Immunosuppression after measles vaccination.

Smedman,-L; Joki,-A; da-Silva,-A-P; Troye-Blomberg,-M; Aronsson,-B; Perlmann,-P

Acta-Paediatr. 1994 Feb; 83(2): 164-8

Acta-paediatrica

The influence of conventional live attenuated measles vaccine on cellular immune responsiveness was investigated in Sweden and Guinea-Bissau. Sixteen children in a residential area in Bissau and 16 living in southern Stockholm were examined before and 8-10 days after vaccination. Lymphoproliferation was measured to concanavalin A (con-A), PPD and tetanus toxoid (TT) using a whole-blood 3H-thymidine incorporation assay. Stimulation indices were significantly lower after vaccination than before, in the case of con-A (p = 0.03) and TT (p = 0.01) in the Guinean children and in the case of PPD (p = 0.009) and TT (p = 0.03) in the Swedish children. Stimulation of lymphocytes from measles-immune children with measles antigens resulted in weak lymphoproliferative responses. These observations may be relevant to the increased mortality found in children immunized with high-titre measles vaccines, as compared to controls, in recent studies. The study confirms the applicability and usefulness under field conditions of the whole blood version of the thymidine incorporation assay.

 

Immunogenicity of high-titre AIK-C or Edmonston-Zagreb vaccines in 3.5-month-old infants, and of medium- or high-titre Edmonston-Zagreb vaccine in 6-month-old infants, in Kinshasa, Zaire.

Cutts,-F-T; Nyandu,-B; Markowitz,-L-E; Forsey,-T; Zell,-E-R; Othepa,-O; Wilkins,-K

Vaccine. 1994 Nov; 12(14): 1311-6

Vaccine-

The effect of measles vaccine potency was evaluated among 485 children aged 6 months, and the effect of vaccine strain was evaluated among 538 children aged 3.5 months, in Kinshasa, Zaire. Children aged 6 months were randomly assigned to receive either high-titre Edmonston-Zagreb (EZ-H), potency 5.7 log10/dose, or medium-titre EZ (EZ-M), potency 4.7 log10/dose, those aged 3.5 months were randomly assigned to receive either AIK-C, potency 5.5 log10/dose, or EZ-H, and were revaccinated with EZ-M vaccine at age 9.5 months. Measles antibodies were measured using the plaque reduction neutralization assay. Among children vaccinated at age 6 months, the seroresponse was significantly higher after EZ-H than EZ-M vaccine, with 92 and 83% seroconverting by 6 months postvaccination and 59 and 40% respectively having antibody titres > 200 mIU. Among children vaccinated at age 3.5 months, only 24% (AIK-C) and 22% (EZ-H) attained antibody titres > or = 200 mIU 6 months postvaccination. After revaccination at age 9.5 months, 81% of children in the AIK-C group and 73% in the EZ-H group had antibody levels > 200 mIU (p = 0.056). A retrospective survey was conducted in January 1993 to determine the mortality experience of vaccine groups, and information was obtained for 94% of the children. A total of 44 deaths (4%) were identified, with no significant differences between groups when stratified by age at vaccination.  Although high-titre EZ vaccine is immunogenic among 6-month-old children, this vaccine is no longer recommended for use because of the finding of increased mortality among recipients of this vaccine in other studies.  The efficacy of two doses of standard titre vaccine requires further study.

 

Increased mortality after high titer measles vaccines: too much of a good thing.

Halsey,-N-A

Pediatr-Infect-Dis-J. 1993 Jun; 12(6): 462-5

Pediatric-infectious-disease-journal,-The

From the article:  “In retrospect, I and other investigators were too easily convinced of the safety of high titer vaccines based on low rates of adverse events in the few weeks after vaccination.  At the time we had no reason to expect sex-specific delayed mortality after further attenuated vaccines.  We are attempting to minimize the impact of the high titer vaccines in the surviving children by providing nutritional supplementation and improved access to medical care.”

 

Immunizations in children.

Nicoll,-A; Begg,-N

Curr-Opin-Pediatr. 1993 Feb; 5(1): 60-7

Current-opinion-in-pediatrics

In 1992, there was a setback in measles vaccination for developing countries as high-titre vaccines were withdrawn following reports of excess mortality in vaccine recipients. The importance of continuing polio vaccination in industrialized countries was emphasized by an outbreak of paralytic polio among an unimmunized community in the Netherlands. Immunization programs are now increasingly using the Jeryl Lynn strain of mumps vaccine following reports of meningoencephalitis associated with the Urabe strain. A hepatitis A vaccine has become generally available and hepatitis B vaccine is being introduced into more childhood programs in countries where the disease is highly prevalent. Trials of group B meningococcal meningitis vaccines have yielded disappointing estimates of efficacy, particularly in younger children. Earlier reports of invasive bacterial infections after pertussis immunization have not been confirmed.

 

Immunologic parameters 2 years after high-titer measles immunization in Peruvian children.

Leon,-M-E; Ward,-B; Kanashiro,-R; Hernandez,-H; Berry,-S; Vaisberg,-A; Escamilla,-J; Campos,-M; Bellomo,-S; Azabache,-V; et-al.

J-Infect-Dis. 1993 Nov; 168(5): 1097-104

Journal-of-infectious-diseases,-The

Immunization with high-titer measles vaccines has been associated with excess mortality in children 2-4 years after vaccination. In this study, immunologic parameters in 64 Peruvian children who had been immunized an average of 27 months earlier with high-titer vaccines were compared with parameters in 76 recipients of low-titer vaccines. Delayed-type hypersensitivity, lymphocyte phenotype distributions by flow cytometry, and lymphoproliferation after phytohemagglutinin (PHA) stimulation were assessed. High-titer recipients had smaller indurations to tetanus, diphtheria, and Proteus (P < .05) antigens, decreased PHA stimulation (P = .04), and a lower percentage of CD4+ lymphocytes (P = .04) than low-titer recipients. After adjustment for sex, concurrent illnesses, and other variables in regression analyses, high-titer recipients had a lower percentage of CD4+ lymphocytes (P = .025) and decreased lymphocyte proliferation to PHA (P = .058). These results may provide a clue to the pathogenesis of delayed excess mortality after high-titer measles vaccination in some developing countries.

 

Expanded programme on immunization (EPI). Safety of high titre measles vaccines.

Anonymous

Wkly-Epidemiol-Rec. 1992 Nov 27; 67(48): 357-61

Weekly-epidemiological-record

Unexpected results suggesting decreased survival when compared with standard titre vaccine administered at 9 months of age have been found in some field studies evaluating the performance of high titre measles vaccine. Analytical difficulties have arisen because the studies were not specifically designed to measure survival. Nonetheless, careful analysis of the results from all of the high titre vaccine trials showed decreased survival of high titre vaccine recipients, in areas with high background mortality rates, compared with recipients of standard measles vaccines at 9 months. No systematic biases could be found in the studies to explain these differences. Statistical analysis of these data suggested that the findings were unlikely to be attributable to chance alone. The panel recommended that high titre measles vaccine derived from the original Edmonston measles vaccine isolate should no longer be recommended for use in immunization programmes. Further post-licensure field studies of new measles vaccines should take into account the results of these studies. Additional detailed epidemiological studies in populations that have received high titre vaccines and their controls were encouraged.

 

Comparison of high titer Edmonston-Zagreb, Biken-CAM and Schwarz measles vaccines in Peruvian infants.

Berry,-S; Hernandez,-H; Kanashiro,-R; Campos,-M; Azabache,-V; Gomez,-G; Gutierrez,-M; Weirs,-B; De-Quadros,-C; Halsey,-N

Pediatr-Infect-Dis-J. 1992 Oct; 11(10): 822-7

Pediatric-infectious-disease-journal,-The

In an effort to identify the optimal dose and strain of measles vaccination for early immunization, Peruvian infants were randomly assigned to receive one of three measles vaccines in varying doses at 5 to 6 or 8 to 9 months of age. Edmonston-Zagreb vaccines were significantly (P < 0.001) more immunogenic than equivalent or higher titers of Schwarz or Biken-CAM vaccines as determined by neutralization antibody response 3 months after vaccination. Eighty-two percent of infants who received high titer Edmonston-Zagreb vaccine at 5 to 6 months of age developed protective concentrations of measles antibody, a response rate similar to that observed after standard titer Schwarz (81%) or high titer Biken-CAM vaccine (81%) at 8 to 9 months of age. No significant differences in the rates of fever, rash or other adverse events were noted by vaccine group 10 to 14 days after vaccination. Although the high titer vaccines are more immunogenic in young infants than standard vaccines, long term safety must be assured before these vaccines can be put into widespread use.

Too bad this advice wasn’t followed. - SM

 

Child mortality after high-titre measles vaccines: prospective study in Senegal.

Garenne,-M; Leroy,-O; Beau,-J-P; Sene,-I

Lancet. 1991 Oct 12; 338(8772): 903-7

Lancet-

The use of Edmonston-Zagreb high-titre (EZ-HT) vaccine at age 6 months has been recommended for countries in which measles before the age of 9 months is a substantial cause of death, but little is known about the long-term effects of high-titre live measles vaccines given early in life. In a randomised vaccine trial in a rural area of Senegal, children were randomly assigned at birth to three vaccine groups: EZ-HT at 5 months (n = 336); Schwarz high-titre (SW-HT) at 5 months (n = 321); and placebo at 5 months followed by standard low-titre Schwarz vaccine at 10 months (standard: n = 358). All children were prospectively followed for 24-39 months in a well-established demographic surveillance system. Child mortality after immunisation was significantly higher in the two groups which received high-titre vaccines than in the group given the standard vaccine. The relative risk of death was 1.80 (95% confidence interval [CI] 1.18-2.74; p = 0.007) in the EZ-HT group and 1.51 (0.97-2.34; p = 0.07) in the SW-HT group compared with the standard group. The three vaccine groups were comparable as regards various social, family, and health characteristics, and there was no difference in mortality between children who received the standard vaccine and those who were eligible for the trial but did not take part for various reasons. The higher risk of death in the two high-titre vaccine groups remained significant in multivariate analyses. These findings suggest a need to reconsider the use of high-titre measles vaccines early in life in less developed countries.