Diagnosing Viral Infections Through T-Cell Receptor Sequencing of Activated CD8+ T Cells.

T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3ß TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3ß sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2-associated CDR3α/ß sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

BACKGROUND: Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. OBJECTIVES: To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. METHODS: Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. RESULTS: Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. CONCLUSION: Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

COVID-19 in three waves in a tertiary referral hospital in Belgium: a comparison of patient characteristics, management, and outcome.

PURPOSE: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021. METHODS: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression. RESULTS: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality. CONCLUSIONS: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution.

Clostridioides difficile recurrence in individuals with and without cancer: a Swedish population-based cohort study.

PURPOSE: Patients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored. METHODS: This Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006-2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status. RESULTS: Compared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73-0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43-1.74; Cancer history: OR = 1.45, 95% CI 1.36-1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76-0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97-1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found. CONCLUSION: The population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high.

Clostridioides difficile infection, recurrence and the associated healthcare consumption in Sweden between 2006 and 2019: a population-based cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). METHODS: This Swedish nationwide population-based cohort study (2006-2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. RESULTS: Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40-18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16-9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84-4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31-3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (< 65 years) than the older (≥ 65 years), and in those with fewer comorbidities, but similar between sexes. Compared to those without recurrence, individuals with recurrence particularly showed a higher rate of hospital admissions (IRR = 1.18, 95% 1.12-1.24). Compared to community-acquired CDI, those with hospital-acquired CDI presented with a higher rate of hospital admissions (IRR = 7.29, 95% CI 6.68-7.96) and a longer length of stay (IRR = 7.64, 95% CI 7.07-8.26). CONCLUSION: CDI was associated with increased health consumption in all affected patient groups. The majority of the CDI burden could be contributed to hospital-acquired CDI (~ 9/10), older patients (~ 3/4) and those with multiple comorbidities (~ 6/10 Charlson score ≥ 3), with 1/5 of the total CDI burden contributed to individuals with recurrence. Yet, relatively speaking the burden was higher among the younger and those with fewer comorbidities, compared to their peers without CDI.

Hospital antibiotic prescribing patterns in adult patients according to the WHO Access, Watch and Reserve classification (AWaRe): results from a worldwide point prevalence survey in 69 countries.

OBJECTIVES: The WHO Access, Watch and Reserve (AWaRe) classification has been developed to support countries and hospitals in promoting rational use of antibiotics while improving access to these essential medicines. We aimed to describe patterns of worldwide antibiotic use according to the AWaRe classification in the adult inpatient population. METHODS: The Global Point Prevalence Survey on Antimicrobial Consumption and Resistance (Global-PPS) collects hospital antibiotic use data using a standardized PPS methodology. Global-PPS 2015, 2017 and 2018 data, collected by 664 hospitals in 69 countries, were categorized into AWaRe groups to calculate proportional AWaRe use, Access-to-Watch ratios and the most common indications for treatment with selected Watch antibiotics. Only prescriptions for systemic antibiotics on adult inpatient wards were analysed. RESULTS: Regional Access use ranged from 28.4% in West and Central Asia to 57.7% in Oceania, whereas Watch use was lowest in Oceania (41.3%) and highest in West and Central Asia (66.1%). Reserve use ranged from 0.03% in sub-Saharan Africa to 4.7% in Latin America. There were large differences in AWaRe prescribing at country level. Watch antibiotics were prescribed for a range of very different indications worldwide, both for therapeutic and prophylactic use. CONCLUSIONS: We observed considerable variations in AWaRe prescribing and high use of Watch antibiotics, particularly in lower- and upper-middle-income countries, followed by high-income countries. The WHO AWaRe classification has an instrumental role to play in local and national stewardship activities to assess prescribing patterns and to inform and evaluate stewardship activities.

Clinical Management of Argentine Hemorrhagic Fever using Ribavirin and Favipiravir, Belgium, 2020.

We report a case of Argentine hemorrhagic fever diagnosed in a woman in Belgium who traveled from a disease-endemic area. Patient management included supportive care and combination therapy with ribavirin and favipiravir. Of 137 potential contacts, including friends, relatives, and healthcare and laboratory workers, none showed development of clinical symptoms of this disease.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs: Two case reports and a review of the literature.

BACKGROUND: Patients suffering from drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs often need to be retreated rapidly. Patch tests prior to the reintroduction of antituberculosis drugs are rarely performed. OBJECTIVES: To highlight those drugs most often involved in DRESS caused by antituberculosis drugs, illustrate the potential value of patch tests to identify these culprit(s), and provide insights into how to rapidly retreat these patients. METHODS: A detailed description of the work-up of two illustrative patients, together with a literature review of similar cases, is provided. RESULTS: All first-line antituberculosis drugs may cause DRESS syndrome, but rifampicin and isoniazid are most frequently involved. Patch tests can be performed sooner than usually advised in the context of DRESS syndrome, and potentially with lower test concentrations, but false-negative results are possible. Sequential reintroduction of patch test-negative drugs is feasible, although the dose and order of drugs to be readministered, as well as the use of concomitant systemic corticosteroids, remain a matter of debate. CONCLUSION: Patch tests in the context of DRESS syndrome caused by antituberculosis drugs, despite their shortcomings, may potentially guide rapid retreatment of these patients.

Antibiotic stewardship interventions in hospitals in low-and middle-income countries: a systematic review.

OBJECTIVE: To review the effectiveness of antibiotic stewardship interventions in hospitals in low- and middle-income countries. METHODS: We searched MEDLINE®, Embase®, Cochrane Central Register of Controlled Trials and regional indexes for studies of interventions to improve appropriate prescribing and use of antibiotics for hospitalized patients in low- and middle-income countries. We included controlled trials, controlled before-and-after studies and interrupted time-series studies published up to December 2017. We report prescribing, clinical and microbiological outcomes using a narrative approach. FINDINGS: We screened 7342 original titles and abstracts, assessed 241 full-text articles and included 27 studies from 2 low-income and 11 middle-income countries. We found a medium (11 studies) or high risk (13 studies) of bias. Generally, all types of interventions (structural, persuasive and enabling) and intervention bundles were reported to improve prescribing and clinical outcomes. However, the studied interventions and reported outcomes varied widely. The most frequent intervention was procalcitonin-guided antibiotic treatment (8 of 27 studies, all randomized controlled trials). The intervention was associated with a relative risk for patients receiving antibiotics ranging between 0.40 and 0.87. CONCLUSION: The majority of studies reported a positive effect of hospital antibiotic stewardship interventions. However, we cannot draw general conclusions about the effectiveness of such interventions in low- and middle-income countries because of low study quality, heterogeneity of interventions and outcomes, and under-representation of certain settings. To strengthen the evidence base, action needs to be taken to address these shortcomings.

Expression of the Plasmodium falciparum Clonally Variant clag3 Genes in Human Infections.

Background: Many genes of the malaria parasite Plasmodium falciparum show clonally variant expression regulated at the epigenetic level. These genes participate in fundamental host-parasite interactions and contribute to adaptive processes. However, little is known about their expression patterns during human infections. A peculiar case of clonally variant genes are the 2 nearly identical clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to resistance to some toxic compounds. Methods: We developed a procedure to characterize the expression of clag3 genes in naturally infected patients and in experimentally infected human volunteers. Results: We provide the first description of clag3 expression during human infections, which revealed mutually exclusive expression and identified the gene predominantly expressed. Adaptation to culture conditions or selection with a toxic compound resulted in isolate-dependent changes in clag3 expression. We also found that clag3 expression patterns were reset during transmission stages. Conclusions: Different environment conditions select for parasites with different clag3 expression patterns, implying functional differences between the proteins encoded. The epigenetic memory is likely erased before parasites start infection of a new human host. Altogether, our findings support the idea that clonally variant genes facilitate the adaptation of parasite populations to changing conditions through bet-hedging strategies.

Antibiotic prescription behaviours in Lao People's Democratic Republic: a knowledge, attitude and practice survey.

OBJECTIVE: To assess the antibiotic prescribing practices of doctors working in the Lao People's Democratic Republic and their knowledge of local antibiotic resistance patterns. METHODS: Doctors attending morning meetings in 25 public hospitals in four provinces were asked to complete a knowledge, attitude and practice survey. The questionnaire contained 43 multiple choice questions that the doctor answered at the time of the meeting. FINDINGS: The response rate was 83.4% (386/463). Two hundred and seventy doctors (59.8%) declared that they had insufficient information about antibiotics. Only 14.0% (54/386) recognized the possibility of cephalosporin cross-resistance in methicillin-resistant Staphylococcus aureus. Most participants had no information about local antibiotic resistance for Salmonella Typhi (211/385, 54.8%) and hospital-acquired pneumonia (253/384, 65.9%). Unnecessary antibiotic prescriptions were considered as harmless by 115 participants and 148 considered locally-available generic antibiotics to be of poor quality. Nearly three-quarters (280/386) of participants agreed that it was difficult to select the correct antibiotics. Most participants (373/386) welcomed educational programmes on antibiotic prescribing and 65.0% (249/383) preferred local over international antibiotic guidelines. CONCLUSION: Doctors in the Lao People's Democratic Republic seem to favour antibiotic prescribing interventions. Health authorities should consider a capacity building programme that incorporates antibiotic prescribing and hospital infection control.

Streptococcal pharyngitis in children: to treat or not to treat?

UNLABELLED: Controversy remains about the need for antibiotic therapy of group A streptococcal (GAS) pharyngitis in high-resource settings. Guidelines on the management of GAS pharyngitis differ considerably, especially in children. We performed a literature search on the diagnosis and treatment of GAS pharyngitis in children and compared different guidelines with current epidemiology and the available evidence on management. Some European guidelines only recommend antibiotic treatment in certain high-risk patients, while many other, including all American, still advise antimicrobial treatment for all children with GAS pharyngitis, given the severity and re-emerging incidence of complications. Empirical antimicrobial treatment in children with sore throat and a high clinical suspicion of GAS pharyngitis will still result in significant overtreatment of nonstreptococcal pharyngitis. This is costly and leads to emerging antibiotic resistance. Early differential diagnosis between viral and GAS pharyngitis, by means of a 'rapid antigen detection test' (RADT) and/or a throat culture, is therefore needed if 'pro treatment' guidelines are used. CONCLUSION: Large scale randomized controlled trials are necessary to assess the value of antibiotics for GAS pharyngitis in high-resource countries, in order to achieve uniform and evidence-based guidelines. The severity and the possibly increasing incidence of complications in school-aged children suggests that testing and treating proven GAS pharyngitis can still be beneficial.

Global prevalence of antibiotic consumption during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Antibiotic use during pregnancy is widespread with notable variations across regions. METHODS: This systematic review and meta-analysis (Prospero protocol CRD42023418979) examines the prevalence and variability of antibiotic use in pregnancy globally and regionally, considering different methodologies and maternal characteristics. We searched Embase, PubMed, and Web of Science for observational studies published in English from the year 2000 and onwards. Random-effect meta-analyses were used to pool the prevalence of antibiotic consumption during pregnancy, presented as percentages with 95% confidence intervals (CI). Joanna Briggs Institute Critical appraisal checklist for prevalence studies was used for bias assessment. FINDINGS: Overall, 116 studies (14 from Africa, 24 from the Americas, six from Eastern Mediterranean, 57 from Europe, four from South-East Asia and 11 from Western Pacific) were included (33,821,194 pregnancies). The majority of studies (84.5%) were appraised with a low risk of bias. The prevalence of antibiotic consumption during pregnancy ranged between 0.04 to 90%, with a pooled estimate of 23.6% (95% CI: 20.1-27.5, I2 =100%). Low-income countries had the highest pooled prevalence (45.3%, 95% CI: 15.4-79.1, I2 =99.6%). Regionally, the Western Pacific had the highest pooled prevalence (34.4%, 95% CI: 13.4-64.1, I2 =100%). The prevalence of antibiotic consumption during pregnancy increased over time in the Americas and Western Pacific. The studies exhibited considerable heterogeneity (I2 >95%), and the trim-and-fill method estimated a potential 10% underestimation of the overall pooled prevalence, suggesting publication bias. INTERPRETATION: This meta-analysis suggests that about 1/4 of women worldwide use antibiotics during pregnancy. This study suggests a high prevalence of antibiotic consumption during pregnancy with disparities according to region and level of country income, ethnicity and whether antibiotics were prescribed or self-medicated. There was a variability in reported findings across age categories, potential bias from small sample sizes, and language bias from including only studies published in English.

Low tuberculosis treatment initiation after positive tuberculosis lipoarabinomannan results.

A positive urine TB-LAM result should lead to TB treatment initiation. TB treatment uptake was low after a positive TB-LAM but negative Xpert test. A lack of trust in TB-LAM results by clinicians and false-positive results may contribute to these results. https://bit.ly/3VGHekC.

Does HIV status affect the aetiology, bacterial resistance patterns and recommended empiric antibiotic treatment in adult patients with bloodstream infection in Cambodia?

OBJECTIVE: The microbiologic causes of bloodstream infections (BSI) may differ between HIV-positive and HIV-negative patients and direct initial empiric antibiotic treatment (i.e. treatment before culture results are available). We retrospectively assessed community-acquired BSI episodes in adults in Cambodia according to HIV status for spectrum of bacterial pathogens, antibiotic resistance patterns and appropriateness of empiric antibiotics. METHODS: Blood cultures were systematically performed in patients suspected of BSI in a referral hospital in Phnom Penh, Cambodia. Data were collected between 1 January 2009 and 31 December 2011. RESULTS: A total of 452 culture-confirmed episodes of BSI were recorded in 435 patients, of whom 17.9% and 82.1% were HIV-positive and HIV-negative, respectively. Escherichia coli accounted for one-third (n = 155, 32.9%) of 471 organisms, with similar rates in both patient groups. Staphylococcus aureus and Salmonella cholereasuis were more frequent in HIV-positive vs. HIV-negative patients (17/88 vs. 38/383 (P = 0.02) and 10/88 vs. 5/383 (P < 0.001)). Burkholderia pseudomallei was more common in HIV-negative than in HIV-positive patients (39/383 vs. 2/88, P < 0.001). High resistance rates among commonly used antibiotics were observed, including 46.6% ceftriaxone resistance among E. coli isolates. Empiric antibiotic treatments were similarly appropriate in both patient groups but did not cover antibiotic-resistant E. coli (both patient groups), S. aureus (both groups) and B. pseudomallei (HIV-negative patients). CONCLUSION: The present data do not warrant different empiric antibiotic regimens for HIV-positive vs. HIV-negative patients in Cambodia. The overall resistance rates compromise the appropriateness of the current treatment guidelines.

Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study.

OBJECTIVES: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age. METHODS: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs. RESULTS: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were ≥65 years, and 54.9% were female. CDI was associated with a 3- to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities. DISCUSSION: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups.

Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding: A mixed-methods evaluation.

During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4≤200cells/µl. Adult participants with tuberculosis symptoms, recruited near-facility in Lesotho and South-Africa between 2021-2022, were offered HIV testing (capillary blood), Xpert MTB/RIF and Ultra, and MGIT culture (sputum). People living with HIV (PLHIV) were offered VISITECT (venous blood) and Alere tuberculosis-lipoarabinomannan (AlereLAM, urine) testing. AHD was defined as a CD4≤200cells/µl on VISITECT or a positive tuberculosis test. A CD4≤200cells/µl on VISITECT triggered Immy cryptococcal antigen (Immy CrAg, plasma) testing. Participants were referred with test results. To evaluate feasibility, we assessed i) acceptability and ii) intervention delivery of point-of-care diagnostics among study staff using questionnaires and group discussions, iii) process compliance, and iv) early effectiveness (12-week survival and treatment status) in PLHIV. Predictors for 12-week survival were assessed with logistic regression. Thematic content analysis and triangulation were performed. Among PLHIV (N = 676, 48.6% of 1392 participants), 7.8% were newly diagnosed, 81.8% on ART, and 10.4% knew their HIV status but were not on ART. Among 676 PLHIV, 41.7% had AHD, 29.9% a CD4≤200cells/µl and 20.6% a tuberculosis diagnosis. Among 200 PLHIV tested with Immy CrAg, 4.0% were positive. The procedures were acceptable for study staff, despite intervention delivery challenges related to supply and the long procedural duration (median: 73 minutes). At 12 weeks, among 276 PLHIV with AHD and 328 without, 3.3% and 0.9% had died, 84.8% and 92.1% were alive and 12.0% and 7.0% had an unknown status, respectively. Neither AHD nor tuberculosis status were associated with survival. Implementing AHD care package diagnostics was feasible during tuberculosis-case finding. AHD was prevalent, and not associated with survival, which is likely explained by the low specificity of VISITECT. Challenges with CD4 testing and preventive treatment uptake require addressing.

Leveraging T-cell receptor - epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution.

Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) - epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. These models were then applied to longitudinal CD8+ TCR repertoires from critical and non-critical COVID-19 patients. In spite of comparable initial CoV-common TCR repertoire depth and CD8+ T-cell depletion, the temporal dynamics of SC2-unique TCRs differed depending on the disease severity. Specifically, while non-critical patients demonstrated a large and diverse SC2-unique TCR repertoire by the second week of the disease, critical patients did not. Furthermore, only non-critical patients exhibited redundancy in the CD8+ T-cell response to both groups of epitopes, SC2-unique and CoV-common. These findings indicate a valuable contribution of the SC2-unique CD8+ TCR repertoires. Therefore, a combination of specific and cross-reactive CD8+ T-cell responses may offer a stronger clinical advantage. Besides tracking the specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire, our analytical framework can be expanded to more epitopes and assist in the assessment and monitoring of CD8+ T-cell response to other infections.

The Emergence of Travel-related Infections in Critical Care Units.

Several tropical or geographically confined infectious diseases may lead to organ failure requiring management in an intensive care unit (ICU), both in endemic low- and middle-income countries where ICU facilities are increasingly being developed and in (nonendemic) high-income countries through an increase in international travel and migration. The ICU physician must know which of these diseases may be encountered and how to recognize, differentiate, and treat them. The four historically most prevalent "tropical" diseases (malaria, enteric fever, dengue, and rickettsiosis) can present with single or multiple organ failure in a very similar manner, which makes differentiation based solely on clinical signs very difficult. Specific but frequently subtle symptoms should be considered and related to the travel history of the patient, the geographic distribution of these diseases, and the incubation period. In the future, ICU physicians may also be more frequently confronted with rare but frequently lethal diseases, such as Ebola and other viral hemorrhagic fevers, leptospirosis, and yellow fever. No one could have foreseen the worldwide 2019-up to now coronavirus disease 2019 (COVID-19) crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was initially spread by travel too. In addition, the actual pandemic due to SARS-CoV-2 reminds us of the actual and potential threat of (re)-emerging pathogens. If left untreated or when treated with a delay, many travel-related diseases remain an important cause of morbidity and even mortality, even when high-quality critical care is provided. Awareness and a high index of suspicion of these diseases is a key skill for the ICU physicians of today and tomorrow to develop.