WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive protection against enteric fever– key considerations and research gaps

WHO preferred product characteristics for... | Gates Open Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://gatesopenresearch.org/js/vendor/ckeditor/' window.reactTheme = 'gates'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); Skip to content Gates Open Research file_upload Submit via VeriXiv search clear search menu close clear Search Browse Gateways & Collections How to Publish Submit via VeriXiv My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Publication Charges Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Contact Blog My Account Submissions Content and Tracking Alerts My Details Sign In Submit via VeriXiv { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://gatesopenresearch.org/articles/9-71" }, "headline": "WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive...", "datePublished": "2025-09-15T17:20:14", "dateModified": "2025-09-15T17:20:14", "author": [ { "@type": "Person", "name": "Ana Belen Ibarz Pavon" }, { "@type": "Person", "name": "John Clemens" }, { "@type": "Person", "name": "Alejandro Craviotto" }, { "@type": "Person", "name": "John A. Crump" }, { "@type": "Person", "name": "Denise O. Garrett" }, { "@type": "Person", "name": "Melita A. Gordon" }, { "@type": "Person", "name": "Jacob John" }, { "@type": "Person", "name": "Karen H. Keddy" }, { "@type": "Person", "name": "Matthew B. Laurens" }, { "@type": "Person", "name": "Xinxue Liu" }, { "@type": "Person", "name": "Florian Marks" }, { "@type": "Person", "name": "Andrew J. Pollard" }, { "@type": "Person", "name": "Senjuti Saha" }, { "@type": "Person", "name": "Annelies Wilder-Smith" } ], "publisher": { "@type": "Organization", "name": "Gates Open Research", "logo": { "@type": "ImageObject", "url": "https://gatesopenresearch.org/img/AMP/Gates_image.png", "height": 600, "width": 47 } }, "image": { "@type": "ImageObject", "url": "https://gatesopenresearch.org/img/AMP/Gates_image.png", "height": 1200, "width": 94 }, "description": "In 2021, Salmonella Paratyphi A caused >2 million illnesses, resulting in >14,000 deaths, most of which occurred among children under 5 years of age in socioeconomically deprived populations. Both typhoid fever and paratyphoid fever occur in such areas, but paratyphoid fever is currently concentrated in South Asia. Typhoid conjugate vaccines are recommended for the control of enteric fever in typhoid-endemic settings; however, there are increasing demands for the development of vaccines that can address enteric fever more broadly by including protection against paratyphoid fever. The WHO preferred product characteristics (PPC) and a research and development (R&D) technology roadmap are normative documents developed with the guidance and contribution of a multidisciplinary expert group following a standard methodological framework. In this paper, we summarize the PPC and R&D roadmap presenting the key attributes for a bivalent Salmonella enterica serovar Typhi and Paratyphi A vaccine, and discuss the identified key research and data gaps needed to optimize vaccine value and to inform public health and policy decisions, with a particular focus in paratyphoid and enteric fever endemic countries." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://gatesopenresearch.org/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://gatesopenresearch.org/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://gatesopenresearch.org/articles/9-71/v1", "name": "WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi..." } } ] } Home Browse WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Ibarz Pavon AB, Clemens J, Craviotto A et al. WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive protection against enteric fever– key considerations and research gaps . Gates Open Res 2025, 9 :71 ( https://doi.org/10.12688/gatesopenres.16364.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Open Letter WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive protection against enteric fever– key considerations and research gaps Ana Belen Ibarz Pavon https://orcid.org/0000-0002-8986-3448 1 , John Clemens 2-4 , Alejandro Craviotto 5 , [...] John A. Crump 6 , Denise O. Garrett 7 , Melita A. Gordon 8,9 , Jacob John 10 , Karen H. Keddy 11 , Matthew B. Laurens 12 , Xinxue Liu 13 , Florian Marks 2 , Andrew J. Pollard 13 , Senjuti Saha 14 , Annelies Wilder-Smith 1 Ana Belen Ibarz Pavon https://orcid.org/0000-0002-8986-3448 1 , John Clemens 2-4 , [...] Alejandro Craviotto 5 , John A. Crump 6 , Denise O. Garrett 7 , Melita A. Gordon 8,9 , Jacob John 10 , Karen H. Keddy 11 , Matthew B. Laurens 12 , Xinxue Liu 13 , Florian Marks 2 , Andrew J. Pollard 13 , Senjuti Saha 14 , Annelies Wilder-Smith 1 PUBLISHED 15 Sep 2025 Author details Author details 1 World Health Organization. Department of Immunization, Vaccines and Biologicals, Geneva, Switzerland 2 International Vaccine Institute, Seoul, South Korea 3 UCLA Fielding School of Public Health, Los Angeles, USA 4 Korea University School of Medicine, Seoul, South Korea 5 Universidad Autonoma de Mexico. Facultad de Medicina, Mexico City, Mexico 6 University of Otago. Centre for International Health., Dunedin, New Zealand 7 Sabin Vaccine Institute, Washington, District of Columbia, USA 8 University of Liverpool. Department of Infection, Veterinary & Ecological Sciences, Liverpool, UK 9 Malawi-Liverpool Wellcome Trust Program. Kamuzu University of Health Sciences, Blantyre, Malawi 10 Christian Medical College Vellore, Vellore, Tamil Nadu, India 11 University of Pretoria. Faculty of Veterinary Science. Department Veterinary Tropical Diseases, Pretoria, South Africa 12 University of Maryland Center for Vaccine Development and Global Health, Baltimore, Maryland, USA 13 University of Oxford Oxford Vaccine Group, Oxford, England, UK 14 Child Health Research Foundation, Dhaka, Dhaka Division, Bangladesh Ana Belen Ibarz Pavon Roles: Conceptualization, Methodology, Project Administration, Validation, Writing – Original Draft Preparation John Clemens Roles: Conceptualization, Validation, Writing – Review & Editing Alejandro Craviotto Roles: Conceptualization, Validation, Writing – Review & Editing John A. Crump Roles: Conceptualization, Validation, Writing – Review & Editing Denise O. Garrett Roles: Conceptualization, Validation, Writing – Review & Editing Melita A. Gordon Roles: Conceptualization, Validation, Writing – Review & Editing Jacob John Roles: Conceptualization, Validation, Writing – Review & Editing Karen H. Keddy Roles: Conceptualization, Validation, Writing – Review & Editing Matthew B. Laurens Roles: Conceptualization, Validation, Writing – Review & Editing Xinxue Liu Roles: Conceptualization, Validation, Writing – Review & Editing Florian Marks Roles: Conceptualization, Validation, Writing – Review & Editing Andrew J. Pollard Roles: Conceptualization, Validation, Writing – Review & Editing Senjuti Saha Roles: Conceptualization, Validation, Writing – Review & Editing Annelies Wilder-Smith Roles: Conceptualization, Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW Originally published as a preprint: https://doi.org/10.12688/verixiv.1752.1 Abstract In 2021, Salmonella Paratyphi A caused >2 million illnesses, resulting in >14,000 deaths, most of which occurred among children under 5 years of age in socioeconomically deprived populations. Both typhoid fever and paratyphoid fever occur in such areas, but paratyphoid fever is currently concentrated in South Asia. Typhoid conjugate vaccines are recommended for the control of enteric fever in typhoid-endemic settings; however, there are increasing demands for the development of vaccines that can address enteric fever more broadly by including protection against paratyphoid fever. The WHO preferred product characteristics (PPC) and a research and development (R&D) technology roadmap are normative documents developed with the guidance and contribution of a multidisciplinary expert group following a standard methodological framework. In this paper, we summarize the PPC and R&D roadmap presenting the key attributes for a bivalent Salmonella enterica serovar Typhi and Paratyphi A vaccine, and discuss the identified key research and data gaps needed to optimize vaccine value and to inform public health and policy decisions, with a particular focus in paratyphoid and enteric fever endemic countries. READ ALL READ LESS Keywords Salmonella enterica, typhoid fever, paratyphoid fever, vaccine Corresponding Author(s) Ana Belen Ibarz Pavon ( [email protected] ) Close Corresponding author: Ana Belen Ibarz Pavon Competing interests: Andrew J. Pollard is Chair of the Uk Department of Health and Social Care’s Joint Committee on Vaccines and Immunisation and was chair of WHOs technical advisory group on vaccines until 2025. He is a contributor to intellectual property on a COVID19 vaccine licensed by Oxford University Innovation to AstraZeneca. Oxford University has received funding for research on Salmonella vaccines from the Bill & Melinda Gates Foundation, the UK Medical Research Council, the Wellcome Trust, The European Commission and the Serum Institute of India. All other authors declare no competing interests in relation to this work. Grant information: This work received support through the Gates Foundation Globa Health Umbrella Grant (INV-005318). The funder had no role in the development of the present manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Ibarz Pavon AB et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Ibarz Pavon AB, Clemens J, Craviotto A et al. WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive protection against enteric fever– key considerations and research gaps . Gates Open Res 2025, 9 :71 ( https://doi.org/10.12688/gatesopenres.16364.1 ) First published: 15 Sep 2025, 9 :71 ( https://doi.org/10.12688/gatesopenres.16364.1 ) Latest published: 15 Sep 2025, 9 :71 ( https://doi.org/10.12688/gatesopenres.16364.1 ) Introduction Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A cause typhoid and paratyphoid fever respectively, which are collectively referred to as enteric fever. Paratyphoid fever may be caused by Salmonella serovars Paratyphi A, B or C, with S. Paratyphi A currently predominating. 1 Salmonella serovars Typhi and Paratyphi A are restricted to human hosts, and transmission occurs through the faecal-oral route via the ingestion of faecally-contaminated food and water. 2 , 3 The disease incubation period is typically 7 to 14 days, and commonly presents with fever, malaise, and mild gastrointestinal symptoms, often indistinguishable from other febrile illnesses. 3 , 4 Globally, in 2017 there were an estimated 11-27 million cases of enteric fever, and >120,000 associated deaths; 75% of illnesses and >85% of deaths are caused by Salmonella Typhi. 5 There is, however, evidence that Salmonella Paratyphi A is responsible for a growing proportion of enteric fever, and in endemic countries such as India or Nepal, paratyphoid fever can account for >40% of enteric fever. 6 – 8 Moreover, the unavailability of reliable routine diagnostic capacity and weak surveillance systems likely result in an underestimation of the true contribution of S. Paratyphi A to the burden of enteric fever. 9 , 10 Geographically, typhoid fever is found worldwide and presents a major public health problem to countries in Asia and sub-Saharan Africa, whereas paratyphoid fever is concentrated in, but is not limited to, countries in Asia and the Middle East. Both typhoid and paratyphoid fever are associated with unsanitary living conditions and lack of access to microbiologically safe water and food. While high population density in urban slums is a known risk factor for both typhoid and paratyphoid fever, typhoid fever in Africa is also frequently found in rural, low-population density sites across the continent. 11 , 12 There are substantial variations on the age distribution of both typhoid and paratyphoid fever across geographies and over time; however, enteric fever appears to be common among young children, and a substantial burden of disease remains until early adulthood. While the highest typhoid fever incidence rates are often found among children under five years of age, paratyphoid fever appears to peak later in life, often between 5 and 15 years of age. 5 Outcomes for enteric fever are improved with timely and appropriate antimicrobial therapy. However, antimicrobial resistance (AMR) is a growing concern. Resistance to traditional first-line treatment - ampicillin, chloramphenicol, and cotrimoxazole - among typhoidal Salmonella strains has been reported since the 1950s. 13 Resistance to all three antimicrobials, or multidrug resistance (MDR), has been documented since the 1980s. 14 , 15 The subsequent use of nalidixic acid and ciprofloxacin as alternative treatments for resistant enteric fever led to the emergence of fluoroquinolone non-susceptibility (FQNS) and ciprofloxacin resistance. Extensively drug resistant (XDR) strains are resistant to traditional first-line antimicrobials, fluoroquinolones, and third-generation cephalosporines: these emerged in Pakistan in 2016 and have spread worldwide through international travel. 16 – 19 While antimicrobial resistance patterns including MDR vary by place and serotype, both S. Typhi and S. Paratyphi A are currently reported to present FQNS at a prevalence of >90%, while XDR strains have been identified only in S. serovar Typhi to date. Access to microbiologically safer water and food, sanitation, and hygiene (WASH) practices remains important measures for the prevention of enteric fever. 21 However, in the absence of the resources required for the provision and development of such infrastructures, vaccines are a more viable alternative. Safe and effective vaccines against typhoid fever exist, and their programmatic use has been recommended by the World Health Organization (WHO) since 2008. The most recent WHO position paper, updated in 2018, recommends the use of typhoid conjugate vaccines (TCV) in the infant immunization schedule from 6 months of age, and promotes TCV introduction into the routine programmatic schedule at 9 months of age or in the second year of life in endemic countries with high disease burdens or with high AMR prevalence. 22 Single dose TCV has demonstrated high protective efficacy in paediatric and young adult populations in endemic areas, ranging from 79-85%. 23 – 28 However, evidence suggests a progressive decline of protection over time, particularly, among those who received the vaccine before the age of 2 years, and the need for a booster dose is currently under review. 29 , 30 While TCVs have been instrumental for typhoid fever control in highly endemic countries, and have successfully contributed to the containment of outbreaks caused by MDR and XDR strains, 18 , 28 the absence of a vaccine to prevent paratyphoid fever remains a critical gap in enteric fever prevention strategies. Current vaccine development efforts are focused on bivalent conjugate vaccine candidates that combine the antigen O:2, which is present in S. Paratyphi A, linked to a carrier protein with an existing TCV construct. 31 , 32 Some of these products are soon to start efficacy evaluations, which should corroborate existing evidence that antibody levels against the O:2 antigen correlate to serum bactericidal activity. 31 – 33 In addition, a live-attenuated vaccine candidate using the CVD 1902 strain of S. Paratyphi A was proven immunogenic in a phase 1 study, and it is currently being investigated for efficacy using a controlled human infection model (CHIM). 34 , 35 Vaccine developers and manufacturers rely on WHO guidance for research and development, regulation and prequalification pathways for novel vaccines. Currently, no such guidance has been released for paratyphoid vaccines, and immune correlates of protection for a paratyphoid vaccine are yet to be established. It is widely acknowledged that phase 3 efficacy trials for a Salmonella Paratyphi A-containing vaccines are unlikely to be logistically and economically feasible due to the lower prevalence of paratyphoid fever in comparison to typhoid fever. Hence, the WHO’s Product Development for Vaccines Advisory Committee (PDVAC) has endorsed a regulatory pathway for bivalent conjugate vaccines that would rely on data obtained from a CHIM in an adult population in a non-endemic country, paired with a phase 3 safety and immunogenicity trial in a target population, and the commitment from manufacturers to conduct post marketing effectiveness studies. 36 , 37 Following a consultative process with vaccine experts, developers, manufacturers, and policy-makers, the WHO has developed a technical research and development roadmap, and defined the preferred product characteristics (PPC) for Salmonella Paratyphi A-containing vaccines, aiming at guiding the work of vaccine developers, manufacturers, and funding bodies in regards to vaccine development and regulatory data requirements, ensuring that critical questions are addressed in a manner to facilitate regulatory processes of national and international bodies, and support robust policy decision-making after the products are available. 38 – 41 These documents provide considerations for bivalent conjugate and live-attenuated products, and highlight the current research gaps that might hinder decision-making in regards to the use and implementation of these vaccines in both: endemic settings where paratyphoid fever constitutes currently a public health concern, and non-endemic settings where Salmonella Paratyphi A could be introduced and fill in the niche that TCV could open by targeting Salmonella Typhi. Rationale and methodology Due to the lower incidence of paratyphoid fever relative to typhoid fever and its geographic distribution, a monovalent Salmonella Paratyphi A vaccine is unlikely to be commercially viable. 42 , 43 However, there is growing interest in addressing the public health burden of paratyphoid fever through the development of a bivalent S. Typhi/Paratyphi A vaccine. 44 – 46 The development of the bivalent Salmonella Typhi/Paratyphi A vaccines PPC and R&D roadmap responded to the need expressed by vaccine developers and manufacturers for WHO normative guidance on the characteristics of a successful vaccine that would have credence with decision-makers in settings endemic for paratyphoid fever, facilitate the regulatory and licensure procedures, and identify the research needs to ensure essential data and information gaps can be addressed during vaccine development. To this end, the WHO convened a Technical Advisory Group on Salmonella Vaccines (TAG-SV), a diverse group of experts with academic, vaccine development and regulatory background who advise the WHO in matters related to the research and development of Salmonella vaccines. The development of the PPC and R&D roadmap followed WHO’s established procedures for the development of normative documents. An initial baseline situation analysis was conducted through a literature review to identify current Salmonella Paratyphi A-containing vaccines in the development pipeline, and to assess where critical data gaps that could hinder their progression to licensure, implementation, and public health decision-making were found, and how to address these in an equitable manner. The TAG-SV conducted an iterative consultative process, structured as a collaborative effort, through technical consultations, and these were supplemented with contributions from external observers from regulatory agencies and manufacturing companies when required. Both the PPC and R&D roadmap documents underwent an open, public consultation, which received input from academic experts, industry partners, and regulatory agencies, and were reviewed and endorsed by PDVAC in December 2024. Vaccines under development There are currently two bivalent conjugate products in development. Both products link the Salmonella Paratyphi A O:2 antigen to a carrier protein, and combine it with a conjugate construct of Salmonella Typhi Vi-polysaccharide. The product most advanced in the development pipeline, the Serum Institute India bivalent paratyphoid A-typhoid conjugate vaccine (SII-PTCV) uses tetanus toxin (TT) as the protein carrier for the Vi-polysaccharide from Salmonella Typhi, and diphtheria toxoid (DT) for the O:2 antigen. The vaccine recently completed a phase 1 study in India that included 60 adults aged 18-45 years who received a single dose of either SII-PTCV, or the monovalent typhoid conjugate vaccine Typbar-TCV. Participants were followed for up to 181 days. The vaccine had a good safety profile, with mostly mild adverse events being reported and no significant differences between the intervention and comparator groups. The vaccine was immunogenic against Vi with a 97.7% and 93.3% seroconversion for anti-Vi IgG and anti-Vi IgA, respectively, in the intervention group 29 days post-vaccination, which was comparable to that observed among Typbar-TCV recipients and was sustained to day 181. The SII-PTCV vaccine was also immunogenic against O:2 with an observed increase in Serum Bactericidal Activity (SBA) titers post-vaccination and a sustained 100% seroconversion among SII-PTCV vaccine recipients but not in the Typbar-TCV control group. 32 A second bivalent conjugate product that uses O:2 and Vi-polysaccharide, both linked to the CRM 197 carrier protein is currently being developed by the GSK Vaccines Institute for Global Health (GVGH). The O:2-CRM 197 construct was shown to be immunogenic in pre-clinical studies in animal models, and reactive against a purposedly selected panel of clinical isolates. This vaccine is now progressing towards completion of phase 1 evaluation. 31 , 33 In addition to conjugate products, an oral live-attenuated bivalent vaccine containing a Salmonella Typhi CVD909 strain, which is the main component of a licensed oral vaccine against typhoid fever – Ty21 - and the CVD1902 strain of Salmonella Paratyphi A is under development by the University of Maryland, in collaboration with Bharat Biotech International and the University of Oxford. An oral live-attenuated monovalent CVD1902 vaccine was tested in healthy volunteers who ingested either a single dose of an increasing number of colony-forming units (CFUs) up to 10 10 or a placebo. The study showed that a single dose of at least 10 9 CFUs of CVD1902? was capable of eliciting cell-mediated immune responses that had the potential to be protective against S. Paratyphi A infection. 34 This vaccine has recently completed a CHIM, and preliminary results indicate that a CVD1902-containing oral vaccine is efficacious in protecting against S. Paratyphi A infection. The next step is now to combine the two strains: the typhoid CVD909 and paratyphoid CVD1902. 35 , 47 Vaccine preferred product characteristics Following the successful development and introduction of vaccines against typhoid fever, the logical next step is the development of a bivalent vaccine for broader control of enteric fever. Public health authorities across endemic and non-endemic countries have increasingly identified a bivalent vaccine containing a Salmonella Paratyphi A component as a critical need. Concern of increasing proportion of enteric fever cases caused by S. Paratyphi A, fear of a possible serovar replacement following the introduction of TCV, and increasing prevalence of AMR have driven demand. 8 , 45 , 48 – 50 The characteristics and use case for a bivalent Salmonella Typhi/Paratyphi A vaccine are mainly driven by the characteristics and most recent recommendations for TCVs. As outlined in Table 1 , the expectation would be for a vaccine that can prevent both typhoid and paratyphoid fever disease and their complications. The vaccine should be suitable to be safely administered from six months of age, and be suitable for administration through the routine infant immunization scheme as well as for its use in campaigns for outbreak control and other events of public health concern, such as an increase in intestinal perforations in a context where microbiologic confirmation of the underlying cause might be constrained. The bivalent vaccine would be expected to confer protection against typhoid fever non-inferior to that observed in TCVs, and be superior to naturally acquired immunity for the Salmonella Paratyphi A component. Regulatory recommendations for such vaccine have already been outlined by PDVAC and WHO, 36 , 37 and post marketing evaluations will be a requirement to corroborate safety, efficacy and immunogenicity findings, and to demonstrate non-interference between the two antigens in the bivalent vaccine, and among other vaccine antigens that might be co-administered within the vaccination schedule. 40 Table 1. Preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccines. 40 Parameter Preferred characteristics Notes Vaccine Type • A conjugated vaccine where the S. Typhi (Vi polysaccharide) and S. Paratyphi A antigens are linked to a protein carrier. • A live attenuated vaccine consisting of two attenuated strains: one S. Typhi, and one S. Paratyphi A. • A monovalent S. Paratyphi A vaccine is unlikely to be an attractive product, as the regions where paratyphoid fever is endemic prioritize the prevention of typhoid fever, which is currently a more prevalent aetiology. Target Population • Primarily targeted to infants from 6 months of age, to be implemented through the EPI and/or through catch-up or dedicated campaigns, and in response to specific situations such as high vulnerability or outbreaks. • The vaccine is primarily conceived for use in routine infant immunization programs. For conjugate products, the recommendation for the age of vaccination will be guided by the most recent recommendations for existing TCV (currently 6 months-65 years). • Use of the vaccine in pre-implementation catch-up campaigns, and its use for the control of outbreaks and other health events will be guided by the most recent recommendations for TCV. • Special consideration to be made for infants/children who have already received at least one dose of TCV, once data on the duration of the immune response to TCV, including modelling studies data, can inform the optimal time to administer a bivalent product. • Live-attenuated vaccines will need to ensure the formulation is appropriate for infants and toddlers to be able to swallow the product; otherwise, an adapted age-recommendation might be required. Schedule • For a conjugate vaccine, a single dose schedule implemented through the routine immunization program is desirable. A two-dose schedule might be feasible. • For live-attenuated vaccines, it is anticipated that, for the primary schedule, multiple doses administered a few days apart will be needed. For conjugated vaccines, s cheduling will be guided by the most up-to-date recommendations for TCVs. Ongoing modelling work will further inform the optimal timing for the primary dose and possible booster to ensure maximum protection during peak enteric fever age, while managing a feasible delivery strategy and cost-effectiveness. Safety • Safety and reactogenicity should be at least as favourable as existing TCV and other WHO-recommended routine parenteral and oral vaccines for use in the EPI, such as pentavalent vaccine, multivalent pneumococcal conjugate vaccine, MCV1 and MCV2, or rotavirus vaccine. Efficacy Targets • For conjugate vaccines, the typhoid component of the bivalent vaccine should the efficacy target is anti-Vi immunological non-inferiority to licensed TCV. The paratyphoid component, the vaccine will be required to demonstrate superiority to natural immunity, documented as a 4-fold rise on antibody titters, or as a GMT ratio >1 compared to natural infection. • For a live attenuated vaccine, vaccine efficacy will need to be demonstrated to both vaccine components, as no comparator is currently available. • While a Phase 3 efficacy trial would be the preferred standard to evaluate a S. Paratyphi A-containing vaccine, this has been deemed unfeasible. Alternatively, demonstration of vaccine effectiveness in a S. Paratyphi A CHIM could be accepted by regulators to grant licensure. • In the absence of phase 3 efficacy data post marketing phase 4 effectiveness studies will be required to corroborate vaccine efficacy. Serovar Coverage • S. Paratyphi A and S. Typhi for bivalent vaccines. Adjuvant Requirement • No adjuvant. • The inclusion of adjuvants might enhance reactogenicity. • Currently licensed TCV products do not contain adjuvants. Immunogenicity • For conjugate vaccines, the immunogenicity target of the S. Paratyphi A component would be superiority to naturally acquired immunity in an endemic population. • Live-attenuated vaccines are expected to generate an immune response targeting several antigens. There are currently no data available to identify which of these components will be relevant for immunogenicity and protection. Coadministration • Non-immunological interference between the two vaccine components in a bivalent S. Typhi/Paratyphi A vaccine. • Non-immunological or safety interference when co-administered with other vaccines in the routine immunization schedule. • Non-interference between the two vaccine antigens can be evaluated during vaccine development. • Non-interference when co-administered with other vaccines will need to be further evaluated in postmarketing phase 4 studies. Route of administration • Conjugated vaccines administered parenterally. Alternatively, a needle-free patch to deliver the product intramuscularly might be developed. • Live-attenuated vaccines administered orally as an enteric-coated capsule or a liquid formulation. Registration, WHO prequalification, and programme suitability • Licensure by a fully- accredited national regulatory agency. • WHO prequalification following standard processes, once the vaccine meets the WHO-defined suitability criteria. Vaccine Value Proposition • Dosage immunization regimen and cost of goods amenable to affordable supply. The vaccine should be cost-effective, and price should not be a barrier to access, including in LMICs. • A vaccine value profile was published in October 2023. 42 Research and development gaps Table 2 outlines the research gaps identified by the TAG-SV and other experts who contributed to the development of the document. 41 The development and implementation of TCVs prompted substantial investment from funders, governments, and other stakeholders to address epidemiology and burden of disease data gaps in preparation to TCV introductions into routine schedules and through immunization campaigns. Laboratory and population-based regional surveillance initiatives such as the Severe Typhoid in Africa (SETA) program, the Surveillance for Enteric Fever in Asia Project (SEAP), Surveillance for Enteric Fever in India (SEFI), and the Strategic Typhoid Alliance Across Africa and Asia (STRAATA) aimed at characterising the incidence and outcomes of enteric fever, with a focus on typhoid fever. 12 , 51 , 52 While these surveillance initiatives have shed light into the burden and distribution of paratyphoid fever and its contribution to the overall burden of enteric fever, substantial uncertainty remains regarding the true disease incidence – particularly by age group – due to small case numbers and resulting statistical limitations. n age sub-groups. 53 – 55 Moreover, while paratyphoid fever is recognised as endemic in Asia and the Middle East, its presence in sub-Saharan Africa is increasingly being documented. 56 – 59 Table 2. Priority activities as expressed in the research and development technology roadmap for bivalent Salmonella Typhi/Paratyphi A vaccines. Key strategic areas Proposed priority activities Research • Implementation/improvement of enteric fever laboratory-based surveillance systems and data completeness and quality • Data reporting and burden of disease estimates • Addressing the diagnostic gaps by: ○ building and sustaining microbiology laboratory capacity for isolation, identification, and serotyping of Salmonella from blood culture ○ development of accurate, easy to use diagnostic alternatives to blood culture • Use of modelling to estimate the impact of a S. Paratyphi A-containing vaccine on disease dynamics, containment of AMR, vaccine cost-effectiveness and cost-benefit analyses Vaccine development • Define the appropriate efficacy trial design and clinical endpoints in a scenario where a phase 3 efficacy trial will not be feasible • Define correlates of protection for S. Paratyphi A antigens, and production of reference standards for vaccine evaluation • Clear regulatory approach and pathway to licensure at national and international level • Immune interference studies for coadministration with other vaccine antigens in the routine immunization schedule Public health impact • Clear understanding of vaccine buy-in needs for ○ Paratyphoid fever endemic countries ○ Typhoid fever endemic countries where S. Paratyphi A? is not currently present ○ Travellers market • Cost-effectiveness and cost-benefit analyses Key capacities • Public health workforce capacity building • Develop effectiveness and safety vigilance systems for post marketing evaluation and surveillance (including enhance laboratory capacity) • Sustainable financing mechanisms and incentives for vaccine supply • Effective communication and stakeholders' engagement Traditionally, in the absence of laboratory capacity for complete Salmonella identification, the term enteric fever has been equated to typhoid fever, which has resulted in an underappreciation of the role of paratyphoid fever. Furthermore, when typing does not extend to distinguishing among Salmonella Paratyphi A, B, and C, paratyphoid fever may be assumed to be mostly caused by S. Paratyphi A. 60 , 61 Building microbiology diagnostic capacity in endemic settings, and developing rapid, easy-to-use, affordable diagnostic tests that can discriminate between invasive Salmonella serovars remain a priority to generate good quality, complete surveillance data suitable for decision-making. Although modelling provides insight, robust primary data remain essential. One of the main requests from vaccine developers has been for clear guidance on the regulatory processes, and the role of CHIM to evaluate vaccine efficacy in the absence of phase 3 data. The WHO’s PDVAC endorsed an alternative regulatory pathway, which would consider the evaluation of efficacy data from a CHIM in non-endemic populations, paired with an immunogenicity and safety study in no less than 3,000 subjects in an endemic, target population, and provided there is commitment from manufacturers for post marketing evaluation of safety, effectiveness, and non-interference. 36 WHO convened an expert consultation with academics, vaccine developers, and regulators, where all key stakeholders expressed their openness to license bivalent vaccines on those bases. 37 Finally, while a favourable vaccine value profile for bivalent Salmonella Typhi/Paratyphi A vaccines was published in 2023, 42 decision-making stakeholders will still need evidence of the cost-benefit and cost-effectiveness of using a bivalent vaccine, and the cost implications in comparison to the use of a monovalent TCV. For this, it is imperative that key capacities are strengthened in-country to ensure nationally-owned and operated sustainable surveillance and reporting systems for enteric fever and other invasive Salmonella diseases, which will, in turn, facilitate the implementation of post marketing evaluations and continuous vigilance of vaccine safety events, and generate evidence-based information to support the implementation of sustainable funding for the use of bivalent vaccines, and market incentives to ensure vaccine supply. Conclusions Despite the advances in the control of enteric fever caused by Salmonella Typhi worldwide, the development of a vaccine that addresses enteric fever more broadly by adding protection against Salmonella Paratyphi A remains a priority for endemic countries. Moreover, the WHO’s vision calls for a broadly protective Salmonella vaccine for the prevention of invasive disease caused by both typhoidal and non-typhoidal Salmonella (NTS) serovars. Quadrivalent vaccines covering the four predominant Salmonella serovars: Salmonella Typhi, Paratyphi A, Typhimurium, and Enteritidis, are increasingly recognized as a strategic priority, particularly in the context of minimizing childhood injections. 62 The bivalent Salmonella Typhi/Paratyphi A vaccine represents a first step towards that vision and, in conjunction with national surveillance and laboratory capacity strengthening, and ongoing improvements in WASH practices, has the potential to significantly reduce the burden of infection and mitigate the spread of AMR in low-and-middle income countries, where populations are most impacted. Competing interests Andrew J. Pollard is Chair of the Uk Department of Health and Social Care’s Joint Committee on Vaccines and Immunisation and was chair of WHOs technical advisory group on vaccines until 2025. He is a contributor to intellectual property on a COVID19 vaccine licensed by Oxford University Innovation to AstraZeneca. Oxford University has received funding for research on Salmonella vaccines from the Bill & Melinda Gates Foundation, the UK Medical Research Council, the Wellcome Trust, The European Commission and the Serum Institute of India. All other authors declare no competing interests in relation to this work. Grant information This work received support through the Gates Foundation Globa Health Umbrella Grant (INV-005318). The funder had no role in the development of the present manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgements The authors would like to thank the WHO Product Development for Vaccines Advisory Committee for the review of the WHO PPC and WHO R&D Roadmap for bivalent Salmonella Typhi/Paratyphi A vaccines, and the many stakeholders who contributed with valuable input during the public consultation. References 1. Kariuki S, Cheesbrough J, Mavridis AK, et al. : Typing of Salmonella enterica Serotype Paratyphi C Isolates from Various Countries by Plasmid Profiles and Pulsed-Field Gel Electrophoresis. J. Clin. Microbiol. 1999 Jun; 37 (6):2058–2060. PubMed Abstract | Publisher Full Text | Free Full Text 2. Bhan MK, Bahl R, Bhatnagar S: Typhoid and paratyphoid fever. Lancet Lond Engl. 2005 Sep 27; 366 (9487):749–762. Publisher Full Text 3. Sanderson KE, Liu SL, Tang L, et al. : Chapter 71 - Salmonella Typhi and Salmonella Paratyphi A. Tang YW, Sussman M, Liu D, et al. , editors. Molecular Medical Microbiology. Boston: Academic Press; Second Edition.2015 [cited 2023 Jul 25]; pp.1275–1306. Reference Source 4. Luby SP: Bacteria: Salmonella Typhi and Salmonella Paratyphi.Motarjemi Y, editor. Encyclopedia of Food Safety. Waltham: Academic Press;2014 [cited 2023 Oct 29]; pp.515–522. Reference Source 5. Stanaway JD, Reiner RC, Blacker BF, et al. : The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect. Dis. 2019 Apr 1; 19 (4):369–381. PubMed Abstract | Publisher Full Text | Free Full Text 6. Zellweger RM, Basnyat B, Shrestha P, et al. : A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital. PLoS Negl. Trop. Dis. 2017 Nov; 11 (11):e0006051. PubMed Abstract | Publisher Full Text | Free Full Text 7. Karki S, Shakya P, Cheng AC, et al. : Trends of etiology and drug resistance in enteric fever in the last two decades in Nepal: a systematic review and meta-analysis. Clin. Infect. Dis. 2013 Nov; 57 (10):e167–e176. PubMed Abstract | Publisher Full Text 8. Sahastrabuddhe S, Carbis R, Wierzba TF, et al. : Increasing rates of Salmonella Paratyphi A and the current status of its vaccine development. Expert Rev. Vaccines. 2013 Sep; 12 (9):1021–1031. Publisher Full Text 9. Arndt MB, Mosites EM, Tian M, et al. : Estimating the Burden of Paratyphoid A in Asia and Africa. PLoS Negl. Trop. Dis. 2014 Jun 5; 8 (6):e2925. PubMed Abstract | Publisher Full Text | Free Full Text 10. Furuse Y: Analysis of research intensity on infectious disease by disease burden reveals which infectious diseases are neglected by researchers. Proc. Natl. Acad. Sci. 2019 Jan 8; 116 (2):478–483. PubMed Abstract | Publisher Full Text | Free Full Text 11. Marks F, von Kalckreuth V , Aaby P, et al. : Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study. Lancet Glob. Health. 2017 Mar 1; 5 (3):e310–e323. PubMed Abstract | Publisher Full Text | Free Full Text 12. Marks F, Im J, Park SE, et al. : Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study. Lancet Glob. Health. 2024 Apr 1; 12 (4):e599–e610. PubMed Abstract | Publisher Full Text | Free Full Text 13. Colquhoun J, Weetch RS: Resistance to chloramphenicol developing during treatment of typhoid fever. Lancet. 1950 Nov 25; 256 (6639):621–623. Publisher Full Text 14. Threlfall EJ, Ward LR: Decreased susceptibility to ciprofloxacin in Salmonella enterica serotype typhi, United Kingdom. Emerg. Infect. Dis. 2001; 7 (3):448–450. PubMed Abstract | Publisher Full Text | Free Full Text 15. Holt KE, Phan MD, Baker S, et al. : Emergence of a Globally Dominant IncHI1 Plasmid Type Associated with Multiple Drug Resistant Typhoid. PLoS Negl. Trop. Dis. 2011 Jul 19; 5 (7):e1245. PubMed Abstract | Publisher Full Text | Free Full Text 16. Saha S, Sajib MSI, Garrett D, et al. : Antimicrobial Resistance in Typhoidal Salmonella: Around the World in 3 Days. Clin. Infect. Dis. 2020 Jul 29; 71 (Supplement_2):S91–S95. PubMed Abstract | Publisher Full Text | Free Full Text 17. Saha SK, Tabassum N, Saha S: Typhoid Conjugate Vaccine: An Urgent Tool to Combat Typhoid and Tackle Antimicrobial Resistance. J. Infect. Dis. 2021 Dec 20; 224 (12 Suppl 2):S788–S791. PubMed Abstract | Publisher Full Text | Free Full Text 18. Yousafzai MT, Karim S, Qureshi S, et al. : Effectiveness of typhoid conjugate vaccine against culture-confirmed Salmonella enterica serotype Typhi in an extensively drug-resistant outbreak setting of Hyderabad, Pakistan: a cohort study. Lancet Glob. Health. 2021 Aug; 9 (8):e1154–e1162. PubMed Abstract | Publisher Full Text | Free Full Text 19. Zakir M, Khan M, Umar MI, et al. : Emerging Trends of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Salmonella Typhi in a Tertiary Care Hospital of Lahore, Pakistan. Microorganisms. 2021 Nov 30; 9 (12):2484. PubMed Abstract | Publisher Full Text | Free Full Text 20. GRAM Typhoid Collaborators: Estimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990-2019: a modelling study. Lancet Glob. Health. 2024 Mar; 12 (3):e406–e418. 21. Waddington CS, Darton TC, Pollard AJ: The challenge of enteric fever. J. Infect. 2014 Jan 1; 68 :S38–S50. Publisher Full Text 22. Typhoid vaccines: WHO position paper - March 2018.[cited 2023 Jul 16]. Reference Source 23. Patel PD, Liang Y, Meiring JE, et al. : Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children. Lancet Lond. Engl. 2024 Feb 3; 403 (10425):459–468. PubMed Abstract | Publisher Full Text | Free Full Text 24. Qadri F, Khanam F, Liu X, et al. : Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial. Lancet. 2021 Aug 21; 398 (10301):675–684. PubMed Abstract | Publisher Full Text | Free Full Text 25. Shakya M, Voysey M, Theiss-Nyland K, et al. : Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial. Lancet Glob. Health. 2021 Nov; 9 (11):e1561–e1568. PubMed Abstract | Publisher Full Text | Free Full Text 26. Hoffman SA, LeBoa C, Date K, et al. : Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India. Clin. Infect. Dis. 2023 Jul 5; 77 (1):138–144. PubMed Abstract | Publisher Full Text | Free Full Text 27. Batool R, Tahir Yousafzai M, Qureshi S, et al. : Effectiveness of typhoid conjugate vaccine against culture-confirmed typhoid in a peri-urban setting in Karachi: A case-control study. Vaccine. 2021 Sep 24; 39 (40):5858–5865. PubMed Abstract | Publisher Full Text 28. Lightowler MS, Manangazira P, Nackers F, et al. : Effectiveness of typhoid conjugate vaccine in Zimbabwe used in response to an outbreak among children and young adults: A matched case control study. Vaccine. 2022 Jul 29; 40 (31):4199–4210. PubMed Abstract | Publisher Full Text 29. Qadri F, Khanam F, Zhang Y, et al. : 5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial. Lancet Lond Engl. 2024 Oct 12; 404 (10461):1419–1429. PubMed Abstract | Publisher Full Text 30. Qamar FN, Qureshi S, Haq Z, et al. : Longevity of immune response after a single dose of typhoid conjugate vaccine against Salmonella Typhi among children in Hyderabad, Pakistan. Int. J. Infect. Dis. 2024 Oct; 147 :107187. Publisher Full Text 31. Alfini R, Carducci M, Massai L, et al. : Design of a Glycoconjugate Vaccine Against Salmonella Paratyphi A. Vaccines. 2024 Nov; 12 (11):1272. PubMed Abstract | Publisher Full Text | Free Full Text 32. Kulkarni PS, Potey AV, Bharati S, et al. : The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial. Lancet Lond. Engl. 2024 Apr 20; 403 (10436):1554–1562. PubMed Abstract | Publisher Full Text 33. Pinto M, Durante S, Carducci M, et al. : The Salmonella Paratyphi A O-Antigen Glycoconjugate Vaccine Is Able to Induce Antibodies with Bactericidal Activity Against a Panel of Clinical Isolates. Vaccines. 2025 Feb; 13 (2):122. PubMed Abstract | Publisher Full Text | Free Full Text 34. Wahid R, Kotloff KL, Levine MM, et al. : Cell mediated immune responses elicited in volunteers following immunization with candidate live oral Salmonella enterica serovar Paratyphi A attenuated vaccine strain CVD 1902. Clin. Immunol. Orlando Fla. 2019 Apr; 201 :61–69. PubMed Abstract | Publisher Full Text | Free Full Text 35. McCann N, Emary K, Singh N, et al. : Accelerating clinical development of a live attenuated vaccine against Salmonella Paratyphi A (VASP): study protocol for an observer-participant-blind randomised control trial of a novel oral vaccine using a human challenge model of Salmonella Paratyphi A infection in healthy adult volunteers. BMJ Open. 2023 May 24; 13 (5):e068966. PubMed Abstract | Publisher Full Text 36. Kaslow D, Karron R: WHO/IVB’s Product Development for Vaccines Advisory Committee (PDVAC) Report from Hybrid F2F/Virtual meeting. Geneva, Switzerland:2022 Dec [cited 2024 Sep 25]. Reference Source 37. Ibarz-Pavon AB, Bielsky MC, Bose R, et al. : Consultation report - considerations for a regulatory pathway for bivalent Salmonella Typhi/Paratyphi A vaccines for use in endemic countries. Vaccine. 2025 May 22; 56 :127189. PubMed Abstract | Publisher Full Text | Free Full Text 38. Product & Delivery Research:[cited 2025 Mar 19]. Reference Source 39. Product development roadmaps:[cited 2025 Mar 19]. Reference Source 40. WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccines. Geneva, Switzerland: World health organization;2025 Jul. License: CC BY-NC-SA 3.0 IGO. Reference Source 41. Salmonella Paratyphi A bivalent vaccine: research and development technology roadmap. Geneva, Switzerland: World Health Organization;2025 Jul. License: CC BY-NC-SA 3.0 IGO. Reference Source 42. Martin LB, Khanam F, Qadri F, et al. : Vaccine value profile for Salmonella enterica serovar Paratyphi A. Vaccine. 2023 Oct 6 [cited 2023 Oct 30]; 41 :S114–S133. PubMed Abstract | Publisher Full Text Reference Source 43. Shakya M, Neuzil KM, Pollard AJ: Prospects of Future Typhoid and Paratyphoid Vaccines in Endemic Countries. J. Infect. Dis. 2021 Aug 10; 224 (Suppl 7):S770–S774. PubMed Abstract | Publisher Full Text | Free Full Text 44. Dong BQ, Yang J, Wang XY, et al. : Trends and disease burden of enteric fever in Guangxi province, China, 1994–2004. Bull. World Health Organ. 2010 Sep 1; 88 (9):689–696. PubMed Abstract | Publisher Full Text | Free Full Text 45. Baker S, Karkey A, Parry C: Are we adequately prepared for the emergence of Salmonella enterica serovar Paratyphi A? Lancet Glob. Health. 2014 Apr 1; 2 (4):e195–e196. PubMed Abstract | Publisher Full Text 46. Martin LB, Simon R, MacLennan CA, et al. : Status of paratyphoid fever vaccine research and development. Vaccine. 2016 Jun 3; 34 (26):2900–2902. PubMed Abstract | Publisher Full Text 47. Dobinson HC, Gibani MM, Jones C, et al. : Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model. Clin. Infect. Dis. 2017 Apr 15; 64 (8):1066–1073. PubMed Abstract | Publisher Full Text | Free Full Text 48. Crump JA, Mintz ED: Global trends in typhoid and paratyphoid Fever. Clin. Infect. Dis. 2010 Jan 15; 50 (2):241–246. PubMed Abstract | Publisher Full Text | Free Full Text 49. da Silva KE , Tanmoy AM, Pragasam AK, et al. : The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study. Lancet Microbe. 2022 Aug; 3 (8):e567–e577. PubMed Abstract | Publisher Full Text | Free Full Text 50. Holt KE, Thomson NR, Wain J, et al. : Multidrug-Resistant Salmonella enterica Serovar Paratyphi A Harbors IncHI1 Plasmids Similar to Those Found in Serovar Typhi. J. Bacteriol. 2007 Jun; 189 (11):4257–4264. PubMed Abstract | Publisher Full Text | Free Full Text 51. Carey ME, MacWright WR, Im J, et al. : The Surveillance for Enteric Fever in Asia Project (SEAP), Severe Typhoid Fever Surveillance in Africa (SETA), Surveillance of Enteric Fever in India (SEFI), and Strategic Typhoid Alliance Across Africa and Asia (STRATAA) Population-based Enteric Fever Studies: A Review of Methodological Similarities and Differences. Clin. Infect. Dis. 2020 Jul 29; 71 (Suppl 2):S102–S110. Publisher Full Text 52. Hancuh M, Walldorf J, Minta AA, et al. : Typhoid Fever Surveillance, Incidence Estimates, and Progress Toward Typhoid Conjugate Vaccine Introduction — Worldwide, 2018–2022. Morb. Mortal. Wkly Rep. 2023 Feb 17; 72 (7):171–176. PubMed Abstract | Publisher Full Text | Free Full Text 53. Britto C, Pollard AJ, Voysey M, et al. : An Appraisal of the Clinical Features of Pediatric Enteric Fever: Systematic Review and Meta-analysis of the Age-Stratified Disease Occurrence. Clin. Infect. Dis. 2017 Jun 1; 64 (11):1604–1611. PubMed Abstract | Publisher Full Text | Free Full Text 54. Saha T, Arisoyin AE, Bollu B, et al. : Enteric Fever: Diagnostic Challenges and the Importance of Early Intervention. Cureus. 2023 Jul; 15 (7):e41831. PubMed Abstract | Publisher Full Text 55. Yousafzai MT, Irfan S, Thobani RS, et al. : Burden of Culture Confirmed Enteric Fever Cases in Karachi, Pakistan: Surveillance For Enteric Fever in Asia Project (SEAP), 2016-2019. Clin. Infect. Dis. 2020 Dec 1; 71 (Suppl 3):S214–S221. PubMed Abstract | Publisher Full Text | Free Full Text 56. Amsalu T, Genet C, Adem SY: Salmonella Typhi and Salmonella Paratyphi prevalence, antimicrobial susceptibility profile and factors associated with enteric fever infection in Bahir Dar, Ethiopia. Sci. Rep. 2021 Apr 1; 11 :7359. PubMed Abstract | Publisher Full Text | Free Full Text 57. Carey ME, Dyson ZA, Ingle DJ, et al. : Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. elife. 12 :e85867. PubMed Abstract | Publisher Full Text | Free Full Text 58. Ndima Etouke TA, Ful Kuh G, Djoumsie Gomseu BE, et al. : Epidemiology of Multidrug-Resistant Salmonella Typhi and Paratyphi Isolated From Stool Culture. J. Trop. Med. 2024; 2024 (1):3480080. PubMed Abstract | Publisher Full Text | Free Full Text 59. Njoya HF, Awolu MM, Christopher TB, et al. : Prevalence and awareness of mode of transmission of typhoid fever in patients diagnosed with Salmonella typhi and paratyphi infections at the Saint Elisabeth General Hospital Shisong, Bui Division. Cameroon. Pan Afr Med J. 2021; 40 :83. 60. Darton TC, Meiring JE, Tonks S, et al. : The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys. BMJ Open. 2017 Jul 2; 7 (6):e016283. PubMed Abstract | Publisher Full Text | Free Full Text 61. Park SE, Toy T, Cruz Espinoza LM, et al. : The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis. Clin. Infect. Dis. 2019 Oct 30; 69 (Suppl 6):S422–S434. PubMed Abstract | Publisher Full Text | Free Full Text 62. MacLennan CA, Stanaway J, Grow S, et al. : Salmonella Combination Vaccines: Moving Beyond Typhoid. Open Forum Infect. Dis. 2023 May; 10 (Suppl 1):S58–S66. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 15 Sep 2025 ADD YOUR COMMENT Comment Author details Author details 1 World Health Organization. Department of Immunization, Vaccines and Biologicals, Geneva, Switzerland 2 International Vaccine Institute, Seoul, South Korea 3 UCLA Fielding School of Public Health, Los Angeles, USA 4 Korea University School of Medicine, Seoul, South Korea 5 Universidad Autonoma de Mexico. Facultad de Medicina, Mexico City, Mexico 6 University of Otago. Centre for International Health., Dunedin, New Zealand 7 Sabin Vaccine Institute, Washington, District of Columbia, USA 8 University of Liverpool. Department of Infection, Veterinary & Ecological Sciences, Liverpool, UK 9 Malawi-Liverpool Wellcome Trust Program. Kamuzu University of Health Sciences, Blantyre, Malawi 10 Christian Medical College Vellore, Vellore, Tamil Nadu, India 11 University of Pretoria. Faculty of Veterinary Science. Department Veterinary Tropical Diseases, Pretoria, South Africa 12 University of Maryland Center for Vaccine Development and Global Health, Baltimore, Maryland, USA 13 University of Oxford Oxford Vaccine Group, Oxford, England, UK 14 Child Health Research Foundation, Dhaka, Dhaka Division, Bangladesh Ana Belen Ibarz Pavon Roles: Conceptualization, Methodology, Project Administration, Validation, Writing – Original Draft Preparation John Clemens Roles: Conceptualization, Validation, Writing – Review & Editing Alejandro Craviotto Roles: Conceptualization, Validation, Writing – Review & Editing John A. Crump Roles: Conceptualization, Validation, Writing – Review & Editing Denise O. Garrett Roles: Conceptualization, Validation, Writing – Review & Editing Melita A. Gordon Roles: Conceptualization, Validation, Writing – Review & Editing Jacob John Roles: Conceptualization, Validation, Writing – Review & Editing Karen H. Keddy Roles: Conceptualization, Validation, Writing – Review & Editing Matthew B. Laurens Roles: Conceptualization, Validation, Writing – Review & Editing Xinxue Liu Roles: Conceptualization, Validation, Writing – Review & Editing Florian Marks Roles: Conceptualization, Validation, Writing – Review & Editing Andrew J. Pollard Roles: Conceptualization, Validation, Writing – Review & Editing Senjuti Saha Roles: Conceptualization, Validation, Writing – Review & Editing Annelies Wilder-Smith Roles: Conceptualization, Supervision, Validation, Writing – Review & Editing Competing interests Andrew J. Pollard is Chair of the Uk Department of Health and Social Care’s Joint Committee on Vaccines and Immunisation and was chair of WHOs technical advisory group on vaccines until 2025. He is a contributor to intellectual property on a COVID19 vaccine licensed by Oxford University Innovation to AstraZeneca. Oxford University has received funding for research on Salmonella vaccines from the Bill & Melinda Gates Foundation, the UK Medical Research Council, the Wellcome Trust, The European Commission and the Serum Institute of India. All other authors declare no competing interests in relation to this work. Grant information This work received support through the Gates Foundation Globa Health Umbrella Grant (INV-005318). The funder had no role in the development of the present manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (1) version 1 Published: 15 Sep 2025, 9:71 https://doi.org/10.12688/gatesopenres.16364.1 Copyright © 2025 Ibarz Pavon AB et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads Gates Open Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Ibarz Pavon AB, Clemens J, Craviotto A et al. WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive protection against enteric fever– key considerations and research gaps . Gates Open Res 2025, 9 :71 ( https://doi.org/10.12688/gatesopenres.16364.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: AWAITING PEER REVIEW AWAITING PEER REVIEW ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 15 Sep 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with Gates Open Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "WHO preferred product characteristics for...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://gatesopenresearch.org/articles/9-71/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://gatesopenresearch.org/articles/9-71/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://gatesopenresearch.org/articles/9-71/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Ibarz Pavon AB et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://gatesopenresearch.org/articles/9-71/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://gatesopenresearch.org/articles/9-71", templates : { twitter : "WHO preferred product characteristics for bivalent Salmonella.... Ibarz Pavon AB et al., published by " + "Gates Open Research" + ", https://gatesopenresearch.org/articles/9-71/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/16364/17766") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "17766"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "99f4211a-18cd-464d-bd89-69c45ab27497"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); Are you a Gates-funded researcher? If you are a previous or current Gates grant holder, sign up for information about developments, publishing and publications from Gates Open Research. First Name * You must provide your first name Last Name * You must provide your last name Email * You must provide a valid email address Institution You must provide an institution. Submit Thank you! We'll keep you updated on any major new updates to Gates Open Research Gates Open Research Browse Gateways How to Publish About Contact Legal For Developers Cookie Notice Privacy Notice RSS Submit via VeriXiv © F1000 Research Limited and its licensors ISSN 2572-4754 var F1000platform = new F1000.Platform({ name: "gates", displayName: "Gates Open Research", hostName: "gatesopenresearch.org", id: "3", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });