Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis.

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.

Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis

ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.

Brazilians' level of knowledge, attitudes and practices towards COVID-19: a cross-sectional study

ABSTRACT BACKGROUND: Brazil is facing increasing cycles of numbers of infected people and deaths resulting from coronavirus disease 2019 (COVID-19). This situation involves a series of factors, including the behavior of the population, that can be decisive for controlling the disease. OBJECTIVE: To determine the knowledge, attitudes and practices of the Brazilian population regarding COVID-19. DESIGN AND SETTING: Cross-sectional survey-type study, conducted using a population sample from different Brazilian states. METHODS: A quantitative, descriptive and analytical approach was used. Sampling was done according to convenience and via snowballing. The data collection instrument was a knowledge, attitudes and practices system. RESULTS: 1,655 people from all over Brazil participated in the survey; 80% were living in the southern region and 70.15% were female. More than 90% had knowledge and good attitudes relating to the means of transmission, preventive care and symptoms associated with COVID-19, although their knowledge and attitudes were not fully reflected in daily practices, for which there was lower adherence (80%). Greater knowledge was correlated with older participants, larger number of children, female sex and marital status; better attitude, with female sex and complete higher education; and better practices, with greater age, larger number of children and female sex. CONCLUSION: A large part of the population has general knowledge about COVID-19, but not all knowledge was applied in practice. Older people, females and university graduates stood out as the best informed and most committed to controlling the disease.

Brazilians' level of knowledge, attitudes and practices towards COVID-19: a cross-sectional study.

BACKGROUND: Brazil is facing increasing cycles of numbers of infected people and deaths resulting from coronavirus disease 2019 (COVID-19). This situation involves a series of factors, including the behavior of the population, that can be decisive for controlling the disease. OBJECTIVE: To determine the knowledge, attitudes and practices of the Brazilian population regarding COVID-19. DESIGN AND SETTING: Cross-sectional survey-type study, conducted using a population sample from different Brazilian states. METHODS: A quantitative, descriptive and analytical approach was used. Sampling was done according to convenience and via snowballing. The data collection instrument was a knowledge, attitudes and practices system. RESULTS: 1,655 people from all over Brazil participated in the survey; 80% were living in the southern region and 70.15% were female. More than 90% had knowledge and good attitudes relating to the means of transmission, preventive care and symptoms associated with COVID-19, although their knowledge and attitudes were not fully reflected in daily practices, for which there was lower adherence (80%). Greater knowledge was correlated with older participants, larger number of children, female sex and marital status; better attitude, with female sex and complete higher education; and better practices, with greater age, larger number of children and female sex. CONCLUSION: A large part of the population has general knowledge about COVID-19, but not all knowledge was applied in practice. Older people, females and university graduates stood out as the best informed and most committed to controlling the disease.

Chronic skull osteomyelitis due to Cryptococcus neoformans: first case report in an HIV-infected patient.

Osteomyelitis due to Cryptococcus neoformans are described in mostly 10% of patients with disseminated cryptococcosis, being direct inoculation even more uncommon. We report the case of an HIV-infected patient with history of recurring itching on his scalp and repetitive local trauma. For eighteen months, he noticed a painful and slow growing lump on his scalp. He was submitted to an excisional biopsy of the lesion but no etiological diagnosis was identified. After this procedure, the post-surgical wound never completely healed. At admission, the patient presented nausea and headache for three days and an open orifice into his skull. Investigations confirmed meningitis and skull osteomyelitis caused by Cryptococcus neoformans. He was treated with bone debridement and combined systemic antifungals, showing good clinical and laboratorial outcome. Cryptococcal disease should be included in the differential diagnoses of chronic osteomyelitis in HIV-infected patients and trauma is a possible source of infection.

Chronic skull osteomyelitis due to Cryptococcus neoformans: first case report in an HIV-infected patient

ABSTRACT Osteomyelitis due to Cryptococcus neoformans are described in mostly 10% of patients with disseminated cryptococcosis, being direct inoculation even more uncommon. We report the case of an HIV-infected patient with history of recurring itching on his scalp and repetitive local trauma. For eighteen months, he noticed a painful and slow growing lump on his scalp. He was submitted to an excisional biopsy of the lesion but no etiological diagnosis was identified. After this procedure, the post-surgical wound never completely healed. At admission, the patient presented nausea and headache for three days and an open orifice into his skull. Investigations confirmed meningitis and skull osteomyelitis caused by Cryptococcus neoformans. He was treated with bone debridement and combined systemic antifungals, showing good clinical and laboratorial outcome. Cryptococcal disease should be included in the differential diagnoses of chronic osteomyelitis in HIV-infected patients and trauma is a possible source of infection.

HIV-1 drug resistance and second-line treatment in children randomized to switch at low versus higher RNA thresholds

BACKGROUND: The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. METHODS: PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end. RESULTS: Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were <400 copies/mL 24 weeks later. CONCLUSIONS: Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance

Both human immunodeficiency virus-infected and human immunodeficiency virus-exposed, uninfected children living in Brazil, Argentina, and Mexico have similar rates of low concentrations of retinol, beta-carotene, and vitamin E.

Our objective was to describe the prevalence of low concentrations of retinol, beta-carotene, and vitamin E in a group of human immunodeficiency virus (HIV)-infected Latin American children and a comparison group of HIV-exposed, uninfected children. Our hypothesis was that the rates of low concentrations of these micronutrients would be higher in the HIV-infected group than those in the HIV-exposed, uninfected group. This was a cross-sectional substudy of a larger cohort study at clinical pediatric HIV centers in Latin America. Serum levels of micronutrients were measured in the first stored sample obtained after each child's first birthday by high-performance liquid chromatography. Low concentrations of retinol, beta-carotene, and vitamin E were defined as serum levels below 0.70, 0.35, and 18.0 micromol/L, respectively. The population for this analysis was 336 children (124 HIV-infected, 212 HIV-exposed, uninfected) aged 1 year or older to younger than 4 years. Rates of low concentrations were 74% for retinol, 27% for beta-carotene, and 89% for vitamin E. These rates were not affected by HIV status. Among the HIV-infected children, those treated with antiretrovirals were less likely to have retinol deficiency, but no other HIV-related factors correlated with micronutrient low serum levels. Low concentrations of retinol, beta-carotene, and vitamin E are very common in children exposed to HIV living in Brazil, Argentina, and Mexico, regardless of HIV-infection status.

Pesquisa clínica: aspectos éticos, científicos e regulatórios / Clinical research: ethical, scientific and regulatory issues

A pesquisa clínica constitui o principal meio para avaliação da eficácia e segurança de novos medicamentos e outras tecnologias médicas. Ainda que os ensaios clínicos estejam se desenvolvendo de maneira muito mais segura e ética do que se observava há décadas atrás, a eliminação de abusos grosseiros traz à tona alguns problemas éticos. Este artigo enfatiza dois grandes problemas éticos e desafios envolvidos na condução da pesquisa clínica: o conflito de interesses e a obtenção do consentimento informado. A maioria dos ensaios clínicos é financiada por indústrias farmacêuticas que apostam volumosas quantias nos produtos sendo avaliados. Além do mais, os cientistas que desenham, conduzem, analisam e publicam os resultados frequentemente recebem compensações financeiras pelas indústrias, tanto na forma de salário como taxas de aconselhamento. O consentimento é o processo pelo qual o paciente é informado e torna-se um participante nas decisões sobre seu manejo clínico. Argumenta-se, entretanto, que a obtenção da assinatura do participante no documento de consentimento informado adiciona muito pouco na qualidade do processo de consentimento. Este artigo também sugere medidas para assegurar a conduta científica e ética apropriada para ensaios clínicos.

Clinical trials are the primary means to evaluate the efficacy and safety of new drugs and other medical technologies. Although clinical trials are conducted far more ethically and safer now than they were some decades ago, the elimination of gross abuses has tended to highlight more subtle ethical problems. This review highlights two major ethical problems and challenges involved in the conduct of clinical trials: conflict of interest and consent process. Most clinical trials are funded by pharmaceutical companies with enormous financial stakes in the products being evaluated. Furthermore, the scientists who design, conduct, analyze, and report clinical trials often receive monetary compensation from drug companies, in the form of either salaries or consulting fees. Consent is a process by which a patient is informed and becomes a participant in decisions regarding their medical management. It is argued, however, that providing a signature to a form adds little to the quality of this process. This review also suggests measures to ensure scientifically and ethically sound clinical trials.

Histoplasmose de laringe / Histoplasmosis of the larynx

A histoplasmose com acometimento único de laringe é uma ocorrência rara da doença, com menos de 100 casos relatados na literatura, quando comparada ao número de pacientes diagnosticados com histoplasmose. Tal localização, quando isolada, pode induzir, erroneamente, ao diagnóstico e tratamento de tuberculose ou câncer de laringe, com casos relatados de tratamentos iniciados para essas doenças. Em um paciente com histoplasmose que desenvolva rouquidão, deve-se pensar no acometimento laríngeo da histoplasmose, enquanto que uma massa laríngea produzindo rouquidão deve incluir em seu diagnóstico diferencial a histoplasmose laríngea. Quando se pensa em histoplasmose como causa de uma lesão laríngea, a biópsia deve ser limitada, removendo a menor quantidade de tecido necessária para o diagnóstico O patologista deve ser avisado da possibilidade do diagnóstico, já que podem ser necessários corantes especiais para o diagnóstico.

The incidence of laryngeal histoplasmosis is low when compared to the total number of cases. Less than 100 cases of laryngeal histoplasmosis have been described in the medical literature. Isolated laryngeal involvement may lead to the misdiagnosis and mistreatment of tuberculosis or laryngeal cancer, according to some reports. The development of hoarseness in a patient with histoplasmosis or a laryngeal mass leading to hoarseness, might be suggestive of laryngeal histoplasmosis. When histoplasmosis is included among the differential diagnoses of a laryngeal lesion, the biopsy should be limited to a small tissue fragment, enough to perform histological tests. The laboratory technicians must be warned about the possibility of histoplasmosis, because special dyes have to be used to confirm this diagnosis.

Histoplasmosis of the larynx.

The incidence of laryngeal histoplasmosis is low when compared to the total number of cases. Less than 100 cases of laryngeal histoplasmosis have been described in the medical literature. Isolated laryngeal involvement may lead to the misdiagnosis and mistreatment of tuberculosis or laryngeal cancer, according to some reports. The development of hoarseness in a patient with histoplasmosis or a laryngeal mass leading to hoarseness, might be suggestive of laryngeal histoplasmosis. When histoplasmosis is included among the differential diagnoses of a laryngeal lesion, the biopsy should be limited to a small tissue fragment, enough to perform histological tests. The laboratory technicians must be warned about the possibility of histoplasmosis, because special dyes have to be used to confirm this diagnosis.

Avaliação longitudinal do crescimento de crianças nascidas de mães infectadas pelo HIV

Objetivos: determinar os efeitos da infecção materna pelo HIV durante a gravidez no crescimento de seus filhos, durante seus dois primeiros anos de vida. Métodos: de junho de 1986 até julho de 1995, 379 crianças nascidas de mães infectadas pelo HIV foram seguidas até completarem 2 anos de vida. Dados antropométricos foram coletados ao nascer e em consultas médicas mensais. Os dados foram convertidos em escores Z de acordo com o padrão NCHS. De acordo com os achados clínicos e laboratoriais as crianças foram divididas em trÊs grupos: não-infectadas, assintomáticas e sintomáticas (AIDS). As médias dos índices antropométricos foram comparadas. Resultados: das 379 crianças, 61 desenvolveram AIDS durante os dois primeiros anos de vida, 116 foram consideradas infectadas pelo HIV, porém assintomáticas e 202 foram consideradas não-infectadas. Não houve diferença estatisticamente significante quanto ao peso ou comprimento ao nascer entre crianças infectadas e não-infectadas. O escore Z médio das curvas de peso para idade revelaram que os três grupos apresentaram os menores índices aos seis meses de idade. A partir dessa idade as trÊs curvas mostram recuperação, porém em patamares distintos. Os patamares médios de WAZ para os grupos de sintomáticos, assintomáticos e não-infectados forma, respectivamente -1.71, -0.84 e +0.03. Padrões semelhantes foram observados na análise do parâmetro comprimento para a idade, com valores médios, respectivamente, de -2.03, -0.88 e -0.47. A análise do parâmetro peso para estatura/comprimento revelou que as curvas apresentadas pelos grupos de crianças assintomáticas e sintomáticas tiveram o mesmo padrão, com escore Z médio de -0.50, e o grupo de crianças não-infectadas desenvolveu-se no patamar +0.36. Conclusão: na nossa amostra a infecção materna pelo HIV não influenciou o peso ou comprimento ao nascer, independentemente da situação de infecção da criança. As crianças infectadas pelo HIV mostraram menores valores médios nos par?âmetros WAZ e HAZ, tornando-se mais alterados após a evolução para AIDS. O parâmetro WHZ foi o menos afetado, mostrando que todos os grupos mantém uma relação harmoniosa entre peso e altura