Role of nucleic acid amplification assays in monitoring treatment response in chagas disease: Usefulness in clinical trials

Chagas disease has become a global health problem due to migration of infected people out of Latin America to non-endemic countries. For more than 40 years, only the nitroimidazole compounds Benznidazole and Nifurtimox, have been used for specific treatment of Trypanosoma cruzi infection with disappointing results, specially due to the long duration of treatment and adverse events in the chronic phase. In the last years, ergosterol inhibitors have been also proposed for specific treatment. Different randomized clinical trials were performed for evaluating their treatment efficacy and safety. One of the greatest concerns in clinical trials is to provide an early surrogate biomarker of response to trypanocidal chemotherapy. Serological response is slow and the classical parasitological tests have poor sensitivity and are time-consuming. Nowadays, PCR is the most helpful tool for assessing treatment response in a short period of time. Different protocols of PCR have been developed, being quantitative real time PCR based on amplification of repetitive satellite or minicircle DNA sequences plus an internal amplification standard, the mostly employed strategies in clinical trials. Standardized protocols and the use of an external quality assessment ensure adequate technical procedures and reliable data. Clinical trials have shown a significant reduction in parasite loads, reaching undetectable DNA levels in bloodstream after specific treatment, however events of treatment failure have also been reported. Treatment failure could be due to inadequate penetrance of the drugs into the affected tissues, to the presence of primary or secondary drug resistance of the infecting strains as well as to the existence of dormant parasite variants reluctant to drug action. The early diagnosis of drug resistance would improve clinical management of Chagas disease patients, allowing dictating alternative therapies with a combination of existing drugs or new anti-T. cruzi agents. The aim of this review was to describe the usefulness of detecting T.cruzi DNA by means of real time PCR assays, as surrogate biomarker in clinical trials for evaluating new drugs for CD or new regimens of available drugs and the possibility to detect treatment failure.Fil: Sulleiro Igual, Elena. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Epidemiological and clinical profile of adult patients with Blastocystis sp. infection in Barcelona, Spain

Background: Blastocystis spp. are among the most frequently observed intestinal parasites in humans. Despite the discovery of Blastocystis approximately 100 years ago, limited information is available regarding its pathogenesis, genetic diversity, and available treatment options. The aim of this study was to describe the epidemiological and clinical characteristics of patients with Blastocystis sp. infections diagnosed at Vall d’Hebron University Hospital (Barcelona, Spain). Methods: A retrospective observational study was performed which included all adult patients who attended Vall d’Hebron University Hospital from February 2009 to March 2014 that had Blastocystis sp. detected in their stool. Results: Four hundred eighteen patients were included, the median age was 36 (18–86) years and 236 (56.5 %) were men. Regarding patient symptoms, 234 (56 %) patients were completely asymptomatic, 92 (22 %) patients had symptoms, and 92 (22 %) patients had symptoms that could be attributed to other causes. Of the 92 patients with symptoms not attributable to other etiologies except for Blastocystis infection, the most frequent symptoms were diarrhea (61 patients, 66.3 %) and abdominal pain (34 patients, 37 %). Additionally, nine (9.8 %) patients had cutaneous manifestations. Thirty-one (7.4 %) patients received specific treatment for Blastocystis infection. The clinical response of treated patients was varied. Five patients experienced complete resolution of symptoms, 12 patients reported improvement of clinical symptoms, eight patients described no clinical improvement, and information was unavailable for six patients. Conclusions: Blastocystis infection was detected in 418 patients, most of them foreign-born. Although the vast majority of patients were asymptomatic, 22 % of patients had gastrointestinal symptoms or cutaneous manifestations in the absence of other causes. Despite the scarce information available, given the safety of antiparasitic treatment, and the percentage of patients who experienced resolution or improvement of symptoms, treatment should be considered in patients with chronic symptoms.This study was supported by the 6th National Plan (PN) of Research + Development + Innovation (I + D + I) 2008–2011, ISCIII-General Division Networks and Cooperative Research Centres + FEDER funds + Collaborative Research Network on Tropical Diseases (RICET): RD12/0018/0020 and RD12/0018/0011.S

A case report of long treatment with Itraconazole in a patient with chronic Chagas disease

Background: Current available treatments (benznidazole and nifurtimox) for Chagas disease (CD) show limited efficacy in chronic phase and frequent undesirable effects. Ergosterol synthesis inhibitors (ESI) had been considered as promising drugs for CD treatment and despite its recent poor results in several clinical trials, different strategies have been proposed to optimize its role in this infection. Case presentation: We present a case of chronic Chagas disease in patient diagnosed with HIV who received treatment for histoplasmosis with itraconazol during twelve months. Even though T. cruzi rt-PCR was persistently negative during treatment, when itraconazol was stopped she presented with a positive blood rt-PCR. Conclusion: Several studies using different ESI had been published for CD treatment. Either in vitro or in vivo assays demonstrated activity against T. cruzi of the different triazole derivatives so different clinical trials had been carried out to evaluate its efficacy and safety. Despite contradictory evidence in the animal model, longer treatments along with other treatment strategies previously proposed suggests that ESI failure rates in positive peripheral blood rt-PCR are higher than that obtained with the current treatments of choice

Profilaxi de la malària en viatgers

Profilaxi de malària; Medicina del viatger; AntipalúdicsProfilaxis de malaria; Medicina del viajero; antipalúdicosMalaria prophylaxis; Traveler medicine; AntimalarialsLa malària representa la primera causa infecciosa de risc de complicacions greus i mort en viatgers internacionals. En el nostre àmbit, la majoria de casos de malària en viatgers correspon a persones que no han realitzat una quimiopro!laxi adequada i/o les estratègies per evitar la picada de mosquits no han funcionat. El col·lectiu més afectat són els immigrants que es desplacen temporalment als seus països d’origen per visitar familiars i amics, per la qual cosa cal insistir, especialment en aquest grup, a adoptar mesures de prevenció especí!ques. És molt important que les persones que han de viatjar a àrees de paludisme endèmic facin una consulta mèdica entre 4-8 setmanes prèvies al viatge. En aquesta consulta, es valorarà el risc de contraure malària i s’assessorarà segons cada cas, tenint en compte les característiques personals, l’itinerari, la durada i el tipus de viatge. Es donaran indicacions sobre les mesures de protecció personal: repel·lents, roba especí!ca i ús de mosquiteres, entre d’altres. També caldrà valorar la indicació de quimiopro!laxi amb fàrmacs. Actualment, els fàrmacs disponibles en el nostre àmbit són atovaquona/proguanil, me"oquina, doxiciclina i cloroquina. A més, s’hauran de tenir en compte situacions especials com l’embaràs i/o la immunosupressió

Approach to amoebic colitis: Epidemiological, clinical and diagnostic considerations in a non-endemic context (Barcelona, 2007-2017)

Amoebic colitis; Non-endemic; BarcelonaColitis amèbica; No-endèmic; BarcelonaColitis Amebiana; No-endémico; BarcelonaBACKGROUND: Amoebic 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 RESULTS: This 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%). CONCLUSIONS: Amoebic 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

Sentinel surveillance of imported dengue via travellers to Europe 2012 to 2014: TropNet data from the DengueTools Research Initiative

Dengue; Vigilància; ImportacióDengue; Vigilancia; ImportaciónDengue; Surveillance; ImportationWe describe the epidemiological pattern and genetic characteristics of 242 acute dengue infections imported to Europe by returning travellers from 2012 to 2014. The overall geographical pattern of imported dengue (South-east Asia > Americas > western Pacific region > Africa) remained stable compared with 1999 to 2010. We isolated the majority of dengue virus genotypes and epidemic lineages causing outbreaks and epidemics in Asia, America and Africa during the study period. Travellers acted as sentinels for four unusual dengue outbreaks (Madeira, 2012–13; Luanda, 2013; Dar es Salaam, 2014; Tokyo, 2014). We were able to characterise dengue viruses imported from regions where currently no virological surveillance data are available. Up to 36% of travellers infected with dengue while travelling returned during the acute phase of the infection (up to 7 days after symptom onset) or became symptomatic after returning to Europe, and 58% of the patients with acute dengue infection were viraemic when seeking medical care. Epidemiological and virological data from dengue-infected international travellers can add an important layer to global surveillance efforts. A considerable number of dengue-infected travellers are viraemic after arrival back home, which poses a risk for dengue introduction and autochthonous transmission in European regions where suitable mosquito vectors are prevalent

Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19)

Altres ajuts: Funding was provided for the Gesta-COVID19 Study by Instituto de Salud Carlos III (ISCIII) (PR(AMI)181/2020) (ISCIII's reference: COV20/00188).Fetal skin edema in the second trimester might be associated with maternal coronavirus disease 2019 (COVID-19). The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection. The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful. Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness

Epidemiology of congenital Chagas disease 6 years after implementation of a public health surveillance system, Catalonia, 2010 to 2015

Chagas disease; Trypanosoma cruzi; CongenitalMalaltia de Chagas; Trypanosoma cruzi; CongènitEnfermedad de Chagas; Trypanosoma cruzi; CongénitoBackgroundChagas disease is endemic in Latin America and affects 8 million people worldwide. In 2010, Catalonia introduced systematic public health surveillance to detect and treat congenital Chagas disease.AimThe objective was to evaluate the health outcomes of the congenital Chagas disease screening programme during the first 6 years (2010-2015) after its introduction in Catalonia.MethodsIn a surveillance system, we screened pregnant women and newborns and other children of positive mothers, and treated Chagas-positive newborns and children. Diagnosis was confirmed for pregnant women and children with two positive serological tests and for newborns with microhaematocrit and/or PCR at birth or serology at age 9 months.ResultsFrom 2010 to 2015, the estimated screening coverage rate increased from 68.4% to 88.6%. In this period, 33,469 pregnant women were tested for Trypanosoma cruzi and 937 positive cases were diagnosed. The overall prevalence was 2.8 cases per 100 pregnancies per year (15.8 in Bolivian women). We followed 82.8% of newborns until serological testing at age 9-12 months and 28 were diagnosed with Chagas disease (congenital transmission rate: 4.17%). Of 518 siblings, 178 (34.3%) were tested and 14 (7.8%) were positive for T. cruzi. Having other children with Chagas disease and the heart clinical form of Chagas disease were maternal risk factors associated with congenital T. cruzi infection (p < 0.05).ConclusionThe increased screening coverage rate indicates consolidation of the programme in Catalonia. The rate of Chagas disease congenital transmission in Catalonia is in accordance with the range in non-endemic countries

A retrospective study on the influence of siblings' relatedness in Bolivian patients with chronic Chagas disease

Brotherhood; Cardiomyopathy; Chagas diseaseGermandat; Cardiomiopatia; Malaltia de chagasHermandad; Cardiomiopatía; Enfermedad de chagasBACKGROUND: Chagas disease is a protozoan infection caused by Trypanosoma cruzi. The disease has a chronic course in which 20-30% of the patients would develop progressive damage to the cardiovascular system and the gastrointestinal tube. We are still unable to predict who will develop end-organ damage but there are some acquired and genetic risk factors already known. RESULTS: We reviewed data from 833 patients with serologically confirmed Chagas disease in this retrospective study. Patients were classified as siblings or non-siblings (controls) and the results of pre-treatment blood PCR assay, end-organ damage (cardiac and/or gastrointestinal), and the presence of delayed type hypersensitivity (DTH) skin involvement in patients treated with benznidazole were analyzed. Siblings were grouped by family and we randomly generated groups of 2 or 3 persons with the remaining controls. We classified the results of each variable as concordant or discordant and compared the concordance in these results among the sibling groups with that among control groups. We identified 71 groups of siblings and randomly generated 299 groups of non-related patients. Pre-treatment blood PCR concordance was significantly higher (19%) among siblings compared to controls (P = 0.02), probably due to a higher frequency in pre-treatment positive results. No other statistically significant differences were found. CONCLUSIONS: A significant difference was found in the concordance of pre-treatment blood PCR for T. cruzi among siblings compared to non-related controls

Microscopic examination after concentration techniques for Blastocystis sp. detection in serial faecal samples : How many samples are needed?

Blastocystis sp. is one of the most frequently observed intestinal parasites in humans. It is suggested that sensitivity of classical parasitological tests for the Blastocystis sp. diagnosis increases when increasing the number of investigated samples, although there is a lack of information. The aim of the study is to evaluate the sensitivity of classical parasitological tests for the Blastocystis sp. diagnosis depending on the number of investigated samples and to determine risk factors associated to high parasite burden. Retrospective study where patients in whom three consecutive stool samples were examined for parasitic diagnosis through microscopic examination at Vall d'Hebron University Hospital (Barcelona, Spain) from January to April 2019 were included. To determine risk factors associated to high parasite burden, a case-control study was performed including patients with at least one positive stool sample for Blastocystis sp.: cases were those patients with only one or two positive stool samples, and controls were those with all three stool positive samples). Clinical records were reviewed from included patients to collect clinical and demographic information. In 2771 patients three consecutive stool samples were examined for parasitic diagnosis, with an overall prevalence of Blastocystis sp. detection of 23.3%. The proportions of positive cases depending on the number of investigated samples were: 22.3% when taking into account the first sample, 22.9% when taking into account the first and second samples, and 23.3% when taking into account the three samples, with no statistically significant differences among them. For the case-control study we finally included 63 cases and 133 controls. No differences were found regarding clinical and demographic characteristics among groups. Prevalence of Blastocystis sp. infection was high in our study (23.3%). The sensitivity of classical parasitological methods for Blastocystis sp. diagnosis did not increase when increasing the number of investigated samples, and no risk factors associated to high parasite burden were identified