RESUMO
Background HIV-associated tuberculosis (TB) has high mortality; however, current triage and prognostic tools offer poor sensitivity and specificity, respectively. We conducted a systematic review of diagnostic and prognostic host-blood transcriptomic signatures of TB in people living with HIV (PLHIV). Methods We systematically searched online databases for studies published in English between 1990-2020. Eligible studies included PLHIV of any age in test or validation cohorts, and used microbiological or composite reference standards for TB diagnosis. Inclusion was not restricted by setting or participant age. Study selection, quality appraisal using the QUADAS-2 tool, and data extraction were conducted independently by two reviewers. Thereafter, narrative synthesis of included studies, and comparison of signatures performance, was performed. Results We screened 1,580 records and included 12 studies evaluating 31 host-blood transcriptomic signatures in 10 test or validation cohorts of PLHIV that differentiated individuals with TB from those with HIV alone, latent Mycobacterium tuberculosis infection, or other diseases (OD). Two (2/10; 20%) cohorts were prospective (29 TB cases; 51 OD) and 8 (80%) case-control (353 TB cases; 606 controls) design. All cohorts (10/10) were recruited in Sub-Saharan Africa and 9/10 (90%) had a high risk of bias. Ten signatures (10/31; 32%) met minimum WHO Target Product Profile (TPP) criteria for TB triage tests. Only one study (1/12; 8%) evaluated prognostic performance of a transcriptomic signature for progression to TB in PLHIV, which did not meet the minimum WHO prognostic TPP. Conclusions Generalisability of reported findings is limited by few studies enrolling PLHIV, limited geographical diversity, and predominantly case-control design, which also introduces spectrum bias. New prospective cohort studies are needed that include PLHIV and are conducted in diverse settings. Further research exploring the effect of HIV clinical, virological, and immunological factors on diagnostic performance is necessary for development and implementation of TB transcriptomic signatures in PLHIV.
RESUMO
Surgical healthcare has been prioritised in the Southern African Development Community (SADC), a regional intergovernmental entity promoting equitable and sustainable economic growth and socioeconomic development. However, challenges remain in translating political prioritisation into effective and equitable surgical healthcare. The AfroSurg Collaborative (AfroSurg) includes clinicians, public health professionals and social scientists from six SADC countries; it was created to identify context-specific, critical areas where research is needed to inform evidence-grounded policy and implementation. In January 2020, 38 AfroSurg members participated in a theory of change (ToC) workshop to agree on a vision: 'An African-led, regional network to enable evidence-based, context-specific, safe surgical care, which is accessible, timely, and affordable for all, capturing the spirit of Ubuntu[1]' and to identify necessary policy and service-delivery knowledge needs to achieve this vision. A unified ToC map was created, and a Delphi survey was conducted to rank the top five priority knowledge needs. In total, 45 knowledge needs were identified; the top five priority areas included (1) mapping of available surgical services, resources and providers; (2) quantifying the burden of surgical disease; (3) identifying the appropriate number of trainees; (4) identifying the type of information that should be collected to inform service planning; and (5) identifying effective strategies that encourage geographical retention of practitioners. Of the top five knowledge needs, four were policy-related, suggesting a dearth of much-needed information to develop regional, evidenced-based surgical policies. The findings from this workshop provide a roadmap to drive locally led research and create a collaborative network for implementing research and interventions. This process could inform discussions in other low-resource settings and enable more evidenced-based surgical policy and service delivery across the SADC countries and beyond.
