Schistosoma haematobium infection and morbidity risk factors for pre-school age children in western Angola: A knowledge, attitudes and practices survey

Schistosomiasis; Medical risk factors; MorbidityEsquistosomiasi; Factors de risc mèdic; MorbilitatEsquistosomiasis; Factores de riesgo médico; MorbilidadBackground Urogenital schistosomiasis is one of the most prevalent parasitic diseases in sub-Saharan Africa. It is a poverty-related disease conditioned by behavioural practices. Methods Our objective is to evaluate the awareness, mindset and habits about urogenital schistosomiasis in the community of Cubal (Angola), as well as its association with infection and urinary tract morbidity in pre-school age children. A cross-sectional study of knowledge, attitudes and practices at home was conducted between February and May 2022 with 250 participants. Results Overall, 93.6% of those surveyed had some prior knowledge about schistosomiasis and, among all the symptoms associated with this disease, blood in the urine was the best known (54.4%). Nevertheless, 57.6% obtained a medium knowledge score. Regarding attitude, the majority of respondents had a high attitude score (79.2%) with 96.0% willing to participate in mass drug administration campaigns. Laundry in the river was the most common risk practice (61.2%) and 55.2% out of the total were classified with a low practice score. Conclusion Low knowledge about symptoms and transmission by caregivers was the outstanding risk factor for infection in pre-school age children (OR = 16.93, 95%CI: 3.93–72.82), and lack of knowledge that avoiding entering the river prevents schistosomiasis was the main risk factor for morbidity in PSAC (OR = 8.14, 95%CI: 1.14–58.25).This research was supported by the Red de Investigación de Centros de Enfermedades Tropicales – RICET of the PN de I+D+I, ISCIII-Subdirección General de Redes y Centros de Investigación Cooperativa RETICS), Ministry of Health and Consumption, Madrid; by CIBER de Enfermedades Infecciosas (Projects CB21/13/00056 and CB21/13/00029), ISCIII, Ministry of Science and Education, Madrid; by Project No. 2021/004 of the PROMETEO Program, Programa de Ayudas para Grupos de Investigación de Excelencia, Generalitat Valenciana, Valencia, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

First field and laboratory evaluation of LAMP assay for malaria diagnosis in Cubal, Angola

Angola; MalariaAngola; MalariaAngola; MalàriaBackground Malaria is a globally distributed infectious disease. According to the World Health Organization, Angola is one of the six countries that account for over half the global malaria burden in terms of both malaria cases and deaths. Diagnosis of malaria still depends on microscopic examination of thin and thick blood smears and rapid diagnostic tests (RDTs), which often lack analytical and clinical sensitivity. Molecular methods could overcome these disadvantages. The aim of this study was to evaluate, for the first time to our knowledge, the performance of a loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria in an endemic area in Cubal, Angola, and to assess the reproducibility at a reference laboratory. Methods A total of 200 blood samples from patients attended at Hospital Nossa Senhora da Paz, Cubal, Angola, were analysed for Plasmodium spp. detection by microscopy, RDTs, and LAMP. LAMP assay was easily performed in a portable heating block, and the results were visualized by a simple colour change. Subsequently, the samples were sent to a reference laboratory in Spain to be reanalysed by the same colorimetric LAMP assay and also in real-time LAMP format. Results In field tests, a total of 67/200 (33.5%) blood samples were microscopy-positive for Plasmodium spp., 98/200 RDT positive, and 112/200 (56%) LAMP positive. Using microscopy as reference standard, field LAMP detected more microscopy-positive samples than RDTs (66/67; 98% vs. 62/67; 92.5%). When samples were reanalysed at a reference laboratory in Spain using both colorimetric and real-time assays, the overall reproducibility achieved 84.5%. Conclusions This is the first study to our knowledge in which LAMP has been clinically evaluated on blood samples in a resource-poor malaria-endemic area. The colorimetric LAMP proved to be more sensitive than microscopy and RDTs for malaria diagnosis in field conditions. Furthermore, LAMP showed an acceptable level of reproducibility in a reference laboratory. The possibility to use LAMP in a real-time format in a portable device reinforces the reliability of the assay for molecular diagnosis of malaria in resource-poor laboratories in endemic areas.The work was supported by the Institute of Health Carlos III, ISCIII, Spain (www.isciii.es) grant number PI22/01721 (PFS), European Union cofinancing by FEDER (Fondo Europeo de Desarrollo Regional) ‘Una manera de hacer Europa’. We also acknowledge support by the Predoctoral Fellowship Program of Junta de Castilla y León cofounded by Fondo Social Europeo: (BDNS Identif.: 422058, BFS) and (BDNS Identif: 487971, BCV)

Prevalence and morbidity of urogenital schistosomiasis among pre-school age children in Cubal, Angola

Morbidity; Urine; SchistosomiasisMorbilidad; Orina; EsquistosomiasisMorbilitat; Orina; EsquistosomiasiBackground: Schistosomiasis is one of the most important neglected tropical diseases, with a great impact on public health and more than 200,000 deaths annually. Schistosoma haematobium causes urinary tract (UT) morbidity. Since schistosomiasis morbidity control programs focus on children older than 5 years, pre-school age children (PSAC) morbidity is not well known. Methods: We conducted a cross-sectional study in Cubal (Angola) among 245 PSAC with the objective of evaluating the prevalence of S. haematobium infection, the intensity of infection, and associated morbidity. For this purpose, urine filtration test followed by microscopic visualization and ultrasound examinations were performed. Results: The estimated overall prevalence of urogenital schistosomiasis was 30.2% (CI 95%; 24.5-35.9), with 20.3% (CI 95%; 15.3-25.3) of the samples analysed showing a high intensity of infection. A total of 54.5% (CI 95%; 47.6-61.8) of infected children presented UT lesions, showing a significant association between schistosomiasis infection and UT morbidity (p-value < 0.001). Bladder wall thickening was the most common lesion, being present in 100% of abnormal ultrasounds. We found that anaemia and severe malnutrition were not significantly associated with the development of UT lesions. Conclusions: S. haematobium infection in PSAC causes great UT detectable morbidities. Therefore, there is an evident need of including them in mass drug administration (MDA) campaigns and consequently the development of an adapted praziquantel treatment dosage for children under 2 years of age.This research was supported by the Red de Investigación de Centros de Enfermedades Tropicales–RICET (Grant No. RD16/0027/0023 and RD16/0027/0003) of the PN de I+D+I, ISCIII-Subdirección General de Redes y Centros de Investigación Cooperativa RETICS), Spanish Ministry of Health and Consumption; by CIBER de Enfermedades Infecciosas (Grant No. CB21/13/00056 and CB21/13/00029), ISCIII, Spanish Ministry of Science and Education; and by the PROMETEO Program, Programa of Ayudas para Grupos de Investigación de Excelencia, Generalitat Valenciana (Grant No. 2021/004)

Cost-effectiveness analysis of an active search to retrieve HCV patients lost to follow-up (RELINK-C strategy) and the impact of COVID-19

Acord transformatiu CRUE-CSICAltres ajuts: Gilead Science

Ultra Deep Sequencing of Circulating Cell-Free DNA as a Potential Tool for Hepatocellular Carcinoma Management

Biomarkers; cfDNA; Liquid biopsyBiomarcadores; cfDNA; Biopsia líquidaBiomarcadors; cfDNA; Biòpsia líquidaBackground: Cell-free DNA (cfDNA) concentrations have been described to be inversely correlated with prognosis in cancer. Mutations in HCC-associated driver genes in cfDNA have been reported, but their relation with patient’s outcome has not been described. Our aim was to elucidate whether mutations found in cfDNA could be representative from those present in HCC tissue, providing the rationale to use the cfDNA to monitor HCC. Methods: Tumoral tissue, paired nontumor adjacent tissue and blood samples were collected from 30 HCC patients undergoing curative therapies. Deep sequencing targeting HCC driver genes was performed. Results: Patients with more than 2 ng/µL of cfDNA at diagnosis had higher mortality (mean OS 24.6 vs. 31.87 months, p = 0.01) (AUC = 0.782). Subjects who died during follow-up, had a significantly higher number of mutated genes (p = 0.015) and number of mutations (p = 0.015) on cfDNA. Number of mutated genes (p = 0.001), detected mutations (p = 0.001) in cfDNA and ratio (number of mutations/cfDNA) (p = 0.003) were significantly associated with recurrence. However, patients with a ratio (number of mutations/cfDNA) above 6 (long-rank p = 0.0003) presented a higher risk of recurrence than those with a ratio under 6. Detection of more than four mutations in cfDNA correlated with higher risk of death (long-rank p = 0.042). Conclusions: In summary, cfDNA and detection of prevalent HCC mutations could have prognostic implications in early-stage HCC patientsThis research was funded by Instituto de Salud Carlos III (ISCIII) (PI18/00961) and (PI21/00714) to B.M. PI19/00301 by Instituto de Salud Carlos III (ISCIII) and Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297 to J.Q., E.V.-A. is a recipient of a predoctoral fellowship from Instituto de Salud Carlos III (ISCIII) (FI18/00027)

Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain

Latent tuberculosis infection; Toxicity; Tuberculosis screeningInfecció tuberculosa latent; Toxicitat; Cribratge de tuberculosiInfección tuberculosa latente; Toxicidad; Cribado de tuberculosisThe screening and treatment of latent tuberculosis infection (LTBI) in countries with a low incidence of TB is a key strategy for the elimination of tuberculosis (TB). However, treatment can result in adverse events (AEs) and have poor adherence. This study aimed to describe treatment outcomes and AEs for LTBI patients at two departments in Vall d'Hebron University Hospital in Barcelona, Spain. A retrospective study was conducted on all persons treated for LTBI between January 2018 and December 2020. Variables collected included demographics, the reason for LTBI screening and treatment initiation, AEs related to treatment, and treatment outcome. Out of 261 persons who initiated LTBI treatment, 145 (55.6%) were men, with a median age of 42.1 years. The indications for LTBI screening were household contact of a TB case in 96 (36.8%) persons, immunosuppressive treatment in 84 (32.2%), and recently arrived migrants from a country with high TB incidence in 81 (31.0%). Sixty-three (24.1%) persons presented at least one AE during treatment, and seven (2.7%) required definitive discontinuation of treatment. In the multivariate analysis, AE development was more frequent in those who started LTBI treatment due to immunosuppression. Overall, 226 (86.6%) completed treatment successfully. We concluded that LTBI screening and treatment groups had different risks for adverse events and treatment outcomes. Persons receiving immunosuppressive treatment were at higher risk of developing AEs, and recently arrived immigrants from countries with a high incidence of TB had greater LTFU. A person-centered adherence and AE management plan is recommended.A.M.L. was supported by a postdoctoral grant “Juan Rodés” (JE21/00027) from the Instituto de Salud Carlos through the Ministry of Economy and Competitiveness, Spain

Utility of the Cobas® Plasma Separation Card as a Sample Collection Device for Serological and Virological Diagnosis of Hepatitis C Virus Infection

Taca de plasma sec; Hepatitis C; Targeta de separació de plasmaMancha de plasma seca; Hepatitis C; Tarjeta de separación de plasmaDried plasma spot; Hepatitis C; Plasma separation cardDiagnosis and clinical management of people infected with hepatitis C virus (HCV) relies on results from a combination of serological and virological tests. The aim of this study was to compare the performance of dried plasma spots (DPS), prepared using the cobas® Plasma Separation Card (PSC), to plasma and serum from venipuncture, for HCV diagnosis. We carried out a prospective study using DPS and paired plasma or serum samples. Serum and DPS samples were analyzed by immunoassay using Elecsys® Anti-HCV II (Roche). Plasma and DPS samples were analyzed using the cobas® HCV viral load and cobas® HCV genotyping tests (Roche). All DPS samples that had high anti-HCV antibody titers in serum were also antibody-positive, as were five of eight samples with moderate titers. Eight samples with low titers in serum were negative with DPS. Among 80 samples with plasma HCV viral loads between 61.5 and 2.2 × 108 IU/mL, 74 were RNA-positive in DPS. The mean viral load difference between plasma and DPS was 2.65 log10 IU/mL. The performance of DPS for detection of serological and virological markers of hepatitis C virus infection was comparable to that of the conventional specimen types. However, the limits of detection were higher for DPS.This work was supported by Roche and a microelimiation grant of Gilead Science (GLD19-0104)

First field study using Strong-LAMP for diagnosis of strongyloidiasis in Cubal, Angola

Angola; Molecular screening; StrongyloidiasisAngola; Cribado molecular; EstrongiloidiasisAngola; Cribratge molecular; EstrogiloidiasiStrongyloides stercoralis infection is a common neglected tropical disease distributed worldwide, mainly in tropical and subtropical climates. The impact of S. stercoralis infections on human health ranges from mild asymptomatic infections to chronic strongyloidiasis unnoticeable until the host is immunosuppressed. In severe strongyloidiasis, a syndrome of hyperinfection and larval dissemination to various organs can occur with high mortality rates. The diagnosis of strongyloidiasis is challenging because of the absence of a single standard reference test with high sensitivity and specificity, which also makes it difficult to estimate the accuracy of other diagnostic tests. This study aimed to evaluate, for the first time, the use of an easy-to-perform loop-mediated isothermal amplification (LAMP) colorimetric assay (named Strong-LAMP) for the molecular screening of strongyloidiasis in stool samples from patients in a low-resource endemic area in Cubal, Angola. To compare different LAMP application scenarios, the performance of the Strong-LAMP under field conditions in Angola was reassessed in a well-equipped reference laboratory in Spain and compared with a quantitative polymerase chain reaction (qPCR) method.This work was supported by the Institute of Health Carlos III, ISCIII, Spain (www.isciii.es) grant number PI22/01721 (P.F.-S.), European Union cofinancing by FEDER (Fondo Europeo de Desarrollo Regional) ‘Una manera de hacer Europa’. We also acknowledge support by the Predoctoral Fellowship Program of Junta de Castilla y León cofunded by Fondo Social Europeo (BDNS (Identif.): 422058, B.F.-S. and BDNS (Identif.): 487971, B.C.-V.)

Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice

Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl4 and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl4 and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression