In Vitro, In Vivo and In Silico Assessment of the Antimicrobial and Immunomodulatory Effects of a Water Buffalo Cathelicidin (WBCATH) in Experimental Pulmonary Tuberculosis.

Tuberculosis (TB) is considered the oldest pandemic in human history. The emergence of multidrug-resistant (MDR) strains is currently considered a serious global health problem. As components of the innate immune response, antimicrobial peptides (AMPs) such as cathelicidins have been proposed to have efficacious antimicrobial activity against Mycobacterium tuberculosis (Mtb). In this work, we assessed a cathelicidin from water buffalo, Bubalus bubalis, (WBCATH), determining in vitro its antitubercular activity (MIC), cytotoxicity and the peptide effect on bacillary loads and cytokines production in infected alveolar macrophages. Our results showed that WBCATH has microbicidal activity against drug-sensitive and MDR Mtb, induces structural mycobacterial damage demonstrated by electron microscopy, improves Mtb killing and induces the production of protective cytokines by murine macrophages. Furthermore, in vivo WBCATH showed decreased bacterial loads in a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria. In addition, a synergistic therapeutic effect was observed when first-line antibiotics were administered with WBCATH. These results were supported by computational modeling of the potential effects of WBCATH on the cellular membrane of Mtb. Thus, this water buffalo-derived cathelicidin could be a promising adjuvant therapy for current anti-TB drugs by enhancing a protective immune response and potentially reducing antibiotic treatment duration.

Evidence of Coinfections between SARS-CoV-2 and Select Arboviruses in Guerrero, Mexico, 2020-2021.

We provide evidence of concurrent and close sequential infections between SARS-CoV-2 and select arboviruses-namely, chikungunya virus (CHIKV); dengue viruses 1, 2, and 3 (DENV1-3), and Zika virus (ZIKV)-in patients in Guerrero, southwest Mexico, in 2020-2021. The study population consisted of 176 febrile patients with laboratory evidence of SARS-CoV-2 infection. Sera from all patients were serologically and antigenically tested for seven arboviruses known to occur in Guerrero. Eighteen patients contained CHIKV IgM, six of whom also contained CHIKV RNA. Another 16 patients contained flavivirus antigen. The flaviviruses responsible for the infections were identified by plaque reduction neutralization test as DENV1 (two patients), DENV2 (five patients), DENV3 (three patients), ZIKV (three patients), and an undetermined flavivirus (three patients). In summary, we identified patients in Guerrero, Mexico, with concurrent or recent sequential infections between SARS-CoV-2 and select arboviruses, exemplifying the importance of performing differential diagnosis in regions where these viruses cocirculate.

Sentinel surveillance for bacterial pneumonia and meningitis in children under the age of 5 in a tertiary pediatric hospital in Colombia - 2016. / Vigilancia centinela de neumonías y meningitis bacterianas en menores de 5 años en un hospital pediátrico de tercer nivel en Colombia - 2016

INTRODUCTION: Bacterial pneumonia and meningitis are vaccine-preventable diseases. Sentinel surveillance provides relevant information about their behavior. OBJECTIVE: To present the data from sentinel surveillance carried out at the Fundación HOMI, Fundación Hospital Pediátrico La Misericordia in 2016. MATERIALS AND METHODS: We conducted a descriptive study from January 1 to December 31, 2016, on the daily surveillance of patients under 5 years of age diagnosed with pneumonia or bacterial meningitis according to PAHO's definitions. We identified the microorganisms using the automated VITEKTM 2 system. Bacterial isolates were sent to the Microbiology Group at the Colombian Instituto Nacional de Salud for confirmation, serotyping, phenotypic, and genotypic characterization. Antimicrobial susceptibility profiles were established. RESULTS: From 1,343 suspected cases of bacterial pneumonia, 654 (48.7%) were probable, 84% had complete Hib vaccination schedules, and 87% had complete pneumococcal vaccination schedules for age. Blood culture was taken in 619 (94.6%) and 41 (6.6%) were positive while S. pneumoniae was isolated in 17 (41%) of them. The most frequent serotype was 19A in five cases (29.4%), and four 19A serotypes were associated with the reference isolate ST320. The incidence rate of probable bacterial pneumonia was 7.3 cases/100 hospitalized patients, and lethality was 2.1%. As for bacterial meningitis, 22 suspected cases were reported, 12 (54%) were probable, four (33%) were confirmed: two by Escherichia coli and two by group C N. meningitidis. The incidence of probable bacterial meningitis was 0.14 cases/100 hospitalized patients. CONCLUSION: Streptococcus pneumoniae serotypes 19A and 3 were the most frequent cause of pneumonia. Spn19A is related to the multi-resistant clone ST320. Strengthening and continuing this strategy will allow understanding the impact of vaccination.

Introducción. La neumonía y la meningitis bacterianas son enfermedades inmunoprevenibles; la vigilancia centinela aporta información relevante acerca de su comportamiento. Objetivo. Presentar los resultados de la vigilancia centinela de neumonía y meningitis llevada a cabo en la HOMI, Fundación Hospital Pediátrico La Misericordia. Materiales y métodos. Se hizo un estudio descriptivo entre el 1 de enero y el 31 diciembre del 2016, de la vigilancia diaria de pacientes menores de 5 años con diagnóstico de neumonía o meningitis bacteriana, según las definiciones de la Organización Panamericana de la Salud (OPS). Los microorganismos fueron identificados usando el sistema automatizado VITEK TM2. Los aislamientos se enviaron al grupo de microbiología del Instituto Nacional de Salud para confirmación, serotipificación, y caracterización genotípica y fenotípica. Asimismo, se establecieron los perfiles de sensibilidad antimicrobiana. Resultados. De 1.343 casos sospechosos de neumonía bacteriana, 654 (48,7 %) fueron probables, el 84 % tenía el esquema de vacunación completo para la edad contra Haemophilus influenzae de tipo b, y el 87 %, contra neumococo. En 619 (94,6 %) pacientes se hizo hemocultivo y 41 (6,6 %) fueron positivos. S. pneumoniae se aisló en 17 (41 %) casos. El serotipo más frecuente fue el 19A, en cinco pacientes (29,4 %), en tanto que cuatro aislamientos de spn19A fueron relacionados con el clon ST320. La tasa de incidencia de neumonía bacteriana probable fue de 7,3 casos/100 pacientes hospitalizados. La letalidad fue de 2,1 %. Hubo 22 casos sospechosos de meningitis bacteriana, 12 (54 %) probables, y cuatro (33 %) confirmados: dos por Escherichia coli y dos por Neisseria meningitidis del grupo C. La incidencia de meningitis bacteriana probable fue de 0,14/100 pacientes hospitalizados. Conclusión. Los serotipos 19A y 3 de S. pneumoniae fueron la causa más frecuente de neumonía. El Spn19A se relacionó con el clon ST320 mulitirresistente. El fortalecimiento continuo de la vigilancia centinela permitirá entender el impacto de la vacunación.

Chikungunya in Guerrero, Mexico, 2019 and Evidence of Gross Underreporting in the Region.

The local public health authorities reported nine cases of chikungunya in Mexico in 2019, none of which occurred in Guerrero, a coastal state in the southwest. To test the hypothesis that chikungunya is grossly underreported in Mexico, acute sera were collected from 639 febrile patients from low-income households in Guerrero in 2019 and serologically assayed for chikungunya virus (CHIKV). Analysis of the sera by plaque reduction neutralization test revealed that 181 (28.3%) patients were seropositive for CHIKV. To identify patients with acute CHIKV infections, a subset of serum samples were tested for CHIKV-specific IgM by ELISA. Serum samples from 21 of 189 (11.1%) patients were positive. These patients met the chikungunya case definition established by the WHO. In conclusion, we provide evidence that CHIKV remains an important public health problem in Mexico and that the true number of cases is severely underestimated.

Co-Circulation of All Four Dengue Viruses and Zika Virus in Guerrero, Mexico, 2019.

A clinical and entomological investigation was performed to identify flavivirus infections in humans and mosquitoes in impoverished areas of Guerrero, a coastal state in southwestern Mexico. A total of 639 patients with acute febrile illness and 830 resting female mosquitoes in low-income communities of Guerrero in 2019 were tested for evidence of flavivirus infection. Sera were collected from all patients and screened at a dilution of 1:20 by plaque reduction neutralization test (PRNT) using dengue virus (DENV)2. A total of 431 (67.4%) patients were seropositive. Sera from a subset of seropositive patients (n = 263) were tested for flavivirus NS1 by enzyme-linked immunosorbent assay. Forty-eight (18.3%) sera contained viral antigen. All NS1-positive sera were titrated and further tested by PRNT using DENV-1 to -4, St. Louis encephalitis virus, West Nile virus, and Zika virus (ZIKV). Seven patients were seropositive for DENV-1, five patients were seropositive for DENV-2, one patient was seropositive for DENV-3, and two patients each were seropositive for DENV-4 and ZIKV. The remainder had secondary flavivirus infections or antibodies to an undetermined flavivirus. Comparative PRNTs were also performed on 60 randomly selected NS1-negative sera, identifying patients seropositive for DENV-2, DENV-3, and ZIKV. The entomological investigation yielded 736 Aedes aegypti and 94 Culex quinquefasciatus that were sorted into 183 pools and 20 pools, respectively. Mosquitoes were assayed for flavivirus RNA by RT-PCR and Sanger sequencing. DENV-2 RNA was detected in three pools of A. aegypti. In summary, we provide evidence for the concurrent circulation of all four DENVs and ZIKV in Guerrero, Mexico. The public health authorities reported no cases of DENV-3, DENV-4, and ZIKV in Guerrero in 2019 and thus, we provide evidence of under-reporting in the region.

Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis.

Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process. Previous studies have reported that autophagy-activating agents eliminate intracellular MDR MTB. Thus, combining a direct antibiotic activity against circulating bacteria with autophagy activation to eliminate bacteria residing inside cells could treat MDR TB. We show that the synthetic peptide, IP-1 (KFLNRFWHWLQLKPGQPMY), induced autophagy in HEK293T cells and macrophages at a low dose (10 µM), while increasing the dose (50 µM) induced cell death; IP-1 induced the secretion of TNFα in macrophages and killed Mtb at a dose where macrophages are not killed by IP-1. Moreover, IP-1 showed significant therapeutic activity in a mice model of progressive pulmonary TB. In terms of the mechanism of action, IP-1 sequesters ATP in vitro and inside living cells. Thus, IP-1 is the first antimicrobial peptide that eliminates MDR MTB infection by combining four activities: reducing ATP levels, bactericidal activity, autophagy activation, and TNFα secretion.

Conocimiento sobre reanimación cardiopulmonar del personal de enfermería / Conocimiento sobre reanimación cardiopulmonar del personal de enfermería

Introducción. La parada cardiorrespiratoria consiste en la interrupción brusca, inesperada y potencialmente reversible de la respiración y circulación espontánea. Representa el extremo más grave de situaciones de emergencia con elevadas tasas de mortalidad. Objetivo. Determinar el nivel de conocimiento acerca de reanimación cardiopulmonar (RCP) en el personal de enfermería de las especialidades troncales del Hospital Nacional de Itauguá en julio de 2023.Materiales y métodos. Estudio observacional descriptivo y analítico en el que se incluyó al personal de enfermería de las especialidades troncales del Hospital Nacional de Itauguá enjulio de 2023. Las variables estudiadas fueron sexo, edad, especialidad troncal y nivel de conocimientos en RCP. Se utilizó el cuestionario de conocimientos para enfermeros sobre reanimación cardio-pulmonar. Para la comparación de conocimientos entre las especialidades se utilizó la prueba chi cuadrado a un nivel de significancia de 0,05. Resultados. Se incluyeron 122enfermeros/as, 36de ginecología/obstetricia, 33 de medicina interna, 30 de pediatría y 23 de cirugía general. La edad media fue 37,63 ± 7,75 años, 69,7% de sexo femenino y 54,9% del departamento Central. El puntaje promedio global fue 5,55±2,72,significativamente (p = 0,001)mayor en la especialidad de cirugía general (6,61±2,39) comparado a la de pediatría (3,40±2,59). El nivel de conocimientos fue insuficiente en el 56,6%de los participantes, 83% de la especialidad de pediatría y 43,5% de cirugía general. Conclusión. El nivel de conocimiento del personal de enfermería sobre reanimación cardiopulmonar es deficiente y sobre todo en la especialidad de pediatría. Palabras clave: conocimiento; reanimación cardiopulmonar; enfermeros

Introduction. Cardiorespiratory arrest consists of the sudden, unexpected and potentially reversible interruption of breathing and spontaneous circulation. It represents the most serious extreme of emergency situations with high mortality rates. Objective. To determine the level of knowledge about cardiopulmonary resuscitation (CPR) in the nursing staff of the core specialties of the "Hospital Nacional de Itauguá" in July 2023. Materials and methods. Descriptive and analytical observational study in which the nursing staff of the core specialties of the "Hospital Nacional of Itauguá"was included in July 2023. The variables studied were sex, age, core specialty and level of knowledge in CPR. The knowledge questionnaire for nurses about cardio-pulmonary resuscitation was used. To compare knowledge between the specialties, the chi-square test was used at a significance level of 0.05. Results.122 nurses were included, 36 from gynecology/obstetrics, 33 from internal medicine, 30 from pediatrics and 23 from general surgery. The mean age was 37.63 ± 7.75 years, 69.7% female and 54.9% from the Central department. The overall average score was 5.55±2.72, significantly (p = 0.001) higher in the specialty of general surgery (6.61±2.39) compared to pediatrics (3.40±2.59). The level of knowledge was insufficient in 56.6% of the participants, 83% in the specialty of pediatrics and 43.5% in general surgery. Conclusion. The level of knowledge of nursing staff about cardiopulmonary resuscitation is poor, especially in the specialty of pediatrics. Key words: knowledge; cardiopulmonary resuscitation; nurses

Influenza vaccine effectiveness against hospitalizations in children and older adults-Data from South America, 2013-2017. A test negative design.

BACKGROUND: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults. METHODS: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6─24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults. RESULTS: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses. CONCLUSIONS: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.

Mortalidad por neumonía y por todas las causas en niños menores de 5 años en Colombia entre el 2005 y 2016 / Pneumonia and all causes mortality in children under 5 year old in Colombia between 2005 and 2016

RESUMEN Introducción: Las infecciones neumocócicas son una de las causas más importantes de enfermedades en niños menores de 5 años en Colombia. Objetivo: Calcular la mortalidad por neumonía y por todas las causas en niños menores de 5 años en Colombia. Métodos: Estudio ecológico, los principales desenlaces del estudio fue mortalidad por todas las causas y neumonía (CIE-10 J12-18). Resultados: Durante el año 2005 al 2016 se encontraron un total de 122.074 muertes por todas las causas, de las cuales 13359 (10.94%) correspondieron a muerte por neumonía, 750 a meningitis (0.61%) y 17.511 a muerte por otras causas respiratorias (14.34%). Conclusiones: Se ha observado una disminución de la mortalidad en las tasas de mortalidad por todas las causas, y las demás estudiadas en este artículo.

ABSTRACT Introduction: Pneumococcal infections are one of the most important causes of diseases in children under 5 years old in Colombia. Objective: Evaluate mortality from pneumonia and all causes in children under 5 years old in Colombia. Methods: Ecological study, the main outcomes of the study was all-cause mortality and pneumonia (ICD-10 J12-18). Results: During 2005 to 2016, a total of 122,074 deaths were found for all causes, of which 13,359 (10.94%) corresponded to death due to pneumonia, 750 to meningitis (0.61%) and 17,511 to death due to other respiratory causes (14.34% ). Conclusions: A decrease in mortality has been observed in all-cause mortality rates, and the others studied death causes in this article.

Sentinel surveillance for bacterial pneumonia and meningitis in children under the age of 5 in a tertiary pediatric hospital in Colombia - 2016 / Vigilancia centinela de neumonías y meningitis bacterianas en menores de 5 años en un hospital pediátrico de tercer nivel en Colombia - 2016

Abstract | Introduction: Bacterial pneumonia and meningitis are vaccine-preventable diseases. Sentinel surveillance provides relevant information about their behavior. Objective: To present the data from sentinel surveillance carried out at the Fundación HOMI, Fundación Hospital Pediátrico La Misericordia in 2016. Materials and methods: We conducted a descriptive study from January 1 to December 31, 2016, on the daily surveillance of patients under 5 years of age diagnosed with pneumonia or bacterial meningitis according to PAHO's definitions. We identified the microorganisms using the automated VITEKTM 2 system. Bacterial isolates were sent to the Microbiology Group at the Colombian Instituto Nacional de Salud for confirmation, serotyping, phenotypic, and genotypic characterization. Antimicrobial susceptibility profiles were established. Results: From 1,343 suspected cases of bacterial pneumonia, 654 (48.7%) were probable, 84% had complete Hib vaccination schedules, and 87% had complete pneumococcal vaccination schedules for age. Blood culture was taken in 619 (94.6%) and 41 (6.6%) were positive while S. pneumoniae was isolated in 17 (41%) of them. The most frequent serotype was 19A in five cases (29.4%), and four 19A serotypes were associated with the reference isolate ST320. The incidence rate of probable bacterial pneumonia was 7.3 cases/100 hospitalized patients, and lethality was 2.1%. As for bacterial meningitis, 22 suspected cases were reported, 12 (54%) were probable, four (33%) were confirmed: two by Escherichia coli and two by group C N. meningitidis. The incidence of probable bacterial meningitis was 0.14 cases/100 hospitalized patients. Conclusion: Streptococcus pneumoniae serotypes 19A and 3 were the most frequent cause of pneumonia. Spn19A is related to the multi-resistant clone ST320. Strengthening and continuing this strategy will allow understanding the impact of vaccination.

Resumen | Introducción. La neumonía y la meningitis bacterianas son enfermedades inmunoprevenibles; la vigilancia centinela aporta información relevante acerca de su comportamiento. Objetivo. Presentar los resultados de la vigilancia centinela de neumonía y meningitis llevada a cabo en la HOMI, Fundación Hospital Pediátrico La Misericordia. Materiales y métodos. Se hizo un estudio descriptivo entre el 1 de enero y el 31 diciembre del 2016, de la vigilancia diaria de pacientes menores de 5 años con diagnóstico de neumonía o meningitis bacteriana, según las definiciones de la Organización Panamericana de la Salud (OPS). Los microorganismos fueron identificados usando el sistema automatizado VITEK TM2. Los aislamientos se enviaron al grupo de microbiología del Instituto Nacional de Salud para confirmación, serotipificación, y caracterización genotípica y fenotípica. Asimismo, se establecieron los perfiles de sensibilidad antimicrobiana. Resultados. De 1.343 casos sospechosos de neumonía bacteriana, 654 (48,7 %) fueron probables, el 84 % tenía el esquema de vacunación completo para la edad contra Haemophilus influenzae de tipo b, y el 87 %, contra neumococo. En 619 (94,6 %) pacientes se hizo hemocultivo y 41 (6,6 %) fueron positivos. S. pneumoniae se aisló en 17 (41 %) casos. El serotipo más frecuente fue el 19A, en cinco pacientes (29,4 %), en tanto que cuatro aislamientos de spn19A fueron relacionados con el clon ST320. La tasa de incidencia de neumonía bacteriana probable fue de 7,3 casos/100 pacientes hospitalizados. La letalidad fue de 2,1 %. Hubo 22 casos sospechosos de meningitis bacteriana, 12 (54 %) probables, y cuatro (33 %) confirmados: dos por Escherichia coli y dos por Neisseria meningitidis del grupo C. La incidencia de meningitis bacteriana probable fue de 0,14/100 pacientes hospitalizados. Conclusión. Los serotipos 19A y 3 de S. pneumoniae fueron la causa más frecuente de neumonía. El Spn19A se relacionó con el clon ST320 mulitirresistente. El fortalecimiento continuo de la vigilancia centinela permitirá entender el impacto de la vacunación.

Evaluation of host and viral factors associated with severe dengue based on the 2009 WHO classification.

BACKGROUND: Dengue fever (DF) is the most prevalent arthropod-borne viral disease affecting humans. The World Health Organization (WHO) proposed a revised classification in 2009 to enable the more effective identification of cases of severe dengue (SD). This was designed primarily as a clinical tool, but it also enables cases of SD to be differentiated into three specific subcategories (severe vascular leakage, severe bleeding, and severe organ dysfunction). However, no study has addressed whether this classification has advantage in estimating factors associated with the progression of disease severity or dengue pathogenesis. We evaluate in a dengue outbreak associated risk factors that could contribute to the development of SD according to the 2009 WHO classification. METHODS: A prospective cross-sectional study was performed during an epidemic of dengue in 2009 in Chiapas, Mexico. Data were analyzed for host and viral factors associated with dengue cases, using the 1997 and 2009 WHO classifications. The cost-benefit ratio (CBR) was also estimated. RESULTS: The sensitivity in the 1997 WHO classification for determining SD was 75%, and the specificity was 97.7%. For the 2009 scheme, these were 100% and 81.1%, respectively. The 2009 classification showed a higher benefit (537%) with a lower cost (10.2%) than the 1997 WHO scheme. A secondary antibody response was strongly associated with SD. Early viral load was higher in cases of SD than in those with DF. Logistic regression analysis identified predictive SD factors (secondary infection, disease phase, viral load) within the 2009 classification. However, within the 1997 scheme it was not possible to differentiate risk factors between DF and dengue hemorrhagic fever or dengue shock syndrome. The critical clinical stage for determining SD progression was the transition from fever to defervescence in which plasma leakage can occur. CONCLUSIONS: The clinical phenotype of SD is influenced by the host (secondary response) and viral factors (viral load). The 2009 WHO classification showed greater sensitivity to identify SD in real time. Timely identification of SD enables accurate early decisions, allowing proper management of health resources for the benefit of patients at risk for SD. This is possible based on the 2009 WHO classification.