Guidelines for intensified tuberculosis case-finding and isoniazid ...

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2.2.5 Patients previously treated for TB (secondary prophylaxis)The Guidelines Group reviewed the evidenceand discussed IPT as secondary prophylaxisfor people who have previously beensuccessfully treated for TB. GRADE assessmentof the evidence from four studies including threerandomized controlled trials [24–26] and oneobservational study [27] showed the value of providingIPT immediately after successful completion ofTB treatment (Annex 7). The Guidelines Groupstrongly recommends that adults and adolescentsliving with HIV who successfully complete their TBtreatment should continue receiving INH for anothersix months and should conditionally receive it for 36months based on the local situation (e.g. high ratesof TB prevalence and transmission) and existingnational guidelines. There was no evidence on thepotential role of IPT for those who had successfullycompleted treatment for multidrug-resistant(MDR) or extensively drug-resistant (XDR) TB.Therefore, the Guidelines Group did not make anyrecommendation on the use of IPT after successfultreatment for MDR or XDR TB.2.2.6 Special populationsPeople living with HIV in congregate settings,such as prisons and centres for refugees orinternally displaced persons, have a higherrisk for and incidence of TB, HIV infection and druguse.[2] Special attention has to be paid to ensurescreening for TB and provision of IPT for these groups.Injecting drug users have a higher risk of coinfectionswith HIV, TB and hepatitis causing viruses. Screeningfor TB and providing IPT for injecting drug usersshould be combined with harm reduction measures,including the provision of testing for hepatitis B andhepatitis C infection, and referral for positive cases.[28] Sound clinical judgement is required to weighthe benefits of IPT among injecting drug users withhepatitis coinfection. IPT should not be provided inthe presence of active hepatitis.2.2.7 Figure 1. Algorithm for TB screening in adults and adolescentsliving with HIV in HIV-prevalent and resource-constrained settingsAdults and adolescents living with HIV*Screen for TB with any one of the following symptoms:**Current coughFeverWeight lossNight sweatsNoYesAssess for contraindications to IPT***Investigate for TB and other diseases****NoGive IPTYesDefer IPTOther diagnosisGive appropriatetreatment andconsider IPTNot TBFollow upandconsider IPTTBTreatforTBScreen for TB regularly at each encounter with a health worker or visit to a health facilityFootnotes to algorithm for adults* Every adult and adolescent should be evaluated for eligibility to receive ART. Infection control measures should be prioritized toreduce M. tuberculosis transmission in all settings that provide care.** Chest radiography can be done if available, but is not required to classify patients into TB and non-TB groups. In high HIVprevalencesettings with a high TB prevalence among people living with HIV (e.g. greater than 10%), strong consideration must begiven to adding other sensitive investigations.*** Contraindications include: active hepatitis (acute or chronic), regular and heavy alcohol consumption, and symptoms of peripheralneuropathy. Past history of TB and current pregnancy should not be contraindications for starting IPT. Although not a requirement forinitiating IPT, TST may be done as a part of eligibility screening in some settings.**** Investigations for TB should be done in accordance with existing national guidelines.18
2.3 Detecting latent TB infection in resource-constrained settings2.3.1 Tuberculin skin test (TST) and IPTTST is not a requirement for initiating IPT in people living with HIV.Strong recommendation, moderate quality of evidencePeople living with HIV who have a positive TST benefit more from IPT;TST can be used where feasible to identify such individuals.Strong recommendation, high quality of evidenceTST relies on a competent immune responseto identify people with latent Mycobacteriumtuberculosis infection. Multiple studies in peopleliving with HIV demonstrate that IPT is more effectivein people with a positive TST than in those with anegative test.[16] In addition, the use of TST couldreduce the number of patients receiving IPT and thenumbers needed to treat to prevent one case of activeTB. However, in resource-constrained settings,operational challenges to the implementation of TSTare significant impediments for access to IPT. Suchchallenges include the costs of procuring tuberculinand administering the test, maintaining an effectivesupply chain, training staff in administering andaccurately reading the test, and the need for thepatient to attend the clinic at least twice over 48–72hours with its associated inconvenience and cost.[29]In addition, the immunological status of the patientand the negative results in anergic patients or thosewith a long lapse between infection and the TSTmay affect its interpretation.[30,31] Although somestudies suggest that using TST is cost-effective,there is a limited supply of tuberculin worldwide, it iscostly to ship and requires an adequate cold chainto ensure accurate test performance (see Annex 8).The Guidelines Group strongly recommends thatin resource-constrained settings, TST shouldnot be a requirement for initiating IPT for peopleliving with HIV. People living with HIV whose TSTstatus is unknown should be started on IPT aftersymptom-based screening for TB. However, giventhat TST-positive patients benefit more from IPTthan those who are TST negative, the test can beused where feasible. People living with HIV who areTST negative should be assessed on a case-bycasebasis for their individual risk of TB exposureand the added advantage of the provision of IPT(e.g. health-care workers, prisoners, miners andothers who live in a high TB transmission setting). Insettings where TST is not available, the GuidelinesGroup encourages national programmes to exploreits expanded use as a potential adjunct to enhancingIPT implementation.2.3.2 Interferon-gamma release assays (IGRA)The Guidelines Group discussed the GRADEassessment of the evidence on the use ofIGRA as a screening tool to identify patientswith latent TB infection (Annex 9). Two types of IGRAwere considered: Quantiferon Gold in tube assayand T-Spot assay. Two studies considered the abilityof IGRA to predict development of TB over time.[32,33] Eight studies evaluated the performance ofQuantiferon Gold in tube assay among HIV-infectedadults with confirmed TB, and one study evaluated itssensitivity among children living with HIV diagnosedwith TB. Similarly, five studies reported the sensitivityof a T-Spot assay among adults living with HIV andTB, and two studies reported its sensitivity amongchildren living with HIV with confirmed TB.However, IGRA cannot generally distinguishbetween active TB disease and latent infection[34] and their performance is compromised amongpeople living with HIV compared to those withoutHIV. Significantly higher rates of indeterminate testresults were found with Quantiferon gold in tube testin persons with HIV compared to persons withoutHIV, and in persons with low CD4 cell countscompared to persons with higher CD4 cell counts.Its sensitivity was also markedly reduced amongpatients with low CD4 counts. Similarly, while moststudies found no impact of low CD4 cell count on thesensitivity of T-Spot assay, at least one study foundthat sensitivity was significantly reduced amongpatients with low CD4 counts.19
Page 1 and 2: Guidelines for intensifiedtuberculo
Page 5: Summary of declarations of interest
Page 10 and 11: 7Providing IPT to people living wit
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Page 14: Strength of recommendationStrongCon
Page 17: 2.2.2.1 Table 1: Comparison of the
Page 21 and 22: varied widely from 34% to 98%, and
Page 23 and 24: study showed that the absence of co
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Page 31 and 32: GRADE profile table 2: TB screening
Page 33 and 34: No. of patientsSummary of findingsE
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Page 39 and 40: No. of patientsSummary of findingsE
Page 41 and 42: Continuous INHprophylaxisNo. of pat
Page 44 and 45: GRADE profile table 9: Efficacy in
Page 46 and 47: GRADE profile table 10: Drug resist
Page 48: Bibliography1. Ayles H et al. Preva

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