BACKGROUND: Recent evidence suggests that the duration of protection by bacillus Calmette-Guerin (BCG) may exceed previous estimates with potential implications for estimating clinical and cost-efficacy. OBJECTIVES: To estimate the protection and duration of protection provided by BCG vaccination against tuberculosis, explore how this protection changes with time since vaccination, and examine the reasons behind the variation in protection and the rate of waning of protection. DATA SOURCES: Electronic databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Databases, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE), Web of Knowledge, Biosciences Information Service (BIOSIS), Latin American and Caribbean Health Sciences Literature (LILACs), MEDCARIB Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from inception to May 2009. Index to Theses, System for Information on Grey Literature in Europe (SIGLE), Centre for Agricultural Bioscience International (CABI) Abstracts, Scopus, Article First, Academic Complete, Africa-Wide Information, Google Scholar, Global Health, British National Bibliography for Report Literature, and clinical trial registration websites were searched from inception to October 2009. REVIEW METHODS: Electronic databases searches, screening of identified studies, data extraction and analysis were undertaken. Meta-analysis was used to present numerical and graphical summaries of clinical efficacy and efficacy by time since vaccination. Evidence of heterogeneity was assessed using the tau-squared statistic. Meta-regression allowed the investigation of observed heterogeneity. Factors investigated included BCG strain, latitude, stringency of pre-BCG vaccination tuberculin testing, age at vaccination, site of disease, study design and vulnerability to biases. Rate of waning of protection was estimated using the ratio of the measure of efficacy after 10 years compared with the efficacy in the first 10 years of a study. RESULTS: Study selection. A total of 21,030 references were identified, providing data on 132 studies after abstract and full-text review. Efficacy. Protection against pulmonary tuberculosis in adults is variable, ranging from substantial protection in the UK MRC trial {rate ratio 0.22 [95% confidence interval (CI) 0.16 to 0.31]}, to absence of clinically important benefit, as in the large Chingleput trial [rate ratio 1.05 (95% CI 0.88 to 1.25)] and greater in latitudes further away from the equator. BCG vaccination efficacy was usually high, and varied little by form of disease (with higher protection against meningeal and miliary tuberculosis) or study design when BCG vaccination was given only to infants or to children after strict screening for tuberculin sensitivity. High levels of protection against death were observed from both trials and observational studies. The observed protective effect of BCG vaccination did not differ by the strain of BCG vaccine used in trials. DURATION: Reviewed studies showed that BCG vaccination protects against pulmonary and extrapulmonary tuberculosis for up to 10 years. Most studies either did not follow up participants for long enough or had very few cases after 15 years. This should not be taken to indicate an absence of effect: five studies (one trial and four observational studies) provided evidence of measurable protection at least 15 years after vaccination. Efficacy declined with time. The rate of decline was variable, with faster decline in latitudes further from the equator and in situations where BCG vaccination was given to tuberculin-sensitive participants after stringent tuberculin testing. LIMITATIONS: The main limitation of this review relates to quality of included trials, most of which were conducted before current standards for reporting were formulated. In addition, data were lacking in some areas and the review had to rely on evidence from observational studies. CONCLUSIONS: BCG vaccination protection against tuberculosis varies between populations, to an extent that cannot be attributed to chance alone. Failure to exclude those already sensitised to mycobacteria and study latitude closer to the equator were associated with lower efficacy. These factors explained most of the observed variation. There is good evidence that BCG vaccination protection declines with time and that protection can last for up to 10 years. Data on protection beyond 15 years are limited; however, a small number of trials and observational studies suggest that BCG vaccination may protect for longer. Further studies are required to investigate the duration of protection by BCG vaccination. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guerin vaccination against tuberculosis

Smallpox and Vaccinia

In PLoS Medicine, volume 3, issue 8: DOI: 10.1371/journal.pmed.0030272

Under the section heading “Expected Death Toll during a Present-Day Mass Vaccination Campaign,” the numbers of expected deaths that were computed for a mass vaccination campaign were displayed as per million; they should be absolute numbers.

The corrected text should be: “Under those assumptions, in the Netherlands mass vaccination with NYCBH would lead to 9.8 deaths (95% CI [0, 30]), mass vaccination with Lister to 55.1 deaths (95% CI [7, 182]), and mass vaccination with Bern would lead to 303.5 deaths (95% CI [19, 1093]). In Germany mass vaccination with NYCBH would lead to 46.2 deaths (95% CI [6, 142]), mass vaccination with Lister would lead to 268.5 deaths (95% CI [39, 875]), and mass vaccination with Bern would lead to 1,381 deaths (95% CI [94, 4909]).”

/pdf/correction-frequency-of-adverse-events-after-vaccination-3f0mioa1h8.pdf

Correction: Frequency of Adverse Events after Vaccination with Different Vaccinia Strains

Observations on the Hæmatology of Calves and Various Breeds of Adult Dairy Cattle

Observations on the Hæmatology of Calves and Various Breeds of Adult Dairy Cattle: PART I (Concluded)

Der Umstand, das in verschiedenen Landern in der letzten Zeit bei Pockenschutzimpfungen immer haufiger subepidermale Impfmethoden angewendet werden, lies es angezeigt erscheinen, Vergleichsuntersuchungen uber etwaige Unterschiede hinsichtlich der Belastung des Organismus sowie der Antikorperbildung nach den verschiedenen Impfverfahren anzustellen. Die Untersuchungen wurden an Jungrindern durchgefuhrt, von denen eine Gruppe cutan mittels Scarifikationsimpfung, eine zweite Gruppe subcutan und eine dritte Gruppe intracutan geimpft wurde. Als Masstab fur die Starke der Reaktion des Organismus auf die Impfungen wurden die Veranderungen des weisen Blutbildes und der Bluteiweiskorper, als Masstab fur die immunisierende Wirkung der Grad der Antikorperbildung herangezogen. Die wesentlichsten hierbei festgestellten Unterschiede waren folgende:

1.

Veranderungen des weiβen Blutbildes: Nach dercutanen Impfung zweimaliger Anstieg der Kurve der neutrophilen, segmentkernigen Leukocyten (mit Gipfelpunkten am Anfang der ersten und Ende der zweiten Woche) sowie starke und anhaltende Abnahme der eosinophilen Leukocyten (bis 0,1%); nach dersubcutanen Impfung nur einmaliger Anstieg der segmentkernigen Leukocyten (in der ersten Woche) und nur geringe sowie kurzer anhaltende Verminderung der eosinophilen Leukocyten (bis 1%); nach derintracutanen Impfung — ahnlich wie nach der cutanen Impfung — zweimaliger Anstieg der segmentkernigen Leukocyten, jedoch in der zweiten Anstiegsphase weniger hoch als bei den cutan geimpften Tieren; daneben Abnahme der Eosinophilen etwa im Ausmas wie nach der subcutanen Impfung, aber erst spatere Ruckkehr zur Norm als bei dieser.




2.

Verhalten der Bluteiweiβkorper: Nach dercutanen Impfung auserordentlich starke Verkurzung desWeltmannschen Koagulationsbandes (im Durchschnitt bis Rohrchen Nr. 1 in der zweiten Woche) und deutliche Zunahme der Zinksulfattrubung (ab Mitte der zweiten Woche); dementsprechend im Elektrophorese-Diagramm wahrend der ersten beiden Wochen deutliche Vermehrung derα- undβ-Globuline (um etwa ein Drittel bzw. fast 100% des Ausgangswertes) und von der Mitte der zweiten Woche an starker und anhaltender Anstieg derγ-Globuline (um mehr als 60%), gleichzeitig erhebliche Abnahme der Albuminwerte; nach dersubcutanen undintracutanen Impfung geringere Verkurzung desWeltmann-schen Koagulationsbandes (im Durchschnitt nur bis Rohrchen Nr. 5 bzw. 4) und nur unbedeutende Zunahme der Zinksulfattrubung; dementsprechend im Elektrophorese-Diagramm nur geringfugige Schwankungen der Albumin- und Globulinwerte.




3.

Bildung von viruliziden Antikorpern: Hochster beobachteter Titer nach dercutanen Impfung 1∶64, nach dersubcutanen Impfung 1∶4 und nach derintracutanen Impfung 1∶8.

Untersuchungen über die Veränderungen des weißen Blutbildes und der Bluteiweißkörper sowie über die Antikörperbildung nach cutaner, subcutaner und intracutaner Einverleibung von Pockenschutzimpfstoff

Incidence of postvaccinal encephalitis in children of different ages after first vaccination

Age and Postvaccinal Encephalitis.

Bei Jungrindern im Durchschnittsgewicht von 283 kg wird mit ACTH, in gleichen Dosen wie beim Menschen (25 mg intramuskular bzw. 10 mg i.c.), der vonThorn u. Mitarb. angegebene Einflus auf das Hamogramm, hingegen kein signifikanter Einflus einer Losung von Adrenalin 1∶1000 in der Menge bis zu 4 cm3 subcutan nachgewiesen.

Ein Beitrag zum funktionellen Verhalten des Hypophysen-Nebennierenrinden-Systems bei künstlicher Vaccina-Infektion des Jungrindes

Es wird uber die Ergebnisse von Liquoruntersuchungen von 238 in der Zeit von 1929–1954 in Osterreich an Encephalitis post vaccinationem erkrankten Kindern im Alter von 6 1/2 Monaten bis 15 Jahre berichtet und die Haufigkeit der einzelnen Liquorveranderungen besprochen. Diese nehmen an Haufigkeit und Intensitat mit dem Alter der Erkrankten zu, so das eine altersbedingte Reaktionsweise des Organismus der Erkrankten angenommen wird. Aus einem Vergleich der Veranderungen des weisen Blutbildes und der Blutkorperchensinkgeschwindigkeit mit den Liquorveranderungen bei Encephalitis post vaccinationem wird fur das Zustandekommen der Gehirnentzundung nach Pockenschutzimpfung ein derzeit im Detail noch unbekannter Vorgang angenommen, durch den ein Prozes im Zentralnervensystem, die Encephalitis post vaccinationem, ausgelost wird, der eigengesetzlich ablauft und nicht wie die Veranderungen des weisen Blutbildes und der Blutkorperchensinkgeschwindigkeit in ihrem Verlauf durch die Vaccineinfektion mitbestimmt wird. Die Haufigkeit und Intensitat der Liquorveranderungen wird durch das Lebensalter der Erkrankten, sohin durch eine besondere altersbedingte Reaktionsweise des Organismus bestimmt.

The reaction of the cerebrospinal fluid in encephalitis post vaccinationem

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