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.
The new nine-valent vaccine against human papillomavirus (HPV) includes the four HPV genotypes (6, 11, 16, and 18) that are targeted by the older quadrivalent HPV vaccine, plus five additional ...oncogenic types (31, 33, 45, 52, and 58) remain significantly associated with high grade lesions. We aimed to determine the prevalence of high-risk HPV genotypes in unvaccinated subjects and the association of these genotypes with the incidence of high-grade lesions. We also assessed which, if either, of these two HPV vaccines could have prevented these cases.
This cross-sectional study, conducted from 4 January 2010 to 30 December 2011, was composed of 595 women attending the Hospital General Universitario de Elche (Spain) gynaecology department who were positively screened for opportunistic cervical cancer by pap smears and HPV detection during a routine gynaecological health check. The pap smear results were classified using the Bethesda system. HPV genotyping was performed with the Linear Array HPV genotyping test, and viruses were classified by the International Agency for Research on Cancer assessment of HPV carcinogenicity. Odds ratios (ORs) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. The prevented fraction among those exposed (PFe-adjusted) was determined as a measure of impact.
At least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 20.5% of subjects. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, and 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR = 3.51 (95% CI, 1.29-9.56), PFe-adjusted = 0.72 (95% CI, 0.22-0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of the women, but these were not significantly associated with high-grade lesions.
The greater protection of the nine-valent HPV vaccine is likely to have a positive impact because, in the absence of genotype 16 or 18 infection, these five genotypes on their own remained significantly associated with high-grade lesions.
IntroductionEnterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated ...with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions.AimOur objective was to investigate the epidemiology and clinical characteristics of the outbreak.MethodsWe carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3'-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries.ResultsMost EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported.ConclusionAn emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.
A 32-year-old woman had an abdominoplasty and mammoplasty surgery in Ecuador. Following surgery, pruritic and slightly suppurative nodular lesions appeared over the abdominal and mammary scars. ...During the following months, satellite papules and nodules arose on distant sites. All bacterial cultures performed grew methicillin-sensitive Staphylococcus aureus and she received oral trimethoprim-sulfamethoxazole, levofloxacin and topical fusidic acid without improvement.
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.
Chagas disease (CD) is a chronic parasitic disease caused by Trypanosoma cruzi and is endemic to continental Latin America. In Spain, the main transmission route is congenital. We aimed to assess ...adherence to regional recommendations of universal screening for CD during pregnancy in Latin American women in the province of Alicante from 2014 to 2018.
Retrospective quality study using two data sources: 1) delivery records of Latin American women that gave birth in the 10 public hospitals of Alicante between January 2014 and December 2018; and 2) records of Chagas serologies carried out in those centers between May 2013 and December 2018. There were 3026 deliveries in Latin American women during the study period; 1178 (38.9%) underwent CD serology. Screening adherence ranged from 17.2% to 59.3% in the different health departments and was higher in Bolivian women (48.3%). Twenty-six deliveries (2.2%) had a positive screening; CD was confirmed in 23 (2%) deliveries of 21 women. Bolivians had the highest seroprevalence (21/112; 18.7%), followed by Colombians (1/333; 0.3%) and Ecuadorians (1/348; 0.3%). Of 21 CD-positive women (19 Bolivians, 1 Colombian, 1 Ecuadorian), infection was already known in 12 (57.1%), and 9 (42.9%) had already been treated. Only 1 of the 12 untreated women (8.3%) was treated postpartum. Follow-up started in 20 of the 23 (87.0%) neonates but was completed only in 11 (47.8%); no cases of congenital transmission were detected. Among the 1848 unscreened deliveries, we estimate 43 undiagnosed cases of CD and 1 to 2 undetected cases of congenital transmission.
Adherence to recommendations of systematic screening for CD in Latin American pregnant women in Alicante can be improved. Strategies to strengthen treatment of postpartum women and monitoring of exposed newborns are needed. Currently, there may be undetected cases of congenital transmission in our province.
Objective
COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be ...one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients.
Study design
Phase I was a case–control study and Phase II a transversal descriptive study.
Subjects and methods
Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied.
Results
275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test.
Conclusion
The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.
ResumenIntroducciónEl trastorno por déficit de atención con hiperactividad (TDAH) y su comorbilidad repercuten en la ansiedad social de niños y adolescentes, no obstante, apenas hay estudios que ...aborden este tema en la adolescencia. El objetivo era evaluar el grado de ansiedad social y analizar la presencia de comorbilidades psiquiátricas (CPS).MetodologíaEstudio observacional transversal en el que se incluyeron pacientes de 12-18 años con diagnóstico confirmado de TDAH (DSM-5). Se recogió información sobre la presencia y tipo de CPS y se evaluó la ansiedad social mediante la escala Social Anxiety Scale for Adolescents (SAS-A). ResultadosParticiparon 46 especialistas de psiquiatría del niño y del adolescente o neuropediatría, que incluyeron a 234 pacientes. El 68,8% (159) eran varones y el 31,2% (72) mujeres, con edad media de 14,9 años (IC 95%: 14,6-15,1). El 51,7% (121) tenía TDAH de tipo combinado (TC), el 37,2% (87) con predominio del déficit de atención (TDA) y el 9% (21) con predominio hiperactivo-impulsivo (TH). El 97,9% (229 pacientes) recibía tratamiento farmacológico: metilfenidato en el 78,6% (184), lisdexanfetamina en el 15% (35) y atomoxetina en el 4,3% (10).El 50,4% (118) presentaba alguna CPS, con predominio de los trastornos del aprendizaje y de la comunicación (47, 20,1%) y los trastornos de ansiedad (45, 19,2%). Se observó un grado de ansiedad social significativamente mayor en comparación con los valores normales de la escala en la población sana. Los adolescentes con TDA presentaron peores puntuaciones en la escala SAS-A en comparación con adolescentes con TH (p = 0,015). La presencia de trastornos de ansiedad comórbidos se relacionó con peores puntuaciones en la escala SAS-A, reflejando una mayor ansiedad social en estos pacientes (p < 0,001). ConclusionesLos adolescentes con diagnóstico de TDA y aquellos con comorbilidades psiquiátricas de tipo ansiedad presentaron un mayor grado de ansiedad social según su puntuación en la escala SAS-A. Este aspecto psicológico debería ser detectado y controlado en los adolescentes con TDAH para favorecer su adaptación social.
Attention-deficit/hyperactivity disorder (ADHD) and its comorbidities have an impact on the social anxiety of children and adolescents, but there are practically no studies addressing this topic in ...adolescence. Our objective was to assess the degree of social anxiety and to analyse the presence of psychiatric comorbidities (PSCs) in adolescents with ADHD.
We conducted a cross-sectional observational study in patients aged 12–18 years with a confirmed diagnosis of ADHD (DSM-5). We collected data on the presence and type of PSCs and assessed social anxiety by means of the Social Anxiety Scale for Adolescents (SAS-A).
Forty-six child and adolescent psychiatrists and paediatric neurologists participated in the study and recruited 234 patients. Of the total patients, 68.8% (159) were male and 31.2% (72) female, with a mean age in the sample of 14.9 years (95% CI, 14.6–15.1). The type of ADHD was combined type (C) in 51.7% (121), predominantly inattentive (PI) in 37.2% (87), and predominantly hyperactive-impulsive (PH) in 9% (21). Of all patients, 97.9% (229) received pharmacological therapy: 78.6% (184) methylphenidate, 15% (35) lisdexamfetamine and 4.3% (10) atomoxetine.We found PSCs in 50.4% of the patients (118), of which the most frequent were learning and communication disorders (20.1%, n=47) and anxiety disorders (19.2%, n=45). The patients scored significantly higher in the SAS-A compared to reference values in the healthy population. The scores in the SAS-A were less favourable in adolescents with the PI type compared to those with the PH type (P=.015). The presence of a comorbid anxiety disorder was associated with worst scores in SAS-A (P<.001) showing an increased social anxiety.
Adolescents with ADHD classified as PI and those with comorbid anxiety had a higher degree of social anxiety as measured by the SAS-A. This psychological aspect must be identified and controlled in adolescents with ADHD to promote their social adaptation.
El trastorno por déficit de atención con hiperactividad (TDAH) y su comorbilidad repercuten en la ansiedad social de niños y adolescentes, no obstante, apenas hay estudios que aborden este tema en la adolescencia. El objetivo era evaluar el grado de ansiedad social y analizar la presencia de comorbilidades psiquiátricas (CPS).
Estudio observacional transversal en el que se incluyeron pacientes de 12-18 años con diagnóstico confirmado de TDAH (DSM-5). Se recogió información sobre la presencia y tipo de CPS y se evaluó la ansiedad social mediante la escala Social Anxiety Scale for Adolescents (SAS-A).
Participaron 46 especialistas de psiquiatría del niño y del adolescente o neuropediatría, que incluyeron a 234 pacientes. El 68,8% (159) eran varones y el 31,2% (72) mujeres, con edad media de 14,9 años (IC 95%: 14,6-15,1). El 51,7% (121) tenía TDAH de tipo combinado (TC), el 37,2% (87) con predominio del déficit de atención (TDA) y el 9% (21) con predominio hiperactivo-impulsivo (TH). El 97,9% (229 pacientes) recibía tratamiento farmacológico: metilfenidato en el 78,6% (184), lisdexanfetamina en el 15% (35) y atomoxetina en el 4,3% (10).
El 50,4% (118) presentaba alguna CPS, con predominio de los trastornos del aprendizaje y de la comunicación (47, 20,1%) y los trastornos de ansiedad (45, 19,2%). Se observó un grado de ansiedad social significativamente mayor en comparación con los valores normales de la escala en la población sana. Los adolescentes con TDA presentaron peores puntuaciones en la escala SAS-A en comparación con adolescentes con TH (p=0,015). La presencia de trastornos de ansiedad comórbidos se relacionó con peores puntuaciones en la escala SAS-A, reflejando una mayor ansiedad social en estos pacientes (p<0,001).
Los adolescentes con diagnóstico de TDA y aquellos con comorbilidades psiquiátricas de tipo ansiedad presentaron un mayor grado de ansiedad social según su puntuación en la escala SAS-A. Este aspecto psicológico debería ser detectado y controlado en los adolescentes con TDAH para favorecer su adaptación social.
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