Paracoccidioidomycosis: Current Status and Future Trends.

Paracoccidioidomycosis (PCM), initially reported in 1908 in the city of São Paulo, Brazil, by Adolpho Lutz, is primarily a systemic and neglected tropical mycosis that may affect individuals with certain risk factors around Latin America, especially Brazil. Paracoccidioides brasiliensis sensu stricto, a classical thermodimorphic fungus associated with PCM, was long considered to represent a monotypic taxon. However, advances in molecular taxonomy revealed several cryptic species, including Paracoccidioides americana, P. restrepiensis, P. venezuelensis, and P. lutzii, that show a preference for skin and mucous membranes, lymph nodes, and respiratory organs but can also affect many other organs. The classical diagnosis of PCM benefits from direct microscopy culture-based, biochemical, and immunological assays in a general microbiology laboratory practice providing a generic identification of the agents. However, molecular assays should be employed to identify Paracoccidioides isolates to the species level, data that would be complemented by epidemiological investigations. From a clinical perspective, all probable and confirmed cases should be treated. The choice of treatment and its duration must be considered, along with the affected organs, process severity, history of previous treatment failure, possibility of administering oral medication, associated diseases, pregnancy, and patient compliance with the proposed treatment regimen. Nevertheless, even after appropriate treatment, there may be relapses, which generally occur 5 years after the apparent cure following treatment, and also, the mycosis may be confused with other diseases. This review provides a comprehensive and critical overview of the immunopathology, laboratory diagnosis, clinical aspects, and current treatment of PCM, highlighting current issues in the identification, treatment, and patient follow-up in light of recent Paracoccidioides species taxonomic developments.

Chromoblastomycosis in Latin America and the Caribbean: Epidemiology over the past 50 years.

Chromoblastomycosis is a chronic disease caused by melanized fungi that mainly affect individuals performing soil-related labor. The objective of this study was to analyze the epidemiological and clinical characteristics of chromoblastomycosis in Latin America and the Caribbean by an extensive literature review. An integrative review was performed of English, French, Portuguese, and Spanish publications in LILACS, SciELO, PubMed, SCOPUS and Web of Science databases covering the period 1969-2019. A total of 1211 articles were identified, of which 132 were included in the review, covering 2081 patients, 80.3% were males, the mean age was 56.1 years. The mean duration of the disease was 10.8 years. The lesions were mainly described in the lower limbs (60%). The most frequent clinical forms were verrucous (46.4%) and tumorous (21.7%). Major disease symptoms and signs consisted of itching and pain. Bacterial infection and functional limitation were important complications. Immunosuppression post-kidney transplantation was the most frequent comorbidity while leprosy was the main concomitant infectious disease. Fonsecaea pedrosoi and Cladophialophora carrionii were the predominant etiological agents. Majority of the cured cases were treated with itraconazole as monotherapy or in combination with other antifungals, surgery or cryosurgery. Chromoblastomycosis affects hundreds of rural workers in Latin America and the Caribbean, causing disability and personal, family and economic losses. It is important to prioritize epidemiological surveillance and early diagnosis of this disease in order to reveal its real prevalence and direct resources to preventive actions, diagnosis and early treatment. LAY SUMMARY: Chromoblastomycosis is a slowly progressing chronic disease caused by melanized fungi. We collected data from South America and the Caribbean covering 1969-2019, the 132 articles included 2081 patients, mean disease duration was 10.8 years. Fonsecaea pedrosoi and Cladophialophora carrionii predominated.

Puzzling paracoccidioidomycosis: Factors associated with the severity of Paracoccidioides lutzii infections.

OBJECTIVES: Historically, the Brazilian Central-West region has had high numbers of paracoccidioidomycosis (PCM) cases caused by the dimorphic fungus Paracoccidioides lutzii. METHODS: This epidemiological, observational, analytical, cross-sectional study was performed to investigate the clinical and laboratory data of 44 PCM patients with a culture-proven P. lutzii infection. All patients were referred to the Systemic Mycosis Center, Júlio Muller University Hospital, Cuiabá, Brazil, during January 2017 to March 2020. The neutrophil to lymphocyte ratio (NLR) was calculated and dichotomized by its median value to include in the identification of factors associated with severity. RESULTS: At admission, 13 (31.7%) patients showed the disseminated multifocal chronic form of PCM and 16 (36.4%) patients met the clinical severity criteria. Treatment prescribed on admission did not follow the recommendations of the Brazilian Guideline for the Clinical Management of Paracoccidioidomycosis in 26% of the severe PCM cases (prevalence ratio 0.26, 95% confidence interval 0.14-0.49; P < 0.0001). Patients with severe PCM had a higher NLR that was greater than the median (≥4.11). CONCLUSIONS: The NLR biomarker complements the criteria for PCM severity. Applying the low-cost NLR test can greatly increase the diagnostic sensitivity when screening patients for PCM and contribute to better control of the disease, management of complications, and therapeutic strategies.

Paracoccidioidomycosis due to P lutzii: The importance of neutrophil/lymphocyte ratio in the symptomatic and asymptomatic phases in severe cases.

BACKGROUND: PCM is a neglected systemic mycosis endemic in Brazil. The middle-west region of Brazil has shown the highest number of PCM by Paracoccidioides lutzii (P lutzii) cases. Differentiating cases of severe PCM from non-severe ones should be a concern at the bedside. Diagnosis of severe PCM by P lutzii is based on the subjectivity of clinical manifestations, which can result in a delay in starting its treatment and, consequently evolution to severe sequelae. There is not laboratory biomarker available to support the early diagnosis of severe PCM that is feasible for all the realities that coexist in Brazil. OBJECTIVES: The aim of this study was to investigate the usefulness of laboratory biomarkers as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) in the diagnosis of severe PCM. PATIENTS/METHODS: ESR, CRP and NLR were analysed for 44 patients with PCM by P lutzii and a Receiver Operation Characteristic (ROC) curve were generated to identify the NLR cut-off point and point out the presence of severe PCM. RESULTS: Sixteen (36.4%) had severe PCM and 28 (63.6%) had non-severe PCM. The mean NLR was higher and statistically significant among patients with severe PCM than among those with non-severe PCM. The area under the ROC curve was 0.859 for the diagnosis of severe PCM. The cut-off point for NLR for the diagnosis of severe PCM was 3.318 (sensitivity of 100%, specificity of 77%). CONCLUSIONS: According to results, it is plausible to conclude that NLR represents a potential biomarker for the diagnosis of severe PCM.

New laboratory perspectives for evaluation of vivax malaria infected patients: a useful tool for infection monitoring

ABSTRACT In recent years, the number of cases with severe Plasmodium vivax malaria has shown an increasing trend. It is, therefore, important to identify routine laboratory markers that best characterize the acute disease phase and can serve as a tool for clinical follow-up of patients. In a cohort study, we followed 87 patients with acute P. vivax monoinfection acquired in an endemic region of the Brazilian Amazon. Forty-two different biochemical and hematological parameters frequently tested in clinical routine were evaluated at the acute phase and the convalescent phase. A total of 42 laboratory tests were performed: biochemical parameters measured were serum lipids levels, aminotransferases, bilirubin, amylase, glucose, urea, creatinine, albumin, globulin, uric acid, C-reactive protein, and alpha-1-acid glycoprotein. Hematological parameters included total and differential white blood cell and platelet counts, hemoglobin concentration, mean platelet volume, platelet width distribution, and plateletcrit. Our results show that several biochemical and hematological parameters were associated with acute phase P. vivax malaria and these parameters reverted to normal values in the convalescent phase. The use of these parameters during diagnosis and follow-up of the infection is a useful clinical tool to evaluate the clinical course and therapeutic response of patients with uncomplicated vivax malaria.

Clinical and epidemiological features of paracoccidioidomycosis due to Paracoccidioides lutzii.

BACKGROUND: The fungus Paracoccidioides lutzii was recently included as a new causative species of paracoccidioidomycosis (PCM) and most cases have been reported from Brazil. According to available epidemiological information, P. lutzii is concentrated in the Middle-West region in Brazil, mainly in the state of Mato Grosso. However, clinical and laboratorial data available on patients infected with P. lutzii remain extremely limited. METHODOLOGY/MAIN FINDINGS: This work describes the clinical manifestations of 34 patients suffering from PCM caused by P. lutzii, treated along 5 years (2011-2017) at a reference service center for systemic mycoses in Mato Grosso, Brazil. Adult rural workers (men), aged between 28 and 67 predominated. All patients had the chronic form of the disease, and the oral mucosa (n = 19; 55.9%), lymph nodes (n = 23; 67.7%), skin (n = 16; 47.1%) and lung (n = 28; 82.4%) were the most affected sites. Alcohol intake (n = 19; 55.9%) and smoking (n = 29; 85.3%) were frequent habits among the patients. No patient suffered from any other life-threatening disease, such as tuberculosis, cancer or other inflammatory or infectious parasitic diseases. The positivity in culture examination (97.1%) was higher than that found for the direct mycological examination (88.2%). Particularly, one patient presented fungemia at diagnosis, which lead to his death. The time elapsed between the initial symptoms and the initiation of treatment of PCM caused by P. lutzii was 19.7 (31.5) months, with most patients diagnosed 7 months after the symptoms' onset. CONCLUSIONS/SIGNIFICANCE: Compared with the classical clinical-epidemiological profile of PCM caused by P. brasiliensis, the results of this descriptive study did not show significant clinical or epidemiological differences that could be attributed to the species P. lutzii. Future studies may confirm or refute the existence of clinical differences between the two fungal species.

Decreased uric acid levels in the acute phase of Plasmodium vivax malaria

Abstract INTRODUCTION Uric acid is one of the compounds associated with the inflammatory process in malaria. It acts as an indicator of cellular damage by activating the immune response and inflammatory process. METHODS: We measured serum concentrations of uric acid in 60 symptomatic patients before and after treatment for malarial infections caused by Plasmodium vivax. RESULTS: Lower serum concentrations of uric acid were found during the acute phase of P. vivax malaria compared to those in its convalescent phase (p < 0.0001). CONCLUSIONS: Patients in the acute phase of malaria had lower uric acid levels than those in its convalescent phase.

Achados otológicos em pacientes pós-infecção pelo zika vírus: estudos de caso / Otological findings in patients following infection with Zika virus: case report

RESUMO O Zika vírus em humanos é transmitido pelo mosquito Aedes aegypti e se tornou uma emergência de saúde pública, conforme declaração da Organização Mundial de Saúde. Estudos relataram a associação do vírus com alterações auditivas em pacientes, pós-infecção. Este estudo foi concebido em função da importância da audição para a comunicação, associado aos poucos relatos sobre o impacto que o Zika vírus pode causar no sistema auditivo de indivíduos adultos. O objetivo do estudo foi caracterizar os achados otológicos em dois pacientes adultos, pós-infecção pelo Zika vírus. Foram descritos os achados otológicos de pacientes de um ambulatório de otorrinolaringologia, que apresentaram queixas auditivas logo após os sintomas clínicos de infecção pelo Zika vírus. Os dois pacientes adultos relataram os seguintes sintomas: mal-estar, erupção cutânea, artralgia, plenitude auricular e perda auditiva. Exame sorológico reagente para Zika vírus (IgG). Os achados audiológicos foram: perda auditiva periférica unilateral em um paciente, alterações de reflexos contralaterais em ambos e do potencial evocado de tronco encefálico em um paciente. Os achados audiológicos demonstram possível envolvimento neuronal nas queixas apresentadas, associado, ou não, ao componente periférico, nos pacientes infectados pelo Zika vírus.

ABSTRACT The Zika virus is transmitted between humans by the Aedes aegypti mosquito and has become a public health emergency, as declared by the World Health Organization. Studies have reported the virus to be associated with hearing alterations in patients, following infection. This study was conceived in view of the importance of hearing for communication, associated with the limited number of reports on the impact of Zika virus on the hearing system of adults. The aim of the study was to characterize the otological findings in two adult patients, following infection with the Zika virus. The otological findings observed in two outpatients of an otorhinolaryngology service were described, both of whom reported hearing complaints immediately following the clinical symptoms of Zika virus infection. Both adult patients reported the following symptoms: discomfort, skin rash, joint pain, auricular fullness, and hearing loss. Serologic testing (IgG) for Zika virus was performed. The audiological findings were unilateral peripheral hearing loss in one of the patients, alterations in contralateral acoustic reflexes in both patients, and alteration in the brainstem auditory-evoked potential in one patient. The audiological findings demonstrate possible neuronal involvement in the manifested complaints, whether or not associated with the peripheral component, in patients infected with Zika virus.

Profile of exoantigens from clinical isolates of Paracoccidioides lutzii IN Mato Grosso, Brazil

The objective of this study was to determine the immunochemical profile of three exoantigen preparations obtained from clinical samples of Paracoccidioides lutzii from the state of Mato Grosso, Brazil. The exoantigens were prepared according to a protocol standardized by Camargo et al. and their immunochemical profiles were analyzed using SDS-PAGE. The observed protein bands exhibited molecular weights of 20, 30, and 130 kDa. The 130 kDa glycoprotein was detected in all three preparations. The detection of this high-molecular-weight protein suggests a distinct immunochemical profile. These differences may help to explain the false negative reactions obtained when using the antigen from P. brasiliensis reference strain B-339. This information is essential for increasing the specificity of serological tests used to monitor the prognosis of patients with paracoccidioidomycosis.

Factors associated with recurrent Plasmodium vivax malaria in Porto Velho, Rondônia State, Brazil, 2009 / Fatores associados às recidivas de malária causada por Plasmodium vivax no Município de Porto Velho, Rondônia, Brasil, 2009 / Fatores associados às recidivas de malária causada por Plasmodium vivax no Município de Porto Velho, Rondônia, Brasil, 2009 / Factores asociados a las recidivas de malaria, causada por Plasmodium vivax, en el municipio de Porto Velho, Rondônia, Brasil, 2009

This open retrospective cohort study aimed to describe the incidence of recurrent Plasmodium vivax malaria and associated factors in Porto Velho, Rondônia State, Brazil, in 2009. Data were collected from the National Information System for Malaria Epidemiological Surveillance. There were 23,365 reported P. vivax malaria cases in 2009, 23% of which were classified as relapses. Incidence density of P. vivax recurrence was 45.1/100 patient-years, mostly occurring between the 4th and 13th week after initiating treatment. Male gender, shorter time since onset of symptoms, and higher parasitemia in the initial infection increased the risk of relapse during the year, with a 10% reduction in relative risk for longer symptoms and 11% and 15% increases in relative risk for males and higher initial parasitemia, respectively. However, the results show low clinical relevance for these associations, thereby limiting their applicability to decision-making at the public health level.

Estudo de coorte histórica aberta, construída com informações registradas no Sistema de Informação de Vigilância Epidemiológica da Malária, com objetivo de descrever a incidência e os fatores associados à recidiva de malária causada pelo Plasmodium vivax em Porto Velho, Rondônia, Brasil. Foram notificados 23.365 casos de malária por P. vivax no município, sendo que 23% deles apresentaram recidiva no decorrer de 2009. A densidade de incidência de recidivas foi de 45,1/100 pacientes-ano, ocorrendo, principalmente, entre a 4a e a 13a semana após o início do tratamento. Ser homem, ter menos tempo de sintomas e ter maior nível de parasitemia na infecção inicial aumentaram o risco de recidiva no decorrer do ano, com 10% de redução relativa do risco para maior tempo de sintomas e de 11% e 15% de incremento relativo do risco para o sexo masculino e maiores níveis de parasitemia, respectivamente. Contudo, os resultados demonstram baixa relevância clínica das associações encontradas, comprometendo a sua aplicabilidade na tomada de decisão em nível de saúde pública.

Estudo de coorte histórica aberta, construída com informações registradas no Sistema de Informação de Vigilância Epidemiológica da Malária, com objetivo de descrever a incidência e os fatores associados à recidiva de malária causada pelo Plasmodium vivax em Porto Velho, Rondônia, Brasil. Foram notificados 23.365 casos de malária por P. vivax no município, sendo que 23% deles apresentaram recidiva no decorrer de 2009. A densidade de incidência de recidivas foi de 45,1/100 pacientes-ano, ocorrendo, principalmente, entre a 4a e a 13a semana após o início do tratamento. Ser homem, ter menos tempo de sintomas e ter maior nível de parasitemia na infecção inicial aumentaram o risco de recidiva no decorrer do ano, com 10% de redução relativa do risco para maior tempo de sintomas e de 11% e 15% de incremento relativo do risco para o sexo masculino e maiores níveis de parasitemia, respectivamente. Contudo, os resultados demonstram baixa relevância clínica das associações encontradas, comprometendo a sua aplicabilidade na tomada de decisão em nível de saúde pública. Recidiva; Plasmodium vivax; Malária.

Estudio de cohorte histórica abierta, construida con información registrada en el Sistema de Información de Vigilancia Epidemiológica de la Malaria, con el objetivo de describir la incidencia y los factores asociados a la reaparición de malaria, causada por el Plasmodium vivax, en Porto Velho, Rondônia, Brasil. Se notificaron 23.365 casos de malaria por P. vivax en el municipio, donde un 23% de ellos presentaron recidiva a lo largo del 2009. La densidad de incidencia de recidivas fue de 45,1/100 pacientes-año, produciéndose, principalmente, entre la 4ª y la 13ª semana tras el inicio del tratamiento. Ser hombre, tener menos tiempo síntomas y tener un mayor nivel de parasitemia en la infección inicial aumentaron el riesgo de recidiva a lo largo del año, con un 10% de reducción relativa del riesgo, para un mayor tiempo de síntomas, y de un 11% y 15% de incremento relativo del riesgo para el sexo masculino y mayores niveles de parasitemia, respectivamente. No obstante, los resultados demostraron baja relevancia clínica de las asociaciones encontradas, comprometiendo su aplicabilidad en la toma de decisiones dentro de la salud pública.

Fatal fungemia due to Paracoccidioides lutzii.

We report the first case of fungemia caused by Paracoccidioides lutzii in a 51-year-old male farm worker from the central-west region of Brazil. The fungus was isolated from blood cultures and the species was confirmed by phylogenetic identification. Despite specific treatment and intensive care, the patient died 39 days after admission.

Rhinocerebral zygomycosis in a diabetic patient / Zigomicose rinocerebral em paciente diabética

Rhinocerebral zygomycosis is the most frequent form of fungal infection caused by members of the Zygomycetes class. A fatal case of rhinocerebral zygomycosis caused by Rhizopus (oryzae) arrhizus with histopathological and mycological diagnosis is reported in a diabetic patient.

Zigomicose rinocerebral é a forma mais frequente das infecções fúngicas causadas por membros da classe Zygomicetes. É relatado um caso fatal de zigomicose rinocerebral por Rhizopus (oryzae) arrhizus com diagnóstico histopatológico e micológico, em paciente diabética.