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Abstract Background Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test. Methods We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain. Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire. Results We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18–76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11–21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive for Schistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positive Schistosoma serology results: pelvic pain (45.2%; OR = 1.57, 95% CI: 1.0–2.4), pain on ejaculation (14.5%; OR = 1.85, 95% CI: 1.0–3.5), dyspareunia (12.4%; OR = 2.45, 95% CI: 1.2–5.2), erectile dysfunction (9.5%; OR = 3.10, 95% CI: 1.3–7.6), self-reported episodes of infertility (32.1%; OR = 1.69, 95% CI: 1.0–2.8), haematuria (55.2%; OR = 2.37, 95% CI: 1.5–3.6), dysuria (52.1%; OR = 2.01, 95% CI: 1.3–3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%; OR = 1.81, 95% CI: 1.0–3.1). Clinical signs tended to cluster. Conclusions Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positive Schistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis. Graphical Abstract

Cryptosporidium spp. is an apicomplexan protozoan parasite associated with gastroenteritis in humans. In 2018, Spain showed 1511 confirmed cases, with a growing trend since 2014. Despite this fact, Cryptosporidium spp. is not usually routinely examined when a parasitological study is ordered, although accurate diagnosis is fundamental to prevent the spread of the illness. The main objectives of the present work is to demonstrate the circulation and to study the epidemiology of cryptosporidiosis in patients who were being tested for the presence of Cryptosporidium spp. parasites in the faeces in the Metropolitan North Area of Barcelona, Maresme, and Vallés Occidental using a two-step algorithm. The stool samples were analysed using the Cryptosporidium/Giardia spp. immunochromatographic test; the positive samples were visualised under a microscope using auramine staining. The proportion of Cryptosporidium spp. cases was around 2% in the studied patients, with a pronounced seasonal incidence peak in late summer–early autumn. In our cohort, weight loss was the main symptom related to confirmed cases. The mean age of confirmed patients was 19 years old, and they were younger than the unconfirmed group. Cryptosporidium spp. is one of the parasites that currently circulate in many areas in Europe. Prevalence must be taken into account for active searching.

Abstract Although there is a low prevalence of parasitological infections in Europe, the diagnosis of intestinal parasites is still difficult and laborious for microbiology laboratories. Currently, antigen detection assays and molecular biology allow a more accurate diagnosis, but these techniques have limitations as they cannot detect all the possible parasites present in the samples. The objective of the study was to evaluate the accuracy and the usefulness of automated microscopy SediMAX2 (77 Elektronika, Budapest, Hungary) in the detection of parasitic infections from feces. A total of 197 formol-fixed stool samples were processed in parallel by wet mount examination and by SediMAX2. Sensitivities, specificities and predictive values were analyzed, reaching a sensitivity of 89.51% and a specificity of 98.15% and a very good positive predictive value (99.22%). SediMAX2 is a good tool for a reliable diagnosis of intestinal parasitic infections. The rapid processing and the flexibilty of storage of images analyzed make its incorporation into the day to day laboratory routine recommendable.

Resumen: Objetivo: Valorar los resultados obtenidos por una red de vigilancia epidemiológica y asistencial de arbovirosis compuesta por médicos y profesionales de enfermería de hospital y atención primaria (AP) formados en su identificación, confirmación diagnóstica y manejo clínico. Emplazamiento: Zona Sanitaria Metropolitana Norte de Barcelona (1.400.000 habitantes; Cataluña, España) durante un año natural. Participantes: Diecisiete médicos (7 de AP y 10 hospitalarios) más 4 enfermeros/as de AP. Tipo de estudio: Estudio observacional prospectivo. Mediciones principales: Se definieron variables demográficas, epidemiológicas (caso autóctono/importado, sospechoso/probable/confirmado) y asistenciales (síntomas, perfil serológico, periodo virémico). Resultados: De los 34 pacientes identificados cumplían criterios de estudio 26 (76,5%) casos; de ellos, se confirmó alguna arbovirosis en 14 (53,8%): 13 fiebres dengues más 1 chikungunya. No se registraron casos de fiebre de zika. Existían antecedentes de viaje a zonas endémicas (23; 88,4%), pero no en 3 casos (11,6%), en los que se consideró la posibilidad de una transmisión autóctona; de ellos, se confirmó un caso de dengue. La incidencia estimada de arbovirosis fue de 0,4 (IC 95%: 0,33-0,51) casos × 10.000 hab./año, que, comparada con la incidencia estimada en la misma área geográfica durante el periodo 2009-2013 (0,19 casos × 10.000 hab./año; IC 95%: 0,07-0,31), mostró un incremento significativo (p = 0,044). Los pacientes en periodo de viremia al momento de la primera visita médica fueron 11 (42,3%). Conclusiones: Un programa de vigilancia epidemiológica intensificada definido a nivel de AP y hospitalario es capaz de detectar significativamente más casos de arbovirosis importadas y transmitidas autóctonamente. Posiblemente asistimos a un aumento en la incidencia de arbovirosis importadas, por lo que las medidas encaminadas a su identificación y confirmación deben reforzarse. Abstract: Objective: To evaluate the results obtained by a surveillance network on arbovirosis composed by doctors and nurses located at hospitals and Primary Care trained in their identification, diagnostic confirmation and clinical management. Location: North Metropolitan Area of Barcelona (1,400,000 inhabitants; Catalonia; Spain) during a calendar year. Participants: Seven Primary Care and 10 hospital physicians plus 4 Primary Care nurses. Type of study: A prospective observational study. Main measurements: Demographic, epidemiological (autochthonous/imported, suspect/probable/confirmed case) and healthcare variables (symptoms, serological profile, viral period) were defined. Results: Of the 34 patients identified, 26 (76.5%) met study criteria. Among them, any arbovirosis was confirmed in 14 (53.8%): 13 dengue plus 1 chikungunya fever. There were no cases of Zika fever. There was a history of travel to endemic areas 23 (88.4%), but not in 3 cases (11.6%) in which the possibility of an indigenous transmission was considered; of them, a case of dengue was confirmed. The estimated incidence of arbovirosis was 0.4 (95% CI: 0.33-0.51) cases × 10,000 hab/year which, when compared to the estimated incidence in the same geographical area during the period 2009-2013 (0.19 cases × 10,000 hab/year; 95% CI: 0.07-0.31), a significant increase was found (P = .044). Patients within viremia period at the time of their first medical visit were 11 (42.3%). Conclusions: An intensified epidemiological surveillance program defined at Primary Care and hospital levels is able to detect significantly more cases of imported and autochthonous arbovirosis. Possibly we are witnessing an increase in the incidence of imported arbovirosis and, thus, measures aimed at their identification and confirmation should be reinforced.

BackgroundSchistosomiasis among migrant populations in Europe is an underdiagnosed infection, yet delayed treatment may have serious long-term consequences. In this study we aimed to characterize the clinical manifestations of Schistosoma infection among migrant women, and the degree of underdiagnosis.MethodsWe carried out a prospective cross-sectional study among a migrant population living in the North Metropolitan Barcelona area and coming from schistosomiasis-endemic countries. We obtained clinical, laboratory and socio-demographic data from electronic clinical records, as well as information about years of residence and previous attendance at health services. Blood sample was obtained and schistosomiasis exposure was assessed using a specific ELISA serological test.ResultsFour hundred and five patients from schistosomiasis-endemic regions were screened, of whom 51 (12.6%) were female. Seropositivity prevalence was 54.8%, but considering women alone we found a prevalence of 58.8% (30 out of 51). The median age of the 51 women was 41.0 years [IQR (35–48)] and the median period of residence in the European Union was 13 years [IQR (10–16)]. Schistosoma-positive women (N = 30) showed a higher prevalence of gynecological signs and symptoms compared to the seronegative women (96.4 vs. 66.6%, p = 0.005). Among seropositive women, the median number of visits to Sexual and Reproductive Health unit prior to diagnosis of schistosomiasis was 41 [IQR (18–65)].ConclusionThe high prevalence of signs and symptoms among seropositive women and number of previous visits suggest a high rate of underdiagnosis and/or delayed diagnosis of Schistosoma infection, particularly female genital schistosomiasis, among migrant females.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigen (Ag) tests have been widely employed to identify patients for a rapid diagnosis and pandemic control. Rapid lateral-flow techniques are currently the most used, but automated technologies have emerged as another viable alternative to molecular methods. We aimed to evaluate the analytical performance of the DiaSorin Liaison SARS-CoV-2 Ag test in asymptomatic population and close contacts, for its use as a tool in pandemic control efforts.Material and Methods: A retrospective study was conducted. A total of 861 samples were included, 291 (34%) were positive for SARS-CoV-2 with cycle threshold (Ct) 106 extrapolated copies/ml were reached a sensitivity of 100% (95% IC 97.0–100.0%). For intermediate viral loads (>105 extrapolated copies/ml or

We aimed to assess the feasibility of TESTA’T COVID strategy among healthcare and education professionals.in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible.

We aimed to assess the feasibility of TESTA'T COVID strategy among healthcare and education professionals.in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible.

Background: Actinotignum schaalii and the genus Aerococcus are considered emerging pathogens, since their isolation has been rising the last years thanks to the improvement of diagnosis techniques, such as the implementation of MALDI-TOF in microbiology laboratories for routine. Their patogenicity is nowadays well described in urinary tract infections affecting susceptible individuals, although both have been isolated from other biological samples. The aim of our study is to evaluate the impact of using mass spectrometry technology on the frequency of isolation of Aerococcus spp and A. schaalii in our hospital. Methods: From January 2014 and December 2015 44.654 urines were collected in our laboratory from patients that were expected to have an UTI. Samples were processed using a flow cytometer and cultured if applicable. After 48 h, microbial growth was assessed. Due to the suspicion of an Aerococcus spp or A. schaalii infection identification test was performed using Vitek2 until 2014 and MALDI-TOF from 2015. Results: Between the period of study, a total of 35 Aerococcus spp/A. schaalii isolates were collected from 34 patients. Six isolates were identified by Vitek2 and the other 29 were identified by MALDI-TOF. Out of 34 patients, 33 had at least one risk factor including age >65 years, immunosuppression or cancer, abnormality of the genitourinary tract, recurrent UTI, diabetes or a catheterization. Conclusions: Since the implementation of the MALDI-TOF in the laboratory the isolation of Aerococcus spp/A. schaalii has increased almost five times. The most frequent patient corresponds to an elderly patient with recurrent UTI and cancer. Resumen: Introducción: Actinotignum schaalii y el género Aerococcus son considerados patógenos emergentes debido al aumento en los últimos años de su aislamiento gracias a la mejora de las técnicas diagnósticas, como la implementación del MALDI-TOF en la rutina de los laboratorios de microbiología. Su patogenicidad está bien descrita en las infecciones del tracto urinario (ITU) en individuos susceptibles, aunque los dos géneros se han aislado también en otras muestras biológicas. El objetivo de nuestro estudio es evaluar el impacto del uso de la espectrometría de masas en la frecuencia de aislamiento de Aerococcus spp/A. schaalii en nuestro hospital. Métodos: Desde enero 2014 a diciembre 2015 se recibieron 44.654 orinas en nuestro hospital procedentes de pacientes con sospecha de ITU. Las muestras fueron procesadas por citometría de flujo y sembradas según criterios establecidos. Pasadas 48 h, se evaluó el crecimiento. Ante la sospecha de infección por Aerococcus spp/A. schaalii, se realizó un test de identificación con Vitek2® hasta 2014 y con MALDI-TOF desde 2015. Resultados: Durante el periodo de estudio se registraron 35 aislamientos de Aerococcus spp/A. schaalii correspondientes a 34 pacientes. Seis aislados se identificaron por Vitek2® y 29 por MALDI-TOF. De los 34 pacientes, 33 tenían como mínimo un factor de riesgo (>65 años, inmunosupresión o cáncer, anormalidades del tracto urinario, ITU recurrente, diabetes o cateterismo). Conclusiones: Desde la implementación del MALDI-TOF en el laboratorio, el aislamiento de Aerococcus spp/A. schaalii ha aumentado 5 veces. El perfil más afectado es el de un individuo de edad avanzada con ITU recurrentes y cáncer. Keywords: Urinary tract infection, Aerococcus spp, Actinotignum schaalii, MALDI-TOF, Palabras clave: Infección del tracto urinario, Aerococcus spp, Actinotignum schaalii, MALDI-TOF

The implementation of vaccination among healthcare workers (HCWs) allowed the management of the pandemic in a manner that differed from that in the first waves. It has been demonstrated that the mRNA vaccines elicit good humoral responses but that there are still breakthrough infections. In summer 2021, a fifth wave emerged, despite the good coverage of HCWs in Spain. We aimed to study the SARS-CoV-2 IgG antibody levels as a marker to predict the possibility of Delta variant infections after vaccination after a seroepidemiological campaign. Of the 5000 participants, a total of 4902 (98.04%) showed a positive result in the serological anti-S test and only 98 (1.96%) were negative. Among the 4368 fully vaccinated participants, only in five cases was the serology negative. Of the total number of participants that received antibody results during the study, 162 were PCR positive in the subsequent two months. Among these, 151 were fully vaccinated (two doses). Significant differences between antibody BAU/mL levels were found between PCR positive and non-PCR positive participants (p < 0.01). The median of BAU/mL was higher in those vaccinated patients with no infection (1260 BAU/mL; 465–2080) versus infected patients (661 BAU/mL; 361–2080). These data support the idea that vaccines play an important role in the control of the pandemic, especially among HCWs at the time of the Delta variant circulation. More studies with other variants of concern must be performed in order to establish a correlation between the levels of IgG and the new infections.

Macrolide and fluoroquinolone resistance (MLr/FQr) in Mycoplasma genitalium (MG) infections is concerning worldwide. Current guidelines recommend performing MLr detection in MG-positive cases to adjust antimicrobial therapy. We aimed to evaluate the usefulness of PCR followed by pyrosequencing for MLr detection in comparison with a one-step commercial assay and to assess the prevalence of MLr and FQr in Badalona, Spain. A total of 415 MG-positive samples by Allplex STI-7 (Seegene) were analyzed for MLr detection by pyrosequencing. From those, 179 samples were further analyzed for MG and MLr by ResistancePlus® MG kit (SpeeDx) and 100 of them also for fluoroquinolone resistance (FQr) by sequencing the parC gene. Regarding MG detection, Allplex and Resistance Plus® showed an overall agreement of 87%, but this value rose to 95.4% if we compare them for MLr detection. Prevalence of MLr was 23.1% in Badalona, but this rate increased to 73.7% in the HIV-positive patients cohort. FQr detection showed 3% of resistant strains. Pyrosequencing is a convenient and cheap technique for MLr detection, but one-step tools should be considered in high-throughput laboratories. Despite the fact that MLr remained moderate and FQr was low in our study, simultaneous MG and MLr detection would improve patient’s management applying resistance-guided treatment strategies.

BackgroundThe rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world has caused a global pandemic, infecting millions of individuals, with an unprecedented impact in health care systems worldwide. Healthcare workers are one of the risk groups that need to be well protected, due to their strategic role in patient management, presently and in prevention of healthcare needs for future outbreaks. Here, we present the results of the first SARS-CoV-2 seroprevalence study in the Northern Metropolitan Area of Barcelona, Spain.MethodsIgG SARS-CoV-2 antibodies were analyzed in serum samples from 7563 healthcare workers of the Northern Metropolitan Area of Barcelona. Samples were collected after the first pandemic wave (from May 4th to May 22nd, 2020) and were analyzed by automated chemiluminescence assays. All samples were tested for IgG anti-S1/S2. Participant samples with negative or equivocal results but with analytical signals above the limit of detection and/or previously confirmed COVID-19 diagnosis were also tested for IgG anti-Nucleocapsid.ResultsA total of 779 of 7563 (10.3%) healthcare workers were positive for anti-SARS-CoV-2 IgG (specific for either S1/S2 or N antigens). No significant differences were observed between those working at primary care or at the reference hospital. Interestingly, among 341 participants with a confirmed COVID-19 diagnosis, 36 (10.55%) tested negative for SARS-CoV-2 IgG (both S1/S2 and recombinant N antigen).ConclusionSeroprevalence of anti-SARS-CoV-2 IgG in the healthcare workers of the North Metropolitan Area of Barcelona was higher than in the general population in the same geographical area. Safety measures have to be stressed in order to protect these essential workers from future pandemic waves.

Abstract Background Malaria remains a major source of morbi-mortality among travellers. In 2007, a consensual multicenter Primary Care-Hospital shared guideline on travel-prior chemoprophylaxis, diagnosis and clinical management of imported malaria was set up in the Barcelona North Metropolitan area. The aim of the study is to assess the evolution of malaria cases in the area as well as its clinical management over the 10 years of its implementation. Results A total of 190 malaria cases, all them imported, have been recorded. The overall estimated malaria crude incidence was of 0.47 cases per 10,000 population/year (95% CI 0.34–0.59) with a slight significant positive slope especially at the expense of an increase in Indian sub-continent Plasmodium vivax cases. The number of patients who attended the pre-travel consultation was low (13.7%) as well as those with prescribed chemoprophylaxis (10%). Severe malaria was diagnosed in 34 (17.9%) patients and ICU admittance was required in 2.6% of them. Organ sequelae (two renal failures and one post-acute distress respiratory syndrome) were recorded in 3 patients at hospital discharge, although all three were recovered at 30 days. None of the patients died. Patients complying with severity criteria were significantly males (p = 0.04), came from Africa (p = 0.02), were mainly non-immigrant travellers (p = 0.01) and were attended in a hospital setting (p

BackgroundAmoebic colitis is the most frequent clinical manifestation of invasive intestinal infection due to Entamoeba histolytica and a common cause of diarrhoea worldwide. Since higher transmission rates are usually related to poor health and exposure to unhygienic conditions, cases reported in Europe usually involve immigrants and international travellers. The goal of this study was to characterise both the clinical and the epidemiological features of a European population diagnosed with amoebic colitis and then to evaluate the diagnostic tools and therapeutic options applied.Methods and resultsThis was a retrospective observational study in which data from all patients diagnosed with amoebic colitis attending at the International Health Units of two tertiary referral hospitals, Germans Trias i Pujol University Hospital (Badalona, North Barcelona Metropolitan Area) and Vall d'Hebron University Hospital (Barcelona city) between 2007 and 2017 were analysed. During the study period 50 patients were diagnosed with amoebic colitis. Thirty-six (72%) were men, and immigrants accounted for 46% of all cases. Antecedents of any international travel were reported for 28 (56%), the most frequent destinations having been the Indian subcontinent, South and Central America and sub-Saharan Africa. Preexisting pathological conditions or any kind of immunosuppression were identified in 29 (58%) patients; of these, 13 (26%) had HIV infection-all of them men who have sex with men-and 5 (10%) had inflammatory bowel disease. Diarrhoea, abdominal pain and dysentery were the most frequently recorded symptoms of invasive amoebae. Diagnosis was made through microbiological study in 45 (90%) and/or histological identification of amoebae in colon biopsies in 10 (20%). After treatment with metronidazole (82%) or tinidazole (8%), all patients had good outcomes. Post-acute intraluminal treatment was indicated in 28 (56%).ConclusionsAmoebic colitis should be suspected in patients with diarrhoea and compatible epidemiological risk factors (immigration, travelling abroad or men who have sex with men), especially if some degree of immunosuppression concurs. These risk factors must be taken into account in any diagnostic approach to inflammatory bowel disease (IBD), and active searches for stool parasites should be performed in such cases to rule out misdiagnosis or simultaneous amoebic infection. Treatment should include intraluminal anti-amoebic treatment in order to avoid relapse and prevent further spread of the disease.

Schistosomiasis, one of the neglected tropical diseases (NTD) listed by the WHO, is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Complications of long-term infestation include liver cirrhosis, bladder tumors and kidney failure. The objective of this study was to carry out a clinical and epidemiological characterization of a schistosomiasis-diagnosed immigrant population with long-term residencein the EU as well as to evaluate the diagnostic methods available to date.A total of 61 individuals with Schistosoma infection who received medical attention between June 2002 and June 2016 at the North Metropolitan International Health Unit in Barcelona (Catalonia, Spain), were included in the study. All patients were sub-Saharan African immigrants. The majority were male (91.8%) with a median age of 34 years. Symptoms attributable to infection such as haematuria, abdominal pain and dysuria were recorded in up to 90% of patients. The percentage of eosinophils decreased amongst older patients (p = 0.002) and those with symptoms associated with urinary tract infections (p = 0.017). Serology was used for diagnosis in 80.3% of the cases, with microscopic examination showing the remaining 9.8% positive for parasite eggs. Direct microbiological diagnosis was more useful in patients with less than 5 years of residence in the EU (p = 0.05). Chronic complications were present in 22 (36%) of the patients, with renal failure affecting 20 (33%). Of these 20, 6(10%) developed terminal renal failure and required hemodialysis, while 3 (5%) received a renal transplantation.Morbidity associated with chronic long-term schistosomiasis is frequent among African immigrants in non-endemic countries. Better diagnostic tools and appropriate early treatment would prevent the development of visceral damage. Thorough screening in selected patients would also be useful to avoid chronic complications.

Our aim was to determine changes in the incidence of CD infection (CDI) following the introduction of a two-step diagnostic algorithm and to analyze CDI cases diagnosed in the study period. We retrospectively studied CDI (January 2009 to July 2018) in adults diagnosed by toxin enzyme immunoassay (EIA) (2009–2012) or toxin-EIA + polymerase chain reaction (PCR) algorithm (2013 onwards). A total of 443 patients with a first episode of CDI were included, 297 (67.1%) toxin-EIA-positive and 146 (32.9%) toxin-EIA-negative/PCR-positive were only identified through the two-step algorithm including the PCR test. The incidence of CDI increased from 0.9 to 4.7/10,000 patient-days (p < 0.01) and 146 (32.9%) toxin-negative CDI were diagnosed. Testing rate increased from 24.4 to 59.5/10,000 patient-days (p < 0.01) and the percentage of positive stools rose from 3.9% to 12.5% (p < 0.01). CD toxin-positive patients had a higher frequency of severe presentation and a lower rate of immunosuppressive drugs and inflammatory bowel disease. Mortality (16.3%) was significantly higher in patients with hematological neoplasm, intensive care unit admission and complicated disease. Recurrences (14.9%) were significantly higher with proton pump inhibitor exposure. The two-step diagnostic algorithm facilitates earlier diagnosis, potentially impacting patient outcomes and nosocomial spread. CD-toxin-positive patients had a more severe clinical presentation, probably due to increased CD bacterial load with higher toxin concentration. This early and easy marker should alert clinicians of potentially more severe outcomes.