Possibility Of Reinfection Research Articles

Genomic Evidence for a Case of Reinfection with SARS-CoV-2

The degree of protective immunity conferred by infection with SARS-CoV-2 is currently unknown. As such, the possibility of reinfection with this virus is not well understood. Herein, we describe the data from an investigation of two instances of SARS-CoV-2 infection in the same individual. Through nucleic acid sequence analysis, the viruses associated with each instance of infection were found to possess a degree of genetic discordance that cannot be explained reasonably through short-term in vivo evolution. We conclude that it is possible for humans to become infected multiple times by SARS-CoV-2, but the generalizability of this finding is not known.

Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2.

IntroductionThe response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions.DevelopmentWe reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus’ action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids.ConclusionGiven the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.

Analytics and Prediction Modeling During the COVID-19 Pandemic

Analytics and Prediction Modeling During the COVID-19 Pandemic

Broadly Neutralizing Antibodies Targeting New Sites of Vulnerability in Hepatitis C Virus E1E2.

Increasing evidence indicates that broadly neutralizing antibodies (bNAbs) play an important role in immune-mediated control of hepatitis C virus (HCV) infection, but the relative contribution of neutralizing antibodies targeting antigenic sites across the HCV envelope (E1 and E2) proteins is unclear. Here, we isolated thirteen E1E2-specific monoclonal antibodies (MAbs) from B cells of a single HCV-infected individual who cleared one genotype 1a infection and then became persistently infected with a second genotype 1a strain. These MAbs bound six distinct discontinuous antigenic sites on the E1 protein, the E2 protein, or the E1E2 heterodimer. Three antigenic sites, designated AS108, AS112 (an N-terminal E1 site), and AS146, were distinct from previously described antigenic regions (ARs) 1 to 5 and E1 sites. Antibodies targeting four sites (AR3, AR4-5, AS108, and AS146) were broadly neutralizing. These MAbs also displayed distinct patterns of relative neutralizing potency (i.e., neutralization profiles) across a panel of diverse HCV strains, which led to complementary neutralizing breadth when they were tested in combination. Overall, this study demonstrates that HCV bNAb epitopes are not restricted to previously described antigenic sites, expanding the number of sites that could be targeted for vaccine development.IMPORTANCE Worldwide, more than 70 million people are infected with hepatitis C virus (HCV), which is a leading cause of hepatocellular carcinoma and liver transplantation. Despite the development of potent direct acting antivirals (DAAs) for HCV treatment, a vaccine is urgently needed due to the high cost of treatment and the possibility of reinfection after cure. Induction of multiple broadly neutralizing antibodies (bNAbs) that target distinct epitopes on the HCV envelope proteins is one approach to vaccine development. However, antigenic sites targeted by bNAbs in individuals with spontaneous control of HCV have not been fully defined. In this study, we characterize 13 monoclonal antibodies (MAbs) from a single person who cleared an HCV infection without treatment, and we identify 3 new sites targeted by neutralizing antibodies. The sites targeted by these MAbs could inform HCV vaccine development.

Clinical outcomes and quality of life after total hip arthroplasty in adult patients with a history of infection of the hip in childhood: a mid-term follow-up study

BackgroundTotal hip arthroplasty for adult patients with a history of infection of the hip in childhood could be a more technically demanding procedure due to complicated anatomy and the possibility of reinfection. Here, we conducted a mid-term analysis of clinical outcomes in such patients after primary cementless total hip arthroplasty (THA).MethodsWe reviewed 101 patients (101 hips; 51 men; mean age, 52.3 years) who underwent cementless THA between 2008 and 2015, at a mean of 24 years (range, 11–43) since the resolution of childhood hip infection. Patients were followed up for a mean of 6.1 years (range, 2.1–9.6). Clinical outcomes and quality of life after THA were assessed at final follow-up.ResultsNo cases of infection were reported during the follow-up, and patients showed significant improvement in Harris Hip Score, for which the mean score increased from 48.5 to 90 points; the modified Merle d’Aubigne and Postel (MAP) Hip Score; the Hip Dysfunction and Osteoarthritis Outcome Score; the SF-12; and mean limb length discrepancy, which decreased from 3.4 to 1.1 cm. During follow-up, four cases of prosthesis dislocation, three of transient sciatic paralysis, seven of femoral fracture, five of heterotopic ossification, and 19 of osteolysis were recorded. Revision surgery was performed for two patients, one for isolated loosening of the acetabular component and another for loosening of the femoral stem.ConclusionCementless THA can effectively treat patients with a quiescent period of infection of the hip of more than 10 years, resulting in good functional outcomes and fewer complications. Risk of infection recurrence after THA in these patients seems extremely low.

Management of Helicobacter pylori in Piedmont, Italy.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium, usually acquired during childhood, whose natural habitat is the gastric lumen. H. pylori is accepted as the most important cause of gastritis and peptic ulcer in humans. Nevertheless, its important role in the pathogenesis of gastric cancer as well as in several extra-gastroduodenal diseases has been confirmed. The aim of this work is to discuss, for the first time in a single article, all publications concerning H. pylori infection arising from Piedmont region, Italy, where in 1893 Giulio Bizzozero was the first who observed and described spiral organisms in the stomach of animal models. A systematic review of all publications on the management of H. pylori in adults in Piedmont, based on a PubMed and a Scopus research from 1965 to 2017 was performed. The discussed aspects are the epidemiology, the study on gastric and extragastric diseases related to H. pylori, the diagnostic methods, the treatment of H. pylori infection, and the possibility of reinfection. In conclusions, with almost 70 publications, Piedmont has proudly maintained the tradition of the father of the H. pylori.

Reassessment of asymptomatic carriers of Plasmodium spp. in an endemic area with a very low incidence of malaria in extra-Amazonian Brazil

BackgroundRegions with residual transmission are potential obstacles to the elimination of malaria. It is, therefore, essential to understand the factors associated with the maintenance of endemic malaria in these areas. The objective was to investigate whether the status of asymptomatic carriers of Plasmodium spp. DNA is maintained in the long term in an extra-Amazonian region of Brazil with low incidence, residual malaria transmission.MethodsAsymptomatic carriers of Plasmodium DNA detected in a survey carried out between 2001 and 2004 were reassessed between 2010 and 2011 using questionnaires, PCR and thick and thin blood smear tests three times at 3-month intervals.ResultsOf the 48 carriers detected between 2001 and 2004, 37 were located. Of these, only two had positive PCR results and, as in the first survey, Plasmodium malariae DNA was detected.ConclusionThe findings suggest that untreated dwellers from this extra-Amazonian region, who initially harbour malaria parasites, may become negative without ever developing apparent symptoms of the disease. Although the possibility of re-infection cannot be ruled out, the finding of two individuals harbouring P. malariae, both in the first and in the second survey, may be compatible with a long-term carrier state for this parasite. Since most clinical cases of malaria in the region are a consequence of infection by Plasmodium vivax, the epidemiological impact of such long-term carriage would be limited.

Global analysis of a mathematical model for HIV and Hepatitis C virus co-infection

Hepatitis C is the leading cause of death among individuals infected with human.Here, we present a deterministic model for HCV and HIV infections transmission anduse the model to assess the potential impact of antiviral therapy. The model isbased on the susceptible-infective-removed-susceptible (SIRS) compartmentalstructure with chronic primary infection and possibility of reinfection. Importantepidemiologic thresholds such as the basic and control reproductionnumbers and a measure of treatment impact are derived. We find that ifthe control reproduction number is greater than unity, there is a locally unstableinfection-free equilibrium and a unique, globally asymptotically stableendemic equilibrium. If the control reproduction number is less than unity, theinfection-free equilibrium is globally asymptotically stable

Global analysis of a mathematical model for Hepatitis C virus transmissions

In this paper, a mathematical model is proposed and analyzed for Hepatitis C virus (HCV) infection transmissions. In this model, both of chronic primary infection and possibility of reinfection are considered. Two thresholds of basic reproduction number R0 and control reproduction number Rc are derived. We get the sufficient conditions for the existence of infection-free equilibrium and endemic equilibrium. The sufficient conditions for the local and global stability of the equilibria are also obtained. Some numerical simulations are performed to prove the theoretical results. At last, some discussions are presented.

Systematic Review of Modelling Approaches for the Cost Effectiveness of HepatitisC Treatment with Direct-Acting Antivirals.

New direct-acting antivirals (DAAs) are highly effective for hepatitisC virus (HCV) treatment. However, their prices have been widely debated. Decision-analytic models can project the long-term value of HCV treatment. Therefore, understanding of the methods used in these models and how they could influence results is important. Our objective was to describe and systematically review the methodological approaches in published cost-effectiveness models of chronic HCV treatment with DAAs. We searched several electronic databases, including Medline, Embase and EconLit, from 2011 to 2015. Study selection was performed by two reviewers independently. We included any cost-effectiveness analysis comparing DAAs with the old standard of care for HCV treatment. We excluded non-English-language studies and studies not reporting quality-adjusted life-years. One reviewer collected data and assessed the quality of reporting, using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Another reviewer crosschecked the abstracted information. The development methods of the included studies were synthetized on the basis of good modelling practice recommendations. Review of 304 citations revealed 36 cost-effectiveness analyses. The reporting quality scores of most articles were rated as acceptable, between 67 and 100%. The majority of the studies were conducted in Europe (50%), followed by the USA (44%). Fifty-six percent of the 36 studies evaluated the cost effectiveness of HCV treatment in both treatment-naive and treatment-experienced patients, 97% included genotype1 patients and 53% evaluated the cost effectiveness of second-generation or oral DAAs in comparison with the previous standard of care or other DAAs. Twenty-one models defined health states in terms of METAVIR fibrosis scores. Only one study used a discrete-event simulation approach, and the remainder used state-transition models. The time horizons varied; however, 89% of studies used a lifetime horizon. One study was conducted from a societal perspective. Thirty-three percent of studies did not conduct any model validation. We also noted that none of the studies modelled HCV treatment as a prevention strategy, 86% of models did not consider the possibility of re-infection with HCV after successful treatment, 97% of studies did not consider indirect economic benefits resulting from HCV treatment and none of the studies evaluating oral DAAs used real-world data. The search was limited by date (from 1January 2011 to 8September 2015) and was also limited to English-language and published reports. Most modelling studies used a similar modelling structure and could have underestimated the value of HCV treatment. Future modelling efforts should consider the benefits of HCV treatment in preventing transmission, extra-hepatic and indirect economic benefits of HCV treatment, real-world cost-effectiveness analysis and cost effectiveness of HCV treatment in low- and middle-income countries.

O20.4 Transmission risk beliefs influence sexual risk behaviour of hiv-positive msm

Introduction Beliefs about the efficacy of antiretroviral treatment for decreasing risk of HIV transmission may influence a person’s sexual risk behaviour. We examined whether individuals’ HIV transmission risk beliefs predicted subsequent engagement in unprotected anal intercourse (UAI) among men who have sex with men (MSM). Methods HIV-positive and HIV-negative MSM were recruited for the longitudinal study in San Francisco using time-location sampling. Participants who completed both the baseline and 6-month follow-up behavioural surveys were included in the analysis (N = 773). Beliefs regarding HIV transmission risk at baseline and reported UAI with any sexual partner during the 6-month interval between the baseline and follow-up surveys were evaluated. Results UAI at baseline was associated with an increased likelihood of UAI at follow-up among both HIV-positive MSM (OR = 6.45, p Conclusion HIV-positive MSM who believed there was less risk of transmitting HIV due to the availability of antiretroviral treatment and post-exposure prophylaxis were more likely to engage in UAI. Concerns about the possibility of re-infection may have influenced some HIV-positive men to refrain from engaging in UAI. These findings suggest the need for prevention messages to highlight treatment adherence and viral suppression as important factors that affect the efficacy of antiretrovirals for reducing HIV transmission risk. Disclosure of interest statement This work was supported by the US National Institutes of Health [R01 MH077509].

Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C

To assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C. Eighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months. Seventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner. The incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID.

Construction of a mathematical model for tuberculosis transmission in highly endemic regions of the Asia-pacific

We present a mathematical model to simulate tuberculosis (TB) transmission in highly endemic regions of the Asia-Pacific, where epidemiology does not appear to be primarily driven by HIV-coinfection. The ten-compartment deterministic model captures many of the observed phenomena important to disease dynamics, including partial and temporary vaccine efficacy, declining risk of active disease following infection, the possibility of reinfection both during the infection latent period and after treatment, multidrug resistant TB (MDR-TB) and de novo resistance during treatment. We found that the model could not be calibrated to the estimated incidence rate without allowing for reinfection during latency, and that even in the presence of a moderate fitness cost and a lower value of R0, MDR-TB becomes the dominant strain at equilibrium. Of the modifiable programmatic parameters, the rate of detection and treatment commencement was the most important determinant of disease rates with each respective strain, while vaccination rates were less important. Improved treatment of drug-susceptible TB did not result in decreased rates of MDR-TB through prevention of de novo resistance, but rather resulted in a modest increase in MDR-TB through strain replacement. This was due to the considerably greater relative contribution of community transmission to MDR-TB incidence, by comparison to de novo amplification of resistance in previously susceptible strains.

Genetic Analysis of Primaquine Tolerance in a Patient with Relapsing Vivax Malaria

Patients with Plasmodium vivax malaria are treated with primaquine to prevent relapse infections. We report primaquine failure in a patient with 3 relapses without any possibility of re-infection. Using whole genome sequencing of the relapsing parasite isolates, we identified single nucleotide variants as candidate molecular markers of resistance.

Reply to Myers et al.

The authors agree with Myers et al. [1] that biodegradable materials represent a useful alternative in the management of tricuspid valve endocarditis repair. Our statement of dividing tricuspid valve repair choices in prosthetic and non-prosthetic techniques adequately sets the main cornerstones of surgical therapy: first, minimizing, as much as possible, the resulting valve regurgitation following repair and second, equally avoiding the use of any prosthetic material [2]. This is particularly important for injecting drug users who bear a high possibility of re-infection in the future. In this context, biodegradable ring annuloplasty of tricuspid valve could be included in non-prosthetic repair techniques, since after a few months not only would it be degraded, but also the subsequent development of a permanent network of fibrous connective tissue will have restored the normal valve function. Unfortunately, our experience with biodegradable ring annuloplasty or matrix scaffolds such as CorMatrix© is poor. On the contrary, others have noted both preliminary and mid-term successful results using biogradable materials [3] even though, their high cost is not to be dismissed, in the current era of stringent budget. On the other hand, in our and most of the surgeons’ opinion, autologous pericardium represents the primary option in the repair of any endocardial defect (congenital/acquired heart disease). Major advantages include its low cost, easyto-use, perfect incorporation within native structures, uncommon colonization by bacteria, rapid endothelization and high endurance even against high pressures of systemic circulation (left ventricle, aorta, etc.) [4]. Besides, patches of fresh autologous pericardium have been used with excellent shortand long-term results, in repairing mitral regurgitation due to annular dilatation, following posterior mitral annuloplasty [5]. Most importantly, the same material appears to be fundamental in the repair of tricuspid valve disease, particularly among patients with a high risk of long-term prosthetic valve endocarditis [6].

Cost–Effectiveness of Hepatitis C Virus Antiviral Treatment for Injection Drug User Populations

Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in most developed countries. HCV antiviral treatment (peginterferon-α + ribavirin) has been shown to be cost-effective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injecting drug users (IDUs) as compared with treating ex/non-IDUs or no treatment. A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after treatment failure, potential reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes measured in quality adjusted life years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic prevalence settings, with ICERs compared with no treatment of £ 521 and £ 2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared with no treatment of £ 6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared with ex/non-IDUs are halved. Despite the possibility of reinfection, the model suggests providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up and its impact on prevalence is warranted.

P53 The cost-effectiveness of HCV antiviral treatment for injecting drug user populations

IntroductionInjecting drug use is the main risk of HCV transmission in most developed countries. Hepatitis C virus antiviral treatment (peginterferon + ribavirin) is cost-effective for patients with no reinfection risk....

Survival in XDR TB: Shifting the Curve and Shifting the Paradigm

Survival in XDR TB: Shifting the Curve and Shifting the Paradigm

Hepatitis C virus (HCV) infection and re-infection among HCV- and HIV/HCV-infected injection drug users

The possibility of re-infection is often cited as a reason for not initiating treatment in injection drug users (IDUs). Recent observational data suggest that the rate of re-infection may be reduced following spontaneous or treatment-induced virologic clearance, although such data are often retrospective and incomplete. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P199 Cite this article as: Conway et al.: Hepatitis C virus (HCV) infection and re-infection among HCV- and HIV/HCV-infected injection drug users. Journal of the International AIDS Society 2010 13(Suppl 4):P199. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112981/

Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility

Hepatitis C virus antiviral treatment is effective for individual patients but few active injecting drug users are treated. We considered the utility of antiviral treatment for primary prevention of hepatitis C. A hepatitis C transmission model among injecting drug users was developed, incorporating treatment (62.5% average sustained viral response) with no retreatment after initial treatment failure, potential re-infection for those cured, equal genotype setting (genotype 1:genotype 2/3), and no immunity. In addition, we examined scenarios with varied treatment response rates, immunity, or retreatment of treatment failures. In the baseline scenario, annually treating 10 infections per 1000 injecting drug users results in a relative decrease in hepatitis C prevalence over 10 years of 31%, 13%, or 7% for baseline (untreated endemic chronic infection) prevalences of 20%, 40%, or 60%, respectively. Sensitivity analyses show that including the potential for immunity has minimal effect on the predictions; prevalence reductions remain even if SVR is assumed to be 25% lower among active IDU than current evidence suggests; retreatment of treatment failures does not alter the short-term (<5 years) projections, but does increase treatment gains within 20 years; hepatitis C free life years gained from treating active injecting drug users are projected to be higher than from treating non-injecting drug users for prevalences below 60%. Despite the possibility of re-infection, modest rates of hepatitis C treatment among active injecting drug users could effectively reduce transmission. Evaluating and extending strategies to treat hepatitis C among active injectors are warranted.