Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.

Rationale: Performance of blood transcriptomic tuberculosis (TB) signatures in longitudinal studies and effects of TB-preventive therapy and coinfection with HIV or respiratory organisms on transcriptomic signatures has not been systematically studied. Objectives: We evaluated longitudinal kinetics of an 11-gene blood transcriptomic TB signature, RISK11, and effects of TB-preventive therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. Methods: RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort, or a longitudinal study in people living with HIV (PLHIV). HIV-uninfected RISK11+ participants were randomized to TPT or no TPT; RISK11- participants received no TPT. PLHIV received standard-of-care antiretroviral therapy and TPT. In the cross-sectional respiratory organisms cohort, viruses and bacteria in nasopharyngeal and oropharyngeal swabs were quantified by real-time quantitative PCR. Measurements and Main Results: RISK11+ status was transient in most of the 128 HIV-negative participants with longitudinal samples; more than 70% of RISK11+ participants reverted to RISK11- by 3 months, irrespective of TPT. By comparison, reversion from a RISK11+ state was less common in 645 PLHIV (42.1%). Non-HIV viral and nontuberculous bacterial organisms were detected in 7.2% and 38.9% of the 1,000 respiratory organisms cohort participants, respectively, and among those investigated for TB, 3.8% had prevalent disease. Median RISK11 scores (%) were higher in participants with viral organisms alone (46.7%), viral and bacterial organisms (42.8%), or prevalent TB (85.7%) than those with bacterial organisms other than TB (13.4%) or no organisms (14.2%). RISK11 could not discriminate between prevalent TB and viral organisms. Conclusions: Positive RISK11 signature status is often transient, possibly due to intercurrent viral infection, highlighting potentially important challenges for implementation of these biomarkers as new tools for TB control.

Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy.

Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.

Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: A multicentre descriptive study.

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.

Characteristics of COVID-19 patients with bacterial coinfection admitted to the hospital from the emergency department in a large regional healthcare system.

INTRODUCTION: The rate of bacterial coinfection with SARS-CoV-2 is poorly defined. The decision to administer antibiotics early in the course of SARS-CoV-2 infection depends on the likelihood of bacterial coinfection. METHODS: We performed a retrospective chart review of all patients admitted through the emergency department with confirmed SARS-CoV-2 infection over a 6-week period in a large healthcare system in the United States. Blood and respiratory culture results were abstracted and adjudicated by multiple authors. The primary outcome was the rate of bacteremia. We secondarily looked to define clinical or laboratory features associated with bacteremia. RESULTS: There were 542 patients admitted with confirmed SARS-CoV-2 infection, with an average age of 62.8 years. Of these, 395 had blood cultures performed upon admission, with six true positive results (1.1% of the total population). An additional 14 patients had positive respiratory cultures treated as true pathogens in the first 72 h. Low blood pressure and elevated white blood cell count, neutrophil count, blood urea nitrogen, and lactate were statistically significantly associated with bacteremia. Clinical outcomes were not statistically significantly different between patients with and without bacteremia. CONCLUSIONS: We found a low rate of bacteremia in patients admitted with confirmed SARS-CoV-2 infection. In hemodynamically stable patients, routine antibiotics may not be warranted in this population.

miRNA expression profiles in liver grafts of HCV and HIV/HCV-infected recipients, 6 months after liver transplantation.

In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro-fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR-101, miR-122, miR-155, miR-192, miR-200c, miR-338, and miR-532 was determined by quantitative real-time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV-infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post-LT. None of the patients was treated with direct-acting anti-HCV drugs. All co-infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR-101 (p = .03), miR-122 (p = .012), and miR-192 (p = .038) were significantly downregulated in HCV/HIV co-infected and HCV mono-infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co-infected ones. Moreover, in co-infected recipients but not in mono-infected ones, miR-101 inversely correlated with the peripheral HCV-RNA levels (r = .41, p = .04) and miR-122 inversely correlated with peripheral HCV-RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02).  In conclusion, as early as 6 months after LT, the presence of HIV-HCV co-infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.

Convalescent plasma, cytomegalovirus infection, and persistent leukopenia in COVID-19 recovery phase: What is the link?

Therapies used to tide over acute crisis of COVID-19 infection may lower the immunity, which can lead to secondary infection or a reactivation of latent infection. We report a 75-years-old male patient who had suffered from severe COVID-19 infection three weeks earlier and who had been treated with corticosteroids and convalescent plasma along with other supportive therapies. At time of discharge he had developed leukopenia which worsened at 1-week follow up visit. On 18th day post-discharge, he became very sick and was brought to our hospital with complaints of severe persistent dysphagia. During evaluation he was diagnosed to have an acute cytomegalovirus infection and severe oropharyngeal thrush. Both COVID-19 and cytomegalovirus are known to cause synergistic decrease in T cells and NK cells leading to immunosuppression. The patient made complete recovery with a course of intravenous ganciclovir and fluconazole. Persistent leukopenia in high risk and severely ill cases should give rise to a suspicion of COVID-19 and cytomegalovirus co-infection.

Candida Bloodstream Infection, a Dire Complication in Hospitalized COVID-19 Patients: Three Cases from a Single Center in Northern Israel.

BACKGROUND: Patients with severe coronavirus disease-2019 (COVID-19) are susceptible to superimposed infections. OBJECTIVES: To describe COVID-19 patients who presented with complications due to Candida bloodstream co-infection (candidemia) and their outcome in a single center in northern Israel (Emek Medical Center) during the second outbreak of COVID-19 in Israel (15 June 2020 to 20 September 2020). METHODS: A retrospective study of COVID-19 patients presenting with candidemia was conducted, including clinical and laboratory data. The incidence of candidemia among hospitalized COVID-19 patients was compared to a historical cohort of non-COVID-19 controls. RESULTS: Three COVID-19 patients complicated with candidemia were documented. All three patients died shortly after the detection of candidemia. Three different Candida sp. were isolated from the blood cultures: C. albicans, C. parapsilosis, and C. glabrata. The incidence of candidemia among COVID-19 patients was 0.679 episodes per 1000 hospital days. CONCLUSIONS: Our small sample suggests a much higher incidence of candidemia among COVID-19 patients compared to a historical cohort of non-COVID-19 controls. All clinicians treating COVID-19 patients in GICU should be aware of this complication.

Lyme Neuroborreliosis: Clinical Outcomes, Controversy, Pathogenesis, and Polymicrobial Infections.

Lyme borreliosis is the object of numerous misconceptions. In this review, we revisit the fundamental manifestations of neuroborreliosis (meningitis, cranial neuritis, and radiculoneuritis), as these have withstood the test of time. We also discuss other manifestations that are less frequent. Stroke, as a manifestation of Lyme neuroborreliosis, is considered in the context of other infections. The summary of the literature regarding clinical outcomes of neuroborreliosis leads to its controversies. We also include new information on pathogenesis and on the polymicrobial nature of tick-borne diseases. In this way, we update the review that we wrote in this journal in 1995. ANN NEUROL 2019;85:21-31.

Faecal microbiota transplantation for eradication of co-infection with Clostridioides difficile and extensively drug-resistant KPC-producing Klebsiella pneumoniae.

Clostridioides difficile infection may be complicated by co-infection with other pathogens. We here describe the successful use of faecal microbiota transplantation to eradicate concomitant C. difficile and extensively drug-resistant (XDR) KPC-producing Klebsiella pneumoniae. Donor microbiota efficiently engrafted in the patient, and a donor-like microbial assemblage persisted in the patient during six months follow-up. The report explores the potential for the donor microbiota to eradicate and replace multi-resistant microorganisms.

Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes.

The COVID-19 pandemic has currently overtaken every other health issue throughout the world. There are numerous ways in which this will impact existing public health issues. Here we reflect on the interactions between COVID-19 and tuberculosis (TB), which still ranks as the leading cause of death from a single infectious disease globally. There may be grave consequences for existing and undiagnosed TB patients globally, particularly in low and middle income countries (LMICs) where TB is endemic and health services poorly equipped. TB control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. This is likely to lead to a reduction in quality of TB care and worse outcomes. Further, TB patients often have underlying co-morbidities and lung damage that may make them prone to more severe COVID-19. The symptoms of TB and COVID-19 can be similar, with for example cough and fever. Not only can this create diagnostic confusion, but it could worsen the stigmatization of TB patients especially in LMICs, given the fear of COVID-19. Children with TB are a vulnerable group especially likely to suffer as part of the "collateral damage". There will be a confounding of symptoms and epidemiological data through co-infection, as happens already with TB-HIV, and this will require unpicking. Lessons for COVID-19 could be learned from the vast experience of running global TB control programmes, while the astonishingly rapid and relatively well co-ordinated response to COVID-19 demonstrates how existing programmes could be significantly improved.

Rapid Diagnosis of a Family Cluster of Pertussis Starting from a Child: a Case Report.

BACKGROUND: Pertussis, caused by Bordetella pertussis (B. pertussis), is a highly transmissible, acute respiratory disease that occurs in many countries. Diagnosis of pertussis continues to be a challenge using traditional tests due to their turn-around time and sensitivity. Herein, we rapidly and accurately screened a family cluster of pertussis from a child and her mother. METHODS: We used an automated nested multiplex PCR system which included B. pertussis, influenza A virus, and 19 other respiratory pathogens. RESULTS: We detected B. pertussis, influenza A virus H1-2009 (FluA-2009), adenovirus, and respiratory syncytial virus (RSV) in the child, and the mother of the child was positive for B. pertussis and FluA-2009. CONCLUSIONS: Active and timely screening for pertussis of adult family members should be considered. The detection of multiple respiratory pathogens may guide effective antibiotic therapies. This could be a novel test for the prevention of pertussis.

Effect of artificial liver support system on short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is difficult to treat and carries a high risk of short-term mortality. This study aimed to explore the effect of artificial liver support system (ALSS) on the survival of HBV-ACLF patients and to investigate which HBV-ACLF patients may benefit from ALSS treatment. We enrolled 132 patients hospitalized for HBV-ACLF according to the criteria of the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) from 425 ACLF patients who were determined to at least meet the Asian Pacific Association for the Study of the Liver criteria and followed up for 90 days. Overall 132 eligible patients were divided into two groups: standard medical treatment (SMT) group, which included 54 patients who underwent SMT alone, and ALSS group, which included 78 patients who underwent ALSS treatment plus SMT. The proportion of HBV-ACLF grade 1, 2, and 3 was 57.69%, 37.18%, and 5.13% in the ALSS group and 51.85%, 35.19%, and 12.96% in the SMT group, respectively. Bacterial infection was present in 43.6% of patients in the ALSS group and in 55.6% of patients in the SMT group. The mortality rates in the ALSS group at 28 and 90 days were significantly lower than those in the SMT group (23.08% vs. 48.15% and 33.33% vs. 57.41%, P < 0.05). ALSS was an independent factor related to both the 28- and 90-day survival of HBV-ACLF patients. Particularly, a higher cumulative survival rate in either patients with HBV-ACLF grade 1 or those with HBV-ACLF with bacterial infection was observed in the ALSS group. Moreover, ALSS had an independent influence on mortality. Based on the COSSH-ACLF criteria, ALSS could better improve the short-term survival of HBV-ACLF patients than SMT alone, especially in those with HBV-ACLF grade 1 or HBV-ACLF with infection.

Secondary purulent infections of the elbow joint: a retrospective, single-center study.

BACKGROUND: Septic arthritis of the elbow joint is a rare condition. Limited data is available on infections of the elbow joint following trauma or prior surgery on this joint. The aim of this study was to describe the etiology, comorbidities, bacterial spectrum and therapy of secondary purulent elbow infections. METHODS: Patients treated in our hospital were selected through retrospective chart review between 2006 and 2015. We included all patients with an empyema of the elbow after a trauma or surgical intervention on this joint. 30 patients between 26 and 82 years (mean: 52.47) were included. RESULTS: Seven patients (23.3%) were female, 23 (76.7%) male. 22 patients (73.3%) had a history of trauma, eight (26.7%) had prior elective surgeries on their elbow. Between one and 25 surgeries (mean: 5.77) were necessary for treatment. In nine patients, debridement and synovectomy were sufficient, eight patients (26.7%) received resection of the elbow joint. One patient was treated with a chronic fistula. In 18 patients (60%), cultures of aspiration/intraoperative swabs were positive for Staphylococcus aureus, four of these were methicillin-resistant. Four patients (13.3%) had positive cultures for Staphylococcus epidermidis, in five patients (16.7%) no bacteria could be cultured. CONCLUSIONS: Secondary infections of the elbow joint are a rare disease with potentially severe courses, requiring aggressive surgical treatment and possibly severely impacting elbow function. Staphylococcus aureus was the most common bacteria in secondary infections and should be addressed by empiric antibiotic treatment when no suspicion for other participating organisms is present.

Umbilical Cord-Derived CD362+ Mesenchymal Stromal Cells Attenuate Polymicrobial Sepsis Induced by Caecal Ligation and Puncture.

Mesenchymal stromal cells (MSCs) have a multimodal, immunomodulatory mechanism of action and are now in clinical trials for single organ and systemic sepsis. However, a number of practicalities around source, homogeneity and therapeutic window remain to be determined. Here, we utilised conditioned medium from CD362+-sorted umbilical cord-human MSCs (UC-hMSCs) for a series of in vitro anti-inflammatory assays and the cryopreserved MSCs themselves in a severe (Series 1) or moderate (Series 2+3) caecal ligation and puncture (CLP) rodent model. Surviving animals were assessed at 48 h post injury induction. MSCs improved human lung, colonic and kidney epithelial cell survival following cytokine activation. In severe systemic sepsis, MSCs administered at 30 min enhanced survival (Series 1), and reduced organ bacterial load. In moderate systemic sepsis (Series 2), MSCs were ineffective when delivered immediately or 24 h later. Of importance, MSCs delivered 4 h post induction of moderate sepsis (Series 3) were effective, improving serum lactate, enhancing bacterial clearance from tissues, reducing pro-inflammatory cytokine concentrations and increasing antimicrobial peptides in serum. While demonstrating benefit and immunomodulation in systemic sepsis, therapeutic efficacy may be limited to a specific point of disease onset, and repeat dosing, MSC enhancement or other contingencies may be necessary.

Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study.

BACKGROUND: Infection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk. METHODS AND FINDINGS: In this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005-2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12-1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88-1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93-1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73-0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04-0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs). CONCLUSIONS: In this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.

Complications of Hemodialysis Catheter Bloodstream Infections: Impact of Infecting Organism.

BACKGROUND: Catheter-related bloodstream infections -(CRBSI) are associated with a high burden of morbidity and mortality, but the impact of infecting organism on clinical outcomes has been poorly studied. METHODS: This retrospective analysis of a prospective vascular access database from a large academic dialysis center investigated whether the organism type affected the clinical presentation or complications of CRBSI. RESULTS: Among 339 patients with suspected CRBSI, an alternate source of infection was identified in 50 (15%). Of 289 patients with CRBSI, 249 grew a single organism and 40 were polymicrobial. Fever and/or rigors were presenting signs in ≥90% of patients with Staphylococcus aureus or Gram-negative CRBSI, but only 61% of Staphylococcus epidermidis infections (p < 0.001). Hospitalization occurred in 67% of patients with S. aureus CRBSI versus 34% of those with S. epidermidis and 40% of those with a Gram-negative bacteria (p < 0.001). Admission to the intensive care unit was required in 14, 9, and 2% (p = 0.06); metastatic infection occurred in 10, 4, and 4% (p = 0.42); and median length of stay among patients admitted to the hospital was 4, 4, and 5.5 days (p = 0.60), respectively. Death due to CRBSI occurred in only 1% of patients with CRBSI. CONCLUSION: CRBSI is confirmed in 85% of catheter-dependent hemodialysis patients in whom it is suspected. S. epidermidis CRBSI tends to present with atypical symptoms. S. aureus CRBSI is more likely to require hospitalization or intensive care admission. Metastatic infection is relatively uncommon, and death due to CRBSI is rare.

Dermacoccus sp. isolated from a brain abscess in a 4-year-old child.

Dermacoccus spp. have rarely been reported as human pathogens. We describe a case of a 4-year-old boy with congenital heart disease who was diagnosed with a brain abscess. The abscess was drained and the sample grew Streptococcus intermedius, Aggregatibacter aphrophilus and Dermacoccus sp.. Dermacoccus grew after 5 days of incubation and the patient was treated with meropenem.

Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host.

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications.

Tuberculosis care for migrant patients in Portugal: a mixed methods study with primary healthcare providers.

BACKGROUND: Tuberculosis (TB) is still a major global health problem. The increasing number of cases observed among foreign-born populations contrasts with the decreasing trends observed in later years in some high-income countries. Healthcare providers are key interveners in the control of TB and HIV-TB infections. In this study, we aimed to explore the perspectives of healthcare providers working in primary care in Portugal about the provision of TB care for migrant patients with TB or HIV-TB co-infection. METHODS: We applied a mixed-methods approach using an online survey and semi-structured interviews with primary healthcare providers. A total of 120 Portuguese healthcare providers participated in the survey, and 17 were interviewed. Survey and interview data were analysed applying descriptive statistics and thematic analysis, respectively. RESULTS: Migrants' lack of knowledge on TB disease and its symptoms was the main reason for advanced-stage presentation of cases. Their high mobility and social isolation affect adherence to treatment. The providers also listed several barriers to migrants' access and use of TB care. The most frequently referred were limited socioeconomic resources, complex bureaucracy at the point of access and registration for healthcare services, especially for undocumented migrants, and obstacles for social protection. Providers also advocated more training initiatives on migrants' health, social and cultural contexts, on HIV and TB integrated care, and on TB scientific update for general practitioners and nurses working at primary healthcare centres. CONCLUSIONS: Future efforts should provide measures to overcome social, economic and administrative obstacles to care for TB-infected migrants, and promote regular training initiatives for national healthcare providers in order to raise awareness and facilitate better care to culturally diverse populations with TB.

Polymicrobial Cerebral Abscess in a Child with Uncorrected Tetralogy of Fallot.

Aggregatibacter aphrophilus and Beta haemolytic Streptococci Lancefield group F are part of the normal oral flora and are known to cause endocarditis, sinusitis, empyema, meningitis and septic arthritis. They are now emerging as a cause of brain abscess particularly in patients with congenital heart diseases. We report a case of a 10-year-old boy with Tetralogy of Fallot (TOF), who presented with fever, headache and drowsiness. Culture yielded the growth of Aggregatibacter aphrophilus and Beta hemolytic streptococci Lancefield group F. He became clinically stable after treatment with ceftriaxone.