bronchoalveolar-lavage-bal-for-research-obtaining-adequate-sample

Bronchoalveolar Lavage (BAL) for Research; Obtaining Adequate Sample Yield

We describe a research technique for fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) using manual hand held suction in order to remove ...

Experimental Human Pneumococcal Carriage

Experimental human pneumococcal carriage (EHPC) is scientifically important because nasopharyngeal carriage of Streptococcus pneumoniae is both the major ...

National Institute for Health Research

Royal Liverpool and Broadgreen University Hospital Trust

Liverpool School of Tropical Medicine

University Hospital Trust

Royal Liverpool and Broadgreen University Hospitals NHS Trust

liverpool school of tropical medicine

&#x9610;&#x91CA;&#xFF1A; &#x80BA;&#x708E;&#x7403;&#x83CC;&#x75AB;&#x82D7;&#x8FD0;&#x8F93;&#x5065;&#x5EB7;&#x6210;&#x4EBA;&#x7684;&#x514D;&#x75AB;&#x548C;&#x4FDD;&#x62A4;&#x6027;&#x4F5C;&#x7528;&#x4E0D;&#x5F97;&#x800C;&#x77E5;&#xFF0C;&#x4F46;&#x4E2D;&#x8001;&#x5E74;&#x4EBA;&#x7684;&#x75BE;&#x75C5;&#x4E0E;&#x6B7B;&#x4EA1;&#x9AD8;&#x7684;&#x623F;&#x4EF7;&#x4F4E;&#x8FD0;&#x8F93;&#x6D41;&#x884C;&#x4E0E;&#x76F8;&#x5173;&#x8054;&#x3002;&#x76EE;&#x6807;&#xFF1A; &#x6211;&#x4EEC;&#x96C7;&#x7528;&#x5B9E;&#x9A8C;&#x4EBA;&#x7C7B;&#x7684;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x75AB;&#x82D7;&#x8FD0;&#x8F93;&#x6A21;&#x578B;&#x8FDB;&#x884C;&#x8C03;&#x67E5;&#x7684;&#x4E00;&#x4E2A;&#x5355;&#x4E00;&#x8FD0;&#x8F93;&#x63D2;&#x66F2;&#x7ED9;&#x5F71;&#x54CD;&#x3002;&#x65B9;&#x6CD5;&#xFF1A; &#x4E03;&#x5341;&#x4E2A;&#x5065;&#x5EB7;&#x6210;&#x5E74;&#x4EBA;&#x53D7;&#x5230;&#x8D28;&#x7591;&#x548C;&#x90A3;&#x4E9B;&#x4E0E;&#x8FD0;&#x8F93; 10 &#x4E86; re-challenged &#x9F3B;&#x4E0E;&#x80BA;&#x708E;&#x94FE;&#x7403;&#x83CC;&#x6D3B; 6B &#x5411;&#x4E0A;&#x81F3; 11 &#x4E2A;&#x6708;&#x540E;&#x7B2C;&#x4E00;&#x96C6;&#x8FD0;&#x8F93;&#x7B2C;&#x4E00;&#x5173;&#x3002;&#x6D4B;&#x91CF;&#x4E86;&#x8840;&#x6E05;&#x548C;&#x9F3B;&#x8154;&#x6E05;&#x6D17;&#x6DB2;&#x6297;&#x4F53;&#x53CD;&#x5E94;&#x4E4B;&#x524D;&#x548C;&#x4E4B;&#x540E;&#x6BCF;&#x4E00;&#x4E2A;&#x6311;&#x6218;&#x3002;&#x6D4B;&#x91CF;&#x548C;&#x4E3B;&#x8981;&#x7ED3;&#x679C;&#xFF1A; &#x5B9E;&#x9A8C;&#x6B96;&#x6C11;&#x5730; 29 &#x79D1;&#x76EE;&#x3002;&#x6CA1;&#x6709;&#x4E3B;&#x9898;&#x88AB;&#x6B96;&#x6C11;&#x7684;&#x5B9E;&#x9A8C; re-challenge &#x8868;&#x660E;&#x521D;&#x59CB;&#x8FD0;&#x8F93;&#x5BF9;&#x968F;&#x540E;&#x611F;&#x67D3;&#x7684;&#x4FDD;&#x62A4;&#x4F5C;&#x7528;&#x3002;&#x8FD0;&#x8F93;&#x589E;&#x52A0;&#x4E24;&#x8005;&#x7C98;&#x819C;&#x548C;&#x8840;&#x6E05; IgG &#x5404;&#x7EA7;&#x5BF9;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x86CB;&#x767D;&#x548C;&#x591A;&#x7CD6;&#xFF0C;&#x5BFC;&#x81F4; opsonophagocytic &#x6D3B;&#x52A8;&#x4E2D;&#x589E;&#x52A0;&#x4E86;&#x56DB;&#x500D;&#x3002;&#x91CD;&#x8981;&#x7684;&#x662F;&#xFF0C;&#x4ECE;&#x6B96;&#x6C11;&#x5730;&#x81E3;&#x6C11; post-carriage &#x8840;&#x6E05;&#x88AB;&#x52A8;&#x8F6C;&#x79FB;&#x6240;&#x8D4B;&#x4E88;&#x7684;&#x4FB5;&#x88AD;&#x6027;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x80BA;&#x708E;&#x5C0F;&#x9F20;&#x6A21;&#x578B;&#x4E2D;&#x7684;&#x5F02;&#x6E90;&#x5E94;&#x53D8;&#x7684;&#x81F4;&#x547D;&#x6311;&#x6218; 70%&#x9632;&#x62A4;&#x3002;&#x8FD9;&#x4E9B;&#x7EA7;&#x522B;&#x90FD;&#x5927;&#x5927;&#x9AD8;&#x4E8E;&#x6240;&#x8D4B;&#x4E88;&#x7684; pre-carriage &#x8840;&#x6E05; &#xFF08;30%&#xFF09; &#x6216;&#x751F;&#x7406;&#x76D0;&#x6C34; &#xFF08;10%&#xFF09; &#x7684;&#x4FDD;&#x62A4;&#x3002;&#x7ED3;&#x8BBA;&#xFF1A; &#x5B9E;&#x9A8C;&#x4EBA;&#x7C7B;&#x8FD0;&#x8F93;&#x5BFC;&#x81F4;&#x6388;&#x4E88;&#x9488;&#x5BF9; re-colonization &#x548C;&#x4FB5;&#x88AD;&#x6027;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x75BE;&#x75C5;&#x9632;&#x62A4;&#x7684;&#x9ECF;&#x819C;&#x548C;&#x5168;&#x8EAB;&#x514D;&#x75AB;&#x53CD;&#x5E94;&#x3002;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x8868;&#x660E;&#x7C98;&#x819C;&#x63A5;&#x79CD;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x75AB;&#x82D7;&#x6218;&#x7565;&#x4E5F;&#x8BB8;&#x91CD;&#x8981;&#x7684;&#x6613;&#x53D7;&#x4F24;&#x5BB3;&#x7684;&#x75C5;&#x4EBA;&#x7FA4;&#x4F53;&#xFF0C;&#x5C24;&#x5176;&#x662F;&#x8001;&#x4EBA;&#xFF0C;&#x4E0D;&#x80FD;&#x8FD0;&#x8F93;&#x3002;

&#x63A7;&#x5236;&#x4EBA;&#x7C7B;&#x611F;&#x67D3;&#x548C; Re-Challenge &#x4E0E;&#x94FE;&#x7403;&#x83CC;&#x80BA;&#x708E;&#x63ED;&#x793A;&#x4E86;&#x9A6C;&#x8F66;&#x5728;&#x5065;&#x5EB7;&#x6210;&#x4EBA;&#x4E2D;&#x7684;&#x4FDD;&#x62A4;&#x6548;&#x679C;&#x3002;

RATIONALE: The immunological and protective role of pneumococcal carriage in healthy adults is not known but high rates of disease and death in elderly are associated with low carriage prevalence. OBJECTIVES: We employed an experimental human pneumococcal carriage model to investigate the immunizing effect of a single carriage episode. METHODS: Seventy healthy adults were challenged and of those with carriage 10 were re-challenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of first carriage episode. Serum and nasal wash antibody response were measured before and after each challenge. MEASUREMENTS AND MAIN RESULTS: 29 subjects were experimentally colonized. No subjects were colonized by experimental re-challenge demonstrating the protective effect of initial carriage against subsequent infection. Carriage increased both mucosal and serum IgG levels to pneumococcal proteins and polysaccharide, resulting in a fourfold increase in opsonophagocytic activity. Importantly, passive transfer of post-carriage sera from colonized subjects conferred 70% protection against lethal challenge by a heterologous strain in a murine model of invasive pneumococcal pneumonia. These levels were significantly higher than the protection conferred by either pre-carriage sera (30%) or saline (10%). CONCLUSIONS: Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against re-colonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies maybe important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.

Controlled Human Infection and Re-Challenge with Streptococcus Pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults.

Justification : Le r&ocirc;le immunologique et protecteur de transport contre le pneumocoque chez les adultes en bonne sant&eacute; est inconnu, mais des taux &eacute;lev&eacute;s de maladies et de d&eacute;c&egrave;s de personnes &acirc;g&eacute;es sont associ&eacute;s &agrave; la pr&eacute;valence faible transport. OBJECTIFS : Nous avons utilis&eacute; un mod&egrave;le de chariot de pneumocoque humaine exp&eacute;rimentale pour &eacute;tudier l&#39;effet immunisant d&#39;un &eacute;pisode unique de transport. M&eacute;thodes : Soixante-dix adultes sains ont &eacute;t&eacute; contest&eacute;s et de ceux avec chariot 10 ont &eacute;t&eacute; re-challenged par voie intranasale avec webcam live 6 b Streptococcus pneumoniae vers le haut &agrave; 11 mois apr&egrave;s le d&eacute;gagement du premier &eacute;pisode de transport. S&eacute;rum et lavage nasal r&eacute;ponse en anticorps ont &eacute;t&eacute; mesur&eacute;s avant et apr&egrave;s chaque d&eacute;fi. MESURES et principaux r&eacute;sultats : 29 sujets ont &eacute;t&eacute; exp&eacute;rimentalement colonis&eacute;s. Aucun sujet n&#39;&eacute;tait colonis&eacute;s par la non-exposition exp&eacute;rimentale d&eacute;montrant l&#39;effet protecteur de transport initial contre une infection ult&eacute;rieure. Transport port&eacute;e tous les deux muqueuses et s&eacute;rum IgG &agrave; pneumocoque prot&eacute;ines et polysaccharides, entra&icirc;neraient une augmentation de quatre fois dans l&#39;activit&eacute; opsonophagocytic. 70 % De protection contre l&#39;infection mortelle a &eacute;t&eacute; conf&eacute;r&eacute; par une souche h&eacute;t&eacute;rologue dans un mod&egrave;le murin de pneumonie &agrave; pneumocoque invasif important, transfert passif des s&eacute;rums viser des sujets colonis&eacute;s. Ces niveaux ont &eacute;t&eacute; significativement plus &eacute;lev&eacute;e que la protection conf&eacute;r&eacute;e par les s&eacute;rums pre-carriage (30 %) ou une solution saline (10 %). CONCLUSIONS : Transport humain exp&eacute;rimental a entra&icirc;n&eacute; des r&eacute;actions immunologiques muqueuses et syst&eacute;miques qui conf&egrave;re une protection contre la recolonisation et maladies invasives &agrave; pneumocoques. Ces donn&eacute;es sugg&egrave;rent que les strat&eacute;gies de vaccination antipneumococcique muqueux peut-&ecirc;tre importants pour le patient vuln&eacute;rable groupes, particuli&egrave;rement les personnes &acirc;g&eacute;es, qui ne subissent pas de transport.

Sous contr&ocirc;le de l&#39;Infection humaine et Re-Challenge avec Streptococcus Pneumoniae r&eacute;v&egrave;le l&#39;efficacit&eacute; protectrice de transport chez les adultes en bonne sant&eacute;.

Begr&uuml;ndung: Die immunologische und sch&uuml;tzende Rolle Pneumokokken Bef&ouml;rderungsbedingungen bei gesunden Erwachsenen ist nicht bekannt, aber hohe Raten von Krankheit und Tod im alten niedrigen Bef&ouml;rderung Pr&auml;valenz zugeordnet sind. Ziele: Wir besch&auml;ftigt eine experimentelle menschlichen Pneumokokken Bef&ouml;rderung-Modell den immunisierenden Effekt einer Einzelwagen-Episode zu untersuchen. Methoden: Siebzig gesunde Erwachsene wurden herausgefordert und derjenigen mit Kutsche 10 wurden re-challenged intranasally mit live-6B Streptococcus Pneumoniae bis bis 11 Monate nach Freigabe der ersten Bef&ouml;rderung Folge. Serum und nasal-Waschanlagen-Antik&ouml;rper-Reaktion wurden vor und nach jeder Herausforderung gemessen. Messungen und Hauptergebnisse: 29 Themen wurden experimentell kolonisiert. Keine Themen wurden durch experimentelle Re-challenge demonstrieren die Schutzwirkung des ersten Bef&ouml;rderung gegen sp&auml;tere Infektionen kolonisiert. Bef&ouml;rderung erh&ouml;ht sowohl Schleimhaut- und Serum IgG Ebenen Pneumokokken Proteine und Polysaccharid, was eine Vervierfachung in Opsonophagocytic Aktivit&auml;t. Wichtig ist, verlieh passiven &Uuml;bertragung der post-carriage Seren von kolonisierten Themen 70 % Schutz gegen t&ouml;dliche Herausforderung durch eine heterologe Belastung in einem murinen Modell von invasiven Pneumokokken Lungenentz&uuml;ndung. Diese Ebenen waren deutlich h&ouml;her als der Schutz durch Nachlauf Seren (30 %) oder Kochsalzl&ouml;sung (10 %). Schlussfolgerungen: Experimentelle menschlichen Bef&ouml;rderung f&uuml;hrte Schleimhaut- und systemische Immunreaktionen, die Schutz gegen Rekolonialisierung und invasive Pneumokokken-Krankheit gew&auml;hrt. Diese Daten legen nahe, dass Schleimhaut Pneumokokken Impfstrategien vielleicht wichtig f&uuml;r gef&auml;hrdete Patienten Gruppen, besonders die &auml;lteren Menschen, die Bef&ouml;rderung nicht aufrechterhalten werden.

Kontrollierte menschliche Infektion und wiederherausfordern mit Streptococcus Pneumoniae enth&uuml;llt die Schutzwirkung von Bef&ouml;rderung bei gesunden Erwachsenen.

Spiegazione logica: Il ruolo immunologico e protettivo di trasporto pneumococcica negli adulti sani non &egrave; noto ma alti tassi di malattia e di morte negli anziani sono associati con prevalenza di trasporto Bassi. OBIETTIVI: Abbiamo impiegato un modello sperimentale trasporto pneumococco umana di indagare l&#39;effetto immunologico di un episodio unico trasporto. Metodi: Settanta adulti sani sono stati contestati e di quelli con carrello 10 erano re-challenged intranasale con Streptococcus pneumoniae 6B live fino a 11 mesi dopo la liquidazione del primo episodio di trasporto. Siero e risposta anticorpale lavaggio nasale sono stati misurati prima e dopo ogni sfida. MISURAZIONI e principali risultati: 29 soggetti sperimentalmente sono stati colonizzati. No soggetti furono colonizzati dai re-challenge sperimentali che dimostrano l&#39;effetto protettivo di trasporto iniziale contro infezione successiva. Trasporto aumentato sia della mucosa e siero IgG livelli di proteine da pneumococco e polisaccaride, risultanti in un aumento di quattro volte in attivit&agrave; opsonophagocytic. Importante, trasferimento passivo di post-carriage sieri di soggetti colonizzate conferito 70% protezione contro sfida letale di un ceppo eterologo in un modello murino di polmonite pneumococcica invasiva. Questi livelli sono stati significativamente superiori la protezione conferita da sieri pre-carriage (30%) o soluzione salina (10%). CONCLUSIONI: Sperimentale trasporto umano portato a risposte immunologiche della mucosa e sistemiche che conferisce protezione contro re-colonization e le malattie invasive da pneumococco. Questi dati suggeriscono che gruppi di strategie di vaccinazione pneumococcica mucosa magari importante per il paziente vulnerabile, specialmente gli anziani, che non sostengono il carrello.

Controllato l&#39;infezione umana e Re-Challenge con Streptococcus Pneumoniae rivela l&#39;efficacia protettiva della carrozza in adulti sani.

&#x53C2;&#x8003;: &#x5065;&#x5E38;&#x6210;&#x4EBA;&#x306B;&#x304A;&#x3051;&#x308B;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x306E;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8;&#x306E;&#x514D;&#x75AB;&#x5B66;&#x7684;&#x304A;&#x3088;&#x3073;&#x4FDD;&#x8B77;&#x306E;&#x5F79;&#x5272;&#x3092;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x306A;&#x3044;&#x304C;&#x3001;&#x75C5;&#x6C17;&#x3084;&#x9AD8;&#x9F62;&#x8005;&#x306E;&#x6B7B;&#x306E;&#x9AD8;&#x3044;&#x7387;&#x304C;&#x4F4E;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8;&#x306E;&#x6709;&#x75C5;&#x7387;&#x3068;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x76EE;&#x6A19;&#xFF1A; &#x5358;&#x4E00;&#x306E;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8; &#x30EA;&#x30BF;&#x30FC;&#x30F3;&#x306E;&#x30A8;&#x30D4;&#x30BD;&#x30FC;&#x30C9;&#x306E;&#x514D;&#x75AB;&#x52B9;&#x679C;&#x3092;&#x8ABF;&#x67FB;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x3001;&#x5B9F;&#x9A13;&#x7684;&#x4EBA;&#x9593;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8; &#x30E2;&#x30C7;&#x30EB;&#x3092;&#x63A1;&#x7528;&#x3057;&#x307E;&#x3059;&#x3002;&#x65B9;&#x6CD5;: 70 &#x5065;&#x5EB7;&#x306A;&#x5927;&#x4EBA;&#x306B;&#x6311;&#x6226;&#x3057;&#x305F;&#x3001;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8;&#x3068;&#x306E;&#x305D;&#x308C;&#x3089;&#x306E; 10 &#x7D4C;&#x30E9;&#x30A4;&#x30D6; 6B &#x9023;&#x9396;&#x7403;&#x83CC;&#x80BA;&#x708E;&#x3092; 11 &#x30F6;&#x6708;&#x30AF;&#x30EA;&#x30A2;&#x30E9;&#x30F3;&#x30B9; &#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8;&#x306E;&#x6700;&#x521D;&#x306E;&#x30A8;&#x30D4;&#x30BD;&#x30FC;&#x30C9;&#x306E;&#x5F8C;&#x306B;&#x518D;&#x3044;&#x305F;&#x3002;&#x8840;&#x6E05;&#x304A;&#x3088;&#x3073;&#x9F3B;&#x6D17;&#x6D44;&#x6297;&#x4F53;&#x5FDC;&#x7B54;&#x306F;&#x524D;&#x306B;&#x3001;&#x3068;&#x5F8C;&#x306E;&#x5404;&#x6311;&#x6226;&#x3092;&#x6E2C;&#x5B9A;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x4E3B;&#x306A;&#x7D50;&#x679C;&#x3068;&#x5B9F;&#x6E2C;&#x7D50;&#x679C;: 29 &#x88AB;&#x9A13;&#x8005;&#x5B9F;&#x9A13;&#x7684;&#x690D;&#x6C11;&#x5730;&#x3068;&#x306A;&#x3063;&#x305F;&#x3002;&#x521D;&#x671F;&#x904B;&#x9001;&#x305D;&#x306E;&#x5F8C;&#x306E;&#x611F;&#x67D3;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4FDD;&#x8B77;&#x52B9;&#x679C;&#x3092;&#x767A;&#x63EE;&#x3059;&#x308B;&#x5B9F;&#x9A13;&#x306E;&#x518D;&#x30C1;&#x30E3;&#x30EC;&#x30F3;&#x30B8;&#x3067;&#x690D;&#x6C11;&#x5730;&#x4E3B;&#x984C;&#x304C;&#x306A;&#x3044;&#x3067;&#x3059;&#x3002;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8;&#x304C;&#x3001;&#x7C98;&#x819C;&#x306E;&#x5897;&#x53CE;&#x3057;&#x3001;&#x8840;&#x6E05; IgG &#x80BA;&#x708E;&#x7403;&#x83CC;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x30FB;&#x591A;&#x7CD6;&#x985E;&#x306B; opsonophagocytic &#x6D3B;&#x52D5;&#x306E; 4 &#x500D;&#x5411;&#x4E0A;&#x30EC;&#x30D9;&#x30EB;&#x3057;&#x307E;&#x3059;&#x3002;&#x91CD;&#x8981;&#x306A;&#x306F;&#x3001;&#x690D;&#x6C11;&#x5730;&#x7531;&#x6765;&#x306E; post-carriage &#x306E;&#x8840;&#x6E05;&#x306E;&#x53D7;&#x8EAB;&#x4F1D;&#x9054;&#x306E;&#x4FB5;&#x8972;&#x6027;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x6027;&#x80BA;&#x708E;&#x30DE;&#x30A6;&#x30B9;&#x30E2;&#x30C7;&#x30EB;&#x306B;&#x304A;&#x3051;&#x308B;&#x7570;&#x7A2E;&#x6B6A;&#x306B;&#x3088;&#x308B;&#x81F4;&#x547D;&#x7684;&#x306A;&#x6311;&#x6226;&#x306B;&#x5BFE;&#x3057;&#x3066; 70 &#xFF05; &#x306E;&#x4FDD;&#x8B77;&#x3092;&#x6388;&#x4E0E;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x306F;&#x3001;&#x672C;&#x8239;&#x306E;&#x8840;&#x6E05; (30%) &#x307E;&#x305F;&#x306F;&#x751F;&#x7406;&#x98DF;&#x5869;&#x6C34; (10%) &#x306E;&#x3044;&#x305A;&#x308C;&#x304B;&#x3092;&#x4E0E;&#x3048;&#x3089;&#x308C;&#x305F;&#x4FDD;&#x8B77;&#x3088;&#x308A;&#x3082;&#x6709;&#x610F;&#x306B;&#x9AD8;&#x304B;&#x3063;&#x305F;&#x3002;&#x7D50;&#x8AD6;: &#x5B9F;&#x9A13;&#x7684;&#x4EBA;&#x9593;&#x30AD;&#x30E3;&#x30EA;&#x30C3;&#x30B8; re-colonization &#x3068;&#x4FB5;&#x8972;&#x6027;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x75BE;&#x60A3;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4FDD;&#x8B77;&#x3092;&#x6388;&#x4E0E;&#x7C98;&#x819C;&#x306E;&#x514D;&#x75AB;&#x5B66;&#x7684;&#x53CD;&#x5FDC;&#x306E;&#x7D50;&#x679C;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x3001;&#x8106;&#x5F31;&#x306A;&#x60A3;&#x8005;&#x306E;&#x305F;&#x3081;&#x304A;&#x305D;&#x3089;&#x304F;&#x91CD;&#x8981;&#x306A;&#x7C98;&#x819C;&#x80BA;&#x708E;&#x7403;&#x83CC;&#x30EF;&#x30AF;&#x30C1;&#x30F3;&#x63A5;&#x7A2E;&#x6226;&#x7565;&#x30B0;&#x30EB;&#x30FC;&#x30D7;&#x306F;&#x3001;&#x7279;&#x306B;&#x5E74;&#x914D;&#x8005;&#x904B;&#x9001;&#x3092;&#x7DAD;&#x6301;&#x3057;&#x3066;&#x3001;&#x304A;&#x52E7;&#x3081;&#x3057;&#x307E;&#x3059;&#x3002;

&#x4EBA;&#x3078;&#x306E;&#x611F;&#x67D3;&#x3092;&#x5236;&#x5FA1;&#x3001;&#x9023;&#x9396;&#x7403;&#x83CC;&#x80BA;&#x708E;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x5065;&#x5EB7;&#x306A;&#x6210;&#x4EBA;&#x306E;&#x904B;&#x9001;&#x306E;&#x9632;&#x5FA1;&#x52B9;&#x679C;&#x3092; Re-Challenge &#x3057;&#x307E;&#x3059;&#x3002;

&#xADFC;&#xAC70;: &#xAC74;&#xAC15; &#xD55C; &#xC131;&#xC778;&#xC5D0;&#xC11C; &#xD3D0; &#xB834;&#xC758; &#xBA74;&#xC5ED; &#xBC0F; &#xBCF4;&#xD638; &#xC5ED;&#xD560; &#xC54C;&#xB824;&#xC838; &#xC788;&#xC9C0; &#xD558;&#xC9C0;&#xB9CC; &#xBCD1;&#xACFC; &#xB178;&#xC778;&#xC5D0; &#xC8FD;&#xC74C;&#xC758; &#xB192;&#xC740; &#xAE08;&#xB9AC; &#xB0AE;&#xC740; &#xC6B4;&#xC1A1; &#xC720;&#xD589;&#xC640; &#xAD00;&#xB828; &#xB41C;. &#xBAA9;&#xD45C;: &#xC6B0;&#xB9AC;&#xB294; &#xB2E8;&#xC77C; &#xCE90;&#xB9AC;&#xC9C0; &#xC5D0;&#xD53C;&#xC18C;&#xB4DC; immunizing &#xD6A8;&#xACFC; &#xC870;&#xC0AC; &#xD558;&#xAE30; &#xC704;&#xD574; &#xC2E4;&#xD5D8; &#xC778;&#xAC04;&#xC758; &#xD3D0; &#xB834; &#xCE90;&#xB9AC;&#xC9C0; &#xBAA8;&#xB378; &#xACE0;&#xC6A9;. &#xBC29;&#xBC95;: 70 &#xAC74;&#xAC15; &#xD55C; &#xC131;&#xC778;&#xB3C4; &#xC804;&#xD588;&#xB2E4; &#xACE0; &#xCE90;&#xB9AC;&#xC9C0;&#xC640; &#xADF8;&#xC758; 10 &#xD588;&#xB2E4; re-challenged intranasally &#xB77C;&#xC774;&#xBE0C; 6B &#xC5F0;&#xC1C4; &#xC0C1; &#xAD6C; &#xADE0; &#xADE0;&#xACFC; &#xCD5C;&#xB300;&#xC758; &#xCCAB; &#xBC88;&#xC9F8; &#xCE90;&#xB9AC;&#xC9C0; &#xC5D0;&#xD53C;&#xC18C;&#xB4DC; &#xD6C4; 11 &#xAC1C;&#xC6D4;. &#xAC01; &#xCC4C;&#xB9B0;&#xC9C0; &#xC804;&#xD6C4; &#xD608; &#xCCAD; &#xBC0F; &#xBE44; &#xAC15; &#xC138;&#xCC99; &#xD56D; &#xCCB4; &#xBC18;&#xC751;&#xC744; &#xCE21;&#xC815; &#xD588;&#xB2E4;. &#xCE21;&#xC815; &#xBC0F; &#xC8FC;&#xC694; &#xACB0;&#xACFC;: 29 &#xACFC;&#xBAA9; &#xC2E4;&#xD5D8;&#xC801;&#xC73C;&#xB85C; &#xC2DD;&#xBBFC;&#xC9C0; &#xD654; &#xD588;&#xB2E4;. &#xC544;&#xBB34; &#xACFC;&#xBAA9; &#xC774;&#xD6C4;&#xC758; &#xAC10;&#xC5FC;&#xC5D0; &#xB300; &#xD55C; &#xCD08;&#xAE30;&#xC758; &#xBCF4;&#xD638; &#xD6A8;&#xACFC; &#xC785;&#xC99D; &#xD558;&#xB294; &#xC2E4;&#xD5D8; &#xAD8C;&#xC5ED;&#xC5D0; &#xC758;&#xD574; &#xC2DD;&#xBBFC;&#xC9C0; &#xD654; &#xD588;&#xB2E4;. &#xCE90;&#xB9AC;&#xC9C0; &#xC810; &#xB9C9; &#xBAA8;&#xB450; &#xC99D;&#xAC00; &#xD608; &#xCCAD; IgG &#xB808;&#xBCA8; &#xD3D0; &#xB834; &#xAD6C; &#xADE0; &#xB2E8;&#xBC31;&#xC9C8; &#xBC0F; &#xB2E4; &#xB2F9; &#xB958;, opsonophagocytic &#xD65C;&#xB3D9;&#xC5D0;&#xC11C; &#xC0AC;&#xC911; &#xC99D;&#xAC00;&#xC758; &#xACB0;&#xACFC;&#xB85C;. &#xC911;&#xC694; &#xD55C; &#xAC83;&#xC740;, &#xC218;&#xB3D9; &#xC804;&#xC1A1;&#xC744; post-carriage &#xC138;&#xB77C; &#xC2DD;&#xBBFC;&#xC9C0; &#xACFC;&#xBAA9;&#xC5D0;&#xC11C;&#xC758; &#xCE68; &#xC724; &#xC131; &#xD3D0; &#xB834; &#xADE0; &#xC131; &#xD3D0; &#xB834;&#xC758; murine &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xBD84;&#xB9AC; &#xBCC0;&#xD615;&#xC5D0; &#xC758;&#xD574; &#xCE58;&#xBA85;&#xC801;&#xC778; &#xACFC;&#xC81C;&#xC5D0; &#xB300; &#xD55C; 70% &#xBCF4;&#xD638;&#xB97C; &#xC218; &#xC5EC;. &#xC774;&#xB7EC;&#xD55C; &#xC218;&#xC900;&#xC740; pre-carriage &#xC138;&#xB77C; (30%) &#xC774;&#xB098; &#xC2DD; &#xC5FC; &#xC218; (10%)&#xC5D0; &#xC758;&#xD574; &#xC218; &#xC5EC; &#xBCF4;&#xD638; &#xBCF4;&#xB2E4; &#xD06C;&#xAC8C; &#xB192;&#xC558;&#xB2E4;. &#xACB0;&#xB860;: &#xC2E4;&#xD5D8; &#xC778;&#xAC04;&#xC758; &#xCE90;&#xB9AC;&#xC9C0; re-colonization &#xBC0F; &#xCE68; &#xC724; &#xC131; &#xD3D0; &#xB834; &#xADE0; &#xC131; &#xC9C8;&#xBCD1;&#xC5D0; &#xB300; &#xD55C; &#xBCF4;&#xD638;&#xB97C; &#xC218; &#xC5EC; &#xD558;&#xB294; &#xC810; &#xB9C9; &#xC870;&#xC9C1;&#xC758; &#xBA74;&#xC5ED; &#xBC18;&#xC751;&#xC744; &#xCD08;&#xB798; &#xD588;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xB370;&#xC774;&#xD130;&#xB294; &#xCDE8;&#xC57D; &#xD55C; &#xD658;&#xC790;&#xC5D0; &#xB300; &#xD55C; &#xC5B4;&#xCA4C;&#xBA74; &#xC911;&#xC694; &#xD55C; &#xC810; &#xB9C9; &#xD3D0; &#xB834; &#xC608;&#xBC29; &#xC811;&#xC885; &#xC804;&#xB7B5; &#xADF8;&#xB8F9;, &#xD2B9;&#xD788; &#xB178;&#xC778; &#xCE90;&#xB9AC;&#xC9C0;&#xB97C; &#xC720;&#xC9C0; &#xD558;&#xC9C0; &#xC54A;&#xB294; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC778;&#xAC04;&#xC758; &#xAC10;&#xC5FC;&#xC744; &#xC81C;&#xC5B4; &#xD558; &#xACE0; &#xAC74;&#xAC15; &#xD55C; &#xC131;&#xC778;&#xC5D0;&#xC11C; &#xC6B4;&#xC1A1; &#xBCF4;&#xD638; &#xD6A8;&#xB2A5; &#xC5F0;&#xC1C4; &#xC0C1; &#xAD6C; &#xADE0; &#xADE0; &#xACC4;&#xC2DC;&#xC640; Re-Challenge.

JUSTIFICACI&Oacute;N: No se conoce la funci&oacute;n inmunol&oacute;gica y protectora de transporte neumoc&oacute;cica en adultos sanos, pero altas tasas de enfermedad y muerte en ancianos se asocian con prevalencia baja del carro. OBJETIVOS: Se emple&oacute; un modelo de carro neumoc&oacute;cica humano experimental para investigar el efecto inmunizante de un episodio solo carro. M&Eacute;TODOS: Setenta adultos sanos fueron desafiados y de aquellos con carro 10 fueron re-challenged intranasal con vivo 6B Streptococcus pneumoniae hasta 11 meses despu&eacute;s de la separaci&oacute;n del primer episodio de transporte. Suero y la respuesta de anticuerpos de lavado nasal fueron medidos antes y despu&eacute;s de cada desaf&iacute;o. MEDIDAS y resultados de la ca&ntilde;er&iacute;a: 29 temas experimentalmente fueron colonizados. No temas fueron colonizadas por re-desaf&iacute;a experimental que demuestran el efecto protector de transporte inicial contra la infecci&oacute;n posterior. Transporte aument&oacute; tanto mucosa y suero IgG los niveles neumoc&oacute;cicas prote&iacute;nas y polisac&aacute;ridos, dando por resultado un aumento cu&aacute;druple en actividad opsonofagoc&iacute;tico. Lo importante, transferencia pasiva de sueros post-carriage de sujetos colonizados confiri&oacute; 70% de protecci&oacute;n contra el desaf&iacute;o mortal de una cepa heter&oacute;loga en un modelo murino de neumon&iacute;a neumoc&oacute;cica invasiva. Estos niveles fueron significativamente mayores que la protecci&oacute;n conferida por los sueros pre-transporte (30%) o soluci&oacute;n salina (10%). CONCLUSIONES: Transporte humano Experimental result&oacute; en las respuestas inmunol&oacute;gicas mucosas y sist&eacute;micas que confiere protecci&oacute;n contra la recolonizaci&oacute;n y la enfermedad neumoc&oacute;cica invasiva. Estos datos sugieren que estrategias de vacunaci&oacute;n antineumoc&oacute;cica mucosa tal vez importantes para paciente vulnerable grupos, particularmente los ancianos, que no sufra el carro.

Controlada la infecci&oacute;n humana y Re-Challenge con Streptococcus Pneumoniae revela la eficacia protectora de transporte en adultos sanos.

Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4(+) T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4(+) T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A(+) CD4(+) T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF(+)/IL-17A(+) co-producing CD4(+) memory T-cells (p<0.01); IFNγ(+) CD4(+) memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4(+) memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = -0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4(+) memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.

Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.

PspA and pneumolysin (Ply) are important protein vaccine candidates. HIV infection is associated with increased susceptibility to pneumococcal pneumonia and concomitantly high pneumococcal carriage rates. Pneumococcal exposure is immunizing at the mucosa in healthy adults and so we wished to determine if the increased pneumococcal exposure in HIV-infected adults would be associated with altered pneumococcal specific antibody responses. We measured serum and bronchoalveolar lavage (BAL) fluid immunoglobulin (Ig)G and IgA to PspA and Ply in HIV-infected and healthy age-matched adults. Naturally generated anti-Ply and anti-PspA IgG levels but not IgA were significantly increased in HIV-infected subjects in BAL independent of the hyperglobulinaemia commonly associated with HIV. There was therefore no evidence of a defect in mucosal responses to pneumococcal protein antigens among HIV-infected adults. With regard to future vaccination strategies, simply increasing mucosal anti-pneumococcal protein Ig levels, without addressing functional protective response, is not likely to be effective in preventing pneumococcal pneumonia in HIV-infected individuals.

Increased IgG but normal IgA anti-pneumococcal protein antibodies in lung of HIV-infected adults.

Many patients with pneumonia and lower respiratory tract infection that could be treated as outpatients according to their clinical severity score, are in fact admitted to hospital. We investigated whether, with medical and social input, these patients could be discharged early and treated at home.Objectives: (1) To assess the feasibility of providing an early supported discharge scheme for patients with pneumonia and lower respiratory tract infection (2) To assess the patient acceptability of a study comprising of randomisation to standard hospital care or early supported discharge scheme.

ArticleTotal : 2	Year
Publication title Cited by 47	2014
Publication title Cited by 80	2013

Article	Year
Controlled Human Infection and Re-Challenge with Streptococcus Pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults. American journal of respiratory and critical care medicine\| PubMed ID: 23370916	2013
Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung. PLoS pathogens\| PubMed ID: 23555269	2013
Increased IgG but normal IgA anti-pneumococcal protein antibodies in lung of HIV-infected adults. Vaccine\| PubMed ID: 23664995	2013
Feasibility study for early supported discharge in adults with respiratory infection in the UK. BMC pulmonary medicine\| PubMed ID: 24571705	2014

Andrea M. Collins

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