Lodderomyces elongisporus as causative organism of oropharyngeal infections - Two case reports.

We report two cases of patients with oropharyngeal infection by Lodderomyces elongisporus. The identification of the two isolates was confirmed after sequencing the ITS1 and ITS4 regions. The antifungal susceptibility test revealed low MIC values for the different antifungals tested. This is the first reported case of L. elongisporus present during an oropharyngeal infection and describes the laboratory methodology employed in the diagnosis.

Distribution and antifungal susceptibility profiles of Candida species isolated from people living with HIV/AIDS in a public hospital in Goiânia, GO, Brazil.

Oropharyngeal candidiasis (OPC) is the most common opportunistic fungal infection of the oral cavity and is a significant clinical problem, particularly in immunocompromised individuals, such as people living with HIV/AIDS (PLWHA). Although Candida albicans is the most frequent pathogen, at least 30 species capable of causing infection have been described. Identifying the infecting organism is necessary because the species respond differently to therapy, and antifungal susceptibility testing is important to determine the appropriate treatment. This study aimed to determine the epidemiological, clinical, and mycological profiles of OPC in hospitalized PLWHA. Clinical samples were collected from 103 PLWHA with suspected candidiasis admitted to the Hospital Estadual of Doenças Tropicais/Hospital Anuar Auad of Goiania, Goias, Brazil, for 14 months. Candida species were identified using phenotypic microbiological techniques and molecular analysis performed by PCR using species-specific primers. The antifungal susceptibility pattern of the isolates against the six antifungal agents was determined using the broth microdilution method. Here, female individuals were the most affected by OPC, presenting a higher risk of oral colonization by Candida spp. The main clinical manifestation was pseudomembranous candidiasis. The number of cases of candidiasis was 87.3% (90/103), with C. albicans being the most common species, followed by C. tropicalis and C. glabrata. In the susceptibility pattern, non-albicans Candida showed higher resistance to than C. albicans. The fast and accurate identification of Candida spp. is very important to identify therapeutic agents for the treatment of oral candidiasis in PLWHA.

False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia

The detection of cryptococcal capsular antigen (CrAg) is very sensitive and specific, however false-negative results have been reported, mostly in cerebrospinal fluid. We report the case of an HIV-infected patient with CD4=42 cells/mL, asthenic, negative serum CrAg lateral flow assay (LFA) and culture-proven cryptococcaemia. Despite the high accuracy of LFA, false-negative result is possible. Careful clinical evaluation and close follow-up are relevant

False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia.

The detection of cryptococcal capsular antigen (CrAg) is very sensitive and specific, however false-negative results have been reported, mostly in cerebrospinal fluid. We report the case of an HIV-infected patient with CD4 = 42 cells/mL, asthenic, negative serum CrAg lateral flow assay (LFA) and culture-proven cryptococcaemia. Despite the high accuracy of LFA, false-negative result is possible. Careful clinical evaluation and close follow-up are relevant.

Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil.

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.

Histoplasmosis, An Underdiagnosed Disease Affecting People Living With HIV/AIDS in Brazil: Results of a Multicenter Prospective Cohort Study Using Both Classical Mycology Tests and Histoplasma Urine Antigen Detection.

BACKGROUND: Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals. METHODS: This was a prospective cohort study (2016-2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. RESULTS: From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm3, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis. CONCLUSIONS: Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm3. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.

Histoplasmosis, an underdiagnosed disease affecting people living with HIV/AIDS in Brazil: Results of a multicenter prospective cohort study using both classical mycology tests and histoplasma urine antigen detection

BACKGROUND: Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals. METHODS: This was a prospective cohort study (2016­2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. RESULTS: From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm3, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis. CONCLUSIONS: Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm3. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries

Investigation of genetic polymorphisms related to the outcome of radiotherapy for prostate cancer patients.

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002-0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006-0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.

Clinical evaluation of normal tissue toxicity induced by ionizing radiation in cases of larygeal carcinoma

Laryngeal cancer is the second most frequent head and neck cancer in the Brazilian male population. For treatment, radiotherapy combined with chemotherapy is now used in substitution for total laryngectomy, becoming the standard treatment for advanced larynx cancer cases, with the aim of organ preservation. However, this method needs assessment of the side effects caused to normal tissue and organ functionality after treatment and the relation of these clinical factors to the individual characteristics of patients. Thus, the clinical characteristics of 229 patients with laryngeal cancer treated with radiotherapy were evaluated by medical records analysis in relation to normal tissue radiosensibility. Significant relations between smoking (p = 0.018) and combined chemoradiotherapy assistance (p = 0.03) were identified with high frequency of treatment suspension cases. The application of combined chemoradiotherapy also resulted in a higher incidence of oral mucositis (p = 0.04), xerostomia (p = 0.001) and treatment side effects to GIT (p = 0.04). Advanced clinical staging was associated with worse prognosis (p = 0.002) and a higher occurrence of treatment failure (p < 0.001). Radiotherapy was also less effective depending on the primary tumor location (p = 0.001)