There is controversy about the likely infectious origin of chronic low back pain, because it has been suggested the possibility of a relationship with infection by Cutibacterium acnes (C. acnes). The ...aim of this study is to compare four methods to determine the presence of a likely infection caused by C. acnes in surgical disc samples. This work is a cross‐sectional observational study in which there are included 23 patients with microdiscectomy indication. Disc samples were taken during surgery and analysis was done by culture, Sanger sequencing, next‐generation sequencing (NGS), and real‐time PCR (qPCR). Furthermore, clinical data collection was conducted, and it was analyzed the presence of the Modic‐like changes on the magnetic resonance imaging. In 5 of the samples from among the 23 patients (21.7%), C. acnes was isolated by culture. However, in none of the samples could its genome be detected through Sanger sequencing, the less sensitive method. Only the qPCR and NGS were able to detect very few copies of the genome of this microorganism in all the samples, with no significant quantitative differences being observed between the patients in whom isolation of the microorganism by culture was evident or not. Furthermore, there were no significant relationships identified between the clinical variables, including Modic alterations and positive cultures. The most sensitive methods to the detect C. acnes were NGS and qPCR. The data obtained do not suggest association between the presence of C. acnes and the clinical process and support the hypothesis that C. acnes is found in these samples only because it is a contamination from the skin microbiome.
Immunoregulatory networks may have a role in controlling parasitemia in the chronic phase of human Chagas disease. The aim was to describe the serum cytokine profile of
Trypanosoma cruzi
in ...chronically infected patients and to evaluate its relationship with parasitemia and Chagas cardiomyopathy.
This prospective observational study included adult patients with chronic Chagas disease. Demographic and clinical data were collected, and peripheral blood samples were used to perform
T. cruzi
real-time polymerase chain reaction (RT-PCR) and determine the serum cytokine profile.
Fifty-eight patients were included; 17 (29.3%) had positive RT-PCR results. This group had a higher median concentration of TNF-α (
p
= 0.003), IL-6 (
p
= 0.021), IL-4 (
p
= 0.031), IL-1β (
p
= 0.036), and IL-17A (
p
= 0.043) than those with a negative RT-PCR. Patients with cardiac involvement had a higher median concentration of IL-5 (
p
= 0.016) than those without
.
These results reinforce the key role that cytokines play in Chagas disease patients with parasitemia and cardiac involvement.
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.
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.
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.
The role of tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6 in the pathogenicity of seasonal flu is unknown.
We analyzed the profiles of these cytokines in 77 flu patients and 17 controls ...with non-flu respiratory infection, using molecular biology techniques (real-time polymerase chain reaction).
Flu patients had lower monocyte counts (p=0.029) and a slightly lower median level of IL-6 (P=0.05) than the control group. Twenty-four flu patients (31.2%) had pneumonia; this group had higher C-reactive proteins (p=0.01) and monocyte levels (p=0.009). Pro-inflammatory cytokines levels did not rise in patients with pneumonia complicating seasonal influenza.
IL-6 levels were lower in adults with influenza.
Seasonal influenza is responsible for high annual morbidity and mortality worldwide, especially in elderly patients. The aim of the study was to analyse the epidemiological, clinical and prognostic ...features of influenza in octogenarians and nonagenarians admitted to a general hospital, as well as risk factors associated with mortality.
Retrospective, cross-sectional, descriptive study in patients admitted and diagnosed with influenza by molecular biology in the General University Hospital of Alicante from 1 January to 31 April 2015.
A total of 219 patients were diagnosed with influenza in the study period: 55 (25.1%) were ≤64 years-old; 77 (35.2%) were aged 65-79; 67 (30.6%) were aged 80-89 years; and 20 (9.1%) were aged ≥90 years. Most flu episodes were caused by influenza A (n=181, 82.6%). Patients aged 80 years or older had lower glomerular filtration rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a greater need for non-invasive mechanical ventilation (22% vs 9.3%; p=0.02), greater co-morbidity due to cardiac insufficiency (40.5% vs. 16.4%; p<0.001) and chronic renal disease (32.9 vs. 20%, p=0.03), and greater mortality (19% vs. 2.9%; p<0.001). In a multivariate analysis, mortality was higher in those aged 80 or over (adjusted odds ratio ORa 9.2, 95% confidence interval CI 1.65-51.1), those who had acquired the flu in a long-term care facility (ORa 11.9, 95% CI 1.06-134), and those with hyperlactataemia (ORa 1.89, 95% CI 1.20-3.00).
Seasonal influenza is a serious problem leading to elevated mortality in octogenarian and nonagenarian patients admitted to a general hospital.
An increase in whooping cough in most of the developed countries has been detected in the last decade.
To determine whether the administration of dTpa vaccine instead of DTPa fifth dose is ...contributing to the appearance of these cases.
A descriptive study based on cases of whooping cough reported during an epidemic period in the city of Alicante in the first 5 months of 2014. Only pertussis cases confirmed by PCR were included in the study, and only those vaccinated with 5 doses were included in the analysis of the period of protection.
A total of 104 cases of pertussis confirmed by PCR were reported, with 85 cases (82%) having had 5 doses of vaccine. The mean time and standard deviation (SD) of protection was 2.1±1.1 years with dTpa, and 5.1±1.5 years with DTPa (p<.001). In the protection, adjusted for age, it was observed that, after 3 years, only 47.6% of people vaccinated with dTpa were still protected, while people vaccinated with DTPa were 100% protected (P<.001).
This study found that people who were properly vaccinated against pertussis and received their last re-vaccination dose with dTpa had a shorter period of protection than those who were vaccinated with DTPa.
Chilblain‐like acral lesions have been identified in some coronavirus disease 2019 (COVID‐19) patients. It has been suggested that these pseudo‐chilblains could be a specific marker of severe acute ...respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Most patients with these lesions have had negative polymerase chain reactions (PCRs), but some authors believe serology tests are likely to give positive results. We designed a prospective study including all patients with pseudo‐chilblains treated in outpatient department in April and May 2020 and then performed SARS‐CoV‐2 PCR and serology tests on all available patients. We evaluated 59 patients, of whom 17 had undergone PCR before the study period, all with negative results. For the present study, we performed 20 additional PCRs, serology tests in 25 patients, and a parvovirus B19 antibody test in 15 patients. All results were negative. Our findings counter the hypothesis that serology is likely to reveal SARS‐CoV‐2 infection in patients with pseudo‐chilblains. One hypothesis for our negative results is that the time period between symptom onset and antibody production is longer in these patients; another is that the lesions are caused by behavioral changes during lockdown rather than SARS‐CoV‐2 infection. We nevertheless maintain that COVID‐19 should be ruled out in people presenting with chilblain‐like lesions.
Infective endocarditis (IE) caused by
represents the third most common cause of IE, with high rates of relapse compared with other bacteria. Interestingly, late relapses (>6 months) have only been ...described in
but here we describe the first reported IE relapse with
more than a year (17 months) after the initial endocarditis episode. Firstly, by multi locus sequence typing (MLST), we demonstrated that both isolates (EF646 and EF641) belong to the same sequence type (ST117). Considering that EF641 was able to overcome starvation and antibiotic treatment conditions surviving for a long period of time, we performed bioinformatic analysis in identifying potential genes involved in virulence and stringent response. Our results showed a 13-nucleotide duplication (positions 1638-1650) in the gene
, resulting in a premature stop codon, with a loss of 167 amino acids from the C-terminal domains of the RelA enzyme. RelA mediates the stringent response in bacteria, modulating levels of the alarmone guanosine tetraphosphate (ppGpp). The
mutant (EF641) was associated with lower growth capacity, the presence of small colony variants, and higher capacity to produce biofilms (compared with the strain EF646), but without differences in antimicrobial susceptibility patterns according to standard procedures during planktonic growth. Instead, EF641 demonstrated tolerance to high doses of teicoplanin when growing in a biofilm. We conclude that all these events would be closely related to the long-term survival of the
and the late relapse of the IE. These data represent the first clinical evidence of mutations in the stringent response (
gene) related with
IE relapse.