Negative impact of clinical misdiagnosis of measles on health workers' confidence in measles vaccine.

We conducted a survey to determine the accuracy of the clinical diagnosis of measles in Zimbabwe. Between December 1996 and February 1997, we collected blood samples and clinical and demographic information from a sample of 105 children with a clinical diagnosis of measles. A clinical case of measles was defined as a person with a history of fever, rash for three or more days, and either cough, coryza, or conjunctivitis. A laboratory-confirmed case of measles or rubella had IgM antibodies against measles virus or rubella virus respectively. A total of 91% of children met the clinical case definition. Among those who met the clinical case definition for measles, 72% were IgM-positive for measles virus only, 23% were IgM-positive for rubella virus only, 3% were IgM-positive for both measles and rubella viruses, and 2% were IgM-negative for both viruses. This study demonstrates the importance of considering selective laboratory confirmation of measles in periods of high disease incidence when the effectiveness of the vaccine is questioned.

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.

Induction of cytokine mRNA in peripheral blood mononuclear cells of infants after the first dose of measles vaccine.

To better characterize the cytokine response to measles virus vaccine, we examined the levels of IL-2, IL-4, IL-5, IL-10, IL-12 and gamma-interferon (gamma-IFN) in measles virus-stimulated peripheral blood mononuclear cells from 18 donors before and 2 weeks after vaccination. Donors were grouped as seropositive or seronegative on the basis of measles-specific IgM antibody present at 2 weeks postvaccination. After vaccination, similar levels of upregulation of IL-2 and gamma-IFN mRNA were observed in the two groups. The majority of donors in both groups did not exhibit an increase in measles specific IL-4 or IL-10 mRNA after vaccination. IL-12 mRNA was not induced by measles virus in any of the donors. A statistically significant upregulation of IL-5 mRNA was observed among seropositive (9/13) compared with seronegative (1/5) donors after vaccination (P=0.09, one tailed Fisher's test). The observed measles specific induction of IL-5 mRNA is suggestive of a possible association between IL-5 production and an antibody response to measles virus.

Timing of development of measles-specific immunoglobulin M and G after primary measles vaccination.

A standard method for diagnosing measles is to detect measles-specific immunoglobulin M (IgM) in the serum of infected persons. Interpreting a positive IgM result from a person with suspected measles can be difficult if the person has recently received a measles vaccine. We have previously demonstrated that measles-specific IgM may persist for at least 8 weeks after primary vaccination, but it is unknown how quickly IgM appears. This study determined the timing of the rise of measles-specific IgM and IgG after primary measles vaccination with Schwartz vaccine. Two hundred eighty 9-month-old children from Ethiopia presenting for routine measles vaccination were enrolled. Sera were collected before and either 1, 2, 3, or 4 weeks after vaccination and tested for measles-specific antibodies by an IgM capture enzyme immunoassay (EIA) and by an indirect IgG EIA. A total of 209 of the 224 children who returned for the second visit had prevaccination sera that were both IgM and IgG negative. The postvaccination IgM positivity rates for these 209 children were 2% at 1 week, 61% at 2 weeks, 79% at 3 weeks, and 60% at 4 weeks. The postvaccination IgG positivity rates were 0% at 1 week, 14% at 2 weeks, 81% at 3 weeks, and 85% at 4 weeks. We conclude that an IgM-positive result obtained by this antibody capture EIA is difficult to interpret if serum is collected between 8 days and 8 weeks after vaccination; in this situation, the diagnosis of measles should be based on an epidemiologic linkage to a confirmed case or on the detection of wild-type measles virus.

The effect of timing of sample collection on the detection of measles-specific IgM in serum and oral fluid samples after primary measles vaccination.

This study compares the timing of the rise and decline of measles-specific IgM in serum samples and in oral fluid samples. Two hundred and eighty 9-month-old infants presenting for routine measles vaccination in Addis Ababa, Ethiopia, were enrolled. Paired serum and oral fluid samples were collected before and 1, 2, 3 or 4 weeks after measles vaccination. Samples were tested by using a modified antibody-capture enzyme immunoassay. For the 321 IgM-negative pre- and post-vaccination serum samples, 317 (99 %) of their corresponding oral fluid samples were IgM-negative. Among the 130 IgM-positive serum samples, 75% of their paired oral fluid samples were IgM-positive, with the percentage rising to 87% after oral fluid samples collected > or =3.5 weeks after vaccination were excluded. Among the post-vaccination serum samples, the percent IgM-positive peaked in week 3 and declined to 79% in week 4. For post-vaccination oral fluid samples, the percent IgM-positive peaked in weeks 2 and 3, and then declined to 43% in week 4. This modified antibody-capture enzyme immunoassay appears to detect vaccine-induced measles-specific IgM in the first 3 weeks after vaccination.

Nonclassic measles infections in an immune population exposed to measles during a college bus trip.

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.

Decline of measles-specific immunoglobulin M antibodies after primary measles, mumps, and rubella vaccination.

Detection of measles-specific immunoglobulin M (IgM) has become the standard diagnostic method for laboratory confirmation of measles. In outbreaks, the interpretation of an IgM-positive result can be complicated when persons with suspected measles receive a dose of measles vaccine as part of outbreak control measures. This investigation evaluated the decay of measles-specific IgM antibodies 1 to 4 months after primary vaccination with measles, mumps, and rubella vaccine (MMRII). Serum samples were obtained from 536 infants vaccinated when they were 15 months old as part of a study to assess primary and secondary measles vaccine failure. Sixty serum specimens per week were selected from specimens collected between 4 and 9 weeks after MMRII vaccination; all 176 available serum specimens collected between 10 and > or = 16 weeks were included. Specimens were tested for the presence of measles-specific IgM by an antibody-capture enzyme immunoassay. The proportion of IgM-positive specimens dropped from 73% at 4 weeks after vaccination to 52% at 5 weeks after vaccination and then declined to 7% by 8 weeks after vaccination. Less than 10% of children remained IgM positive between 9 and 11 weeks. An IgM-negative result helps rule out the diagnosis of measles in a person with suspected infection and a history of recent vaccination. The interpretation of a positive IgM result from a person with a clinically suspected case of measles and a recent history of measles vaccination (especially within 8 weeks) is problematic, and the diagnosis of measles should be based on epidemiologic linkage to a confirmed case or on detection of wild-type measles virus.

Diagnosis of measles with an IgM capture EIA: the optimal timing of specimen collection after rash onset.

The optimal timing for collection of a single serum specimen to diagnose measles by using a monoclonal antibody-capture EIA was evaluated. Results of testing paired serum samples from 166 measles cases with at least 1 IgM-positive specimen were analyzed. Among persons whose second samples were IgM-positive, the seropositivity rate for first samples was 77% when collected within 72 h and 100% when collected 4-11 days after rash onset. Among unvaccinated persons whose first samples were IgM-positive, the rate for IgM positivity of second specimens declined from 100% at 4 days to 94% at 4 weeks after rash onset, then declined further to 63% at 5 weeks. Some previously vaccinated persons became IgM-negative during the third week after rash onset. In general, a single serum specimen collected between 72 h and 4 weeks after rash onset can be used to diagnose most cases of measles with an IgM capture EIA.

Comparative detection of measles-specific IgM in oral fluid and serum from children by an antibody-capture IgM EIA.

In vaccinated populations, the diagnosis of measles often requires laboratory confirmation. Serum tested by EIAs has proven sensitive and specific for diagnosing measles. For comparison of detection of measles-specific IgM in oral fluid and serum samples by an antibody-capture EIA, 163 Ethiopian infants who presented for routine measles vaccination were studied. Paired serum and oral fluid samples were collected before and 2 weeks after vaccination; 269 paired samples were adequate for analyses. Of the 104 serum samples that were IgM-positive, 95 (91%) of the paired oral fluid samples were IgM-positive. Of the 165 serum samples that were IgM-negative, 156 (95%) of the paired oral fluid samples were IgM-negative. The Pearson partial correlation coefficient for optical density readings from postvaccination oral fluid compared with serum was 0.81. Oral fluid appears to be an acceptable alternative to serum for measuring measles-specific IgM antibodies by an antibody-capture EIA.

Serologic evidence of an association between enteroviruses and the onset of type 1 diabetes mellitus. Pittsburgh Diabetes Research Group.

Serum was collected from 128 patients < or = 18 years of age admitted to the Children's Hospital of Pittsburgh with new-onset insulin-dependent diabetes mellitus (IDDM) and from 120 control-patients who were frequency-matched to case-patients for age, sex, and date of bleed. Serum was tested for IgM against 14 enterovirus serotypes: coxsackieviruses B1-B6 and A9, echoviruses 4, 6, 9, 11, 30, and 34, and enterovirus 71. Case-children 13-18 years of age were more likely than control-patients to be IgM-positive for 9 of 14 serotypes (P < or = .05 for each). In contrast, case-children 10-12 years of age and 1-9 years of age were each more likely than age-matched control-children to be IgM positive for 1 serotype (P < or = .05 for each). In addition, the association between IgM positivity and IDDM occurred earlier in girls than in boys. These data support an association between IDDM and enterovirus IgM positivity in older children.

Echovirus 30 infection and aseptic meningitis in parents of children attending a child care center.

In July 1992, 13 parents with children attending a child care center (CCC) developed aseptic meningitis (AM) due to echovirus 30 (E30). To determine the extent of illness and risk factors for transmission, survey and blood specimens were collected from CCC families and teachers and from adult and pediatric controls. Infection was defined as the presence of anti-E30 IgM antibodies. CCC parents (60%, 67/111) and children (75%, 79/105) had significantly higher infection rates than did teachers (14%, 3/22), adult controls (24%, 10/41), and pediatric controls (24%, 17/70). Infected CCC parents had more severe illness (18% [12/65] had AM; 11% [7/65] were hospitalized) than did infected CCC children (3% [2/79] had AM and 1% [1/79] were hospitalized). More frequent handwashing among teachers compared with parents and among mothers of toddlers was associated with significantly lower rates of infection (P < or = .05). Education of parents about good handwashing practices may reduce transmission of E30 and other infectious agents from children to adults.