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Serological response to early measles vaccination.

This study compares the persistence of measles IgG antibody in 239 children vaccinated at 6-8 months of age with 76 children vaccinated after 8 months of age. Among the children vaccinated prior to 9 months, 49 per cent of the children between 16 and 44 months and 33 per cent of children over 54 months had levels of measles IgG antibody conventionally considered protective. Among the children older than 48 months, 67 per cent of children vaccinated before 9 months and 13 per cent of children vaccinated after 8 months had antibody levels below the conventionally accepted protective levels of 0.2 IU/ml. Older children had lower antibody levels than younger children. Measles immunization before 9 months with the standard titer Edmonston-Zagreb vaccine has not provided a large proportion of under-five children with protective levels of measles IgG antibody. A significant proportion of children vaccinated at the currently recommended age also had suboptimal levels. It is difficult to protect the majority of the measles-susceptible population with a single dose regardless of the immunization schedule used. A second dose of measles vaccine may be necessary to increase the herd immunity.

Child, Preschool↗

Measles seroconfirmation using dried capillary blood specimens in filter paper.

Because the incidence of measles has declined in recent years, the potential for confusion of measles with other morbilliform rashes has increased. Routine serologic testing of suspected cases of measles is recommended but it has been hampered, particularly in young infants and children, by the requirement of performing venipuncture. We have compared measles hemagglutination inhibition antibody testing performed on dried capillary whole blood collected on filter paper strips with testing of serum specimens obtained simultaneously by venipuncture. We assessed overall comparability, diagnostic sensitivity and specificity and acceptability and practicality for field use. Of the 125 capillary-venous sets compared, there was a 4-fold difference in hemagglutination inhibition titer between the two types of specimens in only one set (0.8%). Diagnostic sensitivity using capillary blood was 100% and specificity was 96%. Immunoglobulin M assessments on six capillary-venous sets were in complete agreement (three positive in both, three negative in both). In a pilot program of field use, filter paper blood collection was associated with a 97% (36 of 37) success rate in obtaining specimens from individuals with suspected cases of measles. This method of blood collection and testing is an accurate, feasible and acceptable means for seroconfirmation of measles.

Antibodies, Viral↗

Measles vaccine effectiveness in standard and early immunization strategies, Niger, 1995.

BACKGROUND: An Expanded Programme on Immunization was started in late 1987 in Niger, including vaccination against measles with one dose of standard titer Schwarz vaccine given to infants after 9 months of age. During epidemics an early two-dose strategy was implemented (one dose between 6 and 8 months and one dose after 9 months). From January 1, 1995, until May 7, 1995, 13 892 measles cases were reported in Niamey, Niger. METHODS: A retrospective cohort study was conducted in a crowded area of Niamey at the end of the outbreak to assess the effectiveness of measles vaccine in standard (after 9 months) and early (before 9 months) immunization strategies under field conditions. RESULTS: Highest measles incidence rates were observed among children <1 year of age. Vaccine effectiveness estimates increased with age at vaccination from 78% with a single dose administered at 6 months of age to 95% at 9 months. Vaccine effectiveness with the early two dose strategy was 93%. CONCLUSIONS: Immunization with a single dose of standard titer Schwarz vaccine before 9 months of age provided higher clinical protection than expected from seropositivity studies. The early two dose strategy is justified in contexts where measles incidence is high before 9 months of age. Our results raise the issue of lowering the recommended age for measles vaccination in developing countries.

Child, Preschool↗

Measles outbreak in Dublin, 2000.

BACKGROUND: An outbreak of measles occurred in Ireland between December 1999 and July 2000. The majority of cases were in north Dublin, the catchment area of The Children's University Hospital (TCUH). METHODS: Details of all of the 111 children attending the hospital with a diagnosis of measles between December 1999 and July 2000 were prospectively entered into a database. Charts were subsequently reviewed to extract epidemiologic and clinical details. National figures were obtained from the National Disease Surveillance Centre. RESULTS: In the study period 355 attended TCUH with a serologic or clinical diagnosis of measles, and 111 were admitted (47% female, 53% male). The main indications for admission were dehydration in 79%, pneumonia or pneumonitis in 47% and tracheitis in 32%. Thirteen children (11.7% of those admitted) required treatment in the intensive care unit, and in 7 of these mechanical ventilation was necessary. There were 3 deaths as a result of measles. Public health measures to curb spread of the disease included promotion of immunization for susceptible children nationally and recommending administration of measles-mumps-rubella vaccine (MMR) from the age of 6 months, in North Dublin. CONCLUSION: This outbreak of measles posed a major challenge to the hospital and the community for the first half of 2000. The national MMR immunization rate before the outbreak was gravely suboptimal at 79%, whereas the rate in North Dublin, the catchment area of TCUH, was <70%. Three children died as a result of a vaccine-preventable illness.

Age Distribution↗

High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody.

BACKGROUND: Studies among HIV-1-infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. METHODS: To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1-infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1-specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. RESULTS: Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks' gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1-specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). CONCLUSIONS: This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1-exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1-exposed infants.

Adult↗

A solid-phase radioimmunoassay for IgG and IgM antibodies against measles virus.

A solid-phase radioimmunoassay (RIA) was used to determine the presence of IgG and IgM antibodies to measles virus in human serum and cerebrospinal fluid (CSF). Purified measles virus was adsorbed on to polystyrene balls, which were then exposed to serial dilutions of test serum or CSF. The presence of antibody was measured by its capacity to bind 125I-labelled specific anti-human IgG or IgM. Serum from a variety of patients as well as measles-immune clinically healthy persons were tested; binding ratios (using negative human serum controls) were usually between 10 and 30, but with subacute sclerosing panencephalitis (SSPE) ratios were as high as 50. Of ten CSF specimens tested, all but one, which was taken early in the convalescent phase of measles infection, had detectable IgG antibody. In six patients with acute measles, IgM antibodies were found in all serum specimens taken one or more days after the onset of rash. Maximal titers of 1:10000 to 1:40000 were found about 7 days later. Thereafter, IgM titres decreased rapidly but were still detectable at 40 days. A purified ribonucleoprotein of measles virus was also used successfully as an antigen in this RIA method.

Antibodies, Viral↗

Rapid replacement of endemic measles virus genotypes.

Although vaccination campaigns have significantly reduced the number of measles cases worldwide, endemic transmission of measles virus (MV) continues to occur in several continents, including Europe. To obtain current information on measles incidence and molecular data on circulating MVs in Germany, a nationwide measles sentinel was established. Phylogenetic analysis based on the variable part of the N gene from 80 MVs isolated between November 1999 and October 2001 revealed the presence of at least six distinct MV genotypes: B3, C2, D4, D6, G2 and a new variant of D7. Both the incidence and the pattern of MV genotypes differed markedly between the former East and West Germany. In the eastern part, few measles cases, mainly caused by genotypes originating from other countries (B3, D4, G2), were detected. In the western and southern parts, genotypes C2, D6 and D7 were associated with endemic transmission. Surprisingly, the indigenous genotypes predominant during the 1990s - C2 and D6 - disappeared simultaneously over the period of observation coinciding with the emergence and the wide spread of D7 viruses. While the incidence of measles remained constant, all MVs isolated in 2001 were assigned to D7. We note that the haemagglutinin (H) sequence of D7 viruses shows distinct exchanges of certain amino acids in the stem and propeller domain compared to C2, D6 and the MV vaccine strains used. This raises the possibility of a selective advantage of D7 viruses transmitted in the presence of H-specific antibodies.

Adolescent↗

Lymphocyte blast transformation responses in measles infection.

Lymphocyte blast transformation responses were studied in eight patients with natural measles infection. A specific response to purified measles virus antigen and a weaker response to crude measles virus antigen were found after infection. The response to purified measles antigen appeared 1-3 weeks after the beginning of the rash, when the great number of proliferating mononuclear cells found in the peripheral blood during the rash was declining. In the first weeks after onset of the rash also leucocyte and lymphocyte numbers were decreased, and specific responses to purified tuberculin (PPD) and to rubella and mumps virus antigens were suppressed. In mitogen stimulation tests there was no significant suppression of phytohaemagglutinin and concanavalin responses in this small series, but the response to pokeweed mitogen was decreased. The responses to antigens other than measles virus antigens recovered in parallel with the increase of the measles-specific response.

Antigens, Viral↗

The high morbidity associated with a measles outbreak in a west Australian town.

OBJECTIVE: To determine the effectiveness of the measles vaccine and to record the morbidity during a measles outbreak. METHODOLOGY: A retrospective cohort study was carried out. It was a community-based study in Bunbury, Western Australia, between February and May 1994, of 53 cases of measles and their household contacts. RESULTS: Of the 53 cases of measles, 24 were from one high school. Only two cases occurred in the high school class that had received the National Health and Medical Research Council of Australia recommended measles, mumps and rubella (MMR) booster 12 months earlier. Neither had been vaccinated. Vaccine effectiveness was 91% (95% confidence interval 67-97%). Ten cases had complications of measles and a further five were admitted to hospital. Doctors prescribed antibiotics to 29 cases and metoclopramide to five cases. One month elapsed between the day the index case became ill and the first notification to the community health centre. CONCLUSIONS: The low herd immunity that led to this high school outbreak can be attributed to low vaccine coverage. There was a significant morbidity associated with this outbreak that may have been averted if earlier notification had occurred. The MMR booster dose should be offered to all 10-16 year olds to prevent high school outbreaks.

Adolescent↗

Clinical features of measles in immunocompromised children.

Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms.

Adult↗

Measles-associated encephalopathy in children with renal transplants.

Two children, boys of 8 and 13 years, presented with measles-associated encephalopathy several years after kidney transplantation for congenital nephrotic syndrome. In the absence of prior clinical measles, the neurological symptoms initially eluded diagnosis, but retrospective analysis of stored samples facilitated the diagnosis of measles-associated encephalopathy without recourse to biopsy of deep cerebral lesions. Each had received a single dose of measles mumps and rubella vaccine before 12 months of age. Prior vaccination, reduction of immunosuppression and treatment with intravenous immunoglobulin and ribavirin may have contributed to their survival. Persistent measles virus RNA shedding, present in one child, was not controlled by treatment with i.v. ribavirin. Two years later, both patients continue to have functioning allografts with only minimal immunosuppression. These cases illustrate the difficulty in diagnosing measles-associated encephalopathy in the immunocompromised host, even in the era of molecular diagnostics, and highlight the renewed threat of neurological disease in communities with incomplete herd immunity.

Adolescent↗

[A case of adult respiratory distress syndrome likely due to measles and Mycoplasma pneumoniae].

We described a case of adult respiratory distress syndrome (ARDS) likely due to measles and Mycoplasma pneumoniae. A 24-year-old, previously healthy man was referred to our hospital because of respiratory arrest. He was unconscious and cyanotic. He had erythematous and polymorphic eruptions of his extremities and trunk, but his face was spared. His chest roentgenogram showed consolidation with air bronchograms affecting the whole bilateral lungs. After mechanical ventilation with positive end-expiratory pressure and administration of intravenous hydrocortisone and protease inhibitor "urinastatin" and so on, the patient recovered from his critical condition. No attributable organisms were isolated from the specimens investigated in his acute phase. Serological examinations of the specific IgM antibody to measles during the course indicated a recent measles infection. Mycoplasma pneumoniae indirect hemagglutination test rose from a titre of less than 1/40 to 1/60. ARDS is a rare complication of measles or Mycoplasma pneumoniae infection. Moreover he received measles vaccine before 1970 in Japan, so this case was suspected to be atypical measles.

Adult↗

[Measles epidemic and investigation of the vaccination history in Chiba Prefecture in 2000. A report from Chiba epidemiological surveillance of tuberculosis and infectious diseases].

A middle-scale epidemic of measles was occurred in Chiba Prefecture, from the beginning of the year in 2000 to September. The Chiba epidemiological surveillance of tuberculosis and infectious diseases committee conducted an investigation of the vaccination history of measles patients, to obtain the prevailing situation of measles and the efficacy of the vaccination. This report summarized results of the epidemiological investigation of measles vaccination history. A total of 1,665 cases were reported during the period. The ratio of the under 1-year-old (who usually do not receive measles vaccine) to all reported cases was 11.4%. The ratio of the vaccinees for the reported cases was 11.8% and this ratio increased in the 5 years old or over. In particular, the 9-year-old age group (26.2%), and 10-14-year-old age group (23.3%) showed a higher ratio than the other age groups. These results indicate that early vaccine inoculation to the under 1-year old group and improvement of the vaccination rate are necessary to prevent measles epidemic. The results also suggest revaccination to higher age groups might be effective.

Adolescent↗

Development of an enzyme-linked immunosorbent assay for immunoglobulin M antibodies against measles virus.

Measles is a highly contagious respiratory virus infection, with typical clinical symptoms including maculopapular rash, fever, cough, coryza, and conjunctivitis. Despite implementation of widespread vaccination programs throughout the world, the rates of global morbidity and mortality are still considerable. This study was performed to design a reliable indirect enzyme-linked immunosorbent assay (ELISA) to measure measles-specific immunoglobulin M (IgM). First, human IgM was purified, and then an anti-IgM antibody was produced in rabbits and purified in a multistep process. The rabbit IgG against human IgM was conjugated with peroxidase. Measles virus-infected Vero cells produced viral antigen. One hundred serum samples from infants of 9 to 18 months of age, mostly vaccinated, were evaluated for determining the presence of specific IgM antibodies against measles virus. The samples were also evaluated for neutralizing antibodies against measles virus by a microneutralization test (MNT). By comparing the results of the ELISA with those of MNT, it was demonstrated that ELISA had a sensitivity and specificity of 100 and 92%, respectively. On the other hand, when the results obtained by our ELISA system were compared with those of an imported measles virus IgM ELISA kit (EIAgen; Adaltis Italia SPa, Bologna, Italy), a high level of agreement was shown (k = 0.926).

Animals↗

Antibodies against measles virus polypeptides in different disease conditions.

The occurrence of antibodies to the nucleoprotein and matrix (M) antigens of measles virus was determined in early and late measles convalescent sera and in sera from patients with multiple sclerosis, subacute sclerosing panencephalitis, chronic active hepatitis, and atypical measles. Antibodies to the two components were identified separately in serially diluted samples both by radioimmune precipitation assays and by complement fixation tests employing purified nucleoprotein and M components as antigens. The antibody response to M antigen in connection with acute infections was weak, and with time titers of antibodies to M antigen were reduced below detectable levels in most cases. A different situation was seen in patients with atypical measles. A pronounced antibody response to M antigen was shown to be a part of the generally accentuated immune response in these patients. Confirming results of others, it was shown that in spite of the increased antibody titers against most measles components in sera from patients with subacute sclerosing panencephalitis, no or only low titers of antibodies to M antigen were present. However, a similar representation of antibodies to measles virus components was also seen in sera from patients with active chronic hepatitis. The significance of this finding for the interpretation of a weak antibody response to M antigen in the presence of a pronounced antibody response to other components is discussed.

Antibodies, Viral↗

Circulating immune complexes in patients with acute measles and rubella virus infections.

A solid-phase C1q radioimmunoassay was used to test for immune complexes (ICs) in sera obtained longitudinally from patients recovering from acute, uncomplicated measles and rubella virus infections. ICs were detected in 12 (18.5%) of 65 sera from 14 measles patients who did not have prolonged IC formation. Of 12 IC-positive measles sera, 9 were collected 4 weeks or more after rash onset. Transient appearance of detectable circulating ICs occurred sooner in 22 rubella patients who did not have prolonged IC formation. Of 109 rubella sera, 14 (12.8%) were IC-positive, and, of these, 10 were collected within 3 weeks of rash onset. Prolonged IC formation was found for an additional four measles and two rubella virus patients. Fractionation of sera from these six patients revealed that levels of large-sized ICs were highest in the initial 10 days after rash onset. Levels of large-sized ICs then declined to those for medium- and small (approximately immunoglobulin G)-sized ICs. IC-associated virus-specific antigens were detected in some of the sera from the six patients having prolonged IC formation. These results suggest two things: first, measles and rubella virus patients differ in the timing of virus clearance or in the reestablishment of normal immunity after infection; second, virus clearance is prolonged in some measles and rubella virus patients who have seemingly normal recoveries from their infections.

Acute Disease↗

Presence of oligoclonal immunoglobulin G bands and lack of matrix protein antibodies in cerebrospinal fluids and sera of ferrets with measles virus encephalitis.

Young adult ferrets were immunized with measles vaccine and 5 to 6 weeks later inoculated intracerebrally with Vero cells persistently infected with cell-associated strain D.R. of measles virus isolated from a patient with subacute sclerosing panencephalitis. Of nine ferrets which survived the infection for 3 weeks or longer, five showed neurological signs. At the time of death they had widespread inflammation in their brains, and cell-associated virus was isolated from three ferrets sacrificed from 5 weeks to 7 months after inoculation. Four ferrets did not develop clinical signs, but two of these had mild inflammation in the brain 7 months and 2 1/2 years after inoculation, respectively. Cerebrospinal fluids drawn by cisternal puncture from infected ferrets at the time of sacrifice had neutralizing titers against measles virus similar to the titers found in sera, but antibody against the measles virus matrix protein was not detectable. Cerebrospinal fluid showed increased immunoglobulin G (IgG) and had distinct measles virus-specific oligoclonal IgG bands. The intensity of the bands correlated with the neutralizing titers of the fluids. These results confirm and extend earlier findings and indicate that persistent measles virus infection in ferrets is similar to human subacute sclerosing panencephalitis and can be used to study certain aspects of persistent brain infections leading to subacute encephalitis.

Animals↗

Involvement of the central nervous system in acute, uncomplicated measles virus infection.

A prospective study on acute, uncomplicated measles infection was carried out in 59 patients hospitalized for an ordinary measles infection. A clinical and serological diagnosis of an acute measles infection was made in all cases. Serial serum and cerebrospinal fluid (CSF) specimens were taken two to five times from each patient and tested for pleocytosis, albumin, and measles-specific antibodies. Pleocytosis was found in 18 patients (30%), usually shortly after the onset of rash. Nine patients had antibodies against measles virus in their CSF. Six of them seemed to have damage to the blood-brain barrier, but in two cases there was a very high serum antibody titer with a normal serum/CSF ratio. One patient had a local antibody production against measles virus in the central nervous system. Conventional electroencephalography (EEG) was recorded on 22 children, and a separate, quantitative EEG study with two to six consecutive recordings was also performed on a group of nine patients. Moderate or strong slowing of background EEG activity was found in 50% of the patients. In the consecutive recordings, the changes culminated a few days after the onset of rash. No correlation seemed to exist between the changes in the CSF and the age of the patient, on the one hand, and slowing of the EEG, on the other.

Adult↗