Tuberculin skin reactivity after neonatal BCG vaccination in preterm infants in Minas Gerais, Brazil, 2001-2002.

OBJECTIVES: The efficacy of BCG vaccination in preterm babies is unknown, and available data on conversion rates to tuberculin in this age group are scarce and controversial. This study assessed the tuberculin response in preterm infants after BCG vaccination.METHODS: This randomized cohort study was carried out at the Neonatal Department, University Hospital, Federal University of Minas Gerais in Brazil during 2001 and 2002. The BCG vaccine was administered at birth to 65 full-term (control) and 40 preterm newborns. All of them were tested with 5 tuberculin units of purified protein derivative-S approximately 3 months after vaccination.RESULTS: A typical BCG scar was verified in 96.9% of the control group and in 90.0% of the preterm infants (P = 0.19). Indurations > 5 mm in diameter were recorded in 87.7% of the full-term and 67.5% of the preterm infants (P = 0.02). Indurations > 10 mm were recorded in 70.8% of the full-term and 42.5% of the preterm infants (P = 0.007). For indurations > 5 mm the upper and the lower limits of the 95% confidence interval for the difference between proportions were 8.5% to 31.8%, and for indurations > 10 mm these limits were 18.0% to 38.4%. No adverse reactions were observed in the study population.CONCLUSION: BCG vaccination could be recommended for preterm infants upon discharge from the neonatal unit to reduce morbidity and mortality in infants at risk for tuberculous infection, and to increase BCG vaccination coverage rates, especially in countries with high prevalence rates of tuberculosis.     

Tuberculin sensitivity in guinea-pigs after vaccination with varying doses of BCG of 12 different strains.

In several previously reported studies a number of BCG strains, including those most widely used in vaccine production, were ranked according to their in vivo activity in various experimental models in rodents and to the local and allergic response that they provoked in children. In this report, 12 strains are ranked in terms of tuberculin conversion in guinea-pigs according to the minimum sensitizing dose. For 10 of these strains, this minimum dose is very low, ranging from 5 to 50 culturable particles. Thus the traditional practice of tuberculin-testing guinea-pigs that have been vaccinated with a full human dose of BCG (of the order of one million culturable particles) has such a low discriminating power that it is useless as a routine test for currently used vaccines. The ranking obtained in this model was largely but not completely in accordance with similar rankings in other models. The Tokyo strain and, to some extent, the London strain ranked comparatively lower than they do in children. The pronounced lack of virulence of the Prague strain was confirmed.     

Epidemiology of pertussis in a country with high vaccination coverage

Introduction

Pertussis has been a preventable disease in Catalonia since 1965, but the annual number of cases remains high. The aim of this study was to analyze the epidemiology of pertussis in Catalonia and its implications for control purposes.

Methods

An epidemiological study was carried out in Catalonia between 2004 and 2008. Pertussis cases reported to the Department of Health were collected and disease reports were filled out with the case information. Incidence rates, rate ratios (RR) and their 95% confidence intervals (CI) were calculated.

Results

963 cases were reported: 555 (57.6%) were confirmed and 408 (42.4%) were suspected cases. The reported incidence rate was 2.01 × 10⁻⁵ person years in 2004 and 4.34 in 2008. The biggest increase in cases between 2004 and 2008 was observed in the ≥35 years age group (RR: 6.98; 95%CI: 2.11-36.36). 303 (31.5%) patients were hospitalized, of whom 93.7% were aged <1 year. Clinical differences were observed in paroxysmal cough (83.8% in suspected and 76.4% in confirmed cases, p = 0.005), posttussive vomiting (47.1% and 36.1%, respectively, p = 0.001), apnoea (13.7% and 21.3%, respectively, p = 0.003) and fever (20.1% and 12.4%, respectively, p = 0.001).

Conclusion

Pertussis incidence rates increased during the study period, with the greatest increase occurring in the ≥35 years age group. A booster dose of vaccine in young people could reduce the circulation of B. pertussis in adolescents and adults and indirectly reduce the incidence in children.     

Tuberculin sensitivity and skin lesions in children after vaccination with 11 different BCG strains

In previously published studies, a number of BCG strains used in several production laboratories were compared in animal models. Liquid vaccines from the different strains were prepared in one laboratory with a uniform technique, the aim being to obtain uniform in vitro properties. In the studies reported here, such vaccines were compared by means of vaccinating children in India and Denmark and then measuring their post-vaccination skin lesions and tuberculin sensitivity. One strain induced delayed hypersensitivity strikingly weaker than that induced by any of the others, although the vaccine was in no way inferior in terms of exhaustive in vitro tests. Differences among the other strains were slight, although sometimes statistically significant. The implications of such differences are discussed.     

Effect of simultaneous BCG and smallpox vaccination in schoolchildren. Report of a WHO-sponsored preliminary study

The effect of simultaneous BCG and smallpox vaccination and the possible interaction of primary BCG vaccination and smallpox revaccination were studied in 1099 Burmese children arbitrarily allocated to four groups. All were tuberculin-tested and all had received primary smallpox vaccination but had not been vaccinated with BCG. In the first group, no vaccination was performed; in the second, negative reactors received BCG vaccine; the third received smallpox vaccine; and the fourth also received smallpox vaccine, negative reactors also receiving BCG vaccine.     

Tuberculin reactivity among ninth-grade schoolchildren in the city of Havana, Cuba]

OBJECTIVE: To determine the proportion of 14-year-old schoolchildren in the city of Havana, Cuba, with a positive tuberculin skin test, as an indicator of the prevalence of tuberculosis infection among them. METHODS: Using single-stage cluster sampling, 1 936 Mantoux (tuberculin) tests were carried out with ninth-grade students (cohort born in 1985) during the 1999- 2000 school year in 20 basic high schools randomly selected in Havana. The tests were performed according to the standard technique recommended by the World Health Organization, and they were read after 72 hours. The percentage of skin tests that were positive and the average diameter of the indurations were calculated for the cohort overall and for the two genders. The means and the percentages were compared using the chi-square test, with 95% confidence intervals. The computer software used was Epi Info version 6.0. RESULTS: Of the tests read, 96% of them were negative (0-4 mm), 2.5% were doubtful (5-9 mm), and 1.5% were positive (>/=10 mm). The percentage of reactivity was 0.1% when a cutoff value of 15 mm was used. The mean diameter of the indurations was 0.41 mm. No statistically significant difference was found between the genders. CONCLUSIONS: In this study the proportion of schoolchildren with tuberculin reactivity, using an induration-diameter cutoff point of 10 mm, was very low (1.5%), and it was much lower (0.1%) when a cutoff point of 15 mm was used. The skin reactions with an induration diameter of >/=10 mm could be the expression of a natural infection if one takes into account the low frequency of bacillary tuberculosis in Cuba and that there is an inverse relationship between the time elapsed from the BCG vaccination and the intensity of the response to tuberculin. Therefore, that would mean that in this case (l)the point (.)prevalence of tuberculosis infection in this group of schoolchildren wou d be 1.5% ResumenObjetivos. Determinar la proporción de personas que reaccionan a la tuberculina como indicador de la prevalencia de infección tuberculosa en escolares de 14 a?os de Ciudad de La Habana, Cuba. Métodos. Mediante un muestreo monoetápico por conglomerados se aplicaron 1 936 pruebas de Mantoux (tuberculina) a estudiantes de noveno grado del curso escolar 1999-2000 (cohorte de los nacidos en 1985) de 20 escuelas secundarias básicas seleccionadas aleatoriamente en Ciudad de La Habana, Cuba. Las pruebas se realizaron según la técnica estándar recomendada por la Organización Mundial de la Salud y se evaluaron a las 72 horas. Se calcularon los porcentajes de reactividad y el diámetro medio de las induraciones cutáneas en la cohorte y según el sexo. Las comparaciones de medias y porcentajes se realizaron mediante la prueba de ji al cuadrado con 95% de confiabilidad. Se usó el programa Epi Info v. 6.0. Resultados. Noventa y seis por ciento de las pruebas leídas fueron negativas (0-4 mm), 2,5% fueron dudosas (5-9 mm) y 1,5% resultaron positivas ( >/= 10 mm). El porcentaje de reactividad disminuyó a 0,1% cuando se utilizó un valor de corte de 15 mm. El diámetro medio de las induraciones fue de 0,41 mm y no se detectó ninguna diferencia estadísticamente significativa en función del sexo. Conclusiones. La proporción de personas que reaccionaron a la tuberculina, usando como punto de corte un diámetro de induración cutánea de 10 mm, fue muy baja (1,5%) en este estudio y mucho más baja (0,1%) cuando se utilizó 15 mm como punto de corte. Si se toma en cuenta la baja frecuencia de tuberculosis bacilífera en Cuba y que hay una relación inversa entre el tiempo transcurrido desde la aplicación de la vacuna a base del bacilo de Calmette-Guérin (BCG) y la intensidad de la respuesta a la tuberculina, las reacciones cutáneas con un diámetro de induración >/= 10 mm podrían ser la expresión de una infección natural, por lo que, en ese caso, la prevalencia puntual de infección tuberculosa en este grupo de escolares sería de 1,5%.     

Tuberculin sensitivity in a high-risk canine population.

An epidemiologic study of tuberculosis in dogs exposed to humans with recently reported tuberculosis was undertaken in Philadelphia between July 1966 and June 1968. A total of 29 dogs meeting the criteria for inclusion in the high-risk population were studied by history, physical examination, intradermal tuberculin tests, and radiographic and bacteriologic examination. Ten of the 29 dogs showed positive responses to US Department of Agriculture (USDA) standard mammalian tuberculin. Positive tuberculin tests to second strength PPD were demonstrated in five of the 10 responders to USDA mammalian tuberculin. No physical, radiographic or bacteriologic evidence of tuberculosis was found in any of the high-risk animals examined. In a comparison group of 70 dogs without knwon exposure to tuberculosis, two positive responses to USDA tuberculin were demonstrated and none to PPD.     

Tuberculin reactivity in adults after 50 years of universal bacille Calmette-Guerin vaccination in Taiwan

We aimed to assess whether tuberculin reactivity in adults is affected by bacille Calmette-Guerin (BCG) vaccination after 50 years of universal BCG vaccination with 80-95% coverage. A community-based study on tuberculin reactivity in 619 participants was conducted in February 2000 in Keelung city, Taiwan. Information on BCG vaccination policies and annual risk of infection (ARI) in the underlying population was extracted from consecutive national prevalence surveys relating to the period 1952-1997. Compared with the expected ARI estimate, the standardized morbidity ratio of positive tuberculin response for vaccination in infancy was 2.2 (95% CI 0.3-15.5) for those aged <10 years. The corresponding figures for older age groups ranged from 3.6 (95% CI 2.2-5.9) for those aged 10-12 years to 0.7 (95% CI 0.5-0.9) for those aged 57-67 years. This suggests that the effect of BCG vaccination on positive tuberculin response in adults aged >30 years is probably negligible irrespective of age at vaccination or revaccination and that the tuberculin skin test can be used to diagnose TB in control programmes in countries with moderate or high incidence of TB.     

BCG vaccination by bifurcated needle in a pilot vaccination programme.

The bifurcated needle technique for BCG vaccination was compared with intradermal injection in a mass BCG and smallpox vaccination programme in Afghanistan. In all population groups the bifurcated needle technique produced substantial tuberculin sensitivity, which however was significantly inferior to that following intradermal injection. The advantages of the bifurcated needle technique did not result in a significant increase in vaccination coverage and output. Under the present circumstances vaccination by bifurcated needle would probably be more expensive than intradermal vaccination.     

Using surveys of schoolchildren to evaluate coverage with and opportunity for vaccination in Costa Rica]

OBJECTIVE: To identify differences in the level of coverage of and opportunity for vaccination among schoolchildren in three areas in Costa Rica with different characteristics: an urban area (with the highest level of socioeconomic development of the three areas), a rural area (with a medium level of socioeconomic development), and a border area (a rural area in northern Costa Rica, on the border with Nicaragua, with the lowest level of socioeconomic development and the highest proportion of foreign immigrants). METHODOLOGY: Following selection of schools by proportional probability, surveys were used with children chosen at random from the first and second grades of elementary schools in the three areas: urban (961 students), rural (544 students), and border (811 students). The data on the vaccines that had been administered were obtained from the children's vaccination cards. Differences among the three areas were evaluated: (1) in the coverage with BCG; with three doses of diphtheria-tetanuspertussis vaccine (DTP3); with three doses of oral polio vaccine (OPV3); with the first dose of measles-mumps-rubella vaccine (MMR1); and with the second dose of MMR vaccine (MMR2) and (2) in the "opportunity" for the children having received DTP1 + OPV1 before 3 months of age, DTP3 + OPV3 before 7 months of age, and DTP4 + OPV4 + MMR1 before 24 months of age. RESULTS: Out of all the students who had been selected, 80% of them in the urban area had a vaccination card, 73% did in the rural area, and 72% did in the border area (P < 0.05). The coverage levels for BCG, DTP3, and OPV3 were each over 95% in both the urban area and the rural area; however, the coverage levels were significantly lower (P < 0.05) in the border area: BCG, 83%; OPV3, 88%; and DTP3, 88%. Coverage with MMR1 and MMR2 was similar in the three areas. The percentage of schoolchildren with two or more doses of measles vaccine was 98% in the urban area, 92% in the rural area, and 85% in the border area (P < 0.05). In terms of opportunity, 90% of the children had received DTP1 + OPV1 before 3 months of age in the urban area, 89% had in the rural area, and 80% had in the border area (P < 0.05). The percentage of application of the complete basic schedule (DTP4 + OPV4 + MMR1) before 24 months of age was 93% in the urban area, 95% in the rural area, and 84% in the border area (P < 0.05). CONCLUSIONS: The border area had lower coverage of and opportunity for the basic schedule of vaccines, except for MMR. Follow-up campaigns for measles eradication have increased the coverage of the initial and booster doses in all three areas, but the increase has been greatest in the urban area. A greater effort should be made to identify children with an incomplete schedule of vaccinations, with priority going to areas that have a high proportion of immigrants.     

Comparing cytokine production and clinical response following vaccination with BCG Moreau and BCG Russia strains in a Brazilian infant population

IntroductionBCG is the only licensed vaccine against tuberculosis (TB) and, in Brazil, comprises part of the recommended vaccine schedule within the first month of life. Due to a local manufacturing shortage of BCG Moreau, BCG Russia was introduced in 2017 by the Brazilian Ministry of Health.ObjectiveTo evaluate differences in immune responses induced by BCG Moreau and BCG Russia in infants, in addition to scar formation.MethodsThe present case series involved 15 healthy infants who were vaccinated within the first seven days of life with one of two strains of BCG, then followed for 12 weeks or longer. Cytokine levels were measured before and after vaccination in whole blood culture supernatants previously stimulated in vitro with either BCG strain, heat-killed M. tuberculosis H37Rv or in the absence of stimulation. BCG scarring was also documented.ResultsInfants vaccinated with BCG Moreau exhibited increased background IL-2, IL-10 and IL-4 production, yet no differences were found in those vaccinated with BCG Russia. Although both strains induced higher levels of IL-2 and IFN-γ, elevated IL-6, TNF and IL-10 production was also seen in response to BCG Russia. In contrast, no specific responses were observed against heat-killed M. tuberculosis H37Rv, with the exception of increased IL-2 following BCG Moreau vaccination. Although documented in both groups, scarring was milder and less frequent following BCG Russia vaccination.ConclusionsSimilar Th1 profiles were found following immunization with either type of BCG vaccine evaluated herein, with more pronounced cytokine production detected in response to the Russia strain. Overall, vaccination was well-tolerated and scarring evolved as expected for both BCG strains.     

Children on the move and vaccination coverage in a low-income, urban Latino population.

OBJECTIVES: The purpose of this study was to determine the impact of childhood moves and foreign birth on vaccination coverage among Latino children in New York City. METHODS: Vaccination coverage was assessed in a survey of 314 children younger than 5 years at 2 immunization clinics. RESULTS: Forty-seven percent of the study children had moved abroad. After adjustment for health insurance, regular source of care, and country of birth, child moves had no independent effect on vaccination coverage. Foreign-born children had diphtheria-pertussis-tetanus, oral polio vaccine, and measles-mumps-rubella vaccination coverage rates similar to those of US-born children, but they were underimmunized in regard to Haemophilus influenzae type b and hepatitis B. CONCLUSIONS: Foreign birth, but not childhood moves, is a barrier to vaccinations among low-income, urban Latino children.     

Carriage of Streptoccoccus pneumoniae 7 years after implementation of vaccination program in a population with very high and long-lasting coverage, Italy

To evaluate how the 7-valent pneumococcal vaccine (PCV7) programme and the very high vaccination coverage reached for over 4 years affected the prevalence of Streptoccoccus pneumoniae serotypes in the paediatric population and to evaluate demographic, behavioural and risk factors for carriage in the post-vaccination era, a cross-sectional study on nasopharyngeal carriage was performed. Six hundred sixty-nine children under the age of 5, representative of the open population, were enrolled by cluster sampling. High sensitive techniques for detection of multi-serotype carriage, i.e. broth enrichment and real-time PCR and sequential PCRs for detection and typing, respectively, were used. Of the 669 enrolled children, 97.8% were compliant with the recommended PCV7 vaccination schedule. Post-stratification adjustment for age was applied considering the Ligurian population as standard population. Age-weighted carriage rate was 50.1% and 78% of carriers were colonized by more than one serotype. The prevalence of carriage increased with age from 22% in the first year of life, to 48.6% in the second year of life and to 60% in the 25-59 month age group. Age-weighted prevalence of any of the PCV7, PCV10 or PCV13 serotypes was 10.3%, 20.3% and 27.5%, respectively. PCV7 serotypes were mainly represented by serotype 4 that was carried since the 3rd year of life and was responsible for invasive pneumococcal disease (IPD) and non-IPD in adults, but not in children confirming the high vaccine effectiveness. Among the serotypes included in recently available vaccines, serotypes 5 and 19A showed a higher prevalence, being carried by 15.2% and 8.8% of the population, respectively. A multivariate analysis showed that age, the presence of child siblings at home and day care attendance covariates were strongly associated with S. pneumoniae carriage. In conclusion, over 7 years of vaccination with PCV7 and very high coverage in the last 4 years has led to low carriage prevalence in the first year of life rapidly increasing in the following years and high prevalence of non-PCV7 serotypes carriage.     

Comparison of self-report influenza vaccination coverage with data from a population based computerized vaccination registry and factors associated with discordance

Objectives

We aim to compare influenza vaccination coverages obtained using two different methods; a population based computerized vaccination registry and self-reported influenza vaccination status as captured by a population survey.

Methods

The study was conducted in the Autonomous Community of Madrid (ACM), Spain, and refers to the 2011/12 influenza vaccination campaign.Information on influenza vaccination status according to a computerized registry was extracted from the SISPAL database and crossed with the electronic clinical records in primary care (ECRPC). Self-reported vaccine uptake was obtained from subjects living in the ACM included in the 2011–12 Spanish National Health Survey (SNHS). Independent study variables included: age, sex, immigrant status and the presence of high risk chronic conditions. Vaccination coverages were calculated according to study variables. Crude and adjusted prevalence ratios were computed to assess concordance.

Results

The study population included 5,245,238 adults living in the ACM in year 2011 with an individual ECRPC and 1449 adult living the ACM and interviewed in the SNHS from October 2011 to June 2012.The weighted vaccination coverage for the study population according to self-reported data was 19.77% and 15.04% from computerized registries resulting in a crude prevalence ratio (cPR) of 1.31 (95% CI 1.20–1.44) so self-reported data significantly overestimated 31% the registry coverage. Self-reported coverages are always higher than registry based coverages when the study population is stratified by the study variables. Self-reported overestimation was higher among men than women, younger age groups, immigrants and those without chronic conditions. Both methods provide the most concordant estimations for the target population of the influenza vaccine.

Conclusions

Self-report influenza vaccination uptake overestimates vaccination registries coverages. The validity of self-report seems to be negatively affected by socio-demographic variables and the absence of chronic conditions. Possible strategies must be considered and implemented to improve both coverage estimation methods.