Countries should position the W4SS, CRP, CXR and mWRD in combination with diagnostic evaluation using mWRDs and LF-LAM (8) within national TB screening and diagnostic algorithms according to their feasibility, the level of the health facility, resources and equity. Algorithms exploring the available screening tools are presented in the operational handbook, including modelled performance of accuracy and yield (7). While all of the screening tools presented are recommended for all people living with HIV for ease of programming, evidence showed notable accuracy of CRP for TB screening in people not yet receiving ART and that CXR enhanced the sensitivity of the W4SS among people receiving ART, both of which might be considered when choosing algorithms.
Among inpatients on medical wards in settings with a high TB burden, evidence showed that the W4SS, CRP and CXR had limited accuracy, either due to extremely low specificity or suboptimal sensitivity. Therefore, using mWRD as an upfront screening and diagnostic test is warranted, particularly given the urgency of timely diagnosis in this population.
While there are minimal data on optimal frequency of screening across all tools, data presented to the GDG on results from the WHIP3TB trial (evaluating the effectiveness of weekly rifapentine plus isoniazid for 3 months compared with periodic rifapentine plus isoniazid for 3 months and 6 months of daily isoniazid in HIV-positive individuals) (79) underscored the need for more intensified routine screening in addition to the W4SS, even among those receiving ART who have received TPT. The GDG suggested that conducting more intensified screening in addition to the W4SS should occur at the time of an initial diagnosis of HIV or during the first antenatal care visit for pregnant women, and then annually thereafter. To reduce the burden on the patient, screening should be aligned with other routine HIV care visits, such as those for viral load monitoring or for ruling out TB disease prior to initiating TPT, depending on the setting and the national guidelines on HIV. Where applicable, the W4SS should also be conducted as part of a comprehensive clinical evaluation and to inform the need for increased infection control and for other diagnostic tests, such as LF-LAM. Otherwise screening with the W4SS alone should be carried out during all other interactions between patients and health care workers.
Consideration should also be given to the added benefit of including CRP for ruling out TB disease prior to initiating TPT among people living with HIV. In a setting of 1% TB prevalence, among 1000 outpatients screened with the W4SS followed by CRP, 742 would be true negatives and eligible for TPT compared with only 416 found eligible by the W4SS. As is the case for using CXR for ruling out TB disease prior to initiating TPT, restricted access to CRP or CXR should not be a barrier to initiating TPT.
When considering using an mWRD as a TB screening tool among people living with HIV, it should be ensured that universal access to mWRD as a diagnostic test for everyone with presumptive TB is achieved first. The use of an mWRD as a screening tool requires significant resources for implementation, including increased capacity for diagnostic networks and expansion of sample transportation networks. Depending on the feasibility and resources available, countries may choose to prioritize TB screening using mWRDs among certain subpopulations, such as medical inpatients in settings where the TB prevalence is less than 10%, among other patients who are acutely unwell or among pregnant women living with HIV. Screening with an mWRD in lower prevalence settings than those included in the IPD meta-analysis may result in higher false positives should the diagnosis not be confirmed, with the associated overtreatment and related social and economic consequences, including potential delays in starting ART. Careful clinical assessment is recommended to ensure that TB is the primary cause of illness and that other conditions leading to the clinical presentation are also managed. A negative mWRD does not exclude TB. Patients in such settings who are mWRD negative but are manifestly sick may not be able to produce sputum of sufficient quality or may have extrapulmonary TB. For patients with a history of TB within the past 5 years, a positive result may be due to the presence of DNA detected from previously treated TB. Should the patient be unable to provide sputum, other biological specimens should be considered, as indicated (69). The TB prevalence among people living with HIV in medical wards may be calculated as the percentage of people with HIV-related admissions during a 6–12-month period who are diagnosed with TB.
To inform programming and resource planning, countries are encouraged to monitor and evaluate the yield of TB screening among people living with HIV, disaggregated by screening tool.