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Talaromyces marneffei is a pathogenic fungus that causes fatal health complications for patients who are infected with HIV. For the current investigation, sputum samples were collected from 19 immunosuppressed patients from two hospitals located in Baghdad, Iraq by which they were inoculated onto both Sabouraud dextrose agar (SDA) medium at 25 °C and BHI (brain heart infusion) agar at 36±1 °C for growth before being identified using single and nested PCR methods. The 18S rRNA gene sequence of T. marneffei was used to create two sets of oligonucleotide primers, RRF1 and RRH1 which are considered fungus-specific outer primers were employed. Both nested and solo PCRs using the T. marneffei-specific inner primers (Pm1 and Pm2) were carried out. To define the phylogenetic relatedness of this isolate, the MEGA X program was used to align the nuclear ribosomal DNA (rDNA) sequences of T. marneffei. Results showed that the wine-colored pigmented isolates in agar were dimorphic, exhibited bloom-like twigs and spore chains characteristic under the microscope, and were filamentous type colonies with light yellow villi. Finally, immuno-compromised patients in Iraq have T. marneffei in their blood cultures that will be induced to pathogenicity, and the PCR assay is valuable for T. marneffe identifying. Other results from nested PCR revealed that 8 human isolates, from 19, have specific fragments of about 400 bp on the agarose gel.

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.

Stenotrophomonas maltophilia (S. maltophilia) is an intrinsically drug-resistant and biofilm-forming bacteria causing infections in immunocompromised humans. This study reports the isolation of five S. maltophilia strains from saliva and gingival crevicular fluid (GCF) of AIDS patients with periodontitis in São Paulo, Brazil, showing resistance to ceftazidime, strong biofilm formation capacity and a close genetic relationship. The presence of S. maltophilia strains in saliva and CGF of patients with AIDS and periodontitis is a concern for the presence and persistence of intrinsically resistant bacteria in the oral environment, enhancing the risk for the development of severe infections in immunocompromised patients., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

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.)

Extracorporeal membrane oxygenation (ECMO) can affect antimicrobial pharmacokinetics. This case report describes a 33-year-old male with newly diagnosed acquired immunodeficiency syndrome presenting in acute severe type 1 respiratory failure. On investigation, the patient had positive cultures for Candida albicans from respiratory specimens and high blood cytomegalovirus titres, and required venovenous ECMO therapy for refractory respiratory failure. Intravenous fluconazole (6 mg/kg, 24-h) and ganciclovir (5 mg/kg, 12-h) was commenced. Pre-oxygenator, post-oxygenator and arterial blood samples were collected after antibiotic administration, and were analysed for total fluconazole and ganciclovir concentrations. Although there was a 40% increase in the volume of distribution for fluconazole relative to healthy volunteers, the pharmacodynamic targets for prophylaxis were still met. The area under the curve exposure of ganciclovir (50.78 mg•h/L) achieved target thresholds. The ECMO circuit had no appreciable effect on achievement of therapeutic exposures of fluconazole and ganciclovir., Competing Interests: Declaration of Competing Interest None declared., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

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 .

Introduction: Cryptococcus neoformans is an opportunistic pathogen that causes ∼15% mortality in AIDS patients. Rio Grande City, Rio Grande do Sul (RS), Brazil, has the highest national rate of HIV/AIDS, considering cities with population more than 100,000 habitants., Objective: We aimed to evaluate the clinical and epidemiological profile of cryptococcosis in a reference service for HIV-AIDS patients in the South region of Brazil, over seven years. Material and methods A retrospective study was performed including all cryptococcosis cases diagnosed at the University Hospital, Federal University of Rio Grande (UH-FURG) between January 2010 and December 2016., Results: Seventy cases of cryptococcosis were diagnosis from 2010 to 2016 in the UH-FURG in the seven years of the study. These numbers were responsible for 2.1% to 8.1% of the hospitalizations/year for HIV patients. All were caused by C. neoformans infection (95% C. neoformans var. grubii VNI and 5% C. neoformans var. grubii VNII). Neurocryptococcosis was the major clinical manifestation and cryptococcosis was the HIV- defining condition in 40% of patients. The period of hospitalization was an average of 39.3 days (SD=31.3), and more than half of patients (53%; 37/70) died after a mean of 82 days., Discussion: The present study showed the importance of cryptococcosis as an AIDS-defining disease in HIV-AIDS patients in a tertiary hospital from Southern Brazil. More investment is necessary to reduce the impact of this opportunistic mycosis in HIV-AIDS patients from southern Brazil., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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.)

Background Sexually transmitted infections continue to be a major health concern in sub-Saharan Africa where antimicrobial drugs are becoming ineffective due to increasing resistance. Many healthcare seekers in lower socio-economic settings depend on invasive alien plants administered by traditional health practitioners to treat sexually transmitted infections. Methods Roots of selected plants were analysed for phytoconstituents using standard methods. Both the disc diffusion model and microdilution technique were used to determine the inhibition zone and minimum inhibitory concentration (MIC) of plant extracts against six clinical fungal strains and standard strain of Neisseria gonorrhoea. One-way ANOVA was used to find significant differences. Results Different phytoconstituents such as alkaloids, steroids, cardiac glycosides, terpenes, flavonoids, tannins and saponins were qualitatively detected, depending on plant species. Acetone extracted the highest number of phytoconstituents in Senna didymobotrya, while methanol revealed most from Ricinus communis. Senna didymobotrya showed significant inhibition against Candida glabrata, C. krusei, C. parapsilosis and C. tropicalis. Dichloromethane extract of Catharanthus roseus and methanol extract of S. didymobotrya demonstrated excellent MIC values of 0.03 and 0.08 mg/mL, respectively, against C. glabrata. Catharanthus roseus, Opuntia ficus-indica and Ricinus communis demonstrated moderate to good antigonococcal activity, with all exhibiting more than 63% inhibition. Catharanthus roseus had the best antigonococcal activity with a moderate MIC value of 0.63 mg/mL. Conclusion Some of the plant extracts demonstrated potency towards clinically isolated fungal strains and against N. gonorrhoea, which validate the notion that some of the species need further pharmacological studies for isolation and characterisation of active compounds.

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.

We report here a case of disseminated Emergomyces pasteurianus infection from India in a patient with AIDS. The patient presented with weight loss, dyspnoea and multiple non-tender skin lesions over face, neck and chest over 3 months. The case was diagnosed by microscopy, histopathology of sample and isolation of fungus from skin lesion, breast nodule, bone marrow and sputum. The identification of the isolates was confirmed by sequencing internal transcribed spacer region of rDNA, beta-tubulin, actin and intein PRP8. The patient responded well to intravenous amphotericin B deoxycholate followed by itraconazole therapy.

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.

Paracoccidioidomycosis (Pm) is a systemic disease, endemic in the American continent. There are two different clinical forms, the infant-juvenile or subacute form (PmS) and the chronic adult form (PmC). The human immunodeficiency virus (HIV) associated paracoccidioidomycosis (PmHIV) shares characteristics with both of the previously mentioned forms. The objective of this work was to describe the epidemiological, clinical and laboratory features of the PmHIV and to compare them with the ones of PmS and the PmC. A retrospective analysis of 119 patients with paracoccidioidomycosis was performed. Ninety four suffered the chronic form, 11 the subacute one and 14 were coinfected with HIV. Patients with PmHIV presented a CD4+ T lymphocytes median of 70.5 cells/μl, 71.4% had fever, 64.3% had a miliary pattern on the chest radiography, 64.3% had hepatosplenomegaly, 64.3% had mucosal lesions and 50% had skin lesions. One patient died during his hospitalization. The clinical presentation of Pm in patients with HIV resembled the subacute form with fever, hepatomegaly and skin lesions. However, they also tended to present mucosal lesions, positive serology for Pm and pulmonary parenchyma lesions as usually seen in PmC (9/14 PmHIV patients had overlapping features, while 4/14 PmHIV patients clinically resembled PmS and 1/14 PmC). The incidence of Pm has not changed with the burden of AIDS as it has happened with other fungal infections but it appears clinically different from the classic clinical forms of the disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

In the first three decades after AIDS started infecting people in the USA and Canada, before, during and after the emergence of anti-retroviral therapies, numerous "alternative and holistic treatments" for AIDS were debated, tested, circulated, written about and taught. This paper, taking a narrow focus, examines documents that reveal how some people with AIDS developed a logic of care predicated on intimate interactions with microscopic lifeforms-the AIDS virus and the bacteria involved in fermentation, in particular. Focusing on the writings of Jon Greenberg and Sandor Katz, two former members of ACT UP/NY, I show that the men did not just dissent from management by biomedical authority but found new authority about how to care for themselves as people with AIDS from their interactions with non-human microscopic life. The practices and writings of both men demonstrate that Foucault's theory of counter-conduct exists in the history of AIDS as an interspecies process in which microscopic existents lead humans. From Katz and Greenberg, I argue there is an interspecies dimension to counter-conduct that exists as a frame for understanding people who find in non-human life a guide towards unconventional forms of care, revised forms of human behaviour and philosophies for persisting with illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

A set of 185 strains of Candida albicans from patients with vulvovaginal candidiasis (VVC) and from non-VVC clinical sources in southwest China was analysed. Strains were subjected to genotyping using CAI microsatellite typing and amplification of an intron-containing region of the 25S rRNA gene. Microsatellite genotypes of strains from non-VVC sources showed high polymorphism, whereas those of VVC were dominated by few, closely similar genotypes. However, among non-VVC strains, two genotypes were particularly prevalent in patients with lung cancer. 25S rDNA genotype A was dominant in VVC sources (86.7%), whereas genotypes A, B, and C were rather evenly distributed among non-VVC sources; known genotypes D and E were not found. In an experimental mouse model, isolates from lung cancer and AIDS patients proved to have higher virulence than VVC strains. Among 156 mice infected with C. albicans, 19 developed non-invasive urothelial carcinoma. No correlation could be established between parameters of virulence, source of infection, and incidence of carcinoma. C. albicans strains from VVC were less susceptible to itraconazole than the strains from non-VVC sources, whereas there was small difference in antifungal susceptibility between different 25S rDNA genotypes of C. albicans tested against amphotericin B, itraconazole, fluconazole, and flucytosine., (© 2019 The Authors Yeast Published by John Wiley & Sons Ltd.)

Background: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia., Methods: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor., Results: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001)., Conclusions: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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.

The allergic airway diseases, including chronic rhinosinusitis (CRS), asthma, allergic bronchopulmonary mycosis (ABPM) and many others, comprise a heterogeneous collection of inflammatory disorders affecting the upper and lower airways and lung parenchyma that represent the most common chronic diseases of humanity. In addition to their shared tissue tropism, the allergic airway diseases are characterized by a distinct pattern of inflammation involving the accumulation of eosinophils, type 2 macrophages, innate lymphoid cells type 2 (ILC2), IgE-secreting B cells, and T helper type 2 (Th2) cells in airway tissues, and the prominent production of type 2 cytokines including interleukin (IL-) 33, IL-4, IL-5, IL-13, and many others. These factors and related inflammatory molecules induce characteristic remodeling and other changes of the airways that include goblet cell metaplasia, enhanced mucus secretion, smooth muscle hypertrophy, tissue swelling and polyp formation that account for the major clinical manifestations of nasal obstruction, headache, hyposmia, cough, shortness of breath, chest pain, wheezing, and, in the most severe cases of lower airway disease, death due to respiratory failure or disseminated, systemic disease. The syndromic nature of the allergic airway diseases that now include many physiological variants or endotypes suggests that distinct endogenous or environmental factors underlie their expression. However, findings from different perspectives now collectively link these disorders to a single infectious source, the fungi, and a molecular pathogenesis that involves the local production of airway proteinases by these organisms. In this review, we discuss the evidence linking fungi and their proteinases to the surprisingly wide variety of chronic airway and systemic disorders and the immune pathogenesis of these conditions as they relate to environmental fungi. We further discuss the important implications these new findings have for the diagnosis and future therapy of these common conditions., (© 2019 Elsevier Inc. All rights reserved.)

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.

Objective: Luliconazole is an inhibitor for sterol 14-α-demethylase in fungal cells with a broad-spectrum antifungal activity against dermatophytes, Candida albicans, Malassezia species, dematiaceous and hyaline hyphomycetes. Furthermore, luliconazole has been clinically used for the treatment of pityriasis versicolor, dermatophytosis, onychomycosis, cutaneous and mucocutaneous candidiasis. In the present study, we aimed to evaluate in vitro antifungal activity of luliconazole against several strains of Candida species recovered from different clinical materials., Materials and Methods: In the present study, 104 strains of Candida species including, 34 isolates from vaginitis, 23 isolates from AIDS patients with vaginal candidiasis, 24 isolates from neutropenic patients and 24 isolates from tracheal tubes, were examined for susceptibility tests. A serial dilution of luliconazole (4-0.008μg/mL) was tested against different strains of Candida species recovered from different sources., Results: The minimum inhibitory concentration (MIC) range and MIC 90 of vaginal isolates (HIV - ) were 1-0.063 and 1μg/mL. Furthermore, the most of strains (50%) had a MIC of 0.5μg/mL. The MIC ranges were similar (2-0.016μg/mL) for both vaginal (HIV + ) and neutropenic patients isolates, whereas, MIC 90 for them were 0.5 and 1μg/mL, respectively. All tracheal tubes strains were inhibited at the range of 2-0.008μg/mL with MIC 90 =1μg/mL. Totally, the lowest MIC 50 (MIC=0.015μg/mL), MIC 90 (MIC=1μg/mL) and MIC GM (MIC=0.05μg/mL) are correlated to C. glabrata, a non-albicans species., Conclusion: It is concluded that, luliconazole could be an alternative anti-Candida agent, however, in vivo studies must be confirmed usefulness of drug for clinical usage., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To compare clinical characteristics and therapeutic outcomes between HIV and non-HIV patients with Cryptococcus neoformans meningitis (CNM)., Methods: A total of 73 patients with CNM (30 patients without HIV and 43 with HIV) were admitted from January 2012 to January 2017. The clinical manifestations,biochemical and microbiological characteristics of cerebrospinal fluid (CSF) were collected and analyzed., Results: The patients in the two group displayed non-specific symptoms such as headache,fever,nausea and vomiting. Non-HIV CNM patients had more serious inflammatory reaction with higher karyocytes and protein level ( P =0.000, P =0.041,respectively),while had lowere positive rate of primary ink staining in cerebrospinal fluid (70.0% vs. 93.0%, P =0.009),higher misdiagnosis rate (43.3% vs. 14.0%, P =0.005),longer hospitalization duration [(112.27±105.42) d vs. (52.64±39.17) d, P =0.021],higher adverse reactions rate of antifungal treatment was (80.0% vs. 30.2%, P =0.000). However,in HIV CNM patients,40 (93.0%) patients did not receive antiviral therapy before and were diagnosed as AIDS for the first time; the therapeutic effect in this group was very poor with higher mortality (30.2% vs. 13.4%, P =0.000)., Conclusion: Immunity status should be considered in the diagnosis and treatment of CNM,since it is difficult to diagnose with long treatment period and poor prognosis., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

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.)

The increased co-incidence of tuberculosis (TB) and AIDS is compounded by the emergence of opportunistic infections with non-tuberculous mycobacteria (NTM) in patients with HIV/AIDS, and the treatment for these infections differs from that for TB. The high frequency of NTM strains found in patients infected with HIV raises concerns about accurate species identification before deciding proper treatment. A total of 101 isolates from 2014, 137 from 2015, and 162 from 2016 were subjected to 16S rDNA sequencing to identify the species. Forty-one (41/101, 40.6%) were identified as NTM in 2014, 64 (64/137, 46.7%) were identified as NTM in 2015, and 72 (72/162, 44.4%) were identified as NTM in 2016 in Chinese patients infected with HIV. The species of Mycobacteria isolates needs to be rapidly and accurately identified to determine appropriate antibiotic therapy, and this is especially true for patients infected with HIV.

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.

Diagnosis of central nervous system cryptococcosis relies on a spectrum of methods but has improved with lateral flow diagnostic assays that detect capsular polysaccharide antigens of Cryptococcus. Here, we present the case of an HIV-infected African-American man with cryptococcal meningoencephalitis caused by a strain producing little or no capsule., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Cryptococcal meningitis is one of the leading causes of death in HIV/AIDS patients. Our aim was to in order to characterise the epidemiology, antifungal susceptibility pattern and virulence of 28 Cyptococcus sp. strains recovered from 12 AIDS patients during two years in a Spanish single institution. Antifungal susceptibility testing was performed according to the CLSI protocols. Clinical strains were molecularly characterised by serotyping, mating type, PCR fingerprinting (M13 and GACA 4 microsatellites) and analysis of two rDNA regions (IGS1 and ITS). Sequencing of the ERG11 gene was used to explore mechanisms of fluconazole resistance. Differences in virulence between species were studied in a Galleria mellonella infection model. Cryptococcus deneoformans and C. deneoformans x Cryptococcus neoformans hybrids were the most frequent variety (65%) followed by C. neoformans (35%). Strains were categorised according to 13 microsatellite genotypes and mixed infections could be detected in three patients. Twenty-nine per cent of the strains were fluconazole resistant. In one of the patients, the fluconazole resistance phenotype was associated with a point mutation in the ERG11 gene responsible for the amino acid substitution G470R. C. neoformans strains were able to kill G. mellonella larvae more efficiently than C. deneoformans and hybrids between both species. Precisely molecular characterisation of C. neoformans species is important for an accurate patient's management., (© 2016 Blackwell Verlag GmbH.)

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.

Objectives: Bacteria from the intestinal tract of Slovak and American HIV/AIDS patients and Slovak colon cancer patients were tested for the capacity to be internalized by cells of the HL-60 cell line as well as by normal human lymphocytes. They were anticipated to possess a specific characteristic, i.e. a vigorous ability to be internalized by HL-60 cells and human lymphocytes. This assumption was confirmed by gentamicin protection assay., Results: Internalization of bacteria from HIV/AIDS patients frequently resulted in partial (patients SKM1, SKM22) or complete lysis (patients SKK1-1, SKM12) of HL-60 cells. In comparison with intramucosal bacteria isolated from patients with colorectal cancer (TSG, 883, 660, 838, 536, MZRa), their capacity to internalize HL-60 cells was found to be 15-20 times higher (USP15/7, USP1/4, USP3/3, SK725/5). Partial lysis (patients USP15/7, USP3/3 and SKM22) and complete lysis (patients USP1/4, SKK1-1/1, SKM1/6, SKM12/5) were detected also after internalization of bacteria by normal human lymphocytes. Compared to the amount of intracellular bacteria isolated from patients with HIV/AIDS, the ability of bacteria from patients with colorectal cancer to internalize normal human lymphocytes was significantly lower (10-15 times), yet still higher than that of bacteria isolated from healthy people., Conclusions: Our results present the ability of bacteria of colon cancer patients and HIV/AIDS patients to internalize HL-60 cells and normal human lymphocytes. The findings underline the potentially important function of bacteria in the induction of colorectal cancer and immunodeficiency. The particularly high detection ability of bacteria from HIV/AIDS patients to internalize normal human cells emphasizes their potentially important role in the process of AIDS.

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.

Choroidal tuberculosis is present in 5-20% of patients with disseminated tuberculosis, and point-of-care dilated binocular indirect ophthalmoscopy eye examination can provide immediate diagnosis. In geographical areas of high tuberculosis prevalence and in susceptible patients (CD4 counts less than 200 cells per μL) detection of choroidal granulomas should be accepted as evidence of disseminated tuberculosis. With training and proper support, eye screening can be done by HIV/AIDS clinicians, allowing early tuberculosis treatment. In regions with a high burden of tuberculosis, we recommend that eye screening be a standard part of the initial assessment of susceptible patients, including at a minimum all patients with HIV/AIDS with CD4 less than 100 cells per μL with or without eye symptoms, and with or without suspicion of disseminated tuberculosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.)

Objective: To investigate the infection status of Mycoplasma pirum among male HIV/AIDS patients in Jiangsu and analyze the risk factors. The genome sequencing of Mycoplasma pirum was completed for the first time., Methods: Male HIV infected individuals and AIDS patients confirmed in Jiangsu province were enrolled for 4 repeated cross-sectional studies by means of detecting the first flow urine sample and venous blood sample collected and questionnaire survey after informed consent. Genome sequencing was conducted for Mycoplasma pirum by using Illumina Hiseq 2000 sequencing platform., Results: A total of 1 541 HIV/AIDS patients were surveyed in this study. The infection rates of Mycoplasma pirum was 15.4%. The patients who received no HAART had higher risk to be infected with Mycoplasma pirum (OR = 1.344, 95% CI: 1.008-1.792). Otherwise, high CD4⁺T counts was a protective factor for Mycoplasma pirum infection (OR = 0.600, 95% CI: 0.444-0.810). Based on the sequencing result, the genome size of Mycoplasma pirum was 850 704 bp, the GC content was 24.21% the genome contained 708 genes, the total length of genes was 734 085 bp, the average length was 1 037 bp, accounting for 86.29% of genome., Conclusion: More attention should be paid to the high infection rate of Mycoplasma pirum among male HIV/AIDS patients in the future AIDS prevention and control. The first genome sequencing of standard Mycoplasma pirum strain was completed in this study (registering serial number: AZHZ00000001), which can provide evidence for the further research of gene function and pathogenic mechanism of Mycoplasma pirum.