Severe Opportunistic Infections Research Articles

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4—2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Undiagnosed HIV in Patients on Immunosuppressive Medications Presenting with HIV-Associated Kidney Disease.

Approximately 158,500 adults and adolescents in the United States live with undiagnosed human immunodeficiency virus (HIV). Missed or delayed diagnoses adversely affect disease management and outcomes. This is particularly salient for patients receiving immunosuppressive and immunomodulatory therapy for the management of chronic inflammatory conditions, in which additional immunosuppression may increase the risk and severity of opportunistic infections. Despite this risk, comprehensive HIV testing before the initiation of immunosuppressive therapy is not yet the norm. We describe a case series containing the narratives of three patients recently treated with immunosuppressive agents, who presented with signs concerning for HIV-associated kidney diseases and who were found to have undiagnosed HIV later in the treatment course, which, unfortunately, resulted in poor outcomes. Screening for HIV or related illnesses, such as viral hepatitis or mycobacterial co-infections including tuberculosis, is essential before initiating biologic immunosuppression.

P028 Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus

Abstract Background/Aims Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that develops following the reactivation of the John Cunningham virus (JCV) that in rare circumstances can occur in autoimmune disorders such as systemic lupus erythematosus (SLE). We present a 75-year-old female with SLE who had been treated with immunosuppressive therapy (mycophenylate and steroids) for one year. Methods A 75 year-old female presented with sub-acute deterioration of physical and cognitive function over the course of a few months including memory loss, ataxia, dysgraphia, word finding difficulty, confusion, low mood and reduced oral intake. Neurological examination revealed receptive and expressive aphasia, gaze fixation, unilateral weakness, brisk reflexes with positive plantar reflex and rigidity. A diagnosis of PML was made due to the detection of JC virus in the cerebrospinal fluid (234 copies/ml) and brain MRI findings consistent with the disease. Haematology results showed a profound lymphopenia (0.1x109 ). Mycophenolate was held and she was commenced on increasing doses of Mirtazapine up to 45mg. Clinical review at four months found marked improvement in her cognitive and physical abilities. Repeat CSF analysis found JC virus to be undetectable. Results PML has a 20-fold greater incidence in SLE when compared with the general population. Lymphopenia is a common finding in patients with SLE and has been found to correlate with both the risk and severity of opportunistic infections. The cause of this can be multifactorial and immunosuppressive drugs are often implicated however SLE in isolation can cause severe CD4+ lymphopenia leading to an increased risk of PML reactivation. This case demonstrates the importance of monitoring lymphocyte counts in SLE. Current guidance suggests adjusting regimes of immunosuppressive therapy if lymphocyte counts fall below 1x109 however further guidance on its management may be warranted. The heterogenous manifestation of SLE can make differentiating between the neurological syndromes associated with rheumatic disease and PML challenging. Given the management of PML is vastly different to that of SLE in regards to introduction or withdrawal of immunosuppressive therapies, there should be a high index of clinical suspicion in the early stages of investigation. In vitro studies have explored the possibility of mirtazapine (a 5-HT2A antagonist) providing a low-risk treatment option for those with SLE and this warrants further research into its efficacy in treating or preventing PML in this cohort. Our patient had improved symptomology after cessation of mycophenolate and the commencement of Mirtazapine. Conclusion PML is a rare complication of SLE but should be considered in patients admitted with neuropsychiatric presentations, the use of Mirtazapine may provide a low-risk treatment strategy. Disclosure D. Babla: None. Y. Suleman: None. A. Whittington: None. S. Hamdulay: None.

Sociodemographic and clinical characteristics of patients with HIV treated in a hospital in the Colombian Orinoco region 2018-2023

Introduction: The human immunodeficiency virus is a worldwide public health problem, with an average number of infected people between 33.1 and 45.7 million and the death of an average of 630 000 people per year. According to the WHO, only 54% of people infected with HIV know they are infected. Methods: Observational, descriptive, retrospective, retrospective, cross-sectional study of patients who consulted a hospital in the Colombian Orinoquía and who underwent confirmation of HIV diagnosis in the period from 2018 to 2023. Results: 337 patients were obtained, 72.70% male and 23.30% female; the mean age was 34.89 years (SD ± 12.63); 94.07% came from urban areas and 5.93% from rural areas; 56.08% were in the HIV stage and 43.92% in the AIDS stage; according to the mechanisms of transmission, heterosexual 70.92%, homosexual 13.06%, bisexual 9.50%, and maternal infant 6. 53%; the most frequent opportunistic diseases and/or coinfections were cerebral toxoplasmosis (24.32%), esophageal candidiasis (20.27%), pneumonitis pneumonia (17.57%), pulmonary tuberculosis 13.51%, 89.06% of patients started antiretroviral therapy during hospital stay, mortality reported in this cohort of patients diagnosed in the period from 2018 to 2023 was 8.01%. Conclusions: It is important to strengthen actions to improve access to health services for patients living with HIV, avoid prolonged stays in hospital care centers, and prevent severe opportunistic infections that require prolonged treatments leading to drug interactions and affecting adherence to treatments.

First report of blaOXA-181-carrying IncX3 plasmids in multidrug-resistant Enterobacter hormaechei and Serratia nevei recovered from canine and feline opportunistic infections.

blaOXA-181 is a significant carbapenemase-encoding gene, usually associated with an epidemic IncX3 plasmid found in Enterobacterales worldwide. In this article, we revealed six carbapenemase-producing (CP) Enterobacter hormaechei and two CP Serratia nevei strains harboring blaOXA-181-carrying IncX3 and multidrug resistance plasmids recovered from dogs and cats in Thailand. The carriage of these plasmids can promote extensively drug-resistant properties, limiting antimicrobial treatment options in veterinary medicine. Since E. hormaechei and S. nevei harboring blaOXA-181-carrying IncX3 plasmids have not been previously reported in dogs and cats, our findings provide the first evidence of dissemination of the epidemic plasmids in these bacterial species isolated from animal origins. Pets in communities can serve as reservoirs of significant antimicrobial resistance determinants. This situation places a burden on antimicrobial treatment in small animal practice and poses a public health threat.

A Genetic Locus in Elizabethkingia anophelis Associated with Elevated Vancomycin Resistance and Multiple Antibiotic Reduced Susceptibility.

The Gram-negative Elizabethkingia express multiple antibiotic resistance and cause severe opportunistic infections. Vancomycin is commonly used to treat Gram-positive infections and has also been used to treat Elizabethkingia infections, even though Gram-negative organisms possess a vancomycin permeability barrier. Elizabethkingia anophelis appeared relatively vancomycin-susceptible and challenge with this drug led to morphological changes indicating cell lysis. In stark contrast, vancomycin growth challenge revealed that E. anophelis populations refractory to vancomycin emerged. In addition, E. anophelis vancomycin-selected mutants arose at high frequencies and demonstrated elevated vancomycin resistance and reduced susceptibility to other antimicrobials. All mutants possessed a SNP in a gene (vsr1 = vancomycin-susceptibility regulator 1) encoding a PadR family transcriptional regulator located in the putative operon vsr1-ORF551, which is conserved in other Elizabethkingia spp as well. This is the first report linking a padR homologue (vsr1) to antimicrobial resistance in a Gram-negative organism. We provide evidence to support that vsr1 acts as a negative regulator of vsr1-ORF551 and that vsr1-ORF551 upregulation is observed in vancomycin-selected mutants. Vancomycin-selected mutants also demonstrated reduced cell length indicating that cell wall synthesis is affected. ORF551 is a membrane-spanning protein with a small phage shock protein conserved domain. We hypothesize that since vancomycin-resistance is a function of membrane permeability in Gram-negative organisms, it is likely that the antimicrobial resistance mechanism in the vancomycin-selected mutants involves altered drug permeability.

Efficacy and safety of adalimumab in pediatric patients with Crohn’s disease: A systematic review and meta-analysis

PurposeThere is currently no curative treatment for childhood Crohn’s disease (CD). This meta-analysis aimed to validate the efficacy and safety of adalimumab (ADA) in pediatric patients with CD.Materials and methodsWe searched all relevant studies in the PubMed, Web of Science, Embase, and Cochrane Library databases. The primary outcomes were induction (≤ 12 weeks) and maintenance (up to 48 weeks) of remission and response. Secondary outcomes were severe adverse events and opportunistic infections to ADA. The Cochrane bias assessment tool was used to assess the risk of bias in randomized controlled trials. The methodological quality of the single-arm studies was assessed using the methodological index for non-randomized studies tool.ResultsTen clinical trials involving a total of 885 patients were included. Results indicated that 59% (95% confidence interval [CI] 39–80%) of the subjects treated with ADA achieved induction of remission, and 60% (95% CI 35–86%) of the subjects treated with ADA achieved induction of response, 57% (95% CI 44–70%) achieved maintenance of remission, and 63% (95% CI 26–69%) achieved maintenance of response.ConclusionCurrent evidence indicates that ADA is effective in children and adolescents with CD and that adverse events vary but are usually not severe.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023402199.

FEATURES OF HIV-INFECTION IN PATIENTS WITH LATE PRESENTATION WHO RECEIVE DTG-BASED ANTIRETROVIRAL THERAPY REGIMENS

Late presentation of HIV-infection is one of the most serious challenges in providing medical care to HIV-infected patients, because delay in detection and treatment of HIV-infection leads to a gradual decrease in the number of CD4+lymphocytes and the threat of infectious complications and tumor processes.&#x0D; Objective of this study is to find out the features of HIV-infection in people with late presentation of the disease, to evaluate the effectiveness of treatment and factors influencing the emergence of severe opportunistic infections on the background of dolutegravir-based antiretroviral therapy regimens. To achieve this goal, a cohort retrospective study was conducted, during which data from 210 outpatient records were analyzed.&#x0D; Analysis of opportunistic infections depending on the level of lymphocytes at the time of registration showed that in 123 (58.6%) of 210 late presenters, opportunistic infections were diagnosed at lymphocytes level below 200 cells/mL, in 22 people, while severe opportunistic infections were registered at a lymphocytes level above 500 cells/mL.&#x0D; Analysis of the clinical effectiveness of antiretroviral therapy showed that while taking the drugs, some patients continued to develop severe opportunistic infections such as tuberculosis, oropharyngeal candidiasis and severe bacterial diseases. An analysis of the Kaplan-Meier survival curve showed that there is a significant relationship between low baseline lymphocytes counts and the development of late opportunistic infections during treatment.&#x0D; Thus, the majority of HIV-infected patients were diagnosed with wasting syndrome, profound immunosuppression, severe opportunistic infections, and their combination at the time of registration. In some patients, severe late opportunistic infections were diagnosed with a satisfactory lymphocytes count above 500 cells/mL and subsequently on antiretroviral treatment. A low baseline lymphocytes count was identified as a risk factor for the development of severe opportunistic infections on antiretroviral therapy.

Efficacy of Treatment Options for Children with Steroid-Refractory Acute Gvhd

Background: Approximately half of patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (alloHCT) experience steroid-refractory aGVHD (SR-aGVHD) disease. Patients with SR-aGVHD require intense and prolonged immunosuppression resulting in high risk of severe opportunistic infections and risk of relapse of malignancy which ultimately results in significant increase in short- and long-term morbidity and mortality, poor quality of life for children and their families and increases financial burden on families and health care system. Corticosteroids have been the mainstay of therapy for new onset acute GVHD. However, treatment for SR-GVHD in children is a serious unmet need. To date, few therapies have been investigated for SR-aGVHD in robust clinical trials for children. Moreover, long-term benefits and survival data from these trials are often lacking or unclear. A systematic literature review (SLR) was conducted to better understand the efficacy of therapies under investigation in this population. Methods: Literature database searches of Embase, MEDLINE, Cochrane, and Econlit, were performed on 22 May 2023 according to Cochrane guidelines to identify randomized and non-randomized clinical trials in which the pediatric population with SR-aGVHD represented at least 50% of the trial population. Clinical trials extensions and long-term follow-up reports were also included. Studies published in English from 2009 onwards were retrieved. Additional manual searches of relevant conference abstracts published in the past 3 years were performed. Results: Overall, 29 publications (23 unique studies) met the selection criteria, representing a total of 801 patients aged 18 years or younger with SR-aGVHD. A limited number of interventions were investigated in this population and most studies had a non-randomized design (19 out of 23 studies). Overall survival (OS) and response rates (ORR) were analyzed from studies enrolling more than 20 pediatric patients with SR-aGVHD (9 studies, Table), which investigated therapies such as mesenchymal stromal cells (MSC), remestemcel-L (MSC manufactured by Mesoblast), ruxolitinib, etanercept and extracorporeal photopheresis. At least 80% of patients treated with cellular therapies (remestemcel-L/MSC) and etanercept had grade III or IV disease. ORR on day 28 was 92% with etanercept, 77% to 91% with ruxolitinib, 61% to 92% with mesenchymal stromal cells, 61% to 70% with remestemcel-L, and 55% with extracorporeal photopheresis. Durable response rates of 69% at day 56 and 70% at day 100 and were noted for remestemcel-L and ruxolitinib, respectively. OS at 6 months was 69% with remestemcel-L, and 71% with mesenchymal stromal cells. OS at 1 year was reported for remestemcel-L (63%) and etanercept (59%). Long-term survival data beyond 1 year of patients enrolled in the clinical trial was available only for remestemcel-L and showed an OS rate of 51% at 2 years and 49% at 3 and 4 years. 4-year OS probability for patients with grade III or IV (48% in both cases) was similar to that for the overall population. Conclusions: Only a few small size clinical trials were conducted for children with SR-aGVHD which poses a unique challenge for FDA to approve new therapies for SR-aGVHD. Despite a small number (n=9: 5 ruxolitinib arm and 4 control arm) of children (12-18 years) enrolled in REACH II study, ruxolitinib was FDA approved for children&amp;gt;12 years of age. Long-term efficacy outcomes of children enrolled in clinical trials were reported only for remestemcel-L and showed that approximately half survived beyond 3 years. While other reports showed that grade III/IV disease is associated with poorer outcomes compared to grade I/II, similar survival rates were noted for patients with grade II, III and IV treated with remestemcel-L. In children with SR-aGVHD, other therapies such as ruxolitinib or etanercept demonstrated good response rates, however, the associated survival benefit is unclear.

Ocular manifestations of HIV infection at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

The pattern of HIV-associated eye disease has changed with ongoing advancements in highly active antiretroviral therapy (HAART). HIV-infected individuals now live longer, enabling us to observe the long-term effects of HIV and HAART on the eye. There are few recent studies on HIV-related ocular disease in sub-Saharan Africa. To describe the ocular manifestations of HIV in patients attending the Nthabiseng HIV clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. A cross-sectional study was conducted in 2021 and 2022 using convenience sampling of patients at the HIV clinic. The participants' clinical history was taken, their files were reviewed, and they underwent ocular examination. Correlation between eyes was managed by taking disease in one eye as the presence of disease in the participant. Descriptive statistics were used to summarise participant characteristics. Univariate and multivariate logistic regression models were used to assess the odds ratio (OR) of developing HIV-associated ocular diseases, and a p-value of <0.05 was used to define statistical significance. There were 182 participants (139 females and 43 males), with a mean (standard deviation) age of 48.9 (10.6) years. The most common anterior segment diagnoses were conjunctival microangiopathy (34.6%), pinguecula (31.3%) and cataracts (30.2%), while the most common posterior segment finding was peripheral retinal scarring with features in keeping of previous cytomegalovirus retinitis (24.2%). Notably, only 1.1% of patients had HIV retinopathy. A CD4 count <200 cells/μL showed an increased OR for cataracts (OR 4.24; p=0.003) and any anterior segment diagnoses (OR 10.05; p=0.029), while a CD4 count ≥200 cells/μL showed an increased risk of conjunctival microangiopathy (OR 2.14; p=0.017). With the advent of HAART, ocular manifestations of HIV are changing and the incidence of severe ocular opportunistic infections and HIV retinopathy has decreased precipitously. Although this study has shown that patients with a CD4 count <200 cells/μL are at increased risk of developing anterior ocular manifestations of HIV, including cataracts, these diseases are relatively innocuous or easily treatable. Routine ocular screening of HIV patients seems to be substantially less important now than it was in the pre-HAART era.

Macrophage colony-stimulating factor as a weapon against cytomegalovirus.

Cytomegalovirus (CMV) infection is one of the severe opportunistic infections faced by severely immunocompromised patients. High viral loads cause tissue-invasive disease and expose to death or various indirect effects. Substantial progress was made in monitoring active infection, and antiviral drugs were developed. However, dose-limiting toxicities and genotypic resistance limit therapeutic efficacy and vaccine development is hampered by the complex biology of the virus. In this issue of EMBO Molecular Medicine, Kandalla etal (2023) suggest an innovative strategy using the cytokine macrophage colony-stimulating factor (M-CSF) whose clinical development was left behind two decades ago. By stimulating an endogenous immune defense mechanism, M-CSF promotes viral clearance in a mouse model of hematopoietic stem cell transplantation, without impairing stem cell engraftment. These results reactivate the interest in the potential therapeutic use of this cytokine.

Cytomegalovirus colitis unmasking human immunodeficiency virus infection as a cause of IgA vasculitis

BackgroundHuman immunodeficiency virus (HIV) has a protean clinical picture, in rare instances manifesting as systemic autoimmune disorders such as vasculitides. HIV-induced autoimmune diseases often do not respond well to systemic immunosuppressive therapy. Opportunistic infections may occur in patients with either acquired immunodeficiency syndrome (AIDS) or heavy immunosuppressive treatment, and can further complicate the clinical presentation.Case presentationA patient presenting with immunoglobulin A (IgA) vasculitis (IgAV) with treatment-refractory purpuric skin rash and suspect intestinal vasculitis was discovered to have AIDS. HIV was the trigger of IgAV, and cytomegalovirus (CMV) colitis mimicked intestinal vasculitis. Antiretroviral treatment improved both CMV colitis and the control of the autoimmune disease.ConclusionsAn autoimmune disease relapsing despite adequate immunosuppressive treatment and/or the presence of recurrent severe opportunistic infections may be clues to an underlying HIV infection.

Diagnostic difficulties in non-tuberculous mycobacterial infection in lung transplant recipients.

Despite antimicrobial prophylaxis, 34% to 59% of lung transplant recipients experience severe life-threatening opportunistic infections, sometimes caused by Nontuberculous Mycobacteria (NTM) and Nocardia. Although differentiating these infections is of utmost importance for effective treatment, it can be challenging as they share morphological and growth characteristics. Therefore, culture remains the gold standard for laboratory confirmation. With the aid of novel molecular methods performed on the cultured organisms, diagnosis may be accomplished rapidly and precisely. We present a case of a lung transplant recipient with a pulmonary infection where long, thin, beaded, branching filamentous organisms were seen with Acid-Fast Bacilli (AFB) and Modified Gomori's Methenamine Silver (GMS) stains in bronchoalveolar lavage sample. Cytological characteristics led to the suspicion of a Nocardia species infection. However, culture and the PCR-restriction fragment length polymorphism analysis (PRA) identified M. fortuitum. Additionally, antibiotic resistance was detected, which aided in choosing the appropriate treatment. Therefore, to overcome such diagnostic difficulties to differentiate NTM and Nocardia, a multidisciplinary approach including culture, molecular methods, and cytology is needed to enhance clinical outcomes.

Hyphal Growth in Trichosporon asahii Is Accelerated by the Addition of Magnesium.

Fungal dimorphism involves two morphologies: a unicellular yeast cell and a multicellular hyphal form. Invasion of hyphae into human cells causes severe opportunistic infections. The transition between yeast and hyphal forms is associated with the virulence of fungi; however, the mechanism is poorly understood. Therefore, we aimed to identify factors that induce hyphal growth of Trichosporon asahii, a dimorphic basidiomycete that causes trichosporonosis. T. asahii showed poor growth and formed small cells containing large lipid droplets and fragmented mitochondria when cultivated for 16 h in a nutrient-deficient liquid medium. However, these phenotypes were suppressed via the addition of yeast nitrogen base. When T. asahii cells were cultivated in the presence of different compounds present in the yeast nitrogen base, we found that magnesium sulfate was a key factor for inducing cell elongation, and its addition dramatically restored hyphal growth in T. asahii. In T. asahii hyphae, vacuoles were enlarged, the size of lipid droplets was decreased, and mitochondria were distributed throughout the cell cytoplasm and adjacent to the cell walls. Additionally, hyphal growth was disrupted due to treatment with an actin inhibitor. The actin inhibitor latrunculin A disrupted the mitochondrial distribution even in hyphal cells. Furthermore, magnesium sulfate treatment accelerated hyphal growth in T. asahii for 72 h when the cells were cultivated in a nutrient-deficient liquid medium. Collectively, our results suggest that an increase in magnesium levels triggers the transition from the yeast to hyphal form in T. asahii. These findings will support studies on the pathogenesis of fungi and aid in developing treatments. IMPORTANCE Understanding the mechanism underlying fungal dimorphism is crucial to discern its invasion into human cells. Invasion is caused by the hyphal form rather than the yeast form; therefore, it is important to understand the mechanism of transition from the yeast to hyphal form. To study the transition mechanism, we utilized Trichosporon asahii, a dimorphic basidiomycete that causes severe trichosporonosis since there are fewer studies on T. asahii than on ascomycetes. This study suggests that an increase in Mg2+, the most abundant mineral in living cells, triggers growth of filamentous hyphae and increases the distribution of mitochondria throughout the cell cytoplasm and adjacent to the cell walls in T. asahii. Understanding the mechanism of hyphal growth triggered by Mg2+ increase will provide a model system to explore fungal pathogenicity in the future.

Evaluation of BioFire® FilmArray® Pneumonia Panel in Bronchoalveolar Lavage Samples From Immunocompromised Patients With Suspected Pneumonia.

Objectives Immunocompromised patients, specifically those with solid organ transplants or cancer on chemotherapy, are at particularly high risk of severe pneumonia and opportunistic infections. In select patients, bronchoalveolar lavage (BAL) is performed to provide high-quality samples for analysis. We compare BioFire® FilmArray® Pneumonia Panel (BioFire Diagnostics,Salt Lake City, Utah, United States), a multiplex polymerase chain reaction (PCR) assay, with standard of care diagnostics in BAL samples from immunocompromised patients to identify opportunities for this test to affect clinical decision making. Methods Patients hospitalized with pneumonia based on clinical and radiographic findings who underwent evaluation with bronchoscopybetween May 2019 to January 2020 were reviewed. Among those patients undergoing bronchoscopy, those who were immunocompromised were selected for inclusion in the study. BAL specimens submitted to the microbiology laboratory were chosen based onas part of the internal validation of the panel in comparison with sputum culture at our hospitals.We compared the outcomes of the multiplex PCR assay with traditional culture methods and evaluated the role of PCR assay in de-escalating antimicrobial therapy. Results Twenty-four patients were identified for testing with the multiplex PCR assay. Of the 24 patients, 16 were immunocompromised, all with solid or hematological malignancy or a history of organ transplant. Seventeen individual BAL samples from the 16 patients were reviewed. BAL culture results and the multiplex PCR assay were in agreement in 13 samples (76.5%). In four cases, the multiplex PCR assay identified a possible causative pathogen not detected by standard workup. The median time to de-escalation of antimicrobials was three days (interquartile range (IQR) 2-4) from the day of collection of the BAL samples. Conclusions Studies have established the additive role of multiplex PCR testing in addition to traditional diagnostic tools like sputum culture in diagnosing the etiology of pneumonia. Limited data exist specifically looking at immunocompromised patients, in whom a timely and accurate diagnosis is particularly important. There is a potential benefit for performing multiplex PCR assays as an additive diagnostic tool in BAL samples for these patients.

Use of Short Oral Regimens for Treatment of Drug Resistant Tuberculosis in a Patient with HIV Infection

We present the clinical case of effective treatment of tuberculosis in a patient with disseminated pulmonary and extrapulmonary pre-extensive drug resistant tuberculosis, HIV-infection and other severe opportunistic and concomitant infections. Short all-oral regimen has been used for the treatment. This clinical case demonstrates the clinical efficacy of modern treatment regimens, good compatibility with other drugs and management of adverse events without treatment interruption.

Disseminated fusariosis against the background of polychemotherapy in a patient with acute leukemia

Fusariosis is a dangerous disease caused by imperfect fungi of the genus Fusarium; it is a severe opportunistic infection characterized by rapid dissemination of the mycotic process and high mortality. Currently, there is an increase in the frequency of invasive mycoses all over the world, especially in oncohematological patients. This is due not only to the improvement of methods for diagnosing mycoses, but also to more «aggressive» schemes of cytostatic therapy and the widespread use of hematopoietic stem cell and organ transplantation as a rescue therapy.

Profile of People With HIV-AIDS (PLWHA) During The Covid-19 Pandemic By Stress Levels

The COVID-19 pandemic presents complex problems, especially in the health sector, especially for people with HIV-AIDS (PLWHA), who are one of the groups vulnerable to COVID-19 transmission. Psychological responses shown by PLWHA are anxiety and stress. Various factors allegedly affect stress in PLWHA. This study aimed to determine the factors influencing stress levels in PLWHA during the covid-19 pandemic. The research design is descriptive-analytic with a cross-sectional approach using primary data. The sample of 34 people living with HIV in the Kediri area was obtained by purposive sampling. Inclusion criteria were PLWHA aged 20-55 years and cooperative. Exclusion criteria included people living with HIV with advanced complications or severe opportunistic infections. The instrument measuring stress uses the Depression Anxiety Stress Scale 42 (DASS 42). Analysis of the Spearman rank correlation test data showed that there was no relationship between gender and age with stress levels (ρ-value = 0.428 &gt; =0.05, -value = 0.131&gt;α=0.05), and there was a relationship between education, knowledge , social support with stress levels in PLWHA in the Kediri area (ρ-value = 0.000 &gt; =0.05, (r)=-600), -value = 0.000 &lt; =0.05, (r)=-0.658 , p-value &lt; d =0.05, (r)=-799). Respondents can actively increase knowledge related to COVID-19 through accountable information media and be open with families, communities, and health workers to get high support from families, communities and health workers as a priority for vulnerable groups in efforts to prevent COVID-19.

Central tolerance promoted by cell chimerism

Historically, successful allotransplantation was only achieved by utilizing powerful immunosuppressive drugs that were exposing the patient to severe opportunistic infections. The thymus of the transplant recipient renders such therapy obligatory as it constitutively blocks self-reactive T cells while allowing alloreactive T cells to mature and populate the periphery. In 1992, a follow-up study revealed the presence of donor leukocytes in long-term transplant survivors. The stable persistence of recipient and donor leukocytes in the transplanted patient, referred to as “chimerism”, was considered the reason why in some cases it was even possible to stop immunosuppressive treatment without damaging the transplanted organ. Unfortunately, it quickly became evident that stable, persistent allogeneic chimerism was not easily achievable by design. Recently, a novel approach has been identified to help address this clinical gap in knowledge: Cotransplantation of a donor graft with a thymic organoid populated with donor precursor cells generates stable, long-term chimerism in the recipient. In humanized mice, the implantation of thymic organoids, populated with human donor inducible pluripotent stem cell (iPSC)-derived thymic epithelial cells (TECs) and the same donor CD34+ bone marrow precursors, induces tolerance to human leukocyte antigen (HLA)-matched donor tissues/organs. This technology will allow successful allotransplantation of cells/organs even between Major Histocompatibility Complex (MHC)-noncompatible individuals and allow getting rid of immunosuppressive treatments reducing recipient morbidity.

The unique diagnostic and management challenge of a patient with concomitant anti-interferon-gamma autoantibody associated immunodeficiency syndrome, IgG4-related disease, and treatment refractory, disseminated mycobacterium avium complex infection

BackgroundAnti-interferon-gamma autoantibody-associated immunodeficiency syndrome is a rare and underrecognized adult onset immunodeficiency syndrome associated with severe opportunistic infections such as disseminated nontuberculous mycobacterium. Few cases have documented a relationship with IgG4-related disease. Concomitant diagnoses of these diseases present a diagnostic and management challenge.Case presentationA 61 year old man of Southeast Asian descent with pulmonary mycobacterium avium complex infection presented to our hospital system with a new skin rash and worsening lymphadenopathy. He was eventually diagnosed with IgG4-related disease through excisional nodal biopsy. He was managed with immunosuppressive treatment with prednisone, rituximab and cyclophosphamide. He later re-presented with disseminated mycobacterium avium complex infiltration of his joints, bones and prostate. Original titers of anti-interferon-gamma autoantibodies were falsely negative due to being on immunosuppressive therapy for his IgG4-related disease. However, anti-interferon-gamma autoantibody titers were re-sent after immunosuppression was held and returned strongly positive.ConclusionsThis case reviews diagnostic criteria and discusses management strategies with existing challenges in treating a patient with concomitant adult onset immunodeficiency syndrome, IgG4-related disease and a disseminated mycobacterial avium complex infection.