Public Health Operational Guidelines For Typhoid And Paratyphoid

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Interim - Public Health OperationalGuidelines for Typhoid andParatyphoid (Enteric Fever)A joint guideline from Public HealthEngland and the Chartered Institute ofEnvironmental Health

Interim - Public Health Operational Guidelines for Enteric FeverAbout Public Health EnglandPublic Health England exists to protect and improve the nation’s health and wellbeing,and reduce health inequalities. We do this through world-class science, knowledgeand intelligence, advocacy, partnerships and the delivery of specialist public healthservices. We are an executive agency of the Department of Health, and are a distinctdelivery organisation with operational autonomy to advise and support government,local authorities and the NHS in a professionally independent manner.Public Health EnglandWellington House133-155 Waterloo RoadLondon SE1 8UGTel: 020 7654 @PHE ukFacebook: Crown copyright 2017You may re-use this information (excluding logos) free of charge in any format ormedium, under the terms of the Open Government Licence v3.0. To view this licence,visit OGL or email Where we have identified any thirdparty copyright information you will need to obtain permission from the copyrightholders concerned.Published: May 2017PHE publicationsgateway number: 2017049PHE supports the UNSustainable Development Goals2

Interim - Public Health Operational Guidelines for Enteric FeverDOCUMENT INFORMATIONTitleInterim - Public Health Operational Guidelines for Enteric FeverV2.1AuthorTyphoid and Paratyphoid Reference Group (TPRG)Recommended byPHE Gastrointestinal Infections Leads NetworkEndorsed byPHE Centres Health Protection NetworkPHE (national body tbc – awaiting approval)Approved byDebbie Wood, CIEH Executive Director Membership andProfessional DevelopmentDOCUMENT HISTORYDateReason for changeIssue Number1st February 2017PHE update followingevaluationV2.0Minor referenceamendments to Section2 alogrithmsV2.1th9 March 2017DOCUMENT REVIEW PLANResponsibility forReviewPHE Gastrointestinal Infections Leads Network (Disease grouplead)Next Review Date1st February 2020Nominated Lead sign offDate: 21st February 2017 Name: Dr Sooria BalasegaramCONTACT INFORMATIONNameDr Sooria Balasegaram, Public Health EnglandTelephone 44 (0)20 7811

Interim - Public Health Operational Guidelines for Enteric FeverContentsAbout Public Health England2Contents4Introduction51.Case definitions for public health action72.Algorithms for public health management103.Risk assessment134.Microbiology and case management155.Public health management of possible cases166.Public health management of probable and confirmed cases187.Public health management of contacts218. Public health management of cases with positive screening/clearance samples or withprevious documented history of enteric fever239.Outbreaks2610. Primary prevention: role of travel advice and vaccination2611. Resources and Contacts2812. Contributors2913. Appendix: Disease information3014. References364

Interim - Public Health Operational Guidelines for Enteric FeverIntroductionThe aim of this guidance is to support public health practitioners in identifying thesources of typhoid or paratyphoid infection, and reduce the risks of secondarytransmission. This guidance provides information and a framework for HealthProtection Teams (HPTs) and Environmental Health Officers/Local Authorities torespond appropriately to laboratory reports and/or clinical notifications of typhoid andparatyphoid infection.Enteric fever (typhoid or paratyphoid fever) is notifiable by Registered MedicalPractitioners and laboratories under the Health Protection (Notification) Regulations2010.The 2012 guidance was based on the available evidence, comparison of schedulesfrom other non-endemic countries, expert opinion and previous scientific observationsupported by professional consensus of the Typhoid and Paratyphoid Reference Group(TPRG). A summary of the evidence base has been published1. This revised guidancealso reflects the findings from the national evaluation of the public health managementof enteric fever based on the utilisation of the 2012 version of this guidance2.Key updates in this version: only co-travelling contacts in risk groups require screening and other contacts only require‘warn and inform’ advice unless symptomatic further emphasis on the investigation of source of infection for cases unlikely to be travelrelated regardless of whether the case is in a risk groupBox 1: Recommendations for public health management of cases and contactsCases for diagnosis of possible cases: ONE faecal sample ASAP, and exclusions for all cases as per routinegastrointestinal ‘48 hours after last symptom’ rule for clearance of probable/confirmed cases in risk groups: THREE culture negative samples 48 hoursapart, starting at least ONE week after completion of treatment. Advise exclusion or redeploymentuntil clearance. No clearance necessary for cases not in risk group5

Interim - Public Health Operational Guidelines for Enteric Fever if the case’s infection is likely to be travel-related: co-travellers in risk groups require ONE faecalsample ASAP for screening but no exclusion unless symptomatic; all non-travelling contacts andContactsother co-travellers require ‘warn and inform’ information, but no screening samples or exclusionunless symptomatic if the case’s infection is not thought to be travel-related: contacts require ‘warn and inform’information, and may require ONE faecal sample for screening purposes to investigate source if any contacts have a positive faecal sample or become symptomatic, manage as a case, completinga further risk assessment and with appropriate clearance/exclusions depending on risk group oractivities6

Interim - Public Health Operational Guidelines for Enteric Fever1. Case definitions for public health actionTable 1: Typhoid and paratyphoid case definitionsPossible case a person with a clinical history compatible with enteric fever and where theclinician suspects typhoid or paratyphoid as the most likely diagnosisa person with clinical history of fever and malaise and /or gastrointestinalsymptoms with an epidemiological link to a source of enteric fever, eg from ‘warnand inform’ informationa returning traveller reporting a diagnosis abroad with positive serological testingor salmonella PCR from faeces but no documented evidence of a positive bloodor faecal culture positivityProbable case a person with a local laboratory presumptive identification of Salmonella Typhi orParatyphi on faecal and/or blood culture or culture of another sterile site (egurine) , with or without clinical history compatible with enteric fevera returning traveller giving a clinical history compatible with enteric fever anddocumentation of a positive blood/faecal culture (or positive PCR for S. typhi / S.Paratyphi on blood) and/or treatment for enteric fever overseasConfirmed case a person with S. Typhi or S. Paratyphi infection confirmed by the Public HealthEngland Gastrointestinal Bacteria Reference Unit, Salmonella Reference Service(SRS)a person with documented confirmatory evidence from a recognised overseasreference laboratoryTable 2: Definition of a travel-related caseTravel-related caseA case who develops symptoms of enteric fever within 28 days* of travel to anendemic region of the world.* Based on national enhanced surveillance data, 96% of cases with a travel historyhave onset within 28 days of travel. Hence, this guidance defines a case of entericfever as likely acquired abroad (travel-related) if symptoms develop within 28 days ofarriving in the UK after travel to an endemic region.The 28-day timeframe should be used as a guide but should not be seen asprescriptive. Cases outside or at the upper limit of the 28-day period require anassessment of other possible sources and local professional judgement of likelysource is essential, based on the individual details of each case (see Appendix A).7

Interim - Public Health Operational Guidelines for Enteric FeverEndemic regionThe majority of endemic countries are those in the Indian subcontinent, South-EastAsia, sub-Saharan Africa and Latin America **.** Enteric fever may occasionally be acquired from travel to a country outside theseregions: see for country specific entericfever risks.Table 3: Definition of carriersConvalescent carrierA person who is still excreting S. Typhi or S. Paratyphi after two courses ofappropriate antibiotic therapy, but has been excreting for less than 12 months.Chronic carrierA person who continues to excrete S. Typhi or S. Paratyphi for 12 months or more.Table 4: Definition of contactsCONTACTS co-traveller: someone who travelled closely with the case and who is likely tohave been exposed to the same sources of infection as the case (rather thansomeone who merely travelled on the same bus/plane or was in the same tourgroup as the case). They may not necessarily live with the casehousehold: someone who lives/stayed in the same household as the case and/orhas shared a bathroom and/or have eaten food prepared by the case regularlywhilst the case was symptomatic and up to 48 hours after commencement ofantibioticsother contacts: may include close/sexual contacts or close friends/familymembers who have eaten food prepared by the case whilst they weresymptomaticwider contacts: may need to be considered if there is evidence of transmission orfor investigation of non- travel associated casesTable 5: Groups at higher risk of transmitting gastrointestinal pathogens (risk groups)Risk GroupDescriptionAdditional CommentsGroup AAny person of doubtful personal hygiene or withunsatisfactory toilet, hand washing or handdrying facilities at home, work or school.Riskassessmentshouldconsider, forexample,hygienefacilities at theworkplace.8

Interim - Public Health Operational Guidelines for Enteric FeverRisk GroupDescriptionAdditional CommentsGroup BAll children aged five years old or under whoattend school, pre-school, nursery or similarchildcare or minding groups.Group CPeople whose work involves preparing orserving unwrapped food to be served raw or notsubjected to further heating.Group DHealth care worker, social care or nursery staffwho work with young children, the elderly, orother particularly vulnerable people, and whoseactivities increase the risk of transferringinfection via the faeco-oral route. Such activitiesinclude helping with feeding or handling objectsthat could be transferred to the rinformal foodhandlers, egsomeone whoregularlyhelps topreparebuffets for acongregation.Someonemay be aninformalcarer, egcaring for achronicallysick relative.9

Interim - Public Health Operational Guidelines for Enteric Fever2. Algorithms for public healthmanagementThe initial risk assessment (Q1 and Q2) should be completed on the same day asnotification, including out-of-hours as per local arrangements.2.1 Public health management of cases and contactsQUESTION 1.1a) Does the case fit the case definitions for a POSSIBLE, PROBABLE or CONFIRMED case?1b) Is the case symptomatic?1c) Is the case aware of anyone else with the same symptoms?[Refer to Section 1 Table 1]Acutely ill patientorSymptomatic contactsPOSSIBLE caseRecoveredasymptomatic patient(e.g. returning traveller) Clinician to arrange diagnostic tests and manage as clinicallyindicated. Hygiene advice should be given by the clinician managingpatient care. Case should be excluded while symptomatic until 48 hoursafter last symptoms. If positive, manage as probable or confirmed case. Ifnegative, no further action. Clinician to give hygiene advice. Case should be excluded while symptomatic until 48 hoursafter last symptoms. If in a risk group, clinician to take one faecal sample forpublic health purposes. If positive, manage as probable or confirmed case. Ifnegative, no further action.Q2PROBABLE orCONFIRMED caseClinician to arrange appropriateantibiotic therapy.Complete Q2 & Q3 to determinepublic health action.Q3QUESTION 2.Is the case in a risk group? Were they at work whilst symptomatic?Risk group?YESNOSymptomaticat work?[Refer to Section 1 Table 5] Three clearance samples, 48 hours apart,commencing one week after antibioticscompleted. Exclude from risk activities /- redeploy. Hygiene advice Warn and inform case and contacts.If any positiveclearance samples:refer to Box A inalgorithm 2.2If YES, risks assess work hygiene andenvironment Warn and inform workplacecontacts, e.g. via workplace letter. Exclusion until 48 hours after lastsymptom. Hygiene advice. Warn and inform case and contacts.Continue to Q310

Interim - Public Health Operational Guidelines for Enteric FeverQUESTION 3.Did the case travel to an endemic area?[Refer to Section 1 Table 2]96% of cases who have a travel history develop symptoms within 28 days of return from an endemic area. (See Section 1, Table 2 for list of endemic areas.)Case returnedfrom anendemic areawithin the last28 daysCase returnedfrom anendemic areabetween 28and 60 equestionnaire toend of travelsection.Complete whole of theenhanced surveillancequestionnaire. Identify screen co-travellers inrisk groups (one faecal sampleand question about symptoms). Warn and inform other cotravellers, household and othercontacts. If contact symptomaticmanage as POSSIBLE case (seeQ1 of algorithm 2.1).Likely travelrelated?If co-travellerhas positivesample,manage asPROBABLEcase (seeQ1 ofalgorithm2.1)YESNONo or otherrecent travelhistoryGo to Q4Complete whole of theenhanced surveillancequestionnaire.QUESTION 4. Note: For cases with no recent travel history and/or for whom travel is an unlikely source of infection,further contact tracing and assessment of source is necessary.4a) Does the case have a documented history of previous enteric fever?If YES: Move to algorithm 2.2, Box C on the next page.If NO: Go on to Question 4b below.4b) Does the initial risk assessment identify a possible source of transmission? For example: A contact with similar symptoms or with a travel history. A confirmed epidemiological link with a known case. An implicated food item.YES,possiblesourceidentifiedNO sourceidentified Screen (sample) suspected source(individual(s) / environment) if not alreadydone. Screen identified contacts to excludefurther transmission from suspected source:one faecal sample, no exclusion unlesssymptomatic. Symptomatic contacts: manage as possiblecases. Consider provisional control measuresdepending on potential source. Escalate if possible outbreak. Undertake a wider risk assessment including:o Detailed food history (trawlingquestionnaire),o Detailed history of social gatherings,sexual historyo Consider need for wider screening, e.g.workplace contacts, food sources. Screen contacts and environmental sourcesidentified (contacts: one faecal sample, noexclusion unless symptomatic). Manage any symptomatic contact as apossible case.11NOAny positivesamples?Is there still a needto identify source orare there concernsof ongoing risk?NO ongoingriskYESNofurtherpublichealthaction Are there concerns of ongoing risk? Manage positive contacts as newPROBABLE cases (see Q1 ofalgorithm 2.1). If asymptomatic, seealgorithm 2.2 Box B. Consider the need for an outbreak control team. Consider if wider risk assessment and screening isrequired (stone in pond):o Source unknown.o Source known but has wider implications fortransmission, e.g. food source.o Documented secondary transmission(positive contact).YES

Interim - Public Health Operational Guidelines for Enteric Fever2.2 Public health management of cases with positive screening/clearancesamples and those with previous documented history of enteric feverA. Case in risk group with positive clearancesample after first course of treatmentB. Asymptomatic case picked up through screeningIs the case in a risk group or do they undertake riskactivities that mean there is an ongoing public health risk?Discuss rationale for treatment with the case and relevantclinician. Warn and inform contacts.Treat with antibioticsYESNOTreatmentcourse 1All three negativeThree clearance faecal samples at least 48hours apart, starting one week after completionof treatmentAny of the threesamples positiveDischargefrom publichealth followup. Clinicianto manage ifindicatedTreatmentcourse 2Consider re-treatment (second course of antibiotics and/orother treatment options where appropriate), checkingcompliance and sensitivity)Three clearance faecal samples, startingone week after completion of treatment,awaiting results of the previous samplebefore taking the subsequent sampleAll three negativeAny of the threesamples positiveD. CONVALESCENT CARRIERNOIndividual case risk assessment:Assess whether case presents continuing public health riskRefer to ID physician for clinical management- consider ifextended treatment requiredYESMonthly clearance samplesand exclusionIf one monthlysample negative,take two furtherfollow up samplesat least 48 hoursapart, awaitnegative resultC. Case with possible or documented history of entericfever 1 yearAfter 12 months of repeatsampling.E. CHRONIC CARRIER12All three negativeIf any positive:return tomonthlysamples untilnext negativesample

Interim - Public Health Operational Guidelines for Enteric Fever3. Risk assessmentFormalised local arrangements between the HPT and the local authority shouldstipulate who is responsible for conducting the initial risk assessment in any particularcircumstance.The initial risk assessment (Q1 and Q2) needs to be performed as soon as possible onthe same day as notification, including out-of-hours as per local arrangements. This willallow for the early identification of possible source, exclusion of symptomatic cases inrisk groups, and identification and management of symptomatic contacts. Completion ofthe national enhanced surveillance questionnaire can be delayed until the next workingday.Exclusion from workplace, care facility, school and nursery:Risk assessment should not automatically result in exclusions. Redeployment awayfrom activities that involve an unacceptable risk in the workplace/care facility shouldalways be considered as an alternative to exclusion.Any recommendation for exclusion should be based on a risk assessment of possiblesecondary transmission arising from the activities undertaken by the individual case intheir work/care role, and should take account of the hygiene behaviour of the individualas well as infection control measures in place at workplace/care facility.Use of statutory powers for exclusion:Where it is necessary to impose requirements to protect public health there are powersavailable to the local authority contained within the Public Health (Control of Disease)Act 1984 (as amended) and accompanying regulations3.Guidance on the use of these provisions was issued jointly by the Health ProtectionAgency and the Chartered Institute of Environmental Health4. Any exclusion can bearranged by the local authority where the case is resident, or by the local authority oftheir employment or other occupation, for instance education.Clearance for public health purposes:Microbiological clearance for public health purposes is demonstrated through negativefaecal sampling, and in some situations will be required prior to the case/contact beingallowed to resume normal work/school/nursery activities. The number of samples andtimings need to be explained as well as the arrangements for delivery/collection.Risk assessments should be reviewed and updated when new information is obtained,for example as a result of a ‘warn and inform’ letter.13

Interim - Public Health Operational Guidelines for Enteric FeverTo support the risk assessment, complete the national enhanced surveillancequestionnaire and use the case definitions (Section 1, Tables 1-5) and algorithms(Section 2) contained in this guidance.14

Interim - Public Health Operational Guidelines for Enteric Fever4. Microbiology and case management4.1 Microbiological confirmation of diagnosisDefinitive diagnosis of enteric fever is by culture of the S. Typhi or S. Paratyphi fromblood, urine, or from another sterile site or faeces. The causal organisms can beisolated from blood early in the disease and from urine and faeces after the first week.Presumptive culture results should be available within 72 hours.Initiate early discussions with the local PHE consultant microbiologist if further clarity isnecessary about any aspects of diagnosis or investigation.Send all presumptive isolates from local laboratories to the PHE National InfectionsService Gastrointestinal Bacteria Reference Unit, Salmonella Reference Service (SRS)for confirmation and typing.Some returning travellers with symptoms may have serology or a positive PCR onfaeces for Salmonella. Define these travellers as possible cases for management andtake a diagnostic sample. If they have confirmation of a positive PCR on blood for S.typhi or S. paratyhpi, repeat a diagnostic sample but manage them as probable cases.Whole genome sequencing following consultation with the PHE Salmonella ReferenceService may assist in the investigation of travel and non-travel related cases.4.2 Management of probable cases of paratyphoid B:In some cases, provisional laboratory reports of S. Paratyphi B may subsequently beconfirmed by the SRS as Salmonella Java, which causes gastrointestinal illness ratherthan enteric fever. S. Paratyphi B should be suspected as the most likely cause ofillness if: the isolate from the original sending laboratory is from blood the patient has a clinical picture compatible with enteric fever there is a history of travel to an endemic country and/or the case is epidemiologicallylinked to a probable or confirmed caseIf the probable case is in a risk group and/or there is a need for a wide public healthinvestigation, contact the SRS to request that processing of the sample is expedited.4.3 Case managementAdvice on clinical management and treatment is outside the scope of this guidance.Clinicians with a patient whom they suspect may have enteric fever should obtain15

Interim - Public Health Operational Guidelines for Enteric Feveradvice from the local consultant microbiologist or infectious disease physician. Antibioticresistance is increasingly common, thus it is essential to ensure appropriate therapyand confirm antibiotic sensitivity. The SRS offers clinical advice for complicated casesand can confirm antimicrobial susceptibility for presumptive multidrug resistant ts5. Public health management of possiblecasesRefer to Section 1, Table 1 for case definitions for possible cases of enteric fever.Refer to the algorithm in Section 2.1 for public health management.Refer to Appendix A for advice on serologyPossible cases of enteric fever may self-report to their GP or attend hospital. This mayalso occur as a result of ‘warn and inform’ information sent to contacts of a probable orconfirmed case who subsequently develop symptoms. A possible case of enteric fever(see case definitions in Table 1) should be managed as follows: hygiene advice should be given (‘warn and inform’) so that the case and contactsare aware of signs and symptoms and the need to contact their GP for a clinicalassessment should they become symptomatic if acutely ill (including any symptomatic contacts):oa clinician should arrange appropriate diagnostic tests, give hygiene advice andmanage as clinically indicated if recovered and asymptomatic (for example, a returning traveller reporting adiagnosis abroad who presents to their GP without supporting diagnostics or withdiagnosis such as a positive Widal test or Salmonella PCR on faeces and completedtreatment)oclinician should be requested to provide/reinforce hygiene adviceo if they are in a risk group their clinician should be advised to take one faecalsample for public health purposes (screening).The Widal test is unreliable fordiagnosis, thus management of these travellers should be on the basis of thefaecal sample result and the presence of symptoms.all possible cases should be excluded only while symptomatic and until 48 hoursafter last symptoms, regardless of risk group, as recommended for allgastrointestinal diseases. Possible cases who are asymptomatic, and have been for16

Interim - Public Health Operational Guidelines for Enteric Fever at least 48 hours, do not need to be excluded whilst awaiting the result of a faecalsampleif the sample is presumptive positive on culture, the case should then be managedas a new probable/confirmed case including risk assessment of case and contactsand appropriate clearance/exclusions17

Interim - Public Health Operational Guidelines for Enteric Fever6. Public health management of probableand confirmed casesRefer to Section 1, Table 1 for case definitions for probable and confirmed cases ofenteric fever.Refer to the algorithm in Section 2.1 for public health management: all cases and their immediate contacts should be provided with comprehensivehygiene advice (by the HPT, GP or LA depending on local arrangements) especiallyconcerning hand hygiene and preparation of food for household contacts. Adviceshould preferably be given verbally and confirmed in writing (‘warn and inform’information) through local arrangements. The advice should include therecommendation of typhoid immunisation for future travel to endemic areasFurther investigation of case:Q2: Is the case in a risk group?Manage as per algorithm in Section 2.1Based on the risk assessment, a decision should be made as to whether the case is ina risk group for onward transmission of infection (see Section 1, Table 5 for detail of riskgroups): cases in a risk group:oexclusion from risk activities or redeployment until microbiologically cleared ofaecal sampling should commence one week after completion of antibiotictreatment. For all risk groups (A-D), three consecutive negative faecal samplesshould be required at least 48 hours apart for clearance, prior to being allowedto resume normal work/school/nursery activitiesocases with positive clearance samples after treatment should be retreated andmanaged according to Box A in algorithm 2.2, and the text in Section 8.2oif the case was at work whilst symptomatic, a wider risk assessment of workhygiene, contacts and environment should be undertaken. Workplace contactsmay need to be ‘warned and informed’, eg via ‘warn and inform’ information asprovided in Section 11.2.cases not in a risk group:oclearance faecal samples are not requiredocases should be excluded only if symptomatic, and should not return toschool/work until at least 48 hours after resolution of symptoms.18

Interim - Public Health Operational Guidelines for Enteric FeverQ3: Did the case travel to an endemic area?Manage as per algorithm in Section 2.1 if the case has developed symptoms of enteric fever within 28 days of travel to anendemic region of the world: consider as a ‘travel-related’ case. See Section 7.1 formanagement of contactsif travel to an endemic region is identified near the upper limit or outside the 28-daytimeframe: consider other possible non travel-related sources of infection. Thisshould include the possibility of a secondary case from a symptomatic orasymptomatic travel-related case/carrier in the householdcases without a definitive travel history to an endemic area: consider extensiveinvestigation* in an attempt to identify the source of the infection even if cases arenot in a risk group. Household and other close contacts should be screened. Thegenomic sequence can be compared with other cases in the PHE database*This should be undertaken using the national enhanced surveillance enteric feverquestionnaire, and potentially the trawling questionnaire. This will entail a ‘stone inthe pond’ approach to clearance of contacts to widen investigation of a possiblesource of infection, discussed below in Section 8.2. Box 2 outlines areas forinclusion in the wider risk assessment19

Interim - Public Health Operational Guidelines for Enteric FeverBox 2: Investigation and risk assessment of cases without a travel history establish if the case has possible carrier status eg a) previous history of entericfever-like illness, and whether previously confirmed or not. b) history of biliarytract illness. c) born or previously living in an endemic area conduct a detailed assessment of contacts and visitors, within a 28-day* period,including:oIdentifying epidemiological links with other known cases.oAscertaining whether and when household or other contacts have travelled(eg within last 56 days, so as to cover the 28-day period from infection toonset of symptoms for index case following travel and an additional 28days for the contact following exposure to index case).oAscertaining whether household or other contacts such as those handlingfood have had a history of enteric fever-like illness. consider food history and food establishments, as well as any food sources fromabroad (imported foodstuffs); identification of attendance at gatherings orevents. If necessary administer the additional food trawling questionnaire [Link] consider sexual contacts consider in exceptional instances, such as possible outbreaks involving foodhandlers, the need for food and environmental sampling at the home and/orwork place check whole genome sequencing results for relatedness with other cases* The 28-day timeframe should be used as a guide but should not be seen as prescriptive.See Table 2 and Appendix A for rationale20

Interim - Public Health Operational Guidelines for Enteric Fever7. Public health management of contactsAny symptomatic contacts should

2. Algorithms for public health management 10 3. Risk assessment 13 4. Microbiology and case management 15 5. Public health management of possible cases 16 6. Public health management of probable and confirmed cases 18 7. Public health management of contacts 21 8. Public health management of cases with positive screening/clearance samples or with

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