Quantitative PCR as a marker for preemptive therapy and its role in therapeutic control in Trypanosoma cruzi/HIV coinfection.

BACKGROUND: Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. METHODOLOGY: This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. RESULTS: We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/µL, higher viral load, and absence of antiretroviral therapy. CONCLUSION: We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.

Correction: Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

[This corrects the article DOI: 10.1371/journal.pntd.0009809.].

Pyogenic spondylodiscitis: risk factors for therapeutic failure and recurrence / Espondilodiscite piogênica: fatores de risco para falha terapêutica e recorrência / Espondilodiscitis piógena: factores de riesgo para fracaso terapéutico y recurrencia

ABSTRACT Objective: Evaluate the prognostic factors associated with therapeutic failure and recurrence in pyogenic spondylodiscitis (PS). Methods: A historical cohort study was conducted in a reference Brazilian hospital for locomotor system and neurodevelopmental diseases. All patients with PS treated between January 1999 and December 2018 and followed for at least one year were included. PS was defined based on clinical, laboratory, and radiological criteria. Microbiological data and clinical outcomes at the end of follow-up were also collected and analyzed. Results: Fifty patients (mean age 50.94 ± 15.84 years, men 76.00%) were included. After twelve months of follow-up, therapeutic failure was observed in 24.00% (n = 12) and recurrence in 18.00% (n = 09) patients. Among those who were cured, residual symptoms were found in 50.00% (19/38). No deaths were observed. After multivariate analysis, therapeutic failure was associated with the prescription of antibiotic therapy before culture results (p = 0.0153), spinal cord compression (p = 0.0053), and sensory deficits (p = 0.0341). Furthermore, recurrence was associated with previous nonspinal surgeries (p = 0.0350) and spinal cord compression (p = 0.0447). Conclusion: PS causes significant morbidity. The prognosis depends mainly on the clinical presentation at admission, especially when associated with spinal cord compression, which reinforces the importance of early diagnosis. Level of Evidence II; Prognostic Studies.

RESUMO: Objetivo: Avaliar os fatores prognósticos associados à falha terapêutica e à recorrência na espondilodiscite piogênica (EP). Métodos: Um estudo de coorte histórica foi conduzido em um hospital brasileiro de referência nas doenças do sistema locomotor e do neurodesenvolvimento. Todos os pacientes com EP tratados entre janeiro de 1999 e dezembro de 2018 e acompanhados por pelo menos um ano foram incluídos. A EP foi definida com base em critérios clínicos, laboratoriais e radiológicos. Dados microbiológicos e desfechos clínicos ao final do tempo de seguimento também foram coletados e analisados. Resultados: Cinquenta pacientes (idade média 50,94 ± 15,84 anos, homem 76,00%) foram incluídos. Depois de doze meses de seguimento, a falha terapêutica foi observada em 24,00% (n = 12) e a recorrência em 18,00% (n = 09) dos pacientes. Entre os que curaram, sintomas residuais foram constatados em 50,00% (19/38). Nenhuma morte foi observada. Após análise multivariada, a falha terapêutica foi associada à prescrição de antibioticoterapia antes dos resultados de cultura (p = 0,0153), compressão medular (p = 0,0053) e déficits sensoriais (p = 0,0341). Além disso, a recorrência esteve associada a cirurgias não espinhais prévias (p = 0,0350) e à compressão medular (p = 0,0447). Conclusão: A EP causa morbidade significativa. O prognóstico depende principalmente da apresentação clínica na admissão, especialmente da existência de compressão medular, o que reforça a importância do diagnóstico precoce. Nível de Evidência II; Estudos de Prognóstico.

RESUMEN: Objetivo: Evaluar los factores pronósticos asociados con el fracaso terapéutico y la recurrencia en la espondilodiscitis piógena (EP). Métodos: Se realizó un estudio de cohorte histórica en un hospital de referencia brasileño para enfermedades del aparato locomotor y del neurodesarrollo. Se incluyeron todos los pacientes con EP tratados entre enero de 1999 y diciembre de 2018 y seguidos durante al menos un año. La EP se definió en base a criterios clínicos, de laboratorio y radiológicos. También se recopilaron y analizaron los datos microbiológicos y los resultados clínicos al final del tiempo de seguimiento. Resultados: Se incluyeron 50 pacientes (edad media 50,94 ± 15,84 años, sexo masculino 76,00%). A los doce meses de seguimiento, se observó fracaso terapéutico en el 24,00% (n=12) y recurrencia en el 18,00% (n=09) de los pacientes. Entre los que se curaron, se encontraron síntomas residuales en el 50,00% (19/38). No se observaron muertes. Tras el análisis multivariante, el fracaso terapéutico se asoció a la prescripción de antibioticoterapia antes de los resultados del cultivo (p = 0,0153), compresión medular (p = 0,0053) y déficits sensitivos (p = 0,0341). Además, la recurrencia se asoció con cirugías previas no espinales (p = 0,0350) y compresión medular (p = 0,0447). Se incluyeron 50 pacientes (edad media 50,94 ± 15,84 años, sexo masculino 76,00%). A los doce meses de seguimiento, se observó fracaso terapéutico en el 24,00% (n=12) y recurrencia en el 18,00% (n=09) de los pacientes. Entre los que se curaron, se encontraron síntomas residuales en el 50,00% (19/38). No se observaron muertes. Tras el análisis multivariante, el fracaso terapéutico se asoció a la prescripción de antibioticoterapia antes de los resultados del cultivo (p = 0,0153), compresión medular (p = 0,0053) y déficits sensitivos (p = 0,0341). Además, la recurrencia se asoció con cirugías previas no espinales (p = 0,0350) y compresión medular (p = 0,0447). Conclusión: La EP causa una morbilidad significativa. El pronóstico depende principalmente de la presentación clínica al ingreso, especialmente de la existencia de compresión medular, lo que refuerza la importancia del diagnóstico precoz. Nivel de Evidencia II; Estudios de Pronóstico.

Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

OBJECTIVE: Chagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates. METHODS: This is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions. RESULTS: Out of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/µL and median viral load was 17,000 copies/µL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms. CONCLUSION: This study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements.

Echocardiographic Study of the Coronary Sinus in the Indeterminate Form of Chagas Disease.

INTRODUCTION: We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD). METHODS: Differences between the maximum and minimum diameters of the coronary sinus (∆%) on echocardiography were evaluated in individuals with the indeterminate form of CD (n=14) and those without (n=16) CD. The association of the difference with abnormalities detected by echocardiography and myocardial scintigraphy was assessed. RESULTS: The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings. CONCLUSIONS: The coronary sinus evaluation revealed no differences between the groups.

Echocardiographic Study of the Coronary Sinus in the Indeterminate Form of Chagas Disease

Abstract INTRODUCTION: We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD). METHODS: Differences between the maximum and minimum diameters of the coronary sinus (∆%) on echocardiography were evaluated in individuals with the indeterminate form of CD (n=14) and those without (n=16) CD. The association of the difference with abnormalities detected by echocardiography and myocardial scintigraphy was assessed. RESULTS: The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings. CONCLUSIONS: The coronary sinus evaluation revealed no differences between the groups.

Ecological aspects of mosquitoes (Diptera: Culicidae) in the gallery forest of Brasília National Park, Brazil, with an emphasis on potential vectors of yellow fever.

INTRODUCTION: We analyzed the vertical and monthly distributions of culicid species in the gallery forest of Brasília National Park, with an emphasis on the potential vectors of yellow fever (YF). METHODS: Between September 2010 and August 2011, mosquitoes were captured on the ground and in the canopy of the forest for five consecutive days per month, from nine to 15 hours. The mosquitoes were examined to verify natural infection with flaviviruses by isolation in Aedes albopictus Skuse, 1864 cells followed by indirect immunofluorescence. RESULTS: We identified 2,677 culicids distributed in 29 species. Most of the mosquitoes were captured at ground level (69%) during the rainy season (86%). The most abundant species were Sabethes (Sabethes) albiprivus Theobald, 1903; Limatus durhamii Theobald, 1901; Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon, 1924; Haemagogus (Haemagogus) janthinomys Dyar, 1921; Aedes (Ochlerotatus) scapularis Rondani, 1848; Psorophora (Janthinosoma) ferox Von Humboldt, 1819; and Aedes (Ochlerotatus) serratus Theobald, 1901. Limatus durhamii, Limatus durhamii, Psorophora ferox, Aedes scapularis and Aedes serratus showed significant differences (p<0.05) in their habitat use. Limatus durhamii was found more often in the canopy, unlike the other species. During the rainy season, the most abundant species were Sa. albiprivus, Haemagogus leucocelaenus and Limatus durhamii. During the dry season, the potential YF vectors exhibited a very low frequency and abundance, except Aedes scapularis and Aedes serratus. No flavivirus was detected in the 2,677 examined mosquitoes. CONCLUSIONS: We recommend continued and systematic entomological monitoring in areas vulnerable to the transmission of YF in the Federal District of Brazil.

Ecological aspects of mosquitoes (Diptera: Culicidae) in the gallery forest of Brasilia National Park, Brazil, with an emphasis on potential vectors of yellow fever

Introduction We analyzed the vertical and monthly distributions of culicid species in the gallery forest of Brasília National Park, with an emphasis on the potential vectors of yellow fever (YF). Methods Between September 2010 and August 2011, mosquitoes were captured on the ground and in the canopy of the forest for five consecutive days per month, from nine to 15 hours. The mosquitoes were examined to verify natural infection with flaviviruses by isolation in Aedes albopictus Skuse, 1864 cells followed by indirect immunofluorescence. Results We identified 2,677 culicids distributed in 29 species. Most of the mosquitoes were captured at ground level (69%) during the rainy season (86%). The most abundant species were Sabethes (Sabethes) albiprivus Theobald, 1903; Limatus durhamii Theobald, 1901; Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon, 1924; Haemagogus (Haemagogus) janthinomys Dyar, 1921; Aedes (Ochlerotatus) scapularis Rondani, 1848; Psorophora (Janthinosoma) ferox Von Humboldt, 1819; and Aedes (Ochlerotatus) serratus Theobald, 1901. Limatus durhamii, Limatus durhamii, Psorophora ferox, Aedes scapularis and Aedes serratus showed significant differences (p<0.05) in their habitat use. Limatus durhamii was found more often in the canopy, unlike the other species. During the rainy season, the most abundant species were Sa. albiprivus, Haemagogus leucocelaenus and Limatus durhamii. During the dry season, the potential YF vectors exhibited a very low frequency and abundance, except Aedes scapularis and Aedes serratus. No flavivirus was detected in the 2,677 examined mosquitoes. Conclusions We recommend continued and systematic entomological monitoring in areas vulnerable to the transmission of YF in the Federal District of Brazil. .

Mediastinitis and pericardial effusion in a patient with AIDS and disseminated Mycobacterium avium infection: a case report.

We report the case of a 36-year-old man who had acquired immune deficiency syndrome and developed suppurative mediastinitis extending over the left lung and anterior thoracic wall around the sternum, pericardial effusions, splenomegaly, and mesenteric and periaortic lymphadenomegaly due to Mycobacterium avium (genotype I). The organism was isolated from an axillary lymph node and the bone marrow. Mediastinitis associated with disseminated M. avium complex infection is uncommon and, to the best of our knowledge, this manifestation has not reported before.

Mediastinitis and pericardial effusion in a patient with AIDS and disseminated Mycobacterium avium infection: a case report / Mediastinite e derrame pericárdico em um paciente com AIDS e infecção disseminada por Mycobacterium avium: um relato de caso

We report the case of a 36-year-old man who had acquired immune deficiency syndrome and developed suppurative mediastinitis extending over the left lung and anterior thoracic wall around the sternum, pericardial effusions, splenomegaly, and mesenteric and periaortic lymphadenomegaly due to Mycobacterium avium (genotype I). The organism was isolated from an axillary lymph node and the bone marrow. Mediastinitis associated with disseminated M. avium complex infection is uncommon and, to the best of our knowledge, this manifestation has not reported before.

Relatamos o caso de um paciente de 36 anos vivendo com AIDS que desenvolveu mediastinite supurativa com extensão ao pulmão esquerdo e à parede anterior do tórax ao redor do esterno, derrame pericárdico, esplenomegalia e adenomegalia mesentérica e periaórtica, devido ao Mycobacterium avium genótipo I, isolado de linfonodo axilar e da medula óssea. A mediastinite associada à infecção pelo Mycobacterium avium é rara e, até onde conhecemos na literatura publicada, esta forma de apresentação ainda no foi relatada.

Insight into the salivary transcriptome and proteome of Dipetalogaster maxima.

Dipetalogaster maxima is a blood-sucking Hemiptera that inhabits sylvatic areas in Mexico. It usually takes its blood meal from lizards, but following human population growth, it invaded suburban areas, feeding also on humans and domestic animals. Hematophagous insect salivary glands produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. To obtain further insight into the salivary biochemical and pharmacologic complexity of this insect, a cDNA library from its salivary glands was randomly sequenced. Salivary proteins were also submitted to one- and two-dimensional gel electrophoresis (1DE and 2DE) followed by mass spectrometry analysis. We present the analysis of a set of 2728 cDNA sequences, 1375 of which coded for proteins of a putative secretory nature. The saliva 2DE proteome displayed approximately 150 spots. The mass spectrometry analysis revealed mainly lipocalins, pallidipins, antigen 5-like proteins, and apyrases. The redundancy of sequence identification of saliva-secreted proteins suggests that proteins are present in multiple isoforms or derive from gene duplications.

[Paracoccidioidomycosis at Brasilias university hospital]. / Paracoccidioidomicose no Hospital Universitário de Brasília.

Seventy-six paracoccidioidomycosis patients attended at the university hospital of Brasília from 1984 to 2005 were studied. 82.9% were male and the mean age was 42 years. 54.9% of the patients were engaged in farming activities. Among the patients with the chronic form, 87% were smokers and 55.3% consumed alcohol. Among 71 patients without HIV/AIDS coinfection: a) paracoccidioidomycosis was recurrent in 21 (29.6%); b) the chronic or mixed form affected 77.5% of patients, predominantly in the oropharynx (70.9%) and lungs (67.3%), with lymph node lesions in 29.8%, laryngeal lesions in 27.3% and cutaneous lesions in 16.4%; c) in the acute/subacute form, lymph node lesions predominated (81.3%), followed by cutaneous lesions in 43.8%, which resulted in severe disease in 62.5% and moderate disease in 37.5%. Five patients had HIV/AIDS coinfection and three of them presented disseminated fungal infection together with marked immunosuppression.

Paracoccidioidomicose no Hospital Universitário de Brasília / Paracoccidioidomycosis at Brasilia’s University Hospital

Foram estudados 76 pacientes com paracoccidioidomicose, assistidos no Hospital Universitário de Brasília, entre 1984 e 2005. O gênero masculino representou 82,9 por cento e a média de idade foi 42 anos. Atividades agropecuárias caracterizaram 54,9 por cento dos pacientes. Entre pacientes com a forma crônica, 87 por cento eram tabagistas e 55,3 por cento etilistas. Em 71 pacientes sem co-infecção por HIV/aids: a) houve recidiva da paracoccidioidomicose em 21 (29,6 por cento); b) a forma crônica ou mista acometeu 77,5 por cento dos pacientes, com predominância de comprometimento orofaríngeo (70,9 por cento) e pulmonar (67,3 por cento), além de lesões linfonodais (29,8 por cento), laríngeas (27,3 por cento) e cutâneas (16,4 por cento); c) na forma aguda/subaguda, predominou o comprometimento linfonodal (81,3 por cento), seguido por lesões cutâneas (43,8 por cento), resultando doença grave em 62,5 por cento e moderada em 37,5 por cento. Cinco pacientes tinham co-infecção por HIV/aids, dos quais três tiveram a infecção fúngica disseminada associada a acentuada imunodepressão.

Seventy-six paracoccidioidomycosis patients attended at the university hospital of Brasília from 1984 to 2005 were studied. 82.9 percent were male and the mean age was 42 years. 54.9 percent of the patients were engaged in farming activities. Among the patients with the chronic form, 87 percent were smokers and 55.3 percent consumed alcohol. Among 71 patients without HIV/AIDS coinfection: a) paracoccidioidomycosis was recurrent in 21 (29.6 percent); b) the chronic or mixed form affected 77.5 percent of patients, predominantly in the oropharynx (70.9 percent) and lungs (67.3 percent), with lymph node lesions in 29.8 percent, laryngeal lesions in 27.3 percent and cutaneous lesions in 16.4 percent; c) in the acute/subacute form, lymph node lesions predominated (81.3 percent), followed by cutaneous lesions in 43.8 percent, which resulted in severe disease in 62.5 percent and moderate disease in 37.5 percent. Five patients had HIV/AIDS coinfection and three of them presented disseminated fungal infection together with marked immunosuppression.

Reflexões sobre o ensino da Semiologia Médica / Reflections on the teaching of Basic Clinical Skills

A Semiologia Médica representa a ponte entre os ciclos básico e profissionalizante do curso médico. Neste artigo, o ensino da Semiologia é enfatizado como essencial ao raciocínio clínico que irá conduzir ao diagnóstico e ao estabelecimento da boa relação médico-paciente. São levantadas considerações acerca dos objetivos, logística, segmentos envolvidos, estruturação e desenvolvimento do curso, baseadas em experiência vivida na Universidade de Brasília.