Live Measles Research Articles

Trends in varicella and mumps vaccination rates in children under 3 years of age in a tertiary children's hospital in Japan.

In Japan, the voluntary vaccination rate is not known accurately. Although two doses of the measles and rubella vaccines have been part of the universal vaccine program since 2006, the varicella vaccine was added in October 2014 while the mumps vaccine still remains voluntary. The aim of this study was to evaluate trends in the live measles, rubella, varicella and mumps vaccination rates in Japan. This retrospective cohort study was conducted at Tokyo Metropolitan Children's Medical Center between October 2012 and December 2016. Patients aged 1-2years who were admitted to the Department of General Pediatrics were enrolled. The trend in the vaccination rate against measles, rubella, varicella, and mumps was examined. The measles and rubella vaccination rate was 80-90%. The varicella vaccination rate in the second quarter of 2012, the third quarter of 2014, and the fourth quarter of 2016 was 34.6%, 67.1%, and 80.7%, respectively. The mumps vaccination rate in the second quarter of 2012, the third quarter of 2014, and the fourth quarter of 2016 was 27.6%, 59.5%, and 61.8%, respectively. The varicella and mumps vaccination rate improved until 2014 despite the fact that they were voluntary vaccinations. After varicella vaccination was added to the universal vaccination program, the varicella vaccination rate continued to improve. The mumps vaccination, which was not included, failed to improve, suggesting that the universal vaccination program contributed to increasing the uptake of the vaccines it includes.

ДЕЙСТВИЕ КОРЕВОЙ ВАКЦИНЫ НА СОЗРЕВАНИЕ ДЕНДРИТНЫХ КЛЕТОК ЧЕЛОВЕКА IN VITRO

The most important means of measles control is live measles vaccine, the high epidemiological effectiveness of which is confirmed by half a century of its use. There is a question of the need to further improve the effectiveness of vaccine prophylaxis, in particular, by increasing the immunogenicity of the used vaccine given the increase in the morbidity of measles in recent years. Investigation of effect features of existing vaccine variants is necessary to identify possible ways to increase their immunogenicity. We investigated the effect of measles culture live vaccine on the maturation of human dendritic cells – the most specialized antigen-presenting cells involved in the induction of an immune response. In vitro incubation of monocytic derived immature dendritic cells with the vaccine initiates the process of their partial maturation, which is manifested in an increase in the number of cells carrying molecules CD86, CD83 and ICOSL (CD275).At the same time they have a reduced expression level of the HLA-DR molecule and chemokine receptors CCR7 and CXCR5 involved in the migration of dendritic cells to peripheral lymphoid organs. In our opinion, the relative weak side of measles vaccine effect on dendritic cell maturation is a factor limiting the immunogenicity of the vaccine, which must be taken into account when developing new measles vaccines.

The risk of non-specific hospitalised infections following MMR vaccination given with and without inactivated vaccines in the second year of life. Comparative self–controlled case-series study in England

Observational cohort studies in high-income settings have suggested that vaccination order may affect children’s subsequent risk of a heterologous infection, with live vaccines reducing and inactivated vaccines (given on their own or with a live vaccine), increasing the risk. We used the self-controlled case-series method, which automatically controls for the individual level confounding to which such cohort studies are prone, to test this hypothesis. We compared the relative incidence (RI) of infections post-vaccination in two calendar periods in England; in Period 1 (September 2002–August 2006) live measles, mumps, rubella (MMR) vaccine was given on its own and in Period 2 (September 2006–April 2010) inactivated vaccines (7-valent pneumococcal conjugate vaccine (PCV7) and sometimes the combined Haemophilus influenzae type b/meningococcal group C vaccine (Hib-MenC)) were given concomitantly with MMR. Admissions for an infection of the upper or lower respiratory tract, gastrointestinal system or other site in children aged 11–23 months were selected from the Hospital Episode Statistics database in England and linked to child health immunisation histories. The analysis included a total of 24,144 infections in 21,067 children in Period 1 and 36,880 in 31,616 children in Period 2. The RI of admission for any infection in Period 1 was 1.00 (95% confidence interval 0.95–1.06) compared with 0.95 (95% confidence interval 0.90–1.00) in Period 2. Comparing the two periods showed no evidence of a difference in the relative incidence estimates with a ratio of RI of 0.94 (95% confidence interval 0.87–1.02), RIs within 90 days of vaccination were 0.94 (0.91–0.97) in Period 1 and 0.94 (0.91–0.97) in Period 2, consistent with a temporary healthy vaccinee effect. In conclusion, we found no evidence to support the hypothesis that there is a reduction in heterologous infections after MMR on its own or an increase after MMR given concomitantly with an inactivated vaccine.

Cohort profile : Bandim Health Project’s (BHP) rural Health and Demographic Surveillance System (HDSS)—a nationally representative HDSS in Guinea-Bissau

PurposeBandim Health Project (BHP) monitors health and survival of women and children in a nationally representative rural Health and Demographic Surveillance System (HDSS) in Guinea-Bissau. The HDSS was set up...

Measles vaccination of children born to HIV-infected mothers (clinical and immunological aspects)

Vaccination of children born to HIV-infected mothers in accordance with the national Calendar of preventive vaccinations represents an important issue. Upon that, measles incidence rate especially among unvaccinated children has been substantially elevated. Use of live measles vaccine in both HIV-infected children and mothers has some features primarily due to HIV-associated immunocompromised state that was poorly investigated. Here we monitored 212 children aged 12–36 months born to HIV-infected women, 184 HIV-negative children born to HIVinfected women who were included into the group with the diagnosis “Perinatal HIV contact” (R75) after verification. In addition, 28 children were included into the group” HIV infection “(B23), whereas 42 children — into the control group. Live measles vaccine was administered subcutaneously at a dose of 0.5 ml. All children were followed up for 36 weeks. HIV status, measles antibodies level by measured by ELISA and RPG methods, as well as total immunoglobulin A, M, G classes and CD3+, CD4+, CD8+, CD19+ lymphocyte counts were examined. No post-vaccination complications or severe vaccine-induced reactions were reported in HIV-infected patients group. A satisfactory course of the vaccine process in all children born to HIV-infected mothers was observed that did not significantly differ from that one in control group. Children with perinatal HIV contact are able to respond adequately to vaccination with live measles vaccine. The number of children with conditionally protective antibody levels, still remaining seronegative among children with perinatal HIV contact (R75) was comparable to that one in healthy control group. At the same time, children with perinatal HIV contact were shown to display protective antibody level after administering live measles vaccine only in 36.4% of cases, whereas the remainder (63.6%) demonstrated a conditionally protective antibody level or lack it (compared to 76% of children with perinatal HIV contact). Children with perinatal HIV infection who did not respond to the first administered live measles vaccine produced low amount of antibodies after re-vaccination. Seroconversion was observed in up to 68% of cases, whereas protective antibody level was found in up to 33.6% of child ren. On the contrary, children from the perinatal HIV contact group were shown to have protective antibody level in 69.6% of cases upon seroconversion rate reaching 91.3% that did not differ them from those in control group. In the post-vaccination period, suppressive modality of immune reaction tended to increase indirectly evidenced by increased percentage of CD8+ T cell subset.

The Epidemic Process of Measles with Different Strategies of Vaccination in a Large Industrial Center of the Middle Urals

Relevance. Measles infection still does not lose its relevance, as experts everywhere register outbreaks of the disease. The aim of the study is characterization of the measles epidemic process in the context of different strategies for its vaccination in a large industrial city to make adequate management decisions.Materials and methods. The authors used the data of statistical reports on measles incidence in Yekaterinburg in 1950–2017 as the study materials. The authors analyzed data for six periods: pre-vaccination (1950–1961), selective immunization (1962–1965), routine vaccination of children under 8 years (1966–1972), vaccination of children under 14 years (1973–1986), the introduction of mass revaccination of children (1987–2001) and the period of universal vaccination at the stage of elimination of infection (2002–2017).Results. In the pre-vaccination period, the average annual incidence rate was 1381.7 ± 162.9 per 100 ths population, the seasonal increase in the incidence was in december–may, in the structure of age groups dominated by children. During the period of selective immunization, at the stage of testing of the domestic vaccine, there was a slight decrease in the incidence to 1082.8 ± 189.1 per 100 ths population, intra-annual dynamics and age distribution of patients remained virtually unchanged. During routine vaccination of children up to 8 years of age, there was a significant reduction in the incidence to the level of 219.8 ± 110.8 per 100 ths population , which was observed in almost all age groups, with the exception of children 10–14 years and adults. Seasonal manifestations of the epidemic process were similar to previous periods. With an increase in the cohort for vaccination at the expense of children up to 14 years, there was a further decrease in the incidence to 89.9 ± 39.1 per 100 ths population, but in some years measles outbreaks were registered, with an active spread of infection among schoolchildren in educational institutions. The decision to introduce a second vaccination for 6-year olds before school made it possible to achieve a sporadic level of morbidity and to change the main parameters characterizing the epidemic process in all previous periods. The epidemic process has become intermittent. Periodic rises disappeared. When the infection was not spread, the population immunity and vaccination rates were consistent with the recommendations of who experts. However, against this background, 2016 was registered a major outbreak of measles.Conclusion. The use of different tactics of vaccination led to significant changes in the parameters of the epidemic process of measles. However, at the present stage immunization schemes do not control the situation. In this regard, it is necessary to raise the issue of introduction of revaccination against adult measles every 10 years, as well as changes in the antigenic composition of the live measles vaccine, taking into account data on circulating strains of the virus of genetic lines D and H.

Maternal Priming: Bacillus Calmette-Guérin (BCG) Vaccine Scarring in Mothers Enhances the Survival of Their Child With a BCG Vaccine Scar.

Maternal priming might enhance the beneficial nonspecific effects (NSEs) of live measles vaccination (MV). Children with a bacillus Calmette-Guérin (BCG) vaccine scar have a lower mortality rate than those without a scar that is not explained by protection against tuberculosis. We examined the hypothesis that BCG scarring would have a stronger effect on a child if the mother also had a BCG scar. In a randomized controlled trial (RCT) of early MV in children aged 4.5 months, the BCG-scar status of the children and their mother were registered at enrollment at 4.5 months of age. The children were followed up until they were 36 months of age. Using a Cox proportional hazards model, we compared mortality rate ratios according to maternal and child BCG-scar status after adjusting for where the BCG vaccine was given (the national hospital or elsewhere). We censored for other interventions that have immunomodulating effects on child survival, including neonatal vitamin A supplementation and early MV. A total of 2213 children had not received neonatal vitamin A supplementation and early MV; 83% of these children and 44% of the mothers had a BCG scar. Children whose mother had a BCG scar were not more likely to have a BCG scar than those whose mother did not have a BCG scar (risk ratio, 1.01 [95% confidence interval (CI), 0.98-1.05]). Among the children, having a BCG scar was associated with a 41% (95% CI, 5%-64%) lower mortality between the ages of 4.5 and 36 months. The reduction in mortality was 66% (95% CI, 33%-83%) if the mother also had a BCG scar but only 8% (95% CI, -83% to 53%) if the mother had no BCG scar (test of interaction, P = .04). Maternal BCG priming might be important for the effect of BCG vaccination on child survival. Ensuring better BCG vaccine scarring among mothers and children could have a considerable effect on child mortality levels.

Non-live pentavalent vaccines after live measles vaccine may increase mortality

Live measles vaccine (MV) may have beneficial off-target/non-specific effects (NSEs) reducing child mortality beyond prevention of measles infection. In contrast, the non-live pentavalent (Diphtheria-Tetanus-Pertussis-H. influenzae Type B-Hepatitis B) vaccine has no beneficial NSEs. The NSEs are strongest for the most recent vaccine. Hence, sequence of vaccination may affect survival. In Guinea-Bissau, we followed 7094 measles-vaccinated children prospectively from first home visit after 9 months (when MV is scheduled) to 5 years of age. We compared survival by sequence of MV and third Pentavalent vaccine (Penta3; scheduled at 3½ months) in Cox proportional-hazards models. Compared with being vaccinated in-sequence (Penta3-then-MV), having received out-of-sequence Penta3-after-MV before the visit was associated with an adjusted Hazard Ratio (aHR) of 1.19 (95%CI: 0.84–1.69); Receiving missing Penta doses on the visit date tended to be associated with higher mortality (aHR = 1.87 (0.96–3.65)) while not receiving missing doses of Penta was not (aHR = 0.93 (0.57–1.54)), test for interaction p = 0.09.

Revaccination With Measles-Mumps-Rubella Vaccine and Infectious Disease Morbidity: A Danish Register-based Cohort Study.

It has been hypothesized that revaccination with live vaccines is associated with reductions in off-target morbidity and mortality. We examined if revaccination with the live measles, mumps, and rubella vaccine (MMR) is associated with a lower rate of off-target infections. We performed a register-based nationwide cohort study that included 295559 children born in Denmark from April 2004 to December 2010. The cohort were followed from age 47 months (1 month before turning age 4 years, which is the recommended age of the second MMR [MMR-2]) until age 60 months. In Cox regression, we estimated adjusted incidence rate ratios (aIRRs) of antibiotic prescriptions and hospital admissions for any infection comparing MMR-2 as most recent vaccine with not having MMR-2 as the most recent vaccine. There was no association between MMR-2 and antibiotic prescriptions (aIRR, 1.01; 95% confidence interval [CI], 0.99-1.02). The aIRR for the association between MMR-2 and admissions for infection of any duration was 0.93 (95% CI, 0.88-0.98). For admissions for infection lasting 0 to 1 day, the aIRR was 0.97 (95% CI, 0.90-1.03) compared with the aIRR of 0.84 (95% CI, 0.74-0.95) for admissions for infection lasting 2 days or longer (test for equality of aIRRs, P = .039). In this study, revaccination with MMR appeared safe in relation to off-target infections and was associated with a lower rate of severe off-target infections. More studies of the possible association between revaccination with live attenuated vaccines and off-target infections are needed.

National Immunization Campaigns with Oral Polio Vaccine Reduce All-Cause Mortality: A Natural Experiment within Seven Randomized Trials.

A recent WHO review concluded that live BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs) reducing mortality from non-targeted diseases. NSEs of oral polio vaccine (OPV) were not examined. If OPV vaccination campaigns reduce the mortality rate, it would suggest beneficial NSEs. Between 2002 and 2014, Guinea-Bissau had 15 general OPV campaigns and other campaigns with OPV plus vitamin A supplementation (VAS), VAS-only, MV, and H1N1 vaccine. In this period, we conducted seven randomized controlled trials (RCTs) with mortality as main outcome. Within these RCTs, we assessed whether the mortality rate was lower after-campaign than before-campaign. We used Cox models with age as underlying time and further adjusted for low birth-weight, season and time trend in mortality. We calculated the adjusted mortality rate ratio (MRR) for after-campaign vs before-campaign. The mortality rate was lower after OPV-only campaigns than before, the MRR being 0.81 (95% CI = 0.68-0.95). With each additional dose of campaign-OPV the mortality rate declined further (MRR = 0.87 (95% CI: 0.79-0.96) per dose) (test for trend, p = 0.005). No other type of campaign had similar beneficial effects. Depending on initial age and with follow-up to 3 years of age, the number needed to treat with campaign-OPV-only to save one life was between 68 and 230 children. Bissau had no case of polio infection so the results suggest that campaign-OPV has beneficial NSEs. Discontinuation of OPV-campaigns in low-income countries may affect general child mortality levels negatively.

Genome-wide associations of CD46 and IFI44L genetic variants with neutralizing antibody response to measles vaccine.

Population-based studies have revealed 2-10% measles vaccine failure rate even after two vaccine doses. While the mechanisms behind this remain unknown, we hypothesized that host genetic factors are likely to be involved. We performed a genome-wide association study of measles specific neutralizing antibody and IFNγ ELISPOT response in a combined sample of 2872 subjects. We identified two distinct chromosome 1 regions (previously associated with MMR-related febrile seizures), associated with vaccine-induced measles neutralizing antibody titers. The 1q32 region contained 20 significant SNPs in/around the measles virus receptor-encoding CD46 gene, including the intronic rs2724384 (p value=2.64×10-09) and rs2724374 (p value=3.16×10-09) SNPs. The 1q31.1 region contained nine significant SNPs in/around IFI44L, including the intronic rs1333973 (p value=1.41×10-10) and the missense rs273259 (His73Arg, p value=2.87×10-10) SNPs. Analysis of differential exon usage with mRNA-Seq data and RT-PCR suggests the involvement of rs2724374 minor G allele in the CD46 STP region exon B skipping, resulting in shorter CD46 isoforms. Our study reveals common CD46 and IFI44L SNPs associated with measles-specific humoral immunity, and highlights the importance of alternative splicing/virus cellular receptor isoform usage as a mechanism explaining inter-individual variation in immune response after live measles vaccine.

A novel kindred with inherited STAT2 deficiency and severe viral illness

A novel kindred with inherited STAT2 deficiency and severe viral illness

Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: A nationwide register based cohort study

BackgroundIn Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions. MethodsNationwide, retrospective, register based cohort study of 520,859 children born in Denmark 1997–2006, who were followed from 15months to 4years of age. Incidence rate ratios (IRRs) of hospital admissions were estimated by Cox regression and adjusted for background factors including exact age. ResultsBy 2years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13–1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0–15%) increase in infectious disease admissions. ConclusionsSimultaneous administration of MMR and DTaP-IPV-Hib compared with MMR alone may increase the rate of hospital admissions related to lower respiratory tract infections. These findings require replication in other high-income settings.

A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency

A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency

Heterologous and sex differential effects of administering vitamin A supplementation with vaccines.

WHO recommends high-dose vitamin A supplementation (VAS) to children from 6 months to 5 years of age in low-income countries, in order to prevent and treat vitamin A deficiency-associated morbidity and mortality. The current policy does not discriminate this recommendation either by sex or vaccination status of the child. There is accumulating evidence that the effects of VAS on morbidity, mortality and immunological parameters depend on concomitant vaccination status. Moreover, these interactions may manifest differently in males and females. Certain vaccines administered through the Expanded Program on Immunization have been shown to alter all-cause mortality from infections other than the vaccine-targeted disease. This review summarizes the evidence from observational studies and randomized-controlled trials of the effects of VAS on these so-called heterologous or non-specific effects of vaccines, with a focus on sex differences. In general, VAS seems to enhance the heterologous effects of vaccines, particularly for diphtheria-tetanus-pertussis and live measles vaccines, where some studies, although not unanimously, show a stronger interaction between VAS and vaccination in females. We suggest that vaccination status and sex should be considered when evaluating the effects of VAS in early life.

Measles–mumps–rubella vaccination and respiratory syncytial virus-associated hospital contact

BackgroundThe live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles–mumps–rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association was strongest for admissions with lower respiratory infections. ObjectiveTo examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. MethodsNationwide cohort study of laboratory-confirmed RSV hospital contacts at age 14–23 months in all children born in Denmark 1997–2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months. ResultsThe study included 888 RSV hospital contacts in 128,588 person years of follow up (rate 6.8/1000 person years). Having MMR as the most recent vaccine was associated with a reduced rate of RSV hospital contacts compared with having DTaP-IPV-Hib as the most recent vaccine (Incidence rate ratio (IRR), 0.75; 95% confidence interval (CI), 0.63–0.89). After adjustment for potential confounders including exact age in days the IRR was 0.78 (95% CI, 0.66–0.93). The adjusted IRR was 0.74 (95% CI, 0.60–0.92) in males and 0.84 (95% CI, 0.66–1.06) in females (P Interaction, 0.42). There was no association in the first month after MMR vaccination (adjusted IRR, 0.97; 95% CI, 0.76–1.24) but the adjusted IRR was 0.70 (95% CI, 0.58–0.85) from one month after MMR vaccination. ConclusionsMMR vaccination was associated with reduced rate of hospital contacts related to laboratory-confirmed RSV infection. Further research on the association between MMR vaccination and other unrelated pathogens are warranted.

High-dose vitamin A with vaccination after 6 months of age: a randomized trial.

The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortality. We conducted a randomized double-blind trial to evaluate the effect of VAS with vaccines. We randomized children aged 6 to 23 months 1:1 to VAS (100000 IU if aged 6-11 months, 200000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by gender and vaccine. Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up 80 nonaccident deaths occurred (VAS: 38; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.91 (95% confidence interval 0.59-1.41) and differed significantly between boys (MRR 1.92 [0.98-3.75]) and girls (MRR 0.45 [0.24-0.87]) (P = .003 for interaction between VAS and gender). At enrollment, 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines, and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group. This is the first randomized controlled trial to assess the effect of the policy on overall mortality. VAS had no overall effect, but the effect differed significantly by gender. More trials to ensure an optimal evidence-based vitamin A policy are warranted.

Live Vaccine Against Measles, Mumps, and Rubella and the Risk of Hospital Admissions for Nontargeted Infections

In low-income countries, live measles vaccine reduces mortality from causes other than measles infection. Such nonspecific effects of vaccines might also be important for the health of children in high-income settings. To examine whether the live vaccine against measles, mumps, and rubella (MMR) is associated with lower rates of hospital admissions for infections among children in Denmark. Population-based cohort study of Danish children born 1997-2006 and followed up from ages 11 months to 2 years (last follow-up, August 31, 2008). Nationwide Danish registers provided data on vaccinations and hospital admissions. The recommended vaccination schedule was inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12 months and MMR at age 15 months. Incidence rate ratios (IRRs) of hospital admissions for any infection, comparing receipt of MMR vs DTaP-IPV-Hib as the most recent vaccine. Risks, risk difference, and number needed to vaccinate were calculated for receiving MMR on time. The study included 495,987 children contributing with 56,889 hospital admissions for any type of infection during 509,427 person-years (rate, 11.2 per 100 person-years). For the 456,043 children who followed the recommended schedule and received MMR after the third dose of DTaP-IPV-Hib, MMR (rate, 8.9 per 100 person-years) vs the third dose of DTaP-IPV-Hib (rate, 12.4 per 100 person-years) as the most recent vaccine was associated with an adjusted IRR of 0.86 (95% CI, 0.84-0.88) for any admission for infection. There were 19,219 children immunized out of sequence. The adjusted IRR was 0.87 (95% CI, 0.80-0.95) for those receiving MMR (rate, 9.9 per 100 person-years) after the second dose of DTaP-IPV-Hib (rate, 15.1 per 100 person-years). However, in the 1981 children who subsequently received the third dose of DTaP-IPV-Hib (rate, 12.8 per 100 person-years) after MMR, the IRR for hospital admissions for infection was significantly greater (adjusted IRR, 1.62 [95% CI, 1.28-2.05]). The risk of admission for an infection between ages 16 months and 24 months was 4.6% (95% CI, 4.5%-4.7%) for receiving MMR on time and 5.1% (95% CI, 5.0%-5.2%) for not receiving MMR on time. The risk difference was 0.5 percentage point (95% CI, 0.4-0.6), and the number needed to vaccinate with MMR before age 16 months to prevent 1 admission for any infection was 201 (95% CI, 159-272). In a cohort of Danish children, receipt of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated with a lower rate of hospital admissions for any infections. These findings require replication in other high-income populations.

Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein

The recent identification of a novel human coronavirus responsible of a SARS-like illness in the Middle-East a decade after the SARS pandemic, demonstrates that reemergence of a SARS-like coronavirus from an animal reservoir remains a credible threat. Because SARS is contracted by aerosolized contamination of the respiratory tract, a vaccine inducing mucosal long-term protection would be an asset to control new epidemics. To this aim, we generated live attenuated recombinant measles vaccine (MV) candidates expressing either the membrane-anchored SARS-CoV spike (S) protein or its secreted soluble ectodomain (Ssol). In mice susceptible to measles virus, recombinant MV expressing the anchored full-length S induced the highest titers of neutralizing antibodies and fully protected immunized animals from intranasal infectious challenge with SARS-CoV. As compared to immunization with adjuvanted recombinant Ssol protein, recombinant MV induced stronger and Th1-biased responses, a hallmark of live attenuated viruses and a highly desirable feature for an antiviral vaccine.

Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau

BackgroundStudies from low-income countries indicate that co-administration of inactivated diphtheria–tetanus–pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP–H. Influenza type B–Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. MethodsIn 2007–2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6–23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. ResultsWhile DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20–8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79–33.4). ConclusionIn line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality.