Mapping the infectious burden in VEXAS syndrome: a systematic review and rationale for prevention.

Opportunistic Infections, Is Non Hodgkin Lymphoma One of the Risk Factors for Mortality?

Skin and subcutaneous infections

Varicella-Zoster Virus Meningoencephalitis in a Lung Transplant Recipient

Higher risks of infection are associated with some targeted drugs used to treat solid organ and hematological malignancies, and an individual patient’s risk of infection is strongly influenced by underlying diseases and concomitant or prior treatments. This review focuses on risk levels and specific suggestions for management, analyzing groups of agents associated with a significant effect on the risk of infection. Due to limited clinical experience and ongoing advances in these therapies, recommendations may be revised in the near future. Bruton tyrosine kinase (BTK) inhibitors are associated with a higher rate of infections, including invasive fungal infection, especially in the first months of treatment and in patients with advanced, pretreated disease. Phosphatidylinositol 3-kinase (PI3K) inhibitors are associated with an increased risk of Pneumocystis pneumonia and cytomegalovirus (CMV) reactivation. Venetoclax is associated with cytopenias, respiratory infections, and fever and neutropenia. Janus kinase (JAK) inhibitors may predispose patients to opportunistic and fungal infections; need for prophylaxis should be assessed on an individual basis. Mammalian target of rapamycin (mTOR) inhibitors have been linked to a higher risk of general and opportunistic infections. Breakpoint cluster region-Abelson (BCR-ABL) inhibitors are associated with neutropenia, especially over the first months of treatment. Anti-CD20 agents may cause defects in the adaptative immune response, hypogammaglobulinemia, neutropenia, and hepatitis B reactivation. Alemtuzumab is associated with profound and long-lasting immunosuppression; screening is recommended for latent infections and prevention strategies against CMV, herpesvirus, and Pneumocystis infections. Checkpoint inhibitors (CIs) may cause immune-related adverse events for which prolonged treatment with corticosteroids is needed: prophylaxis against Pneumocystis is recommended.

Herpes zoster (HZ), or shingles, is caused by the reactivation of varicella zoster virus (VZV) and typically presents as an acute, painful dermatomal rash, but can lead to long-term, distressing complications such as postherpetic neuralgia (PHN). Increasing trends in HZ cases are evident globally among the aging population; however, reviews investigating the epidemiology and clinical management of HZ in Turkey are lacking. Therefore, a literature review of local studies in Turkey was conducted to identify the data available and identify gaps in the literature. Literature searches were carried out in PubMed and local journals to retrieve published articles that reported surveillance data, seroepidemiology, patient outcomes, or clinical management related to HZ or VZV in Turkey until April30, 2022. Studies included primary data reports, case studies, secondary data reviews, and epidemiological studies in healthy or at-risk populations; HZ was the primary focus of the review. No studies reported VZV or HZ epidemiological data at a national level. One large retrospective study in Istanbul reported that HZ incidence rates significantly increased in adults 18-44years of age between 2011 and 2019. Four single-center studies reported the proportion of dermatological patients with HZ at 0.43-1.56%. PHN was the most common reported complication, occurring in 8-58.9% of patients with HZ. However, out of 39 identified case reports, HZ ophthalmicus was the most frequently reported complication. Two studies highlighted poor disease awareness and risk perception of HZ among Turkish citizens. Overall, there were limited comprehensive epidemiological data on HZ in Turkey. However, the abundance of case studies on HZ complications indicates a strong disease presence and diverse clinical management in Turkey. Further research will be important to understand the impact of HZ, increase disease awareness, and support the introduction of new preventative strategies.

Herpes zoster (HZ) has been observed to occur after COVID-19 infection and vaccination; however, knowledge regarding the demographic data, clinical presentations, and treatment outcomes of HZ is limited. To compare the demographic data, clinical manifestations, treatments, and outcomes of patients with and without HZ within 14 days of COVID-19 infection or vaccination. This prospective cohort study involving patients diagnosed with cutaneous HZ was conducted at a dermatology clinic from October 2021 to January 2023. Among a total of 232 patients with HZ, the median age was 62.0 years and 59.1% were female. HZ developed in 23 (9.9%) and four (1.7%) patients after COVID-19 vaccination and infection, respectively. The mean duration from vaccination and the median duration from infection to HZ onset were 5.7 and 8.5 days, respectively. The proportion of female patients was significantly higher in the group of patients with COVID-19 vaccination or infection than in those without such a history (P = 0.035). Patients who developed HZ following the recent COVID-19 infection had a median age of 42.5 years, which was lower than that of the other groups. Dissemination occurred in 8.7% of the patients after COVID-19 vaccination. HZ recurrence was reported in five cases, of which 80% had been vaccinated or infected with COVID-19 during the previous 21 days. All patients had similar durations of antiviral treatment, crust-off time, and duration of neuralgia. HZ after COVID-19 vaccination is more frequently observed in females, while HZ after COVID-19 infection tends to occur in younger patients. Disseminated HZ is more common in patients recently vaccinated against COVID-19. COVID-19 vaccination or infection may trigger recurrent HZ infection.

Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella upon primary infection and zoster upon reactivation from latency in sensory ganglion neurons. The replication of herpesviruses requires manipulation of cell signaling pathways. Notably, CREB, a factor involved in the regulation of several cellular processes, is activated upon infection of T cells with VZV. Here, we report that VZV infection also induced CREB phosphorylation in fibroblasts and that XX-650-23, a newly identified inhibitor of the phosphorylated-CREB (pCREB) interaction with p300/CBP, restricted cell-cell spread of VZV in vitro CREB phosphorylation did not require the viral open reading frame 47 (ORF47) and ORF66 kinases encoded by VZV. Evaluating the biological relevance of these observations during VZV infection of human skin xenografts in the SCID mouse model of VZV pathogenesis showed both that pCREB was upregulated in infected skin and that treatment with XX-650-23 reduced infectious-virus production and limited lesion formation compared to treatment with a vehicle control. Thus, processes of CREB activation and p300/CBP binding are important for VZV skin infection and may be targeted for antiviral drug development. Varicella-zoster virus (VZV) is a common pathogen that causes chicken pox and shingles. As with all herpesviruses, the infection is acquired for life, and the virus can periodically reactivate from latency. Although VZV infection is usually benign with few or no deleterious consequences, infection can be life threatening in immunocompromised patients. Otherwise healthy elderly individuals who develop zoster as a consequence of viral reactivation are at risk for postherpetic neuralgia (PHN), a painful and long-lasting complication. Current vaccines use a live attenuated virus that is usually safe but cannot be given to many immunodeficient patients and retains the capacity to establish latency and reactivate, causing zoster. Antiviral drugs are effective against severe VZV infections but have little impact on PHN. A better understanding of virus-host cell interactions is relevant for developing improved therapies to safely interfere with cellular processes that are crucial for VZV pathogenesis.

The protein product of varicella-zoster virus (VZV) ORF47 is a serine/threonine protein kinase and tegument component. Evaluation of two recombinants of the Oka strain, rOka47DeltaC, with a C-terminal truncation of ORF47, and rOka47D-N, with a point mutation in the conserved kinase motif, showed that ORF47 kinase function was necessary for optimal VZV replication in human skin xenografts in SCID mice but not in cultured cells. We now demonstrate that rOka47DeltaC and rOka47D-N mutants do not infect human T-cell xenografts. Differences in the growth of kinase-defective ORF47 mutants allowed an examination of requirements for VZV pathogenesis in skin and T cells in vivo. Although virion assembly was reduced and no virion transport to cell surfaces was observed, epidermal cell fusion persisted, and VZV polykaryocytes were generated by rOka47DeltaC and rOka47D-N in skin. Virion assembly was also impaired in vitro, but VZV-induced cell fusion continued to cause syncytia in cultured cells infected with rOka47DeltaC or rOka47D-N. Intracellular trafficking of envelope glycoprotein E and the ORF47 and IE62 proteins, components of the tegument, was aberrant without ORF47 kinase activity. In summary, normal VZV virion assembly appears to require ORF47 kinase function. Cell fusion was induced by ORF47 mutants in skin, and cell-cell spread occurred even though virion formation was deficient. VZV-infected T cells do not undergo cell fusion, and impaired virion assembly by ORF47 mutants was associated with a complete elimination of T-cell infectivity. These observations suggest a differential requirement for cell fusion and virion formation in the pathogenesis of VZV infection in skin and T cells.

Existen pocos estudios que reporten datos acerca de autopsias de pacientes con VIH en Sudamérica y ninguno que documente los resultados post mórtem en los pacientes con VIH/SIDA en el Perú. Objetivos: Determinar el espectro de las infecciones oportunistas y las causas de mortalidad en pacientes VIH-positivos en un hospital público en Lima. Asimismo, se revisa la información clínico-epidemiológica con respecto a la infección con VIH en el Perú. Materiales y métodos: Se incluyeron en este análisis retrospectivo, 16 autopsias relacionadas con VIH del Hospital Dos de Mayo, realizadas entre 1999-2004. Resultados: La causa primaria de la muerte fue establecida en 12 pacientes: uno murió de neoplasia y 11 de enfermedades infecciosas, incluyendo tres con infección pulmonar, siete con infección disemina - da, y dos con infección del sistema nervioso central (un caso presentó patología dual). Las infecciones oportunistas fueron identificadas en 14 casos, incluyendo citomegalovirus, histoplasmosis, criptococcosis, toxoplasmosis, neumonía por Pneumocistis , aspergilosis, tuberculosis, virus de la varicela-zoster y criptosporidiosis. Catorce pacientes tenían por lo menos una enfermedad relacionada con el SIDA que no había sido sospechada clínicamente ni diagnosticada antes de la muerte. Por otra parte, 82% de los diagnósticos considerados de significancia clínica importante, no habían sido sospechados antes de la muerte. Conclusiones: El espectro y la frecuencia de ciertas infecciones oportunistas reportadas en el presente estudio lo diferencia de otros estudios de autopsias realizados en Sudamérica; destacando la importancia de realizar necropsias en VIH/SIDA en países de recursos limitados, con el fin de observar los patrones locales específicos de la enfermedad.

The increasing number of opportunistic fungal infections in neutropenic cancer patients has become of major concern. Postmortem examinations have shown that more than half of the deaths attributed to infection were due to disseminated fungal infections. Candida species are the major pathogens. Unfortunately, the early diagnosis of serious fungal invasion is exceedingly difficult in these patients, since the manifestations of infection are ill-defined and the organisms can only rarely be isolated from blood cultures. Therefore, empirical antifungal therapy in febrile patients early in the course of disease appears necessary to prevent fungal superinfections and to control clinically undetected fungal invasion. Even if a fungal infection is diagnosed, treatment options are limited to a small number of drugs, and the chance of successful treatment is slim. Amphotericin B remains the most effective drug for systemic fungal infection; however, it is also the most toxic antimicrobical in use. Reduction of its toxicity and, simultaneously, improvement of its effectiveness can be achieved by incorporation into liposomes, although liposomal amphotericin B is not yet available commercially. The newer azoles, such as ketoconazole, vibunazole, and itraconazole are orally active and less toxic. Azoles have been successfully used in the treatment of superficial candidal infections; they are not very active in systemic candidiasis. Inhibitors of the cell wall biosynthesis of candida species include inhibitors of chitin and glucan biosynthesis. Echinocandins and papulacandins interfer with the glucan synthesis and show good anticandidal activity. Their therapeutic potential is currently being explored in clinical trials. Neutropenic patients and particularly bone marrow transplant (BMT) recipients are, in addition to fungal infections, at very high risk for herpesvirus infections: herpes simplex virus (HSV) 0-20 days after BMT, cytomegalovirus (CMV) 40-80 days after BMT, varicella zoster virus (VZV) 100-160 days after BMT, and Epstein-Barr virus (EBV) 14-21 days after BMT. Acyclovir and vidarabine are, at present, the only antiviral drugs available for HSV and VZV infections, acyclovir apparently being the more effective. It is also the drug of choice for prevention of HSV infections in severely immunocompromised, i.e., BMT, patients. Bromovinyldeoxyuridine seems to be suitable for systemic treatment of HSV-1 and VZV infections in these patients. Its potency in inhibiting HSV-1 and VZV replication is superior to that of ACV, and in therapeutic doses it is nontoxic to hematopoietic progenitor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Viral screening before initiation of biologics in patients with inflammatory bowel disease during the COVID-19 outbreak

Antiviral Therapy in Patients With Hematologic Malignancies, Transplantation, and Aplastic Anemia

Objective To investigate the clinical features, treatment effect and prognosis of Herpes Zoster(HZ) among patients with acquired immunodeficiency syndrome (AIDS). Methods Clinical data of 72 AIDS-HZ patients in our hospital were retrospectively reviewed, then the data including clinical characteristics, laboratory examination, treatment and the prognosis of patients were statistically analyzed. Results Our study showed that the majority of these patients were male (65.28%) and Uyghur (79.17%), with a mean age of 37.22±8.26 years. 39(54.17%)patients have a history of intravenous drug using (IDUs). The rash was common seen in the trunk (68.06%) and limbs (26.39%), two or more than two were seen in 12 patients (16.67%). 21(29.17%) were combined by skin infections and 67 patients (93.06%) complained with pain. Forty seven(65.28%) patients had a lower CD4+ T lymphocyte counts (<350 cells/ μl). The cure rate was 75% (54/72) and the effective rate was 100% after standard treatment (including antiretroviral therapy, drugs and analgesia therapy). Conclusions HIV/AIDS-HZ is common in male Uygur patients in Xinjiang. More than half of the cases are IDUs and have a lower CD4 count (<350 cells/ μl). Herpes zoster may occurred as a manifestation of immune reconstitution after HAART. However, most of patients with HIV/AIDS-HZ case had a good prognosis after standard treatment. Key words: HIV; AIDS; Herpes zoster; Clinical features

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or high-dose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count less than 50 cells/microL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 mumol/L for acyclovir, 1.4 compared with 0.8 mumol/L for vidarabine, and 123 compared with 117 mumol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.

Fourteen varicella zoster virus antigens were identified that induce antibodies during primary and recurrent infections. These antigens, which included the major nucleocapsid polypeptide (molecular weight, 155,000) and three glycoproteins (molecular weights, 130,000, 88,000, and 60,000, respectively) plus a number of minor antigens, were identified in radioimmunoprecipitation assays, using [35S]methionine-labeled extracts of cells infected with varicella zoster virus and sera from patients with primary and recurrent viral infections. No significant and reproducible differences were observed between early convalescent sera from cases with natural chicken pox and sera from cases with zoster in their ability react with viral antigens. Sera that were taken many years after episodes of chicken pox still retained their ability to react with the major viral antigens.