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Guidelines on the Management of Latent Tuberculosis Infection. Geneva: World Health Organization; 2015.

Cover of Guidelines on the Management of Latent Tuberculosis Infection

Guidelines on the Management of Latent Tuberculosis Infection.

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2Recommendations

The Panel issued recommendations on the identification of individuals for latent TB testing and treatment, the algorithmic approach to test and treat LTBI, and the treatment options. The recommendations of the Panel were mainly based on critical appraisal of the evidence, the balance of anticipated benefits and harms, the values and preferences of clients and health-care providers as well as resource implications.

The overall logical approach conformed to the Panel for the development of the guidelines and the formulation of the recommendations was as follows: (1) identification of the risk groups that are eligible for treatment of latent TB infection (recommendation in section 2.1, page 13); followed by (2) evaluation of the accuracy and drawbacks of the screening tests (recommendation in section 2.2, page 15); and (3) evaluation of the effectiveness and harms of the treatment regimens to prevent progression (recommendation in section 2.3, page 18).

2.1. Identification of at-risk populations for LTBI testing and treatment

In high-income and upper middle-income countries with estimated TB incidence less than 100 per 100 000 population

  • Systematic testing and treatment of LTBI should be performed in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor (TNF) treatment, patients receiving dialysis, patients preparing for organ or haematologic transplantation and patients with silicosis. Either interferon-gamma release assays (IGRA) or Mantoux tuberculin skin test (TST) should be used to test for LTBI. (Strong recommendation, low to very low quality of evidence)
  • Systematic testing and treatment of LTBI should be considered for prisoners, health workers, immigrants from high TB burden countries, homeless persons and illicit drug users. Either IGRA or TST should be used to test for LTBI. (Conditional recommendation, low to very low quality of evidence)
  • Systematic testing for LTBI is not recommended in people with diabetes, people with harmful alcohol use, tobacco smokers, and underweight people unless they are already included in the above recommendations. (Conditional recommendation, very low quality of evidence)

For resource-limited countries and other middle-income countries that do not belong to the above category (according to existing and valid WHO guidelines) (5,6):

  • People living with HIV and children below 5 years of age who are household or close contacts of people with TB and who, after an appropriate clinical evaluation, are found not to have active TB but have LTBI should be treated. (Strong recommendation, high quality of evidence)

Remarks: Testing and treatment of LTBI should adhere to strict human rights and the highest ethical considerations. For example, positive test results or status of treatment for LTBI should not affect a person's immigration status or delay the ability to immigrate. For people living with HIV and child contacts below 5 years of age, the existing WHO guidelines should be consulted (5,6).

The rationale for the Panel to make strong recommendations despite low to very low quality of evidence was based on its strong judgment on the increased likelihood of progression to active TB disease and the benefits of treatment outweighing the potential harms in the identified at-risk population groups. Similarly, the Panel made its conditional recommendations primarily because of the weak quality of the evidence and implementation considerations.

2.1.1. Summary of the evidence

Three systematic reviews were conducted to determine which at-risk population groups would be prioritized for LTBI testing and treatment among 24 pre-defined population groups. Evidence on increased prevalence of LTBI, risk of progression from LTBI to active TB disease and increased incidence of active TB was available for the following 15 risk groups: (i) adult and child TB contacts, (ii) health-care workers and students, (iii) people living with HIV, (iv) patients receiving dialysis, (v) immigrants from high TB burden countries, (vi) patients initiating anti-tumour necrosis factor (TNF) therapy, (vii) illicit drug users, (viii) prisoners, (ix) homeless people, (x) patients receiving organ and haematologic transplantation, (xi) patients with silicosis, (xii) patients with diabetes, (xiii) people with harmful alcohol use, (xiv) tobacco smokers, and (xv) underweight people.

The first systematic review assessed the prevalence of M. tuberculosis infection as determined either by TST or commercially available IGRAs. A total of 276 studies (with 299 entries) were included. Comparison between LTBI prevalence among risk groups and prevalence among the general population was made using LTBI prevalence estimates derived from modelling (2); and pooled risk ratios were calculated for the risk groups. A considerable heterogeneity in risk ratios was observed. Nevertheless, increased risk of LTBI was reported for both TST and IGRA in at least 65% of the studies for the following risk groups: prisoners, homeless people, elderly people, immigrants from high TB burden countries, adult and child TB contacts, and illicit drug users.

A second systematic review assessed the risk of progression from LTBI to active TB. Eight individual studies provided the evidence of an increased risk of progression for the following categories: people living with HIV, adult contacts of TB cases, patients undergoing dialysis, underweight people, individuals with fibrotic radiologic lesions and recent converters to the TST.

The third systematic review was conducted to compare the pooled incidence rate ratio of active TB in the pre-defined risk groups compared with the general population. Data of increased risk of active TB were reported in the following risk groups: people living with HIV, adult and child contacts to a TB case, patients with silicosis, health-care workers (including students), immigrants from high TB burden countries, prisoners, homeless, patients receiving dialysis, patients receiving anti-TNF drugs, patients with cancer, people with diabetes mellitus, people with harmful alcohol use, tobacco smokers and underweight people.

2.1.2. Balance of benefits and harms

The Panel reviewed the evidence generated from the systematic reviews and discussed each of the population risk groups identified in detail for the prevalence of latent TB, risk of progression into active TB and the incidence of active TB compared with the general population. The Panel concluded that there is clear evidence of benefit from systematic testing and treating of LTBI in the following groups: people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-TNF treatment, patients receiving dialysis, patients preparing for organ or haematologic transplantation, and patients with silicosis.

The Panel concluded that the evidence of benefits outweighing harms in the following population risk groups is weak, but judged that the benefits of systematic testing and treating may outweigh the harms: health-care workers, immigrants from high TB burden countries, prisoners, homeless persons and illicit drug users. The decision to systematically test for and treat LTBI in these population groups should be in accordance with local TB epidemiology and context, health system structures, availability of resources and overall health priorities. Priority must be given to individuals with history of recent infection status conversion, tested either by IGRA or TST, from negative to positive. Similarly, the Panel concluded that recent immigrants from high TB burden countries to low TB burden countries should be prioritized. However, the Panel underscored that a person's status—tested positive for LTBI or receiving LTBI treatment — should not affect the process, procedure and status of immigration.

The Panel noted the paucity of data on the benefits and harms of systematic latent TB testing and treatment in diabetic patients, people with harmful alcohol use, tobacco smokers and underweight people and concluded that the benefits of systematic and routine testing and treatment in these risk groups do not outweigh the risks unless individuals/patients also belong to the groups mentioned in the above recommendations.

The Panel recognized the potential limitations of the systematic reviews, which were restricted to a single database (Medline) over a 10-year period for both the comparison of prevalence of LTBI and progression to active TB disease in a specific risk group over the general population. It also noted that the inclusion of studies with no restriction on publication year or language through contacting 30 experts in the field mitigated this limitation. The Panel judged that the available evidence was adequate to issue the recommendations particularly taking into consideration the urgent need for WHO guidelines. It also emphasized the importance of further research on the benefits and harms of LTBI testing and treatment in persons with silica exposure, patients receiving steroid treatment, patients with rheumatologic conditions, indigenous populations and cancer patients.

2.1.3. Values and preferences of clients and health-care providers

Individual benefit outweighing risk should be the mainstay of latent TB testing and treatment. The Panel agreed that prioritization of groups based on their risk and the local and national context (e.g. epidemiology, resource availability) will be acceptable by individuals as well as key stakeholders including clinicians and programme managers. It was noted that the high risk of ongoing TB transmission in certain risk groups, such as health-care workers (including students), prisoners (including prison staff), homeless and illicit drug users, require attention so that the benefit of treatment is not compromised through reinfection. The TB prevention value of antiretroviral therapy for people living with HIV was also noted.

2.1.4. Resource considerations

The decision of national TB programmes and other stakeholders to identify the priority risk groups for programmatic management of LTBI needs to consider availability and efficient use of resources. The Panel noted that prioritizing high-risk groups, such as people living with HIV, immigrants from high TB burden countries and contacts with TB cases for latent TB testing and treatment have the potential to yield savings for the health-care system. However, cost-effectiveness analyses based on rigorous empirical data are scarce for other risk groups.

2.2. Algorithm to test and treat LTBI

  • Individuals should be asked about symptoms of TB before being tested for LTBI. Chest radiography can be done if efforts are intended also for active TB case finding. Individuals with TB symptoms or any radiological abnormality should be investigated further for active TB and other conditions. (Strong recommendation, very low quality of evidence)
  • Either TST or IGRA can be used to test for LTBI in high-income and upper middle-income countries with estimated TB incidence less than 100 per 100 000. (Strong recommendation, very low quality of evidence)
  • IGRA should not replace TST in low-income and other middle-income countries. (Strong recommendation, very low quality of evidence) (8)

Remark: HIV testing should be incorporated into the medical evaluation of LTBI treatment candidates based on national or local policies.

The rationale for the Panel's decision for a strong recommendation for symptom screening and chest radiography prior to initiating treatment was due to the crucial importance of exclusion of active TB disease and inclusion of LTBI for better patient outcomes. Similarly, the rationale for a strong recommendation that IGRA should not replace TST in low-income and other middle-income countries, despite the very low level of evidence, is justified by the Panel's consideration of patient relevant outcomes, performance of the test in these settings and costs (8).

2.2.1. Summary of the evidence

A systematic review was conducted to determine the sensitivity and specificity of symptoms, and chest radiography screening for active pulmonary TB in HIV-negative persons and persons with unknown HIV status. The review identified 11 studies from general population surveys that provided data on screening with either symptoms or with chest radiography or with both. To illustrate how different screening and diagnostic algorithms are expected to perform in ruling-out active TB, a model was constructed to compare the following seven screening strategies: (i) any TB symptom, (ii) chest radiography with any abnormality, (iii) a combination of chest radiography with any abnormality or any TB symptom, (iv) chest radiography with suggestive TB abnormalities, (v) cough more than 2–3 weeks, (vi) if there is cough more than 2–3 weeks then chest radiography as a follow up test, and (vii) if any TB symptom is present then chest radiography. The combination of any abnormality in chest radiography and/or presence of any TB suggestive symptoms (i.e. any one of cough, haemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath and fatigue) would offer the highest sensitivity and negative predictive value to rule out TB.

Figure 1. Algorithm for targeted diagnosis and treatment of LTBI in individuals from risk groups.

Figure 1

Algorithm for targeted diagnosis and treatment of LTBI in individuals from risk groups. * Any symptoms of TB include any one of: cough, haemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, fatigue. HIV test could be offered (more...)

A systematic review was conducted to explore tests and clinical proxies that can best identify individuals most-at-risk of progression to incident TB disease. While the systematic review did not identify any clinical parameters that would assist in the prediction of progression to active TB diseases, 29 studies were about the predictive utility of IGRA and TST. The main effect measure of interest was the risk ratio, comparing TB incidence following a positive test results versus a negative test result in individuals not receiving preventive therapy, or alternatively the incidence rate ratio in the few studies that reported the person years of follow-up amongst test positives and test negatives. The overall pooled risk ratio estimate for the TST was 2.64 (95% CI: 2.04–3.43, n = 22 studies) and 8.45 (95% CI: 4.13–17.31, n = 16 studies) for IGRA. The pooled risk ratio estimate for IGRA was 13.55 (95% CI: 6.08–30.21) in high-income and upper middle-income countries with TB incidence less than 100 per 100 000 compared to 2.32 in the remaining countries (95% CI: 1.41–3.81).

Because it was difficult to judge if the differences in the pooled estimates of risk ratios for TST and IGRA were due to true differences between the tests or if they reflected the result of heterogeneous study populations included in the analysis, the main data analysis was limited to the eight studies that compared TST and IGRA to each other in the same study population (head-to-head analysis). This analysis showed the pooled risk ratio estimate for TST to be 2.58 (95% CI: 1.72–3.88) and for IGRA 4.94 (95% CI: 1.79–13.65). The pooled risk ratio in the three studies that evaluated both the TST and IGRA was 2.07 (95% CI: 1.38–3.11) for the TST and 2.40 (95% CI: 1.26–4.60) for IGRA. In both analyses, the confidence intervals around effect measures for the TST and IGRA overlapped and were imprecise. There was insufficient data to provide evidence on predictive utility of the tests among specific high-risk subpopulations or groups.

Table 1. Pooled estimates in the predictive utility of IGRA and TST in head-to-head studies that evaluated incident active TB in untreated individuals.

Table 1

Pooled estimates in the predictive utility of IGRA and TST in head-to-head studies that evaluated incident active TB in untreated individuals.

2.2.2. Balance of benefits and harms

The Panel reviewed the evidence generated from the systematic reviews and discussed benefits and harms of the alternative screening options to rule out active TB. The Panel noted the potential limitation of using data from the general population as a proxy for ruling out active TB among at-risk populations. However, it concluded that this would have no implication in the development of the algorithm that will be used to test and treat individuals from high-risk populations. The Panel reiterated that active TB disease should be excluded before LTBI testing and treatment.

2.2.3. Values and preferences of clients and health-care providers

Symptom screening and chest radiography were considered acceptable for individuals and programme managers, and the benefit outweighs increased costs and logistic demand.

The Panel noted that comparative analysis between TST and IGRA in the head-to-head studies showed no evidence that one test should be preferred over the other to assess progression to TB disease. The Panel also noted that equity and access could vary depending on the type of test used. For example, the single visit required for IGRA compared to two consultation visits required for TST may favour client preferences. However, the Panel could not be confident of the overall programmatic impact of this in terms of access and equity for clients due to the additional cost required. It was noted that serial testing for LTBI including for health-care workers was beyond the scope of these guidelines.

2.2.4. Resource considerations

The Panel noted that resource requirements could vary and that the decision to implement LTBI testing and treatment needs to consider several factors, including the structure of the health system, feasibility of implementation, infrastructure requirements and Bacillus Calmette–Guérin (BCG) vaccination coverage. The Panel noted that the incremental cost-effectiveness of IGRAs compared to TST appeared to be influenced mainly by the accuracy of the two diagnostic tests, with BCG vaccination playing a decisive role in reducing the specificity of TST and leading the choice towards IGRA-only strategies. However, IGRAs are more costly and technically complex to do than the TST. Given comparable performance but increased cost, replacing TST with IGRAs as a public health intervention in low-income and other middle-income countries is not recommended (8).

2.3. Treatment options for LTBI

The following treatment options are recommended for the treatment of LTBI: 6-month isoniazid, or 9-month isoniazid, or 3-month regimen of weekly rifapentine plus isoniazid, or 3–4 months isoniazid plus rifampicin, or 3–4 months rifampicin alone. (Strong recommendation, moderate to high quality of evidence)

Remark: There was consensus of the Panel on the equivalence of 6-month isoniazid, 9-month isoniazid, and 3-month rifapentine plus isoniazid. However, the Panel could not reach a consensus and voted on the equivalence of 3–4 months isoniazid plus rifampicin and 3–4 months rifampicin alone as alternative options to 6-month isoniazid. Sixty per cent of the Panel members voted for 4-month rifampicin alone as an equivalent option to 6-month isoniazid while 53% voted for 3–4 months isoniazid plus rifampicin as an equivalent option to 6-month isoniazid. Rifampicin- and rifapentine-containing regimens should be prescribed with caution to people living with HIV who are on antiretroviral treatment due to potential drug-to-drug interactions. See annex 3 for drug dosage.

2.3.1. Summary of the evidence

A systematic review was conducted to evaluate the efficacy and safety of treatment for LTBI (11). Fifty three studies, all of which were randomized controlled trials and recorded at least one of the two pre-specified endpoints (preventing active TB, hepatotoxicity of Grade III or above), were included. Data from the systematic review was available for 15 treatment regimens, although relatively few direct comparisons were reported, some with sparse data, particularly for modern regimens. Pyrazinamide-containing regimens were excluded from further consideration because of reported toxicity. The estimate of the rates of severe hepatotoxicity and death of pyrazinamide-containing regimens was measured in comparison with an historical isoniazid control (10). Rifampin-pyrazinamide combinations had fatality and hospitalization rates of 0.9 (95% CI: 0.4–1.9) and 2.8 (95% CI: 1.8–4.3) per 1000 rifampicin–pyrazinamide therapy initiations, respectively, compared with fatality rates of 0.0–0.3 deaths per 1000 persons in individuals under isoniazid preventive therapy.

No placebo or treatment trial directly compared the efficacy and safety of the 9-month isoniazid regimen. It was also noted that clinical trials comparing the 3-month regimen of weekly rifapentine plus isoniazid with placebo or no treatment were not available. This is because when the 3-month weekly rifapentine plus isoniazid regimen trials were being carried out,comparison with placebo/no treatment arms was not ethically acceptable.

The expert panel comparatively appraised the evidence on efficacy and safety of available treatment options. The results of the pair-wise comparisons with placebo are reported in Table 2 — isoniazid for 6 months was used as a reference comparator in the analysis of rates of incident TB, and hepatotoxicity (Grade III/IV) with other regimens (Table 3).

Table 2. Regimens that showed significant efficacy when compared to placebo and profile of heptotoxicity.

Table 2

Regimens that showed significant efficacy when compared to placebo and profile of heptotoxicity.

Table 3. Comparison of efficacy of 6-month isoniazid with other regimens for the development of incident TB and hepatotoxicity.

Table 3

Comparison of efficacy of 6-month isoniazid with other regimens for the development of incident TB and hepatotoxicity.

In general these comparisons did not show the superiority of one regimen over any other. However, in terms of safety, a 3–4 months rifampicin regimen and a 3-month weekly rifapentine plus isoniazid regimen had fewer hepatotoxicity events compared to the 6-month and 9-month isoniazid regimen, respectively.

In the absence of any direct comparison of efficacy of 6- and 9-month isoniazid, the Panel reviewed a reanalysis of the United States Public Health Service (USPHS) trials conducted in the 1950s and 1960s that concluded that optimal protection from isoniazid appears to be obtained by nine months (12). Based on this, the Panel judged that 9-month isoniazid can be considered as an equivalent treatment option to 6-month isoniazid.

2.3.2. Balance of benefits and harms

The Panel reviewed the evidence for efficacy of the different treatment regimens against incident TB compared to the placebo, the hepatotoxicity profile of each regimen, and the comparison of the different regimens against 6-month isoniazid as a reference. The Panel unanimously agreed on the equivalence of 6-month isoniazid, 9-month isoniazid and 3-month weekly rifapentine plus isoniazid regimens as alternative treatment options to each other. However, the Panel could not reach a consensus and voted on the equivalence of 3–4 months isoniazid plus rifampicin and 3–4 months rifampicin alone to 6-month isoniazid. Sixty per cent of the Panel members who attended the meeting voted for 3–4 months rifampicin alone as an equivalent option to 6-month isoniazid while 53% of them voted for 3–4 months isoniazid plus rifampicin as an equivalent option to 6-month isoniazid. For this reason, the Panel concluded that the following regimens can be recommended as options to treat LTBI: 6-month isoniazid, or 9-month isoniazid, or 3-month weekly rifapentine plus isoniazid, or 3–4 months rifampicin alone, or 3–4 months isoniazid plus rifampicin. The Panel also noted that the risk of hepatotoxicity is considerably low in children compared to adults (13).

2.3.3. Values and preferences of clients and health-care providers

The Panel agreed that shorter duration regimens are preferred over longer duration regimens from the perspective of individuals receiving treatment, clinicians providing the treatment and programme managers, and concluded that the 3-month regimen of weekly rifapentine plus isoniazid has advantage over the other regimens. Similarly, the Panel agreed that 6-month isoniazid is preferred over 9-month isoniazid due to resource requirements, feasibility and acceptability by patients. The Panel noted the reported positive acceptability of rifampicin- and rifapentine-containing regimens by individuals receiving treatment, and further concluded that the rifampicin (3–4 months isoniazid plus rifampicin and 4-month rifampicin only) and isoniazid (6- and 9-month) containing regimens could be self-administered by individuals receiving treatment. The Panel noted that the 3-month weekly rifapentine plus isoniazid regimen should be given under direct observation as the evidence available so far is based on this circumstance. It also noted that such provision of rifapentine under direct supervision will lower acceptability by individuals receiving treatment. Therefore, it was strongly suggested to revisit this once further evidence is available on the value of self-administration. Rifampicin- and rifapentine-containing regimens should be prescribed with caution to people living with HIV who are on antiretroviral treatment due to potential drug-to-drug interactions. The Panel expressed concern about the current high cost of rifapentine and absence of registration in many countries that limits its availability, with consequent inequities in access.

2.3.4. Resource considerations

The Panel noted that different treatment options have different resource requirements and concluded that programme managers need to decide upon the treatment options taking into consideration their resource capacity and national and local context. The Panel further noted that the need for direct supervision of the 3-month weekly rifapentine plus isoniazid regimen increases resource requirements, in addition to the current high cost of the drug.

2.4. Preventive treatment for contacts of MDR-TB cases

Serious limitations of the quality of evidence prevent drawing any recommendations on MDR-TB preventive therapy as a public health measure. Strict clinical observation and close monitoring for the development of active TB disease for at least two years is preferred over the provision of preventive treatment for contacts with MDR-TB cases.

2.4.1. Summary of the evidence

A systematic review was conducted to define the effectiveness of anti-TB drugs in preventing active TB in contacts of MDR-TB patients. Four studies were included for the analysis; all were cohort studies of which one (14) was a prospective study exclusively involving children below 5 years of age while the others were retrospective studies involving both adults and children (1517). Drug regimens used for preventive treatment varied widely across the studies. For the final analysis, two of the studies in which all or majority of MDR-TB contacts received preventive treatment with isoniazid (14, 16) were excluded. The other study contained only 11 contacts receiving a regimen with at least one active agent and was excluded because of its small size (16). Therefore, the quality of evidence was determined only for one comparison study which used a tailored regimen taking into account the resistance pattern of the index case among childhood contacts (14). In this single study two of 41 children receiving tailored preventive therapy developed TB (confirmed and probable TB) compared to 13 of 64 children not receiving preventive treatment (OR=0.2, 95% CI: 0.04–0.94).

2.4.2. Balance of benefits and harms

The Panel noted the scarcity of available evidence on effectiveness and safety of using anti-TB drugs to prevent active TB among adult and childhood contacts of MDR-TB cases. Regimens that can be used for the treatment of contacts with MDR-TB are known to have poor safety and tolerability particularly among adults. Additionally, regimens used for the treatment of contacts of MDR-TB cases, which are often composed of one or two drugs, are inadequate to treat active disease should this develop, carrying the further risk of acquisition of additional resistance. Many healthy children who will not develop MDR-TB will be placed on potentially toxic regimens for which paediatric formulations are unavailable. Moreover, the tailoring of regimens is further hampered by the lack of reliable drug susceptibility testing for certain drugs (e.g. ethionamide, pyrazinamide, ethambutol).

2.4.3. Values and preferences of clients and health-care providers

The Panel emphasized the urgent need for adequately powered randomized controlled trials to define the benefits and harms of treatment of MDR-TB contacts for clients and health-care providers. The Panel expressed its concern that wider use of treatment of MDR contacts without established evidence would set a precedent and challenge the conduct of essential clinical trials. In addition, it is noted that the infecting strains in the contact may have a different resistance pattern to those of the source case. This may happen because of coincidental infection from another index case, mixed strains in the index case, or infection from the index case before the strain in the latter acquired resistance. The lack of paediatric formulations for some drugs was mentioned as a concern.

2.4.4. Resource considerations

The Panel recognized that determination of the drug susceptibility profile for drugs to be used as preventive treatment for MDR contacts poses both technical and logistic challenges. Furthermore, the need for close clinical monitoring and follow-up of contacts and prescribing treatment regimens will incur extra costs and strain the capacity of MDR-treatment services. Broad implementation of preventive treatment may divert precious second-line drugs of proven effectiveness (levofloxacin, moxifloxacin and ethionamide) from curative services. The need for active pharmacovigilance for individuals put on preventive treatment for MDR-TB has resource implications (18).

2.4.5. Conclusions

The Panel noted the serious limitations of the quality of evidence to draw any recommendations on MDR-TB preventive therapy as a public health measure. Weighing the lack of evidence against the severe consequences of developing MDR-TB, the Panel concluded that the management of contacts of MDR-TB patients needs to be guided by a comprehensive individual risk assessment that takes into consideration the balance between risk and benefits for the individual. Strict clinical observation and close monitoring for the development of active TB disease for at least two years is preferred over the provision of preventive treatment for contacts with MDR-TB cases. On the other hand, it should be noted that, in circumstances where there is a reasonable likelihood that the exposed person may have also been exposed to drug-susceptible TB, the individual should be given a course of standard LTBI treatment according to national guidelines. However, the Panel noted that clinicians as part of sound clinical practice can consider individually tailored treatment regimens based on the drug susceptibility profile of the index case particularly for child contacts below 5 years of age when benefits can outweigh harms with reasonable confidence, and keep in mind the technical shortcomings of drug susceptibility testing for many of the second-line anti-TB drugs. In individual cases where preventive therapy is considered for contacts of MDR-TB cases, the programme needs to ensure that the necessary resources are in place to provide quality-assured drug susceptibility testing, all the necessary medications, and to monitor closely for harms, breakthrough disease and acquired resistance.

Copyright © World Health Organization 2015.

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