Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

INTRODUCTION: Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. MATERIALS AND METHODS: Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. RESULTS: Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p < 0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p < 0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). CONCLUSIONS: Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

Clinical impact of rapid molecular detection of respiratory pathogens in patients with acute respiratory infection.

BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality worldwide. There is a need to demonstrate the clinical impact of using the new, rapid and sensitive molecular assays in prospectively designed studies. OBJECTIVES: To study the impact on medical management of a rapid molecular assay in patients with respiratory infections. STUDY DESIGN: A prospective, randomized, non-blinded study was performed in patients presenting to the Emergency Department during two respiratory seasons (2016-2017). Diagnosis was performed by FilmArray Respiratory Panel (FilmArray-RP) or by immunofluorescence assay (IFA). RESULTS: A total of 432 patients (156 children and 276 adults) were analyzed. Diagnosis with FilmArray-RP was associated with significant changes in medical management including withholding antibiotic prescriptions (OR:15.52, 95%CI:1.99-120.83 in adults and OR:12.23, 95%CI:1.56-96.09 in children), and reduction in complementary studies in children (OR:9.64, 95%CI:2.13-43.63) compared to IFA. Decrease in oseltamivir prescriptions was significantly higher in adults in the FilmArray-RP group (p = 0.042; OR:1.19, 95%CI:0.51-2.79) compared to adults managed with IFA. Diagnostic yield was significantly higher by FilmArray-RP (81%) than by IFA (31%)(p < 0.001). The median time from sample collection to reporting was 1 h 52 min by FilmArray-RP and 26 h by IFA (p < 0.001). CONCLUSIONS: The high respiratory viruses' detection rate and availability of results within two hours when using FilmArray-RP were associated with decreases in antibiotic prescriptions and complementary studies and more accurate use of oseltamivir.

Re-conceptualizing Neurosis as a Degree of Egocentricity: Ethical Issues in Psychological Theory.

Psychology's historical rejection of ethics has led to an oversimplification of the origins and treatments of mental disorders. In this article, we present an analysis of how classical neurosis can be reformulated from an ethical and psychological interaction. We focus on the crucial role that egocentricity plays and argue that this term can help to clarify how ego defensive ethical decisions can undermine psychological capacities and contribute to a progressive depersonalization that can result in typical clinical disorders. In Christian anthropology, the virtues, especially humility and love have a crucial role in the positive growth of human affective and cognitive capacities. In addition, the person in his/her nature is endowed with the capacity to transcend the self and to escape egocentricity through self-giving love of God and of others. This capacity of self-giving is diametrically opposed to egocentricity and opens a new way for possible psychological recovery.

Cyclic recovery of adenovirus in a stem cell transplant recipient: an inverse association with graft-versus-host disease.

Adenovirus (AdV) infections have been increasingly recognized as significant pathogens that may cause severe morbidity and mortality among stem cell transplant (SCT) recipients. AdV can cause localized infections such as hemorrhagic cystitis (HC), pneumonia, hepatitis and also disseminated disease that can lead to death. We report a case of severe hemorrhagic cystitis in a SCT recipient who died 83 days after transplant. In this patient, AdV recovery was not constantly detected. In fact, fluctuations of the AdV detection in leukocytes and urine were observed by culture and PCR. When analyzing this viral cyclic recovery with different signs or symptoms in the patient, we observed an inverse association with the presence of acute graft-versus-host disease (GVHD). Whether these fluctuations represent donor-derived reactivity, indirectly manifested by the presence of GVHD, requires further study. This is the first case describing a dynamic pattern of AdV replication in leukocytes and urine samples from a patient with severe HC and the temporal correlation with GVHD.

Prediction of severe disseminated adenovirus infection by serum PCR.

Adenoviruses are increasingly recognised as viral pathogens that can cause fatal infections in immunocompromised patients, particularly recipients of haematopoietic stem-cell grafts. Adenovirus infections are not easily diagnosed and the development of a severe infection cannot be predicted by standard culture techniques. In a pilot study, we investigated the value of adenovirus DNA detection in serum as a marker of disseminated disease in 14 patients with defined patterns of adenovirus infections. The results show that the appearance of adenoviral DNA in serum preceded the development of a severe or fatal adenovirus infection. Because proper management is dependent on early diagnosis and differentiation from other conditions, this test may be a valuable tool in the management of adenovirus infection.

Detection of adenoviruses (AdV) in culture-negative environmental samples by PCR during an AdV-associated respiratory disease outbreak.

Since 1954, adenoviruses (AdV) have been recognized as an important cause of acute respiratory disease (ARD) among U.S. military recruits. Until recently, routine oral vaccination for AdV serotypes 4 and 7 eliminated epidemic AdV-associated ARD in this population. Now that the manufacturer has ceased production, vaccination has ended and AdV epidemics have reappeared. As part of a prospective epidemiological study during the high-risk ARD season, serial samples were obtained from ventilation system filters and tested for AdV by culture and PCR. An outbreak occurred during this surveillance. Of 59 air filters, 26 (44%) were AdV positive only by PCR. Sequence analysis confirmed the presence of AdV serotype 4, the implicated outbreak serotype. The number of AdV-related hospitalizations was directly correlated with the proportion of filters containing AdV; correlation coefficients were 0.86 (Pearson) and 0.90 (Spearman's rho). This is the first report describing a PCR method to detect airborne AdV during an ARD outbreak. It suggests that this technique can detect and quantify AdV-associated ARD exposure and may enable further definition of environmental effects on AdV-associated ARD spread.

PCR detection of adenovirus in a bone marrow transplant recipient: hemorrhagic cystitis as a presenting manifestation of disseminated disease.

Adenoviruses (AdV), causing fatal disseminated infections in bone marrow transplant (BMT) recipients, are associated not only with hemorrhagic cystitis (HC) but also with hepatitis, conjunctivitis, and viral interstitial pneumonia. The importance of this virus as a cause of disseminated disease, however, has remained underappreciated. AdV infection has been diagnosed primarily through the use of cell culture. The fact that cell culture is insensitive for detecting this virus has hindered recognition of the role that AdV may play in morbidity and mortality in BMT recipients. To emphasize these points, we describe a patient who presented with HC due to AdV serotype 11, genotype c, and died with disseminated infection. In addition to cell culture, this study used a newly developed PCR-based method, capable of detecting all AdV serotypes tested, including different genotypes of serotype 11. The PCR result was positive in all culture-positive samples, including samples of urine, conjunctiva, and bronchoalveolar lavage (BAL). Importantly, the PCR method provided evidence of urinary shedding of AdV in a pretransplant, culture-negative specimen and showed dissemination in a subset of culture-negative specimens, including BAL, blood, and bone marrow samples. The lack of widespread awareness of the fact that localized infections may presage dissemination, and the previous associated lack of rapid, sensitive diagnostic assays, has impaired recognition of AdV infections in patients undergoing BMT. Early detection may contribute to therapy modification and avoidance of unwarranted diagnostic procedures. It may also assist in epidemiologic control of this highly infectious pathogen and lead to a renewed interest in preventive and therapeutic approaches.

PCR method for detection of adenovirus in urine of healthy and human immunodeficiency virus-infected individuals.

Adenoviruses (AdV) cause diseases that range from localized, self-limited illnesses to fatal infections in immunocompromised patients. Culture is assumed to be sensitive but requires viable virus and up to 3 weeks for detection, and it can be inhibited by bacterial contamination. A new PCR method amplifying a region of the hexon gene was developed in order to detect AdV in urine more rapidly and with greater sensitivity than obtainable by culture technology. All 18 serotypes tested were detected. Quantitatively, with optimized urine processing, AdV PCR detected 0.2 PFU/ml (serotype 11) and 10 DNA copies/ml (serotype 2). Serially collected urine samples from human immunodeficiency virus (HIV)-infected patients with concurrent cytomegalovirus retinitis were divided into three groups: AdV culture-positive samples, AdV culture-negative or bacterially contaminated samples from patients with a history of AdV culture-positive urines, and AdV culture-negative samples from patients without a history of AdV culture positivity. Urine samples from healthy adults were also tested by culture and PCR to screen for asymptomatic shedding. Amplification was assessed with and without prior DNA purification. AdV was detected by PCR in 90% of culture-positive urines (100% of unclotted samples, e.g., those culture positive after storage for PCR testing), 71% of culture-negative or bacterially contaminated urines from AdV-infected patients, and 28% from AdV culture-negative patients. Healthy volunteers were culture negative for AdV, and 96% were PCR negative. The new AdV PCR method is rapid and sensitive and can detect viral DNA in samples for which culturing is problematic. The role of AdV replication during HIV infection merits further investigation with sensitive tools such as PCR.

Strategies for malaria control in Colombia.

Attempts at malaria eradication this century have been highly effective but early successes have not been sustained. This has been ascribed to the lack of community involvement in these campaigns. Colombia has put huge effort into malaria control on a number of fronts, from vaccine development to the evaluation of the integrated use of more traditional methods. William Rojas, Fernando Peñaranda and Mouricio Echavarria describe a pilot programme for integrated malaria control in Colombia whose success they attribute to committed community participation.

Reduction of malaria prevalence after introduction of Romanomermis culicivorax (Mermithidae: Nematoda) in larval Anopheles habitats in Colombia.

The worldwide resurgence of malaria has become a major public health problem. New methods of controlling the vectors of the disease are required, and we therefore studied the biological control of Anopheles albimanus by Romanomermis culicivorax in Colombia. The investigation was carried out in El Valle and Nuquí, two towns on the northern Pacific coast of the country. All of the mosquito larval habitats surrounding El Valle were seeded with the eggs and adults of R. culicivorax. The nematode established itself in the new habitat and recycled over 27 months. The larval population of A. albimanus, the only malarial vector detected in the two towns, decreased in El Valle. In contrast, no change in the larval populations of the vector was detected in ponds located near Nuquí, the untreated control town. A rapid and progressive decrease of the prevalence of malaria among schoolchildren in El Valle was observed during the 2-year evaluation period.

[Cellulitis in pediatrics. Diagnostic and therapeutic considerations]. / Celulitis en pediatría. Consideraciones diagnósticas y terapéuticas.

The clinical histories of 180 cases of cellulitis or phlegmona diffusa were studied at the Hospital de Pediatría del Centro Medico Nacional. The disease prevailed in infants and preschool children. Staphylococcus aureus was the etiological agent most frequently found, but with the presence of enterobacteriaceae in 39% of patients under 2 years of age. One third of the children with cellulitis showed one or several complications. Lethality reached 5% (9 cases), but always related to septicemia from S. aureus. In 14.4%, osteoarthritis was present; frequently there was: fever for over 5 days in spite of adequate treatment, a history of late initiation of the antimicrobial drug (over 1 week) and phlogosis or functional limitation. The radiological picture that shows the bony lesion was evident only after two weeks. One half these cases remained with sequelae. Considerations are made on the adequate plans for antibiotic treatment and the early diagnosis of the osteoarticular complication.

Specificity of avoidance deficits produced by 6-hydroxydopamine lesions of the nigrostriatal system of the rat.

Microinjections of 6-hydroxydopamine (6-OHDA) into the dopaminergic nigrostriatal system (NS) of the rat impaired acquisition of a two-way avoidance response. This effect was independent of nutritional deficiencies since it was observed even when a special postoperative treatment ensured a comparable state of nutrition in control and experimental rats. It was likewise independent of locomotor disturbances. A third question remains open: Doses of 6-OHDA that impaired acquisition of an active avoidance response produced lesions that were, to a great extent, nonspecific. Therefore, behavioral effects of these doses cannot be entirely ascribed to selective destruction of the NS.