Immunocompromised State Research Articles

Clinico-Epidmological Study and Outcome of COVID 19 Infection in Children with Hemato-Oncological Disorders

Abstract Background Severe acute respiratory syndrome Coronavirus 2 (SARS-Cov2) outbreak has caused a pandemic rapidly impacting on the way of life of the entire world. Several studies reported the specific role of an immunocompromised status as a possible risk factor for CoV-related pneumonia. The detrimental impacts of COVID-19 pandemic on childhood cancer are multiple including a delay in diagnosis and starting treatment, the impact of infection, and the uncertainty about the decision for chemotherapy in polymerase chain reaction–positive asymptomatic patients. Aim of the Work The study aimed to Measure the frequency of COVID-19 infection among children with hemato-oncological disorder in a period from 27 February 2022 till 27 March 2023 and to develop a registry dataset which can be used as a template for national registry for children with hemato-oncological disorder with proven COVID19 infection. Patients and Methods This is a retrospective cohort non-interventional study in which we recruited 620 child and adolescents patients who attended the pediatric hematology oncology unit, Ain Shams University, Children’s hospital in a period from 27 February 2022 till 27 March 2023. Results This is a cohort study included 620 immunocompromised children including 319 patients with hematological malignancies, 30 patients with solid malignancy, 271 patients with benign hematology. Our findings showed that 620 patients, 87 of them were found to be COVID-19 positive. The median age of COVID-19 the patients was 5 years (range: 0.75–16 years). The median duration of COVID-19 positivity of the patients was 12 days (range: 3–38 days). There was significant increase in the percentage of patients with positive chest X-ray, abnormal echo, patients with organomegaly in abdominal US in COVID-19 group than non COVID-19 group. Conclusion The percentage of patients with COVID-19 were higher among patients with hematological malignancies and benign hematological diseases especially acute lymphoplastic leukemia and aplastic anemia respectively. COVID-19 was tolerable among immunocompromised patients. Mortality was associated with abnormal neurological examination in patients with COVID-19 disease.

Comprehensive Analysis of Garcin Syndrome: A Systematic Review of the Etiology, Diagnosis, and Treatment.

Garcin syndrome is a rare neurological condition characterized by progressive unilateral involvement of multiple cranial nerves, without typical intracranial hypertension. It is often linked with aggressive malignancies and invasive infections; hence, it presents significant diagnostic and therapeutic challenges. Despite the advances in medical technology, the prognosis still remains poor, and there is limited literature on comprehensive reviews regarding its etiology, diagnosis, and management. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic review was performed in order to compile updated evidence related to Garcin syndrome. The PubMed and Scopus databases were comprehensively searched using the search terms "Garcin syndrome" AND ("etiology" OR "diagnosis" OR "treatment" OR "management"). Information was obtained from case reports and focused on common etiologies, clinical presentations, diagnostic methodologies, treatment protocols, and outcomes. The review discussed very diverse etiologies of Garcin syndrome. The most common among these were skull base tumors, metastatic lesions, and invasive infections like mucormycosis. Most of these were multiple cranial nerve (CN) involvements in which CN V (trigeminal nerve), CN VII (facial nerve), or CN XII (hypoglossal nerve) involvement was common. Advanced imaging, especially MRI, played a very crucial role in diagnosis, showing the presence of extensive bony destruction with the involvement of cranial nerves. Treatment was varied according to the etiology, ranging from chemotherapy and radiotherapy in neoplastic cases to active surgical intervention supported by antifungal therapy in infected cases. Garcin syndrome is a clinical challenge due to its diverse etiologies and complex management profile. While early diagnosis and intervention are emphasized, the prognosis remains grave, especially in cases presenting with metastatic disease or immunocompromised states. Future research should focus on better, more sensitive diagnostic modalities and the investigation of newer therapeutic approaches for Garcin syndrome patients.

Coexistence of Tuberculosis and Malignancy in a Single Cervical Lymph Node: A Case Series.

Background: The coexistence of tuberculosis (TB) and malignancy within the same lymph node is a rare, if not exceptional, pathology, with only a few cases reported. Methods: We collected patients who presented concomitant TB and malignancy within the same cervical lymph node diagnosed during the period (2010-2023). Results: Ten patients were included. They received or were receiving treatment for cancer or TB in 7 cases. All patients presented with recurrent or new lymph nodes despite being under treatment. The 3 remaining patients did not have a history of cancer or TB. Histopathological examination confirmed the coexistence of TB and malignancy within the same lymph node. Histological types of diagnosed cancers included laryngeal squamous cell carcinoma, papillary thyroid carcinoma, nasopharyngeal carcinoma, medullary carcinoma of the thyroid gland, Hodgkin lymphoma, and non-Hodgkin lymphoma. All patients received treatment for TB and cancer. Two patients died from septic complication in 1 case and from pulmonary complication due to miliary TB in 1 case. Conclusions: Concomitant TB and malignancy are possible, especially in countries with a high incidence of TB. Immunocompromised states related to cancer, and its treatments can add the risk of flare-up of a latent infection.

Purulent pericarditis and cardiac tamponade in HIV: a case report on a dreaded complication of streptococcus pneumoniae

Introduction and importance: Purulent pericarditis is an uncommon complication of Streptococcus pneumoniae, which commonly occurs in an immunocompromised state such as HIV and can lead to life-threatening complications such as cardiac tamponade and potentially death if untreated. Early identification, pericardiocentesis, and general measures such as antibiotics and anti-inflammatory medications can be life-saving. Case presentation: We present a case of a 64-year-old male with HIV who presented with clinical symptoms suggestive of pericarditis. Chest imaging revealed multifocal airspace diseases and moderate pericardial effusion. He had worsening lactic acidosis, and bedside point-of-care ultrasound showed pericardial effusion with features suggestive of cardiac tamponade. His lactic acidosis improved with emergency pericardiocentesis. Blood and pericardial fluid cultures revealed Streptococcus pneumoniae. He was further treated with intravenous antibiotics, colchicine, and ibuprofen. Clinical discussion: Although Streptococcus pneumoniae is a common etiology of community-acquired pneumonia (CAP), it has not been cited as the leading cause of pericarditis or pericardial effusion. In immunocompromised patients, it is necessary to consider a broad differential diagnosis as an etiology of acute chest pain, as it may be challenging to differentiate pleuritic and pericarditic chest pain from clinical presentation only. Moreover, infectious etiology of acute pericarditis and pericardial effusion should be considered in this patient population, especially those with HIV. At the same time, it is crucial to promptly identify and treat cardiac tamponade to prevent further deterioration. Conclusion: Our case provides insight into the diagnosis and management of CAP and its potential complication of purulent pericarditis and cardiac tamponade in immunocompromised patients.

Safety and Pharmacokinetics of Nirsevimab in Immunocompromised Children.

Immunocompromised children may have increased risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI), potentially leading to prolonged hospitalization, intensive care, and death. The open-label phase II MUSIC trial evaluated the safety and pharmacokinetics of nirsevimab, an extended half-life monoclonal antibody against RSV, in immunocompromised children aged ≤24 months. Participants received a single intramuscular injection of nirsevimab (first RSV season: 50 mg if <5 kg/100 mg if ≥5 kg; second season: 200 mg). Safety, antidrug antibodies, and pharmacokinetics were evaluated to day 361. Participants (n = 100) had ≥1 immunocompromising conditions: primary immunodeficiency (n = 33), previous transplantation (n = 16), HIV infection (n = 8) or treatment with high-dose systemic corticosteroids (n = 29), immunosuppressive chemotherapy (n = 20), or other immunosuppressive therapies (n = 15). Six children experienced eight treatment-related adverse events (none categorized as serious). Three deaths occurred, all were unrelated to treatment. Eleven children, developed antidrug antibodies, with minimal effects on pharmacokinetics and no apparent impact on safety. Nirsevimab serum concentrations at day 151 were similar to those effective in preventing medically attended RSV LRTI in healthy infants. Fourteen children had increased nirsevimab clearance. No protocol-defined medically attended RSV LRTIs occured through day 151. Among immunocompromised children aged ≤24 months, nirsevimab was well tolerated with no safety concerns and serum concentrations were supportive of efficacy. A subset of children with increased nirsevimab clearance, had conditions potentially associated with protein loss; however, the impact on efficacy is unknown.

Unveiling the Impact of Human Herpesviruses-Associated on CNS Infections: An Observational Study.

This retrospective cohort study included 895 patients suspected of viral CNS infections, utilizing molecular diagnosis via qPCR to identify HHVs in cerebrospinal fluid (CSF) samples. This was conducted at a reference tertiary care hospital for infectious diseases in the western Brazilian Amazon from January 2015 to December 2022, focusing on the Herpesviridae family's clinical repercussions and of Cytomegalovirus in CNS infections. The findings revealed that 7.5% of the analyzed samples tested positive for HHVs, with Human Cytomegalovirus (HCMV) and Epstein-Barr Virus (EBV) being the most prevalent. A significant association was found between HHVs and neurological diseases such as encephalitis and meningitis, especially among people living with HIV/AIDS (PLWHA), highlighting the opportunistic nature of these viruses. The study underscores the critical role of CSF analysis in diagnosing CNS infections and the complexity of managing these infections in HIV patients due to their immunocompromised status. The results emphasize the need for comprehensive diagnostic approaches and tailored treatment strategies for CNS infections in immunocompromised individuals. The study calls for ongoing research and advancements in clinical practice to improve patient outcomes facing CNS infections, particularly those caused by HHVs.

APOBEC family reshapes the immune microenvironment and therapy sensitivity in clear cell renal cell carcinoma

Emerging evidence suggests that the APOBEC family is implicated in multiple cancers and might be utilized as a new target for cancer detection and treatment. However, the dysregulation and clinical implication of the APOBEC family in clear cell renal cell cancer (ccRCC) remain elusive. TCGA multiomics data facilitated a comprehensive exploration of the APOBEC family across cancers, including ccRCC. Remodeling analysis classified ccRCC patients into two distinct subgroups: APOBEC family pattern cancer subtype 1 (APCS1) and subtype 2 (APCS2). The study investigated differences in clinical parameters, tumor immune microenvironment, therapeutic responsiveness, and genomic mutation landscapes between these subtypes. An APOBEC family-related risk model was developed and validated for predicting ccRCC patient prognosis, demonstrating good sensitivity and specificity. Finally, the overview of APOBEC3B function was investigated in multiple cancers and verified in clinical samples. APCS1 and APCS2 demonstrated considerably distinct clinical features and biological processes in ccRCC. APCS1, an aggressive subtype, has advanced clinical stage and a poor prognosis. APCS1 exhibited an oncogenic and metabolically active phenotype. APCS1 also exhibited a greater tumor mutation load and immunocompromised condition, resulting in immunological dysfunction and immune checkpoint treatment resistance. The genomic copy number variation of APCS1, including arm gain and loss, was much more than that of APCS2, which may help explain the tired immune system. Furthermore, the two subtypes have distinct drug sensitivity patterns in clinical specimens and matching cell lines. Finally, we developed a predictive risk model based on subtype biomarkers that performed well for ccRCC patients and validated the clinical impact of APOBEC3B. Aberrant APOBEC family expression patterns might modify the tumor immune microenvironment by increasing the genome mutation frequency, thus inducing an immune-exhausted phenotype. APOBEC family-based molecular subtypes could strengthen the understanding of ccRCC characterization and guide clinical treatment. Targeting APOBEC3B may be regarded as a new therapeutic target for ccRCC.

Clinical and microbiological characteristics and follow-up of invasive Listeria monocytogenes infection among hospitalized patients: real-world experience of 16 years from Hungary

PurposeInvasive Listeria monocytogenes infection is rare, but can lead to life-threatening complications among high-risk patients. Our aim was to assess characteristics and follow-up of adults hospitalized with invasive L. monocytogenes infection.MethodsA retrospective observational cohort study was conducted at a national referral center between 2004 and 2019. Patients with proven invasive listeriosis, defined by the European Centre for Disease Prevention and Control criteria, were included. Data collection and follow-up were performed using the hospital electronic system, up until the last documented visit. The primary outcome was in-hospital all-cause mortality, secondary outcomes included residual neurological symptoms, brain abscess occurrence, and requirement for intensive care unit (ICU) admission.ResultsAltogether, 63 cases were identified (57.1% male, median age 58.8 ± 21.7 years), and 28/63 developed a complicated disease course (44.4%). At diagnosis, 38/63 (60.3%) presented with sepsis, 54/63 (85.7%) had central nervous system involvement, while 9/63 (14.3%) presented with isolated bacteremia. Frequent clinical symptoms included fever (53/63, 84.1%), altered mental state (49/63, 77.8%), with immunocompromised conditions apparent in 56/63 (88.9%). L. monocytogenes was isolated from blood (37/54, 68.5%) and cerebrospinal fluid (48/55, 87.3%), showing in vitro full susceptibility to ampicillin and meropenem (100% each), gentamicin (86.0%) and trimethoprim/sulfamethoxazole (97.7%). In-hospital all-cause mortality was 17/63 (27.0%), and ICU admission was required in 28/63 (44.4%). At discharge, residual neurological deficits (11/46, 23.9%) and brain abscess formation (6/46, 13.0%) were common.ConclusionAmong hospitalized adult patients with comorbidities, invasive L. monocytogenes infections are associated with high mortality and neurological complications during follow-up.

Risk factors for positive follow-up blood cultures in critically ill adults with Gram-negative bacteraemia.

To evaluate the utility of follow-up blood cultures (FUBCs) for Gram-negative bloodstream infection (BSI) in ICU patients and identify risk factors for repeat positive cultures. This was a single-centre, retrospective cohort study of critically ill adults with Gram-negative BSI between 1 January 2015 and 1 January 2020. Critically ill patients with one or more blood cultures positive for a Gram-negative organism were included. Descriptive and inferential statistics were performed with an alpha of 0.05. A total of 148 critically ill patients with Gram-negative BSI were included, with 42 patients (28.4%) having one or more positive FUBCs. The majority (66.2%) were admitted to a medical ICU. The most common organisms isolated were Escherichia coli (n = 56, 37.8%) and Klebsiella pneumoniae (n = 26, 17.6%). Significant patient risk factors associated with a positive FUBC on univariate regression included: MDR organisms, immunocompromised status, fever, vasopressor use at time of FUBC, lack of source control attainment, and higher quick Pitt bacteraemia score. Multivariable penalized logistic regression indicated that lack of source control containment and less time from index to FUBC remained significantly associated with repeat positive FUBC. This is the first study to investigate the use of FUBC for Gram-negative BSI in exclusively ICU patients. Risk factors for repeat positive FUBC in this population include lack of source control and less time between index and FUBC. Prospective studies are needed to fully elucidate the role of FUBCs in critically ill patients with Gram-negative BSI.

Using machine learning to predict bacteremia in urgent care patients on the basis of triage data and laboratory results

BackgroundDespite advancements in antimicrobial therapies, bacteremia remains a life-threatening condition. Appropriate antimicrobials must be promptly administered to ensure patient survival. However, diagnosing bacteremia based on blood cultures is time-consuming and not something emergency department (ED) personnel are routinely trained to do. MethodsThis retrospective cohort study developed several machine learning (ML) models to predict bacteremia in adults initially presenting with fever or hypothermia, comprising logistic regression, random forest, extreme gradient boosting, support vector machine, k-nearest neighbor, multilayer perceptron, and ensemble models. Random oversampling and synthetic minority oversampling techniques were adopted to balance the dataset. The variables included demographic characteristics, comorbidities, immunocompromised status, clinical characteristics, subjective symptoms reported during ED triage, and laboratory data. The study outcome was an episode of bacteremia. ResultsOf the 5063 patients with initial fever or hypothermia from whom blood cultures were obtained, 128 (2.5 %) were diagnosed with bacteremia. We combined 36 selected variables and 10 symptoms subjectively reported by patients into features for analysis in our models. The ensemble model outperformed other models, with an area under the receiver operating characteristic curve (AUROC) of 0.930 and an F1-score of 0.735. The AUROC of all models was higher than 0.80. ConclusionThe ML models developed effectively predicted bacteremia among febrile or hypothermic patients in the ED, with all models demonstrating high AUROC values and rapid processing times. The findings suggest that ED clinicians can effectively utilize ML techniques to develop predictive models for addressing clinical challenges.

500. PRIMARY ESOPHAGEAL LYMPHOMA: UNDERSTANDING PROGNOSTIC FACTORS AND OUTCOMES

Abstract Background Primary Esophageal Lymphoma (PEL) represents a rare subtype of gastrointestinal lymphomas, posing unique diagnostic and therapeutic challenges. Given its rarity, comprehensive insights into its prognostic factors and outcomes remain limited. This study examines the epidemiology, treatment modalities, and outcomes of PEL, aiming to identify significant prognostic factors that influence patient survival. Methods A systematic review of the literature was conducted across PubMed/Medline and Scopus databases, focusing on cases of adult PEL. Data extraction included demographic information, treatment modality, and patient outcomes. Survival rates were calculated, and prognostic factors were analyzed through unifactorial analysis. Results Out of 56 studies, 69 cases of PEL were analyzed, with a male-to-female ratio of 2.8:1 and mean age of 55.5 years. Patients were predominantly treated with chemotherapy (52.1%) while 20% underwent surgical treatment. The mean survival reported was 49.3 months with one-, three-, and five-year survival rates of 84.5%, 72.3%, and 28.9%, respectively, exhibiting a less favorable prognosis compared to common lymphoma types. Survival analysis revealed that local lymphadenopathy had a significant impact on prognosis (p=0.008), while gender, age, treatment approach, and type of lymphoma were not significant determinants of survival. Immunocompromised status showed a marginally significant effect on survival (p= 0.053). Discussion The study highlights the less favorable prognosis of PEL compared to more common lymphomas, emphasizing the importance of recognizing patients with unfavorable prognostic factors such as local lymphadenopathy and immunocompromised status. The findings advocate for the establishment of an international patient registry to better understand and manage PEL, aiming to standardize diagnostic criteria and treatment strategies.

Unlocking the potential of flavonoid-infused drug delivery systems for diabetic wound healing with a mechanistic exploration.

Diabetes is one of the common endocrine disorders generally characterized by elevated levels of blood sugar. It can originate either from the inability of the pancreas to synthesize insulin, which is considered as an autoimmune disorder, or the reduced production of insulin, considered as insulin resistivity. A wound can be defined as a condition of damage to living tissues including skin, mucous membrane and other organs as well. Wounds get complicated with respect to time based on specific processes like diabetes mellitus, obesity and immunocompromised conditions. Proper growth and functionality of the epidermis gets sustained due to impaired diabetic wound healing which shows a sign of dysregulated wound healing process. In comparison with synthetic medications, phytochemicals like flavonoids, tannins, alkaloids and glycosides have gained enormous importance relying on their distinct potential to heal diabetic wounds. Flavonoids are one of the most promising and important groups of natural compounds which can be used to treat acute as well as chronic wounds. Flavonoids show excellent properties due to the presence of hydroxyl groups in their chemical structure, which makes this class of compounds different from others. Based on the novel principles of nanotechnology via utilizing suitable drug delivery systems, the delivery of bioactive constituents from plant source amplifies the wound-healing mechanism, minimizes complexities and enhances bioavailability. Hence, the encapsulation and applicability of flavonoids with an emphasis on mechanistic route and wound-healing therapeutics have been highlighted in the subsequent study with focus on multiple drug delivery systems.

Lymphotropic polyomavirus and Merkel cell polyomavirus in patients infected with HIV or hepatitis B or C virus

BackgroundLPV and MCV emerge as recent additions to the Polyomaviridae family, capable of inducing important infections. Studies have suggested the presence of LPV in human populations, with potential involvement in central nervous system (CNS) diseases. Additionally, MCV, closely related to LPV, has been implicated in Merkel cell carcinoma (MCC). This study aimed to explore the prevalence of LPV and MCV in individuals with compromised immunity due to chronic viral infections. Methods340 specimens, including HIV PCR-positive, HBV PCR-positive, HCV PCR-positive, and HIV/HBV/HCV negative sera, underwent screening via PCR technique to identify LPV and MCV genomes. Subsequently, sequencing was employed to validate the viral identity. ResultsOut of all specimens, MCV DNA was detected in 8.52 % of participants, with a significantly higher prevalence in HIV-positive individuals (26.4 %). LPV was detected in only one HIV-positive patient. No co-detection of MCV and LPV was observed. Phylogenetic analysis confirmed the genetic similarity of the detected MCV strains to known references, while the LPV sequence showed 99 % identity to the published sequences of LPV-K38. ConclusionThis research provides insights into the prevalence of LPV and MCV in individuals with chronic viral infections. The study highlights the potential association between MCV and immunocompromised states, emphasizing the need for comprehensive investigations to understand the epidemiology, transmission routes, and clinical implications of these polyomaviruses in human populations.

Superinfection of Mucormycosis in Post-COVID-19 Patients with Diabetes at Tertiary Care Hospital in Eastern Uttar Pradesh

Introduction and Objectives: To determine the prevalence of mucormycosis in post COVID-19 patients. To understand the risk factor mainly diabetes and its association with post COVID-19 mucormycosis.Method and Material: This a retrospective observational study of post-COVID-19 patients associated with mucormycosis which were managed in a tertiary care centre of Eastern UP from March 2021 to February 2022. The tissue sample for study was taken from surgical and medicine wards of the centre and the study was conducted in Microbiology Department. The procedures followed to process the sample were: 10% KOH mount after teasing the tissue. Culture on Sabouraud dextrose agar (SDA) with chloremphenicol and the fungal growth was stained with lactose phenol cotton blue (LPCB) for microscopyConclusion: There has been a surge in cases of mucormycosis in COVID-19 era. Uncontrolled diabetes and other immunocompromised states predispose to its development mainly in adult patients where diabetes is the most important predisposing factor. Although, early presentation and intervention play a very important part. Tight glycemic control, Amphotericin B and surgical debridement can lead to favourable outcomes.

Elliptical excision and primary closure of nasal defect to achieve best esthetic outcome: A case series of 50 patients.

To evaluate the cosmetic result of nasal of an elliptical excision and primary closure on small nasal defect by using Scar assessment using the Stony Brook Scar Evaluation Scale (SBSES) score. This retrospective interventional study was conducted in a private clinic over a 2-year duration. Patients aged 18-60 years with nasal defects <1.5 cm were enrolled after obtaining informed consent. Exclusion criteria included immunocompromised status, keloidal tendency, local site infection, bleeding disorder, age <18 years, and lack of consent. Scar assessment using the SBSES was performed at the end of 6 months. Statistical analysis included summary statistics, analysis of variance tests, and a significance level of P < 0.05. The study included 50 patients, with 54% males and 46% females. The most common age group was 21-40 years, and melanocytic nevi was the most common cause for excision. Lesions were excised mainly from the lateral wall and dorsum of the nose. The mean SBSES score was 3.79 ± 0.467. The best cosmetic outcome was observed in lesions involving the dorsum followed by the root of the nose. No significant difference was found among the SBSES scores for various subunits. Elliptical excision with primary closure is a simple and effective technique for small nasal defects, providing good cosmetic results. The location of the nasal defect influences the cosmetic outcome, with better results observed in areas with thinner skin and increased skin laxity.

Beyond dermatomes disseminated Herpes zoster in the immunocompetent: two rare cases

Herpes zoster is typically a localized reactivation of the varicella-zoster virus (VZV) that occurs in individuals following a primary varicella infection (chickenpox). Disseminated herpes zoster, characterized by widespread vesicular lesions beyond the primary dermatome, is uncommon and usually associated with immunocompromised states. Till date only 25 immunocompetent patients with disseminated HZ have been reported in literature. We report two such cases of disseminated HZ in immunocompetent individuals. The 1st patient is a 53-year-old woman with painful, itchy multiple grouped erythematous papules, vesicles, and bullae over right T8-T9 dermatome and multiple papules, crusted papules, and vesicles over face associated with fever and fatigue. The 2nd patient is an 8-year-old boy with multiple grouped clear vesicles and bullae with erythematous base involving the left S1-S5 dermatome. Multiple discrete erythematous papules and vesicles (active and crusted) were noted over trunk, right forearm, left arm, bilateral thigh and left mandibular area. Routine laboratory investigations were within normal limits. Tzanck smears were done, and multinucleated giant cells were seen in both cases. They were treated with antivirals and showed improvement. We have reported these two cases of disseminated HZ due to their occurrence in immunocompetent patients, which is a very rare phenomenon.

PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection.

To evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA) - the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the United States (US) Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72h of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date and findings support use of RBL to prevent rCDI in a broad patient population. The study is registered at ClinicalTrials.gov (NCT03931941).

Chronic innate immune impairment and ZIKV persistence in the gastrointestinal tract during SIV infection in pigtail macaques.

Mosquito borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused global epidemics in areas with high HIV prevalence due to the expanded geographic range of arthropod vectors. Despite the occurrence of large flavivirus outbreaks in countries with high HIV prevalence, there is little knowledge regarding the effects of flavivirus infection in people living with HIV (PLWH). Here, we use a pigtail macaque model of HIV/AIDS to investigate the impact of simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication and pathogenesis. Early acute SIV infection induced expansion of peripheral ZIKV cellular targets and increased innate immune activation and peripheral blood mononuclear cells (PBMC) from SIV infected macaques were less permissive to ZIKV infection in vitro. In SIV-ZIKV co-infected animals, we found increased persistence of ZIKV in the periphery and tissues corresponding to alterations in innate cellular (monocytes, neutrophils) recruitment to the blood and tissues, decreased anti-ZIKV immunity, and chronic peripheral inflammatory and innate immune gene expression. Collectively, these findings suggest that untreated SIV infection may impair cellular innate responses and create an environment of chronic immune activation that promotes prolonged ZIKV viremia and persistence in the gastrointestinal tract. These results suggest that PLWH or other immunocompromised individuals could be at a higher risk for chronic ZIKV replication, which in turn could increase the timeframe of ZIKV transmission. Thus, PLWH are important populations to target during the deployment of vaccine and treatment strategies against ZIKV.

Rapid intra-host diversification and evolution of SARS-CoV-2 in advanced HIV infection

Previous studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions, but the processes responsible for these observations are incompletely understood. Here we use high-throughput, single-genome amplification and sequencing (HT-SGS) to sequence SARS-CoV-2 spike genes from people with HIV (PWH, n = 22) and people without HIV (PWOH, n = 25). In PWOH and PWH with CD4 T cell counts (i.e., CD4 counts) ≥ 200 cells/μL, we find that most SARS-CoV-2 genomes sampled in each person share one spike sequence. By contrast, in people with advanced HIV infection (i.e., CD4 counts < 200 cells/μL), HT-SGS reveals a median of 46 distinct linked groupings of spike mutations per person. Elevated intra-host spike diversity in people with advanced HIV infection is detected immediately after COVID-19 symptom onset, and early intra-host spike diversity predicts SARS-CoV-2 shedding duration among PWH. Analysis of longitudinal timepoints reveals rapid fluctuations in spike sequence populations, replacement of founder sequences by groups of new haplotypes, and positive selection at functionally important residues. These findings demonstrate remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern.

CHALLENGE IN TREATING OPTIC NEURITIS IN PATIENT WITH CEREBRAL TOXOPLASMOSIS RELATED TO IMMUNOCOMPROMISED CONDITION

Introduction: This study aimed to discuss the prognosis of optic neuritis in a patient with cerebral toxoplasmosis related to an immunocompromised condition. Case Report: A 28-year-old female complained of blurred vision and double vision 2 weeks before admission, accompanied by headache, low extremities weakness, dysphonia, and dysphagia. Visual acuity of both eyes was 6/30 and worsened to 6/60 in a couple of days. Anterior segment examination revealed anisocoria pupil, and RAPD was positive in the left eye. Funduscopic examination showed a blurry margin and hyperemia of the optic nerve head. There was impaired eye movement, indicating oculomotor and abducens nerve palsies. High titer of IgG Antibody Toxoplasma (264) and very low titer of CD4 (&lt;50) with non-reactive HIV rapid test were found in laboratory findings. Multiple ring enhancement was shown in MRI finding. Unfortunately, patient passed away during hospitalization due to respiratory failure. Discussion: Toxoplasmosis-associated optic neuritis is rare and usually becomes potentially serious. Although parasite detection by microscopy and bioassay is considered the gold standard for the diagnosis of toxoplasmosis, clinical diagnosis relies more on serological examination methods. The high proportion of deaths from this disease is mostly caused by late diagnosis of the infection. Conclusion: Optic neuritis that accompanied by systemic disorders needs special attention and comprehensive treatment among multidisciplinary divisions, especially in the immunocompromised condition. Early detection and primary prevention are important to improve prognosis and survival rate.