ABSTRACT
Objective: To assess the outcomes of a contact-tracing programme to increase the diagnosis of tuberculosis in Cubal, Angola and offer preventive treatment to high-risk groups. Methods: A health centre-based contact-tracing programme was launched in Hospital Nossa Senhora da Paz in March 2015 and we followed the programme until 2022. In that time, staffing and testing varied which we categorized as four periods: medical staff reinforcement, 2015-2017, with a doctor seconded from Vall d'Hebron University Hospital, Spain; routine staff, 2017-2021, with no external medical support; community directly observed treatment (DOT), 2018-2019 with community worker support; and enhanced contact tracing, 2021-2022, with funding that allowed free chest radiographs, molecular and gastric aspirate testing. We assessed differences in contacts seen each month, and testing and treatment offered across the four periods. Findings: Overall, the programme evaluated 1978 contacts from 969 index cases. Participation in the programme was low, although it increased significantly during the community DOT period. Only 16.6% (329/1978) of contacts had a chest radiograph. Microbiological confirmation increased to 72.2% (26/36) after including molecular testing, and 10.1% (200/1978) of contacts received treatment for tuberculosis. Of 457 contacts younger than 5 years, 36 (7.9%) received preventive tuberculosis treatment. Half of the contacts were lost to follow-up before a final decision was taken on treatment. Conclusion: Contact tracing increased the diagnosis of tuberculosis although engagement with the programme was low and loss to follow-up was high. Participation increased during community DOT. Community-based screening should be explored to improve participation and diagnosis.
Subject(s)
Contact Tracing , Tuberculosis , Humans , Angola/epidemiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Mass ScreeningABSTRACT
PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.
Subject(s)
Quality of Life , Tuberculosis , Adult , Child , Humans , Prospective Studies , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/microbiology , Longitudinal Studies , C-Reactive ProteinABSTRACT
Adaptive platform trials can be more efficient than classic trials for developing new treatments. Moving from culture-based to simpler- or faster-to-measure biomarkers as efficacy surrogates may enhance this advantage. We performed a systematic review of treatment efficacy biomarkers in adults with tuberculosis. Platform trials can span different development phases. We grouped biomarkers as: α, bacterial load estimates used in phase 2a trials; ß, early and end-of treatment endpoints, phase 2b-c trials; γ, post-treatment or trial-level estimates, phase 2c-3 trials. We considered as analysis unit (biomarker entry) each combination of biomarker, predicted outcome, and their respective measurement times or intervals. Performance metrics included: sensitivity, specificity, area under the receiver-operator curve (AUC), and correlation measures, ,and classified as poor, promising, or good. Eighty-six studies included 22864 participants. From 1356 biomarker entries, 318 were reported with the performance metrics of interest, with 103 promising and 41 good predictors. Group results: α, mycobacterial RNA and Lipoarabinomannan in sputum, and host metabolites in urine; ß, mycobacterial RNA and host transcriptomic or cytokine signatures for early treatment response; γ, host transcriptomics for recurrence. A combination of biomarkers from different categories could help designing more efficient platform trials. Efforts to develop efficacy surrogates should be better coordinated.
ABSTRACT
OBJECTIVES: Strongyloidiasis is a nematode infection caused by Strongyloides stercoralis. Previous studies have addressed the possibility of the parasite to establish a complex relationship with the host that could affect the risk of developing diabetes mellitus or modify its presentation. This study aims to evaluate the potential impact of strongyloidiasis in diabetes mellitus and other metabolic diseases. METHODS: Case-control observational retrospective study that included 95 S. stercoralis-infected patients and 83 non-infected individuals. Epidemiological and clinical variables were retrieved from medical records, and a statistical analysis was carried out to explore any association between strongyloidiasis and diabetes mellitus and other metabolic diseases. RESULTS: Most of the patients were men (99, 55.60%) with a mean age of 42.53 ± SD 14 years. Twelve (6.70%) patients were diabetic; 30 (16.90%) presented arterial hypertension; 28 (15.70%) had dyslipidaemia; and 10 (5.60%) had thyroid pathology. When comparing patients with strongyloidiasis and uninfected patients, no differences were found regarding diabetes mellitus or other metabolic diseases. CONCLUSIONS: The results obtained in the present study do not confirm any type of association between strongyloidiasis and diabetes mellitus or other metabolic diseases.
Subject(s)
Diabetes Mellitus , Strongyloides stercoralis , Strongyloidiasis , Adult , Animals , Female , Humans , Male , Case-Control Studies , Retrospective StudiesABSTRACT
PURPOSE: We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. METHODS: We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission. CONCLUSION: Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.
Subject(s)
COVID-19 , COVID-19/epidemiology , Cohort Studies , Hospitalization , Humans , Incidence , Patient Readmission , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
Multidrug-resistant (MDR) tuberculosis (TB), resistant to isoniazid and rifampicin, continues to be one of the most important threats to controlling the TB epidemic. Over the last few years, there have been promising pharmacological advances in the paradigm of MDR TB treatment: new and repurposed drugs have shown excellent bactericidal and sterilizing activity against Mycobacterium tuberculosis and several all-oral short regimens to treat MDR TB have shown promising results. The purpose of this comprehensive review is to summarize the most important drugs currently used to treat MDR TB, the recommended regimens to treat MDR TB, and we also summarize new insights into the treatment of patients with MDR TB.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Humans , Isoniazid/therapeutic use , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
The World Health Organization (WHO) estimates that over three billion people are at risk of acquiring malaria, a parasitic infection that produces more than 200 million new infections and nearly half a million deaths each year. Expanding the access to early diagnosis and treatment is one of the most effective ways to prevent disease complications, reduce patient mortality, and curb the community transmission. However, none of the diagnostic methods used currently for malaria detection, including light microscopy, polymerase chain reaction (PCR), and rapid diagnostic tests (RDTs), can provide simultaneously fast results, high sensitivity, and parasitaemia quantitation with minimal user intervention. Here, we present a magneto-immunoassay that, based on the unique combination of magnetic beads (MB), an enzymatic signal amplifier (Poly-HRP), and chemiluminescence detection, provides fast, sensitive, and quantitative malaria diagnosis with easy user manipulation. This assay quantifies Plasmodium falciparum lactate dehydrogenase (PfLDH) in lysed whole blood samples in <15 min, exhibiting a limit of detection (LOD) of 0.02 ng mL-1 and providing patient stratification consistent with the reference methods. These figures of merit surpass the performance of the magneto-immunoassays reported previously for Plasmodium detection and demonstrate for the first time that the proposed combination of MB, Poly-HRP, and chemiluminescence detection produces extremely fast, simple, and efficient assays that approach the requirements of point-of-care (POC) malaria surveillance.
Subject(s)
Malaria , Plasmodium , Humans , Immunoassay , Malaria/diagnosis , Plasmodium falciparum , Sensitivity and SpecificityABSTRACT
BackgroundSeveral clinical trials have assessed the protective potential of chloroquine and hydroxychloroquine. Chronic exposure to such drugs might lower the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or severe coronavirus disease (COVID-19).AimTo assess COVID-19 incidence and risk of hospitalisation in a cohort of patients chronically taking chloroquine/hydroxychloroquine.MethodsWe used linked health administration databases to follow a cohort of patients with chronic prescription of hydroxychloroquine/chloroquine and a control cohort matched by age, sex and primary care service area, between 1 January and 30 April 2020. COVID-19 cases were identified using International Classification of Diseases 10 codes.ResultsWe analysed a cohort of 6,746 patients (80% female) with active prescriptions for hydroxychloroquine/chloroquine, and 13,492 controls. During follow-up, there were 97 (1.4%) COVID-19 cases in the exposed cohort and 183 (1.4%) among controls. The incidence rate was very similar between the two groups (12.05 vs 11.35 cases/100,000 person-days). The exposed cohort was not at lower risk of infection compared with controls (hazard ratio (HR): 1.08; 95% confidence interval (CI): 0.83-1.44; p = 0.50). Forty cases (0.6%) were admitted to hospital in the exposed cohort and 50 (0.4%) in the control cohort, suggesting a higher hospitalisation rate in the former, though differences were not confirmed after adjustment (HR: 1·46; 95% CI: 0.91-2.34; p = 0.10).ConclusionsPatients chronically exposed to chloroquine/hydroxychloroquine did not differ in risk of COVID-19 nor hospitalisation, compared with controls. As controls were mainly female, findings might not be generalisable to a male population.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Chloroquine/adverse effects , Female , Humans , Hydroxychloroquine/adverse effects , Incidence , Male , Prospective Studies , SARS-CoV-2 , Spain/epidemiologyABSTRACT
Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.
Subject(s)
Hantavirus Pulmonary Syndrome/epidemiology , Travel , Adult , Hantavirus Pulmonary Syndrome/diagnosis , Hantavirus Pulmonary Syndrome/etiology , Hantavirus Pulmonary Syndrome/virology , Humans , Male , Nepal/epidemiology , Puumala virus , Spain/epidemiologyABSTRACT
Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.
Subject(s)
Typhoid Fever , Adolescent , Anti-Bacterial Agents/pharmacology , Asia , Child , Drug Resistance, Microbial , Humans , India , Salmonella paratyphi A , Salmonella typhi , Travel , Travel-Related Illness , Typhoid Fever/drug therapy , Typhoid Fever/epidemiologyABSTRACT
Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.
Subject(s)
Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma , Interferon-gamma Release Tests , Latent Tuberculosis/diagnosis , Mycobacterium tuberculosis/genetics , RNA, Messenger/genetics , Sensitivity and Specificity , Tuberculosis/diagnosisABSTRACT
OBJECTIVES: To provide information regarding the prevalence of strongyloidiasis among migrants coming from Strongyloides stercoralis-endemic areas who reside in Spain. METHODS: Systematic review of the literature and meta-analysis of studies showing prevalence of S. stercoralis infection among migrants from Latin America, Africa, Eastern Europe, Asia and Oceania who reside in Spain. We included articles published until 30 April 2019 without language restriction. The keywords used for the search included 'Strongyloides stercoralis', 'strongyloidiasis', 'Spain', 'screening' and 'migrants'. RESULTS: Twenty-four studies were included in the review and meta-analysis, comprising 12 386 screened people. Eleven studies (7020 patients) evaluated the presence of S. stercoralis infection only through investigation of larvae in faeces, showing an overall prevalence of 1% (95%CI 1-1%). Thirteen studies (5366 patients) used a serological test, showing an overall prevalence of 14% (95%CI 11-17%). Strongyloidiasis seroprevalence was 20% (95%CI 15-24%) among migrants from sub-Saharan Africa, 14% (95%CI 10-18%) among those from Latin America and 8% (95%CI 5-11%) among migrants from North Africa. CONCLUSIONS: Migrants coming from strongyloidiasis-endemic areas living in Spain had a high S. stercoralis infection prevalence, particularly those from sub-Saharan Africa and Latin America. This population should be screened using serology as the most sensitive test for S. stercoralis infection. This could be easily implemented at primary care level.
OBJECTIFS: Fournir des informations sur la prévalence de la strongyloïdose parmi les migrants résidant en Espagne et provenant de zones endémiques pour Strongyloides stercoralis. MÉTHODES: Revue systématique de la littérature et méta-analyse des études montrant la prévalence de l'infection à S. stercoralis parmi les migrants d'Amérique latine, d'Afrique, d'Europe de l'Est, d'Asie et d'Océanie qui résident en Espagne. Nous avons inclus des articles publiés jusqu'au 30 avril e 2019 sans restriction de langue. Les mots clés utilisés pour la recherche comprenaient "Strongyloides stercoralis", "strongyloïdose", "Espagne", "dépistage" et "migrants". RÉSULTATS: Vingt-quatre études ont été incluses dans la revue et la méta-analyse, comprenant 12.386 personnes dépistées. Onze études (7.020 patients) ont évalué la présence d'une infection à S. stercoralis uniquement en examinant les larves dans les selles, montrant une prévalence globale de 1% (IC95%: 1-1%). Treize études (5.366 patients) ont utilisé un test sérologique, montrant une prévalence globale de 14% (IC95%: 11-17%). La séroprévalence de la strongyloïdose était de 20% (IC95%: 15-24%) chez les migrants d'Afrique subsaharienne, 14% (IC95%: 10-18%) chez ceux d'Amérique latine et 8% (IC95%: 5-11%) chez ceux d'Afrique du Nord. CONCLUSIONS: Les migrants en provenance de zones d'endémie pour la strongyloïdose vivant en Espagne avaient une prévalence élevée d'infection à S. stercoralis, en particulier ceux d'Afrique subsaharienne et d'Amérique latine. Cette population devrait être dépistée en utilisant la sérologie comme le test le plus sensible pour l' infection à S. stercoralis. Cela pourrait être facilement mis en Åuvre au niveau des soins primaires.
Subject(s)
Emigrants and Immigrants , Strongyloidiasis/epidemiology , Humans , Mass Screening/methods , Spain/epidemiology , Strongyloidiasis/ethnology , Strongyloidiasis/prevention & controlABSTRACT
OBJECTIVE: Telemedicine uses information and communication technologies to provide services in the field where the distance is a critical factor. The aim of the present study is to describe the experience of a synchronous telemedicine between two hospitals in Spain and Angola. METHODS: This is a retrospective observational study of all synchronous telemedicine sessions conducted between the Hospital Nossa Senhora da Paz in Angola and the Vall d'Hebron University Hospital in Spain from January 2011 to December 2014. RESULTS: Seventy-two cases were discussed in the telemedicine sessions. The average age of patients was 18.02 (SD 13.75) years and mostly women (54.38 percent). Reasons to discuss the cases were 46.47 percent doubts in the diagnosis and therapeutic management, 15.47 percent were purely formative cases, and only 8.45 percent treatment doubt. At the time of presentation, 29 percent of the patients were already diagnosed, 95 percent of whom with infectious disease diagnostic, and from the undiagnosed patients 36 percent presented a febrile syndrome. CONCLUSION: This study shows the viability of synchronous telemedicine between European and African countries without an excessively sophisticated technology.
Subject(s)
Telemedicine , Adolescent , Angola , Female , Hospitals , Humans , Retrospective Studies , SpainABSTRACT
Blastocystis sp. is the most common intestinal parasite isolated in humans. The aim of the study was to describe the risk factors associated to Blastocystis sp. detection. A case-control retrospective study was carried out at Vall d'Hebron University Hospital (Barcelona, Spain), which receives all fecal samples collected in Barcelona at primary care level. Eligible patients were patients older than 18 years in whom three consecutive stool samples were examined for parasitic diagnosis from January to December 2017. Positive patients for Blastocystis sp. were assigned as cases whereas negative patients were assigned as controls. Overall, 4174 patients were eligible for the study, from whom 724 (17.3%) had Blastocystis sp. detection. From these, 170 cases (Blastocystis sp. positive) and 170 controls (Blastocystis sp. negative) were randomly selected for inclusion. One hundred and twenty-six (37.1%) of them were immigrants, and 171 (50.3%) patients had traveled out of Spain the year before. The majority of individuals had jobs with no direct contact with other people (health personnel, teachers, and caregivers) (85.6%), and 29.4% were in usual contact with animals. Regarding clinical information, 68.2% of patients presented digestive symptoms, 3.5% presented an immunosuppressant condition, and 6.5% were infected by other intestinal parasites. Variables associated to Blastocystis sp. detection were being born in Africa, having traveled abroad, and working in direct contact with other people. Having other intestinal parasitic infections had a protective value. Our study provides new insights into the epidemiology of Blastocystis sp. in industrialized countries.
Subject(s)
Blastocystis Infections/epidemiology , Blastocystis/isolation & purification , Communicable Diseases, Imported/parasitology , Feces/parasitology , Adolescent , Adult , Aged , Case-Control Studies , Communicable Diseases, Imported/epidemiology , Emigrants and Immigrants , Female , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Spain/epidemiology , Young AdultABSTRACT
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.
Subject(s)
Chagas Disease/drug therapy , Itraconazole/therapeutic use , Trypanocidal Agents/therapeutic use , Adult , Animals , CD4 Lymphocyte Count , Chagas Disease/complications , Chronic Disease , Female , HIV Infections/complications , HIV Infections/diagnosis , Humans , Itraconazole/pharmacology , Tomography, X-Ray Computed , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effectsABSTRACT
OBJECTIVE: To understand Zika virus (ZIKV) dynamics in fluids of infected individuals and the risk of sexual transmission. METHODS: Prospective study at two centres in Spain. Patients with probable or confirmed diagnosis of ZIKV infection were clinically followed up, and fluid samples were collected from saliva, serum, urine and semen or vaginal secretion following the study protocol. Non-traveller-sexual partners were offered to participate. RESULTS: From January 2016 to December 2016, we included a total of 11 traveller patients and six sexual contacts. Six patients were male, with a median age of 38 years (IQR 30-45). We performed 61 RT-PCR determinations, seven of which were positive. Positive results were retrieved from serum, urine, semen and vaginal tract. One of four women tested positive for ZIKV RNA in vaginal swabs collected during the first 45 days after symptoms onset. Clearance occurred between day 37 and day 69 after symptoms onset. One of five men tested positive for ZIKV RNA in semen collected during the first 45 days after symptoms onset. Clearance occurred between day 23 and 107 after symptoms onset. Six patients had sexual relations during the defined period. All tested patients were negative for ZIKV infection by serological testing. CONCLUSION: ZIKV shedding persistence in genital fluids occurs in a significant number of symptomatic patients after visiting an endemic area. We did not find any ZIKV seroconversion among the three male contacts who were investigated. Diagnostic algorithms may be updated to include genital tract fluid specimens in the diagnostic process.
Subject(s)
RNA, Viral/analysis , Semen/virology , Travel , Zika Virus Infection/virology , Zika Virus/isolation & purification , Adult , Female , Humans , Male , Prospective Studies , Spain , Virus SheddingABSTRACT
BACKGROUND: Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models. METHODS: We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14. RESULTS: The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment. CONCLUSIONS: Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).
Subject(s)
Chagas Disease/drug therapy , Nitroimidazoles/administration & dosage , Triazoles/administration & dosage , Trypanocidal Agents/therapeutic use , Adult , Chronic Disease , DNA, Protozoan/analysis , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Nitroimidazoles/adverse effects , Prospective Studies , Transaminases/blood , Treatment Outcome , Triazoles/adverse effects , Trypanocidal Agents/adverse effects , Trypanosoma cruzi/genetics , Trypanosoma cruzi/isolation & purificationABSTRACT
OBJECTIVES: In a previous study performed by our group, Strongyloides stercoralis infection in patients with Chagas disease was associated with higher proportion of Trypanosoma cruzi DNA detection in peripheral blood. The aim of the study was to confirm this association in a larger cohort of patients. METHODS: Cross-sectional study of all patients with Chagas disease diagnosed from 2005 to 2015 during blood donation at the Catalan Blood Bank. Demographic data and T. cruzi RT-PCR were collected. S. stercoralis infection diagnosis was based on a serological test. RESULTS: Two hundred and two blood donors were included. T. cruzi RT-PCR was positive in 72 (35.6%) patients, and S. stercoralis serology was positive in 22 (10.9%) patients. Patients with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR than those with negative serology (54.5% vs. 33.3%, P = 0.050), and the difference increased when taking a serological index cut-off of 2.5, which increases the specificity of the test to detect a confirmed strongyloidiasis (60% vs. 33%, P = 0.017). CONCLUSIONS: Patients with Chagas disease with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR in peripheral blood than those with negative serology, which reflects the potential immunomodulatory effects of S. stercoralis in T. cruzi co-infected patients.
Subject(s)
Chagas Disease/parasitology , DNA/blood , Strongyloides stercoralis/growth & development , Strongyloidiasis/complications , Trypanosoma cruzi/growth & development , Adolescent , Adult , Animals , Chagas Disease/blood , Female , Humans , Male , Middle Aged , Trypanosoma cruzi/genetics , Young AdultABSTRACT
The constant migration flows have favored the presence of people with Chagas disease in regions traditionally regarded as non-endemic, such as North America, Europe, Asia and Oceania. This has forced both health authorities and professionals to be updated in order to respond to such a demand for assistance. Recent years have led to significant progress in the field of diagnosis and treatment of Chagas disease, one of the most neglected tropical diseases. Recent clinical trials are providing new evidence that makes the management of these patients, a constant challenge for the professionals involved. Innovative diagnostic tools and therapeutic regimens, allow us to face the future of Chagas disease with optimism.