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1.
PLoS One ; 19(5): e0283037, 2024.
Article in English | MEDLINE | ID: mdl-38713667

ABSTRACT

COVID-19 affects children less seriously than adults; however, severe cases and deaths are documented. This study objective is to determine socio-demographic, clinical and laboratory indicators associated with severe pediatric COVID-19 and mortality at hospital entrance. A multicenter, retrospective, cross-sectional study was performed in 13 tertiary hospitals in Bolivia. Clinical records were collected retrospectively from patients less than 18 years of age and positive for SARS-CoV-2 infection. All variables were measured at hospital entrance; outcomes of interest were ICU admission and death. A score for disease severity was developed using a logistic regression model. 209 patients were included in the analysis. By the end of the study, 43 (20.6%) of children were admitted to the Intensive care unit (ICU), and 17 (8.1%) died. Five indicators were independently predictive of COVID-19 severity: age below 10 years OR: 3.3 (CI95%: 1.1-10.4), days with symptoms to medical care OR: 2.8 (CI95%: 1.2-6.5), breathing difficulty OR: 3.4 (CI95%: 1.4-8.2), vomiting OR: 3.3 (CI95%: 1.4-7.4), cutaneous lesions OR: 5.6 (CI95%: 1.9-16.6). Presence of three or more of these risk factors at hospital entrance predicted severe disease in COVID-19 positive children. Age, presence of underlying illness, male sex, breathing difficulty, and dehydration were predictive of death in COVID-19 children. Our study identifies several predictors of severe pediatric COVID-19 and death. Incorporating these predictors, we developed a tool that clinicians can use to identify children at high risk of severe COVID-19 in limited-resource settings.


Subject(s)
COVID-19 , SARS-CoV-2 , Severity of Illness Index , Humans , COVID-19/mortality , COVID-19/epidemiology , COVID-19/diagnosis , Child , Male , Female , Child, Preschool , Adolescent , Retrospective Studies , Cross-Sectional Studies , Infant , SARS-CoV-2/isolation & purification , Bolivia/epidemiology , Hospitalization , Intensive Care Units/statistics & numerical data , Risk Factors , Sociodemographic Factors
2.
mBio ; : e0345123, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38651896

ABSTRACT

The airway milieu of individuals with muco-obstructive airway diseases (MADs) is defined by the accumulation of dehydrated mucus due to hyperabsorption of airway surface liquid and defective mucociliary clearance. Pathological mucus becomes progressively more viscous with age and disease severity due to the concentration and overproduction of mucin and accumulation of host-derived extracellular DNA (eDNA). Respiratory mucus of MADs provides a niche for recurrent and persistent colonization by respiratory pathogens, including Pseudomonas aeruginosa, which is responsible for the majority of morbidity and mortality in MADs. Despite high concentration inhaled antibiotic therapies and the absence of antibiotic resistance, antipseudomonal treatment failure in MADs remains a significant clinical challenge. Understanding the drivers of antibiotic tolerance is essential for developing more effective treatments that eradicate persistent infections. The complex and dynamic environment of diseased airways makes it difficult to model antibiotic efficacy in vitro. We aimed to understand how mucin and eDNA concentrations, the two dominant polymers in respiratory mucus, alter the antibiotic tolerance of P. aeruginosa. Our results demonstrate that polymer concentration and molecular weight affect P. aeruginosa survival post antibiotic challenge. Polymer-driven antibiotic tolerance was not explicitly associated with reduced antibiotic diffusion. Lastly, we established a robust and standardized in vitro model for recapitulating the ex vivo antibiotic tolerance of P. aeruginosa observed in expectorated sputum across age, underlying MAD etiology, and disease severity, which revealed the inherent variability in intrinsic antibiotic tolerance of host-evolved P. aeruginosa populations. IMPORTANCE: Antibiotic treatment failure in Pseudomonas aeruginosa chronic lung infections is associated with increased morbidity and mortality, illustrating the clinical challenge of bacterial infection control. Understanding the underlying infection environment, as well as the host and bacterial factors driving antibiotic tolerance and the ability to accurately recapitulate these factors in vitro, is crucial for improving antibiotic treatment outcomes. Here, we demonstrate that increasing concentration and molecular weight of mucin and host eDNA drive increased antibiotic tolerance to tobramycin. Through systematic testing and modeling, we identified a biologically relevant in vitro condition that recapitulates antibiotic tolerance observed in ex vivo treated sputum. Ultimately, this study revealed a dominant effect of in vivo evolved bacterial populations in defining inter-subject ex vivo antibiotic tolerance and establishes a robust and translatable in vitro model for therapeutic development.

3.
PLoS One ; 19(3): e0301016, 2024.
Article in English | MEDLINE | ID: mdl-38547181

ABSTRACT

Saliva is a readily accessible and inexpensive biological specimen that enables investigation of the oral microbiome, which can serve as a biomarker of oral and systemic health. There are two routine approaches to collect saliva, stimulated and unstimulated; however, there is no consensus on how sampling method influences oral microbiome metrics. In this study, we analyzed paired saliva samples (unstimulated and stimulated) from 88 individuals, aged 7-18 years. Using 16S rRNA gene sequencing, we investigated the differences in bacterial microbiome composition between sample types and determined how sampling method affects the distribution of taxa associated with untreated dental caries and gingivitis. Our analyses indicated significant differences in microbiome composition between the sample types. Both sampling methods were able to detect significant differences in microbiome composition between healthy subjects and subjects with untreated caries. However, only stimulated saliva revealed a significant association between microbiome diversity and composition in individuals with diagnosed gingivitis. Furthermore, taxa previously associated with dental caries and gingivitis were preferentially enriched in individuals with each respective disease only in stimulated saliva. Our study suggests that stimulated saliva provides a more nuanced readout of microbiome composition and taxa distribution associated with untreated dental caries and gingivitis compared to unstimulated saliva.


Subject(s)
Dental Caries , Gingivitis , Microbiota , Humans , Saliva/microbiology , RNA, Ribosomal, 16S/genetics , Microbiota/genetics
4.
bioRxiv ; 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38187602

ABSTRACT

The airway milieu of individuals with muco-obstructive airway diseases (MADs) is defined by the accumulation of dehydrated mucus due to hyperabsorption of airway surface liquid and defective mucociliary clearance. Pathological mucus becomes progressively more viscous with age and disease severity due to the concentration and overproduction of mucin and accumulation of host-derived extracellular DNA (eDNA). Respiratory mucus of MADs provides a niche for recurrent and persistent colonization by respiratory pathogens, including Pseudomonas aeruginosa , which is responsible for the majority of morbidity and mortality in MADs. Despite high concentration inhaled antibiotic therapies and the absence of antibiotic resistance, antipseudomonal treatment failure in MADs remains a significant clinical challenge. Understanding the drivers of antibiotic recalcitrance is essential for developing more effective treatments that eradicate persistent infections. The complex and dynamic environment of diseased airways makes it difficult to model antibiotic efficacy in vitro . We aimed to understand how mucin and eDNA concentrations, the two dominant polymers in respiratory mucus, alter the antibiotic tolerance of P. aeruginosa . Our results demonstrate that polymer concentration and molecular weight affect P. aeruginosa survival post antibiotic challenge. Polymer-driven antibiotic tolerance was not explicitly associated with reduced antibiotic diffusion. Lastly, we established a robust and standardized in vitro model for recapitulating the ex vivo antibiotic tolerance of P. aeruginosa observed in expectorated sputum across age, underlying MAD etiology, and disease severity, which revealed the inherent variability in intrinsic antibiotic tolerance of host-evolved P. aeruginosa populations. Importance: Antibiotic treatment failure in Pseudomonas aeruginosa chronic lung infections is associated with increased morbidity and mortality, illustrating the clinical challenge of bacterial infection control. Understanding the underlying infection environment, as well as the host and bacterial factors driving antibiotic tolerance and the ability to accurately recapitulate these factors in vitro , is crucial for improving antibiotic treatment outcomes. Here, we demonstrate that increasing concentration and molecular weight of mucin and host eDNA drive increased antibiotic tolerance to tobramycin. Through systematic testing and modeling, we identified a biologically relevant in vitro condition that recapitulates antibiotic tolerance observed in ex vivo treated sputum. Ultimately, this study revealed a dominant effect of in vivo evolved bacterial populations in defining inter-subject ex vivo antibiotic tolerance and establishes a robust and translatable in vitro model for therapeutic development.

5.
Rev Peru Med Exp Salud Publica ; 39(3): 336-344, 2022.
Article in Spanish, English | MEDLINE | ID: mdl-36478167

ABSTRACT

OBJECTIVES.: To evaluate the variation of hematological profiles of patients infected with uncomplicated Plasmodium vivax (Pv) and P. falciparum (Pf) malaria before, during and after treatment in a population of the Loreto region. MATERIALS AND METHODS.: This study was conducted between 2010 and 2012, in Zungarococha (Iquitos). The 425 participants had three visits (visit 1-day 0-before treatment, visit 2-day 7-during treatment, visit 3-day 28-after treatment), complete blood count, microscopic and molecular diagnosis (PCR). RESULTS.: At the first visit, 93 (21.9%) participants were found positive for Pv and 34 (8.0%) for Pf. All positives showed a reduction in hematocrit, white blood cell count (WBC), ablated and segmented neutrophils, eosinophils and platelets (p<0.001) compared to the negative group. A higher percentage of ablated neutrophils was found in Pf and segmented neutrophils in Pv compared to the negative group. Variations in hematological profiles were observed after treatment for both species; ablated neutrophils decreased, platelets increased, eosinophils increased at day 7 and declined at day 28, hematocrit and segmented neutrophils decreased at day 7 and normalized at day 28. Interspecies differences over time showed a bigger daily decrease in ablated neutrophils in Pv-infected when compared to Pf. CONCLUSIONS.: The hematological profile in uncomplicated malaria-positive patients varies over time during and after treatment. These are indicators of disease progression and help in the therapeutic surveillance of Plasmodium-infected patients.


OBJETIVOS.: Evaluar la variación de los perfiles hematológicos antes, durante y después del tratamiento de pacientes infectados con malaria no complicada por Plasmodium vivax (Pv) y P. falciparum (Pf) en una población de la región Loreto. MATERIALES Y MÉTODOS.: El estudio se realizó entre 2010 y 2012, en Zungarococha (Iquitos). Los 425 participantes tuvieron tres visitas (visita 1-día 0-antes del tratamiento, visita 2-día 7-durante tratamiento, visita 3-día 28-después del tratamiento), hemograma completo, diagnóstico microscópico y molecular (PCR). RESULTADOS.: En la primera visita, se encontraron 93 (21,9%) positivos a Pv y 34 (8,0%) a Pf. Todos los positivos mostraron una reducción en los indicadores hematológicos de hematocrito, recuento de glóbulos blancos (RGB), neutrófilos abastonados y segmentados, eosinófilos y plaquetas (p<0.001) en comparación con el grupo negativo. Se encontró un porcentaje mayor de neutrófilos abastonados en Pf y de neutrófilos segmentados en Pv comparado al grupo negativo. Se observó variaciones en los perfiles hematológicos después del tratamiento para ambas especies, los neutrófilos abastonados disminuyeron, las plaquetas aumentaron, los eosinófilos se incrementaron al día 7 y decaen el día 28, el hematocrito y los neutrófilos segmentados disminuyeron al día 7 y se normalizaron el día 28. Las diferencias entre especies en el tiempo mostraron una disminución diaria de neutrófilos abastonados en infectados con Pv que en Pf. CONCLUSIONES.: El perfil hematológico en pacientes positivos a malaria no complicada varía en el tiempo durante y después del tratamiento. Estos son indicadores de la progresión de la enfermedad y ayudan en la vigilancia terapéutica de pacientes infectados con Plasmodium.


Subject(s)
Humans , Peru/epidemiology
6.
Rev. peru. med. exp. salud publica ; 39(3): 336-344, jul.-sep. 2022. tab, graf
Article in Spanish | LILACS | ID: biblio-1410004

ABSTRACT

RESUMEN Objetivos. Evaluar la variación de los perfiles hematológicos antes, durante y después del tratamiento de pacientes infectados con malaria no complicada por Plasmodium vivax (Pv) y P. falciparum (Pf) en una población de la región Loreto. Materiales y métodos. El estudio se realizó entre 2010 y 2012, en Zungarococha (Iquitos). Los 425 participantes tuvieron tres visitas (visita 1-día 0-antes del tratamiento, visita 2-día 7-durante tratamiento, visita 3-día 28-después del tratamiento), hemograma completo, diagnóstico microscópico y molecular (PCR). Resultados. En la primera visita, se encontraron 93 (21,9%) positivos a Pv y 34 (8,0%) a Pf. Todos los positivos mostraron una reducción en los indicadores hematológicos de hematocrito, recuento de glóbulos blancos (RGB), neutrófilos abastonados y segmentados, eosinófilos y plaquetas (p<0.001) en comparación con el grupo negativo. Se encontró un porcentaje mayor de neutrófilos abastonados en Pf y de neutrófilos segmentados en Pv comparado al grupo negativo. Se observó variaciones en los perfiles hematológicos después del tratamiento para ambas especies, los neutrófilos abastonados disminuyeron, las plaquetas aumentaron, los eosinófilos se incrementaron al día 7 y decaen el día 28, el hematocrito y los neutrófilos segmentados disminuyeron al día 7 y se normalizaron el día 28. Las diferencias entre especies en el tiempo mostraron una disminución diaria de neutrófilos abastonados en infectados con Pv que en Pf. Conclusiones. El perfil hematológico en pacientes positivos a malaria no complicada varía en el tiempo durante y después del tratamiento. Estos son indicadores de la progresión de la enfermedad y ayudan en la vigilancia terapéutica de pacientes infectados con Plasmodium.


ABSTRACT Objectives. To evaluate the variation of hematological profiles of patients infected with uncomplicated Plasmodium vivax (Pv) and P. falciparum (Pf) malaria before, during and after treatment in a population of the Loreto region. Materials and methods. This study was conducted between 2010 and 2012, in Zungarococha (Iquitos). The 425 participants had three visits (visit 1-day 0-before treatment, visit 2-day 7-during treatment, visit 3-day 28-after treatment), complete blood count, microscopic and molecular diagnosis (PCR). Results. At the first visit, 93 (21.9%) participants were found positive for Pv and 34 (8.0%) for Pf. All positives showed a reduction in hematocrit, white blood cell count (WBC), ablated and segmented neutrophils, eosinophils and platelets (p<0.001) compared to the negative group. A higher percentage of ablated neutrophils was found in Pf and segmented neutrophils in Pv compared to the negative group. Variations in hematological profiles were observed after treatment for both species; ablated neutrophils decreased, platelets increased, eosinophils increased at day 7 and declined at day 28, hematocrit and segmented neutrophils decreased at day 7 and normalized at day 28. Interspecies differences over time showed a bigger daily decrease in ablated neutrophils in Pv-infected when compared to Pf. Conclusions. The hematological profile in uncomplicated malaria-positive patients varies over time during and after treatment. These are indicators of disease progression and help in the therapeutic surveillance of Plasmodium-infected patients.


Subject(s)
Humans , Male , Female , Patients , Blood Cell Count , Malaria , Parasitic Diseases , Plasmodium , Tropical Medicine , Public Health Surveillance , Neutrophils
7.
Am J Trop Med Hyg ; 105(5): 1187-1192, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34491223

ABSTRACT

The mechanism of vertical transmission of Trypanosoma cruzi is poorly understood. In this study, we evaluated the role of IgG subclasses in the congenital transmission of Chagas disease. We conducted a case-control study in a public maternity hospital in Santa Cruz, Bolivia, enrolling women at delivery. Thirty women who transmitted T. cruzi to their newborns (cases), and 51 women who did not (controls) were randomly selected from 676 total seropositive women. Trypanosoma cruzi-specific IgG1, IgG2, and IgG3 levels were measured by in-house ELISA. The IgG4 levels were unmeasurable as a result of low levels in all participants. Quantitative polymerase chain reaction results and demographic factors were also analyzed. One-unit increases in normalized absorbance ratio of IgG1 or IgG2 levels increased the odds of congenital T. cruzi transmission in Chagas-seropositive women by 2.0 (95% CI: 1.1-3.6) and 2.27 (95% CI: 0.9-5.7), adjusted for age and previous blood transfusion. Odds of congenital transmission were 7.0 times higher in parasitemic mothers (95% CI: 2.3-21.3, P < 0.01) compared with nonparasitemic mothers. We observed that all mothers with IgG1 ≥ 4 were transmitters (sensitivity = 20%, specificity = 100%). Additionally, no mothers with IgG2 < 1.13 were transmitters (sensitivity = 100%, specificity = 21.6%). We demonstrated that IgG subclasses and parasite presence in blood are associated with vertical transmission of T. cruzi and could identify women at increased risk for congenital transmission by measuring IgG subclasses. These measures have potential as objective screening tests to predict the congenital transmission of Chagas.


Subject(s)
Chagas Disease/diagnosis , Chagas Disease/immunology , Chagas Disease/transmission , Immunoglobulin G/blood , Infectious Disease Transmission, Vertical , Pregnancy Complications, Parasitic/diagnosis , Pregnancy Complications, Parasitic/immunology , Trypanosoma cruzi/immunology , Adult , Bolivia , Case-Control Studies , Chagas Disease/blood , Female , Healthy Volunteers , Humans , Infant, Newborn , Male , Pregnancy , Risk Factors
8.
Biomedica ; 39(2): 323-329, 2019 06 15.
Article in English, Spanish | MEDLINE | ID: mdl-31529819

ABSTRACT

Introduction. Unjustified authorship or "gift authorship" is an inadequate practice of authorship that consists of naming as authors people who do not meet the authorship criteria. Reports of scientific research are often published as original articles in scientific journals and may present these inappropriate practices. Objectives. Determine the prevalence of gift authorship in original articles for publication. Materials and methods. Descriptive study in which the authorship contributions section of all the articles published between 2013 and the first quarter of 2017 in a Peruvian magazine was reviewed. Gift authorship was considered when an author did not meet at least one of the criteria established by the International Committee of Medical Journal Editors (ICMJE). Results. Of the 209 original articles published, 11 were excluded because they did not report authorship contributions. The prevalence of gift authorship was 53.5% (106). The critreria least met were the final approval of the manuscript (23.2%) and the writing and critical review of this manuscript. (16.8%). Conclusions. It is necessary that educational institutions train researchers to distinguish between authorship and contribution. In addition, it is necessary that the journals request and corroborate the reported contributions.


Introducción. La autoría injustificada o 'autoría de regalo' es una práctica inadecuada que consiste en nombrar como autores a personas que no cumplen los criterios de autoría. Los informes de investigaciones científicas suelen ser publicados como artículos originales en revistas científicas y pueden presentar estas prácticas inadecuadas. Objetivos. Determinar la prevalencia de autoría de regalo en publicaciones de artículos originales. Materiales y métodos. Se trata de un estudio descriptivo en el cual se revisó la sección de contribuciones de autoría de todos los artículos publicados en una revista peruana desde enero de 2013 hasta marzo de 2017. Se consideró una autoría de regalo cuando un autor no cumplía con, al menos, uno de los criterios establecidos por el International Committee of Medical Journal Editors (ICMJE). Resultados. De los 209 artículos originales publicados, 11 fueron excluidos debido a que no reportaron las contribuciones de autoría. La prevalencia de autoría de regalo de los 198 artículos incluidos fue de 106 (53,5 %). Los criterios que menos cumplieron fueron la aprobación final del manuscrito (23,2 %), y su redacción y revisión crítica (16,8 %). Conclusiones. Es necesario que las instituciones educativas capaciten a los investigadores para que discriminen entre autoría y contribución. Además, es necesario que las revistas soliciten y corroboren las contribuciones reportadas.


Subject(s)
Authorship/standards , Bibliometrics , Guidelines as Topic , Humans , Periodicals as Topic/standards , Peru , Publishing/standards , Writing
9.
Biomédica (Bogotá) ; 39(2): 323-329, ene.-jun. 2019. graf
Article in Spanish | LILACS | ID: biblio-1011444

ABSTRACT

Resumen Introducción. La autoría injustificada o 'autoría de regalo' es una práctica inadecuada que consiste en nombrar como autores a personas que no cumplen los criterios de autoría. Los informes de investigaciones científicas suelen ser publicados como artículos originales en revistas científicas y pueden presentar estas prácticas inadecuadas. Objetivos. Determinar la prevalencia de autoría de regalo en publicaciones de artículos originales. Materiales y métodos. Se trata de un estudio descriptivo en el cual se revisó la sección de contribuciones de autoría de todos los artículos publicados en una revista peruana desde enero de 2013 hasta marzo de 2017. Se consideró una autoría de regalo cuando un autor no cumplía con, al menos, uno de los criterios establecidos por el International Committee of Medical Journal Editors (ICMJE). Resultados. De los 209 artículos originales publicados, 11 fueron excluidos debido a que no reportaron las contribuciones de autoría. La prevalencia de autoría de regalo de los 198 artículos incluidos fue de 106 (53,5 %). Los criterios que menos cumplieron fueron la aprobación final del manuscrito (23,2 %), y su redacción y revisión crítica (16,8 %). Conclusiones. Es necesario que las instituciones educativas capaciten a los investigadores para que discriminen entre autoría y contribución. Además, es necesario que las revistas soliciten y corroboren las contribuciones reportadas.


Abstract Introduction: Unjustified authorship or "gift authorship" is an inadequate practice of authorship that consists of naming as authors people who do not meet the authorship criteria. Reports of scientific research are often published as original articles in scientific journals and may present these inappropriate practices. Objective: Determine the prevalence of gift authorship in original articles for publication. Materials and methods:. Descriptive study in which the authorship contributions section of all the articles published between 2013 and the first quarter of 2017 in a Peruvian magazine was reviewed. Gift authorship was considered when an author did not meet at least one of the criteria established by the International Committee of Medical Journal Editors (ICMJE). Results: Of the 209 original articles published, 11 were excluded because they did not report authorship contributions. The prevalence of gift authorship was 53.5% (106). The critreria least met were the final approval of the manuscript (23.2%) and the writing and critical review of this manuscript. (16.8%). Conclusions: It is necessary that educational institutions train researchers to distinguish between authorship and contribution. In addition, it is necessary that the journals request and corroborate the reported contributions.


Subject(s)
Humans , Authorship/standards , Periodicals as Topic/standards , Peru , Publishing/standards , Writing , Bibliometrics , Guidelines as Topic
10.
J Infect Dis ; 219(4): 609-618, 2019 01 29.
Article in English | MEDLINE | ID: mdl-30252099

ABSTRACT

Background: Congenital Trypanosoma cruzi infection accounts for an estimated 22% of new cases of Chagas disease in Latin America. However, neonatal diagnosis is challenging, as 9-month follow-up for immunoglobulin G testing is poor, quantitative polymerase chain reaction (qPCR) analysis is not routinely performed, and the micromethod misses ≥40% of congenital infections. Methods: Biorepository samples from new mothers and their infants from Piura, Peru, (an area of nonendemicity), and Santa Cruz, Bolivia (an area of endemicity) were accessed. Infant specimens were assessed using the micromethod, qPCR analysis, and a trypomastigote excretory secretory antigen (TESA) blot for detection of immunoglobulin M (IgM)-specific shed acute phase antigen (SAPA) bands, using qPCR as the gold standard. Results: When compared to qPCR, IgM TESA blot was both sensitive and specific for congenital Chagas disease diagnosis. Cumulative sensitivity (whether only 4 bands or all 6 bands were present) was 80% (95% confidence interval [CI], 59%-92%). Specificity was 94% (95% CI, 92%-96%) in the area of endemicity and 100% in the area of nonendemicity. SAPA bands occurred sequentially and in pairs, and parasite loads correlated highly with the number of SAPA bands present. The micromethod detected infection in fewer than half of infected infants. Conclusions: The IgM TESA blot for detection of SAPA bands is rapid, relatively inexpensive, and more sensitive than the micromethod and may be a useful point-of-care test for detection of congenital T. cruzi infection.


Subject(s)
Chagas Disease/congenital , Chagas Disease/diagnosis , Diagnostic Tests, Routine/methods , Glycoproteins/blood , Immunoblotting/methods , Immunoglobulin M/immunology , Neuraminidase/blood , Trypanosoma cruzi/immunology , Antibodies, Protozoan/immunology , Bolivia , Female , Humans , Infant , Infant, Newborn , Male , Peru , Pregnancy , Sensitivity and Specificity
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