Immunodeficiency Research Articles

IL-7-dependent and -independent lineages of IL-7R-dependent human T cells.

Infants with biallelic IL7R loss-of-function variants have severe combined immune deficiency (SCID) characterized by the absence of autologous T lymphocytes, but normal counts of circulating B and NK cells (T-B+NK+ SCID). We report 6 adults (aged 22 to 59 years) from 4 kindreds and 3 ancestries (Colombian, Israeli Arab, Japanese) carrying homozygous IL7 loss-of-function variants resulting in combined immunodeficiency (CID). Deep immunophenotyping revealed relatively normal counts and/or proportions of myeloid, B, NK, and innate lymphoid cells. By contrast, the patients had profound T cell lymphopenia, with low proportions of innate-like adaptive mucosal-associated invariant T and invariant NK T cells. They also had low blood counts of T cell receptor (TCR) excision circles, recent thymic emigrant T cells and naive CD4+ T cells, and low overall TCR repertoire diversity, collectively indicating impaired thymic output. The proportions of effector memory CD4+ and CD8+ T cells were high, indicating IL-7-independent homeostatic T cell proliferation in the periphery. Intriguingly, the proportions of other T cell subsets, including TCRγδ+ T cells and some TCRαβ+ T cell subsets (including Th1, Tfh, and Treg) were little affected. Peripheral CD4+ T cells displayed poor proliferation, but normal cytokine production upon stimulation with mitogens in vitro. Thus, inherited IL-7 deficiency impairs T cell development less severely and in a more subset-specific manner than IL-7R deficiency. These findings suggest that another IL-7R-binding cytokine, possibly thymic stromal lymphopoietin, governs an IL-7-independent pathway of human T cell development.

Case study: May human norovirus infection be associated with premature delivery?

Human norovirus (HuNoV) is the leading cause of acute gastroenteritis. The varying severity of chronic infection in patients with underlying immune deficiencies poses additional burdens on public health. However, the potential effects of HuNoV infection during pregnancy, a specific immune perturbed state, have been rarely reported. Recently, four cases of HuNoV-infected patients in the late stages of pregnancy were admitted to the Guangzhou Women and Children's Medical Center, and premature rupture of membranes as primary adverse outcome was observed in these cases. Samples of fetal accessory tissue were collected from two of these cases at delivery to explore the potential pathogenesis. Pathological analysis showed placental malperfusion in both maternal and fetal vascular, while a decrease in vessels was not observed in villi of placenta. There was obvious pathological change in the chorion of fetal membrane, accompanied by a tendency of Th-1 immune bias. Notably, aggregation of M2 macrophages was observed in the chorion of the fetal membrane, potentially recruited for tissue repair. Next-generation sequencing showed minimal changes in immune pathways within placenta tissue. A gene panel associated with immunosuppression was identified in the fetal membrane of HuNoV-infected women compared to those of normal parturient. Taken together, this study provides clues for the association between the HuNoV and premature delivery, which requires the attention of the clinicians.

Persistently Low IgG2 Levels in a Subset of Patients Following Hematopoietic Cell Transplantation.

Infectious diseases remain a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Secondary hypogammaglobulinemia is a risk factor for infectious diseases. Total immunoglobulin G (IgG) levels and the history of infectious diseases are an integral part of determining the indication for immunoglobulin replacement therapy. The clinical significance of IgG2 levels is not well established. Guidelines recommend using pathogen-specific IgG to evaluate patients with potential secondary immunodeficiency. However, it is difficult in practice to perform such testing. IgG2 may correlate well with pathogen-specific IgG but the clinical significance of IgG2 is not well established. To assess the prevalence of low IgG2 levels with normal IgG after HCT, we cross-sectionally measured the levels of several immunoglobulins, including IgG, IgA, IgM, and IgG2, after HCT, and we assessed the correlation between them. Among 121 patients who underwent cross-sectional measurements of IgG, IgA, IgM, and IgG2 levels after HCT, 114 had normal IgG2 levels (normal IgG2 group, ≥ 100mg/dL) and 7 had low IgG2 levels (low IgG2 group, < 100mg/dL). These 7 patients were allogeneic HCT recipients. All 7 patients with low IgG2 had cGVHD and 4/7 patients had normal total IgG levels. IgG2 levels may be low even in patients with normal IgG levels years after allogeneic HCT. Therefore, our study suggests that when patients develop infectious diseases, especially multiple episodes, it is recommended to measure IgG2 levels to exclude the possibility of secondary hypogammaglobulinemia after allogeneic HCT.

Implementation of Covid-19 assessment in 5 rural oncology clinics and resulting impact on immunization culture.

291 Background: Patients with cancer are at-risk for increased severity of infections due to compromised immunity, potentially leading to poorer patient outcomes. We aimed to increase documentation of Covid-19 assessment from 0% to 60% by implementing a quality improvement intervention impacting each patient encounter, beginning in a pilot rural oncology clinic. Methods: We engaged in a quality improvement initiative to implement, improve, and sustain a new process for COVID-19 assessment. A method to easily document Covid-19 status was needed in the EMR (OncoEMR). A Covid-19 verification, binary (yes-vaccinated/no-not vaccinated) checkbox tool was created and integrated into the patient assessment workflow and OncoEMR. This tool was piloted at one, then four additional rural clinics, but was available across the system. Spontaneous uptake in CARTI’s other nine clinics allowed us to identify early adopters who then became the champions to promote the application throughout the entire CARTI health system. Results: Beginning in May 2023, the pilot clinic assessment results reached 52% (n=25/48) after 4-weeks, and the tool was implemented into four additional rural clinics. An assessment rate of 57% (n=282/496) was achieved after 8 weeks at the other rural clinics and subsequently implemented throughout all CARTI clinics. In March 2024, Covid-19 assessment rates exceeded our initial aim of 60% reaching 88% (n=1692/1918) in the 5 rural clinics and 73% (n=8849/12195) throughout the entire health system. An initiation of immunization culture change was observed as a result of the initiative. Conclusions: Successful implementation of Covid-19 assessment tool was initiated by nursing and physician innovators and amplified by early adopters who propagated a cultural change emphasizing the importance of immunizations as part of cancer patient care. The resulting culture change resonates throughout the CARTI health system with dedication to increasing positive patient outcomes through completion of routine vaccinations for all who are eligible. With the continued support of innovators, CARTI has maintained Covid-19 assessment rates above 50% for the past nine months and plans to implement further immunization standards focusing on Covid-19 and other CDC recommended vaccines including the flu, shingles, pneumococcal and TdaP.

Monitoring the Seroprevalence of Herpes Simplex Virus-1 Among Egyptian Hemodialysis Patients

Background: Hemodialysis patients are at high risk for infections due to their compromised immune systems. Herpes Simplex Virus (HSV) infections can lead to severe complications in this population. Despite its clinical significance, comprehensive data on the seroprevalence of HSV among hemodialysis patients are limited. Objective: This study aims to evaluate the seroprevalence of HSV-1 among Egyptian hemodialysis patients. Methods: A cross-sectional study was conducted with 218 participants (116 females and 102 males). Among these, 132 (60.6%) were undergoing hemodialysis, while 86 (39.4%) had normal kidney function and were free from HCV, CMV, and HIV infections. Serum samples were analyzed for IgG antibodies against HSV-1. Statistical analyses were performed to determine HSV seroprevalence. Results: The study observed a significantly higher prevalence of HSV-1-IgG antibodies in hemodialysis patients (84.1%) compared to the control group (66.3%, P&lt;0.01). Additionally, HSV-1-IgM positivity was also higher in the hemodialysis group (41.6%) compared to the control group (32.6%, P&lt;0.05). These findings highlight the need for vigilant monitoring and preventive strategies for HSV infections in hemodialysis patients.

The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.

Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance. The aim of this review was to comprehensively review the published literature on letermovir and maribavir drug resistance and to describe the clinical scenarios in which they may emerge. For letermovir, the most frequently detected resistance mutations occur in the UL56 gene (C325Y/W/F) and confer total resistance. Maribavir resistance mutations most often occur in the UL97 gene and resistance-associated variants (RAVs) T409M, H411Y, C480F have all been detected. The clinical context in which letermovir and maribavir resistance occurs include high viral loads at initiation, intensified immunosuppression, subtherapeutic drug exposure because of poor adherence, drug interactions, and inadequate central nervous system (CNS) penetration. Emergence of resistance mutations generally occurs within the first 3 months of initiation. The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.

Clinicopathological Study of Herpes Simplex Esophagitis in a Tertiary Centre in India

Introduction and objectives: Herpes Simplex Virus (HSV) is a common viral pathogen, known to cause symptomatic disease in the immunocompromised hosts; however, it may occur in healthy individuals as well. Among the varied manifestations of the disease, involving skin, central nervous system and gastrointestinal systems, HSV esophagitis is a less studied entity from the Indian perspective. The aim of the study is to compare clinical, histologic and serologic data of HSV esophagitis patients. Materials and methods: 27 cases, proved to have HSV esophagitis on endoscopic biopsy were included, and the pertinent clinical and serologic characteristics were studied. Results: We found a male preponderance (p&lt;0.01), which has been a well-established risk factor. Other risk factors are retroviral coinfection, Type 2 Diabetes Mellitus, immunosuppression, chemoradiation etc. among others. Eleven patients had retroviral coinfection, with CD4 counts of &gt; 200/μL in all. Anti HSV 1 IgM antibody was most commonly detected on serology. HSV esophagitis affects immunocompromised patients more often than immunocompetent ones. Odynophagia and dysphagia are the most common symptoms. Histological evaluation for the characteristic inclusions helps in early diagnosis. The novelty of this study rests on the clinicopathological and serologic correlation, for a better understanding of the disease process, to prompt future large scale studies on the same. Conclusion: Herpes simplex esophagitis is most seen in immunocompromised patients. Apart from retroviral illness, other risk factors include diabetes mellitus, patients undergoing chemotherapy and other malignancy. CD4 counts in our series was &gt;200/μL, in contrast to the cutoff of &lt;200/μL described in literature.

Severe Skin and Soft Tissue Infection of Patients Admitted to Intensive Care Units

Skin and soft tissue infections (SSTIs) can occasionally progress to life-threatening conditions, such as septic shock, requiring intensive care unit admission. Their risk factors include diabetes mellitus, chronic renal failure, chronic vascular disease, malignancy, and acquired immune deficiency syndrome. However, early diagnosis is challenging due to initially benign skin lesions and the absence of systemic symptoms such as fever. This review focuses on severe bacterial infections such as necrotizing fasciitis, gas gangrene, and toxic shock syndrome, examining their etiology and management. These severe SSTIs should be understood for the early diagnosis, appropriate treatment, and improved patient outcomes. Dermatologists play a vital role in recognizing and managing these infections

Poncet rheumatism secondary to ceco-appendicular tuberculosis in systemic lupus erythematosus

Background. Poncet’s rheumatism (RP) is an aseptic reactive arthritis secondary to active tuberculosis. Systemic lupus erythematosus (SLE) and tuberculosis are intricately related with an increase in the risk of tuberculosis in SLE. We present an original case of Poncet’s disease secondary to appendicular tuberculosis in patient with lupus disease. Case report. A 36-year-old female was followed in internal medicine for systemic lupus. In September 2023, she suffered from digestive complaints and polyarthritis. Infectious investigation and microbiologic study of joint fluid was negative. She had tenderness on pressure on the right iliac fossa. The computed tomography (CT) found an appendicular mucocele. She underwent laparotomy with right colectomy. Macroscopic aspect revealed tumorous lesion suggestive for malignancy. Histological study concluded to granulomatous inflammation with epithelioid and gigantocellular granulomas with anhist necrosis. Ceco-appendicular tuberculosis was retained. The patient received the anti-tuberculosis therapy with good progress. Conclusions. Early recognition of atypical location of tuberculosis leads to initiate appropriate treatment especially in immune compromise statue patient.

Evaluation of Nurses’ Attitudes toward Human Immuno Deficiency

Background: HIV nursing protocols, including rapid HIV testing, face weaknesses such as improper data collection and ambiguity. To reduce stigmatization, interventions should promote the adoption of nursing practices that influence stigmatization experiences. The International Nursing Network for HIV Research recommends collaboration, global partnerships, and scientific work to increase nurses' impact in HIV research. Nurses' experiences with HIV/AIDS patients can impact their health and the spread of the virus. Barriers to HIV treatment include lack of knowledge, demotivation, resistance, and lack of adherence to treatment guidelines. Nurse involvement in HIV prevention is crucial for improving patient outcomes. Objective(s): This study aims to evaluate nurses' attitudes toward human Immuno deficiency. Methodology: A quasi-experimental design was conducted in 7 January 2024 to 7 May 2024, The study at Al Musayyib General Hospital in Babylon, Iraq, involved 100 nursing professionals in a health education program. The program aimed to improve nurses' understanding and attitudes towards HIV/AIDS. The program's effectiveness was assessed through questionnaires. Results: The study found that nurses aged 23-less than 30 years, predominantly female, had moderate attitudes towards the human immunodeficiency virus. However, there was no significant relationship between nurses' attitudes and sociodemographic variables or professional variables such as education, years of experience, knowledge development, or participation in training courses. The majority of nurses were urban residents. Conclusion: Healthcare professionals should therefore follow national infection prevention guidelines when working in hospitals. To increase nurses' understanding and proficiency in this area, policy designers ought to train them in infection prevention. Further research should include a qualitative study in order to obtain more detailed information. Recommendation: Institutions may enhance their knowledge of HIV care practices by conducting frequent training sessions for nursing staff, personalizing instructional materials, gauging and reviewing attitude levels, encouraging peer learning, and expanding the scope of research. In order to provide effective HIV care, this will assist nurses in expanding their knowledge and adjusting their attitude.

Evaluation of Nurses’ Attitudes toward Human Immuno Deficiency

Background: HIV nursing protocols, including rapid HIV testing, face weaknesses such as improper data collection and ambiguity. To reduce stigmatization, interventions should promote the adoption of nursing practices that influence stigmatization experiences. The International Nursing Network for HIV Research recommends collaboration, global partnerships, and scientific work to increase nurses' impact in HIV research. Nurses' experiences with HIV/AIDS patients can impact their health and the spread of the virus. Barriers to HIV treatment include lack of knowledge, demotivation, resistance, and lack of adherence to treatment guidelines. Nurse involvement in HIV prevention is crucial for improving patient outcomes. Objective(s): This study aims to evaluate nurses' attitudes toward human Immuno deficiency. Methodology: A quasi-experimental design was conducted in 7 January 2024 to 7 May 2024, The study at Al Musayyib General Hospital in Babylon, Iraq, involved 100 nursing professionals in a health education program. The program aimed to improve nurses' understanding and attitudes towards HIV/AIDS. The program's effectiveness was assessed through questionnaires. Results: The study found that nurses aged 23-less than 30 years, predominantly female, had moderate attitudes towards the human immunodeficiency virus. However, there was no significant relationship between nurses' attitudes and sociodemographic variables or professional variables such as education, years of experience, knowledge development, or participation in training courses. The majority of nurses were urban residents. Conclusion: Healthcare professionals should therefore follow national infection prevention guidelines when working in hospitals. To increase nurses' understanding and proficiency in this area, policy designers ought to train them in infection prevention. Further research should include a qualitative study in order to obtain more detailed information. Recommendation: Institutions may enhance their knowledge of HIV care practices by conducting frequent training sessions for nursing staff, personalizing instructional materials, gauging and reviewing attitude levels, encouraging peer learning, and expanding the scope of research. In order to provide effective HIV care, this will assist nurses in expanding their knowledge and adjusting their attitude.

Safety of different amphotericin B formulations among AIDS patients with invasive fungal disease: a retrospective observational study

We conducted a retrospective, observational study among acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis or talaromycosis to assess AmB formulations-related adverse events (AEs). Total 205 eligible patients were enrolled. Of them, 139 received AmB therapy, 51 received liposomal AmB (L-AmB) therapy, and 15 received AmB cholesteryl sulfate complex (ABCD) therapy. The incidences of total AEs between the AmB, L-AmB and ABCD group had no significant differences. The ABCD group had significantly higher incidences of hepatotoxicity and hematological toxicity than the AmB and L-AmB groups. The incidence of grade 3–4 hematological toxicity in the ABCD group was significantly higher than that in the AmB and L-AmB groups. Multinomial logistic regression models showed that compared with AmB, ABCD had a higher risk for the occurrence of grade 3–4 hematological toxicity (aOR = 43.924, 95%CI 6.296-306.418; p < 0.001). We demonstrated that ABCD was more prone to hepatotoxicity and hematological toxicity than AmB and L-AmB among AIDS patients, which is worth noting.

Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies.

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.

Molecular architecture of chitin and chitosan-dominated cell walls in zygomycetous fungal pathogens by solid-state NMR

Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our pathophysiological understanding of these infections, particularly the role of fungal cell walls in growth and immune response, remains limited. Here we conducted multidimensional solid-state NMR analysis to examine cell walls in five Mucorales species, including key mucormycosis causative agents like Rhizopus and Mucor species. We show that the rigid core of the cell wall primarily comprises highly polymorphic chitin and chitosan, with minimal quantities of β-glucans linked to a specific chitin subtype. Chitosan emerges as a pivotal molecule preserving hydration and dynamics. Some proteins are entrapped within this semi-crystalline chitin/chitosan layer, stabilized by the sidechains of hydrophobic amino acid residues, and situated distantly from β-glucans. The mobile domain contains galactan- and mannan-based polysaccharides, along with polymeric α-fucoses. Treatment with the chitin synthase inhibitor nikkomycin removes the β-glucan-chitin/chitosan complex, leaving the other chitin and chitosan allomorphs untouched while simultaneously thickening and rigidifying the cell wall. These findings shed light on the organization of Mucorales cell walls and emphasize the necessity for a deeper understanding of the diverse families of chitin synthases and deacetylases as potential targets for novel antifungal therapies.

Transplantation for immune dysregulatory disorders: current themes and future expectations.

Primary immune regulatory disorders (PIRDs) are an increasing indication for hematopoietic stem cell transplant (HCT) in pediatric patients. Here, we provide an updated overview of HCT for PIRDs, and discuss future avenues for improvement in outcomes. There are now more than 50 described monogenic PIRDs, which impact all aspects of immune tolerance, regulation, and suppression. Disease characteristics are highly variable, and HCT remains the only option for cure. We review advances in targeted therapies for individual PIRDs, which have significantly improved outcomes and the ability to safely bridge to transplant. Additionally, advances in GVHD prevention, graft manipulation, personalized conditioning regimens, and supportive care have all increased survival after HCT. The high inflammatory state increases the risk of nonengraftment, rejection, and autologous reconstitution. Therapy to reduce the inflammatory state may further improve outcomes. In addition, although younger patients with fewer comorbidities have better outcomes, the clinical courses of these diseases may be extremely variable thereby complicating the decision to proceed to HCT. HCT for PIRDs is a growing consideration in cell therapy. Yet, there remain significant gaps in our understanding of which patients this curative therapy could benefit the most. Here, we review the current data supporting HCT for PIRDs as well as areas for future improvement.

Borrelia burgdorferi infections in children and adolescents in Switzerland - a seroprevalence study 2023/2024 (BOBUINCA).

Lyme borreliosis is one of the most prevalent tick-borne diseases in Europe. Studies on seroprevalence of Borrelia burgdorferi IgG antibodies in children are rare. The aim of this study was to determine the seroprevalence of B. burgdorferi IgG antibodies in children and adolescents residing in North-Western Switzerland and neighbouring countries. Prospective cross-sectional observational single-centre study using left-over plasma of asymptomatic paediatric patients. Included were children aged 1-17 years living in North-Western Switzerland and bordering areas of France and Germany. Excluded were children with symptoms of Lyme borreliosis or a chronic disease possibly affecting plasma antibodies (immunodeficiency syndrome, systemic lupus erythematosus) or with such medication (e.g., intravenous immunoglobuline treatment, allogenic stem cell transplantation, immunosuppressive treatment) as well as refugees seeking asylum. IgG antibodies against B. burgdorferi were measured by ELISA and positive or borderline results by line blot. Positivity was defined as scenario 1: ELISA positive/line blot positive or borderline OR ELISA borderline/line blot positive. Scenario 2: ELISA positive or borderline/line blot positive. A multivariable logistic regression model for seropositivity was applied. 962 children were included (mean age 9.63 years, standard deviation 5.01, 54.5% males). Seroprevalence for scenario 1 was 13.3% (95% CI: 11.2-15.6) and for scenario 2 11.2% (95% CI: 9.3-13.4). Seroprevalence (scenario 1) was comparable for age groups, sex and rural versus urban residence. This study shows an increased seroprevalence for B. burgdorferi in the paediatric age compared to previous childhood studies. We also found an increased risk for B. burgdorferi infection at young age.

Characteristics of Endemic Mycoses Talaromyces marneffei Infection Associated with Inborn Errors of Immunity.

Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children. We conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies. A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected. Fifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals. The XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes.

Entangled Connections: HIV and HPV Interplay in Cervical Cancer-A Comprehensive Review.

Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment.

Human immunodeficiency virus cascade-continuum of care stages and outcomes in a hospital in southern Brazil.

The human immunodeficiency virus (HIV) continuum of care cascade illustrates the 90-90-90 goals defined by the Joint United Nations Program on HIV/acquired immunodeficiency syndrome (UNAIDS). The care cascade includes the following five steps: Diagnosis, linkage to care, retention in care, adherence to antiretroviral therapy (ART), and viral suppression. To elaborate the HIV cascade of patients diagnosed with HIV at the Nossa Senhora da Conceição Hospital (HNSC) and to determine possible local causes for the loss of patients between each step of the cascade. This retrospective cohort study included patients diagnosed with HIV infection from January 1, 2015 to December 31, 2016 and followed up until July 31, 2019. The data were analyzed by IBM SPSS software version 25, and Poisson regression with simple robust variance was used to analyze variables in relation to each step of the cascade. Variables with P < 0.20 were included in multivariable analysis, and P < 0.05 was considered significant. Pearson's χ 2 test was used to compare the groups of patients followed up at the HNSC and those followed up at other sites. The results were lower than those expected by the UNAIDS, with 94% of patients linked, 91% retained, 81% adhering to ART, and 84% in viral suppression. Age and site of follow-up were the variables with the highest statistical significance. A comparison showed that the cascade of patients from the HNSC had superior results than outpatients, with a significant difference in the last step of the cascade. The specialized and continued care provided at the HNSC was associated with better results and was closer to the goals set by the UNAIDS. The development of the HIV cascade using local data allowed for the stratification and evaluation of risk factors associated with the losses occurring between each step of the cascade.

Pulmonary and Hepatic Tuberculosis in a Single Individual

Tuberculosis (TB) is a contagious bacterial infection caused by the Mycobacterium tuberculosis bacterium. It primarily affects the lungs but can also target other parts of the body, known as extra pulmonary tuberculosis (EPTB). TB spreads through the air when an infected person coughs, sneezes, or talks.[1] Asia bears a significant burden of TB cases worldwide, accounting for approximately 60% of the global TB incidence. The region's large population, varying health systems, and socioeconomic factors contribute to this high prevalence. Countries like India, China, Indonesia, and Bangladesh have particularly high TB rates.[1,2] India has the highest number of TB cases globally, making it a major concern for public health. Factors such as poverty, overcrowding, inadequate healthcare infrastructure, and limited access to diagnostics and treatment contribute to the high prevalence. The Indian government has implemented various initiatives to combat TB and improve prevention, diagnosis, and treatment services.[3] Despite the rapid decline in tuberculosis (TB) prevalence globally following the introduction of anti-TB medications in the 1940s, recent years have witnessed a resurgence in TB incidence rates. This resurgence can be attributed to various factors including governmental complacency, inadequate public health interventions, HIV coinfection, intravenous drug abuse, multidrug resistance, and an increasing number of immunocompromised individuals.[1] As a consequence, hepatic tuberculosis, which is part of disseminated tuberculosis, has been observed in 50-80% of cases, reflecting the growing prevalence of TB. Hepatic TB often presents challenges in clinical diagnosis due to its atypical symptoms and imaging findings, leading to potential misdiagnosis and delayed treatment initiation.[2-3] Through our literature review, it became apparent that the majority of existing studies are comprised of case reports, highlighting a lack of comprehensive understanding in diagnosing and treating hepatic tuberculosis.[4] An immunocompromised host refers to an individual with a weakened immune system, making them more susceptible to infections and diseases. This can result from conditions such as HIV/AIDS, chemotherapy, organ transplantation, or certain medications that suppress the immune response.[5] Immunocompromised individuals face a higher risk of contracting TB due to their weakened immune defenses. The risk of developing active TB disease is significantly increased in this population. Timely diagnosis and appropriate management are crucial to prevent serious complications and mortality.[5] In immunocompromised hosts, TB can manifest in various extra pulmonary sites outside the lungs. Common sites of EPTB involvement include the lymph nodes, bones and joints, central nervous system, genitourinary system, gastrointestinal tract, and skin. Prompt recognition and appropriate treatment are essential to prevent complications and morbidity associated with EPTB.[6] By understanding the prevalence of TB in Asia and India, the impact on immunocompromised individuals, the definition of disseminated TB, and the sites of EPTB in immunocompromised hosts, we can better address and manage this public health issue. Increased awareness, early diagnosis, and effective treatment strategies are crucial in reducing the burden of TB and improving patient outcomes.[7]