Original articleStudies with the purified protein derivative of human and avian tuberculins in south queensland
Abstract
734 children at a secondary school in South Queensland had their sensitivities to human and avian PPD investigated by a simultaneous intradermal injection using first a small (5 TU human and 4 TU avian) dose on each child then a large (100 TU human and 80 TU avian) dose on negative reactors of 4 mm. or less diameter of induration. The results were analysed according to whether the individual had not had a previous skin test or a BCG vaccination (non-BCG group), or had had a previous BCG vaccination because of a negative Heaf test (BCG group).
The non-BCG children with no previous skin test as a group had a much higher sensitivity rate to the avian PPD than to the human PPD; and the reactions were larger to the avian than the human antigen. This was similar to the pattern of Brisbane children two years previously.
The BCG children also had a larger mean reaction size to the avian PPD than the human PPD, but this was not so marked as in the non-BCG children. This larger reaction to the avian antigen bore no relation to the time since BCG vaccination, the pattern of the correlation of reaction sizes remaining similar from five months since vaccination to several years afterwards.
In a second study, school children with an average age of 13 years were skin tested with low dose PPD human and PPD avian by the intradermal (Mantoux) method prior to routine BCG vaccination.
Correlation of reaction sizes three days after the tests gave a pattern. indicating a high rate of sensitization amongst these children to avian PPD and some cross sensitization to human PPD. The sensitizing agent is thought to be a Battey Group III organism which is commonly isolated from human sources in Queensland and is also widely distribution in nature. This also has a close antigenic relationship with the avian bacillus.
All children with a reaction size of 4 mm. or less of induration to the human PPD were given BCG vaccination, the size of the reaction to avian PPD being ignored. The BCG vaccine was the Danish strain manufactured in Melbourne.
Seven weeks after vaccination, retesting showed that reactions to both antigens were larger and more frequent, but that those to avian PPD were larger than those to human PPD. It is suggested that the effect of this particular BCG vaccine in these children, who have some experience of mycobacterial infection, possibly with a Battey Group III organism, had a greater cross-sensitizing effect than direct sensitizing effect. The results may also be influenced by human PPD not being the homologous antigen of BCG.
Résumé
734 enfants d'une école secondary du South Queensland ont été testes à la PPD humaine et aviaire par des injections intradermiques simultanees utilisant d'abord une dose faible (5 UT humaine et 4 UT aviaire) pour chaque enfant, puis une dose plus importante (100 UT humaine et 80 UT aviaire) pour les reacteurs negatifs ayant 4 mm. ou moins de diamètre d'induration. Les résultats ont été analysés selon que les sujets n'avaient pas eu un test cutane anterieur ou une vaccination par le BCG (groupe sans BCG), ou avait eu une vaccination par le BCG a la suite d'un test de Heaf negatif (groupe BCG).
Le groupe d'enfants sans BCG n'ayant pas eu de test cutane anterieurement avait un taux de sensibilite plus elevé vis-a-vis de la PPD aviaire que de la PPD humaine; et les réactions étaient plus importantes a l'antigene aviaire qu'à l'antigène humain. Les résultats sont semblables a ceux obtenus chez les enfants de Brisbone deux ans auparavant.
Les enfants ayant reçu le BCG presentaient aussi un diametre moyen de reaction plus grands a la PPD aviaire qu'à la PPD humaine, mais de façon moins nette que dans le groupe sans BCG. Cette reaction plus importante a l'antigene aviaire n'avait aucune relation avec le temps ecoule depuis la vaccination par le BCG, la droite de correlation de la taille des reactions restant semblable de cinq mois apres la vaccination a plusieurs années apres.
Dans une deuxieme étude, des écoliers d'une moyenne d'ǎge de 13 ans ont eu des tests cutanés avec de faibles doses de PPD humaine et aviaire par la methode intradermique (Mantoux) avant une vaccination BCG de routine.
La correlation de la taille des reactions trois jours apres les tests a tonne une droite indiquant un taux elevd de sensibilisation, parmi ces enfants, a la PPD aviaire et une certaine sensibilité croisée à la PPD humaine. L'agent sensibilisant doit etre un bacille Battey du groupe III qui est communément isolé de source humaine dans le Queensland et est largement répandu dans la nature. 11 a aussi des relations antigéniques importantes avec le bacille aviaire.
Tous les enfants ayant une réaction dont la taille était inférieure ou égale à 4 mm. d'induration, étaient vaccinés par le BCG, la taille de la réaction à la PPD aviaire étant ignorée. Le vaccin BCG etait la sourhe Danoise préparée à Melbourne.
Des tests refaits sept semaines après la vaccination ont montré que les réactions aux deux antigènes étaient plus importantes et plus fréquentes, mais que celles à la PPD aviaire l'emportaient sur celles à la PPD humaine. It semble que ce vaccin BCG particulier chez ces enfants, qui avaient déjà subi une certaine infection mycobactérienne, sans doute un bacille Battey du groupe 111, avait un effet plus prononce sur la sensibilisation croisée, que sur la sensibilisation directe. Les résultats peuvent aussi etre influences par la PPD humaine qui West pas l'antigene homologue du BCG.
Resumen
En 734 niños de una escuela secundaria de Sud Queensland se estudió la sensibilidad cutánea con PPD humano y aviario, por medio de una infeccion intradérmica simultánea, usando primero una dosis pequeña (5 UT humanas y 4 UT aviarias) y luego una dosis mayor (100 UT humanas y 80 UT aviarias) en los reactores negativos con una induracion de 4 mm. de diámetro o menos. Se estudiaron los resultados teniendo en cuenta si el individuo no habia tenido test cutaneo ni BCG previos (grupo no BCG) o habia sido vacunado previamente con BCG debido a un test de Heaf negativo (grupo BCG).
Los niños no vacunados con BCG y sin prueba cutanea previa tenian con mayor frecuencia hipersensibilidad al PPD aviario que al PPD humano y las reacciones al antigeno aviario eran mayores que al humano. Esto fue analogo a to observado con ninos de Brisbane dos años antes.
Los niños vacunados con BCG tambien tenian, en promedio, una reaction mayor at PPD aviario que al PPD humano, pero no en forma tan marcada como sucedia en los niños no vacunados. Esta reaction mayor frente al antigeno aviario no tenia relatión con el tiempo transcurrido desde la vacunacion, ya que los promedios de tamano de las reacciones e eran similares para quienes llevaban 5 meses de vacunados como para aquellos que Ilevaban varios años.
En un segundo estudio se efectuaron tests cutaneos a niños de 13 años de edad promedio con dosis bajas de PPD humano y PPD aviario, por via intradermica (Mantoux), previos a la vacunacion BCG.
La correlación del tamaño de ]as reacciones, a los 3 días, mostro una frecuencia mas elevada de sensibilidad al PPD aviario y algo de sensibilidad cruzada al PPD humano. Se cree que el agente sensibilizante es un germen del Grupo III Battey, comunmente aislado del hombre en Queensland y muy difundido en la naturaleza. Este germen tiene una íntima relación antigénica con el bacilo aviario.
Todos los niños con una reaccion al PPD humano de 4 mm. o menos fueron vacunados con BCG, ignorandose el tamano de la reaccion al PPD aviario. Se use la cepa dinamarquesa de BCG, preparada en Melbourne.
Los tests repetidos 7 semanas despues de la vacunación mostraron que las reacciones a ambos antigenos eran mas frecuentes y mas grandes, pero que ]as producidas por el PPD aviario eran mas grandes que las del PPD humano. Se sugiere que el efecto de esta vacuna BCG en estos ninos, que han tenido previamente algun concato con una mycobacteria, posiblemente del grupo III Battey, ha sido más de sensiblización cruzada que de sensibilización directa. Los resultados pueden tambien haber sido influenciados por el hecho de que el PPD humano no sea el antigeno homologo del BCG.
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Epidemiological studies of tuberculin sensitivity. II. Response to experimental infection with mycobacteria isolated from human sources
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Cited by (8)
Dose response models and a quantitative microbial risk assessment framework for the Mycobacterium avium complex that account for recent developments in molecular biology, taxonomy, and epidemiology
2017, Water ResearchCitation Excerpt :However, sensitization to mycobacterial antigens can also be provoked by the Calmette-Guérin (BCG) vaccine (Farhat et al., 2006), and because MAC infections are not nationally notifiable, time periods of recorded disease and sensitization typically do not overlap. Studies of mycobacterial exposure have shown high levels of mycobacterial skin reactivity and lack of NTM-associated disease outcomes in the studied populations and/or have targeted healthy or disease populations for testing rather than a random sample where both antigen and disease status were determined (Abrahams and Harland, 1968; Bardana et al., 1973; Bermudez et al., 1989; Kwamanga et al., 1995; Lee et al., 1991; Shachor et al., 1997; Thayer et al., 1990; von Reyn et al., 2001, von Reyn et al., 1993a). However, according to a survey of PPD-B (M. intracellulare) skin reactivity of 18- to 25- year old men in the southeastern coastal United States, greater than 60% showed a positive skin reaction, indicating they are, or at some stage were colonized or infected but did not show signs of disease (Edwards et al., 1969).
Mycobacterium avium complex (MAC) is a group of environmentally-transmitted pathogens of great public health importance. This group is known to be harbored, amplified, and selected for more human-virulent characteristics by amoeba species in aquatic biofilms. However, a quantitative microbial risk assessment (QMRA) has not been performed due to the lack of dose response models resulting from significant heterogeneity within even a single species or subspecies of MAC, as well as the range of human susceptibilities to mycobacterial disease. The primary human-relevant species and subspecies responsible for the majority of the human disease burden and present in drinking water, biofilms, and soil are M. avium subsp. hominissuis, M. intracellulare, and M. chimaera. A critical review of the published literature identified important health endpoints, exposure routes, and susceptible populations for MAC risk assessment. In addition, data sets for quantitative dose-response functions were extracted from published in vivo animal dosing experiments. As a result, seven new exponential dose response models for human-relevant species of MAC with endpoints of lung lesions, death, disseminated infection, liver infection, and lymph node lesions are proposed. Although current physical and biochemical tests used in clinical settings do not differentiate between M. avium and M. intracellulare, differentiating between environmental species and subspecies of the MAC can aid in the assessment of health risks and control of MAC sources. A framework is proposed for incorporating the proposed dose response models into susceptible population- and exposure route-specific QMRA models.
Gastroesophageal reflux disease, acid suppression, and Mycobacterium avium complex pulmonary disease
2007, ChestWeekly symptoms of gastroesophageal reflux disease (GERD) occur in 20% of the population, and GERD has been implicated in the pathophysiology of many respiratory diseases. Microaspiration of contaminated water is a potential portal of entry for Mycobacterium avium complex (MAC) organisms into the respiratory tract, and acid-suppression therapy may enhance the survival of mycobacteria in the stomach. This study aimed to assess the prevalence of GERD, swallowing disorders, reflux symptoms, and acid-suppression therapy in patients with MAC lung disease (MAC positive [MAC+]), and to compare these patients to control subjects without MAC lung disease (MAC negative [MAC−]).
Clinical information was collected on 58 MAC+ patients and 58 age- and sex-matched MAC− patients who were asked to complete a DeMeester questionnaire of reflux symptoms and to identify any acid-suppressive medication consumed.
A clinical diagnosis of GERD was documented in 23 of 52 MAC+ patients (44.2%), compared to 16 MAC− patients (27.6%) [p = 0.019]. MAC+ patients consumed significantly more histamine type 2 receptor antagonists and prokinetic agents, and MAC− patients consumed more antacids. The mean DeMeester questionnaire score (± SD) for MAC+ patients was 1.39 ± 1.8, and for MAC− patients was 0.88 ± 1.4. (p = 0.098). Aspiration was suspected in nine MAC+ patients (15.5%), compared to three MAC− patients (5.2%) [p = 0.032]. There was no association between GERD and radiologic presentation of MAC disease. Consolidation and nodules > 5 mm were more common in those receiving acid suppression than those who were not.
GERD, acid suppression, and clinically suspected aspiration are more common in patients with MAC lung disease than in similar patients without MAC disease.
Seven hundred and fifty Brisbane school children were tuberculin tested, in paired groups, with purified protein derivatives of Mycobacterium tuberculosis, bovis, BCG and avium.
Reaction to avian PPD were stronger than to any of the others used. This finding may be of some importance in interpreting the variation in protection afforded by BCG vaccination.
Cent cinquante écoliers de Brisbane ont été testes à la tuberculine; ils ont reçu chacun deux des tuberculines suivantes : PPD de M. tuberculosis, bovis, BCG et avium.
Les réactions à la PPD aviaire se sont montrées plus fortes que celles à l'un quelconque des autres antigènes utilisés. Ce résultat n'est pas sans intérêt en vue de ('interpretation des variations dans la protection conférée par la vaccination BCG.
Se realizó una prueba de tuberculina en 750 escolares de Brisbane, en grupos pareados, utilizando derivados proteino-purificados de los Micobacterios tuberculosis, bovis, BCG y avium.
Las reacciones al PPD avian fueron más intensas que a cualquiera de los otros. Est resultado puede ser importance en la interpretación de las variaciones en la protección conferida por la vacuna BCG.
Mycobacterium avium infections in man
1973, The American Journal of MedicineA disseminated infection with Mycobacterium avium, serotype 1, is described in a 63 year old woman with reticulum cell sarcoma. The organism was demonstrated in vivo in lymph nodes, bone marrow, urine and sputum, and at autopsy within an intraocular abscess.
Previous reports of human infections with Myco. avium describe cases of chronic, cavitary pulmonary disease, frequently occurring in patients with pneumoconiosis, cervical lymphadenopathy in children, and disseminated infection. Infected birds and mammals, and soil rich in bird droppings appear to constitute natural reservoirs of infection. However, extensive exposure to birds or the carcasses of slaughtered animals has been documented in only a minority of cases.
Myco. avium can be reliably identified only by serotyping or by inoculation into chickens, rabbits and guinea pigs. Skin tests with avian purified protein derivative together with standard purified protein derivatives and antigens prepared from other mycobacteria may be helpful in diagnosis prior to isolation and identification of the organism. Although localized infections have apparently been cured by surgical excision, more extensive infections have been reported to be progressive or fatal and have responded poorly to chemotherapy.
Original mycobacterial sin
1970, TubercleSchool children in Queensland have, in general, greater reactions to avian than to human PPD. After vaccination with BCG they still show a predominance of avian reactions.
A group of children who had been vaccinated shortly after birth were tested with avian and human PPD up to 16 years after vaccination. There was a significant excess of children with greater human reactions.
It is suggested that the first mycobacterial infection may set the antigenic reaction pattern. Secondary infection by an antigenically similar mycobacterium would then not alter the pattern of response. A similar phenomen has been reported with influenza viruses.
Des écoliers qu Queensland ont, en général, des réactions plus fortes à la tuberculine PPD aviaire, qu'à la tuberculine PPD humaine. Aprés vaccination par le B.C.G., la prédominance des réactions à la tuberculine aviaire persiste.
On a controlé, chez un groupe d'enfants vaccinés peu après la naissance, les réactions aux tuberculines PPD humaine et aviaire durant les 16 années qui ont suivi la vaccination. Une prédominance significative d'enfants présentant des réactions plus fortes à la tuberculine humaine, a été trouvée.
Les auteurs suggèrent que la première infection à mycobactéries peut établir le sens de la réaction antigènique. Une infection secondaire par des mycobactéries de caractère antigénique similaire, pourrait alors ne plus changer le sens de la réaction. Un phénomène semblable a été observé avec le virus de l'influenza.
Los niños escolares de Queensland presentan, en general, reacciones más intensas al PPD aviario que al humano. Después de ser vacunados con BCG sigue habiendo una predominancia de las reacciones aviarias.
Un grouo de niños vacunados poco después de nacer fueron controlados con PPD aviario y humano hasta 16 años después de vacunados. Una mayoría significativa de niños presentaron reacciones humanas mayores.
Se sugiere que la primera infección micobacteriana establece la reacción antigénica predominante. Una infección posterior con otra mycobacteria antigénicamente similar no alteraría el esquema de respuesta. Un fenómeno análogo ha sido communicado con los virus de la influenza.
Schulkindern weisen in Queensland im allgemeinen eine stärkere Reaktion auf aviäres als auf humanes PPD auf. Auch nach BCG-Impfung ist die aviäre Reaktion stärker.
Eine Gruppe von Kindern, die kurz nach der Geburt geimpft worden war, wurde 16 Jahre danach mit aviärem und humanem PPD getestet. Es gab eine signifikant größere Zahl von Kindern mit stärkerer Reaktion auf humanes PPD.
Es wird angenommen, daß die erste mykobakterielle Infektion das Muster der Antigenreaktion bestimmt. Eine Zweitinfektion mit einem Mykobakterium von ähnlicher Antigenstruktur ändert die Reaktionsweise nicht. Ein ähnliches Phänomen wurde beim Influenzavirus beobachtet.
Changing epidemiology of pulmonary nontuberculous mycobacteria infections
2010, Emerging Infectious Diseases
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