Point-of-care ultrasound for tuberculosis and HIV-revisiting the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol and its differential diagnoses.

BACKGROUND: The 'Focused assessment with sonography for HIV-associated tuberculosis' (FASH) protocol has been applied and researched for over a decade in HIV-infected patients with suspected extra-pulmonary tuberculosis. Interpretation of target FASH features may be challenging as they can also indicate alternative opportunistic diseases. OBJECTIVES: The primary aim of the review was summarizing the accumulated evidence on the diagnostic accuracy of the FASH protocol including description of diagnoses of target FASH features. SOURCES: Literature was searched using PubMed, Google Scholar, and publications referencing the original FASH publications; data from identified studies were compiled with data from studies identified by a preceding Cochrane review. A meta-analysis was performed based on a generalized linearized mixed model. Data on differential diagnoses were compiled by literature review and retrospective evaluation of clinical data. CONTENT: We identified ten studies; abdominal target FASH features were most studied. Sensitivity and specificity estimates were 39% (95% CI 25-54) and 89% (95% CI 83-96) for enlarged lymph nodes (ten studies), and 30% (95% CI 16-45%) and 93% (95% CI 89-98%) for hypoechoic spleen lesions (eight studies). In people living with HIV differential diagnoses of target FASH features are multiple and primarily include other opportunistic infections and malignancies such as non-tuberculous mycobacterial infection, bacillary angiomatosis, hepato-splenic brucellosis, meliodiosis, visceral leishmaniasis, invasive fungal infections, and lymphoma as well as Kaposi sarcoma. Ultrasound-guided diagnostic sampling may assist obtention of a definitive diagnosis. IMPLICATIONS: On the basis of current evidence, although limited by methodology, and personal experience, we recommend basic ultrasound training, including the FASH protocol and ultrasound-guided diagnostic interventions, for all healthcare providers working with people living with HIV in resource-limited settings.

HIV infection rather than concurrent opportunistic infections drives most systemic procoagulant, vascular and damage responses - a prospective cohort study in central Africa.

BACKGROUND: HIV infection is accompanied by various systemic host responses, including activation of coagulation and the vascular endothelium. We sought to determine the impact of opportunistic coinfections in a central African setting. METHODS: This prospective study included 98 HIV-infected individuals in Gabon initiating combination antiretroviral therapy (cART) and followed them up for 6 months. Patients were stratified according to the presence of active tuberculosis (TB; n=19), mucocutaneous opportunistic infection (n=9) or no opportunistic infection (n=70). HIV-uninfected subjects were included as controls (n=32). Plasma concentrations of 14 markers of coagulation, endothelial activation, extracellular matrix formation and tissue damage were measured with a multiplex assay at baseline and months 3 and 6 after cART initiation. RESULTS: HIV-infected patients showed elevated plasma levels of all biomarkers measured with exception of protein C, which was reduced. Concurrent TB was only associated with elevated concentrations of D-dimer, metallopeptidase inhibitor 1 and Tenascin-C. Mucocutaneous coinfection did not alter HIV-associated responses. Most markers measured declined but remained elevated despite response to cART. CONCLUSIONS: HIV infection is associated with systemic pro-coagulant, vascular and damage responses. In an ambulatory setting, concurrent opportunistic infections have little if any influence on these responses and normalization is incomplete after response to cART. This suggests that these responses are mainly driven by HIV-associated immune activation and less so by opportunistic infections.