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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.

Global Health↗

RESPONSE OF VOLTA CHILDREN TO LIVE ATTENUATED MEASLES VIRUS VACCINE.

Experience so far with the Enders B-level Edmonston strain of live attenuated measles vaccine has been principally with children in the USA in whom natural measles carries a low mortality. Measles is associated with an appreciably higher mortality rate in developing countries; in Upper Volta, climate, nutritional status, degree of parasitic infestation and concurrent infections may contribute to this. The present report summarizes a pilot study in Ouagadougou, Upper Volta, designed to obtain information on the response of Volta children to Enders vaccine and to determine the feasibility of using this vaccine on a large scale.The observations indicate that Volta children, despite the hazards of natural measles, respond in essentially the same manner to live vaccine given alone or with gamma-globulin as do children in other areas. The febrile reactions which characterize infection with the attenuated measles virus were of insufficient importance to warrant the concurrent use of gamma-globulin in a forthcoming mass measles vaccination campaign in Upper Volta.

Africa↗

Immunoglobulin M antibody response to measles virus following primary and secondary vaccination and natural virus infection.

The use of IgM antibody detection for the classification of the primary and secondary measles antibody response in persons following primary and secondary vaccination and natural measles virus infection was examined. Of 32 nonimmune children receiving primary measles vaccination, 31 (97%) developed IgM antibodies, consistent with a primary antibody response. Of 21 previously vaccinated children with low levels of preexisting IgG antibodies who responded to revaccination, none developed detectable IgM antibodies, whereas 33 of 35 (94%) with no detectable preexisting IgG antibodies developed an IgM response. Of a sample of 57 measles cases with a prior history of vaccination, 55 (96%) had detectable IgM antibodies. Of these, 30 (55%) were classified as having a primary antibody response and 25 (45%) a secondary antibody response based on differences in their ratios of IgM to IgG antibodies. Differences in the severity of clinical symptoms between these 2 groups were consistent with this classification scheme. These findings suggest that 1) an IgM response follows primary measles vaccination in the immunologically naive, 2) an IgM response is absent on revaccination of those previously immunized, and 3) an IgM response may follow clinical measles virus infection independent of prior immunization status.

Adolescent↗

Interruption of measles transmission in Gipuzkoa (Basque Country), Spain.

Measles vaccine was introduced in Gipuzkoa (Basque country, Spain) in 1978 and was replaced by the measles, mumps, and rubella (MMR) vaccine for children aged 12-15 months in 1981. A second dose of the MMR vaccine was introduced in 1992. Both doses of the MMR vaccine were well accepted by the population and high coverage was achieved (95% and 91% for the first and second doses respectively for the period 1993-2002). Measles virus circulation was interrupted in the second half of the 1990s: no cases of indigenous measles were notified between 1998 and 2003, and only imported cases have been confirmed during this period. These data indicate that the measles vaccination programme implemented has been effective. Nevertheless, to avoid measles outbreaks following viral introduction, high MMR vaccine coverage levels for the two doses have to be maintained (>95%).

Child↗

Quantitation of measles-specific IgG. Its presence in CSF and brain extracts of patients with multiple sclerosis.

Twenty of 41 patients with multiple sclerosis (MS) and five of 30 patients with other neurological diseases had measles antibody titers in their CSF when examined in hemagglutination inhibition and neutralization tests. Quantitation of measles-specific IgG in CSF of patients with MS with significant measles antibody titers showed that less than 5% of the total IgG was measles virus specific. In contrast, using the identical quantitation procedures, 30% to 60% of the total IgG in CSF of patients with subacute sclerosing panencephalitis was found to be measles specific. Thus, only a very minor portion of the total IgG in CSF of patients with MS is synthesized against measles virus. When measles hemagglutination inhibition, complement fixation, and neutralizing antibody titers were measured in individual oligoclonal IgG bands isolated from neutral pH brain extracts of two patients with MS, low titers were present in all the oligoclonal bands rather than being restricted to any single band.

Antibodies, Viral↗

Severe complications of measles requiring intensive care in infants and young children.

OBJECTIVE: To evaluate the characteristics of severe complications of measles in patients admitted to a pediatric intensive care unit. DESIGN: Clinical description of a case series. SETTING: The Pediatric Intensive Care Unit of Soroka Medical Center, Beer-Sheva, Israel, during a measles epidemic. PATIENTS: Fifteen pediatric patients with measles requiring intensive care. RESULTS: Fifteen of 237 hospitalized children with measles required intensive care in the Pediatric Intensive Care Unit. Eleven patients were malnourished; none had been vaccinated for measles. All 15 patients required mechanical ventilation for pneumonia that had caused severe respiratory distress. Twelve of 15 patients were severely hypoxemic before intubation. Seven had a clinical syndrome consistent with adult respiratory distress syndrome. Other complications on admission to the intensive care unit included spontaneous pneumothorax in three patients, empyema in two, encephalopathy in seven, shock in three, sepsis in five, hypocalcemia in 11, thrombocytopenia in eight, and coagulopathy in seven. Complications during treatment included pneumothorax in four patients, fibrosing alveolitis in one, brain infarct in one, thrombus formation in three, and nosocomial sepsis in one. Four patients had long-term sequelae (chronic lung disease, subacute sclerosing panencephalitis, hemiplegia, and partial amputation of a limb), and seven patients recovered uneventfully. Four patients died; all had adult respiratory distress syndrome, three had pneumothorax, and one had nosocomial sepsis. CONCLUSIONS: Patients with measles who require intensive care have a high risk for death or long-term complications, even when treated in a modern pediatric intensive care unit. Adult respiratory distress syndrome and air leaks were the most severe complications in these patients. To reduce the severity of these complications, mechanical ventilation should be based on using the lowest possible inspiratory pressure and fraction of inspired oxygen, while accepting an arterial oxygen pressure less than 60 mm Hg. Secondary bacteremia was an early and prominent complication, and antibiotic treatment should be instituted early in patients with measles requiring intensive care.

Bacteremia↗

Response to measles, mumps, and rubella revaccination among HIV-positive and HIV-negative children and adolescents with hemophilia. Hemophilia Growth and Development Study.

The effect of human immunodeficiency virus (HIV) infection on response to measles, mumps, and rubella revaccination in children and adolescents with hemophilia was evaluated. Antibody levels of measles, mumps, and rubella were assayed at baseline and two annual examinations in 207 HIV-positive and 126 HIV-negative hemophiliacs participating in the Hemophilia Growth and Development Study (HGDS). Response to revaccination was analyzed for participants whose antibody levels were below the cut-off at the start of a year-long observation period. Among HIV-positive participants, antibody levels were below cut-off in 52 subjects for measles, in 71 for mumps, and in 96 for rubella. Among HIV-negative participants, antibody levels were low in 23 subjects for measles, in 23 for mumps, and in 31 for rubella. For measles and mumps antigens, revaccination was associated with a significant increase in redraw antibody levels for HIV-negative participants. Although there was an increase in the mean measles titers for revaccinated HIV-positive participants, it was not significant. Revaccination was associated with an increase in rubella antibodies in HIV-positive and HIV-negative participants. Revaccination with measles and mumps was associated with an increase in antibody levels in HIV-negative participants but not in HIV-positive participants. Both HIV-positive and HIV-negative participants responded to rubella revaccination with an increase in antibody levels.

Adolescent↗

Vitamin A for treating measles in children.

BACKGROUND: Measles is a major cause of childhood morbidity and mortality. Vitamin A deficiency is a recognized risk factor for severe measles infections. The World Health Organization (WHO) recommends administration of an oral dose of vitamin A (200,000 international units (IU), or 100,000 IU in infants) each day for two days to children with measles when they live in areas where vitamin A deficiency may be present. OBJECTIVES: To determine whether vitamin A therapy, commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other secondary complications in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1980 to December 2004) and looked for unpublished studies. 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 authors. The analysis of dichotomous outcomes was done using the StatXact software and results expressed as relative risk (RR) with 95% confidence interval (CI). Subgroup analyses were carried out for dose, formulation, age, hospitalization and pneumonia-specific mortality. Weighted mean differences (WMD) with 95% CI were calculated for continuous outcomes. MAIN RESULTS: There was no significant reduction in the risk of mortality in the vitamin A group when all the studies were pooled using the random-effects model (RR 0.70; 95% CI 0.42 to 1.15). Using two doses of vitamin A (200,000 IU) on consecutive days was associated with a reduction in the risk of mortality in children under the age of two years (RR 0.18; 95% CI 0.03 to 0.61) and a 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 was associated with a reduced risk of mortality among children with measles. There was a reduction in the incidence of croup (RR 0.53; 95% CI 0.29 to 0.89) but no significant reduction in the incidence of pneumonia (RR 0.92; 95% CI 0.69 to 1.22) or diarrhoea (RR 0.80; 95% CI 0.27 to 2.34) with two doses. AUTHORS' CONCLUSIONS: Although we found no overall significant reduction in mortality with vitamin A therapy for children with measles there was evidence that two doses were associated with a reduced risk of mortality and pneumonia-specific mortality in children under the age of two years. There were no trials that directly compared a single dose with two doses.

Adolescent↗

Comparative detection of measles and rubella IgM and IgG derived from filter paper blood and serum samples.

We compared the use of serum and filter paper blood spots as specimen sources for the detection of measles- and rubella-specific IgM and IgG. We collected capillary blood into microtainer tubes and onto filter paper spots from 60 children and 60 healthy adults. The blood was collected from 12-15-month-old children approximately 3 weeks after primary vaccination with measles, mumps, rubella vaccine, and the sample-pairs were tested for measles-specific IgM and IgG antibodies by using a capture antibody EIA and an indirect EIA, respectively. We tested sample-pairs from a subset of participants for rubella- specific IgM and IgG antibodies by using commercially available capture IgM (Captia) and indirect IgG (Wampole) assays. The concordance of results from serum and filter paper blood spots was high for all assays: 98% for measles IgM, 93% for measles IgG, 94% for rubella IgM, and 93% for rubella IgG, and increased to between 96-100% for all four assays when indeterminate samples were excluded. The correlation coefficients for EIA signals were 0.99 and 0.77 for measles IgM and IgG, respectively, and 0.92 and 0.94 for rubella IgM and IgG, respectively. The cut-off values used for filter paper samples were the same as those used for serum samples for all tests except for the rubella IgM assay. The use of filter paper blood spots is a promising future option for the detection of measles- and rubella-specific antibodies.

Adult↗

The cellular receptor for measles virus--elusive no more.

The identity of the measles virus receptor has been controversial. Several years ago CD46 was identified as a cellular receptor for the Edmonston strain of measles virus, but most clinical isolates of measles virus, which are most efficiently isolated in the marmoset B cell line B95a, cannot grow in many CD46+ cell lines. Although some researchers attributed it to post-entry block in viral replication, others believed that there is a receptor other than CD46 for wild-type measles viruses. A new study showed that human signalling lymphocytic activation molecule (SLAM; also known as CDw150) is a cellular receptor for measles virus, including the Edmonston strain. SLAM is expressed on lymphocytes and dendritic cells, and plays an important role in lymphocyte activation. The identification of SLAM as a measles virus receptor nicely explains the pathogenesis of measles virus infection.

Antigens, CD↗

Measles immunisation coverage in urban slums.

A cross-sectional, community-based study was conducted in 32 slums of Udaipur city to assess the prevalence of missed opportunities for measles immunization, reason for their occurrence and potential impact of avoiding them on measles immunization coverage. Two hundred and sixty-five children, between the age of 9 and 24 months were enlisted for the study, using a practical cluster sampling method. Immunization status of the children, visits to health facilities after 9 months of age and reasons for non-immunization were noted. Missed opportunities for measles immunization was defined as any visit by an eligible child to a health facility, which did not result in his/her vaccination. Measles immunization coverage amongst the study population was 50.61%. The prevalence of missed opportunities for measles immunization was 14.3%. Not offering measles immunization at curative visits (86.9%) was the major reason for missing opportunities. Avoiding all missed opportunities could have increased the measles immunization coverage to 64.9%.

Child, Preschool↗

Clinical significance of the serum surfactant protein D and KL-6 levels in patients with measles complicated by interstitial pneumonia.

UNLABELLED: To examine the value of surfactant protein D and KL-6 as markers for the diagnosis and the severity of interstitial pneumonia caused by measles infection, surfactant protein D, KL-6 and lactic acid dehydrogenase were measured serially in three patients with measles complicated by interstitial pneumonia as compared to ten measles infected patients without interstitial pneumonia. The serum surfactant protein D and KL-6 levels were higher in patients with measles and interstitial pneumonia as compared to those with measles without interstitial pneumonia. In patients with measles and interstitial pneumonia, the respiratory distress and the alveolar-arterial oxygen differences improved after steroid pulse therapy while the serum surfactant protein D level decreased dramatically under the cut-off level and earlier than the KL-6 level. On the contrary, the serum KL-6 level increased transiently and it took longer to decrease below the cut-off level as compared to the pattern observed for serum surfactant protein D. The serum lactic acid dehydrogenase level changes were between those of the surfactant protein D and KL-6 levels. CONCLUSION: Surfactant protein D and KL-6 are easily measured and useful markers for the diagnosis of interstitial pneumonia caused by measles infection. Early decrease of surfactant protein D contrasts with the transient increase of KL-6 levels after prednisolone pulse therapy.

Antigens↗

Measles antibodies and immunoglobulins in sera from patients with subacute sclerosing panencephalitis (SSPE) and from an infected ferret.

Cellulose acetate electrophoresis of sera from 2 patients with SSPE revealed a slow-moving and a fast-moving gamma-globulin band. The IgG fractions from sera were isolated by the combination of starch block electrophoresis, Sephadex gel filtration and isoelectric focusing techniques. The purity of each protein was tested by immunoelectrophoresis using a potent goat anti-whole human serum. The isolated IgG preparations were tested in HI, CF and N tests against measles virus envelope, measles virus nucleocapsid and whole measles virus, respectively. The results showed that isolated IgG fractions, having different electrophoretic mobilities, contained high titers of HI, CF and N antibodies, and these titers were proportional to the protein concentration of IgG. Although both IgG fractions appeared to show an increase of K-type chain, neither fraction was devoid of L-type chain. These results indicate that the homogeneous IgG bands observed in the SSPE serum were not monoclonal as they failed to show selective increase of one type of light chain and uneven distribution of measles antibody activity. These findings were compared with the results from a ferret, which developed encephalitis 2 months after intracerebral inoculation with cell-associated measles virus derived from the brain of an SSPE patient. The electrophoretic pattern of the ferret serum was similar to that of the human. High titers of measles HI and N antibodies were seen in the isolated slow- and fast-moving IgG's. The similarities observed in the human and ferret IgG's, with respect to homogeneous bands in electrophoresis and measles HI and H antibody activities, suggest that the ferret may be a useful animal model for studying the immune mechanism of SSPE.

Animals↗

Histocompatibility types and measles antibodies in multiple sclerosis.

The relationship between HLA antigens and measles antibody titers was investigated in 105 multiple sclerosis (MS) patients. HLA antigens were determined serologically by a micro-lymphocytotoxicity test and measles antibody titers were determined by the hemagglutination inhibition test. There was an increased frequency of HLA-B7 and HLA-Bw35 antigens and a decreased frequency of HLA-A2, HLA-B12, and HLA-Bw40 antigens in MS. Measles antibody titers were significantly higher in MS than in control cases. In the MS patients, the chi-square test for homogeneity did not show any significant difference between the presence or absence of antigens HLA-A3, HLA-B7, HLA-B8 HLA-A2 or HLA-B12 when compared with measles antibody titers. The chi-square test for association did not show any significant difference between the presence or absence of these antigens compared with measles antibody titers above 1:64 or 1:128 or 1:256. However, there were significantly higher measles antibody geometric mean titers in MS patients with HLA-A3 antigen or lacking HLA-A2 antigen. In the case of HLA-A3, this was reflected in the female but not in the male patients. The increased measles HI antibody titer in MS may be related to the increased frequency of HLA-A3, or the decreased frequency of HLA-A2, or both.

Antibodies, Viral↗

Measles virus-specific immunoglobulin D antibody in cerebrospinal fluid and serum from patients with subacute sclerosing panencephalitis and multiple sclerosis.

Quantitation of measles-specific immunoglobulin D (IgD) antibody was carried out in cerebrospinal fluid (CSF) and serum samples from 18 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS) and seven normal controls with high measles antibody titers in serum, using polyclonal and monoclonal antibodies specific for human IgD and enzyme-linked immunosorbent assay. Measles-specific IgD activity was significantly higher in CSF and serum from SSPE patients compared to that found in patients with MS or normal controls. The IgD antibody to measles virus was not due to high levels of measles-specific IgG since significant measles IgD activity was found after eluting IgG from SSPE serum. The increased level of measles-specific IgD found in SSPE sera is consistent with the levels observed in patients with acute and chronic viral infections.

Enzyme-Linked Immunosorbent Assay↗

Replication of measles virus in the human plasma cell leukemia-derived LICR-LON-HMy2 cell line.

Measles virus is usually grown in human or monkey fibroblast cells. We now show that LICR-LON-HMy2 (LL2) cells, a human plasma cell leukemia-derived line which grows in suspension culture, will permissively support replication of measles virus to an extent achievable with Vero cells. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of measles virions produced by LL2 cells showed a polypeptide pattern typical of measles virus. As well, measles virus-infected LL2 cells, like infected Vero cells, were found to secrete large amounts of virus hemagglutinin, but not other virus proteins. We thus conclude that LL2 cells can be effectively used to produce milligram amounts of measles virus and that virus-clarified culture medium from measles virus-infected LL2 cells is a potential source for purifying virus hemagglutinin.

Animals↗

Direct in situ reverse transcriptase polymerase chain reaction for detection of measles virus.

New methods are described for combined intracellular reverse transcription (RT) and polymerase chain reaction (PCR) using single primer pairs, with direct incorporation of digoxigenin-11-dUTP into amplificants (direct in situ RT/PCR). Routinely used fixatives and minimal pre-treatments were employed. Target sequences of measles virus nucleocapsid (N) and phosphoprotein genes were detected within measles virus infected Vero cells, both in suspension and in formalin-fixed sections, that had been treated by in situ reverse transcription and 30 cycles of direct in situ PCR. Uninfected cells, omission of Taq polymerase, and irrelevant primers were used as controls. Distribution of measles virus within infected cells was determined by in situ hybridisation and immunocytochemistry for measles virus N gene and protein, respectively. Confirmation of amplification within sections was by gel electrophoresis, Southern blotting and sequencing of extracted amplicons. In the majority of cases, measles-infected cells exhibited intense cytoplasmic signal after direct in situ PCR; this was not seen in uninfected cells or infected cells reacted either with irrelevant primers or without Taq polymerase. Unfixed cells in suspension required nested reaction. Measles-specific in situ hybridisation and immunocytochemistry gave an identical signal distribution in sections. Nuclear artifact occurred in some sections and was unpredictable, although it was greatest either in areas of cellular damage, following DNase predigestion, or with vigorous protease pre-treatment. In situ RT-PCR is feasible for measles virus in acutely infected cells both in sections and in suspension. Further work is required to improve the procedure and to eliminate artefactual nuclear signal.

Animals↗

A comparison of hospital policies for measles, mumps, and rubella infection control in Los Angeles County, 1989 and 1992.

BACKGROUND: A survey was conducted in 1992 in Los Angeles County, California, to assess changes since an earlier survey in 1989 in the numbers of acute care hospitals that had established policies on measles, mumps, and rubella infection control and the extent to which these policies were implemented. METHODS: A questionnaire inquiring about measles, mumps, and rubella infection control was sent to ICPs of 133 acute care hospitals in Los Angeles County. The results were compared with those of a similar survey conducted in 1989. The increase in the number of hospitals with such policies between 1989 and 1992 was analyzed. RESULTS: In 1989, 29 (28%), 9 (9%), and 65 (64%) of the 102 respondent hospitals had measles, mumps, and rubella infection control policies, respectively. Larger proportions of the 95 respondent hospitals in 1992 had measles (56, 59%), mumps (15, 16%), and rubella (69, 73%) infection control policies. CONCLUSIONS: The number of hospitals with infection control policies for measles, mumps, and rubella increased from 1989 to 1992. Efficiency and scope of such policies varied, however, and could be improved by making the policies mandatory, requiring written documentation of employee immunity, and extending policies to cover all employees. The most dramatic increase was in the number of hospitals with infection control policies for measles; this increase may have been caused by the 1987 to 1989 measles epidemic in Los Angeles County, by increased awareness of the Immunization Practices Advisory Committee recommendations, or by increased sensitivity to the issue of infection control triggered by the 1989 survey.

California↗