Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links ...within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened.
We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 95% CI 0.02-1.10, p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region.
In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.
INTRODUCTIONThe aim of this study is to assess epidemiological, clinical and laboratory characteristics of primary infection by Epstein-Barr virus (EBV) in children without previous diagnosis of any ...immune disease and its relationship with clinical presentation. PATIENTS AND METHODSA retrospective study was conducted on all children from 0 to 15 years with IgM against viral capsid of EBV positive or indeterminate during a 22 month period. Epidemiological, clinical and laboratory data were analysed and compared between typical (mononucleosis syndrome) and non-typical clinical symptoms. RESULTSThe study included a total of 103 children, with a median age of 7 years (3-12.5 years). Almost two-thirds (63%) of patients had typical clinical signs, with a mononucleosis syndrome, and 37% had a non-typical presentation. The non-typical clinical group had a lower age (P=.03) and took less antibiotic than the typical clinical group (P=.015). From laboratory studies, there were no differences between the groups, except in RCP, which was higher in typical clinical group (P=.04). Heterophile antibodies were positive in 33% of patients. An indeterminate IgM against viral capsid was present in 20% of the patients, and most of them had an oligosymptomatic or atypical presentation. An IgM positive for other viruses was found in 21%, and 3 of them were suspicious of false positive for EBV. CONCLUSIONSIn the studied population, a primary infection due to EBV is common in younger ages, and they have usually an oligosymptomatic clinical presentation. A very low percentage of positive heterophile antibodies were found. Cases with indeterminate IgM against viral capsid are more frequent in the non-typical clinical group. Co-infection with other viruses is common.
In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based ...antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting.
In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay.
WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8-94·4) for isoniazid, 73·3% (44·9-92·2) for rifampicin, 50·0% (21·1-78·9) for ethambutol, and 57·1% (34·0-78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected.
We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting.
European Research Council and the Spanish Ministerio de Ciencia.
Here we report two cases of isolation of Aurantimonas altamirensis from pleural fluid and blood. The strains were identified by 16S rRNA gene sequencing. A. altamirensis appears to be a rare pathogen ...involved in unusual infectious processes, and must be isolated and studied at the molecular level for correct clinical diagnosis.
ResumenIntroducciónEl objetivo de este estudio es conocer las características epidemiológicas, clínicas y analíticas de la primoinfección por el virus de Epstein-Barr (VEB) en niños sin diagnóstico ...previo de ninguna enfermedad inmune y su relación con la forma de presentación clínica.Pacientes y métodosEstudio retrospectivo de pacientes entre 0 y 15 años con IgM sérica frente a la cápside viral del VEB positiva o indeterminada, durante un período de 22 meses. Se analizaron datos epidemiológicos, clínicos y de laboratorio y se compararon según tuvieran una clínica típica (síndrome mononucleósico) o no típica.ResultadosSe incluyeron 103 niños. La mediana de la edad fue de 7 años (3-12,5 años). El 63% de los pacientes presentaron clínica típica o síndrome mononucleósico y el 37% una clínica no típica. La edad fue significativamente menor en el grupo de clínica no típica (p = 0,03) y recibieron menos tratamiento antibiótico (p = 0,015). En los parámetros analíticos no hubo diferencias estadísticamente significativas excepto en la PCR, discretamente más elevada en el grupo de clínica típica (p = 0,04). El 33% de los pacientes tuvieron anticuerpos heterófilos positivos. El 20% tuvieron una IgM frente a la cápside viral indeterminada, la mayoría con clínica oligosintomática o atípica. El 21% tuvieron IgM positivas para otros virus y 3 de ellos fueron posibles falsos positivos para el VEB. ConclusionesEn nuestra población, la primoinfección por VEB es frecuente en niños de menor edad, y en ellos predominan las formas oligosintomáticas. El porcentaje de anticuerpos heterófilos positivos ha sido muy bajo en nuestra muestra. Los casos con IgM frente a la cápside viral indeterminada son más frecuentes en el grupo de clínica no típica. Es común detectar coinfección con otros virus.
Consecutive adult patients admitted to the hospital with community-acquired pneumonia from January 2000 to September 2003 were included in this prospective observational cohort study. A total of 459 ...patients, 259 treated with levofloxacin in single drug therapy at a dose of 500
mg once a day and 209 with the combination of ceftriaxone plus clarithromycin at a dose of 2
g once a day and 500
mg every 12
h, respectively, were included. The hospital admission decision was made using a clinical guideline based on the Pneumonia Severity Index (PSI). Fifteen (6%) patients died in the group treated with levofloxacin in single drug therapy and 25 (12%) in the group treated with ceftriaxone plus clarithromycin (
P = 0.024). The mortality differences between both treatment groups, adjusted by the PSI score, show an OR of 0.39 (95% CI 0.17–0.87). There were no statistically significant differences between the duration of treatments or hospital stay. These data suggest that levofloxacin as single drug therapy is more effective than the combination of ceftriaxone plus clarithromycin in the treatment of moderate to severe pneumonia that requires hospitalization.
Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission ...dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.
The aim of this study is to assess epidemiological, clinical and laboratory characteristics of primary infection by Epstein–Barr virus (EBV) in children without previous diagnosis of any immune ...disease and its relationship with clinical presentation.
A retrospective study was conducted on all children from 0 to 15 years with IgM against viral capsid of EBV positive or indeterminate during a 22 month period. Epidemiological, clinical and laboratory data were analysed and compared between typical (mononucleosis syndrome) and non-typical clinical symptoms.
The study included a total of 103 children, with a median age of 7 years (3–12.5 years). Almost two-thirds (63%) of patients had typical clinical signs, with a mononucleosis syndrome, and 37% had a non-typical presentation. The non-typical clinical group had a lower age (P=.03) and took less antibiotic than the typical clinical group (P=.015). From laboratory studies, there were no differences between the groups, except in RCP, which was higher in typical clinical group (P=.04). Heterophile antibodies were positive in 33% of patients. An indeterminate IgM against viral capsid was present in 20% of the patients, and most of them had an oligosymptomatic or atypical presentation. An IgM positive for other viruses was found in 21%, and 3 of them were suspicious of false positive for EBV.
In the studied population, a primary infection due to EBV is common in younger ages, and they have usually an oligosymptomatic clinical presentation. A very low percentage of positive heterophile antibodies were found. Cases with indeterminate IgM against viral capsid are more frequent in the non-typical clinical group. Co-infection with other viruses is common.
El objetivo de este estudio es conocer las características epidemiológicas, clínicas y analíticas de la primoinfección por el virus de Epstein-Barr (VEB) en niños sin diagnóstico previo de ninguna enfermedad inmune y su relación con la forma de presentación clínica.
Estudio retrospectivo de pacientes entre 0 y 15 años con IgM sérica frente a la cápside viral del VEB positiva o indeterminada, durante un período de 22 meses. Se analizaron datos epidemiológicos, clínicos y de laboratorio y se compararon según tuvieran una clínica típica (síndrome mononucleósico) o no típica.
Se incluyeron 103 niños. La mediana de la edad fue de 7 años (3-12.5 años). El 63% de los pacientes presentaron clínica típica o síndrome mononucleósico y el 37% una clínica no típica. La edad fue significativamente menor en el grupo de clínica no típica (p=0,03) y recibieron menos tratamiento antibiótico (p=0,015). En los parámetros analíticos no hubo diferencias estadísticamente significativas excepto en la PCR, discretamente más elevada en el grupo de clínica típica (p=0,04). El 33% de los pacientes tuvieron anticuerpos heterófilos positivos. El 20% tuvieron una IgM frente a la cápside viral indeterminada, la mayoría con clínica oligosintomática o atípica. El 21% tuvieron IgM positivas para otros virus y 3 de ellos fueron posibles falsos positivos para el VEB.
En nuestra población, la primoinfección por VEB es frecuente en niños de menor edad, y en ellos predominan las formas oligosintomáticas. El porcentaje de anticuerpos heterófilos positivos ha sido muy bajo en nuestra muestra. Los casos con IgM frente a la cápside viral indeterminada son más frecuentes en el grupo de clínica no típica. Es común detectar coinfección con otros virus.
Determinar el porcentaje de Staphylococcus aureus resistente a meticilina (SARM) entre los pacientes ingresados en un servicio de urgencias del Hospital Lluís Alcanyís de Xàtiva (Valencia), España, ...desde enero a junio de 2012.
Los datos se recogieron mediante un cuestionario con los siguientes ítems: edad, sexo, antecedentes personales, tratamiento antibiótico previo, ingresos hospitalarios anteriores y origen. Los médicos de Urgencias utilizaron torundas humedecidas con suero fisiológico (TranSystems® COPAN) para recoger el material de las fosas nasales de los pacientes citados.
Se estudiaron 120 pacientes con alto riesgo de colonización por SARM. Se detectaron 19 (15,83%) pacientes con aislamientos positivos para SARM; de ellos, el 52,63% eran mujeres, con una edad media de 66,6 años. Solo 5 (26,31%) pacientes habían tomado antibiótico previamente, 4 (21,05%) habían tenido algún ingreso hospitalario anterior, 7 (36,84%) provenían de residencias de la tercera edad, 12 (63,15%) estaban en su domicilio, 4 (21,05%) tenían obesidad mórbida, 9 (47,36%) padecían diabetes mellitus, 6 (31,57%) presentaban enfermedad pulmonar obstructiva crónica y ninguno tenía alergia a betalactámicos.
La proporción de infecciones por SARM fue del 16%. Los cultivos de vigilancia activa deben ser considerados en pacientes con alto riesgo de colonización por SARM e ingresados desde Urgencias.
To determine the percentage of methicillin-resistant Staphylococcus aureus (MRSA) among patients admitted from an emergency department of the Hospital Lluís Alcanyís de Xàtiva (Valencia), Spain, from January to June 2012.
The data were collected using a questionnaire with the following items: age, sex, personal history, previous antibiotic treatment, previous hospital admission, and origin. The emergency department doctors used swabs moistened with physiological saline (TranSystems® COPAN) to collect the material from the nasal cavity of the cited patients.
A total of 120 patients with a high risk of MRSA colonisation were studied. Positive isolation of MRSA was detected in 19 (15.83%) patients, of whom 52.63% were women, with a median age of 66.6 years. Only 5 (26.31%) patients had taken antibiotics previously, 4 (21.05%) had a previous admission, 7 (36.84%) were from homes for the elderly, 12 (63.15%) were from home, 4 (21.05%) had morbid obesity, 9 (47.36%) suffered from diabetes mellitus, 6 (31.57%) with chronic obstructive pulmonary disease, and none of them were allergic to beta-lactams.
The proportion of infections due to MRSA was 16%. Active surveillance cultures must be considered in patients with a high risk of MRSA colonisation and admitted from emergency departments.
Introduction: The aim of this study is to assess epidemiological, clinical and laboratory characteristics of primary infection by Epstein–Barr virus (EBV) in children without previous diagnosis of ...any immune disease and its relationship with clinical presentation. Patients and methods: A retrospective study was conducted on all children from 0 to 15 years with IgM against viral capsid of EBV positive or indeterminate during a 22 month period. Epidemiological, clinical and laboratory data were analysed and compared between typical (mononucleosis syndrome) and non-typical clinical symptoms. Results: The study included a total of 103 children, with a median age of 7 years (3–12.5 years). Almost two-thirds (63%) of patients had typical clinical signs, with a mononucleosis syndrome, and 37% had a non-typical presentation. The non-typical clinical group had a lower age (P = .03) and took less antibiotic than the typical clinical group (P = .015). From laboratory studies, there were no differences between the groups, except in RCP, which was higher in typical clinical group (P = .04). Heterophile antibodies were positive in 33% of patients. An indeterminate IgM against viral capsid was present in 20% of the patients, and most of them had an oligosymptomatic or atypical presentation. An IgM positive for other viruses was found in 21%, and 3 of them were suspicious of false positive for EBV. Conclusions: In the studied population, a primary infection due to EBV is common in younger ages, and they have usually an oligosymptomatic clinical presentation. A very low percentage of positive heterophile antibodies were found. Cases with indeterminate IgM against viral capsid are more frequent in the non-typical clinical group. Co-infection with other viruses is common. Resumen: Introducción: El objetivo de este estudio es conocer las características epidemiológicas, clínicas y analíticas de la primoinfección por el virus de Epstein-Barr (VEB) en niños sin diagnóstico previo de ninguna enfermedad inmune y su relación con la forma de presentación clínica. Pacientes y métodos: Estudio retrospectivo de pacientes entre 0 y 15 años con IgM sérica frente a la cápside viral del VEB positiva o indeterminada, durante un período de 22 meses. Se analizaron datos epidemiológicos, clínicos y de laboratorio y se compararon según tuvieran una clínica típica (síndrome mononucleósico) o no típica. Resultados: Se incluyeron 103 niños. La mediana de la edad fue de 7 años (3-12.5 años). El 63% de los pacientes presentaron clínica típica o síndrome mononucleósico y el 37% una clínica no típica. La edad fue significativamente menor en el grupo de clínica no típica (p = 0,03) y recibieron menos tratamiento antibiótico (p = 0,015). En los parámetros analíticos no hubo diferencias estadísticamente significativas excepto en la PCR, discretamente más elevada en el grupo de clínica típica (p = 0,04). El 33% de los pacientes tuvieron anticuerpos heterófilos positivos. El 20% tuvieron una IgM frente a la cápside viral indeterminada, la mayoría con clínica oligosintomática o atípica. El 21% tuvieron IgM positivas para otros virus y 3 de ellos fueron posibles falsos positivos para el VEB. Conclusiones: En nuestra población, la primoinfección por VEB es frecuente en niños de menor edad, y en ellos predominan las formas oligosintomáticas. El porcentaje de anticuerpos heterófilos positivos ha sido muy bajo en nuestra muestra. Los casos con IgM frente a la cápside viral indeterminada son más frecuentes en el grupo de clínica no típica. Es común detectar coinfección con otros virus.
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