The prevalence of cryptococcal antigenemia in serum of human immunodeficiency viruses-infected patients of iran

BACKGROUND: Cryptococcus species are the most prevalent opportunistic agents found in patients with HIV which may result in life-threatening cryptococcal meningitis (CM). A non-invasive way for diagnosis of CM is the detection of cryptococcal antigen (CrAg) in the blood to reduce either the mortality rate or the treatment complications associated with antiretroviral therapy. Not much information is available in CM among HIV patients in Iran. AIM: Thus, in the current study, we aimed to evaluate the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a referral HIV/TB hospital in Tehran-Iran. METHODS: In this cross-sectional study, blood samples were screened for CrAg using a rapid latex agglutination test between 2017 and 2018 at Masih Daneshvari Hospital (Tehran-Iran) as referral land center for HIV/TB patients. Based on CD4 counts, 106 HIV-positive infected patients including 101 (95.3) males and 5 (4.7) females with the mean ± standard deviation age of 42.40 ± 10.687 and 36.50 ± 6.403 years enrolled in the study. The patients were categorized into 4 groups, (a) <50, (b) 50�100, (c) 101�200, and (d)>200 CD4+ T cells/µL. Whole blood was obtained with EDTA (for flow cytometry of CD4 counts) or without for harvesting serum for determination of CrAg in serum. RESULTS: The results showed only one positive case for CrAg, indicating that CrAg is rare in Iranian HIV patients (overall estimation is lower than 0.01). CONCLUSIONS: With the paucity of information about the prevalence of cryptococcosis in Iran, there is a need for better screening tests and strategies for detection of CrAg in addition to the prevention and treatment approaches of CM. © 2020 Monireh Kamali, Payam Tabarsi, Khorshid Badihi, Esmaeil Mortaz

Reduced Phagocytic Capacity of Blood Monocyte/Macrophages in Tuberculosis Patients Is Further Reduced by Smoking.

Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients

Primary multi-drug resistant tuberculosis presented as lymphadenitis in a patient without HIV infection

Primary multi-drug resistant extrapulmonary tuberculosis is an uncommon form of the disease, but it seems that by increasing the number drug resistant tuberculosis around the world, the number of cases of primary multidrug resistant tuberculosis with extrapulmonary presentation also is going to rise. In this report, we describe a 19- year old, HIV negative man with primary multi-drug resistant TB lymphadenitis, presented with cervical lymphadenopathy and sinus discharge at the site of involved lymph nodes. The Acid Fast Bacilli (AFB) smear of sputum was negative but the AFB smear of discharged fluid as well as the excisional biopsy of the lymph nodes confirmed the M. tuberculosis infection. The patient underwent the treatment with a combination of isoniazide, clofazimine, pyrazinamide, ofloxacin and amikacin with promising results. By increasing the number of drug resistant tuberculosis patients around the world, appropriate diagnosis and treatment of different presentations of the disease need a special attention

Increased activation and expansion of a CD57+ subset within peripheral CD8+ T lymphocytes in mycobacterium tuberculosis-infected patients

Background: Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M. tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M. tuberculosis replication. Methods: In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated γδ and αβ receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant patients) and 20 control subjects, using flowcytometry. Results: We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects (P < 0.003). Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings (P < 0.002). This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ (P < 0.003). No significant changes were observed in the percentages of CDB+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects (P < 0.002), but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases (P < 0.0001). No significant changes were observed in percentages of γδ receptor-bearing T cells between different groups. Conclusion: We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype

Pulmonary Mycobacterium Simiae infection and HTLV1 infection: an incidental co-infection or a predisposing factor?

There is little information on atypical mycobacterium and human T lymphothropic virus Type I (HTLV-I) co-infection. We present the first case of pulmonary M. simiae infection in co-infection with HTLV-1, confirmed by ELISA antibody test and Western Blot. We discuss the clinical characteristics and laboratory tests of the patient and presumptive immunological relation. We propose that in patients with the HTLV infection and pulmonary symptoms and signs compatible with tuberculosis, evaluation for atypical mycobacteriosis may be recommendable

Evaluation of interleukin-2 to detect active and latent tuberculosis among household contacts of pulmonary tuberculosis cases

Background: The interferon-gamma release assays (IGRAs) are the most important diagnostic approach to Mycobacterium tuberculosis infection diagnosis. However, they cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis (TB). Some recent studies suggested that interleukin-2 (IL-2) response to M. tuberculosis could be utilized as a potential biomarker to discriminate active disease from LTBI. Objectives: The current study aimed at evaluating the potential role of IL-2 to detect both active TB and LTBI among household contacts of patients with pulmonary TB in two TB-endemic regions of Iran. Methods: A total of 650 household contacts of patients with TB were invited to participate in the current study. All subjects were diagnosed on extensive clinical evaluation of active TB and LTBI based on clinical manifestations and laboratory findings. The IGRA test was performed using QuantiFERON®-TB Gold Plus. The serum level of IL-2 was measured using the ELISA Development Kit. Results: A total of 237 household contacts entered the final analysis, including 132 patients with LTBI and three with active TB. In addition, 14 subjects were included as TB controls and 102 as TB-uninfected controls. The serum level of IL-2 was significantly higher in active TB and LTBI patients than TB-uninfected controls. The ROC curve was plotted between active TB and LTBI, revealing that the cutoff point of 25.5 pg/mL identifies the active form with 88.24 sensitivity and 36.36 specificity. Conclusions: The current study indicated that the IL-2 assay could not discriminate between active TB and LTBI with acceptable sensitivity. © 2021, Author(s)

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART