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The risk of biological threats has been constantly increasing in recent years. This is due both to the adaptation of avian and animal pathogens to the human organism as a result of the expansion of the area of human activity and to the development of biotechnologies. Viruses predominate among these pathogens. Examples in recent years are the COVID-19 pandemic and the continued spread of monkeypox (MPX). The situation requires the search for objects for research that would have a high informative value and could help in assessing and predicting the spread of infections. The article analyzed and assessed the potential and importance of virological monitoring of wastewater as an element of surveillance for emergent and re-emergent infections, using the example of some of them (enterovirus infections - poliomyelitis and infection caused by enterovirus D68, COVID-19, and MPX). Monitoring of enteroviruses in wastewater is a routine practice in many countries. Poliomyelitis is subject to eradication, and its incidence is extremely low. The study of wastewater makes it possible to indirectly detect the circulation of poliovirus among people, determine its molecular genetic characteristics ("wild", vaccine, vaccine-derived poliovirus), the duration of circulation, and ways of spread and take appropriate measures in a timely manner. Enterovirus type D68 gained relevance as a re-emergent infection starting in 2014. Large outbreaks caused by it began to be registered in the USA, Canada, and then in the European region. Previously, the virus caused minor respiratory symptoms, but now it has become the cause of severe acute respiratory disease, particularly in children, and has also acquired neurovirulent properties. Its monitoring in wastewater allows for assessing the actual intensity of the epidemic process of this infection in certain territories and in certain countries, which cannot always be done based on clinical diagnosis without an additional etiological diagnosis. During the 3 years of the pandemic, SARS-CoV-2 has taken root in the human population, but a new parasitic system continues to develop. Wastewater monitoring makes it possible to assess the intensity of the epidemic process of COVID-19, which is supported by manifest forms of infection, asymptomatic persistence of the virus, and convalescents. It also allows for analyzing the effectiveness of quarantine and other restrictive measures, detecting genetic changes in the virus and trends in the formation of new variants of the virus. Since May 2022, MPX has gone beyond the borders of endemic countries and began to spread rapidly, acquiring the character of a re-emergent infection. A variant of the pathogen (clade 3) began to evolve and became transmissible from person to person. The disease it causes began to radically differ from the previously known MRC due to changes in pathogenesis and epidemiological features. First of all, this concerns the pronounced anthroponotic characteristics of re-emergent MPX in comparison with the zoonotic manifestations of the previously known endemic MPX. The article discusses the results of studies conducted in different countries on the determination of MPX virus (MPXV) nucleic acids in wastewater samples using OPG002 gene analysis of all MPXVs (G2R_G), the West African clade (G2R_WA), and virus reference genomes of MPXV of the outbreak in 2022 (G2R_NML). Thus, virological monitoring of wastewater can be used as an effective element of surveillance for most infectious diseases, in particular, emergent and re-emergent ones. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein–Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host disease. The higher frequency initially paralleled a poor outcome, due to limited therapeutic options, and scarcity of controlled trials in a rare disease context. In the last 2 decades, insight into the relationship between EBV and the immune system, and advances in early diagnosis, monitoring and treatment have changed the approach to the management of PTLDs after HSCT, and significantly ameliorated the prognosis. In this review, we summarize literature on the impact of combined viro-immunologic assessment on PTLD management, describe the various strategies for PTLD prevention and preemptive/curative treatment, and discuss the potential of novel immune-based therapies in the containment of this malignant complication.

Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein–Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host disease. The higher frequency initially paralleled a poor outcome, due to limited therapeutic options, and scarcity of controlled trials in a rare disease context. In the last 2 decades, insight into the relationship between EBV and the immune system, and advances in early diagnosis, monitoring and treatment have changed the approach to the management of PTLDs after HSCT, and significantly ameliorated the prognosis. In this review, we summarize literature on the impact of combined viro-immunologic assessment on PTLD management, describe the various strategies for PTLD prevention and preemptive/curative treatment, and discuss the potential of novel immune-based therapies in the containment of this malignant complication. [ABSTRACT FROM AUTHOR]

Résumé Moins de 30 ans après la découverte du virus de l'hépatite C, sa structure, son cycle de réplication et sa biologie sont largement caractérisés. En parallèle, le développement intense d'outils diagnostiques rapides, sensibles et automatisés, tenant compte de l'importante variabilité génétique virale, permet aujourd'hui un dépistage sérologique et un suivi virologique de l'efficacité thérapeutique. Summary Less than 30 years after the discovery of the hepatitis C virus, its structure, its replication cycle and its biology have been fully characterised. Simultaneously, the intensive development of rapid, sensitive and automated diagnostic tools which take into account significant viral variability, has resulted in serological screening and virological monitoring of the efficacy of the treatment. [ABSTRACT FROM AUTHOR]

Background: More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to minimize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance. Methods: We systematically reviewed publications and conference abstracts published between January 2006 and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)-infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta-analysis. Intention-to-treat (ITT) analysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure. Results: Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 included cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2-77.2) suppression after 6 months and 61.8% (95% CI, 44.0-79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. Conclusions: Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years. [ABSTRACT FROM AUTHOR]

Introduction: The current expansion of antiretroviral treatment (ART) in the developing world without routine virological monitoring still raises concerns on the outcome of the strategy in terms of virological success and drug resistance burden. We assessed the virological outcome and drug resistance mutations in patients with 36 months' ART experience, and monitored according to the WHO public health approach in Cameroon. Methods: We consecutively recruited between 2008 and 2009 patients attending a national reference clinic in Yaoundé - Cameroon, for their routine medical visits at month 36±2. Observance data and treatment histories were extracted from medical records. Blood samples were collected for viral load (VL) testing and genotyping of drug resistance when HIV-1 RNA⩾1000 copies/ml. Results: Overall, 376 HIV-1 infected adults were recruited during the study period. All, but four who received PMTCT, were ART-naïve at treatment initiation, and 371/376 (98.7%) started on a first-line regimen that included 3TC+d4T/AZT+NVP/EFV. Sixty-six (17.6%) patients experienced virological failure (VL⩾1000 copies/ml) and 53 carried a resistant virus, thus representing 81.5% (53/65) of the patients who failed. Forty-two out of 53 were resistant to nucleoside and non-nucleoside reversetranscriptase inhibitors (NRTIs+NNRTIs), one to protease inhibitors (PI) and NNRTIs, two to NRTIs only and eight to NNRTIs only. Among patients with NRTI resistance, 18/44 (40.9%) carried Thymidine Analog Mutations (TAMs), and 13/44 (29.5%) accumulated at least three NRTI resistance mutations. Observed NNRTI resistance mutations affected drugs of the regimen, essentially nevirapine and efavirenz, but several patients (10/51, 19.6%) accumulated mutations that may have compromised etravirine use. Conclusions: We observed a moderate level of virological failure after 36 months of treatment, but a high proportion of patients who failed developed drug resistance. Although we found that for the majority of patients, second-line regimens recommended in Cameroon would be still effective, accumulated resistance mutations are of concern and may compromise future treatment strategies, stressing the need for virological monitoring in resource-limited settings [ABSTRACT FROM AUTHOR]

When assessing patients with chronic hepatitis B virus (HBV) infection, consider the state of viral replication, the immune response and whether viral mutations could be present, as well as evidence for liver disease or extrahepatic manifestations. In wild-type infections, loss of hepatitis B e antigen (HBeAg), gain of anti-HBe and disappearance of HBV DNA from serum indicate immunosuppression of viral replication, or ‘nonreplicative chronic HBV infection’. This ‘healthy carrier’ state must be distinguished from HBeAg-negative chronic hepatitis B (CHB) resulting from precore and core promoter mutations. HBeAg-negative CHB is common with genotypes D (Mediterranean region, south Asia) and C (north Asia) infections. Age, disease activity (alanine aminotransferase level) and severity (fibrosis stage, cirrhosis) influence treatment decisions. Following the marginal effectiveness of interferon and often temporary effectiveness of lamivudine due to drug resistance, treatment of CHB is entering a new era. Adefovir, entecavir, tenofovir, telbivudine and clevudine have equal or superior antiviral efficacy to lamivudine, whereas several agents are effective against lamivudine-resistant HBV. Pegylated-interferon (peginterferon) is superior to conventional interferon for obtaining sustained immunosuppression of HBV without drug resistance. Antiviral suppression of HBV replication for 2–5 years reverses hepatic fibrosis, prevents cirrhosis and, when cirrhosis is established, improves liver function, prevents hepatic decompensation and lowers the risk of liver cancer. Before embarking on immunosuppressive chemotherapy or organ transplantation in patients with chronic HBV infection, it is important to start antiviral therapy to prevent hepatitis flares. Antiviral therapy can be effective against membranous glomerulonephritis and polyarteritis nodosa caused by HBV. Further improvements in treatment of CHB are needed to prevent drug resistance and permanently suppress viral replication by eradicating viral templates or stimulating host immune responsiveness to HBV. [ABSTRACT FROM AUTHOR]

Abstract The management of chronic viral hepatitis has changed significantly with the availability of effective antiviral agents. There is now a high probability that timely intervention can arrest development of cirrhosis, thereby preventing mortality from portal hypertension, liver failure and liver cancer. This two-part review discusses the implications of this new era of antiviral therapy for physicians. The present review is about chronic hepatitis C virus (HCV); a similar review that considers the treatment of hepatitis B virus will be published in a later issue of the Internal Medicine Journal. Chronic HCV infection is common, but fibrotic progression of liver disease is slow and variable; many infected persons never develop cirrhosis. Case selection for antiviral therapy is crucial. The most effective therapy is a pegylated (long-acting) interferon with ribavirin. Sustained viral response (SVR) (absent viraemia 6 months after completing treatment) can be obtained in 40−60% of individuals infected with genotype 1 and in approximately 67% with genotype 4 after 12 months of treatment. Response rates are higher (75−85%) with genotypes 2 and 3 after only 6 months of treatment. Late relapse is negligible after SVR. This viral cure reverses hepatic fibrosis, reduces the risk of liver failure and of hepato­cellular carcinoma. Combination therapy requires a supportive setting to minimize the impact of side-effects and maximize therapeutic effectiveness. Overall management of HCV-infected persons must also embrace measures to improve quality of life by preventing or dealing with psychosocial issues and advocating lifestyle changes to counter comorbidity from alcohol, central obesity and insulin resistance. These latter factors favour fibrotic disease progression, complications of cirrhosis (such as hepatocellular carcinoma) and development of type 2 diabetes mellitus, as well as eroding the chances of SVR with antiviral therapy. (Intern Med J 2004; 34: 324−337) [ABSTRACT FROM AUTHOR]

Abstract: Background: Virological monitoring with sensitive assays and subsequent introduction of antiviral preemptive therapy has become a routine strategy in the management of stem cell transplant recipients. Several techniques have been used and each has advantages and disadvantages. Objective: The objective of this review is to discuss the drawbacks of virological monitoring alone for the management of CMV in stem cell transplant recipients. Study design: Publications on the success of CMV viral load monitoring were reviewed with special emphasis on the timing of CMV disease after stem cell transplantation. Results and conclusions: During recent years CMV disease has more frequently been documented later after transplantation and has been associated with the absence of CMV-specific immune responses. Repeated antiviral therapy carries the risk of toxicity and the development of resistance. Hence virological monitoring might be insufficient for optimal management of these patients. This realization has spurred interest in evaluating assays for immunological monitoring as a means of improving control of potential CMV disease after transplantation. [Copyright &y& Elsevier]

Background: This prospective pilot study explored same-day point-of-care viral load testing in a setting in Ghana that has yet to implement virological monitoring of antiretroviral therapy (ART)., Methods: Consecutive patients accessing outpatient care while on ART underwent HIV-1 RNA quantification by Xpert. Those with viraemia at the first measurement (T0) received immediate adherence counselling and were reassessed 8 weeks later (T1). Predictors of virological status were determined by logistic regression analysis. Drug resistance-associated mutations (RAMs) were detected by Sanger sequencing., Findings: At T0, participants had received treatment for a median of 8·9 years; 297/333 (89·2%) were on NNRTI-based ART. The viral load was ≥40 copies/mL in 164/333 (49·2%) patients and ≥1000 copies/mL in 71/333 (21·3%). In the latter group, 50/65 (76·9%) and 55/65 (84·6%) harboured NRTI and NNRTI RAMs, respectively, and 27/65 (41·5%) had ≥1 tenofovir RAM. Among 150/164 (91·5%) viraemic patients that reattended at T1, 32/150 (21·3%) showed resuppression <40 copies/mL, comprising 1/65 (1·5%) subjects with T0 viral load ≥1000 copies/mL and 31/85 (36·5%) subjects with lower levels. A T0 viral load ≥1000 copies/mL and detection of RAMs predicted ongoing T1 viraemia independently of self-reported adherence levels. Among participants with T0 viral load ≥1000 copies/mL, 23/65 (35·4%) showed resuppression <1000 copies/mL; the response was more likely among those with higher adherence levels and no RAMs., Interpretation: Same-day point-of-care viral load testing was feasible and revealed poor virological control and suboptimal resuppression rates despite adherence counselling. Controlled studies should determine optimal triaging modalities for same-day versus deferred viral load testing., Funding: University of Liverpool, South Tees Infectious Diseases Research Fund., Competing Interests: Dr. Smith reports personal fees from Gilead Sciences and ViiV, outside the submitted work; Dr. Chadwick reports personal fees from Gilead, outside the submitted work; Dr. Geretti reports grants from BMS, Gilead, Janssen, and ViiV, and personal fees from Roche Pharma Research & Early Discovery, outside the submitted work. All other authors have nothing to disclose., (© 2019 Published by Elsevier Ltd.)

Polyomaviruses BK and JC are ubiquitous viruses with high seroprevalence rates in general population. Following primary infection, polyomaviruses BK and JC persist latently in different sites, particularly in the reno-urinary tract. Reactivation from latency may occur in normal subjects with asymptomatic viruria, while it can be associated to nephropathy (PVAN) in kidney transplantat recipients. PVAN may occur in 1%-10% of renal transplant patients with loss of the transplanted organ in 30% up to 80% of the cases. Etiology of PVAN is mainly attributable to BK virus, although approximately 5% of the cases may be due to JC. Pathogenesis of PVAN is still unknown, although viral replication and the lack of immune control play a major role. Immunosuppression represents the condicio sine qua non for the development of PVAN and the modulation of anti-rejection treatment represents the first line of intervention, given the lack of specific antiviral agents. At moment, an appropriate immunemodulation can only be accomplished by early identification of viral reactivacation by evaluation of polyomavirus load on serum and/or urine specimens, particularly in the first year post-trasplantation. Viro-immunological monitoring of specific cellular immune response could be useful to identify patients unable to recover cellular immunity posttransplantation, that are at higher risk of viral reactivation with development of PVAN. Herein, the main features of polyomaviruses BK and JC, biological properties, clinical characteristics, etiopathogenesis, monitoring and diagnosing of PVAN will be described and discussed, with an extended citation of related relevant literature data.