Posts filed under ‘Antivirales no HIV’

Is cytomegalovirus reactivation increasing the mortality of patients with severe sepsis?

Crit Care. 2011;15(2):138.

Kalil AC1, Florescu DF.

Author information

1 Department of Internal Medicine, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198, USA. akalil@unmc.edu

Abstract

Cytomegalovirus (CMV) is a ubiquitous virus present in approximately two-thirds of the healthy population.

This virus rarely causes an active disease in healthy individuals, but it is among the most common opportunistic infections in immunocompromised patients such as solid organ transplant recipients, patients receiving chemotherapy for cancer or patients with human immunodeficiency virus.

Critically ill patients who are immunocompetent before intensive care unit admission may also become more prone to develop active CMV infection if they have prolonged hospitalizations, high disease severity, and severe sepsis.

The development of active CMV infection in these critically ill patients has been associated with a significantly higher risk of death in several previous studies.

The present issue of Critical Care brings a new study by Heininger and colleagues in which the authors found that patients with severe sepsis who developed active CMV infection had significantly longer intensive care unit and hospital stays, prolonged mechanical ventilation, but no changes in mortality compared to patients without CMV infection.

We discuss the possible reasons for their findings (for example, selection bias and low (20%) statistical power to detect mortality endpoints), and also perform an update of our previous meta-analysis with the addition of Heininger and colleagues’ study to verify whether the higher mortality rate with CMV holds.

Our updated meta-analysis with approximately 1,000 patients shows that active CMV infection continues to be associated with a significant 81% higher mortality rate than that in critically ill patients without active CMV infection.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219353/pdf/cc10093.pdf

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March 24, 2018 at 10:58 am

Adenovirus Type 4 Respiratory Infections among Civilian Adults, Northeastern United States, 2011–2015

Emerg Infect Dis. 2018 V.24 N.2 P.201-209

Adriana E. KajonComments to Author , Daryl M. Lamson, Camden R. Bair, Xiaoyan Lu, Marie L. Landry, Marilyn Menegus2, Dean D. Erdman, and Kirsten St. George

Author affiliations: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA (A.E. Kajon, C.R. Bair); New York State Department of Health, Albany, New York, USA (D.M. Lamson, K. St. George); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (X. Lu, D.D. Erdman); Yale University School of Medicine, New Haven, Connecticut, USA (M.L. Landry); University of Rochester Medical Center, Rochester, New York, USA (M. Menegus)

Abstract

Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011–2015.

Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities.

HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases.

Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician’s office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults.

FULL TEXT

https://wwwnc.cdc.gov/eid/article/24/2/17-1407_article

PDF

https://wwwnc.cdc.gov/eid/article/24/2/pdfs/17-1407.pdf

 

 

February 9, 2018 at 6:47 pm

Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community.

Proc Natl Acad Sci U S A 2018 Jan; 115:1081.

Yan J et al

Significance

Lack of human data on influenza virus aerosol shedding fuels debate over the importance of airborne transmission. We provide overwhelming evidence that humans generate infectious aerosols and quantitative data to improve mathematical models of transmission and public health interventions. We show that sneezing is rare and not important for—and that coughing is not required for—influenza virus aerosolization. Our findings, that upper and lower airway infection are independent and that fine-particle exhaled aerosols reflect infection in the lung, opened a pathway for a deeper understanding of the human biology of influenza infection and transmission. Our observation of an association between repeated vaccination and increased viral aerosol generation demonstrated the power of our method, but needs confirmation.

Abstract

Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1–3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.

FULL TEXT

http://www.pnas.org/content/115/5/1081

PDF

http://www.pnas.org/content/pnas/115/5/1081.full.pdf

February 8, 2018 at 8:40 pm

IDSA/AASLD Response to Cochrane Review on Direct-Acting Antivirals for Hepatitis C

Clinical Infectious Diseases December 2017 V.65 N.11

EDITOR’S CHOICE

William G Powderly; Susanna Naggie; Arthur Y Kim; Hugo E Vargas; Raymond T Chung …

A recent Cochrane Review with the stated objective to assess the benefits and harms of direct-acting antiviral (DAA) therapy for people with chronic hepatitis C virus (HCV) infection raised alarms within the hepatology and infectious diseases communities because the authors concluded that there was insufficient evidence to confirm or reject an effect of DAA therapy on HCV-related morbidity (cirrhosis, hepatic decompensation, or hepatocellular carcinoma) or all-cause mortality [1]. The authors also concluded that the clinical relevance of sustained virological response (SVR) obtained with DAAs is questionable, as it is a nonvalidated surrogate outcome. The Review further stated that because all DAA trials and outcome results were at high risk of bias, their results presumably overestimated benefit and underestimated harm. Indeed, the plain language summary stated that the lack of valid evidence and the possibility of potentially harming people with chronic hepatitis should be considered before treating people with hepatitis C using DAAs. Based on the findings of this Review, the authors concluded that additional randomized clinical trials are needed to assess the long-term clinical effects of DAAs…

PDF (hacer CLIC en PDF)

https://academic.oup.com/cid/article/65/11/1773/3965298

November 29, 2017 at 8:21 am

The road to elimination of hepatitis C: analysis of cures versus new infections in 91 countries

Journal of Virus Eradication July 2017

Andrew M Hill1* , Sanjay Nath2 , Bryony Simmons2

1 Department of Translational Medicine, University of Liverpool, UK

2 Faculty of Medicine, Imperial College London, UK

Abstract

Background

Hepatitis C (HCV) can only be eradicated if annual rates of cure (SVR) are consistently and significantly higher than new HCV infections, across many countries. In 2016, the WHO called for a 90% reduction in new HCV infection by 2030. Direct-acting antivirals (DAA) can cure the majority of those treated, at around 90% in most populations, at potentially very low prices. We compared the net annual change in epidemic size across 91 countries using data on SVR, new HCV infections, and deaths. In a further 109 countries, we projected this figure using regional averages of epidemic size.

Methods

Epidemiological data for 2016 were extracted from national reports, publications and the Polaris Observatory. There were 91/210 countries with data on SVR, HCV-related deaths and new infections available for analysis; 109 countries had net change in epidemic size projected from the regional prevalence of HCV, extrapolated to their population size. ‘Net cure’ was defined as the number of people with SVR, minus new HCV infections, plus HCV-related deaths in 2016.

Results

For the 91 countries analysed, there were 57.3 million people with chronic HCV infection in 2016. In the remaining 109 countries, the projected epidemic size was 12.2 million, giving a global epidemic size of 69.6 million. Across the 91 countries, there was a fall from 57.3 to 56.9 million people in 2017, a 0.7% reduction. The projected global net change was from 69.6 to 69.3 million, a 0.4% reduction. Ten countries had at least five times more people reaching SVR than new HCV infections, including Egypt and USA. In 47/91 countries, there were more HCV infections than SVR in 2016.

Conclusion

Very few countries are on target to achieve elimination of HCV as a public health problem by 2030. While the North American, North African/Middle East and Western European regions have shown small declines in prevalence, the epidemic is growing in sub-Saharan Africa and Eastern Europe. Far higher rates of DAA treatment are required for worldwide elimination of HCV.

FULL TEXT

http://viruseradication.com/journal-details/The_road_to_elimination_of_hepatitis_C:_analysis_of_cures_versus_new_infections_in_91_countries/

September 25, 2017 at 8:21 am

Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases April 2017 V.4 N.2

Philippe Lachance; Justin Chen; Robin Featherstone; Wendy I. Sligl

Background.

The aim of our systematic review was to investigate the association between cytomegalovirus (CMV) reactivation and outcomes in immunocompetent critically ill patients.

Methods.

We searched electronic databases and gray literature for original studies and abstracts published between 1990 and October 2016. The review was limited to studies including critically ill immunocompetent patients. Cytomegalovirus reactivation was defined as positive polymerase chain reaction, pp65 antigenemia, or viral culture from blood or bronchoalveolar lavage. Selected patient-centered outcomes included mortality, duration of mechanical ventilation, need for renal replacement therapy (RRT), and nosocomial infections. Health resource utilization outcomes included intensive care unit and hospital lengths of stay.

Results.

Twenty-two studies were included. In our primary analysis, CMV reactivation was associated with increased ICU mortality (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.87–3.47), overall mortality (OR, 2.02; 95% CI, 1.60–2.56), duration of mechanical ventilation (mean difference 6.60 days; 95% CI, 3.09–10.12), nosocomial infections (OR, 3.20; 95% CI, 2.05–4.98), need for RRT (OR, 2.37; 95% CI, 1.31–4.31), and ICU length of stay (mean difference 8.18 days; 95% CI, 6.14–10.22). In addition, numerous sensitivity analyses were performed.

Conclusions.

In this meta-analysis, CMV reactivation was associated with worse clinical outcomes and greater health resource utilization in critically ill patients. However, it remains unclear whether CMV reactivation plays a causal role or if it is a surrogate for more severe illness.

PDF

https://watermark.silverchair.com/api/watermark?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdcwggHTBgkqhkiG9w0BBwagggHEMIIBwAIBADCCAbkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMgS29QRsi_OI3SkaMAgEQgIIBigRs9nl2ylsVhYS_sYzV1Exhw5kNEVc_CDMHi9al85en5nmbiM0fSguSAPaX7eVjsRODgkAPeEpkpHFXtT5ee2umJp97CEvGaAbkiVReIdzG4W2RNfMvE2sN1dsphR2nXEn42SJyigJqE4fzz8cIaXZ_D-EACpZzDmIRmUo86ZcUsycSI2PzFbJFj19cTvvoID75bRPJGugrZ8SAfBf6V6-1IrrVl8xG1P7LAmi8eED3QPkcOjtAWOyzyW8WPYJ_5JOJPPAUzlNTmWAKP_9QjSg3NBavgOdzFrhwpzWnF7DYh5qVYp2bg2jrG3iXICmUVNPuC32npr3L2qEWvfmA4-_gQfRgRLvm8G42pCbdO1bBp5NGgHoMFnGHIlF3s-z4Xx7as7oIryKBJsd-MG9CE5kkL9d_x6nJLEr-WqRPZF6rmWl_0VWYfbOyAIn7u3OJrtX9NrLBsFWsmCxKa7Ghsvbvfkk9jpoerEn8x48ljyevLRq7bimX0gm-Vgo3GtltcVdajTLQ5-rUsEQ

September 3, 2017 at 6:43 pm

Editor’s Choice: Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don’t Change a Thing

Clinical Infectious Diseases January 1, 2017 V.64 N.1 P.92-99

Susanna Naggie, David P. Holland, Mark S. Sulkowski, and David L. Thomas

1Duke Clinical Research Institute

2Duke University School of Medicine, Durham, North Carolina

3Emory University School of Medicine, Atlanta, Georgia

4Johns Hopkins School of Medicine, Baltimore, Maryland

Currently, 380 000–400 000 occupational exposures to blood-borne pathogens occur annually in the United States. The management for occupational HIV or hepatitis B virus exposures includes postexposure prophylaxis (PEP) when necessary; however, PEP is not recommended for hepatitis C virus (HCV) exposures.

Recent approval of HCV direct-acting antivirals (DAAs) has renewed discussions as to whether these therapies could be used to prevent infection after exposure. There are no published studies addressing this question, but the prescribing of DAAs for PEP has been reported.

We will discuss the differences in transmission of the 3 most common blood-borne pathogens, the natural history of early HCV infection, and the scientific rationale for PEP.

In particular, we will discuss how the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use.

PDF

https://cid.oxfordjournals.org/content/64/1/92.full.pdf+html

 

 

Clinical Infectious Diseases January 1, 2017 V.64 N.1 P.100-101

Editor’s Choice: Editorial Commentary: Decision Science at Work: The Case of Hepatitis C Virus Postexposure Prophylaxis

Joshua A. Barocas and Benjamin P. Linas

1Division of Infectious Diseases, Massachusetts General Hospital

2Boston University Schools of Medicine and Public Health

3Boston Medical Center, Massachusetts

In this issue of Clinical Infectious Diseases, Naggie et al discuss clinical decision making and present the results of a decision analysis examining the cost of hepatitis C virus (HCV) postexposure prophylaxis (PEP) among healthcare workers who experience a needlestick exposure to HCV-positive body fluids.

The authors discuss that, in an era when we can cure essentially all HCV infections, there are only 3 motivations for PEP. First, it may make sense to use PEP to prevent infections if doing so would decrease HCV transmission during the period of active HCV viremia. The paper succinctly reviews the evidence and quickly makes clear that among healthcare workers in the United States with a known HCV exposure, basic universal precautions reduce the risk of forward transmission to essentially zero.

A second motivation might be cost. Given that HCV medications are expensive, a shorter course PEP may be cost saving compared with full treatment for HCV infection. To address the possible economic rationale for PEP, the authors developed a decision tree to estimate the costs of PEP for HCV in a hypothetical cohort of 100 healthcare workers who had suffered a needlestick injury. They used the model to compare the outcomes with PEP to those with a strategy of “no PEP and treat only patients who develop chronic HCV infection.”

A few notable assumptions were made—namely, that PEP was 100% effective at preventing infection, while treatment for chronic HCV was only 98% effective with the first line of therapy. In addition, individuals who failed first-line treatment for chronic HCV infection were retreated with 100% . . .

PDF

https://cid.oxfordjournals.org/content/64/1/100.full.pdf+html

August 19, 2017 at 10:30 am

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