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1.
Epidemiol Infect ; 149: e75, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33722335

RESUMO

We investigated whether countries with higher coverage of childhood live vaccines [BCG or measles-containing-vaccine (MCV)] have reduced risk of coronavirus disease 2019 (COVID-19)-related mortality, while accounting for known systems differences between countries. In this ecological study of 140 countries using publicly available national-level data, higher vaccine coverage, representing estimated proportion of people vaccinated during the last 14 years, was associated with lower COVID-19 deaths. The associations attenuated for both vaccine variables, and MCV coverage became no longer significant once adjusted for published estimates of the Healthcare access and quality index (HAQI), a validated summary score of healthcare quality indicators. The magnitude of association between BCG coverage and COVID-19 death rate varied according to HAQI, and MCV coverage had little effect on the association between BCG and COVID-19 deaths. While there are associations between live vaccine coverage and COVID-19 outcomes, the vaccine coverage variables themselves were strongly correlated with COVID-19 testing rate, HAQI and life expectancy. This suggests that the population-level associations may be further confounded by differences in structural health systems and policies. Cluster randomised studies of booster vaccines would be ideal to evaluate the efficacy of trained immunity in preventing COVID-19 infections and mortality in vaccinated populations and on community transmission.


Assuntos
/imunologia , Imunidade Inata/imunologia , Cobertura Vacinal/estatística & dados numéricos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Assistência à Saúde/normas , Assistência à Saúde/estatística & dados numéricos , Humanos , Imunização Secundária/normas , Imunização Secundária/estatística & dados numéricos , Modelos Lineares , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Qualidade da Assistência à Saúde/normas , Qualidade da Assistência à Saúde/estatística & dados numéricos
2.
Nat Commun ; 12(1): 132, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420104

RESUMO

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.


Assuntos
Poluentes Ambientais/efeitos adversos , Feto/imunologia , Exposição Materna/efeitos adversos , Sarampo/sangue , Praguicidas/efeitos adversos , Adulto , Anticorpos Antivirais/sangue , Pré-Escolar , Ensaios Clínicos Fase III como Assunto , Feminino , Sangue Fetal/química , Seguimentos , Humanos , Sistema Imunitário/efeitos dos fármacos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Malária/prevenção & controle , Troca Materno-Fetal/imunologia , Sarampo/imunologia , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Controle de Mosquitos/métodos , Praguicidas/análise , Fenilcarbamatos/efeitos adversos , Fenilcarbamatos/análise , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
BMC Infect Dis ; 20(1): 481, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32635891

RESUMO

BACKGROUND: Ethiopia has low measles immunization coverage and little is known about the disparities surrounding what coverage is provided. This study assessed disparities in measles immunization and its change over time using the four Ethiopia Demographic and Health Surveys conducted between 2000 and 2016. METHODS: This is a cross-sectional analysis of data using Ethiopia Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. We used the World Health Organization's (WHO) Health Equity Assessment Toolkit (HEAT) to present the inequalities. Four measures of inequality were calculated: Difference (D), Ratio (R), Population Attributable Fraction (PAF) and Population Attributable Risk (PAR). The results were disaggregated by wealth, education, residence, sex and sub-national regions and 95% Uncertainty Intervals (UIs) were computed for each point estimate to boost confidence of the findings. RESULTS: Measles immunization coverage was higher among the richest and secondary and above schools' subgroup by nearly 30 to 31 percentage points based on point estimates (D = 31%; 95% CI; 19.48, 42.66) and 29.8 percentage points (D = 29.8%; 95% CI; 16.57, 43.06) as compared to the poorest and no education subgroup respectively in the 2016 survey. Still, in the 2016 survey, substantial economic status (PAF = 36.73; 95%CI: 29.78, 43.68), (R = 1.71; 95%CI: 1.35, 2.08), education status (PAF = 45.07; 95% CI: 41.95, 48.18), (R = 1.60; 95% CI: 1.30, 1.90), place of residence (PAF = 39.84, 95% CI: 38.40, 41.27), (R = 1.47, 95% CI: 1.20, 1. 74) and regional (PAF = 71.35, 95% CI: 31.76, 110.95), (R = 3.09, 95%CI: 2.01, 4.17) inequality were observed with both simple and complex measures. There was no statistically significant difference in the prevalence of measles immunization between male and female children in all the studied years, as indicated, for instance, by measures of PAF in 2000 (PAF = 0; 95%CI: - 6.79, 6.79), 2005 (PAF = 0; 95%CI: - 6.04, 6.04), 2011(PAF = 0; 95%CI: - 3.79, 3.79) and 2016 (PAF = 2.66; - 1.67; 6.99). Overall, the inequality of measles immunization narrowed significantly by at least some of the measures between the first and the last survey periods across all the studied subgroups. CONCLUSIONS: National, regional and district levels of government should make a pledge to reduce inequalities in coverage of measles immunization. Equity-sensitive strategies, sufficient human and financial resources as well as continued research and monitoring of immunization coverage inequalities are necessary to achieve related sustainable development goals.


Assuntos
Disparidades em Assistência à Saúde/tendências , Vacina contra Sarampo/uso terapêutico , Sarampo/epidemiologia , Sarampo/prevenção & controle , Cobertura Vacinal/economia , Cobertura Vacinal/tendências , Vacinação/tendências , Criança , Pré-Escolar , Estudos Transversais , Etiópia/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Masculino , Sarampo/virologia , Vacina contra Sarampo/imunologia , Morbillivirus/imunologia , Pobreza , Inquéritos e Questionários , Organização Mundial da Saúde
4.
BMC Infect Dis ; 20(1): 251, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32223757

RESUMO

BACKGROUND: The objectives of this review were to evaluate the effect of age at administration of the first dose of a measles-containing vaccine (MCV1) on protection against measles and on antibody response after one- and two-dose measles vaccinations. METHODS: We conducted a systematic review of the PubMed/MEDLINE, Embase, Web of Science and Cochrane databases (1964-2017) to identify observational studies estimating vaccine effectiveness and/or measles attack rates by age at first vaccination as well as experimental studies comparing seroconversion by age at first vaccination. Random effect models were used to pool measles risk ratios (RR), measles odds ratios (OR) and seroconversion RR of MCV1 administered at < 9, 9-11 or ≥ 15 months compared with 12 or 12-14 months of age. RESULTS: We included 41 and 67 studies in the measles protection and immunogenicity analyses. Older age at MCV1, from 6 to ≥15 months, improved antibody response and measles protection among one-dose recipients. Pooled measles RR ranged from 3.56 (95%CI: 1.28, 9.88) for MCV1 at < 9 months to 0.48 (95%CI: 0.36, 0.63) for MCV1 at ≥15 months, both compared to 12-14 months. Pooled seroconversion RR ranged from 0.93 (95%CI: 0.90, 0.96) for MCV1 at 9-11 months to 1.03 (95%CI: 1.00, 1.06) for MCV1 at ≥15 months, both compared to 12 months. After a second dose, serological studies reported high seropositivity regardless of age at administration of MCV1 while epidemiological data based on few studies suggested lower protection with earlier age at MCV1. CONCLUSIONS: Earlier age at MCV1 decreases measles protection and immunogenicity after one dose and might still have an impact on vaccine failures after two doses of measles vaccine. While two-dose vaccination coverage is most critical to interrupt measles transmission, older age at first vaccination may be necessary to keep the high level of population immunity needed to maintain it.


Assuntos
Esquemas de Imunização , Vacina contra Sarampo/imunologia , Vacina contra Sarampo/uso terapêutico , Sarampo/prevenção & controle , Fatores Etários , Idoso , Humanos , Lactente , Sarampo/epidemiologia , Estudos Observacionais como Assunto , Razão de Chances
6.
BMC Infect Dis ; 20(1): 197, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32138688

RESUMO

BACKGROUND: The incidence rate of measles in China reached a nadir in 2012 after 2 supplementary immunization activities (SIAs) were undertaken in 2009 and 2010. However, the disease began re-emerging in 2013, with a high prevalence rate observed in 2013-2014 in the southern province of Guangdong. In this study, we assessed the changes that occurred in measles epidemiology during 2009-2016, particularly between 2009 and 2011 (when the influence of the SIAs were in full effect) and between 2012 and 2016 (when this influence subsided). METHODS: Data from 22,362 patients with measles diagnosed between 2009 and 2016, and whose diagnoses were confirmed clinically and/or with laboratory testing, were extracted from the National Infectious Disease Monitoring Information System. Descriptive analyses were performed, and changes in epidemiological characteristics between 2009 and 2011 and 2012-2016 were compared. RESULTS: There was a substantial surge in 0-8-month-old patients after 2012; the incidence rate increased from 4.0 per 100,000 population in 2011 (10.3% of the total) to 280 per 100,000 population in 2013 (32.8% of the total). Patients aged 0-6 years represented 73.4% of the total increase between 2011 and 2013. Compared with 2009-2011, adults aged ≥25 years accounted for a higher proportion of patients in 2013 and after (p < 0.01), and were highest in 2016 (31% of the patient total). CONCLUSION: Despite the remarkable results achieved by SIAs in terms of providing herd immunity, the 2013 resurgence of measles revealed insufficient immunization coverage among children. Therefore routine immunization programs should be strengthened, and supplementary vaccinations targeting adults should also be contemplated.


Assuntos
Sarampo/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Imunidade Coletiva , Programas de Imunização/métodos , Programas de Imunização/tendências , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/imunologia , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Estudos Retrospectivos , Cobertura Vacinal/estatística & dados numéricos , Cobertura Vacinal/tendências , Adulto Jovem
8.
Am J Trop Med Hyg ; 102(1): 164-176, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769388

RESUMO

Accurate and cost-effective identification of areas where co-endemic infections occur would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots collected during cross-sectional lymphatic filariasis surveys in coastal Kenya were used for exploratory integrated detection of IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp., Ascaris lumbricoides, and Strongyloides stercoralis) as well as for detection of responses to immunizing agents used against vaccine-preventable diseases (VPDs) (measles, diphtheria, and tetanus) using a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against filarial antigens were generally higher in Ndau Island (P < 0.0001), which also had the highest prevalence of filarial antigenemia compared with other communities. Antibody responses to the Plasmodium species antigens circumsporozoite protein (CSP) and merozoite surface protein-1 (MSP-1)19 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (P < 0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against S. mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to VPDs. Seroprotection to tetanus was generally lower in Kwale County than in other counties. This study has demonstrated that MBA holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Anticorpos Antiprotozoários/sangue , Imunoglobulina G/sangue , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/imunologia , Estudos Soroepidemiológicos , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Difteria/prevenção & controle , Vacina contra Difteria e Tétano/imunologia , Humanos , Quênia , Sarampo/prevenção & controle , Vacina contra Sarampo/imunologia , Tétano/prevenção & controle
10.
Tohoku J Exp Med ; 249(4): 265-273, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31852852

RESUMO

In Japan, some measles outbreaks were initiated by a tourist from oversea and foreign workers recently. Moreover, rubella outbreak emerged since July 2018 mainly in the South Kanto, and the outbreak is currently ongoing in 2019. It is important to maintain a high measles-rubella combined vaccine (MR) coverage for measles-rubella control. Vaccination coverage for the second dose of MR (MR2) is 90.8% in Tokyo in 2016, which was the third worst among all prefectures in Japan. The purpose of this study was to clarify determinant factors of vaccination coverage for MR2 in Tokyo. Data were obtained for 49 wards and cities in Tokyo in 2016. We regressed vaccination coverage of MR2 on the times of notification by mail, the proportion of households receiving welfare payments, and the proportion of non-Japanese elementary school students. In addition to the simplest specification, five factors were included separately as explanatory variables: the proportion of public health nurses; the ratio of the number of pediatric medical facilities to the number of preschool and elementary school children; the moving-in rate; the proportion of households with a single parent; and the proportion of households with husband and wife both working. Results show that a high proportion of households receiving welfare payments, notification by two or more letters, and moving-in rate or a lower proportion of non-Japanese elementary school students improve coverage. In conclusion, the health authorities can exert efforts to reduce burden of time spent for vaccination and provide sufficient information to improve coverage.


Assuntos
Vacina contra Sarampo/imunologia , Vacina contra Rubéola/imunologia , Cobertura Vacinal , Criança , Pré-Escolar , Relação Dose-Resposta Imunológica , Humanos , Fatores de Tempo , Tóquio
11.
Pediatrics ; 144(6)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31753911

RESUMO

BACKGROUND: Infants are often assumed to be immune to measles through maternal antibodies transferred during pregnancy and, in many countries, receive their first measles-containing vaccine at 12 to 15 months. Immunity may wane before this time in measles-eliminated settings, placing infants at risk for measles and complications. We investigated humoral immunity to measles in infants <12 months of age in Ontario, Canada. METHODS: We selected sera collected at a tertiary pediatric hospital from infants <12 months who were born at ≥37 weeks' gestational age. We excluded infants with conditions that affect antibody levels. We selected ≤25 sera from 8 predetermined age bands and tested them for measles-neutralizing antibody using the plaque-reduction neutralization test. We calculated the proportion immune at each age band, and predictors of infant susceptibility were assessed by using multivariable logistic regression and Poisson regression. RESULTS: Of 196 infant sera, 56% (110 of 196) were from boys, and 35% (69 of 196) were from infants with underlying medical conditions. In the first month, 20% (5 of 25) of infants had antibodies below the protective threshold, which increased to 92% (22 of 24) by 3 months. By 6 months, all infants had titers below the protective threshold. In a multivariable analysis, infant age was the strongest predictor of susceptibility (odds ratio = 2.13 for each additional month increase; 95% confidence interval: 1.52-2.97). CONCLUSIONS: Most infants were susceptible to measles by 3 months of age in this elimination setting. Our findings inform important policy discussions relating to the timing of the first dose of measles-containing vaccine and infant postexposure prophylaxis recommendations.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacina contra Sarampo/imunologia , Sarampo/prevenção & controle , Fatores Etários , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Imunidade Materno-Adquirida , Esquemas de Imunização , Lactente , Masculino , Vacina contra Sarampo/administração & dosagem , Ontário , Testes Sorológicos
14.
Viruses ; 11(10)2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623390

RESUMO

Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation.


Assuntos
Regulação Viral da Expressão Gênica , Interleucina-12/agonistas , Interleucina-15/agonistas , Vacina contra Sarampo/imunologia , Adenocarcinoma , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Colo , Modelos Animais de Doenças , Feminino , Genes Virais , Imunoterapia , Interleucina-12/genética , Interleucina-15/genética , Células Matadoras Naturais/imunologia , Sarampo , Camundongos , Camundongos Endogâmicos C57BL , Vírus Oncolíticos , Transcriptoma , Vacinas Sintéticas , Proteínas Virais de Fusão/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Eur J Epidemiol ; 34(10): 897-915, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31624970

RESUMO

Measles vaccination schedules and targets of herd immunity have been designed according to the paradigm that the vaccine is as protective as natural infection, and the virus has remained of a single serotype over many decades. As a result, ongoing measles resurgence is mostly attributed to gaps in immunization. Using official data, we investigated the correlation between the rate of vaccine coverage reported and aggregated at the national level, and the incidence of cases. We discussed the limits of this indicator considered in isolation. We provide a literature overview of measles vaccine efficacy and failures. We questioned whether measles strains could escape the vaccine. Immunization tools and strategies for measles control deserve to be optimized in the current context.


Assuntos
Surtos de Doenças/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Vírus do Sarampo/efeitos dos fármacos , Sarampo/prevenção & controle , Genótipo , Humanos , Vírus do Sarampo/genética , Vacinação
16.
Vaccine ; 37(43): 6463-6469, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500970

RESUMO

BACKGROUND: In 2017, measles elimination was verified in Bhutan, and the country appears to have sufficiently high vaccination coverage to achieve rubella elimination. However, a measles and rubella serosurvey was conducted to find if any hidden immunity gaps existed that could threaten Bhutan's elimination status. METHODS: A nationwide, three-stage, cluster seroprevalence survey was conducted among individuals aged 1-4, 5-17, and >20 years in 2017. Demographic information and children's vaccination history were collected, and a blood specimen was drawn. Serum was tested for measles and rubella immunoglobulin G (IgG). Frequencies, weighted proportions, and prevalence ratios for measles and rubella seropositivity were calculated by demographic and vaccination history, taking into account the study design. RESULTS: Of the 1325 individuals tested, 1045 (81%, 95% CI 78%-85%) were measles IgG seropositive, and 1290 (97%, 95% CI 95%-99%) were rubella IgG seropositive. Rubella IgG seropositivity was high in all three age strata, but only 47% of those aged 5-17 years were measles IgG seropositive. Additionally, only 41% of those aged 5-17 years who had documented receipt of two doses of measles- or measles-rubella-containing vaccine were seropositive for measles IgG, but almost all these children were rubella IgG seropositive. CONCLUSIONS: An unexpected measles immunity gap was identified among children 5-17 years of age. It is unclear why this immunity gap exists; however, it could have led to a large outbreak and threatened sustaining of measles elimination in Bhutan. Based on this finding, a mass vaccination campaign was conducted to close the immunity gap.


Assuntos
Sarampo/imunologia , Sarampo/prevenção & controle , Rubéola (Sarampo Alemão)/imunologia , Rubéola (Sarampo Alemão)/prevenção & controle , Adolescente , Butão , Criança , Pré-Escolar , Estudos Transversais , Erradicação de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Vacina contra Sarampo/imunologia , Vacina contra Rubéola/imunologia , Estudos Soroepidemiológicos , Vacinação/estatística & dados numéricos , Adulto Jovem
18.
Lancet Infect Dis ; 19(11): 1235-1245, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31548079

RESUMO

BACKGROUND: Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines. FINDINGS: Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33-0·66; I2=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I2=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I2=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I2=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low. INTERPRETATION: MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity. FUNDING: WHO.


Assuntos
Anticorpos Antivirais/sangue , Esquemas de Imunização , Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Sarampo/prevenção & controle , Fatores Etários , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Imunidade Celular , Lactente , Masculino , Vacina contra Sarampo/administração & dosagem , Medição de Risco , Resultado do Tratamento
19.
Lancet Infect Dis ; 19(11): 1246-1254, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31548081

RESUMO

BACKGROUND: Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses. METHODS: For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines. FINDINGS: Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96-99; I2=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89-100; I2=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low. INTERPRETATION: Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain. FUNDING: WHO.


Assuntos
Imunidade Celular , Imunidade Humoral , Esquemas de Imunização , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Sarampo/prevenção & controle , Fatores Etários , Anticorpos Antivirais/sangue , Feminino , Humanos , Lactente , Masculino , Linfócitos T/imunologia , Resultado do Tratamento
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