The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production.

As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.

The effect of vitamin A supplementation administered with missing vaccines during national immunization days in Guinea-Bissau.

BACKGROUND: WHO recommends high-dose Vitamin A supplementation (VAS) at vaccination contacts after 6 months of age. It has not been studied whether the effect of VAS on mortality depends on the type of vaccine. We have hypothesized that VAS administered with measles vaccine (MV) is more beneficial than VAS with diphtheria-tetanus-pertussis (DTP) vaccine. We assessed the effect of VAS administered with different vaccines during national immunization days (NIDs). METHODS: In 2003, VAS was distributed during NIDs in Guinea-Bissau. Children 6 months or older were given VAS, and if they were missing vaccines, these were often given as well. We compared survival between children who had received VAS alone, VAS with DTP or DTP + MV, or VAS with MV. We also compared the survival between participants and non-participants. We followed 6- to 17-month old children until 18 months of age and analysed survival in Cox models. RESULTS: Twenty of 982 VAS-recipients died during follow-up. The mortality rate ratio (MRR) for VAS with DTP + MV or VAS with DTP was 3.43 (1.36-8.61) compared with VAS only. There were no deaths among those who received VAS with MV alone (P = 0.0005 for homogeneity of VAS effects). Children who received VAS with DTP had higher mortality than non-participants who did not receive VAS [MRR = 3.04 (1.31-7.07)]. CONCLUSION: The study design does not allow for definite conclusions. However, the results are compatible with our a priori hypothesis that VAS is more beneficial when given with MV and potentially harmful when given with DTP. Randomized trials testing the impact on mortality of the current WHO policy seem warranted.

Aerosol measles vaccination in macaques: preclinical studies of immune responses and safety.

The comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different routes of administration in the immunocompetent and the immunocompromised host. Immunogenicity and protective efficacy of aerosol vaccination using devices similar to those previously used in humans were comparable to those in animals vaccinated by injection. No evidence for a safety hazard associated with the route of vaccination was detected. The results of this study support further clinical evaluation of aerosol vaccination for measles.

[Reactions after MMR vaccination]. / Reaktioner efter MFR-vaccination.

Four months after introducing routine vaccination against measles, mumps and German measles (MMR-vaccination) in Denmark, a questionnaire study of reactions in vaccinated children was carried out. There were significantly fewer reactions in children who had previously developed immunity to measles, either by having had the disease or by vaccination. The reaction frequency after MMR-vaccination of children immune to measles was no greater than that after other vaccinations. Moreover, for all vaccinations, the frequency of reaction was found to decrease significantly with increasing age. The study suggests that a large proportion of the so-called reactions were not caused by vaccination, but were due to common viral infections occurring at random and concurrently with it. The reactions that arose in connection with MMR-vaccination are considered to be of minor importance when compared with often prolonged and more severe course of these diseases.