Immunogenetic analysis and serum viral antibody titers in multiple sclerosis.

In order to investigate the possible relationships between multiple sclerosis (MS) and the factors of genetic predisposition and exposure to infectious agents, studies were undertaken in 59 male patients with MS to determine the histocompatibility antigen (HL-A) type and the serum antibody titer to rubeola hemagglutinin (HA), rubeola envelope antigen (V), rubeola nucleocapsid antigen (S), rubella, herpes simplex, cytomegalovirus, and parainfluenza 1. The incidence of HL-A7 was significantly higher, and HL-A12 incidence was significantly lower, in the MS group than in control groups. The geometric mean titers to rubeola HA and to the V and S antigens were lower in the HL-A7 positive control patients than in either the non-HL-A7 controls or the MS patients. There were no specific relationships of the rubeola titer to HL-A12. Antibody titers to the other viruses studied were not significantly different in MS patients as compared to controls, nor was there any relationship of HL-A7 or HL-A12 and serum titer to those viruses. This study provides further evidence of a genetic predisposition to MS, and of a relationship between rubeola and this disease. These findings suggests that the failure of MS to appear in individuals who might be genetically predisposed to this disorder may be related to their immune response to rubeola.

Measles outbreak in a pediatric practice: airborne transmission in an office setting.

In February 1981, a measles outbreak occurred in a pediatric practice in DeKalb County, GA. The source case, a 12-year-old boy vaccinated against measles at 11 1/2 months of age, was in the office for one hour on the second day of rash, primarily in a single examining room. On examination, he was noted to be coughing vigorously. Seven secondary cases of measles occurred due to exposure in the office. Four children had transient contact with the source patient as he entered or exited through the waiting room; only one of the four had face-to-face contact within 1 m of the source patient. The three other children who contracted measles were never in the same room with the source patient; one of the three arrived at the office one hour after the source patient had left. The risk of measles for unvaccinated infants (attack rate 80%, 4/5) was 10.8 times the risk for vaccinated children (attack rate 7%, 2/27) (P = .022, Fisher exact test, two-tailed). Airflow studies demonstrated that droplet nuclei generated in the examining room used by the source patient were dispersed throughout the entire office suite. Airborne spread of measles from a vigorously coughing child was the most likely mode of transmission. The outbreak supports the fact that measles virus when it becomes airborne can survive at least one hour. The rarity of reports of similar outbreaks suggests that airborne spread is unusual. Modern office design with tight insulation and a substantial proportion of recirculated ventilation may predispose to airborne transmission.

Impact of revaccinating children who initially received measles vaccine before 10 months of age.

Two hundred fifty-four infants who had received measles vaccine at less than 10 months of age were revaccinated at greater than or equal to 15 months of age, and their immune responses were compared with 129 control infants who received their first doses of measles vaccine at greater than or equal to 15 months of age. Sera were collected at the time of revaccination (study infants) or primary vaccination (control infants), 3 weeks, and 8 months later and tested for antibody by hemagglutination inhibition (HI), enzyme-linked immunosorbent assay (ELISA), and cytopathic effect neutralization (CPEN). Of the 121 study infants who were initially HI negative, 116 (95.9%) made HI antibody 3 weeks postrevaccination compared with 126 (99.2%) of 127 control infants (P = 0.19). Of the 63 study infants with no initial detectable antibody by any of the three tests, 14 (22.2%) had a measles-specific IgM response 3 weeks postrevaccination compared with 37 of 50 (74.0%) randomly chosen control infants. By 8 months after revaccination, the 121 initially HI-negative study infants were significantly less likely to have detectable HI antibodies than control infants (52.1% v 97.6%) (P less than .001). However, 96.7% of these 121 study infants had detectable neutralizing antibody 8 months postrevaccination, an antibody thought to correlate best with protection. This study confirms the altered immune response to revaccination in infants first vaccinated prior to 10 months of age; however, the data suggest that most of these infants were successfully primed and are probably protected after revaccination.

Immunogenicity and safety of measles vaccine in ill African children.

A concurrent prospective study was conducted in Rwanda to compare the immunogenicity and safety of live, attenuated measles vaccine in ill and well children. Five hundred and eighteen children aged 8 to 19 months were selected from children attending the acute care and immunization services of two clinics. Two hundred and sixty-seven ill children and 251 well children were enrolled and examined. Serological tests were performed on blood samples obtained before and 40 days after measles immunization. Among the 208 ill children and 215 well children who were seronegative at baseline and had unequivocal follow-up serological results, seroconversion rates were 81% and 80%, respectively. Side effects were modest and were equally frequent in the two study groups (15.4% among ill children versus 15.1% among well children). These results support a change in measles immunization policy in developing countries with respect to immunization of children with acute illnesses. Such a change would make a great contribution to decreasing the enormous burden of measles in the developing world through increased immunization coverage.

False-positive rubella hemagglutination-inhibition (HAI) titers in neonates and children with conjugated hyperbilirubinemia.

Two neonates, one with extrahepatic biliary atresia and one with cystic fibrosis, and a 9-year-old child with atresia of the common bile duct had conjugated hyperbilirubinemia and elevated rubella HAI titers when kaolin pretreatment of serum was used. A beta-lipoprotein fraction of the serum that is frequently found in association with biliary obstruction was shown to be the probable source of the rubella HAI inhibitor. This beta-lipoprotein was not removed by standard kaolin treatment of serum, but was removed almost completely by dextran sulfate--calcium chloride treatment. In the presence of conjugated hyperbilirubinemia, routine kaolin pretreatment of serum is an inadequate measure for the removal of interfering substances, as false-positive rubella HAI results are obtained consistently.

Infectious disease patterns in the Waorani, an isolated Amerindian population.

The Waorani Indians of eastern Ecuador provide a unique opportunity for studying exposure of an isolated human population to various infectious disease agents. Using serologic tests to determine antibody prevalence, skin test data, and stool examination for parasites, we have been able to construct a profile of infectious diseases which are endemic, and others which have been introduced into the Waorani population. These findings are compared with similar data reported from elsewhere in the Amazon. Serologic studies demonstrating the presence of antibody to measles and poliovirus type 3 after vaccination indicate that the Waorani respond normally to viral challenge with these agents. The question of genetic inability among aboriginal Amerindians to respond to viral agents is discussed. Finally, general recommendations are made regarding the future health care of the Waorani.

Evaluation of a mass measles immunization campaign in Yaoundé, Cameroun.

A mass measles immunization campaign carried out in Yaoundé, Cameroun, has been evaluated. Sixty per cent of the children were immune to measles at the time of the campaign. Only 51% of the susceptible children received vaccine. This was caused by a lack of attendance at the vaccination centres and errors in the selection of children given vaccine. The vaccine administered was relatively ineffective: 40% seroconversion. Difficulties which probably contributed to the low seroconversion rate included sub-optimal vaccine titre, inadequate doses of vaccine, and the relatively long time of vaccine utilization under tropical temperatures. Overall, 83% of the vaccine given to the vaccinating team was wasted. Future immunization campaigns can be improved through better screening of the children, improved handling of the vaccine, the use of marker vaccines, and improved health education.

Available rubella serologic tests.

Serologic techniques for the detection of antibodies to rubella virus provide the approach of choice for laboratory diagnosis of acute and congenital rubella infections and for the determination of rubella immunity status. Rubella serodiagnostic tests currently being used in clinical laboratories are described in this review. Advantages, limitations, and relative sensitivities and specificities of these tests are presented. The reactivity and specificity of rubella antibody tests have been shown to vary from laboratory to laboratory and from one manufacturer's kit to another. The need is clearly apparent for a universally accepted reference standard that will allow sensitivities and alternative assays to be compared directly and a meaningful immune cutoff level to be established. Incorporating such standards into the available rubella tests would eliminate much of the diagnostic uncertainty associated with rubella infections during pregnancy.

Herpes simplex virus microneutralization: a simplification of the test.

The herpes simplex virus (HSV) microneutralization test has been simplified; its use has been demonstrated for the identification of HSV isolates as type 1 (HSV-1) or type 2 (HSV-2) and for the measurement of antibodies to HSV-1 and HSV-2. In this test, the relation between the neutralization titer and virus input is linear, and thus test results can be expressed as corrected neutralization titers, rather than as the more complex neutralizing potency values previously proposed. By means of this test, 45 of 46 clinical isolates of HSV were unequivocally identified as either HSV-1 or HSV-2. Evaluation of neutralizing antibody to HSV infection was more difficult because some neutralizing antibody to the heterotypic HSV is produced after primary infection with HSV-1 or HSV-2, because patients previously infected with one HSV type may show a variety of serological responses to subsequent heterotypic infection, and because human sera obtained early after primary HSV infection may not yet exhibit a type-specific response.

Rubella antibody persistence after immunization.

A comparative field trial of three live, attenuated rubella virus vaccines (Cendehill, HPV 77 DE-5, and HPV-77 DK-12) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Following initial seroconversion rates of more than 98%, periodic serological testing of the study population was conducted to assess the durability of vaccine-induced immunity. In February 1980, ten years after the initiation of the study, 741 of the 5,153 original susceptible vaccinees were still enrolled in the study. After a drop of approximately 50% in mean hemagglutination-inhibition (HI) titer for each of the vaccine groups during the first four years following vaccination, the HI titer levels for all three groups have been generally stable between years 4 and 10. The frequency of reversion to an HI titer of less than 10 has remained less than 0.5% per year. A measurable HI antibody level has persisted in more than 97% of all vaccines over the ten-year period. This study indicates that when potent rubella vaccine is administered properly, a high seroconversion rate and a high rate of antibody persistence should be expected.

Serological response to rubella revaccination.

To document the serological response, 21 seronegative rubella vaccinees (hemagglutination inhibition [HI] titer less than 10) were revaccinated with RA 27/3 rubella vaccine. All demonstrated an anamnestic response. Although RA 27/3 vaccine was an effective booster, antibody boost was not maintained in some persons. Of 15 persons tested, 24 to 27 months after revaccination, six had a significant HI antibody drop (fourfold or greater); only one had lost all detectable HI antibody. Although all 21 study participants were initially HI seronegative by rubella HI testing, 16 (76.2%) possessed neutralization and/or enzyme-linked immunosorbent assay antibodies before revaccination. As more persons with vaccine-induced immunity join the adult population pool, more sensitive test methods may be needed to assess serological status accurately.

Epidemic measles in a highly vaccinated population.

During November, 1975, to May, 1976, measles occurred at a rate of 20.3 cases per 1000 in a purported immunized population, of whom historical and serologic survey revealed that 9 per cent had no history of either measles illness or vaccination and 18 per cent did not have detectable measles antibody. Antibody was detectable in 92 per cent of those vaccinated at greater than or equal to 13 months, 80 per cent at 12 months and 67 per cent of those vaccinated when less than one year old (P less than 0.001), but no significant differences existed with increasing years since vaccination (P greater than 0.1). A second vaccination increased detectable antibody prevalence only in those originally vaccinated when less than nine months old (42 to 80 per cent, P less than 0.02). During a measles outbreak, more cases occurred in those receiving vaccine when less than 12 months old than in those vaccinated at greater than or equal to 12 months (37 per cent vs. 9 per cent, P less than 0.001). A second vaccination protected those originally vaccinated at less than 12 months (35 per cent ill without a second vaccination vs. 2 per cent with, P less than 0.001). Thus, a single measles vaccination of children less than 12 months old does not protect; a second vaccination will protect this group.

Evaluation of a measles-smallpox vaccination campaign by a sero-epidemiologic method.

An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign.

Rubella reinfection during pregnancy. A case of mistaken diagnosis of congenital rubella.

A case of subclinical rubella reinfection during pregnancy with serologic findings in the offspring initially led to an erroneous diagnosis of fetal infection. Laboratory diagnosis of congenital rubella infection, based on finding hemagglutination-inhibition (HI) activity in immunoglobulin M (IgM) fractions of newborn's serum after sucrose gradient fractionation, was questioned when apparent IgM-HI activity was to be probably due to nonspecific inhibitors, which resulted from bacterial action on the beta-lipoprotein in the serum. These findings emphasize some pitfalls encountered in arriving at a diagnosis based soley on serologic data. This case also illustrates the importance of keeping serum samples sterile when performing serologic tests.

Measles in patients suspected of having Rocky Mountain spotted fever.

Diagnostic titer rises of measles antibody were observed in six of 46 paired sera from persons originally suspected of having Rocky Mountain spotted fever and found to be serologically negative for this disease. Atypical or typical measles is now occurring relatively more frequently in adolescents and young adults and should be considered in the differential diagnosis for patients in these age groups who have undiagnosed febrile rash illnesses.

Experience with electron microscopy in the differential diagnosis of smallpox.

The usefulness of negative-contrast electron microscopy in the rapid differential diagnosis of poxvirus and herpesvirus exanthems is described in this study of 301 specimens from patients with vesicular exanthematous diseases. Specimens from patients with smallpox, various forms of vaccination complications, varicella, zoster (shingles), and herpes simplex are included in this evaluation. Electron microscopy, when applied to the study of lesion material, was found to be more sensitive than the classical techniques of virus isolation in the diagnosis of both poxvirus and herpes/varicella virus infections. However, since specific identification of a virus within a group cannot be made morphologically by electron microscopy, it is recommended that both electron microscopy and virus isolation methods be employed for the routine differential diagnosis of vesicular exanthematous diseases in the reference diagnostic laboratory.