Groups Of Immunosuppressed Patients Research Articles

A review of the clinical characteristics and management of immunosuppressed patients living with HIV or solid organ transplants infected with SARS-CoV-2 omicron variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron strain was first detected in South Africa in November 2021. Although clinical responses to SARS-CoV-2 depend on host immunity, it remains uncertain how immunosuppression affects subsequent coronavirus disease 2019-related (COVID-19-related) incidence, severity, and mortality, especially with respect to the omicron strain. Conversely, immunosuppressants are often thought to predispose to infection. To explore the associations between host immunity and infection with SARS-CoV-2 omicron variants, here we discuss two groups of immunosuppressed patients: organ transplant recipients, who generally receive exogenous immunosuppressants, and Human Immunodeficiency Virus (HIV)-infected patients, who often have disease-related immunosuppression. In summarizing the clinical features and prognoses of HIV-infected patients and human organ transplant recipients infected with SARS-CoV-2 omicron variants, we provide new insights into the pathogenesis of omicron SARS-CoV-2 and provide a framework for the management of these patients now and in the future.

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series.

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients.

Identification of immunosuppressive signature subtypes and prognostic risk signatures in triple-negative breast cancer.

Immune checkpoint blockade (ICB) therapy has transformed the treatment of triple-negative breast cancer (TNBC) in recent years. However, some TNBC patients with high programmed death-ligand 1 (PD-L1) expression levels develop immune checkpoint resistance. Hence, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to construct prognostic models of patient survival outcomes in order to understand biological mechanisms operating within the tumor microenvironment. RNA sequence (RNA-seq) data from 303 TNBC samples were analyzed using an unsupervised cluster analysis approach to reveal distinctive cellular gene expression patterns within the TNBC tumor microenvironment (TME). A panel of T cell exhaustion signatures, immunosuppressive cell subtypes and clinical features were correlated with the immunotherapeutic response, as assessed according to gene expression patterns. The test dataset was then used to confirm the occurrence of immune depletion status and prognostic features and to formulate clinical treatment recommendations. Concurrently, a reliable risk prediction model and clinical treatment strategy were proposed based on TME immunosuppressive signature differences between TNBC patients with good versus poor survival status and other clinical prognostic factors. Significantly enriched TNBC microenvironment T cell depletion signatures were detected in the analyzed RNA-seq data. A high proportion of certain immunosuppressive cell subtypes, 9 inhibitory checkpoints and enhanced anti-inflammatory cytokine expression profiles were noted in 21.4% of TNBC patients that led to the designation of this group of immunosuppressed patients as the immune depletion class (IDC). Although IDC group TNBC samples contained tumor-infiltrating lymphocytes present at high densities, IDC patient prognosis was poor. Notably, PD-L1 expression was relatively elevated in IDC patients that indicated their cancers were resistant to ICB treatment. Based on these findings, a set of gene expression signatures predicting IDC group PD-L1 resistance was identified then used to develop risk models for use in predicting clinical therapeutic outcomes. A novel TNBC immunosuppressive tumor microenvironment subtype associated with strong PD-L1 expression and possible resistance to ICB treatment was identified. This comprehensive gene expression pattern may provide fresh insights into drug resistance mechanisms for use in optimizing immunotherapeutic approaches for TNBC patients.

Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients-A Comparison between Different Immunomodulating Conditions.

Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to immunocompetent controls. Studies on other immunosuppressed patient groups are scarce. This study was aimed at assessing the effects of different immunomodulating conditions on patients diagnosed with cSCC. We sought to compare the clinical features, treatments, and survival rates among the different study groups, as well as outcomes to those of immunocompetent controls with cSCC. A retrospective analysis of 465 cSCC patients, both immunosuppressed (IS) and immunocompetent controls. Etiologies for immunosuppression included SOTR, CLL, chronic kidney disease (CKD), psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Compared to the control group, IS patients demonstrated several significant differences. These include higher rates of positive resection margins, higher recurrence rates, and multiple SCC tumors. Patients in the IS group, who were also given immunomodulating agents, demonstrated even lower survival rates. Cox regression analysis demonstrated statistically significant decreased overall survival (OS) rates for IS patients compared to the controls (OR = 1.9, p = 0.031). SOTR patients tend to have multiple cSCC tumors (35%), with the highest number of primary tumors compared to controls (2.54 tumors per patient on average, p < 0.001), but also compared to all other IS groups. The average SCC lesion size in the SOTR group was the smallest, measuring at 13.5 mm, compared to the control group and all other IS groups. Decreased survival rates were seen on Cox regression analysis compared to controls (HR = 2.4, p = 0.001), but also to all other IS groups. CLL patients also had the highest rates of positive margins compared to controls (36% vs. 9%, p < 0.01) and to all other IS groups. They were also most likely to get adjuvant or definitive oncological treatments, either radiotherapy or chemotherapy, compared to controls (36% vs. 15%, p = 0.02) and to other IS groups. Patients in the CKD group demonstrated the highest rates for multiple cSCC (OR = 4.7, p = 0.001) and the worst rates of survival on Cox regression analysis (HR = 3.2, p = 0.001). Both rheumatoid arthritis and psoriasis patients demonstrated the shortest disease-free survival rates (2.9y ± 1.1, 2.3y ± 0.7, respectively), compared to controls (4.1y ± 2.8) and to all other IS groups. Among cSCC patients, immunosuppression due to SOTR, CLL, CKD, RA, and psoriasis is associated with worse outcomes compared to controls and other IS groups. These patients should be regarded as high-risk for developing aggressive cSCC tumors. This study is the first to assess and compare cSCC outcomes among multiple IS patient groups.

Overview of Human cytomegalovirus (CMV) Infections

Human cytomegalovirus (CMV), one of the viruses well adapted to the human body, goes into a silent phase after the first infection (primary infection), which is mostly asymptomatic. In the latent phase, the virus presence continues throughout the life of the host, with its ability to form latent infection where viral activity is at very low levels. However, this silence is lost in immunocompromised or immunosuppressed patient groups such as AIDS (Acquired Immune Deficiency Syndrome) patients, solid organ transplant recipients, and patients with hematological malignancies and the reactivated virus may appear with serious diseases. CMV infections are also important due to congenital infections and related complications caused during the fetal period when the immune system is not sufficiently developed. Immune system deficiency is an important risk factor for reactivation of CMV infections, with another perspective CMV, which is one of the largest viruses associated with human infections, is an infectious agent that exhibits immunomodulatory effects by suppressing or activating the immune response with a large number of proteins it encodes. Research on the oncogenic potential of CMV has not yet provided clear evidence. The absence of an approved preventive vaccine against CMV and the current problems associated with antiviral therapy have made it critically important to monitor viral reactivation and antiviral resistance, mainly by CMV-DNA tests, in the management of CMV infections. Although some difficulties remain in obtaining comparable test results and in defining threshold viral load values for antiviral therapy, an increasing number of studies are leading to the development of new diagnostic and therapeutic approaches. In this review article, while providing an overview of CMV infections, that are mentioned viral characteristics, current approaches new diagnosis and treatment strategies.

A real-world prospective cohort study of immunogenicity and reactogenicity of ChAdOx1-S[recombinant] among patients with immune-mediated dermatological diseases

Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce. To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination. This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination. Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD. Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.

Cellular and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients: An observational cohort study.

Background: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.Methods: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.Results: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators (P < 0.001), mycophenolate (P = 0.002), and B cell lymphoma (P = 0.004); those associated with low cellular response rates included S1P receptor modulators (P < 0.001) and mycophenolate (P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.Conclusions: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation

Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice. To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB ® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs. Prospective within-patient comparative diagnostic accuracy study. Secondary care. Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. The index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results. Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test. A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT.TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT.TB, the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway. The recruitment target for the HIV co-infected population was not achieved. Although T-SPOT.TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise. The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK.

Transplant in the age of global warming: What is known about the impact of emerging tropical arbovirus infections

Climate change and human migration continue to impact the infectious risks of transplantation, as emerging infections are newly recognised in transplant candidates and recipients. Limited data about the risks of these novel pathogens in transplant make decisions about the optimal timing and safety of transplant challenging, particularly in areas experiencing the initial presentation of new arboviruses. This presentation will focus on information available about the clinical manifestations of Dengue, Chikungunya, and Zika virus infections in transplant recipients. The limitations and challenges of laboratory diagnosis in the transplant candidate and recipient will be discussed, and the existing data on clinical syndromes reviewed. Recommendations for patient management and infection avoidance will also be covered, along with current clinical guidelines regarding transplant donor and candidate eligibility for transplant in areas experiencing active arbovirus infection transmission. Some infectious risks are inherent to the transplant process, and widely acceptable due to the significant benefits of transplant. Understanding the implications of emerging infections on the immunocompromised transplant population remains a work in progress, and research in this area is essential to successfully mitigate risk. The morbidity and mortality of West Nile virus infection in transplant recipients demonstrates the potentially severe manifestations of arbovirus infection in this population, and the need to closely monitor outcomes whenever novel infectious agents initially present in unique immunosuppressed patient groups.

Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection.

BackgroundLung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing.MethodsWe re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR.ResultsIn completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract.ConclusionThis study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.

Cancer risks after solid organ transplantation and after long-term dialysis.

Immunosuppression involves an inability to control virus infections and increased incidence of virus-associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent. To provide a reliable and generalizable estimate, with high statistical power and long follow-up time, we assessed cancer risks using comprehensive, population-based registries in two different countries and from two different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long-term dialysis patients (LDPs)). National registries in Denmark and Sweden identified 20,804 OTRs and 31,140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated. We found highly similar results, both for the two different countries and for the two different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non-melanoma skin cancer (NMSC), non-Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid. The SIR for overall cancer among OTRs was 3.5 [n = 2,142, 95% CI, 3.4-3.7] in Sweden, 2.9 [n = 1,110, 95% CI, 2.8-3.1] in Denmark and 1.6 [n = 1,713, 95% CI, 1.5-1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n = 994, 95% CI, 42-47.5] in Sweden and 41.5 [n = 445, 95% CI, 37.8-45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n = 304, 95% CI, 4.7-5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression-related susceptibility to viral infections.

Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumatoid arthritis: A prospective, open-label, multi-centre study

BackgroundTick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX). MethodsTBE vaccine, FSME-Immune® or Encepur®, was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test. ResultsThe study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05). ConclusionsStandard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.

Haematuria in Postrenal Transplant Patients

Haematuria has a prevalence of 12% in the postrenal transplant patient population. It heralds potentially dangerous causes which could threaten graft loss. It is important to consider causes in light of the unique, urological, and immunological standpoints of these patients. We review the literature on common causes of haematuria in postrenal transplant patients and suggest the salient approach to the evaluation of this condition. A major cause of haematuria is urinary tract infections. There should be a higher index of suspicion for mycobacterial, fungal, and viral infection in this group of immunosuppressed patients. Measures recommended in the prevention of urinary tract infections include early removal of foreign bodies as well as prophylactic antibiotics during the early transplant phase. Another common cause of haematuria is that of malignancies, in particular, renal cell carcinomas. When surgically managing cancer in the setting of a renal transplant, one has to be mindful of the limited retropubic space and the need to protect the anastomoses. Other causes include graft rejections, recurrences of primary disease, and calculus formation. It is important to perform a comprehensive evaluation with the aid of an experienced multidisciplinary transplant team.

Prevalence and risk factors for betaherpesvirus DNAemia in children >3 weeks and

Betaherpesviruses are established causes of morbidity and mortality in immunosuppressed patient groups but have been little studied in sub-Saharan Africa, the epicenter of the human immunodeficiency virus (HIV) pandemic. In this region, primary infections with human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) type 6 are endemic in infancy, but the clinical impact of these infections among pediatric inpatient groups is poorly characterized and assumptive, based largely on data from Western populations. We used TaqMan polymerase chain reaction to screen sera from a group of 303 pediatric inpatients aged between 3 weeks and 2 years, at the University Teaching Hospital in Lusaka, Zambia. We report the prevalence of DNAemia and viral loads within this patient group, and evaluate possible clinical associations/risk factors for betaherpesvirus infections in these hospitalized children. We detected betaherpesvirus DNAemia in 59.1% (179/303) of children. HCMV was the most prevalent (41.3%), followed by HHV-6B (20.5%), HHV-7 (20.1%), and HHV-6A (0.3%). HIV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.37-3.90; P = .002), being underweight (OR, 1.82; 95% CI, 1.06-3.12; P = .03), and an admission diagnosis of suspected meningitis (OR, 5.72; 95% CI, 1.07-30.5; P = .041) were independently associated with an increased odds of HCMV DNAemia. Conversely, HHV-6B and HHV-7 DNAemia were not associated with HIV, underweight, or admission diagnosis. Median HCMV viral load was moderately but significantly higher in HIV-infected children. Highly prevalent HCMV DNAemia was independently associated with HIV infection and being underweight across all age groups, and was also associated with meningitis, with previously underappreciated implications for the health and development of African children.

Rejection-mediated Regression of Melanocytic Naevi in an Immunosuppressed Organ Transplant Recipient

© 2014 The Authors. doi: 10.2340/00015555-1789 Journal Compilation © 2014 Acta Dermato-Venereologica. ISSN 0001-5555 Eruptive melanocytic naevi and/or excess of melanocytic naevi have been reported in several groups of immunosuppressed patients. The eruption of melanocytic naevi after immunosuppression is a peculiar phenomenon indicating that the immune system may play a major role in limitating proliferation of melanocytes (1). In this article we describe a patient with excess of post-transplant melanocytic naevi that spontaneously disappeared after graft rejection.

Immunsuppressive Behandlung als Risikofaktor für das Auftreten einer Clostridium-difficile-Infektion (CDI)

Toxigenic Clostridium difficile strains are known as the most common infectious cause of antibiotic-associated intestinal disease and nosocomial diarrhoea. The increased incidence of hypervirulent strains gives rise to worldwide concern. In particular, courses with multiple recurrences are observed in the presence of immunosuppression. In this retrospective controlled observational study we aimed to determine immunosuppression as an independent risk factor for symptomatic CDI and to identify characteristics and differences of immunocompromised patients with respect to disease severity, disease progression, intestinal manifestations, recurrence rates and other factors. We compared symptoms and clinical features of 55 immunosuppressed patients with confirmed CDI with those of 50 patients without immunosuppressive medication (mean age 59.3 years ± 16.2 vs. 69.2 years ± 15.0) who were treated at the Departments of Internal Medicine I and IV of the University Hospital Halle (Saale), Germany, between 2006 and 2009. Multivariate analysis using binary logistic regression was performed for a control group of 105 patients without CDI. In this group, there were 62 patients without evidence of immunosuppression and 43 immunosuppressed patients (mean age 66.9 years ± 12.4 vs. 56.0 years ± 13.7). The clinical courses of the two groups differed considerably. Immunosuppressed patients were significantly more frequently colonised with Clostridium difficile without clinically detectable manifestation or only mild clinical symptoms not requiring therapy (22 vs. 2 %, p = 0.003), while there were similar numbers of moderate (46 vs. 52 %, p = 0.503) but less severe CDI cases (27 vs. 40 %, p = 0.167). Relapses were observed more frequently in the group of immunosuppressed patients (15 vs. 6 %, p = 0.153). Multivariate analysis using logistic regression identified immunosuppression as an independent risk factor for CDI (OR = 2.75), in addition to prior antibiotic therapy (OR = 10.15) and PPI intake (OR = 2.93). We conclude that immunosuppression has to be regarded as an independent risk factor for CDI. Immunosuppressive treatment increases the risk of colonisation and infection with Clostridium difficile and leads to a higher relapse rate in patients with CDI.

Intestinal Protozoa in Immunosuppression: A Medical Hassle

Introduction: Immunity forms the backbone of our very existence and opportunistic infections have plagued the immunosuppressed since long. A significant morbidity and mortality is attributable to intestinal parasitosis in the immunocompromised population. Objectives: This study aims to study the prevalence of intestinal protozoa in various immunosuppressed groups and to correlate degree of immunosuppression with protozoal infections. Material and Methods: The study was conducted on 400 patients divided into 4 groups: Group I (HIV patients), Group II (patients on chemotherapy/chemotherapy and radiotherapy for various malignancies), and Group III (diabetes patients) and Group IV included children presenting with diarrhea. Group I, II and III included patients with and without gastrointestinal symptoms. Stool samples were investigated microscopically for cysts/trophozoites after concentration with formol-ether method. Iodine wet mount and Modified acid fast staining methods were used. Result: Intestinal protozoa were detected in 40.75% (163/400); more commonly in patients with higher degree of immunosuppression (CD4 count 7: 95.3% in diabetics and moderate to severe malnutrition: 61.8%. Most common protozoa associated was Cryptosporidium in 66 patients (40.5%) followed by, Entamoeba histolytica in 48 (29.4%), Giardia lamblia in 35 (21.5%), Isosporabelliin 9 (5.5%), Blastocystis hominis in 4 (2.5%), Cyclospora cayetenensis in 1 (0.61%). Conclusion: High prevalence of intestinal protozoa was seen in all groups of immunosuppressed patients and a significant association seen between degree of immune suppression and protozoal infection. Focus needs to be on routine screening of all immunosuppressed patients and their immune reconstitution.

Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity

We used real-time polymerase chain reaction (PCR) targeting the cdc2 gene and direct fluorescent microscopy examination (DFME) to evaluate the prevalence of Pneumocystis jirovecii among immunocompetent patients without clinical pulmonary infection and immunosuppressed patients evaluated for opportunistic pulmonary infections. Among 102 bronchoalveolar lavage samples collected from immunocompetent patients without infection, none tested positive for P. jirovecii by either DFME or real-time PCR despite the presence of other comorbidities. Among patients with suspected pulmonary infection and tested with either assay, real-time PCR produced a higher number of positive results compared to DFME and increased P. jirovecii detection by 7% when added to DFME-negative samples. Real-time PCR may have increased sensitivity for P. jirovecii detection over DFME and decrease the risk of sample contamination compared to conventional and nested PCR. The use of single-copy gene targets (e.g., cdc2) may lower the rate of “colonization” detection and confer a high predictive value for Pneumocystis pneumonia.

Invasive fungal infections in lung transplantation: role of aerosolised amphotericin B

Immunocompromised patients, especially solid organ transplant (SOT) and hematopoietic stem cell transplant recipients, have a high morbidity and mortality rate as a result of invasive fungal infections (IFIs). Therefore, effective and correct prophylaxis of these IFIs continues to be an important issue in these patient populations. Fungal infections in the lung are most often due to Aspergillus spp., but other non- Aspergillus moulds such as Mucor spp. can also cause pulmonary infections. Lung transplant recipients have the highest incidence of invasive aspergillosis of all SOT patients. Prophylaxis should consider the risk factors affecting each group of patients. As the lung is the target organ of most fungal infections due to moulds, aerosolised antifungal prophylaxis has been potentially considered to be a safe and effective strategy. Administration of a nebulised antibiotic achieves high local concentration of the drug, avoiding undesirable systemic effects and drug interactions. The use of aerosolised amphotericin B (AmB) as prophylaxis or co-adjuvant treatment for pulmonary fungal infections has been reported in several groups of immunosuppressed patients. Lipid formulations of AmB penetrate the lung better and have a longer half-life than amphotericin B deoxycholate (ABD). Prophylaxis with aerosolised lipid-based AmB products has several advantages over ABD: it can be administered at much longer intervals and is equally effective and better tolerated. Although several studies have been published using aerosolised AmB both as deoxycholate and lipid formulations, available data remain inconclusive owing a lack of standardisation of administration procedures and doses.

Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study

We report results in 41 consecutive patients with chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) after fludarabine, melphalan, and alemtuzumab conditioning. Donors were 24 HLA-matched siblings and 17 unrelated volunteers, 4 of them mismatched with recipients. All but 3 patients had initial hematologic recovery, but 5 more patients had secondary graft failure. Median intervals to neutrophil (greater than 0.5 x 10(9)/L) and platelet (greater than 20 x 10(9)/L) recovery were 14 days (range, 9-30 days) and 11 days (range, 8-45 days), respectively. Eleven (27%) patients had relapses and received escalated donor lymphocyte infusions, but only 3 of them had sustained responses. Acute and chronic graft-versus-host disease (GVHD) was observed in 17 (41%) and 13 (33%) patients, respectively. Seventeen (41%) patients have died, 5 of progressive disease. The 2-year overall survival and transplantation-related mortality (TRM) rates were 51% (95% confidence interval [CI], 33%-69%) and 26% (95% CI, 14%-46%), respectively. The alemtuzumabbased regimen was feasible and effective in patients with CLL with a relatively low rate of GVHD. However, TRM remains relatively high as a result of a variety of viral and fungal infections. Studies are ongoing to address the efficacy of reduced doses of alemtuzumab in this group of immunosuppressed patients.