Advanced Acquired Immunodeficiency Syndrome Research Articles

Mycobacterium genavense Mycobacteremia in a Host with Advanced AIDS

Abstract Nontuberculous mycobacteria and Pneumocystis jirovecii pneumonia (PCP) are important opportunistic pathogens in patients with advanced immunodeficiency. We present a case of a 38-year-old male who presented with fever, cough, breathlessness, and constitutional symptoms and, on evaluation, was found to have advanced acquired immunodeficiency syndrome (AIDS), possible PCP, and mycobacteremia caused by Mycobacterium genavense. We report what seems to be the first case report of M. genavense mycobacteremia in a host with AIDS from India.

Compartmentalized T cell profile in the lungs of patients with HIV-1-associated pulmonary Kaposi sarcoma.

Pulmonary Kaposi sarcoma (pKS) caused by Human herpesvirus 8 (HHV-8) is a devastating form of KS in patients with advanced acquired immunodeficiency syndrome (AIDS) and is associated with increased morbidity and mortality. Blood T cells play a central role in the response of HIV-1 and HHV-8. However, little information is available on T cells in the alveolar space of HIV-1-associated pKS patients.Therefore, we examined CD8+ and CD4+ T cells in the alveolar space in comparison with the blood of patients with pKS. We recruited 26 HIV-1 positive patients with KS, including 15 patients with pKS. Bronchoalveolar lavage (BAL) cells and blood mononuclear cells were analyzed for T cell memory phenotypes, surface markers associated with exhaustion, and intracellular cytokine staining (ICS) using flow cytometry. HIV-1 and HHV-8 viral loads were measured in plasma by quantitative PCR.BAL T cells showed reduced inflammatory capacities and significantly diminished polyfunctionality compared to blood T cells from patients with pKS. This was not accompanied by increased expression of exhaustion markers, such as TIM-3 and PD-1.More importantly, we found a negative correlation between the production of MIP1-β and TNF-α in T cells in BAL and blood, indicating compartmentalised immune responses to pKS and accentuated chronic HIV-1/HHV-8 pathogenesis via T cells in the lungs of people with pKS.

Clinical characteristics and risk factors for poor prognosis among HIV patients with Talaromyces marneffei bloodstream infection

BackgroundTalaromyces marneffei (TM) bloodstream infection is common in Acquired Immunodeficiency Syndrome (AIDS) patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyzed the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determined the outcomes of hospitalization after diagnosis in our hospital over the past 5 years.MethodsFrom January 2015 to July 2020, 87 cases of TM detected by blood culture in patients admitted to our center were collected. The admission complaints, blood cells, biochemistry, CD4 and CD8 cell counts and 1,3-β-D-glucan (BDG), procalcitonin (PCT), CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis (60 cases). Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM turnaround in blood culture. The difference was statistically significant when the P value was < 0.05.ResultsA total of 87 patients were collected, with a median age of 34 years, a median hemoglobin of 94 g/L and CD4 count of 7/μl. The rate of TM bloodstream infection among all in-hospital patients increased from 0.99% in 2015 to 2.09% in 2020(half year). Patients with TM bloodstream infection with CD8 count < 200/μl had a 12.6-fold higher risk of poor prognosis than those with CD8 count > 200/μl (p = 0.04), and those with BDG < 100 pg/mL had a 34.9-fold higher risk of poor prognosis than those with BDG > 100 pg/mL (p = 0.01).ConclusionsTM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/μl is with an increased risk of poor prognosis.

Mucocutaneous Histoplasmosisin an Immunocompetent Patient: A CaseReport from Non-Endemic Region in North India

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; called disseminated histoplasmosis, Histoplasmosis is common among AIDS patients because of their suppressed immunity. Pulmonary histoplasmosis and disseminated histoplasmosis involving the skin can be a major cause of morbidity and mortality in patients with advanced acquired immunodeficiency syndrome and in patients with lymphoma. A 45 year old male, farmer by occupation, presented with multiple, painful nodules and ulcers over the tongue, angle of mouth and lips and dysphagia for 6 months. He also had numerous painful papulo nodular eruptions on head, trunk, and extremities for 5 months. The lesion on the palate started as a small swelling which gradually increased in size and then ulcerate. After appropriate analysis the patient was treated with Itraconazole because of its easy availability and lesser cost.

Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa.

Cryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) viremia may be associated with increased mortality in persons living with HIV who have tuberculosis. It is unknown whether concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections. We prospectively enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010-2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival rates among those with and without CMV viremia. Of 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL, interquartile range [IQR] 259-2390). All samples tested were positive on immunoglobin G serology. The median CD4+ T cell count was 19 cells/µL (IQR 9-70) and did not differ by the presence of CMV viremia (P = .47). The 10-week mortality rates were 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (hazard ratio 2.19, 95% confidence interval [CI] 1.07-4.49; P = .03), which remained significant after a multivariate adjustment for known risk factors of mortality (adjusted hazard ratio 3.25, 95% CI 1.49-7.10; P = .003). Serum and cerebrospinal fluid cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation responses did not differ between groups. Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with an over 2-fold higher mortality rate. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect an underlying immune dysfunction (ie, cause vs effect). NCT01075152.

Drug resistance and pathogenic spectrum of patients coinfected with nontuberculous mycobacteria and human-immunodeficiency virus in Chengdu, China.

Background:Human-immunodeficiency virus (HIV) infection is increasing worldwide and nontuberculous mycobacteria (NTM) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. Data on patients coinfected with HIV and NTM are limited. Thus, this study aimed to analyze the clinical characteristics, drug resistance, and pathogen spectrum of patients coinfected with both HIV and NTM in the Chengdu area of China.Methods:Data of 59 patients coinfected with both HIV and NTM collected from the Public Health Clinical Center of Chengdu, between January 2014 and December 2018, were analyzed. NTM drug sensitivity testing was performed using the microporous plate ratio method. Data were analyzed using SPSS 19.0, and the change in drug resistance rate was analyzed using the chi-square (χ2) test.Results:Seven species/complex of NTM were identified from patients coinfected with HIV and NTM in this study, with Mycobacterium avium–intracellulare complex (52.5%) and M. kansasii (27.1%) as the predominant species. Male patients were more affected 50/59 (84.7%); the mean age of the 59 cases was 45 years. The clinical characteristics mainly included anemia (86.4%), cough and expectoration (79.7%). The baseline CD4 count was <50 cells/μL (84.7%). Patients were mainly in advanced acquired immunodeficiency syndrome (AIDS) stage. Chest imaging mainly showed patchy shadows (42.4%) and nodules (32.2%), with various degrees of AIDS-defining diseases. The drug resistance of NTM was severe, and the rate of isoniazid resistance (100.0%) was the highest, followed by rifampicin (94.9%), streptomycin (94.9%), ofloxacin (93.2%), and others. Ethambutol (52.5%) and clarithromycin (33.9%) were relatively low. No significant difference was found in the drug resistance rate of NTM strain against nine antituberculosis drugs in 5 years (P > 0.05).Conclusions:The immune level of patients coinfected with HIV and NTM is low in advanced AIDS stage; more male are affected in patients who are mainly infected with MAC and M. kansasii and with serious drug resistance. The drug resistance rate of ethambutol and clarithromycin is relatively low.

Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation

PurposeTo describe a case of disseminated cryptococcal meningitis with multifocal choroiditis and provide optical coherence tomography (OCT) findings correlated with described histopathology in a patient with advanced acquired immunodeficiency syndrome (AIDS). ObservationsThe patient was a 54-year-old man with AIDS who presented with dyspnea and headache followed by acute vision loss. OCT demonstrated a lesion with a small area of fluid that was limited by a more prominent and irregular external limiting membrane with underlying nodular choroidal thickening, mild RPE disorganization, and hyperreflectivity of the overlying photoreceptor layer. Patient was found to have disseminated cryptococcal infection and passed away despite aggressive therapy. Autopsy was performed including bilateral enucleation and a Cryptococcus lesion was confirmed on histopathology. Conclusion and importanceThis case highlights the clinical, imaging, and histopathologic findings of cryptococcal choroiditis and provides a review of the updated treatment recommendations for disseminated infection in a patient with advanced AIDS. Although currently fundoscopy has proven most useful in directing the diagnostic algorithm in choroiditis in the setting of advanced immunosuppression, OCT may provide insight into the spread of Cryptococcus within the eye.

Fatal disseminated cytomegalovirus infection with necrotizing oophoritis in a patient with acquired immunodeficiency syndrome

Disseminated human cytomegalovirus (CMV) disease occurs mainly as a congenital infection and among immunocompromised hosts. Patients with acquired immunodeficiency syndrome (AIDS) are at increased risk for CMV infection, and the most prevalent clinical manifestation is retinitis, followed by colitis, esophagitis, pneumonitis, and encephalitis. CMV oophoritis is poorly described in the literature with some cases reported in patients with hematological or solid malignancies, bone marrow or solid organ transplantation, immunosuppressive therapy, and advanced AIDS cases. We report the case of a 61-year-old woman with a recent diagnosis of AIDS, which was associated with a wasting syndrome. The patient presented with abdominal pain, headache, cutaneous vesicular lesions on the abdomen, anemia, lymphopenia, and hyponatremia; she died suddenly on the fourth day of hospitalization. The autopsy was performed and demonstrated disseminated CMV infection with hemorrhagic encephalitis as the immediate cause of death. Additionally, pneumonitis, extensive adrenalitis, ulcerated enteritis, focal hepatitis, and necrotizing oophoritis were found.

Cytomegalovirus Retinitis: A Review.

Cytomegalovirus (CMV) is a ubiquitous DNA herpes virus that causes significant morbidity and mortality in immunocompromised individuals. CMV retinitis is a potentially blinding manifestation of CMV infection that was commonly seen in advanced acquired immunodeficiency syndrome (AIDS) in the era before modern combination antiretroviral therapy era, but is also recognized in patients with immune deficiency from multiple causes. The advent of and advances in antiretroviral therapies for human immunodeficiency virus have decreased the incidence of CMV retinitis by over 90% among AIDS patients, and improved visual outcomes in those affected. The diagnosis is generally a clinical one, and treatment modalities include systemic and intravitreal antiviral medications. Retinal detachment and immune recovery uveitis are sight-threatening complications of CMV retinitis that require specific treatments.

Role of PU.1 Down-Regulation for the Development of Primary Effusion Lymphoma

Introduction: Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion without tumor masses in body cavities especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is universally associated with Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) infection. The prognosis of PEL is extremely poor due to its aggressiveness and resistance to conventional chemotherapy. Therefore, the understanding of the molecular pathogenesis of PEL is vital to develop novel therapeutic strategies. PU.1, one of the Ets family transcription factors, has been reported to be down-regulated in some B-cell malignancies and acute myeloid leukemia. In this study, we examined the methylation of the PU.1 promoter and enhancer regions in PEL cell lines and performed the restoration of PU.1 in PEL cells in vitro and in vivo.Methods:PU.1 mRNA expressions of eight PEL cell lines were examined by polymerase chain reaction (PCR). PU.1 was conditionally expressed using tet-on system in three PEL cell lines. The bisulfite sequencing was performed to analyze the methylation of the PU.1 promoter and enhancer regions in PEL cells. The DNA methyltransferase inhibitor, 5-Azacytidine, was used as an experimental tool for demethylation. The anti-proliferative activities of restoring PU.1 or 5-Azacytidine in PEL cell lines were measured by the methylthiotetrazole method. Apoptosis was quantified using Annexin V antibody. To evaluate the association of PU.1 with TRAIL promoter, we analyzed its recruitment to the promoter by luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. BCBL-1 cells that expressed tet-inducible PU.1 were injected intraperitoneally into NOD/Rag-2/Jak3double-deficient mice to assess the in vivo efficacy of restoring PU.1. Organ invasion by BCBL-1 cells was evaluated by immunohistochemistry.Results: The expression of PU.1 mRNA in PEL cell lines was weaker than in the human monoblast leukemia cell line, U937, which expresses PU.1 mRNA. The promoter and enhancer regions of the PU.1 gene were highly methylated in PEL cells. The treatment with 5-Azacytidine up-regulated the expression of PU.1 mRNA. Restoration of PU.1 or treatment with 5-Azacytidine inhibited cell proliferation. PU.1 up-regulated TRAIL gene expression among apoptosis-related genes and caused apoptosis. PU.1 induced the transactivation of TRAIL promoter in the reporter assay. Disruption of the PU.1 binding site repressed its transactivation. PU.1 was recruited to TRAIL promoter in the ChIP assay. Although PU.1 induced the master regulator of viral replication, ORF50 expression, the expression of ORF57, which is essential for virus production as a posttranscriptional activator, decreased. PU.1 suppressed ORF 57 by the occupancy of IRF7 in the ORF57 promoter region. Restoration of PU.1 inhibited the ascites formation and organ invasion significantly in vivo compared with control mice.Conclusions: The up-regulation of PU.1 induces growth inhibition and apoptosis via the direct transactivation of TRAIL and modulates viral transactivation via the up-regulation of IRF7. PU.1 is a tumor suppressor in PEL and its down-regulation has a critical role in PEL development. The targeting of PU.1 could be a therapeutic approach in patients with PEL. DisclosuresNo relevant conflicts of interest to declare.

Disseminated MAC: Broadening the Differential for Diarrhea in a Patient with Advanced AIDS

Diarrhea is a common problem in acquired immunodeficiency syndrome (AIDS). Aside from noninfectious causes, such as AIDS enteropathy and drug-induced diarrhea, the most common causes are opportunistic infections (OI). Disseminated Mycobacterium avium complex (MAC) is the most common OI with an incidence of 20% per year. There has been a dramatic decline in the incidence of disseminated MAC since the advent of highly active antiretroviral therapy (HAART). Clinicians must be familiar with the causes of diarrhea in AIDS to ensure timely institution of appropriate interventions. A fifty year old male with AIDS and CD4 count of three presented to the hospital with fever, encephalopathy, and failure to thrive. He was found to be septic with a urinary tract infection and bacteremia secondary to Escherichia coli, as well as Epstein-Barr virus (EBV) encephalitis. His hospital course was complicated by pancytopenia, and a bone marrow (BM) biopsy was performed due to concern for lymphoma in the setting of a positive EBV serology. Two weeks into hospitalization, he was resumed on his prior regimen of HAART, which included Ritonavir, Atazanavir, Emtricitabine and Tenofovir. One week later, he developed profuse, watery diarrhea. Stool studies were sent and while initially only positive for norovirus, two days later, acid-fast bacilli was also isolated. He began a regimen of Azithromycin, Isoniazid, Moxifloxacin, and Ethambutol to cover for both MAC and M. tuberculosis. His BM biopsy and blood cultures later resulted and were positive for MAC, confirming the diagnosis of disseminated MAC. Before HAART, diarrhea, which increases in frequency and severity as immune function declines, afflicted 40% to 80% of AIDS patients. With the initiation of HAART in a person with severe AIDS however, the risk of immune reconstitution inflammatory syndrome (IRIS) is significant and needs to be considered. Given the timing of this patient's diarrhea after resuming HAART, he most likely developed disseminated MAC secondary to IRIS. Although this patient initially tested positive for norovirus, which by itself would explain his diarrhea, comprehensive work-up led to the diagnosis of diarrhea secondary to disseminated MAC, and in turn, appropriate treatment. In an immunocompromised patient, multiple pathogens may be playing a role, and concomitant disease must always be considered.

Progressive outer retinal necrosis syndrome in the course of systemic lupus erythematosus

Progressive outer retinal necrosis syndrome (PORN) is a severe clinical variant of necrotizing herpetic chorioretinitis, which occurs almost exclusively in patients with advanced acquired immunodeficiency syndrome (AIDS). To date, only a few cases of PORN have been reported in patients, mostly among those who were immunocompromised. To our knowledge, only one case of PORN in a patient with systemic lupus erythematosus (SLE) has been described. We report the case of a 44-year old HIV-negative patient with lupus nephritis, whom was being treated by mycophenolate mophetil (MMF), arechin and prednisone. After 14 months of MMF therapy, the patient revealed PORN symptoms; and several months later, the patient developed Type B primary central nervous system lymphoma (PCNSL). PORN is usually compared to acute retinal necrosis (ARN) syndrome, because of having the same causative agent: varicella zoster virus (VZV). There are also some similarities in clinical findings. Our observation supports the hypothesis that PORN symptoms in HIV-negative patients can be an intermediate form between ARN and PORN, and can vary according to the patient's immune status.

Invasive Pulmonary Aspergillosis in Patients with Non-Decompensated Liver Cirrhosis: A Case Report

Introduction: Invasive pulmonary aspergillosis (IPA) is a fatal disease usually occurring in patients with neutropenia resulted from chemotherapy for malignancy. The other risk factors include consuming corticosteroids, organ transplant and advanced acquired immunodeficiency syndrome (AIDS). Recently, the incidence of IPA in immunocompetent patients without any history of organ transplant or malignancy has been increasing. Patients with advanced cirrhosis are one of the cases involved in this infection. Case Presentation: In this case study, we report invasive pulmonary aspergillosis in a 50-year-old patient (from Sari, Iran), who had gradual abdominal pain and ascites, cough and respiratory distress. Radiographic signs showed a round infiltration in the upper part of the right lung. Despite receiving 48-hour antibiotics therapy, the fever had not subsided. In CT-guided needle lung biopsy, septate and acutely angled hyphae (dichotomous) were seen. In CT-guided needle lung biopsy, septate and acutely angled hyphae (dichotomous) were seen. Direct examination of the sputum showed septate hyphae compatible with a filamentous fungus. According to morphologicalandmolecular characterization, Aspergillus fumigatuswasconfirmed. Minimuminhibitory concentration (MIC) values of antifungal agents were determined based on the clinical and laboratory standard institute (CLSI) M38-A2. Treatment with intravenous amphotericin B was changed to oral voriconazole 200 mg, twice a day. The patient did not have any kind of residual lung lesion within the six-month follow-up and the cirrhosis was under control and she currently has no respiratory symptoms or signs. Conclusions: In patients with liver cirrhosis, when there is evidence of severe pulmonary disease without proper response to treatment, the possibility of invasive pulmonary fungal infection should be considered.

A Case of Nontuberculous Mycobacterium Infection Complicated by an Esophagomediastinal Fistula in a Human Immunodeficiency Virus Patient

An esophagomediastinal fistula is rare complication of nontuberculous mycobacterium infection. Here, we report the case of a patient with advanced acquired immunodeficiency syndrome who presented with a fever, cough, and dyspnea, and was eventually diagnosed with nontuberculous mycobacterium infection. Computed tomography revealed multiple lymphadenopathy with an esophagomediastinal fistula. The patient was treated with anti-mycobacterial medications and endoscopic fistula closure. (Korean J Med 2015;88:612-616)

Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma

BackgroundRecently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo. MethodsSurface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model. ResultsSurface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice. ConclusionCD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL.

New Approaches to the Diagnosis and Treatment of Cryptococcal Meningitis

Cryptococcal meningitis remains one of the leading causes of morbidity and mortality among immunosuppressed individuals, particularly those with advanced acquired immunodeficiency syndrome. The greatest burden of disease is in sub-Saharan Africa and Asia where there is limited access to diagnostics and treatment for the disease. The authors review the available tools for diagnosing cryptococcal meningitis and review treatment for cryptococcal meningitis, highlighting the evidence behind current treatment guidelines.

Evaluation Of Targeting CD47-SIRPα Using Primary Effusion Lymphoma Xenograft Mouse Model

IntroductionRecently, the critical roles of CD47 on the surface of resistant cancer cells and its ligand, signal regulatory protein alpha (SIRPα), have been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion without tumor masses in body cavities especially in advanced advanced acquired immunodeficiency syndrome (AIDS). The lack of optimal therapy combined with the aggressive nature of PEL results in a short median survival of less than 6 months. There is therefore a need for the development of new therapies. In this study, we transplanted PEL cells intraperitoneally into immunodeficient mice and evaluated the effect of targeting CD47-SIRPα signal with anti-CD47 antibody (Ab) and NOD-specific SIRPα on PEL. MethodsSurface CD47 expressions of six PEL cell lines and peripheral blood mononuclear cells (PBMC) from six different donors were examined by flow cytometry. The antiproliferative activities of anti-CD47Ab against PEL cell lines were measured by the methylthiotetrazole (MTT) method. Efficacy of anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. In a direct xenograft mouse model, primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient mice to assess the in vivo efficacy of anti-CD47 Ab. To clarify the effect of NOD-specific SIRPα on PEL, we compared the phagocytic activities of peritoneal macrophages against PEL and the in vivo engraftment of PEL among Rag-2/Jak3 double-deficient mice with NOD and non-NOD (Balb/c and C57/BL6) genetic backgrounds. Organ invasion by PEL cells was evaluated by immunohistochemistry and flow cytometry. ResultsSurface CD47 of PEL cell lines was highly expressed compared with that of PBMC. Anti-CD47 Ab did not have a direct antitumor effect against PEL cell lines. Treatment with anti-CD47 Ab promoted phagocytic activities of mouse peritoneal macrophages and human macrophages in vitro. In addition, the expression of CD47 was significantly correlated with the fold increase of phagocytic activity. Treatment with anti-CD47 Ab inhibited the ascites formation and organ invasion completely in vivo compared with control IgG-treated mice. Anti-CD47 Ab-treated mice seemed to stay in healthy and show no apparent change. Although the numbers of peritoneal macrophages were not different among Rag-2/Jak3 double-deficient mice with NOD and non-NOD genetic backgrounds, the phagocytic activity in NOD mice was significantly decreased compared with non-NOD mice. Consistent with the data of phagocytosis assay, the development of PEL cells in NOD mice was superior to those in non-NOD mice. ConclusionsCD47 and SIRPα play the pivotal role in the immune evasion of PEL. NOD-specific SIRPα polymorphism has been reported to produce signals for macrophages not to engulf human cells. Thus, NOD-specific SIRPα is considered to contribute to the attenuation of macrophage phagocytosis and enable the development of PEL. CD47-SIRPα signal could be a therapeutic target for the immunotherapy of PEL. Disclosures:No relevant conflicts of interest to declare.

Interventions for the prevention of mycobacterium avium complex in adults and children with HIV

Mycobacterium avium complex (MAC) infection is a common complication of advanced acquired immunodeficiency syndrome (AIDS) disease and is an independent predictor of mortality and shortened survival. To determine the effectiveness and safety of interventions aimed at preventing MAC infection in adults and children with HIV infection. We searched MEDLINE, EMBASE, and The Cochrane Library (search date December 2012). Randomised controlled trials comparing different strategies for preventing MAC infection in HIV-infected individuals. Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details. Development of MAC infection and survival were compared using risk ratios (RR) and 95% confidence intervals (CI). The quality of evidence has been assessed using the GRADE methodology. Eight studies met the inclusion criteria. Placebo-controlled trials: There was no statistically significant difference between clofazimine and no treatment groups in the number of patients that developed MAC infection (RR 1.01; 95% CI 0.37 to 2.80). Rifabutin (one study; RR 0.48; 95% CI 0.35 to 0.67), azithromycin (three studies; RR 0.37; 95% CI 0.19 to 0.74) and clarithromycin (one study; RR 0.35; 95% CI 0.21 to 0.58) were more effective than placebo in preventing the development of MAC infection. There was no statistically significant difference between those treated with clofazimine (one study; RR 0.98; 95% CI 0.41 to 2.32), rifabutin (one study RR 0.91; 95% CI 0.78 to 1.05), azithromycin (three studies, pooled RR 0.96; 95% CI 0.69 to 1.32) and placebo in number of reported deaths. One study found that the risk of death was reduced by 22% in patients treated with clarithromycin compared to those treated with placebo (RR 0.78; 95% CI 0.64 to 0.96). Monotherapy vs. monotherapy: Patients treated with clarithromycin (RR 0.60; 95% CI 0.41 to 0.89) and azithromycin (RR 0.60; 95% CI 0.40 to 0.89) were 40% less likely to develop MAC infection than those treated with rifabutin. There was no statistically significant difference between those treated with clarithromycin (RR 0.98; 95% CI 0.83 to 1.15), azithromycin (RR 0.98; 95% CI 0.77 to 1.24) and rifabutin in the number of reported deaths. Combination therapy versus monotherapy: There was no statistically significant difference between patients treated with a combination of rifabutin and clarithromycin and those treated with clarithromycin alone (RR 0.74; 95% CI 0.46 to 1.20); and those treated with combination of rifabutin and azithromycin and those treated with azithromycin alone (RR 0.59; 95% CI 1.03). Patients treated with a combination of rifabutin plus clarithromycin were 56% less likely to develop MAC infection than those treated with rifabutin alone (RR 0.44; 95% CI 0.29 to 0.69). Patients treated with a combination of rifabutin plus azithromycin were 65% less likely to develop MAC infection than those treated with rifabutin alone (RR 0.35; 95% CI 0.21 to 0.59). There was no statistically significant difference in the number of reported deaths in all the four different comparisons of prophylactic agents. Based on limited data, azithromycin or clarithromycin appeared to be a prophylactic agent of choice for MAC infection. Further studies are needed, especially direct comparison of clarithromycin and azithromycin. In additions, studies that will compare different doses and regimens are needed.

Isolated Case of Gastrointestinal Histoplasmosis in a Young Male Patient Diagnosed with Acquired Immunodeficiency Syndrome (AIDS) Presenting as Fever of Unknown Origin

Purpose: In this case, we discuss a 23-year-old male from Ecuador recently diagnosed with AIDS (Anti Retroviral [AR] Naive, CD4 count 49, VL 105260 copies/ml) presented with one week of subjective fever and night sweats. Additionally, the patient complained of one to two weeks of productive cough, intermittent abdominal pain and watery non bloody diarrhea. On presentation, patient was febrile to 101.2 F. His physical examination was remarkable only for oral thrush. The patient was placed on contact isolation for possible Tuberculosis (TB) and admitted to Medicine Service for further work up. All initial blood tests, imagining and cultures results were negative. Patient had negative smear and sputum cultures for AFB. Serum Cryptococcal Antigen and Toxoplasmosis antibody were found to be negative. The patient continued to be febrile during his hospital stay and Gallium Scan was done to evaluate for the source of fever. This test showed increased uptake in mid-abdomen specifically in proximal ascending colon. Subsequently, Abdominal Computerized Tomography (CT) scan with contrast demonstrated extensive retroperitoneal and mesenteric adenopathy as well as splenomegaly. Based on this imaging, Surgery performed laproscopic biopsy of the mesenteric lymph node. Pathology of the lymph node showed caseating necrotizing granulomatous inflammation. Gomori-Grocott methenamine Silver (GMS) stain for histoplasmosis and urinary antigen for histoplasmosis were positive. Tissue cultures from surgical biopsy were negative for tuberculosis and malignancy. Patient was discharged with outpatient infectious disease service follow-up. He was started on antiretroviral therapy and itraconazole that resolved his persistent fever without significant complication. Conclusion: Histoplasmosis is usually described as disseminated in the Advanced AIDS population, but this case highlights the fact that, there is subgroup of the patients who would have isolated gastrointestinal histoplasmosis. Histoplasmosis as a localized infection should be part of differential diagnosis in advanced AIDS patients who present with persistent fever of unclear etiology.

Mycobacterium avium-intracellulare brain abscess in HIV-positive patient

Mycobacterial opportunistic infections are a major cause of morbidity and mortality among patients living with HIV (PLHIV) worldwide. Nontuberculous mycobacterial (NTM) infection is one of the leading causes of opportunistic infection in patients with advanced acquired immunodeficiency syndrome i.e., with CD4 count less than 50/cu.mm. Mycobacterium avium complex (MAC) is among the most common opportunistic bacterial infections in those patients with advanced immunodeficiency apart from cryptococcal meningitis, progressive multifocal leukoencephalopathy, etc. Common presentations of mycobacterium avium complex are fever, lymphadenitis and respiratory disease. Immune reconstitution disease is also known to manifest with MAC infections in PLHIV on highly active antiretroviral therapy. Very few cases of central nervous system involvement due to NTM infection have been described. We are reporting a case of advanced acquired immunodeficiency who presented with brain abscess due to Mycobacterium avium intracellulare.