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Histoplasmosis is caused by the fungus Histoplasma capsulatum and is often fatal for individuals with acquired immunodeficiency syndrome (AIDS). Delayed diagnosis is a major factor in worsening coinfection, as it can be mistaken for other diseases. Thus, rapid identification of Histoplasma in immunocompromised patients is essential. Molecular techniques, particularly polymerase chain reaction (PCR), were used in this study to identify H. capsulatum in patients coinfected with histoplasmosis and AIDS. Blood samples from 14 individuals with AIDS and disseminated histoplasmosis were collected and analyzed. The PCR method successfully amplified the fungal region in whole blood samples, while PCR-RFLP analysis confirmed a consistent profile in the samples. Genetic sequencing further confirmed the fungal species. Compared to clinical tests such as fungal culture and urinary antigen detection, molecular analysis proved faster, more sensitive, and cost-effective. These molecular markers can potentially be incorporated into routine diagnostics in the future. Further studies are needed to expand and enhance this diagnostic approach, particularly in patients with nonprogressive clinical forms of histoplasmosis.

Infections caused by non-neoformans Cryptococcus spp., including Cryptococcus laurentii, previously thought to be saprophyte and non-pathogenic, have become more common during the past few years, particularly in immunocompromised hosts. To the best of our knowledge here, we present the first case of meningitis in an immunocompromised patient due to a fungus that has never been reported in Pakistan. Our patient, a 40-year old male, who had acquired immunodeficiency syndrome (AIDS) was diagnosed as Cryptococcus laurentti meningitis, with a rare neurological manifestation i.e., cryptococcomas and lepto-meningitis. We presume that exposure to pigeon droppings and acquired immunodeficiency syndrome were the risk factors for this case report. He was treated with liposomal Amphotericin (LAMB) and fluconazole but unfortunately, he rapidly deteriorated and ultimately succumbed to the infection. This case underscores the significance of prompt diagnosis and vigorous treatment of Cryptococcus laurentii meningitis, as well as the need for continued surveillance in immunocompromised individuals.

Rationale: Bordetella bronchiseptica is a common cause of upper respiratory tract infections in domesticated dogs and cats and a rare zoonotic pathogen in immunocompromised humans. With increasing numbers of people acquiring pets and spending time with them in confined spaces due to COVID-19 lockdowns, it is important to be aware of adverse health consequences brought about by this interaction. We present a case of B bronchiseptica pneumonia in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and review key characteristics of an additional 30 cases of B bronchiseptica infections in 29 patients with HIV/AIDS that were identified by literature review., Patient Concerns: A 61-year-old male with HIV/AIDS who was not on antiretroviral therapy and had advanced immunosuppression with a CD4+ T-lymphocyte count of 3 cells/μL sought medical attention for multiple somatic issues including subjective fevers, shortness of breath, and intermittent chest pain., Diagnosis: Computed tomography of the chest identified bilateral nodular opacities in the lower lobes with scattered areas of ground glass opacities. B bronchiseptica was identified in sputum culture by mass spectrometry followed by supplementary biochemical testing., Interventions: Empiric broad-spectrum antibiotics were initiated and changed to levofloxacin after susceptibility testing was completed., Outcomes: The patient was discharged after symptomatic improvement with levofloxacin., Lessons: Pneumonia with interstitial infiltrates in the setting of advanced CD4 lymphocyte depletion is the most common clinical syndrome caused by B bronchiseptica in patients with HIV/AIDS, and may be accompanied by sepsis. Advanced immune suppression, as well as chronic medical conditions, for example, alcoholism, diabetes, and renal failure that compromise host defenses are also commonly found in cases of B bronchiseptica infection in patients who do not have HIV infection. Reported animal contact among patients was not universal. Isolates were susceptible to aminoglycosides, carbapenems, fluoroquinolones, but typically resistant to most cephalosporins., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS). Despite the wide use of effective antiretroviral and antifungal therapy in AIDS patients, CM is still a major morbidity and mortality cause. Understanding the immune response in cryptococcal infection may help to improve the treatment strategies., Methods: We established a prospective cohort of twelve AIDS patients with CM (HIV + CM+) admitted to the hospital from 2019 to 2020. All patients were examined at the baseline, 2 weeks, and 4 weeks thereafter. The level of 19 cytokines in cerebrospinal fluid (CSF) were recorded to analyze the characteristics and dynamic changes of Th1/Th2 immune response. Meanwhile, six AIDS patients without CM (HIV + CM-) and seventeen healthy subjects (HIV-CM-) were included as control groups for CSF assessment., Results: The HIV+ CM+ group had higher CSF IFN-γ, TNF-α, IL-6, IL-7, IL-8, IL-10, IL-12 (P40), IL-15, IL-18, CCL2 levels but lower IL-4 when compared with the HIV-CM- group at baseline. And they also had a higher level of IL-12 (P40) and IL-17A compared with HIV + CM- patients. Except one patient dropped out of the study, eleven HIV + CM+ patients received induction antifungal therapy and regular CSF testing, and the mortality rate was 9.1% (1/11) and 18.2% (2/11) respectively at week 2 and week 4. Compared with baseline CSF cytokines, IL-2, IL-13, IL-17A, and VEGF-A decreased in week 2, and the VEGF-A levels further decreased in week 4. But there was no difference in the levels of all cytokines between survivors and the dead., Conclusion: No evidence of Th1/Th2 imbalance was found in AIDS patients with CM. However, the CSF cytokine network may provide new clues for the treatment of AIDS patients with CM., Trial Registration: This trial was prospectively registered in 2019.7.16. The registered number is ChiCTR1900024565 .

Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1β in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.

Background: Candida species are considered as the cause of one of the most important opportunistic fungal diseases. Accurate identification of Candida species is important because of antifungal susceptibility patterns are different among these species, so proper identification helps in the selection of antifungal drugs for the prevention and treatment. Phenotypic methods for identification of Candida species, which are widely used in clinical microbiology laboratories, have some limitations. Real-time PCR followed by the high-resolution melting analysis (HRMA) is a novel approach for the rapid recognition of pathogenic fungi. Molecular phylogeny is essential for obtaining a better understanding of the evolution of the genus Candida and the identification of the relative degree of the Candida species. The purpose of this study was molecular identification of Candida isolates by Real-time PCR-high-resolution melting analysis and investigation of the genetic diversity of Candida species., Methods: Two hundred and thirty-two Candida isolates including 111 Candida isolates obtained from 96 HIV/AIDS patients and 121 Candida isolates obtained from 98 non-HIV persons were identified by real-time PCR and high-resolution melting curve analysis. To evaluate genetic diversity and relationships among Candida species, PCR products of nine clinical Candida isolates, as a representative of each kind of species, were randomly selected for DNA sequence analysis., Results: In HIV/AIDS patients, six species of Candida spp. were identified as follows: C albicans (n = 64; 57.7%), C glabrata (n = 31; 27.92%), C parapsilosis (n = 9; 8.1%), C tropicalis (n = 4; 3.6%), C krusei (n = 2; 1.8%), and C kefyr (n = 1; 0.90%). In non-HIV persons, we identified eight species of Candida including C albicans (n = 46; 38.33%) followed by C glabrata and C krusei (each one, n = 18; 15%), C tropicalis (n = 13; 10.83%), C lusitaniae (n = 12; 5.17%), C parapsilosis (n = 10; 4.31%), and C kefyr and C guillermondii (each one, n = 2; 1.66%). Also, the phylogenetic analysis showed the presence of two main clades and six separate subclades. Accordingly, about 88.9% of the isolates were located in clade I and 11.10% of the studied isolates were in clade II., Conclusions: Real-time PCR followed by high-resolution melting analysis (HRMA) is known as a reliable, fast, and simple approach for detection and accurate identification of Candida species, especially in clinical samples., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

The morbidity and mortality of HIV type-1 (HIV-1)-related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV-1 replication and gradual recovery of CD4 + T-cell counts. However, ∼10-40% of HIV-1-infected individuals fail to achieve normalization of CD4 + T-cell counts despite persistent virological suppression. These patients are referred to as "inadequate immunological responders," "immunodiscordant responders," or "immunological non-responders (INRs)" who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non-AIDS events and present higher rates of mortality than HIV-1-infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV-1-infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene., (© 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology.)

Background: Adolescents living with HIV/AIDS (ALHIV) are a particularly vulnerable but often overlooked group in the HIV response despite additional disease management challenges., Methods: All ALHIV (10-19 years), on ART for ≥6 months, presenting to care at a Médecins Sans Frontières (MSF) clinic in Myanmar from January-April 2016 were eligible for the quantitative study component (clinical history, medical examination, laboratory investigation). A subset of these respondents were invited to participate in qualitative interviews. Interviews and focus groups were also conducted with other key informants (care givers, clinicians)., Results: Of 177 ALHIV, 56% (100) were aged 9-13 years and 77 (44%) were 14-19. 49% (86) had been orphaned by one parent, and 19% (33) by both. 59% (104) were severely underweight (BMI < 16). 47% presented with advanced HIV (WHO stage III/IV). 93% were virally supressed (< 250 copies/mL). 38 (21%) of ALHIV were on a second-line ART after first-line virological failure. Qualitative interviewing highlighted factors limiting adherence and the central role that HIV counsellors play for both ALHIV patients and caregivers., Conclusions: Our study shows good clinical, immunological, and virological outcomes for a cohort of Myanmar adolescents living with HIV, despite a majority being severely underweight, presenting with Stage III or IV illness, and the prevalence of comorbid infections (TB). Many treatment and adherence challenges were articulated in qualitative interviewing but emphasized the importance of actively engaging adolescents in their treatment. Comprehensive HIV care for this population must include routine viral load testing and social support programs.

Objective: To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment., Methods: 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software., Results: Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4 + CD38 + HLA-DR + T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS., Conclusions: Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.

Chemoprophylaxis (antibiotic prophylaxis) is a long relied-upon means of opportunistic infection management among HIV/AIDS patients, but its use represents an evolutionary tradeoff: Despite the benefits of chemoprophylaxis, widespread use of antibiotics creates a selective advantage for drug-resistant bacterial strains. Especially in the developing world, with combined resource limitations, antibiotic misuse, and often-poor infection control, the emergence of antibiotic resistance may pose a critical health risk. Extending previous work that demonstrated that this risk is heightened when a significant proportion of the population is HIV/AIDS-immunocompromised, we work to address the relationship between HIV/AIDS patients' use of antibiotic chemoprophylaxis and the emergence of resistance. We apply an SEIR compartmental model, parameterized to reflect varying percentages of chemoprophylaxis use among HIV/AIDS+ patients in a resource-limited setting, to investigate the magnitude of the risk of prophylaxis-associated emergence versus the individual-level benefits it is presumed to provide. The results from this model suggest that, while still providing tangible benefits to the individual, chemoprophylaxis is associated with negligible decreases in population-wide morbidity and mortality from bacterial infection, and may also fail to provide assumed efficacy in reduction of TB prevalence., Competing Interests: The authors have declared that no competing interests exist.

Background: Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis., Case Presentation: We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient's treatment, but unfortunately, he died three days later. Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy., Conclusions: Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.

Objective: In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4+ T lymphocytes., Methods: Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4+ T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4+ T lymphocyte values were evaluated using the Spearman correlation coefficient., Results: The levels of TNF-α and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4+ T lymphocytes was lower. The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faecium were much higher. The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-α and IL-6 and the CD4+ T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium., Conclusions: The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4+ T lymphocytes and the levels of TNF-α and IL-6.

Background: Tuberculosis (TB) and HIV co-infection challenges treatment and worsens the outcome of TB treatment. This study aimed to assess the outcome of TB treatment and factors facilitating treatment success among people living with HIV/AIDS in Fako Division of the South West Region of Cameroon., Methods: A hospital-based retrospective cohort study was conducted by manually reviewing medical records of HIV/TB co-infected patients from January 2010 to September 2017. A structured data collection form was used to review the medical records of HIV patients co-infected with TB aged 10 years and older. Patients with incomplete files were dropped from the study. Treatment success was defined as the sum of patients who were declared cured and those who had completed treatment, as per the World Health Organization's recommendations. Data were analyzed using Statistical Package for Social Sciences version 21. Bivariate and multivariate logistic regression model was carried out to identify factors facilitating successful TB treatment outcome. Significance was obtained through adjusted odds ratio with its 95% confidence interval and a p<0.05., Results: A total of 2,986 files were reviewed but 2,928 (98.1%) were retained. Out of the 2,928 medical files of adult TB patients reviewed, 1,041 (35.6%, [95% CI 33.8%-37.3%]) were HIV/TB co-infected. The 1,041 co-infected patients had a mean age of 37.07 (SD of10.02) years and 56.3% were females. The treatment outcome of TB patients were 795(76.4%) cured, 23(2.2%) treatment completed, 99(9.5%) were lost to follow-up, 16 (1.5%) failed, 72(6.9%) died and 36(3.5%) transferred out. A successful treatment outcome was achieved in 818(78.6%,[95% CI: 76.0%-81.0%]) patients. Being a female [COR 1.61, 95% CI: 1.19-2.17, p = 0.002], receiving TB treatment in 2014 [COR 2.00, 95% CI: 1.11-3.60, p = 0.021] and 2015 [COR 2.50, 95% CI: 1.39-4.50, p = 0.002], having relapsed TB infection [COR 0.46, 95% CI: 0.23-0.93, p = 0.031], receiving ART [COR 1.95, 95% CI: 1.28-2.97, p = 0.002] and Cotrimoxazole [COR 2.03, 95% CI: 1.12-3.66, p = 0.019] were factors significantly associated with successful treatment. After adjusting for confounders, successful treatment outcome were associated with being a female [AOR 1.6; 95% CI: 1.21-2.22, p = 0.001], diagnosis of TB in 2014 [AOR 1.90; 95% CI: 1.04-3.45, p = 0.036] and 2015 [AOR 2.43; 95% CI: 1.33-4.43, p = 0.004]., Conclusion: There is a high TB treatment success rate among HIV/TB co-infected patients in our setting, although below the target set by the WHO. Specific interventions aimed at enhancing patient outcomes are recommended., Competing Interests: The authors have declared that no competing interests exist.

Background: Owing to similar clinical presentations, as of cutaneous disease of different etiologies, and extreme rarity in the global incidence; primary cutaneous actinomycosis often remains as diagnostic challenges., Case Presentation: Herein, we describe a case of primary cutaneous actinomycosis, erroneously treated as cutaneous tuberculosis, in a patient living with AIDS. On clinical examination, the characteristic lesion, resembling cutaneous tuberculosis, observed on the dorsum of a left leg. No other lesion elsewhere on the body was observed, however. Cytological examinations of the stabbed biopsy were negative for malignant cells; although hyper-keratosis and mild-acanthosis of epidermis, acute inflammatory infiltrates comprising plasma cell, macrophages and neutrophils were observed in the upper and mid dermis. The pus aspirated from lesion grew a molar tooth, adherent colonies in microaerophilic condition. Further, identifications and susceptibility pattern against recommended antibiotics were assessed as per the CLSI (Clinical and Laboratory Standard Institute) guidelines. Subsequently, the case was then, diagnosed as primary cutaneous actinomycosis. Radiographic imaging of abdomen and lungs were normal; no feature of disseminated actinomycosis seen. Penicillin G followed by Penicillin V, was prescribed for 12 months. The patient underwent progressive changes and no relapse noted on periodic follow-up., Conclusion: The case underscores cutaneous actinomycosis requires a diagnosis consideration, especially in People Living with HIV/AIDS (PLHA), where myriad of opportunistic cutaneous infections are common.

Background: Cryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100-200 cells/μl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive., Methods: Prospective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/μl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis., Results: Of 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% (95% CI, 4.7-12.4). In CD4 ≤100 cells/μl group it was 7.5% (95% CI, 4.1-12.6) and 9.1% (95% CI, 3.4-19.0) in the group with CD4 101 to 199 cells/μl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% (95% CI, 1.4-13.1). One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months., Conclusions: CrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100 versus CD4 101-199 cells/μl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/μl in similar settings., Competing Interests: The authors have declared that no competing interests exist.

Cryptococcosis is a systemic mycosis with a chronic or subacute progression caused by the inhalation of dehydrated yeasts or basidiospores. The causative agents are C. gattii and C. neoformans. The latter is more commonly associated with cellular immunodeficiency and is not rare in patients with Acquired Immunodeficiency Syndrome (AIDS). Cryptococcosis is common in pregnant women with AIDS; however, it is uncommon for the placenta to be affected, with few reported cases in the literature. We present the case of a pregnant woman with AIDS who had placental and pulmonary cryptococcosis associated with fungemia, with a satisfactory clinical outcome obtained after therapy.

Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n = 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P = 0.01). Ferritin > 5000 ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P = 0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P = 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA.

Rhodococcus equi is a facultative aerobic, intracellular, non-motile, non-spore-forming, Gram-positive, weakly acid-fast coccobacillus belonging to the group of nocardioform actinomycetes. R. equi infections are rare opportunistic illnesses in patients with Acquired Immunodeficiency Syndrome (AIDS), associated with a high mortality rate. The most common clinical presentation of R. equi infections is a chronic cavitary pneumonia. Due to its acid-fastness, R. equi can be mistaken for others acid-fast organisms, as Mycobacterium tuberculosis. In turn, R. equi is also a gram-positive pleomorphic bacteria and can be mistaken for diphtheroids or Micrococcus organisms, being accidentally disregarded as oral contaminants in sputum cultures. Therefore, in Brazil, a highly prevalent tuberculosis (TB) country, pulmonary infections caused by R. equi may mimic pulmonary TB and represent a diagnostic challenge. Here, we report on a case of chronic cavitary pneumonia by R. equi in a Human Immunodeficiency Virus (HIV)-infected patient, focusing on diagnostic aspects.

The neurotropic parasite Toxoplasma gondii is a globally distributed parasitic protozoan among mammalian hosts, including humans. During the course of infection, the CNS is the most commonly damaged organ among invaded tissues. The polymorphic rhoptry protein 18 (ROP18) is a key serine (Ser)/threonine (Thr) kinase that phosphorylates host proteins to modulate acute virulence. However, the basis of neurotropism and the specific substrates through which ROP18 exerts neuropathogenesis remain unknown. Using mass spectrometry, we performed proteomic analysis of proteins that selectively bind to active ROP18 and identified RTN1-C, an endoplasmic reticulum (ER) protein that is preferentially expressed in the CNS. We demonstrated that ROP18 is associated with the N-terminal portion of RTN1-C and specifically phosphorylates RTN1-C at Ser7/134 and Thr4/8/118. ROP18 phosphorylation of RTN1-C triggers ER stress-mediated apoptosis in neural cells. Remarkably, ROP18 phosphorylation of RTN1-C enhances glucose-regulated protein 78 (GRP78) acetylation by attenuating the activity of histone deacetylase (HDAC), and this event is associated with an increase of neural apoptosis. These results clearly demonstrate that both RTN1-C and HDACs are involved in T. gondii ROP18-mediated pathogenesis of encephalitis during Toxoplasma infection., Competing Interests: The authors declare no conflict of interest.

Acquired immune deficiency syndrome (AIDS), caused by infection with human immunodeficiency virus (HIV), is associated with gastrointestinal disease, systemic immune activation and changes in the gut microbiota. Here, we aim to investigate the gut microbiota patterns of HIV-infected individuals and HIV-uninfected individuals in populations from South China. We enrolled 33 patients with HIV (14 participants treated with highly active antiretroviral therapy [HAART] for more than 3 months; the remaining 19 individuals had not received treatment) and 35 healthy controls (HC) for a cross-sectional comparison of gut microbiota using stool samples. Gut microbial communities were profiled by sequencing the bacterial 16S rRNA genes. Dysbiosis was more common among patients with AIDS compared with healthy individuals. Dysbiosis was characterized by decreased α-diversity, low mean counts of Bacteroidetes, Faecalibacterium, Prevotella, Bacteroides vulgatus, Dialister and Roseburia inulnivorans, and high mean counts of Proteobacteria, Enterococcus, Streptococcus, Lactobacillus, Lachnociostridium, Ruminococcus gnavus and Streptococcus vestibularis. Increased abundance of Bacilli was observed in homosexual patients. Proteobacteria were higher among heterosexual patients with HIV infections. Tenericutes were higher among patients with history of intravenous drug abuse. Restoration of gut microbiota diversity and a significant increase in abundance of Faecalibacterium, Blautia and Bacteroides were found in patients receiving HAART compared to those who did not receive. HIV infection-associated dysbiosis is characterized by decreased levels of α-diversity and Bacteroidetes, increased levels of Proteobacteria and the alterations of gut microbiota correlate with the route of HIV transmission. The imbalanced faecal microbiota of HIV infection is partially restored after therapy., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Tsukamurella pulmonis is an aerobic gram-positive and rod-shaped organism that causes central catheter-related bloodstream infections in immunocompromised hosts. However, peripherally inserted central catheter (PICC)-related bloodstream infections due to this organism have not been reported., Case Presentation: We describe a case of a 48-year-old man with acquired immunodeficiency syndrome and diffuse large B cell lymphoma who received five courses of chemotherapy including rituximab , cyclophosphamide , doxorubicin hydrochloride , vincristine , and prednisone via a PICC. Five days after the last chemotherapy course, he presented with a high fever and shaking chills. His absolute neutrophil count was 4200/μL. Cultures obtained from blood and PICC culture revealed T. pulmonis. The colony count of T. pulmonis grown from PICC culture was 10 3 colony-forming units. Therefore, he was diagnosed with T. pulmonis bacteremia resulting from PICC-related bloodstream infection. The patient's condition improved and he became afebrile within 48 h after intravenous administration of cefozopran hydrochloride, which is a fourth generation cephalosporin., Conclusions: PICCs can be associated with T. pulmonis bacteremia, and fourth generation cephalosporins may be effective treatment.

Objective:: To evaluate the frequency of and factors associated with indeterminate interferon-gamma release assay (IGRA) results in people living with HIV/AIDS (PLWHA)., Methods:: We tested 81 PLWHA in the central-west region of Brazil, using the tuberculin skin test and an IGRA. Information on sociodemographic and clinical variables was gathered through the use of questionnaires and from medical records. The association of those variables with indeterminate results was analyzed by calculating the adjusted ORs in a multivariate logistic regression model. Concordance was evaluated by determining the kappa statistic., Results:: Among the 81 patients evaluated, the tuberculin skin test results were positive in 18 (22.2%) of the patients, and the IGRA results were positive in 10 (12.3%), with a kappa of 0.62. The IGRA results were indeterminate in 22 (27.1%) of the patients (95% CI: 17.8-38.1%). The odds of obtaining indeterminate results were significantly higher in smokers (adjusted OR = 6.0; 95% CI: 1.4-26.7) and in samples stored for less than 35 days (adjusted OR = 14.0; 95% CI: 3.1-64.2). Patients with advanced immunosuppression (CD4+ T-cell count < 200 cells/mm3) were at a higher risk for indeterminate results (OR adjusted for smoking and inadequate duration of sample storage = 4.7; 95% CI: 0.91-24.0), although the difference was not significant., Conclusions:: The high prevalence of indeterminate results can be a major limitation for the routine use of IGRAs in PLWHA. The need to repeat the test increases its costs and should be taken into account in cost-effectiveness studies. The processing of samples can significantly alter the results., Objetivo:: Avaliar a frequência de resultados indeterminados de um interferon-gamma release assay (IGRA, ensaio de liberação de interferon-gama) e os fatores relacionados com esses resultados em pessoas vivendo com HIV/AIDS (PVHA)., Métodos:: Foram avaliadas 81 PVHA na região Centro-Oeste do Brasil, por meio do teste tuberculínico e de um IGRA. Informações a respeito de variáveis sociodemográficas e clínicas foram obtidas por meio de questionários e prontuários médicos. A relação entre essas variáveis e os resultados indeterminados foi avaliada por meio do cálculo da OR ajustada em um modelo de regressão logística multivariada. A concordância foi avaliada por meio do coeficiente kappa., Resultados:: Os resultados do teste tuberculínico e do IGRA foram positivos em 18 (22,2%) e 10 (12,3%), respectivamente, dos 81 pacientes avaliados (κ = 0,62). O resultado do IGRA foi indeterminado em 22 (27,1%) dos pacientes (IC95%: 17,8-38,1%). A chance de resultados indeterminados foi significativamente maior em fumantes (OR ajustada = 6,0; IC95%: 1,4-26,7) e em amostras armazenadas durante menos de 35 dias (OR ajustada = 14,0; IC95%: 3,1-64,2). Pacientes com imunossupressão avançada (contagem de células T CD4+ < 200 células/mm3) apresentaram maior risco de resultados indeterminados (OR ajustada para tabagismo e tempo inadequado de armazenamento das amostras = 4,7; IC95%: 0,91-24,0), embora a diferença não tenha sido significativa., Conclusões:: A alta prevalência de resultados indeterminados pode ser um grande obstáculo ao uso rotineiro de IGRAs em PVHA. A necessidade de repetir o teste aumenta seu custo e deve ser levada em conta em estudos da relação entre custo e eficácia. O processamento das amostras pode alterar significativamente os resultados.

Background: HIV-associated tuberculosis (TB) co-infection remains an enormous burden to international public health. Post-mortem studies have highlighted the high proportion of HIV-positive adults admitted to hospital with TB. Determine TB-LAM and Xpert MTB/RIF assays can substantially increase diagnostic yield of TB within one day of hospital admission. However, it remains unclear if this approach can impact clinical outcomes. The STAMP trial aims to test the hypothesis that the implementation a urine-based screening strategy for TB can reduce all cause-mortality among HIV-positive patients admitted to hospital when compared to current, sputum-based screening., Methods: The trial is a pragmatic, individually randomised, multi-country (Malawi and South Africa) clinical trial with two study arms (1:1 recruitment). Unselected HIV-positive patients admitted to medical wards, irrespective of presentation, meeting the inclusion criteria and giving consent will be randomized to screening for TB using either: (i) 'standard of care'- testing of sputum using the Xpert MTB/RIF assay (Xpert) or (ii) 'intervention'- testing of sputum using Xpert and testing of urine using (a) Determine TB-LAM lateral-flow assay and (b) Xpert following concentration of urine by centrifugation. Patients will be excluded if they have received TB treatment in the previous 12 months, if they have received isoniazid preventive therapy in the last 6 months, if they are aged <18 years or they live outside the pre-specified geographical area. Results will be provided to the responsible medical team as soon as available to inform decisions regarding TB treatment. Both the study and routine medical team will be masked to study arm allocation. 1300 patients will be enrolled per arm (equal numbers at the two trial sites). The primary endpoint is all-cause mortality at 56 days. An economic analysis will be conducted to project long-term outcomes for shorter-term trial data, including cost-effectiveness., Discussion: This pragmatic trial assesses an intervention to reduce the high mortality caused by HIV-associated TB, which could feasibly be scaled up in high-burden settings if shown to be efficacious and cost-effective. We discuss the challenges of designing a trial to assess the impact on mortality of laboratory-based TB screening interventions given frequent initiation of empirical treatment and a failure of several previous clinical trials to demonstrate an impact on clinical outcomes. We also elaborate on the practical and ethical issues of 'testing a test' in general., Trial Registration: ISRCTN Registry ( ISRCTN71603869 ) prospectively registered 08 May 2015; the South African National Controlled Trials Registry (DOH-27-1015-5185) prospectively registered October 2015.

Obstract: To identify Mycobacteria isolated from AIDS patients and to evaluate the diagnostic value of MBP64 antigen Colloidal Gold Diagnostic Kit in distinguishing Mycobacterium tuberculosis (MTB) and Nontuberculous mycobacteria (NTM). Methods: A total of 140 Mycobacteria isolates from AIDS patients were collected and identified by using 16SrDNA PCR assay as well as immune colloidal gold technique (MBP64 antigen Colloidal Gold Diagnostic Kit). The sensitivity and specificity of Colloidal Gold method was analyzed. Results: With the results of 16SrDNA PCR assay as gold standard, the sensitivity and specificity of Colloidal Gold method in distinguishing MTB and NTM were 96.00% and 96.84%, respectively. Among 140 samples, 114 were identified by 16SrDNA PCR assay, among which 50 (43.86%) were identified as MTB, and 63 (55.26%) were identified as NTM. The most popular NTM in AIDS patients were Mycobacterium gordonae, Mycobacterium avium and Mycobacterium kansasii . Conclusion: NTM is of high prevalence in AIDS patients, and MBP64 antigen Colloidal Gold Diagnostic Kit can be used as an effective technique in distinguishing NTM and MTB.

Haemophagocytic lymphohistiocytosis is an uncommon syndrome that results from an uncontrolled activation of macrophages and lymphocytes resulting in the compromise of multiple organs that is potentially fatal without timely treatment. It can be hereditary or a secondary result of infectious processes, neoplasms or autoimmune conditions. We present the case of a patient with HIV/AIDS who developed hemophagocytic lymphohistiocytosis as well as disseminated intravascular coagulation associated with histoplasmosis and who was successfully treated with amphotericin B, steroids and transitory dialytic support.

Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Microbes have co-evolved with human beings for millions of years. They play a very important role in maintaining the health of the host. With the advancement in next generation sequencing technology, the microbiome profiling in the host can be obtained under different circumstances. This review focuses on the current knowledge of the alteration of complex microbial communities upon the infection of different pathogens, such as human immunodeficiency virus, hepatitis B virus, influenza virus, and Mycobacterium tuberculosis, at different body sites. It is believed that the increased understanding of the correlation between infectious disease and the alteration of the microbiome can contribute to better management of disease progression in the future. However, future studies may need to be more integrative so as to establish the exact causality of diseases by analyzing the correlation between microorganisms within the human host and the pathogenesis of infectious diseases.

Hemophagocytic lymphohistiocytosis (HLH) is traditionally regarded as a rapidly progressive and often fatal illness. In patients with AIDS, HLH usually occurs secondary to opportunistic infections. Although popular guidelines exist for the diagnosis and management of HLH in general, no formal study has evaluated their applicability among adult patients who develop HLH in the setting of AIDS and opportunistic infections. The study reports on a case of HLH in a patient with AIDS and disseminated histoplasmosis. Eighteen other previously reported cases of HLH in the setting of AIDS and histoplasmosis were reviewed. Majority of the cases occurred in patients with a CD4 count of less than 70 cells/mm(3). Overall mortality was 44%. Not getting antifungal treatment and having Histoplasma in blood were the 2 main risk factors for death. Among the patients who had a timely diagnosis of histoplasmosis and were initiated on antifungal therapy, the survival rates were significantly better, especially in the post-2000 ad period., (© The Author(s) 2015.)

Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT) proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT) is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes), consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP) when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.

Unlabelled: Cryptococcus neoformans strains isolated from patients with AIDS secrete acid phosphatase, but the identity and role of the enzyme(s) responsible have not been elucidated. By combining a one-dimensional electrophoresis step with mass spectrometry, a canonically secreted acid phosphatase, CNAG&#95;02944 (Aph1), was identified in the secretome of the highly virulent serotype A strain H99. We created an APH1 deletion mutant (Δaph1) and showed that Δaph1-infected Galleria mellonella and mice survived longer than those infected with the wild type (WT), demonstrating that Aph1 contributes to cryptococcal virulence. Phosphate starvation induced APH1 expression and secretion of catalytically active acid phosphatase in the WT, but not in the Δaph1 mutant, indicating that Aph1 is the major extracellular acid phosphatase in C. neoformans and that it is phosphate repressible. DsRed-tagged Aph1 was transported to the fungal cell periphery and vacuoles via endosome-like structures and was enriched in bud necks. A similar pattern of Aph1 localization was observed in cryptococci cocultured with THP-1 monocytes, suggesting that Aph1 is produced during host infection. In contrast to Aph1, but consistent with our previous biochemical data, green fluorescent protein (GFP)-tagged phospholipase B1 (Plb1) was predominantly localized at the cell periphery, with no evidence of endosome-mediated export. Despite use of different intracellular transport routes by Plb1 and Aph1, secretion of both proteins was compromised in a Δsec14-1 mutant. Secretions from the WT, but not from Δaph1, hydrolyzed a range of physiological substrates, including phosphotyrosine, glucose-1-phosphate, β-glycerol phosphate, AMP, and mannose-6-phosphate, suggesting that the role of Aph1 is to recycle phosphate from macromolecules in cryptococcal vacuoles and to scavenge phosphate from the extracellular environment., Importance: Infections with the AIDS-related fungal pathogen Cryptococcus neoformans cause more than 600,000 deaths per year worldwide. Strains of Cryptococcus neoformans isolated from patients with AIDS secrete acid phosphatase; however, the identity and role of the enzyme(s) are unknown. We have analyzed the secretome of the highly virulent serotype A strain H99 and identified Aph1, a canonically secreted acid phosphatase. By creating an APH1 deletion mutant and an Aph1-DsRed-expressing strain, we demonstrate that Aph1 is the major extracellular and vacuolar acid phosphatase in C. neoformans and that it is phosphate repressible. Furthermore, we show that Aph1 is produced in cryptococci during coculture with THP-1 monocytes and contributes to fungal virulence in Galleria mellonella and mouse models of cryptococcosis. Our findings suggest that Aph1 is secreted to the environment to scavenge phosphate from a wide range of physiological substrates and is targeted to vacuoles to recycle phosphate from the expendable macromolecules., (Copyright © 2014 Lev et al.)

Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four distinct molecular types: VGI, VGII, VGIII, and VGIV, with no evidence of nuclear genetic exchange, indicating these represent distinct species. C. gattii VGII isolates are causing the Pacific Northwest outbreak, whereas VGIII isolates frequently infect HIV/AIDS patients in Southern California. VGI, VGII, and VGIII have been isolated from patients and animals in the Western US, suggesting these molecular types occur in the environment. However, only two environmental isolates of C. gattii have ever been reported from California: CBS7750 (VGII) and WM161 (VGIII). The incongruence of frequent clinical presence and uncommon environmental isolation suggests an unknown C. gattii reservoir in California. Here we report frequent isolation of C. gattii VGIII MATα and MATa isolates and infrequent isolation of VGI MATα from environmental sources in Southern California. VGIII isolates were obtained from soil debris associated with tree species not previously reported as hosts from sites near residences of infected patients. These isolates are fertile under laboratory conditions, produce abundant spores, and are part of both locally and more distantly recombining populations. MLST and whole genome sequence analysis provide compelling evidence that these environmental isolates are the source of human infections. Isolates displayed wide-ranging virulence in macrophage and animal models. When clinical and environmental isolates with indistinguishable MLST profiles were compared, environmental isolates were less virulent. Taken together, our studies reveal an environmental source and risk of C. gattii to HIV/AIDS patients with implications for the >1,000,000 cryptococcal infections occurring annually for which the causative isolate is rarely assigned species status. Thus, the C. gattii global health burden could be more substantial than currently appreciated.

A human immunodeficiency virus-1 (HIV-1)-positive male undergoing antiretroviral therapy was diagnosed with an axillary lymph node abscess caused by Corynebacterium ulcerans, and an environmental survey revealed that the patient's cat as the source of infection.

HIV infection has changed the scenario of infectious disease. HIV-associated immunodeficiency resulted in a wide spectrum of new opportunistic infections. After introduction of antiretroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS) became an important challenge in management of 10% to 25% of the patients. Meta-analyses of IRIS from various reports published worldwide by Monika Muller et al described 12% IRIS incidence and 15.7% IRIS tuberculosis. Among IRIS tuberculosis, central nervous system involvement with IRIS tuberculous meningitis forms only 7%. Only 9 cases of tuberculous brain abscess is reported in patients with AIDS so far. The IRIS tuberculous brain abscess is very rare, and so far only 1 case is reported as a paradoxical reaction after ART initiation. Here, we report a case of recurrent IRIS tuberculosis meningitis and brain abscess.

Objective: To evaluate the added value of QuantiFERON TB-Gold in-Tube (QTF-GIT) over the tuberculin skin testing (TST) for detecting latent tuberculosis (TB) infection (LTBI) among patients with AIDS in a city with a low TB incidence rate (11.1/100,000 inhabitants) and universal BCG coverage., Methods: Three hundred consecutive patients with AIDS in eight outpatient sexually transmitted disease public clinics in Brasilia were submitted to QFT-IT and TST between May 2011 and March 2013. A positive result of either test was considered to be LTBI., Results: Median CD4-cell count was 477.5 cells/mm(3); 295 (98.3%) were using antiretroviral therapy. Eighteen patients (6%, 95% CI: 3.6%-9.3%) had LTBI, of whom 4 (1.3%, 95% CI: 0.04%-2.63%) had only a positive TST, 8 (2.7%, 95% CI: 0.8%-4.5%) had only a QFT-GIT positive test, and 6 (2%, 95% CI: 0.4%-3.6%) had positive results for both tests. This represents an 81.8% relative increase in LTBI detection when QFT-GIT is added to TST. The concordance between both tests was 96% (k = 0.48)., Conclusions: The QFT-GIT alone was more effective to detect LTBI than TST alone and had an 81% added value as an add-on sequential test in this population with mild immunosuppression. The cost-effectiveness of these strategies remains to be evaluated.

Objective: to evaluate the prevalence of nasal colonization with Staphylococcus aureus in individuals with HIV/AIDS under inpatient treatment in a teaching hospital in the state of São Paulo (Brazil)., Method: a cross-sectional study undertaken in two units specialized in attending people living with HIV/AIDS, in the period August 2011 - July 2012. Socio-demographic and clinical data was collected through individual interviews and from the medical records; samples of nasal secretion were collected with Stuart swabs on the first day of inpatient treatment. Ethical aspects were respected., Result: of the 229 individuals with HIV/AIDS hospitalized in this period, 169 participated in the study, with Staphylococcus aureus being identified in the culture tests of 46 (27.2%) of the individuals, resistance to oxacillin being evidenced in 10 (21.8%) participants., Conclusion: the results of the research indicate that the prevalence of colonization with Staphylococcus aureus in individuals with HIV/AIDS in the specialized units was considered relevant, possibly contributing to future investigations and, moreover, to the implementation of measures to prevent and control this pathogen in this population.

Mycobacterium avium complex (MAC) infection causes disseminated disease in immunocompromised hosts, such as human immunodeficiency virus (HIV)-positive patients, and pulmonary disease in persons without systemic immunosuppression, which has been increasing in many countries. In Japan, the incidence of pulmonary MAC disease caused by M. avium is about 7 times higher than that caused by M. intracellulare. To explore the bacterial factors that affect the pathological state of MAC disease caused by M. avium, we determined the complete genome sequence of the previously unreported M. avium subsp. hominissuis strain TH135 isolated from a HIV-negative patient with pulmonary MAC disease and compared it with the known genomic sequence of M. avium strain 104 derived from an acquired immunodeficiency syndrome patient with MAC disease. The genome of strain TH135 consists of a 4,951,217-bp circular chromosome with 4,636 coding sequences. Comparative analysis revealed that 4,012 genes are shared between the two strains, and strains TH135 and 104 have 624 and 1,108 unique genes, respectively. Many strain-specific regions including virulence-associated genes were found in genomes of both strains, and except for some regions, the G+C content in the specific regions was low compared with the mean G+C content of the corresponding chromosome. Screening of clinical isolates for genes located in the strain-specific regions revealed that the detection rates of strain TH135-specific genes were relatively high in specimens isolated from pulmonary MAC disease patients, while, those of strain 104-specific genes were relatively high in those from HIV-positive patients. Collectively, M. avium strains that cause pulmonary and disseminated disease possess genetically distinct features, and it suggests that the acquisition of specific genes during strain evolution has played an important role in the pathological manifestations of MAC disease.

Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

Disseminated histoplasmosis is an emerging infection in patients with cellular immune deficiency in non-endemic countries, caused by the migration from endemic regions and the development of travels. Diagnosis can be challenging in this context because rapid diagnostic tools such as Histoplasma antigen detection or appropriate molecular tools are generally unavailable, serology is often negative in immunosuppressed patients, and isolation of the fungus from cultures often takes several weeks. Here, we report the contribution of galactomannan serum detection for the management of an HIV-infected patient with disseminated histoplasmosis.

Background: Penicillium marneffei (P. marneffei) is an emerging pathogenic fungus that can cause invasive mycosis in patients with AIDS. The epidemiological features of P. marneffei infection in AIDS patients in Guangdong province remain unclear so far. This study aimed to investigate the genetic diversity within a population of 163 P. marneffei isolates obtained from AIDS patients and search for the dominant clinical strains in Guangdong province., Methods: One hundred and sixty-three P. marneffei isolates obtained from AIDS patients in Guangdong province during January 2004 and December 2009 were studied by randomly amplified polymorphic DNA (RAPD) using two random primers (H2 and H22). The degree of similarity between samples was calculated through similarity coefficients from RAPD fragment data and the dendrogram was assessed using the unweighted pair group method with arithmetic mean (UPGMA)., Results: Two primers showed a high degree of discrimination and good stability. Primer H2 yielded eight different patterns (H2-1 to H2-8) among 163 isolates with the discriminatory power being 0.413. Primer H22 identified seven types (H22-1 to H22-7) among 163 isolates with the discriminatory power being 0.467. Genetic similarity coefficients based on RAPD data among 163 P. marneffei isolates ranged from 0.681 to 0.957, 61.96% of which were no less than 0.83. The discriminatory power of the two primers was 0.524. One hundred and sixty-three P. marneffei isolates were clustered into nine distinct groups (groups I to IX) at the similarity coefficient value of 0.83 and group I was the most common, including 101 strains (61.96%)., Conclusion: The RAPD analyses could provide important information as to the degree of genetic diversity and the relationship among clinical P. marneffei isolates, revealing genetic polymorphism and dominant strains.

Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome architecture in some, but not all, lineages.

Objective: To investigate the clinical feature of cryptosporidium infection in HIV/AIDS patients with chronic diarrhea., Methods: 253 Stool samples were collected from HIV/AIDS patients with chronic diarrhea during Nov.2009 to Dec.2010. The samples were concentrated by Formalin-Ethyl Acetate Sedimentation technique and stained by Modified acid-fast stain (AFS) for the identification of oocysts by microscopy. Divided the cases into three groups according to their CD4 cell counts (< 200, ≥ 200 and < 500, ≥ 500/µl); meanwhile the cases were divided into three groups by their age (20 - 35, 36 - 55, 56 - 69). Analyzed the groups by comparison., Results: The total infection rate of Cryptosporidium in AIDS patients was 12.6% in 253 cases. CD4(+) T-lymphocyte counts was related to the infection rates of cryptosporidium, the difference was statistically significant (χ(2) = 10.33, P < 0.01): the infection rate were 20.4% (20/98), 9.23% (12/130), 0 (0/25) separately. In the 32 Cryptosporidium positive cases, 22 (68.8%) cases stood with diarrhea above 5 times per day, the three kind of CD4 counts level were separately 15 (15/20), 7 (7/12), 0. The difference was no statistically significant (P > 0.05). HIV/AIDS patients with chronic diarrhea who progressed during asymptomatic period, pre-AIDS period, AIDS period, had the infection rate of 0(0/7), 21.3% (19/89), 8.3% (13/157) respectively, the difference was statistically significant (χ(2) = 9.822, P < 0.01); 22 out of 32 Cryptosporidium positive cases in HIV patients were diagnosed with enteritis, the infection rate in urban area and rural area was 6.5% (7/104) and 16.8% (25/149) separately, the difference was statistically significant (χ(2) = 5.596, P < 0.05). Comparing different age groups, Cryptosporidium infection status were separately 7.3% (4/55), 13.4% (22/164), 17.6% (6/34). Each group's comparative difference was no statistically significant (χ(2) = 2.29, P > 0.05)., Conclusion: The infection rate of cryptosporidium and clinical severity of cryptosporidium infection are statistically correlated with CD4(+) T-lymphocyte counts, with AIDS stage, with HIV associated proctitis.

Penicillium marneffei (P. marneffei) is considered an indicator pathogen of AIDS, and the endemicity and clinical features of P. marneffei have been described. While, how the co-infection of P. marneffei exacerbate deterioration of the immune response remains poorly understood. Here we isolated P. marneffei from the cutaneous lesions of AIDS patients and analyzed its effects on HIV-1-dendritic cells (DCs) interaction. We demonstrated that the monocyte-derived dendritic cells (MDDCs) could be activated by both thermally dimorphic forms of P. marneffei for significantly promoting HIV-1 trans-infection of CD4(+) T cells, while these activated MDDCs were refractory to HIV-1 infection. Mechanistically, P. marneffei-activated MDDCs endocytosed large amounts of HIV-1 and sequestrated the internalized viruses into tetrapasnin CD81(+) compartments potentially for proteolysis escaping. The activated MDDCs increased expression of intercellular adhesion molecule 1 and facilitated the formation of DC-T-cell conjunctions, where much more viruses were recruited. Moreover, we found that P. marneffei-stimulated MDDCs efficiently activated resting CD4(+) T cells and induced more susceptible targets for viral infection. Our findings demonstrate that DC function and its interaction with HIV-1 have been modulated by opportunistic pathogens such as P. marneffei for viral dissemination and infection amplification, highlighting the importance of understanding DC-HIV-1 interaction for viral immunopathogenesis elucidation.

Background: T-SPOT.TB is a novel test for tuberculosis infection with higher sensitivity and specificity than the traditional tuberculin skin test (TST). However, there are no longitudinal data in the literature evaluating T-SPOT.TB for Mycobacterium tuberculosis in patients with acquired immune deficiency syndrome (AIDS) on highly active antiretroviral therapy (HAART). The objective of this study was to assess the value of T-SPOT.TB longitudinally in AIDS patients on HAART without prophylaxis for tuberculosis., Methods: A prospective observational study was conducted in 50 AIDS patients on HAART. None of the subjects had evidence of active tuberculosis. T-SPOT.TB, a T-cell-based interferon gamma released assay, was performed at the onset of the study and repeated 24 months thereafter. Subjects were evaluated every 6 months during the 36-month follow-up., Results: Twenty-one (42%) AIDS patients on HAART tested positive by T-SPOT.TB (95%CI 28.3% - 55.7%). The pooled spot-forming cells of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides were 68/million peripheral blood mononuclear cell (PBMC) (interquartile range 44 - 220). The average number of CD4 cells in subjects was (305 +/- 152) cells/microl, and there was no significant difference in T-SPOT.TB response rates between subjects with CD4 cell counts < 200 cells/microl (7/15 (46.7%), 95%CI 21.5% - 71.9%) and those with CD4 cell counts >/= 200 cells/microl (14/35 (40.0%), 95%CI 23.8% - 56.2%, P = 0.662). In the 32 subjects who completed the 24-month follow-up, 10 underwent T-SPOT.TB reversion, one had T-SPOT.TB conversion, six remained positive and 15 remained negative. None of them advanced to active tuberculosis during the 36-month follow-up., Conclusion: The inactive status of tuberculosis infection may be maintained for a long period in AIDS patients on HAART.

Human immunodeficiency virus-1 (HIV-1) impairs tumor necrosis factor-alpha (TNF-alpha)-mediated macrophage apoptosis induced by Mycobacterium tuberculosis (Mtb). HIV Nef protein plays an important role in the pathogenesis of AIDS. We have tested the hypothesis that exogenous Nef is a factor that inhibits TNF-alpha production/apoptosis in macrophages infected with Mtb. We demonstrate that Mtb and Nef individually trigger TNF-alpha production in macrophages. However, TNF-alpha production is dampened when the two are present simultaneously, probably through cross-regulation of the individual signaling pathways leading to activation of the TNF-alpha promoter. Mtb-induced TNF-alpha production is abrogated upon mutation of the Ets, Egr, Sp1, CRE, or AP1 binding sites on the TNF-alpha promoter, whereas Nef-mediated promoter activation depends only on the CRE and AP1 binding sites, pointing to differences in the mechanisms of activation of the promoter. Mtb-dependent promoter activation depends on the mitogen-activated kinase (MAPK) kinase kinase ASK1 and on MEK/ERK signaling. Nef inhibits ASK1/p38 MAPK-dependent Mtb-induced TNF-alpha production probably by inhibiting binding of ATF2 to the TNF-alpha promoter. It also inhibits MEK/ERK-dependent Mtb-induced binding of FosB to the promoter. Nef-driven TNF-alpha production occurs in an ASK1-independent, Rac1/PAK1/p38 MAPK-dependent, and MEK/ERK-independent manner. The signaling pathways used by Mtb and Nef to trigger TNF-alpha production are therefore distinctly different. In addition to attenuating Mtb-dependent TNF-alpha promoter activation, Nef also reduces Mtb-dependent TNF-alpha mRNA stability probably through its ability to inhibit ASK1/p38 MAPK signaling. These results provide new insight into how HIV Nef probably exacerbates tuberculosis infection by virtue of its ability to dampen Mtb-induced TNF-alpha production.

Objective: To summarize the characteristics of clinical manifestation, chest radiology and microbiology of Rhodococcus equi pneumonia among patients with AIDS., Methods: Total 1908 AIDS patients who have therapy in Longtan hospital of Guang Xi province since May 2007 to Nov 2009, 15 patients (0.79%) who were co-infected with Rhodococcus equi, and average age was 35 +/- 13 years, we retrospectively reviewed clinical manifestations, chest radiology and microbiology of nine HIV-infected patients complicated with Rhodococcus equi pneumonia., Results: 14 patients presented with pneumonia or lung abscess, the clinical manifestations included fever (100%), cough and expectoration (93.3%), bellyache (26.7%), etc. And 5 patients Hb lower than 60 g/L, CD(4)(+)T cell count was between (1 - 51) x 10(6)/L, average was (20 +/- 16) x 10(6)/L, Patients presented with consolidation of lung. X-ray, or CT of lung showed large patchy consolidation image, inanition, atelectasis in the lung. Rhodococcus equi could be cultured from sputum, blood, tissue obtained through lung puncture, broncho-alveolar lavage fluid, etc. Though susceptible antibiotics were used, the focus in the lung was absorbed slowly, All of 15 patients begin with HAART, after 33 day to 2 years follow up 4 patients die and alive patients have perfect immune-rebuilt., Conclusions: Rhodococcus equi infection, an unusual disease, can be seen in AIDS patients and can be cured only with long-term effective antibiotic.