Anton Reepalu

BACKGROUND: Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia. METHODS: Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture. RESULTS: TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm(3), this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. CONCLUSIONS: Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

BACKGROUND: The World Health Organization (WHO) tuberculosis (TB) symptom screening instrument (WHO-TB) can identify human immunodeficiency virus (HIV)-infected individuals at low risk of tuberculosis (TB); however, many patients report WHO-TB symptoms and require further TB investigations. We hypothesized that further clinical scoring could classify subjects with a positive WHO-TB screening result (WHO-TB(+)) for the likelihood of TB. METHODS: HIV-infected adults eligible to initiate antiretroviral therapy (ART) were recruited and prospectively followed at 5 Ethiopian health centers. Irrespective of symptoms, all participants underwent sputum bacteriological testing for TB. Symptoms, physical findings, hemoglobin, and CD4 cell count results were compared between subjects with and those without bacteriologically confirmed TB. Variables associated with TB in WHO-TB(+) individuals were used to construct a scoring algorithm with multiple logistic regression analysis. RESULTS: Among 812 participants, 137 (16.9%) had TB. One hundred fifty-nine persons (20%) had a negative WHO-TB screen, 10 of whom had TB (negative predictive value [NPV], 94% [95% confidence interval {CI}, 90%-97.5%]). For WHO-TB(+) subjects, the following variables were independently associated with TB, and were assigned 1 point each in the clinical scoring algorithm: cough, Karnofsky score ≤80, mid-upper arm circumference <20 cm, lymphadenopathy, and hemoglobin <10 g/dL. Among subjects with 0-1 points, 20 of 255 had TB (NPV, 92% [95% CI, 89%-95%]), vs 19 of 34 participants with ≥4 points (positive predictive value, 56% [95% CI, 39%-73%]). The use of WHO-TB alone identified 159 of 784 (20%) with a low risk of TB, vs 414 of 784 (53%) using WHO-TB followed by clinical scoring (P< .001). The difference in proportions of confirmed TB in these subsets was nonsignificant (6.3% vs 7.2%; P= .69). CONCLUSIONS: Clinical scoring can further classify HIV-infected adults with positive WHO-TB screen to assess the risk of TB, and would reduce the number of patients in need of further TB investigations before starting ART. CLINICAL TRIALS REGISTRATION: NCT01433796.

Abstract Objective To assess the diagnostic performance of urine lipoarabinomannan ( LAM ) detection for TB screening in HIV ‐positive adults in E thiopia. Methods Testing for LAM was performed using the Determine TB ‐ LAM lateral flow assay on urine samples from participants in a prospective cohort with baseline bacteriological categorisation for active TB in sputum. Characteristics of TB patients with regard to LAM status were determined. Participants were followed for 6 months to evaluate survival, retention in care and incident TB . Results Positive LAM results were found in 78/757 participants. Among 128 subjects with definite (confirmed by culture and/or Xpert MTB / RIF ) TB , 33 were LAM ‐positive (25.8%); the respective figure for clinically diagnosed cases was 2/20 (10%). Five of the remaining 43 LAM ‐positive individuals had died during the 6‐month follow‐up period, whereas 38 remained in care without clinical signs of TB . The overall sensitivity, specificity, positive predictive value ( PPV ) and negative predictive value ( NPV ) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients, LAM positivity was associated with higher WHO clinical stage, lower body mass index ( BMI ), CD 4 cell and haemoglobin levels, and with increased mortality. A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 (38.2%) of definite TB cases; among those with CD 4 count ≤100 cells/mm 3 , this proportion was 66.7%. Conclusions The performance of urine LAM testing for TB detection was poor in this population. However, this was improved among subjects with CD 4 count ≤100 cells/mm 3 . In combination with sputum microscopy urine, LAM could be considered for targeted TB screening in this subgroup.

Abstract Background Traditional models to predict intensive care outcomes do not perform well in COVID‐19. We undertook a comprehensive study of factors affecting mortality and functional outcome after severe COVID‐19. Methods In this prospective multicentre cohort study, we enrolled laboratory‐confirmed, critically ill COVID‐19 patients at six ICUs in the Skåne Region, Sweden, between May 11, 2020, and May 10, 2021. Demographics and clinical data were collected. ICU burden was defined as the total number of ICU‐treated COVID‐19 patients in the region on admission. Surviving patients had a follow‐up at 90 days for assessment of functional outcome using the Glasgow Outcome Scale‐Extended (GOSE), an ordinal scale (1–8) with GOSE ≥5 representing a favourable outcome. The primary outcome was 90‐day mortality; the secondary outcome was functional outcome at 90 days. Results Among 498 included patients, 74% were male with a median age of 66 years and a median body mass index (BMI) of 30 kg/m 2 . Invasive mechanical ventilation was employed in 72%. Mortality in the ICU, in‐hospital and at 90 days was 30%, 38% and 39%, respectively. Mortality increased markedly at age 60 and older. Increasing ICU burden was independently associated with a two‐fold increase in mortality. Higher BMI was not associated with increased mortality. Besides age and ICU burden, smoking status, cortisone use, P a CO 2 &gt;7 kPa, and inflammatory markers on admission were independent factors of 90‐day mortality. Lower GOSE at 90 days was associated with a longer stay in the ICU. Conclusion In critically ill COVID‐19 patients, the 90‐day mortality was 39% and increased considerably at age 60 or older. The ICU burden was associated with mortality, whereas a high BMI was not. A longer stay in the ICU was associated with unfavourable functional outcomes at 90 days.