be associated with reduced survival for female recipients compared with girls who have received the standard low-dose measles vaccine, and this difference in survival was not due to suboptimal protection against measles infection. Contrary to usual assumptions. against measles infection. Contrary to usual assumptions, standard low-dose measles vaccine reduces mortality even more when given before 9 months of age, the age currently recommended by WHO. The beneficial impact of standard vaccine is apparently temporary, lasting 1 to 2 years, whereas it should increase with the age of the child. The beneficial effect seems to be particularly strong for girls. The most likely interpretation of these observations, is that standard low-dose measles vaccine has a non-specific beneficial effect. Contrary to current assumptions, children who survive the acute phase of measles infection may have a survival advantage compared with unimmunized, uninfected children.(ABSTRACT TRUNCATED AT 400 WORDS)

Cause of Death↗
PubMed2000

Antibiotics for preventing pneumonia in children with measles.

BACKGROUND: Measles causes more than a million deaths a year, of which most are children under five years of age who die from pneumonia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics given to children with measles on reducing pneumonia or mortality, and to assess whether antibiotics should be given to all children with measles in communities with a high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE (1980-1999) and the specialized trials register of the Acute Respiratory Infections Group in August 1999, and all relevant journals in the University of Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised or controlled trials of antibiotics for children with measles. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Six trials with 1304 children were included. All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls. REVIEWER'S CONCLUSIONS: The quality of the trials reviewed was poor, and they provide very weak evidence for giving antibiotics to all children with measles. Available evidence suggests that antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Anti-Bacterial Agents↗
PubMed2001

Immune responses to measles and measles vaccine: challenges for measles control.

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.

Animals↗
PubMed1992

Performance and reliability of the Enzygnost measles enzyme-linked immuno-sorbent assay for detection of measles virus-specific immunoglobulin M antibody during a large measles epidemic.

Evaluation of the Enzygnost Measles Enzyme-Linked Immuno-Sorbent Assay kit (Behring) performance to detect specific immunoglobulin M (IgM) was carried out with 3,297 single serum samples and 898 paired serum samples collected during a measles epidemic (10,184 reported cases) in Quebec, Canada. Anti-measles IgM and IgG were detected by using the Enzygnost kit with the appropriate conjugates. Complement-fixing (CF) antibody (Ab) titers were assessed by the laboratory branch complement fixation micromethod. The Centers for Disease Control's clinical measles case definition was used. A modification of the manufacturer's optical density interpretation algorithm was introduced to allow for equivocal results, in addition to positive and negative ones. These three categories differed as to their association with a significant increase in CF Ab titer and the time between the onset of symptoms and phlebotomy. The IgM positivity rate for complement fixation-confirmed measles cases was 96.6% for vaccinated subjects and 100% for nonvaccinated subjects. The daily percentage of IgM seropositivity that was detected for subjects who became IgM positive within 30 days increased gradually from 40 to 90% for sera taken 1 to 7 days after the onset of symptoms, and it plateaued at 100% for sera taken 16 to 30 days after the onset of symptoms. IgM seropositivity was strongly associated with IgG seroconversion, CF Ab titer increase, and clinical measles (P less than 0.0001). Reproducibility was 100% for nonreactive sera and 99.1% for reactive sera. In conclusion, the Enzygnost Measles Enzyme-Linked Immuno-Sorbent Assay kit performed adequately to confirm measles virus infection during this epidemic. A second serum sample should be tested when an early-acute-phase serum sample is IgM negative.

Adolescent↗
PubMed1986

[Studies on the interaction between cells infected with measles virus and anti-measles antibody. I. Cytotoxic antibody activity of sera obtained from patients with natural measles and subacute sclerosing panencephalitis by use of chronically infected cell lines].

Sera obtained from patients with natural measles and subacute sclerosing panencephalitis (SSPE) showed cytotoxic activity in the presence of complement on cells persistently infected with either measles virus (Schwarz and TYCSA strains) or SSPE virus (Halle and Mantooth strains). The cytotoxic activity was demonstrated in both IgG and IgM fractions of measles convalescent sera, but only in IgG fraction of SSPE sera. Measles convalescent sera completely lost the cytotoxic activity to all carrier cell lines, when absorbed with any one of the cell lines, indicating that the viral surface antigens of these cell lines infected with measles or SSPE virus were identical. On the other hand, the cytotoxic activity of SSPE sera could not be readily absorbed with these cells. Thus, the affinity of SSPE sera for the viral surface antigens might be lower than that of measles convalescent sera.

Adult↗
PubMed2002

Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren.

OBJECTIVE: To compare antibody responses and side-effects of aerosolized and injected measles vaccines after revaccination of children enrolling in elementary schools. METHODS: Vaccines for measles (Edmonston-Zagreb) or measles-rubella (Edmonston-Zagreb with RA27/3) were given by aerosol or injection to four groups of children. An additional group received Schwarz measles vaccine by injection. These five groups received vaccines in usual standard titre doses. A sixth group received only 1000 plaque-forming units of Edmonston-Zagreb vaccine by aerosol. The groups were randomized by school. Concentrations of neutralizing antibodies were determined in blood specimens taken at baseline and four months after vaccination from randomized subgroups (n = 28-31) of children in each group. FINDINGS: After baseline antibody titres were controlled for, the frequencies of fourfold or greater increases in neutralizing antibodies did not differ significantly between the three groups that received vaccine by aerosol (range 52%-64%), but they were significantly higher than those for the three groups that received injected vaccine (range 4%-23%). Mean increases in titres and post-vaccination geometric mean titres paralleled these findings. Fewer side-effects were noted after aerosol than injection administration of vaccine. CONCLUSION: Immunogenicity of measles vaccine when administered by aerosol is superior to that when the vaccine is given by injection. This advantage persists with aerosolized doses less than or equal to one-fifth of usual injected doses. The efficacy and cost-effectiveness of measles vaccination by aerosol should be further evaluated in mass campaigns.

Aerosols↗
PubMed1986

[Studies on the interaction between cells infected with measles virus and anti-measles antibody. II. Production and application of monoclonal antibodies against measles virus].

Somatic cell hybrids which produced antibodies against measles virus were established by fusing the spleen cells of BALB/c mice immunizing with purified measles virus and the myeloma cell line P3.653 using polyethylene glycol 1,000. Mouse ascites were obtained by inoculating several hybridoma clones, and 2 ascites showed to have high HI titer antibodies. Location of the measles virus antigens on the cells infected with measles virus could be analysed by indirect immunofluorescence technique using these monoclonal antibodies. Reversed passive hemagglutination-inhibition (R-PHI) titers checked by chicken blood cells coated with 2 monoclonal antibodies were parallel with the HI tiers by African green monkey blood cells. These antibodies will be valuable for many virological investigation, for instance, for the detailed antigenic analysis of measles virus and for searching the location of measles virus antigens in the infected cells or tissues.

Animals↗
PubMedDate not supplied

[Several indices of humoral anti-measles immunity in children, previously immunized with live measles vaccine, who have developed measles].

The dynamics of the total content of measles antibody with reference to their physico-chemical nature and the dynamics of the content of the main classes of serum immunoglobulins (A, M, G) in children previously vaccinated and not vaccinated with live measles vaccine who developed measles were studied. Measles in the vaccines was found to run a course of the type of primary and secondary infection. In the former case, the normal dynamics of specific antibody was found with timely change of synthesis of antibody of various physico-chemical nature. In the latter case, immunity to measles developed according to the secondary type and was characterized by the absence of IgM measles antibody. The secondary immunological response was also characterized by higher antibody titers in the first days of the disease and decreased content of IgG and IgM in sera in the convalescent stage. Besides, in such children, hyperthermia occurred 3 times less frequently.

Adolescent↗
PubMed1992

Epidemiological studies on measles in Karachi, Pakistan--mothers' knowledge, attitude and beliefs about measles and measles vaccine.

In order to gather information on the factors affecting the spread of measles vaccine in Pakistan, 287 mothers living in Karachi were interviewed concerning their knowledge, attitude and beliefs about measles and measles vaccine. Measles had been highly prevalent, mainly among infants between 9 and 18 months of age. The severity of the illness and the frequency of complications were well known and the importance of immunizations was well recognized. In traditional combined families grandparents had made the decision to take children for immunization, but many mothers had begun to feel that they were responsible for participation in the programme. The vaccine acceptance rate had increased sharply in recent years, primarily due to local health educators' activities and mass media such as TV programmes. The present findings confirm the importance of continuous effort toward promotion of primary health care by collaboration of motivated mothers and community health workers.

Adult↗
PubMed1994

Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons.

BACKGROUND: Measles is the most transmissible disease known to man. During the 1980s, the number of measles cases in the United States rose dramatically. Surprisingly, 20% to 40% of these cases occurred in persons who had been appropriately immunized against measles. In response, the United States adopted a two-dose universal measles immunization program. We critically examine the effect of vaccine failure in measles occurring in immunized persons. METHODS: We performed a computerized bibliographic literature search (National Library of Medicine) for all English-language articles dealing with measles outbreaks. We limited our search to reports of US and Canadian school-based outbreaks of measles, and we spoke with experts to get estimates of vaccine failure rates. In addition, we devised a hypothetical model of a school where measles immunization rates could be varied, vaccine failure rates could be calculated, and the percentage of measles cases occurring in immunized students could be determined. RESULTS: We found 18 reports of measles outbreaks in very highly immunized school populations where 71% to 99.8% of students were immunized against measles. Despite these high rates of immunization, 30% to 100% (mean, 77%) of all measles cases in these outbreaks occurred in previously immunized students. In our hypothetical school model, after more than 95% of schoolchildren are immunized against measles, the majority of measles cases occur in appropriately immunized children. CONCLUSIONS: The apparent paradox is that as measles immunization rates rise to high levels in a population, measles becomes a disease of immunized persons. Because of the failure rate of the vaccine and the unique transmissibility of the measles virus, the currently available measles vaccine, used in a single-dose strategy, is unlikely to completely eliminate measles. The long-term success of a two-dose strategy to eliminate measles remains to be determined.

Canada↗
PubMed2003

The survival benefit of measles immunization may not be explained entirely by the prevention of measles disease: a community study from rural Bangladesh.

OBJECTIVE: To examine whether the reduction in childhood mortality after immunization can be explained by the prevention of measles and its long-term effects. METHODS: and Data We re-analysed an existing data set from Matlab, Bangladesh. During 1982-1985, measles immunization was used from 9 months of age in half of the study area, and the other half was used as an unvaccinated control area. A total of 8134 immunized children had been matched by age with 8134 non-immunized children; 578 children died during the follow-up period of 3 years. Using these data, we calculated the vaccine effectiveness against death (VED) controlling for significant factors in a matched analysis. In the absence of measles, there should be no difference in mortality between immunized, uninfected children and non-immunized, uninfected children. We therefore calculated VED after the exclusion of all measles cases in the survival analysis. To assess the long-term effects of measles, we compared survival of unvaccinated children after measles disease with children who had not yet contracted measles. RESULTS: Prior to immunization and again after 1985, childhood mortality rates were 10% lower in the area that had received immunization. Though measles deaths only constituted 12.4% of the non-accidental deaths, the VED controlling for significant factors was 49% (95% CI: 38-58%). The vaccine was protective against measles death throughout the study, but it also had a marked effect against other causes of death, particularly diarrhoea and oedema. This effect may have been particularly strong in the first 6 months after immunization (VED = 74, 95% CI: 57-84%). The VED was only reduced from 49% to 43% (95% CI: 31-54%) when measles cases were excluded in the survival analysis. Controlling for background factors, mortality among measles cases was increased during the acute phase (0-45 days) (mortality ratio [MR] = 17.35, 95% CI: 11.9-25.3) and in the following 1(1/2) months (MR = 2.35, 95% CI: 0.95-5.84). However, post-measles cases had significantly lower mortality than uninfected, non-immunized children in the following 9 months (MR = 0.40, 95% CI: 0.16, 0.98). CONCLUSIONS: The non-randomized character of the original study and the possibility of uncontrolled confounding between the two areas prevent a precise estimate of the effectiveness of measles vaccine, but it is likely to have been substantial. Though there may have been some underreporting of cases of measles, the prevention of measles infection can only explain a limited part of the observed impact of measles immunization in Bangladesh. Furthermore, mortality may be reduced after the acute phase of measles infection. The observations from Bangladesh are consistent with recent research from Africa suggesting that measles immunization may have non-specific beneficial effects on survival.

Bangladesh↗
PubMed2001

Vitamin A for treating measles in children.

BACKGROUND: Measles is a leading cause of childhood morbidity and mortality. Vitamin A deficiency is a recognised risk factor for severe measles. The World Health Organization (WHO) recommends administration of an oral dose of 200,000 IU (or 100,000 IU in infants) of vitamin A per day for two days to children with measles in areas where vitamin A deficiency may be present. OBJECTIVES: The purpose of this review is to determine whether vitamin A when commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other complications in children. SEARCH STRATEGY: MEDLINE and the Cochrane Library, Issue 4, 1999 were searched. SELECTION CRITERIA: Only randomized controlled trials in which children with measles were given vitamin A or placebo along with standard treatment were considered. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two reviewers. The analysis of dichotomous outcomes was done using the StatExact software package. Sub-group analyses were done for dose, formulation, age, hospitalisation and pneumonia specific mortality. Weighted mean difference with 95% CI were calculated for continuous outcomes. MAIN RESULTS: The relative risks (RR) and 95% Confidence Intervals (CI) are based on the estimates from the StatExact software package. There was no significant reduction in mortality in the vitamin A group when all the studies were pooled together (RR 0.60; 95% CI 0.32 to 1.12)(Statexact estimate). There was a 64% reduction in the risk of mortality in children who were given two doses of 200,000 IU of vitamin A (RR=0.36; 95% CI 0.14 to 0.82) as compared to placebo. Two doses of water based vitamin A were associated with a 81% reduction in risk of mortality (RR=0.19; 95% CI 0.02 to 0.85) as compared to 48% seen in two doses of oil based preparation (RR=0.52; 95% CI 0.16 to 1.40). Two doses of oil and water based vitamin A were associated with a 82% reduction in the risk of mortality in children under the age of 2 years (RR=0.18; 95% CI 0.03 to 0.61) and a 67% reduction in the risk of pneumonia specific mortality (RR=0.33; 95% CI 0.08 to 0.92). There was no evidence that vitamin A in a single dose of 200,000 IU was associated with a reduced risk of mortality among children with measles (RR=0.77; 95% CI 0.34 to 1.78). Sub-groups like age, dose, formulation, hospitalisation and case fatality in the study area were highly correlated and there were not enough studies to separate out the individual effects of these factors. There was a 47% reduction in the incidence of croup (RR=0.53; 95% CI 0.29 to 0.89), while there was no significant reduction in the incidence of pneumonia (RR=0.92; 95% CI 0.69 to 1.22) or of diarrhoea (RR=0.80; 95% CI 0.27 to 2.34). Duration of diarrhoea was measured in days and there was a reduction in its duration of almost two days WMD -1.92, 95% CI -3.40 to -0.44. Only one study evaluated otitis media and found a 74% reduction in its incidence (RR=0.26, 95% CI, 0.05 to 0.92). We did not find evidence that a single dose of 200,000 IU of vitamin A per day, given in oil-based formulation in areas with low case fatality, was associated with reduced mortality among children with measles. However, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. REVIEWER'S CONCLUSIONS: Although we did not find evidence that a single dose of 200,000 IU of vitamin A per day was associated with reduced mortality among children with measles, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. The effect was greater in children under the age of two years. There were no trials that compared a single dose with two doses, although the precision of the estimates of trials that used a single dose were similar to the trials that used two doses.

Adolescent↗
PubMed2003

Frequency of measles virus-specific CD4+ and CD8+ T cells in subjects seronegative or highly seropositive for measles vaccine.

The protective effect of measles immunization is due to humoral and cell-mediated immune responses. Little is known about cell-mediated immunity (CMI) to measles vaccine virus, the relative contribution of CD4(+) and CD8(+) T cells to variability in such immune responses, and the immunologic longevity of the CMI after measles vaccination in humans. Our study characterizes cellular immune response in subjects seronegative or highly seropositive for measles vaccine immunoglobulin G-specific antibody, aged 15 to 25 years, previously immunized with two doses of measles-mumps-rubella II vaccine. We evaluated the ability of subjects to respond to measles vaccine virus by measuring measles virus-specific T-cell proliferation. We examined the frequencies of measles virus-specific memory Th1 and Th2 cells by an ELISPOT assay. Our results demonstrated that proliferation of T cells in seronegative subjects was significantly lower than that for highly seropositive subjects (P = 0.003). Gamma interferon (IFN-gamma) secretion predominated over interleukin 4 (IL-4) secretion in response to measles virus in both groups. The median frequency of measles virus-reactive CD8(+) T cells secreting IFN-gamma was 0.09% in seronegative subjects and 0.43% in highly seropositive subjects (P = 0.04). The median frequency of CD4(+) T cells secreting IL-4 in response to measles virus was 0.03% in seronegative subjects and 0.09% in highly seropositive subjects (P = 0.005). These data confirm the presence of measles virus-specific cellular immune responses post-measles vaccine immunization in humans. The detection of measles virus-induced IFN-gamma and IL-4 production by ELISPOT can be used to identify measles virus-specific low-frequency memory T cells in subjects immunized with measles vaccine. These differences agree in directionality with the observed antibody response phenotype.

Adolescent↗