a-model-for-experimental-exposure-humans-to-larval-ixodes-scapularis

A Model for Experimental Exposure of Humans to Larval <em>Ixodes scapularis</em> Ticks

Tickborne diseases are a significant public health problem in the United States and worldwide. Ticks are obligate blood-feeding arthropods; an ixodid tick ...

National Institutes of Health

The smallpox vaccine is associated with more serious adverse events than any other live attenuated vaccine in use today. Although studies have examined serum cytokine levels in primary vaccine recipients at 1 and 3-5 weeks after vaccination with the smallpox vaccine, serial measurements have not been performed, and studies in revaccinated subjects have not been conducted.

Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine.

&#x6162;&#x6027;&#x6D3B;&#x52A8;&#x6027; EBV &#x75BE;&#x75C5; (CAEBV) &#x662F;&#x6297;&#x4F53;&#x7684;&#x6DCB;&#x5DF4;&#x589E;&#x751F;&#x6027;&#x75BE;&#x75C5;&#xFF0C;&#x7279;&#x5F81;&#x662F;&#x6297;&#x4F53;&#x7684; EBV &#x6216; EBV DNA &#x8840;&#x6DB2;&#x548C; EBV RNA &#x6216;&#x86CB;&#x767D;&#x8D28;&#x5728;&#x4F53;&#x5185;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x4E2D;&#x6C34;&#x5E73;&#x663E;&#x8457;&#x5347;&#x9AD8;&#x3002;&#x6211;&#x4EEC;&#x5728;&#x8FC7;&#x53BB; 28 &#x5E74;&#x4E2D;&#xFF0C;&#x5305;&#x62EC;&#x5728;&#x7F8E;&#x56FD;&#x7684;&#x9020;&#x8840;&#x5E72;&#x7EC6;&#x80DE;&#x79FB;&#x690D;&#x6CBB;&#x7597;&#x7684;&#x7B2C; 8 &#x4F8B;&#x4E0E; CAEBV &#x63D0;&#x4EA4;&#x6211;&#x4EEC;&#x7684;&#x7ECF;&#x9A8C;&#x3002;&#x5927;&#x591A;&#x6570;&#x60C5;&#x51B5;&#x4E0B;&#xFF0C;CAEBV &#x7684;&#x62A5;&#x544A;&#x6765;&#x81EA;&#x65E5;&#x672C;&#x3002;&#x4E0E; CAEBV &#x5728;&#x65E5;&#x672C;&#xFF0C;&#x4F4D;&#x7F6E; EBV &#x51E0;&#x4E4E;&#x603B;&#x662F;&#x88AB;&#x53D1;&#x73B0;&#x5728; T &#x6216;&#x81EA;&#x7136;&#x6740;&#x624B; (NK) &#x7EC6;&#x80DE;&#x7EC4;&#x7EC7;&#x4E2D;&#x7684;&#xFF0C;&#x4E0D;&#x540C; EBV &#x662F;&#x901A;&#x5E38;&#x5728;&#x4ECE;&#x6211;&#x4EEC;&#x7684;&#x75C5;&#x4EBA;&#x4F53;&#x5185;&#x7684; B &#x7EC6;&#x80DE;&#x4E2D;&#x68C0;&#x6D4B;&#x5230;&#x3002;&#x5927;&#x591A;&#x6570;&#x60A3;&#x8005;&#x63D0;&#x51FA;&#x4E0E;&#x6DCB;&#x5DF4;&#x7ED3;&#x80BF;&#x5927;&#x548C;&#x813E;&#x80BF;&#x5927; &#xFF1B;&#x5E38;&#x89C1;&#x53D1;&#x70ED;&#x3001; &#x809D;&#x708E;&#x3001; &#x548C;&#x5168;&#x8840;&#x7EC6;&#x80DE;&#x51CF;&#x5C11;&#x3002;&#x5927;&#x591A;&#x6570;&#x60A3;&#x8005;&#x6B7B;&#x4E8E;&#x611F;&#x67D3;&#x6216;&#x6E10;&#x8FDB;&#x7684;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x8F6C;&#x5316;&#x3002;&#x4E0E;&#x4E0D;&#x540C;&#x7684;&#x6848;&#x4EF6;&#x62A5;&#x544A;&#x6765;&#x81EA;&#x65E5;&#x672C;&#xFF0C;&#x6211;&#x4EEC;&#x7684;&#x75C5;&#x4EBA;&#x5F80;&#x5F80;&#x8868;&#x660E; B &#x7EC6;&#x80DE;&#x548C; hypogammaglobulinemia &#x7684;&#x9010;&#x6B65;&#x4E27;&#x5931;&#x3002;&#x867D;&#x7136;&#x4ECE;&#x65E5;&#x672C; CAEBV &#x60A3;&#x8005;&#x7684; NK &#x7EC6;&#x80DE;&#x6570;&#x76EE;&#x6B63;&#x5E38;&#x6216;&#x589E;&#x52A0;&#xFF0C;&#x5F88;&#x591A;&#x6211;&#x4EEC;&#x7684;&#x75C5;&#x4EBA;&#x51CF;&#x5C11;&#x4E86; NK &#x7EC6;&#x80DE;&#x6570;&#x91CF;&#x3002;&#x514D;&#x75AB;&#x6291;&#x5236;&#x5242;&#x3001; &#x5229;&#x59A5;&#x6614;&#x5355;&#x6297;&#x3001; &#x81EA;&#x4F53;&#x7684;&#x7EC6;&#x80DE;&#x6BD2;&#x6027; T &#x7EC6;&#x80DE;&#x6216;&#x7EC6;&#x80DE;&#x6BD2;&#x5316;&#x7597;&#x5F80;&#x5F80;&#x5BFC;&#x81F4;&#x77ED;&#x671F;&#x5B66;&#x8D39;&#x51CF;&#x514D;&#xFF0C;&#x867D;&#x7136;&#x4ED6;&#x4EEC;&#x4E0D;&#x662F;&#x6CBB;&#x7597;&#x3002;&#x9020;&#x8840;&#x5E72;&#x7EC6;&#x80DE;&#x79FB;&#x690D;&#x662F;&#x901A;&#x5E38;&#x4E3A; CAEBV&#xFF0C;&#x5373;&#x4F7F;&#x5728;&#x672A;&#x54CD;&#x5E94;&#x5316;&#x7597;&#x7684;&#x79EF;&#x6781;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x589E;&#x751F;&#x6027;&#x75BE;&#x75C5;&#x60A3;&#x8005;&#x7684;&#x7597;&#x6548;&#x3002;&#x8FD9;&#x4E9B;&#x7814;&#x7A76;&#x5728; http://www.clinicaltrials.gov &#x4F5C;&#x4E3A; NCT00032513 CAEBV&#x3001; NCT00062868 &#x548C; NCT00058812 &#x4E3A;&#x6CE8;&#x518C; EBV &#x7279;&#x5B9A; T &#x7EC6;&#x80DE;&#x7684;&#x7814;&#x7A76;&#x548C; NCT00578539 &#x4E3A;&#x9020;&#x8840;&#x5E72;&#x7EC6;&#x80DE;&#x79FB;&#x690D;&#x534F;&#x8BAE;&#x3002;

&#x8868;&#x5F81;&#x53CA;&#x6CBB;&#x7597;&#x6162;&#x6027;&#x6D3B;&#x52A8;&#x7231;&#x6CFC;&#x65AF;&#x5766;-&#x5DF4;&#x5C14;&#x75C5;&#x6BD2;&#x75C5;&#xFF1A; &#x7F8E;&#x56FD; 28 &#x5E74;&#x7684;&#x7ECF;&#x9A8C;&#x3002;

Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoietic stem cell transplantation in the United States. Most cases of CAEBV have been reported from Japan. Unlike CAEBV in Japan, where EBV is nearly always found in T or natural killer (NK) cells in tissues, EBV was usually detected in B cells in tissues from our patients. Most patients presented with lymphadenopathy and splenomegaly; fever, hepatitis, and pancytopenia were common. Most patients died of infection or progressive lymphoproliferation. Unlike cases reported from Japan, our patients often showed a progressive loss of B cells and hypogammaglobulinemia. Although patients with CAEBV from Japan have normal or increased numbers of NK cells, many of our patients had reduced NK-cell numbers. Although immunosuppressive agents, rituximab, autologous cytotoxic T cells, or cytotoxic chemotherapy often resulted in short-term remissions, they were not curative. Hematopoietic stem cell transplantation was often curative for CAEBV, even in patients with active lymphoproliferative disease that was unresponsive to chemotherapy. These studies are registered at http://www.clinicaltrials.gov as NCT00032513 for CAEBV, NCT00062868 and NCT00058812 for EBV-specific T-cell studies, and NCT00578539 for the hematopoietic stem cell transplantation protocol.

Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States.

Maladie chronique de l&#39;EBV active (CAEBV) est un trouble lymphoprolif&eacute;ratif caract&eacute;ris&eacute; par un taux sensiblement &eacute;lev&eacute; d&#39;anticorps contre l&#39;EBV ou ADN EBV dans le sang et les EBV ARN ou les prot&eacute;ines dans les lymphocytes dans les tissus. Nous pr&eacute;sentons notre exp&eacute;rience avec CAEBV au cours des 28 derni&egrave;res ann&eacute;es, y compris les 8 premiers cas trait&eacute;s par la transplantation de cellules souches h&eacute;matopo&iuml;&eacute;tiques aux &Eacute;tats-Unis. Plupart des cas de CAEBV ont &eacute;t&eacute; signal&eacute;s du Japon. Contrairement &agrave; CAEBV au Japon, o&ugrave; EBV se trouve presque toujours en T ou des cellules (NK) tueuses naturels dans les tissus, EBV a &eacute;t&eacute; g&eacute;n&eacute;ralement d&eacute;tect&eacute; dans les cellules B dans les tissus de nos patients. La plupart des patients pr&eacute;sent&eacute;es une ad&eacute;nopathie et spl&eacute;nom&eacute;galie ; fi&egrave;vre, h&eacute;patite et pancytop&eacute;nie &eacute;taient fr&eacute;quents. La plupart des patients sont morts d&#39;infection ou progressifs lymphoprolif&eacute;ration. Contrairement aux cas rapport&eacute;s du Japon, nos patients ont souvent montrent une perte progressive des cellules B et hypogammaglobulin&eacute;mie. Bien que les patients atteints de CAEBV du Japon ont un nombre normal ou augment&eacute; de cellules NK, beaucoup de nos patients avaient r&eacute;duit le nombre de cellules NK. Bien que les agents immunosuppresseurs, rituximab, les cellules T cytotoxiques autologues ou chimioth&eacute;rapie cytotoxique ont souvent donn&eacute; lieu &agrave; des remises &agrave; court terme, ils n&#39;&eacute;taient pas curatifs. Cellules souches h&eacute;matopo&iuml;&eacute;tiques &eacute;tait souvent curatifs pour CAEBV, m&ecirc;me chez les patients avec maladie lymphoprolif&eacute;rative actif qui &eacute;tait insensible &agrave; la chimioth&eacute;rapie. Ces &eacute;tudes sont ajoutent au http://www.clinicaltrials.gov comme NCT00032513 pour CAEBV, NCT00062868 et NCT00058812 pour les &eacute;tudes de lymphocytes T sp&eacute;cifiques EBV et NCT00578539 pour le protocole de transplantation de cellules souches h&eacute;matopo&iuml;&eacute;tiques.

Caract&eacute;risation et traitement de la maladie chronique active virus Epstein - Barr : une exp&eacute;rience de 28 ans aux Etats-Unis.

Chronischer aktiver EBV-Krankheit (CAEBV) ist eine Lymphoproliferative Erkrankung mit deutlich erh&ouml;hte Konzentrationen von Antik&ouml;rpern gegen EBV oder EBV-DNA im Blut und EBV-RNA oder Proteine in Lymphozyten in Geweben. Wir pr&auml;sentieren unsere Erfahrung mit CAEBV w&auml;hrend der letzten 28 Jahre, einschlie&szlig;lich die ersten 8 F&auml;lle mit h&auml;matopoetischen Stammzelltransplantation in den Vereinigten Staaten behandelt. Die meisten F&auml;lle von CAEBV berichtet aus Japan. Im Gegensatz zu CAEBV in Japan, wo der EBV fast immer in T oder nat&uuml;rlichen killer (NK) Zellen in Geweben gefunden wird, wurde EBV in B-Zellen in Geweben aus unserer Patienten in der Regel erkannt. Die meisten Patienten mit Lymphadenopathie und Splenomegalie dargestellt; Fieber, Hepatitis und Panzytopenie waren &uuml;blich. Die meisten Patienten starben an Infektionen oder Progressive disseminiert. Im Gegensatz zu F&auml;llen berichtet aus Japan, unsere Patienten zeigte oft einen progressiven Verlust von B-Zellen und Hypogammaglobulin&auml;mie. Obwohl Patienten mit CAEBV aus Japan normal oder erh&ouml;ht Zahl der NK-Zellen haben, hatten viele unserer Patienten NK-Zell-Zahlen reduziert. Obwohl Immunsuppressiva, Rituximab, autologe zytotoxische T-Zellen oder zytotoxische Chemotherapie oft kurzfristige Remissionen gef&uuml;hrt, waren sie nicht heilenden. H&auml;matopoetische Stammzelltransplantation war oft kurative f&uuml;r CAEBV, sogar bei Patienten mit aktiven Lymphoproliferative Krankheit, die zur Chemotherapie nicht mehr reagierte. Diese Studien sind bei http://www.clinicaltrials.gov als NCT00032513 f&uuml;r CAEBV, NCT00062868 und NCT00058812 f&uuml;r EBV-spezifische T-Zell-Studien und NCT00578539 f&uuml;r das h&auml;matopoetische Stammzellen-Transplantation-Protokoll eingetragen.

Charakterisierung und Behandlung chronisch aktive Epstein - Barr-Virus-Krankheit: ein 28 Jahre Erfahrung in den Vereinigten Staaten.

Malattia cronica di EBV attiva (CAEBV) &egrave; una malattia linfoproliferativa caratterizzata da livelli marcatamente elevati di anticorpi per EBV o EBV DNA nel sangue ed EBV RNA o proteina nei linfociti nei tessuti. Vi presentiamo la nostra esperienza con CAEBV negli ultimi 28 anni, compresi i primi 8 casi trattati con trapianto di cellule staminali ematopoietiche negli Stati Uniti. La maggior parte dei casi di CAEBV sono stati segnalati dal Giappone. A differenza di CAEBV in Giappone, dove EBV &egrave; quasi sempre trovato in T o naturale killer (NK) cellule nei tessuti, EBV solitamente &egrave; stato rilevato nelle cellule B nei tessuti dai nostri pazienti. La maggior parte dei pazienti ha presentati con linfoadenopatia e splenomegalia; febbre, epatite e pancitopenia erano comuni. La maggior parte dei pazienti &egrave; morto di infezione o progressiva linfoproliferazione. A differenza dei casi segnalati dal Giappone, i nostri pazienti spesso hanno mostrato una progressiva perdita di cellule B e ipogammaglobulinemia. Anche se i pazienti con CAEBV dal Giappone hanno numeri normali o aumentati delle cellule NK, molti dei nostri pazienti aveva ridotto numero di cellule NK. Anche se gli agenti immunosoppressivi, rituximab, cellule di T linfociti autologhe o chemioterapia citotossica spesso portato a remissioni a breve termine, non erano curative. Trapianto di cellule staminali ematopoietiche &egrave; stato spesso curativo per CAEBV, anche nei pazienti con malattia linfoproliferativa attivo che &egrave; stato non risponde alla chemioterapia. Questi studi sono registrati presso http://www.clinicaltrials.gov come NCT00032513 per CAEBV, NCT00062868 e NCT00058812 per gli studi di EBV-specifiche delle cellule T e NCT00578539 per il protocollo di trapianto di cellule staminali ematopoietiche.

Caratterizzazione e trattamento della malattia cronica attiva virus Epstein - Barr: a 28 anni di esperienza negli Stati Uniti.

&#x6162;&#x6027;&#x30A2;&#x30AF;&#x30C6;&#x30A3;&#x30D6; EBV &#x75C5; (CAEBV) EBV &#x307E;&#x305F;&#x306F; eb &#x30A6;&#x30A4;&#x30EB;&#x30B9; DNA &#x8840;&#x3068; EBV RNA &#x307E;&#x305F;&#x306F;&#x86CB;&#x767D;&#x8CEA;&#x306E;&#x7D44;&#x7E54;&#x306B;&#x304A;&#x3051;&#x308B;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x6297;&#x4F53;&#x306E;&#x8457;&#x3057;&#x304F;&#x9AD8;&#x3044;&#x30EC;&#x30D9;&#x30EB;&#x306B;&#x3088;&#x3063;&#x3066;&#x7279;&#x5FB4;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x308B;&#x30EA;&#x30F3;&#x30D1;&#x5897;&#x6B96;&#x6027;&#x75BE;&#x60A3;&#x3067;&#x3059;&#x3002;&#x30A2;&#x30E1;&#x30EA;&#x30AB;&#x5408;&#x8846;&#x56FD;&#x306B;&#x304A;&#x3051;&#x308B;&#x9020;&#x8840;&#x5E79;&#x7D30;&#x80DE;&#x79FB;&#x690D;&#x3067;&#x306E;&#x6700;&#x521D;&#x306E; 8 &#x75C7;&#x4F8B;&#x3092;&#x542B;&#x3080;&#x6700;&#x5F8C;&#x306E; 28 &#x5E74;&#x9593; CAEBV &#x3068;&#x79C1;&#x305F;&#x3061;&#x306E;&#x7D4C;&#x9A13;&#x3092;&#x63D0;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;CAEBV &#x306E;&#x307B;&#x3068;&#x3093;&#x3069;&#x306E;&#x5834;&#x5408;&#x306F;&#x3001;&#x65E5;&#x672C;&#x304B;&#x3089;&#x5831;&#x544A;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;CAEBV &#x304C; EBV &#x306E;&#x307B;&#x307C;&#x5E38;&#x306B; T &#x307E;&#x305F;&#x306F;&#x30CA;&#x30C1;&#x30E5;&#x30E9;&#x30EB; &#x30AD;&#x30E9;&#x30FC; (NK) &#x7D30;&#x80DE;&#x7D44;&#x7E54;&#x4E2D;&#x306B;&#x898B;&#x3064;&#x304B;&#x3063;&#x305F;&#x3001;&#x65E5;&#x672C;&#x3068;&#x306F;&#x7570;&#x306A;&#x308A; EBV &#x901A;&#x5E38;&#x60A3;&#x8005;&#x3055;&#x307E;&#x304B;&#x3089;&#x7D44;&#x7E54;&#x306B;&#x304A;&#x3051;&#x308B; B &#x7D30;&#x80DE;&#x304C;&#x691C;&#x51FA;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x307B;&#x3068;&#x3093;&#x3069;&#x306E;&#x60A3;&#x8005;&#x306F;&#x30EA;&#x30F3;&#x30D1;&#x7BC0;&#x75C7;&#x3068;&#x813E;&#x816B;&#x3092;&#x63D0;&#x793A;;&#x767A;&#x71B1;&#x3001;&#x809D;&#x708E;, &#x6C4E;&#x8840;&#x7403;&#x6E1B;&#x5C11;&#x306F;&#x5171;&#x901A;&#x3067;&#x3057;&#x305F;&#x3002;&#x307B;&#x3068;&#x3093;&#x3069;&#x306E;&#x60A3;&#x8005;&#x306E;&#x611F;&#x67D3;&#x75C7;&#x3084;&#x30D7;&#x30ED;&#x30B0;&#x30EC;&#x30C3;&#x30B7;&#x30D6;&#x5E7C;&#x6B7B;&#x4EA1;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x30B1;&#x30FC;&#x30B9;&#x3068;&#x306F;&#x7570;&#x306A;&#x308A;&#x3001;&#x65E5;&#x672C;&#x304B;&#x3089;&#x306F;&#x3001;&#x79C1;&#x305F;&#x3061;&#x306E;&#x60A3;&#x8005;&#x306F;&#x3057;&#x3070;&#x3057;&#x3070; B &#x7D30;&#x80DE;&#x3068;&#x4F4E;&#x30AC;&#x30F3;&#x30DE;&#x30B0;&#x30ED;&#x30D6;&#x30EA;&#x30F3;&#x8840;&#x75C7;&#x306E;&#x9032;&#x6B69;&#x7684;&#x306A;&#x640D;&#x5931;&#x3092;&#x793A;&#x3057;&#x305F;&#x5831;&#x544A;&#x3002;CAEBV &#x65E5;&#x672C;&#x304B;&#x3089;&#x60A3;&#x8005;&#x304C; NK &#x7D30;&#x80DE;&#x306E;&#x6B63;&#x5E38;&#x307E;&#x305F;&#x306F;&#x5897;&#x52A0;&#x6570;&#x304C;&#x3001;&#x591A;&#x304F;&#x306E;&#x6211;&#x3005; &#x306E;&#x60A3;&#x8005;&#x306E; NK &#x7D30;&#x80DE;&#x6570;&#x3092;&#x6E1B;&#x5C11;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x514D;&#x75AB;&#x6291;&#x5236;&#x5264;&#x3001;&#x30EA;&#x30C4;&#x30AD;&#x30B7;&#x30DE;&#x30D6;&#x3001;&#x81EA;&#x5BB6;&#x7D30;&#x80DE;&#x50B7;&#x5BB3;&#x6027; T &#x7D30;&#x80DE;&#x307E;&#x305F;&#x306F;&#x7D30;&#x80DE;&#x6BD2;&#x6027;&#x5316;&#x5B66;&#x7642;&#x6CD5;&#x306E;&#x77ED;&#x671F;&#x7684;&#x306A;&#x5BDB;&#x89E3;&#x306F;&#x3057;&#x3070;&#x3057;&#x3070;&#x7D50;&#x679C;&#x304C;&#x3001;&#x5F7C;&#x3089;&#x306F;&#x6CBB;&#x7652;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x9020;&#x8840;&#x5E79;&#x7D30;&#x80DE;&#x79FB;&#x690D;&#x306F;&#x3001;&#x3057;&#x3070;&#x3057;&#x3070; CAEBV &#x306E;&#x6CBB;&#x7652;&#x304C;&#x5316;&#x5B66;&#x7642;&#x6CD5;&#x306B;&#x53CD;&#x5FDC;&#x3057;&#x306A;&#x3044;&#x30A2;&#x30AF;&#x30C6;&#x30A3;&#x30D6;&#x306A;&#x30EA;&#x30F3;&#x30D1;&#x5897;&#x6B96;&#x6027;&#x75BE;&#x60A3;&#x60A3;&#x8005;&#x306B;&#x304A;&#x3044;&#x3066;&#x3082;&#x3060;&#x3063;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x7814;&#x7A76;&#x3067; http://www.clinicaltrials.gov NCT00032513 &#x3068;&#x3057;&#x3066; CAEBV&#x3001;NCT00062868&#x3001;NCT00058812 &#x306E; eb &#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x7279;&#x7570;&#x7684; T &#x7D30;&#x80DE;&#x7814;&#x7A76;&#x3068; NCT00578539 &#x306E;&#x9020;&#x8840;&#x5E79;&#x7D30;&#x80DE;&#x79FB;&#x690D;&#x306E;&#x30D7;&#x30ED;&#x30C8;&#x30B3;&#x30EB;&#x304C;&#x767B;&#x9332;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;

&#x30AD;&#x30E3;&#x30E9;&#x30AF;&#x30BF;&#x30EA;&#x30BC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3068;&#x6162;&#x6027;&#x30A2;&#x30AF;&#x30C6;&#x30A3;&#x30D6; Eb &#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x75BE;&#x60A3;&#x306E;&#x6CBB;&#x7642;: &#x30A2;&#x30E1;&#x30EA;&#x30AB;&#x5408;&#x8846;&#x56FD;&#x306E; 28 &#x5E74;&#x306E;&#x7D4C;&#x9A13;&#x3002;

&#xB9CC;&#xC131; &#xD65C;&#xC131; EBV &#xC9C8;&#xBCD1; (CAEBV) lymphoproliferative &#xC7A5;&#xC560; &#xD608;&#xC561; &#xBC0F; EBV RNA &#xB610;&#xB294; &#xB2E8;&#xBC31;&#xC9C8;&#xC774; &#xC138;&#xD3EC; &#xC870;&#xC9C1;&#xC5D0;&#xC11C; EBV &#xB610;&#xB294; EBV DNA &#xD56D; &#xCCB4;&#xC758; &#xD604;&#xC800; &#xD558; &#xAC8C; &#xB192;&#xC740; &#xC218;&#xC900;&#xC5D0; &#xC758;&#xD574; &#xD2B9;&#xC9D5;&#xC785;&#xB2C8;&#xB2E4;. &#xBBF8;&#xAD6D;&#xC5D0;&#xC11C; &#xC870; &#xD608; &#xC904;&#xAE30; &#xC138;&#xD3EC; &#xC774;&#xC2DD;&#xC73C;&#xB85C; &#xCE58;&#xB8CC; &#xD558;&#xB294; &#xCC98;&#xC74C; 8 &#xCF00;&#xC774;&#xC2A4; &#xD3EC;&#xD568; &#xD558; &#xC5EC; &#xC9C0;&#xB09C; 28 &#xB144; &#xB3D9;&#xC548; CAEBV&#xC640; &#xC6B0;&#xB9AC;&#xC758; &#xD658;&#xACBD;&#xC744; &#xC18C;&#xAC1C;. CAEBV&#xC758; &#xB300;&#xBD80;&#xBD84;&#xC758; &#xACBD;&#xC6B0; &#xC77C;&#xBCF8;&#xC5D0;&#xC11C; &#xBCF4;&#xACE0; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC77C;&#xBCF8;, EBV&#xAC00; &#xAC70;&#xC758; &#xD56D;&#xC0C1; &#xC788;&#xB294; T &#xB610;&#xB294; &#xC790;&#xC5F0; &#xD0AC;&#xB7EC; (NK) &#xC138;&#xD3EC; &#xC870;&#xC9C1;&#xC5D0;, CAEBV&#xC640;&#xB294; &#xB2EC;&#xB9AC; EBV &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xC870;&#xC9C1;&#xC5D0;&#xC11C; B &#xC138;&#xD3EC;&#xC5D0;&#xC11C; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xAC10;&#xC9C0; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xB300;&#xBD80;&#xBD84;&#xC758; &#xD658;&#xC790; lymphadenopathy&#xC640;&#xB85C;; &#xAC04;&#xC5FC;, &#xBC1C;&#xC5F4;&#xACFC; pancytopenia &#xC77C;&#xBC18;&#xC801; &#xC774;&#xC5C8;&#xB2E4;&#xC785;&#xB2C8;&#xB2E4;. &#xB300;&#xBD80;&#xBD84;&#xC758; &#xD658;&#xC790;&#xB294; &#xAC10;&#xC5FC;&#xC774; &#xB098; &#xC9C4; lymphoproliferation &#xC8FD; &#xC5C8; &#xB2E4;. &#xACBD;&#xC6B0;&#xC640;&#xB294; &#xB2EC;&#xB9AC; &#xC77C;&#xBCF8;&#xC5D0;&#xC11C; &#xBCF4;&#xACE0; &#xD558;&#xB294; &#xC6B0;&#xB9AC;&#xC758; &#xD658;&#xC790; &#xC790;&#xC8FC; &#xBCF4;&#xC5EC; B &#xC138;&#xD3EC;&#xC640; hypogammaglobulinemia&#xC758; &#xC9C4;&#xBCF4;&#xC801;&#xC778; &#xC190;&#xC2E4;. &#xD658;&#xC790; &#xC77C;&#xBCF8;&#xC5D0;&#xC11C; CAEBV NK &#xC138;&#xD3EC;&#xC758; &#xC815;&#xC0C1; &#xB610;&#xB294; &#xC99D;&#xAC00; &#xB41C; &#xC22B;&#xC790;&#xB97C;&#xAC00;&#xC9C0;&#xACE0;, &#xBE44;&#xB85D; &#xB9CE;&#xC740; &#xD658;&#xC790;&#xC758; NK &#xC138;&#xD3EC; &#xC22B;&#xC790;&#xB97C; &#xAC10;&#xC18C; &#xD588;&#xB2E4;. &#xBA74;&#xC5ED; &#xC5D0;&#xC774;&#xC804;&#xD2B8;, rituximab, &#xD5CC; &#xC138;&#xD3EC; &#xB3C5;&#xC131; T &#xC138;&#xD3EC; &#xB610;&#xB294; cytotoxic &#xD654;&#xD559; &#xC694;&#xBC95; &#xC885;&#xC885; &#xB2E8;&#xAE30; remissions &#xACB0;&#xACFC;, &#xBE44;&#xB85D; &#xADF8;&#xB4E4;&#xC740; &#xCE58;&#xB8CC; &#xD588;&#xB2E4;. &#xC870; &#xD608; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xAC00; &#xC2DD;&#xC740; &#xC885;&#xC885; CAEBV, &#xB300; &#xD55C; &#xD654;&#xD559; &#xC694;&#xBC95;&#xC5D0; &#xBC18;&#xC751; &#xD558;&#xC9C0; &#xC54A;&#xC740; active lymphoproliferative &#xC9C8;&#xBCD1;&#xC744; &#xAC00;&#xC9C4; &#xD658;&#xC790; &#xC5D0;&#xC11C;&#xB3C4; &#xCE58;&#xB8CC; &#xD588;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xC5F0;&#xAD6C;&#xB294; &#xB4F1;&#xB85D; http://www.clinicaltrials.gov&#xC5D0; NCT00032513 CAEBV, NCT00062868 &#xBC0F; nct00058812&#xC5D0; &#xB300; &#xD55C; EBV &#xAD00;&#xB828; T-&#xC138;&#xD3EC; &#xC5F0;&#xAD6C;&#xC640; nct00578539&#xC5D0; &#xB300; &#xD55C; &#xC870; &#xD608; &#xC904;&#xAE30; &#xC138;&#xD3EC; &#xC774;&#xC2DD; &#xD504;&#xB85C;&#xD1A0;&#xCF5C;&#xC5D0; &#xB300; &#xD55C;.

&#xD2B9;&#xC131;&#xD654; &#xBC0F; &#xB9CC;&#xC131; &#xD65C;&#xC131; &#xC5E1; &#xC2A4;&#xD0C0;&#xC778;-&#xBC14; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xC9C8;&#xD658;&#xC758; &#xCE58;&#xB8CC;: &#xBBF8;&#xAD6D;&#xC5D0;&#xC11C; 28 &#xB144; &#xACBD;&#xD5D8;.

Enfermedad cr&oacute;nica de EBV activa (CAEBV) es un trastorno linfoproliferativo caracterizado por niveles marcado elevados de anticuerpos a EBV o VEB en la sangre y EBV ARN o prote&iacute;na en los linfocitos en los tejidos. Presentamos nuestra experiencia con CAEBV durante los &uacute;ltimos 28 a&ntilde;os, incluyendo los 8 primeros casos tratados con trasplante de c&eacute;lulas madre hematopoy&eacute;ticas en los Estados Unidos. Mayor&iacute;a de los casos de CAEBV ha divulgado de Jap&oacute;n. A diferencia de CAEBV en Jap&oacute;n, donde la EBV se encuentra casi siempre en T o las c&eacute;lulas asesinas naturales (NK) en tejidos, EBV fue detectado generalmente en las c&eacute;lulas de B en los tejidos de nuestros pacientes. Mayor&iacute;a de los pacientes presentada con linfadenopat&iacute;a y la esplenomegalia; fiebre, hepatitis y pancitopenia eran comunes. Mayor&iacute;a de los pacientes muri&oacute; de infecci&oacute;n o progresiva linfoproliferaci&oacute;n. A diferencia de casos notificados de Jap&oacute;n, a menudo, nuestros pacientes demostraron una p&eacute;rdida progresiva de las c&eacute;lulas B e Hipogammaglobulinemia. Aunque los pacientes con CAEBV de Jap&oacute;n tienen n&uacute;meros normales o aumento de las c&eacute;lulas NK, muchos de nuestros pacientes hab&iacute;an reducido el n&uacute;mero de c&eacute;lulas NK. Aunque agentes inmunosupresores, rituximab, las c&eacute;lulas T citot&oacute;xicas aut&oacute;logas o quimioterapia citot&oacute;xica a menudo result&oacute; en remisiones a corto plazo, no eran curativos. Trasplante de c&eacute;lulas madre hematopoy&eacute;ticas a menudo era curativo para CAEBV, incluso en pacientes con enfermedad linfoproliferativa activa que era insensible a la quimioterapia. Estos estudios est&aacute;n registrados en http://www.clinicaltrials.gov como NCT00032513 para CAEBV, NCT00062868 y NCT00058812 para estudios de EBV-espec&iacute;fica T-cell y NCT00578539 para el protocolo de trasplante de c&eacute;lulas madre hematopoy&eacute;ticas.

Caracterizaci&oacute;n y tratamiento de la enfermedad cr&oacute;nica activa Epstein - Barr virus: una experiencia de 28 a&ntilde;os en los Estados Unidos.

Molluscum contagiosum virus (MCV) is a poxvirus that causes localized papules in healthy persons. We evaluated a woman with severe immunodeficiency and disseminated MCV. During treatment with CMX-001, an antiviral with activity against other poxviruses, MCV DNA was detected in 20% of plasma samples. When the patient was not receiving CMX-001, MCV DNA was detected in 50% of samples. We also noted improvement in warts on her fingers during CMX-001 therapy. Although MCV is caused by direct inoculation of virus into skin in healthy persons, in a severely immunocompromised person MCV DNA was present in blood and may spread by viremia.

Detection of molluscum contagiosum virus (MCV) DNA in the plasma of an immunocompromised patient and possible reduction of MCV DNA with CMX-001.

Chronic active Epstein-Barr virus infection: a novel cause of lymphocytic variant hypereosinophilic syndrome.

Animal studies suggest that Borrelia burgdorferi, the agent of Lyme disease, may persist after antibiotic therapy and can be detected by various means including xenodiagnosis using the natural tick vector (Ixodes scapularis). No convincing evidence exists for the persistence of viable spirochetes after recommended courses of antibiotic therapy in humans. We determined the safety of using I. scapularis larvae for the xenodiagnosis of B. burgdorferi infection in humans.

Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study.

Lyme disease is the most common vector-borne disease in the United States. Some patients report persistent or intermittent subjective symptoms of mild to moderate intensity after antibiotic treatment for Lyme disease. We sought to evaluate trends in clinical and quality-of-life (QOL) measures in a cohort of patients with Lyme disease enrolled in a natural history study at the National Institutes of Health from 2001-2014.

Long-term Follow-up of Patients With Lyme Disease: Longitudinal Analysis of Clinical and Quality-of-life Measures.

Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture.

Xenodiagnosis is the use of a natural vector to detect the presence of an organism, and xenodiagnosis using Ixodes ticks has long been used by entomologists in Lyme disease research to provide evidence of the host's infectious status with Borrelia burgdorferi. We developed the methodology and performed the first human research study using uninfected larval Ixodes scapularis ticks to assess evidence of B. burgdorferi infection. Here, we describe in detail the methodology used for the procedure. Xenodiagnosis using Ixodes ticks in humans remains an experimental method and must be performed under an approved clinical research protocol.

Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans.

The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection.

Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide.

A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection.

Patients with classic hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that whites were less likely to develop systemic EBV disease (1/10) than nonwhites (5/6). All (10/10) of the white patients were generally in good health at last follow-up, while two-thirds (4/6) of the nonwhite patients required hematopoietic stem cell transplantation. Nonwhite patients had later age of onset of HVLPD than white patients (median age, 8 vs 5 years) and higher levels of EBV DNA (median, 1 515 000 vs 250 000 copies/ml) and more often had low numbers of NK cells (83% vs 50% of patients) and T-cell clones in the blood (83% vs 30% of patients). RNA-sequencing analysis of an HVLPD skin lesion in a white patient compared with his normal skin showed increased expression of interferon-γ and chemokines that attract T cells and NK cells. Thus, white patients with HVLPD were less likely to have systemic disease with EBV and had a much better prognosis than nonwhite patients. This trial was registered at www.clinicaltrials.gov as #NCT00369421 and #NCT00032513.

Hydroa vacciniforme-like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites.

Corrigendum to: Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

Article	Year
Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine. The Journal of infectious diseases\| PubMed ID: 20214479	2010
Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood\| PubMed ID: 21454450	2011
Detection of molluscum contagiosum virus (MCV) DNA in the plasma of an immunocompromised patient and possible reduction of MCV DNA with CMX-001. The Journal of infectious diseases\| PubMed ID: 22262788	2012
Chronic active Epstein-Barr virus infection: a novel cause of lymphocytic variant hypereosinophilic syndrome. Blood\| PubMed ID: 23520331	2013
Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America\| PubMed ID: 24523212	2014
Long-term Follow-up of Patients With Lyme Disease: Longitudinal Analysis of Clinical and Quality-of-life Measures. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America\| PubMed ID: 27025825	2016
Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. Journal of clinical microbiology\| PubMed ID: 28878005	2017
Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 29032557	2018
Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling. The Journal of infectious diseases\| PubMed ID: 29099929	2017
A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection. The Journal of infectious diseases\| PubMed ID: 31058977	2019
Hydroa vacciniforme-like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites. Blood\| PubMed ID: 31064750	2019
Corrigendum to: Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling. The Journal of infectious diseases\| PubMed ID: 32966578	2021

Siu Ping Turk

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