Compromised Cellular Immunity Research Articles

Frequency of cryptococcal antigenemia in hiv treatment naïve patients with CD4 count below 200/ml

Background: Cryptococcosis is a dangerous opportunistic fungal infection that poses a significant threat to individuals with advanced HIV/AIDS and compromised cellular immunity. The objective was to determine the frequency of asymptomatic cryptococcal antigenemia in treatment naïve HIV patients. Material and Methods: This cross-sectional study was conducted at The Indus Hospital and Health Network, Karachi from July to December 2022. We included all consecutive HIV patients of age > 18 years, either gender, who were treatment naïve, with CD4 counts ≤200/μL, and did not have any symptoms of cryptococcal infection. Cryptococcal antigen (CrAg) was tested in blood based on the Direct Agglutination test. Results: A total of 100 HIV patients were enrolled. The mean age was 35.12 ± 10.93 years. The majority (78%) of the subjects were males, and 2/3rd were sexually active; exposure to birds was identified in 31% of patients. Most of the patients enrolled belonged to WHO HIV stage 1 (61%), followed by stage 4 (30%). The median CD4 count was 103.5 (IQR: 56.5 – 126.5) /μL. 48 patients had CD4 count between 101 to 200/μL, while 51 patients had CD4 count ≤100/μL. Only 2 patients were found to have CrAg positive making an overall prevalence of 2%. Both patients had a CD4 count ≤ 100/μL (n = 2/51, 3.9%). 30% of patients had other opportunistic co-infections (n = 30). Conclusion: The prevalence of asymptomatic cryptococcosis in the treatment naïve HIV is low in the Pakistani population. A routine CrAg screening can be individualized and avoided in selected patients with CD4 count >100/μL in a resource-limited country like Pakistan. Keywords: AIDS, HIV stages, Asymptomatic, Opportunistic infection.

Infection of the entomopathogenic fungus Metarhizium rileyi suppresses cellular immunity and activates humoral antibacterial immunity of the host Spodoptera frugiperda.

Metarhizium rileyi is an entomopathogenic fungus with promising potential for controlling agricultural pests, including Spodoptera frugiperda. Following penetration of the host through the cuticle, M. rileyi cells transform into in vivo blastospores or hyphal bodies, propagating within the hemocoel. However, the strategies and molecular mechanisms by which M. rileyi survives upon exposure to the powerful insect immune system remain unclear. We determined the pathogenicity of M. rileyi and found that either conidial immersion or blastospore injection significantly decreased S. frugiperda survival in a dose-dependent manner. Injection of M. rileyi blastospores decreased the number of S. frugiperda hemocytes and impaired host cellular reactions such as nodulation, encapsulation and phagocytosis. Blastospore injection led to increased antibacterial activity in plasma at 48 h post-injection (hpi). RNA-sequencing analyses identified a large number of antimicrobial peptide genes upregulated in the fat body of M. rileyi-infected larvae at 48 hpi, which may be attributable to the activation of Toll and IMD signaling pathway. This study demonstrates that the compromised cellular immunity of the insect host is due to the marked decrease in hemocytes and impaired cellular cytoskeletons, which may facilitate early infection by M. rileyi. Late in the course of infection, the enhanced antibacterial activity of plasma, which may be in response to intestinal evading bacteria, cannot inhibit hyphal growth in hemolymph. Our data provide a comprehensive resource for exploring the molecular mechanism employed by M. rileyi to overcome S. frugiperda immunity. © 2022 Society of Chemical Industry.

The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Timely Diagnosis of Histoplasmosis in Non-endemic Countries: A Laboratory Challenge.

Human histoplasmosis is a fungal infection caused by the inhalation of microconidia of the thermally dimorphic fungi Histoplasma capsulatum. Autochthonous cases of histoplasmosis have been diagnosed in almost every country, but it is considered an endemic infection in specific areas of the world. Many of them are popular travel destinations or the source of migratory movements. Thus, the vast majority of the registered cases in non-endemic countries are imported. They correspond to people having been exposed to the fungus in endemic locations as immigrants, expatriates, transient workers or tourists, with reported cases also associated to organ donation. Misdiagnosis and delays in initiation of treatment are not uncommon in cases of imported histoplasmosis. They are associated to high fatality-rates specially in patients with compromised cellular immunity in which progressive disseminated forms develop. The diagnosis of this infection in non-endemic countries is hampered by the lack of clinical suspicion and a dearth of available diagnostic tools adequate to offer rapid and accurate results. Non-culture-based assays such as nucleic-acid amplification tests present as a suitable alternative in this situation, offering improved sensitivity and specificity, shortened turnaround time, and increased biosafety by avoiding culture manipulation. In non-endemic regions, molecular techniques are being used mainly in laboratories from countries that have registered an increase in the incidence of imported cases. However, the number of published techniques is limited and lack consensus. Efforts are currently under way to standardize nucleic acid amplification-based techniques for its implementation in areas registering a rising number of imported cases.

Interferon-γ-dependent protection against Neospora caninum infection conferred by mucosal immunization in IL-12/IL-23 p40-deficient mice

We have recently demonstrated the effectiveness of an intranasal immunization approach against Neospora caninum infection in immunosufficient mice. Generated evidence indicated that antibodies could be mediating the observed protection. We similarly immunized IL-12/IL-23 p40 chain-deficient (Il12b−/−) mice, which have impaired cellular immunity, to further explore the host protective mechanism conferred by the used immunization strategy. The immunized mice presented lower parasitic burdens after intraperitoneal infection with N. caninum and also had elevated levels of parasite-specific antibodies. However, passive immunization with antibodies purified from immunized donors conferred only limited protection to infected Il12b−/− recipients. Despite their intrinsic IL-12 deficiency, the immunized Il12b−/− mice mounted a parasite-specific immune response that was mediated by interferon-γ (IFN-γ). Neutralization of IFN-γ in the immunized mice abrogated the observed protective effect of the immunization. These results show altogether that the used immunization strategy overcome the cellular immunity defect of Il12b−/− mice and conferred protection from N. caninum infection. The observed protective effect was predominantly mediated by IFN-γ and to a lesser extent but non-negligibly by IgG antibodies. These results also highlight that in a host with compromised cellular immunity, the immune response against intracellular pathogens could be markedly boosted by immunization.

Histoplasma Capsulatum: Mechanisms for Pathogenesis.

Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts can be clinically silent or it can lead to life-threatening systemic disease, which can occur in immunologically intact or deficient hosts, albeit severe disease is more likely in the setting of compromised cellular immunity. H. capsulatum yeast cells are highly adapted to the mammalian host as they can effectively survive within intracellular niches in select phagocytic cells. Understanding the biological response by both the host and H. capsulatum will facilitate improved approaches to prevent and/or modify disease. This review presents our current understanding of the major pathogenic mechanisms involved in histoplasmosis.

An Itchy Problem: A Clinical Case of Crusted Scabies.

Scabies is an infestation of the skin by the mite Sarcoptes scabiei. A more severe form called crusted or Norwegian scabies may occur in immunosuppressed patients and the elderly. Crusted scabies mostly differs from normal scabies by the exuberance of its lesions, body distribution and high contagiousness, and requires different and more prolonged treatment. Early recognition of the lesions and isolation precautions are crucial for disease control and prevention of transmission. The authors describe a clinical case of crusted scabies with pruritus and exuberant cutaneous lesions.LEARNING POINTSCrusted scabies is an infestation of the skin by the mite Sarcoptes scabiei that is highly contagious and results in an intensely pruritic eruption with exuberant cutaneous lesions.Crusted scabies occurs in patients with AIDS, lymphoma or compromised cellular immunity, and sometimes in older patients. It is characterized by an elevated burden of mites and does not have a characteristic distribution pattern.This disease requires strict isolation measures and treatment which differs from and is more prolonged than for scabies.

A nationwide survey of common viral infections in childhood among patients with primary immunodeficiency diseases

Patients with primary immunodeficiency diseases (PID) are highly susceptible to various microorganisms. However, no population-based studies have been performed among common viral pathogens, such as respiratory syncytial virus (RSV), rotavirus (RV), varicella-zoster virus (VZV) and influenza virus (IV). The objective of this study was to reveal the clinical burden of these four infections among PID patients in Japan. We conducted a nationwide survey by sending questionnaires to 898 hospitals with pediatric departments throughout Japan. Nine hundred ten PID patients from 621 hospitals were registered (response rate: 69.2%). Fifty-four of the patients were hospitalized due to these viral infections. The durations of hospitalization due to RSV and RV infections differed significantly in the PID patients with and without cellular immunodeficiency (12.0 vs 6.5 days, p=0.041; and 14.0 vs 6.0 days, p=0.031, respectively). There was no significant difference in the duration of hospitalization in PID patients with and without cellular immunodeficiency who were hospitalized with IV infections (7.3 vs 6.1 days, p=0.53). Special attention should be paid to PID patients with compromised cellular immunity who present with RSV and RV infection due to their high risk for severe disease.

Progressive multifocal leukoencephalopathy and black fungus in a patient with rheumatoid arthritis without severe lymphocytopenia

Introduction:Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating brain infection caused by JC polyomavirus (JCV), primarily seen in patients with severely compromised cellular immunity. Clinical presentation varies depending on the affected white matter. PML prognosis is variable and effective treatments are lacking.Case presentation:A 75-year-old Chinese woman with type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis, treated with low-dose methotrexate and prednisolone for 2.5 years, developed a Pleurostomophora richardsiae infection of her left arm. After 6 months of treating this rare black fungus infection with voriconazole, surgery and immunosuppression discontinuation, she presented with progressive afebrile encephalopathy with right-sided hemiparesis. There were no signs of inflammation or metabolic abnormalities. Brain magnetic resonance imaging revealed diffuse frontal white matter lesions and a cerebrospinal fluid PCR confirmed PML due to JC virus. Severe lymphopenia was never present, and at PML diagnosis, CD4 and CD8 T-cell counts were 454 mm−3 and 277 mm−3. CD8 T-cells were able to respond to JCV VP1 peptide stimulation with TNFα secretion. Peripheral B-cell count was only 8 mm−3. Mirtazapine and Maraviroc were started, but unfortunately, she rapidly deteriorated and died 5 weeks after PML diagnosis.Conclusion:Although peripheral lymphocyte counts were never low and CD4 T-cell count was close to normal, the persistent black fungus infection was a hallmark of severely compromised cellular immunity. The unexpected extremely low absolute B-cell count might suggest a protective role for B-cells. The paradoxical, clinical PML onset months after immunosuppressive discontinuation suggests that it was only discovered in the context of an immune reconstitution inflammatory syndrome.

Clostridium difficile in a HIV-infected cohort

Clostridium difficile is the most commonly reported infectious diarrhoea in HIV-infected patients in the United States. We set out to determine the incidence, risk factors and clinical presentation of C. difficile infections (CDIs) in a cohort of HIV-infected individuals. We performed a nested, case-control analysis with four non-CDI controls randomly selected for each case. We assessed the incidence of CDI in the Johns Hopkins HIV Clinical Cohort between 1 July 2003 and 31 December 2010. Incident cases were defined as first positive C. difficile cytotoxin assay or PCR for toxin B gene. We used conditional logistic regression models to assess risk factors for CDI. We abstracted data on the clinical presentation and outcomes from case chart review. We identified 154 incident CDI cases for an incidence of 8.3 cases per 1000 patient years. No unique clinical features of HIV-associated CDI were identified. In multivariate analysis, risk of CDI was independently increased for CD4 cell count of 50 cells/μl or less [adjusted odds ratio (AOR) 20.7, 95% confidence interval (CI) 2.8-151.4], hospital onset CDI (AOR 26.7, 95% CI 3.1-231.2) and use of clindamycin (AOR 27.6, 95% CI 2.2-339.4), fluoroquinolones (AOR 4.5, 95% CI 1.2-17.5), macrolides (AOR 6.3, 95% CI 1.8-22.1), gastric acid suppressants (AOR 3.1, 95% CI 1.4-6.9) or immunosuppressive agents (AOR 6.8, 95% CI 1.2-39.6). The incidence of CDI in HIV-infected patients was twice that previously reported. Our data show that compromised cellular immunity, as defined by CD4 cell count of 50 cells/μl or less, is a risk factor for CDI. Clinicians should be aware of the increased CDI risk, particularly in those with severe CD4 cell count suppression.

Disseminated bread yeast fungaemia in a baker's wife with acute myeloid leukaemia

A 58-year-old baker's wife was diagnosed with acute myeloid leukaemia. Induction therapy was initiated with idarubicin, cytarabine and clofarabine (Dutch Trial Registry #NTR2187), with concomitant prophylactic use of ciprofloxacin, trimethoprim-sulfamethoxazole, valaciclovir and amphotericin B oral suspension. Routine surveillance cultures from the oral cavity were positive for fluconazole-sensitive yeasts, but no other commensal microorganisms. Soon after induction treatment, the patient developed abdominal pain and febrile neutropenia. Abdominal ultrasound examination identified multiple hypodense lesions in the liver (left) and the spleen. A liver biopsy was performed, showing fungal micro-organisms (right, periodic acid-Schiff-diastase stain). Polymerase chain reaction for fungal 18S ribosomal RNA was performed and subsequent sequencing identified Saccharomyces cerevisiae, also known as baker's yeast. In our patient, work-related intestinal colonization most likely preceded baker's yeast invasion of the intestinal wall during chemotherapy-induced neutropenic enterocolitis, eventually leading to fungaemia. About 1% of patients with haematological malignancies are colonized with S. cerevisiae at diagnosis. Symptomatic S. cerevisiae infections are rare, but have been described in critically ill and immunocompromised patients. The combination of neutropenic enterocolitis and compromised cellular immunity after clofarabine treatment may have put our patient at an increased risk of developing symptomatic fungaemia. After failure of empirical treatment with voriconazole, she was successfully treated with caspofungin.

Infección asociada a catéter central por Cryptococcus laurentii en niño críticamente enfermo: a propósito de un caso y revisión del tema

Cryptococcosis is a fungal infection that predominantly affects patients with compromised cellular immunity. Cryptococcus neoformans is the most common pathogen of this class. Endovascular catheter-related infection is a rare entity described for Cryptococcus laurentii and, in exceptional cases, for C. neoformans. A case of a 3-month-old child with adenovirus acute bronchiolitis which lead to respiratory failure requiring inotropy and developing multiple infectious complications is presented. Cryptococcus laurentii was isolated in the culture from the tip of the central catheter, which could not be obtained in blood cultures. He was treated with amphotericin B in a cumulative dose of 10 mg/kg with negative control cultures. From a respiratory point of view, evolution was not good, with a failure from mechanical ventilation and posterior death.

Subclinical Dissemination of Coccidioidomycosis in a Liver Transplant Recipient

Coccidioidomycosis is common in the southwestern United States, northern Mexico, and areas of South America. Coccidioides immitis and Coccidioides posadasii form arthroconidia that, if inhaled, can cause respiratory infection. Rarely, the organism disseminates throughout the body, causing disease in bones, lymph nodes, skin, joints, and brain in most severe cases. Certain populations are at higher risk for dissemination, including persons with compromised cellular immunity. This group includes patients with human immunodeficiency virus, patients undergoing immunosuppression for rheumatologic disorders, and patients receiving antirejection therapy after organ transplant. For patients undergoing a solid organ transplant in endemic areas, screening for past or present coccidioidal disease is completed pretransplantation. Those with known disease are given triazole therapy to prevent reactivation of disease posttransplantation. Usually, transplantation is postponed if the disease is active. We present a patient with known, active coccidioidomycosis who underwent successful liver transplant and later had subclinical posttransplantation peritoneal dissemination.

Infectious Risk of Continuous Peripheral Nerve Blocks

Infectious Risk of Continuous Peripheral Nerve Blocks

Disseminated infection due to Mycobacterium chelonae with scleritis, spondylodiscitis and spinal epidural abscess

Mycobacteria other than tuberculosis (MOTT) have a low incidence as pathogens in human pathology. The most frequent clinical expression is the disseminated disease in subjects with compromised cellular immunity. Bacteriological characteristics in culture can generate confusion with other pathogens, which delays the appropriate diagnosis and treatment. We present a case of a disseminated infection due to Mycobacterium chelonae with scleritis, spondylodiscitis and spinal epidural abscess in a man with a medical background of cellular immunity deficit induced by therapeutic drugs. The antibiotic scheme of twenty-one weeks, during the follow-up period, controlled the infection, however, the optimum duration of treatment has not been established.

Safety and immunogenicity of a live-attenuated auxotrophic candidate vaccine against the intracellular pathogen Rhodococcus equi

Rhodococcus equi causes serious pneumonia in neonatal foals and is an opportunistic pathogen of people with compromised cellular immunity. No effective vaccine against R. equi disease in foals is available. We tested the safety and immunogenicity of a live, fully attenuated riboflavin auxotrophic candidate vaccine strain of R. equi (R. equi rib-). We demonstrated that R. equi rib- is immunogenic and capable of inducing IFN-gamma responses in immunocompetent BALB/c mice, yet it is safe even in an immunocompromised SCID mouse infection model. Moreover, it protects immunocompetent mice against virulent R. equi challenge. In foals, R. equi rib- was likewise safe and stimulated serum R. equi-specific immune responses. A preliminary immunization strategy did not afford protection against virulent R. equi challenge and therefore, optimization of the vaccine formulation and or vaccination protocol will be necessary.

A syndrome of immunodeficiency, autoimmunity, and spondylometaphyseal dysplasia

We treated a 5-year-old boy, in our hospital in south India, who had a history of recurrent respiratory infections, tuberculosis, and severe varicella infection. He was short in build and a radiological examination revealed evidence of spondylometaphyseal dysplasia. Investigation of the immune system was suggestive of compromised cellular immunity. Immunofluorescence and immunoblot assay for antibodies detected underlying multiple disorders such as systemic lupus erythematosus (SLE), autoimmune thrombocytopenia, and juvenile rheumatoid arthritis (JRA). Roifman et al. described a similar syndrome in 2000 and 2003, which was characterized by spondylometaphyseal dyplasia, combined immunodeficiency, and autoimmunity and called it Roifman-Costa syndrome (OMIM 607944). Hence a diagnosis of Roifman-Costa syndrome was made. Ours shall be the first report of such a condition from the Indian subcontinent and hence the communication.

Cerebral toxoplasmosis in a patient with common variable immunodeficiency

Cerebral toxoplasmosis is commonly seen as an opportunistic disease in patients with compromised cellular immunity.1 Thus far, purely humoral immune defects, as seen in common variable immunodeficiency (CVID), have not been described to facilitate cerebral toxoplasmosis. Here, we present a patient with intracerebral mass lesions caused by toxoplasmosis, which were apparently facilitated by a humoral immune defect with combined immunoglobulin (Ig) A, IgG, and IgM deficiency. A 52-year-old woman subacutely developed gait difficulties, impaired upper limb coordination, and swallowing and articulation difficulties. The patient had a history of CVID, which had been substituted with 10 g Igs every month. Four weeks before neurologic symptoms, an attack of autoimmune hemolytic anemia was managed with prednisolone in a dosage that was tapered from 100 to 30 mg/d. Clinically, the patient had moderate spastic tetraparesis and severe dysarthria and dysphagia. C-reactive protein was slightly elevated to 1.1 mmol/L. Temperature, white blood cells, and differential hemogram revealed no abnormalities. Lymphocytic subpopulations were normal, except for an elevation of CD19+ B cells to 0.63/nL (normal range, 0.1 to 0.4). Igs were decreased with IgA <5 …

Complicated and fatal Strongyloides infection in Canadians: risk factors, diagnosis and management.

Strongyloidiasis, which is caused by the nematode Strongyloides stercoralis, is a common and persistent infection, particularly in developing countries. In the setting of compromised cellular immunity, it can result in fulminant dissemination with case-fatality rates of over 70%. The majority of new Canadian immigrants come from countries where Strongyloides is highly endemic; therefore, the burden of Strongyloides may be underappreciated in Canada. Because early diagnosis and therapy can have a marked impact on disease outcome, screening for this infection should be considered mandatory for patients who have a history of travel or residence in a disease-endemic area and risk factors for disseminated disease (e.g., corticosteroid use and human T-lymphotropic virus type I infection).

Rescue of CD8 T cell–mediated antimicrobial immunity with a nonspecific inflammatory stimulus

Reconstitution of protective immunity by adoptive transfer of pathogen-specific T cells has been successful in patients with compromised cellular immunity. The in vivo effectiveness of in vitro–expanded CD8 CTLs is variable, however. For example, adoptively transferred Listeria monocytogenes–specific CD8 CTLs only confer protective immunity if challenge infection occurs within 48 hours of T cell infusion. Herein we show that transferred CTLs persist in lymphoid compartments for many weeks, but that their response to bacterial challenge decreases during the first week following transfer. While T cells transferred less than 48 hours before infection proliferate, those transferred 7 days before infection die. Remarkably, treatment of mice with anti-CD40 at the time of T cell infusion reprograms transferred T cells, allowing them to proliferate and confer protective immunity upon bacterial challenge 7 days later. Our study demonstrates, for the first time to our knowledge that CD40-mediated stimuli can influence CD8 T cell activation independent of concurrent antigen exposure. The ability to modulate long-term responsiveness of CD8 T cells with a transient, nonspecific inflammatory stimulus has importation implications for adoptive immunotherapy.