First report of putative Leishmania RNA virus 2 (LRV2) in Leishmania infantum strains from canine and human visceral leishmaniasis cases in the southeast of Brazil

BACKGROUND Leishmania RNA virus 1 (LRV1) is commonly found in South American Leishmania parasites belonging to the subgenus Viannia, whereas Leishmania RNA virus 2 (LRV2) was previously thought to be restricted to the Old-World pathogens of the subgenus Leishmania. OBJECTIVES In this study, we investigated the presence of LRV2 in strains of Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), originating from different hosts, clinical forms, and geographical regions. METHODS A total of seventy-one isolates were screened for LRV2 using semi-nested reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. FINDINGS We detected LRV2 in two L. infantum isolates (CUR268 and HP-EMO) from canine and human cases, respectively. MAIN CONCLUSIONS To the best of our knowledge, this is the first detection of LRV2 in the New World.

Effectiveness of palivizumab immunoprophylaxis in infants with respiratory syncytial virus disease in Colombia.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the most important childhood infections. OBJECTIVE: To evaluate the effectiveness and safety of palivizumab immunoprophylaxis in preterm infants at a high risk of severe respiratory syncytial virus infection during the RSV season in Colombia. METHODOLOGY: A prospective observational non-comparative multicenter study in six Colombian cities. At the beginning of the RSV infection season, palivizumab prophylaxis, up to five doses, was administered to infants born at ≤32 weeks of gestation, infants younger than six months, infants under one year of age with bronchopulmonary dysplasia (BPD), infants one year or less of age with hemodynamically significant acyanotic and non-acyanotic congenital heart disease (CHD), and with follow-up during the immunoprophylaxis until one month after the last dose. RESULTS: The study enrolled 600 patients, 91.8% of which were born at ≤ 32 weeks of gestation. BPD was observed in 54.9% of infants. 49% were born at < 32 weeks gestation and presented BPD. 6.9% had hemodynamically significant acyanotic and non-acyanotic CHD 53.3% received three or more doses of palivizumab. The mean interval between doses was 39.6 days. 1.8% of patients were hospitalized due to a confirmed RSV infection. Overall mortality was 1.2%, whereas the mortality by RSV in infants undergoing prophylaxis was 0.2%. CONCLUSIONS: Palivizumab was a clinically effective, well-tolerated treatment in the Colombian population. The safety profile of palivizumab reflects the findings from previous studies in developed countries.

Lung cancer patients with COVID-19 in Spain: GRAVID study.

INTRODUCTION: Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. METHODS: Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). RESULTS: A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. CONCLUSIONS: Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2.

In situ cellular immune response in non-ulcerated skin lesions due to Leishmania (L.) infantum chagasi infection.

BACKGROUND: Skin lesions of patients affected by non-ulcerated cutaneous leishmaniasis (NUCL) caused by L. (L.) infantum chagasi are characterized by lymphohistiocytic inflammatory infiltrate associated with epithelioid granuloma and scarce parasitism. However, the in situ cellular immune response of these patients is unclear. Therefore, the aim of the present study was to characterize the cellular immune response in the skin lesions of patients affected by NUCL. METHODS: Twenty biopsies were processed by immunohistochemistry using primary antibodies to T lymphocytes (CD4, CD8), NK cells, B lymphocytes, macrophages, nitric oxide synthase and interferon-gamma. RESULTS: Immunohistochemistry revealed higher expression of all cellular types and molecules (IFN-γ, iNOS) in the dermis of diseased skin compared to the skin of healthy individuals (p < 0.05). Morphometric analysis performed in the skin lesions sections showed the predominance of CD8+ T lymphocytes in the mononuclear infiltrate, followed by macrophages, mostly iNOS+, a response that could be mediated by IFN-γ. CONCLUSION: Our study improves knowledge of the cellular immune response in non-ulcerated or atypical cutaneous leishmaniasis caused by L. (L.) infantum chagasi in Central America and pointed to the pivotal participation of CD8+ T lymphocytes in the host defense mechanisms against the parasite in patients with NUCL.

In situ cellular immune response in non-ulcerated skin lesions due to Leishmania (L) infantum chagasi infection

Skin lesions of patients affected by non-ulcerated cutaneous leishmaniasis (NUCL) caused by L. (L.) infantum chagasi are characterized by lymphohistiocytic inflammatory infiltrate associated with epithelioid granuloma and scarce parasitism. However, the in situ cellular immune response of these patients is unclear. Therefore, the aim of the present study was to characterize the cellular immune response in the skin lesions of patients affected by NUCL. Methods Twenty biopsies were processed by immunohistochemistry using primary antibodies to T lymphocytes (CD4, CD8), NK cells, B lymphocytes, macrophages, nitric oxide synthase and interferon-gamma. Results Immunohistochemistry revealed higher expression of all cellular types and molecules (IFN-γ, iNOS) in the dermis of diseased skin compared to the skin of healthy individuals (p < 0.05). Morphometric analysis performed in the skin lesions sections showed the predominance of CD8+ T lymphocytes in the mononuclear infiltrate, followed by macrophages, mostly iNOS+, a response that could be mediated by IFN-γ. Conclusion Our study improves knowledge of the cellular immune response in non-ulcerated or atypical cutaneous leishmaniasis caused by L. (L.) infantum chagasi in Central America and pointed to the pivotal participation of CD8+ T lymphocytes in the host defense mechanisms against the parasite in patients with NUCL.(AU)

Lipophosphoglycans from dermotropic Leishmania infantum are more pro-inflammatory than those from viscerotropic strains.

Although Leishmania infantum is well-known as the aethiological agent of visceral leishmaniasis (VL), in some Central American countries it may cause atypical non-ulcerated cutaneous leishmaniasis (NUCL). However, the mechanisms favoring its establishment in the skin are still unknown. Lipophosphoglycan (LPG) is the major Leishmania multivirulence factor involved in parasite-host interaction. In the case of viscerotropic L. infantum, it causes an immunosuppression during the interaction with macrophages. Here, we investigated the biochemical and functional roles of LPGs from four dermotropic L. infantum strains from Honduras during in vitro interaction with murine macrophages. LPGs were extracted, purified and their repeat units analysed. They did not have side chains consisting of Gal(ß1,4)Man(α1)-PO4 common to all LPGs. Peritoneal macrophages from BALB/c and C57BL/6 were exposed to LPG for nitric oxide (NO) and cytokine (TNF-α and, IL-6) production. LPGs from dermotropic strains from Honduras triggered higher NO and cytokine levels compared to those from viscerotropic strains. In conclusion, LPGs from dermotropic strains are devoid of side-chains and exhibit high pro-inflammatory activity.

FOLFOXIRI plus biologics in advanced colorectal cancer.

INTRODUCTION: The combination of oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (FOLFOXIRI) results in improved outcomes compared with standard chemotherapy when used in frontline to treat patients with metastatic colorectal cancer (mCRC). FOLFOXIRI has been recently combined with biologic agents aiming further improvement in outcomes. AREAS COVERED: This manuscript provides a comprehensive review of the results achieved by the FOLFOXIRI+biologic combination when used as first-line treatment in patients with mCRC. The search retrieved 19 clinical trial reports and 7 ongoing trials. The results are discussed focusing on secondary resection of metastatic disease, impact of sidedness (right-left primary tumor site), and impact of biomarkers. EXPERT OPINION: Panitumumab is the only biologic that has proved its value when added to FOLFOXIRI in a randomized clinical trial. FOLFOXIRI-bevacizumab has the widest data from two large randomized phase III trials, being an option to be used in both the palliative and the conversion-therapy settings. However, the true benefit from adding bevacizumab remains to be established as it has not been evaluated in a randomized setting yet. Data on response rates and secondary resection rates are promising with the FOLFOXIRI-anti-EGFR combinations and may constitute a valuable option. Results of ongoing head-to-head studies will shed additional light on this issue.

Infective endocarditis in patients with cancer: a consequence of invasive procedures or a harbinger of neoplasm?: A prospective, multicenter cohort.

The aim of the study was to draw a comparison between the characteristics of infective endocarditis (IE) in patients with cancer and those of IE in noncancer patients.Patients with IE, according to the modified Duke criteria, were prospectively included in the GAMES registry between January 2008 and February 2014 in 30 hospitals. Patients with active cancer were compared with noncancer patients.During the study period, 161 episodes of IE fulfilled the inclusion criteria. We studied 2 populations: patients whose cancer was diagnosed before IE (73.9%) and those whose cancer and IE were diagnosed simultaneously (26.1%). The latter more frequently had community-acquired IE (67.5% vs 26.4%, P < .01), severe sepsis (28.6% vs 11.1%, P = .013), and IE caused by gastrointestinal streptococci (42.9% vs 16.8%, P < .01). However, catheter source (7.1% vs 29.4%, P = .003), invasive procedures (26.2% vs 44.5%, P = .044), and immunosuppressants (9.5% vs 35.6%, P = .002) were less frequent.When compared with noncancer patients, patients with cancer were more often male (75.2% vs 67.7%, P = .049), with a higher comorbidity index (7 vs 4). In addition, IE was more often nosocomial (48.7% vs 29%) and originated in catheters (23.6% vs 6.2%) (all P < .01). Prosthetic endocarditis (21.7% vs 30.3%, P = .022) and surgery when indicated (24.2% vs 46.5%, P < .01) were less common. In-hospital mortality (34.8% vs 25.8%, P = .012) and 1-year mortality (47.8% vs 30.9%, P < .01) were higher in cancer patients, although 30-day mortality was not (24.8% vs 19.3%, P = .087).A significant proportion of cases of IE (5.6%) were recorded in cancer patients, mainly as a consequence of medical interventions. IE may be a harbinger of occult cancer, particularly that of gastrointestinal or urinary origin.

[Fever of unknown origin: a challenge for the pediatric infectious diseases specialist]. / Síndrome febril prolongado: un desafío para el infectólogo pediatra.

INTRODUCTION: Prolonged febrile syndrome (PFS) is defined as fever 7-10 days, with initial study does not allow etiologic diagnosis. OBJECTIVE: To describe the main causes of the PFS and its temporal behavior in Pediatric Infectious Diseases Unit Outpatient Care of Complejo Asistencial Dr. Sótero del Río (CASR). PATIENTS AND METHODS: A descriptive, prospective study between january 2007-december 2012, about 153 patients from 6 weeks to 14 years 11 months old, diagnosed with PFS, tab completing clinical and laboratory monitoring. RESULTS: etiology was obtained in 67.9%, the causes were infection (88.4%), neoplasms (4.8%), rheumatological (4.8%) and Kawasaki disease (2.8%). The most important infectious causes were enteric fevers (typhoid and paratyphoid) (18.4%), urinary tract infection (11.9%), Bartonella henselae infections and adenovirus (8.7%) each one and Epstein Barr virus (7.6%). Ninety eight percent of patients had complete resolution, 60.7% did not require hospitalization and mortality was 0%. DISCUSSION: As in previous pediatric clinical series the infections were the most frequent causes. Enteric fever persists as principal cause, however, the epidemiological evidence is oscillating in time endorsing the local statistics can count over the years to improve the diagnostic and therapeutic approach.

Síndrome febril prolongado: un desafío para el infectólogo pediatra / Fever of unknown origin: a challenge for the pediatric infectious diseases specialist

Introduction: Prolonged febrile syndrome (PFS) is defined as fever 7-10 days, with initial study does not allow etiologic diagnosis. Objective: To describe the main causes of the PFS and its temporal behavior in Pediatric Infectious Diseases Unit Outpatient Care of Complejo Asistencial Dr. Sótero del Río (CASR). Patients and Methods: A descriptive, prospective study between january 2007-december 2012, about 153 patients from 6 weeks to 14 years 11 months old, diagnosed with PFS, tab completing clinical and laboratory monitoring. Results: etiology was obtained in 67.9%, the causes were infection (88.4%), neoplasms (4.8%), rheumatological (4.8%) and Kawasaki disease (2.8%). The most important infectious causes were enteric fevers (typhoid and paratyphoid) (18.4%), urinary tract infection (11.9%), Bartonella henselae infections and adenovirus (8.7%) each one and Epstein Barr virus (7.6%). Ninety eight percent of patients had complete resolution, 60.7% did not require hospitalization and mortality was 0%. Discussion: As in previous pediatric clinical series the infections were the most frequent causes. Enteric fever persists as principal cause, however, the epidemiological evidence is oscillating in time endorsing the local statistics can count over the years to improve the diagnostic and therapeutic approach.

Introducción: El síndrome febril prolongado (SFP) se define como fiebre entre 7-10 días, con estudio inicial que no permite un diagnóstico etiológico. Objetivo: Describir las principales etiologías del SFP y su comportamiento temporal en la unidad de infectología pediátrica ambulatoria del Complejo Asistencial Dr. Sótero del Río (CASR). Pacientes y Método: Estudio descriptivo, prospectivo, entre enero de 2007-diciembre de 2012. Análisis de 153 pacientes entre 6 semanas y 14 años 11 meses de edad, con diagnóstico de SFP, que completaron ficha de seguimiento clínico-laboratorial. Resultados: Se obtuvo diagnóstico etiológico en 67,9%, las causas fueron: infecciones (88,4%), neoplasias (4,8%), reumatológicas (4,8%) y enfermedad de Kawasaki (2,8%). Las causas infecciosas más importantes fueron: fiebres entéricas (tifoidea y paratifoidea) (18,4%), infección del tracto urinario (11,9%), enfermedades por Bartonella henselae y adenovirus (8,7%) cada uno y virus de Epstein Barr (7,6%). El 98% de los pacientes tuvo resolución completa, 60,7% no requirió hospitalización y no se registraron decesos. Discusión: Como en las series clínicas antes publicadas, las infecciones fueron la causa más frecuente de SFP. La fiebre entérica persiste como causa principal; sin embargo, se evidencia una situación epidemiológica oscilante en el tiempo justificando la necesidad de contar con estadísticas locales a lo largo de los años para mejorar el enfoque diagnóstico y terapéutico.

La vacuna polio oral en lactantes no interfiere con la detección de enterovirus en sangre / Oral polio vaccine in infants does not interfere in detection of enterovirus in blood

Introduction: There is not known if a viraemia post-oral polio vaccine (OPV) is detectable by modern molecular techniques. Such viraemia could affect the performance of the real time-polymerase chain reaction (PCR) for non polio enterovirus (EV) detection, technique of growing clinical use for the study of febrile infants. Objective: To determine viraemia post-first dose of OPV in healthy infants, by molecular techniques. Patients and Methods: 50 infants less than three months without previous VPO were randomized in 5 groups: a control group with pre-vaccination blood sample (BS), group 1 BS at day 2, group 2 BS at day 4, group 3, BS at day 6 and group 4, BS at day 8 post-vaccination. Conventional and specific PCR for poliovirus and real time PCR for non polio EV were performed in BS and in OPV samples. Results: No genetic material of poliovirus was detected in any infant, while in 9 of them (18%) non polio EV was identified. Real time PCR for EV did not amplify poliovirus from OPV samples. Discussion: Results suggest that no post VPO viraemia detectable by molecular methods exists. Considering that real time PCR for EV does not allow to identify polio virus, no false positives of the test are expected as a result of a recent VPO vaccination. We documented presence of non polio EV in blood of healthy asymptomatic infants.

Introducción: No existen estudios que indiquen si la vacuna polio oral (VPO) produce viremia detectable mediante métodos moleculares. Una eventual viremia podría afectar el rendimiento de la RPC tiempo real para detectar enterovirus (EV) no polio, examen de creciente uso clínico en lactantes pequeños con fiebre sin foco. Objetivo: Determinar viremia post VPO en lactantes sanos, por métodos moleculares. Métodos: 50 menores de 3 meses, al momento de recibir su primera VPO se distribuyeron en forma aleatoria en 5 grupos: control, muestra de sangre pre-vacunación; grupo 1, muestra al 2° día; grupo 2, al 4° día; grupo 3, al 6° día y grupo 4, al 8° día post-vacunación. Se realizó RPC convencional específica para virus polio y RPC tiempo real para EV no polio en las muestras de sangre y en muestras de VPO. Resultados: No se identificó presencia de material genético de virus polio en lactante alguno, mientras que en 9 (18%) se identificó presencia de EV no polio. La RPC tiempo real para EV no polio no amplificó material genético a partir de las muestras de VPO. Discusión: Los resultados sugieren que no existe viremia post-VPO detectable por métodos moleculares. Considerando que la RPC tiempo real de EV no polio de uso clínico no permite identificar la presencia de virus polio, estos hallazgos indican que no existirán falsos positivos de este examen como resultado de una vacunación VPO reciente. Adicionalmente se documentó presencia de EV no polio en sangre de lactantes asintomáticos.

Comparación en la medición del panículo adiposo por técnica de ultrasonido y calibrador / Comparison of calibrator and ultrasonic technique in the measurement of the adipose panniculus

Con la finalidad de evaluar la técnica de ultrasonido y calibrador en la determinacion del panículo adiposo, se realizaron mediciones por ambas técnicas en los pliegues triceps, subescapular y abdominal. Se reportan los resultados obtenidos y se concluye que el calibrador y el ultrasonido son dos métodos igualmente efectivos en la medición del paniculo adiposo, habiendose obtenido la correlación más alta a nivel abdominal. El calibrador es una técnica no dolorosa, simple de usar, portatil y es dificultosa de utilizar en personas con obsidad masiva. El ultrasonido es una promesa en cubrir dichas limitaciones, pero constituye una técnica estaria al alcance de muy pocos clínicos