Archive for February, 2011

Dose‐Dependent Risk of Neutropenia after 7‐Day Courses of Artesunate Monotherapy in Cambodian Patients with Acute Plasmodium falciparum Malaria

Clinical Infectious Diseases 15 December 2010  V.51  N.12 e.105-114

Delia Bethell,1 Youry Se,1 Chanthap Lon,1 Duong Socheat,2 David Saunders,1 Paktiya TejaIsavadharm,1 Phisit Khemawoot,1 Sea Darapiseth,2 Jessica Lin,1 Sabaithip Sriwichai,1 Worachet Kuntawungin,1 Sittidech Surasri,1 Sue J. Lee,3 Ses Sarim,4 Stuart Tyner,1 Bryan Smith,1 and Mark M. Fukuda1

1Armed Forces Research Institute of Medical Sciences, Bagkok, Thailand; 2Center for Parasitology, Entomology and Malaria Control, Pnom Penh, Cambodia; 3Mahidol Oxford Research Unit, Bangkok, Thailand; and 4Tasanh Health Center, Samlot, Cambodia

Background

Fears of emerging artemisinin resistance in western Cambodia have prompted a series of clinical trials investigating whether slow responses to antimalarial treatment can be overcome by increasing doses of drug.

Methods

Patients with uncomplicated malaria were allocated 1 of 3 oral artesunate monotherapy regimens (2, 4, or 6 mg/kg/day for 7 days) and were observed for 42 days. A series of safety measures, including complete blood count on days 0, 3, 6, and 14, was implemented because of a lack of safety data for these experimental doses.

Results

After 3 doses, geometric mean absolute neutrophil counts were reduced in all groups, and 2 patients required artesunate to be discontinued because of neutropenia (absolute neutrophil count, <1.0×103 cells/μL). Recipients of the 6 mg/kg/day dosage had significantly lower geometric mean absolute neutrophil counts than did recipients of the 2 and 4 mg/kg/day dosages at 6 and 14 days (P<.001 for each). Overall, 5 (19%) of 26 patients who received the 6 mg/kg/day dosage became neutropenic within 14 days, triggering a cohort‐halting rule and ending the trial early. Pharmacokinetic data from neutropenic patients showed wide variance, with plasma clearance occurring significantly slower in neutropenic patients than in nonneutropenic patients.

Conclusions

Artesunate remains a crucial drug for the treatment of malaria, and determining optimal dosing regimens is vital to overcome emerging resistant parasite strains along the Thai‐Cambodian border. However, future experimental dosing studies must be designed with care, because the safety of such regimens can no longer be assumed. The artemisinin derivatives remain one of the safest classes of antimalarial drugs, but this study demonstrates that the dosing limit may have been reached.

abstract

http://www.journals.uchicago.edu/doi/abs/10.1086/657402

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/657402

February 24, 2011 at 6:15 pm Leave a comment

Protective Efficacy of Seasonal Influenza Vaccination against Seasonal and Pandemic Influenza Virus Infection during 2009 in Hong Kong Benjamin

Clinical Infectious Diseases 15 December 2010  V.51  N.12 p.1370-79

J. Cowling,1 Sophia Ng,1 Edward S. K. Ma,2 Calvin K. Y. Cheng,1 Winnie Wai,1 Vicky J. Fang,1 KwokHung Chan,2 Dennis K. M. Ip,1 Susan S. Chiu,3 J. S. Malik Peiris,2,4,a and Gabriel M. Leung1,a

1Infectious Disease Epidemiology Group, School of Public Health, Li Ka Shing Faculty of Medicine, Departments of 2Microbiology and 3Pediatrics and Adolescent Medicine, The University of Hong Kong, and 4HKUPasteur Research Centre, Hong Kong Special Administrative Region, China

Background

The relationship between seasonal influenza vaccine and susceptibility to 2009 pandemic A/H1N1 virus infection is not fully understood.

Methods

One child 6–15 years of age from each of 119 households was randomized to receive 1 dose of inactivated trivalent seasonal influenza vaccine (TIV) or saline placebo in November 2008. Serum samples were collected from study subjects and their household contacts before and 1 month after vaccination (December 2008), after winter (April 2009) and summer influenza (September–October 2009) seasons. Seasonal and pandemic influenza were confirmed by serum hemagglutinination inhibition, viral neutralization titers, and reverse‐transcription polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes.

Results

TIV recipients had lower rates of serologically confirmed seasonal A/H1N1 infection (TIV group, 8%; placebo group, 21%;  ) and A/H3N2 infection (7% vs 12%;  ), but higher rates of pandemic A/H1N1 infection (32% vs 17%;  ). In multivariable analysis, those infected with seasonal influenza A during the study had a lower risk of laboratory‐confirmed pandemic A/H1N1 infection (adjusted odds ratio [OR], 0.35; 95% confidence interval [CI], 0.14–0.87), and receipt of seasonal TIV was unassociated with risk of pandemic A/H1N1 infection (adjusted OR, 1.11; 95% CI, 0.54–2.26).

Conclusions

TIV protected against strain‐matched infection in children. Seasonal influenza infection appeared to confer cross‐protection against pandemic influenza. Whether prior seasonal influenza vaccination affects the risk of infection with the pandemic strain requires additional study.

Clinical trials registration.ClinicalTrials.gov number NCT00792051.

abstract

http://www.journals.uchicago.edu/doi/abs/10.1086/657311

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/657311

EDITORIAL COMMENTARY

How Did the 2008–2009 Seasonal Influenza Vaccine Affect the Pandemic?

W. Paul Glezen

Department of Molecular Virology and Microbiology and Department of Pediatrics, Baylor College of Medicine, Houston, Texas

Full Text

http://www.journals.uchicago.edu/doi/full/10.1086/657312

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/657312

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February 24, 2011 at 6:13 pm Leave a comment

Preserving the Lifesaving Power of Antimicrobial Agents

JAMA February 22, 2011

James M. Hughes, MD

Infectious Diseases Society of America, Arlington, Virginia, and Department of Medicine and Hubert Department of Global Health, School of Medicine and Rollins School of Public Health, Emory University, Atlanta, Georgia.

Corresponding Author: James M. Hughes, MD, Emory University, 1462 Clifton Rd, Ste 446 Mailstop 1370/004/1AD, Atlanta, GA 30322 (jmhughe@emory.edu).

Among the most important medicines ever discovered, antimicrobial agents have saved millions of lives and improved the outcomes for countless patients since these drugs were introduced in the early 1930s. However, the effectiveness of these lifesaving resources is at risk. Many medical advances that physicians and patients take for granted—including cancer treatment, surgery, transplantation, and neonatal care—are endangered by increasing antibiotic resistance and a distressing decline in the antibiotic research and development pipeline …

Full Text

http://jama.ama-assn.org/content/early/2011/02/21/jama.2011.279.full?etoc=

PDF

http://jama.ama-assn.org/content/early/2011/02/21/jama.2011.279.full.pdf+html

February 22, 2011 at 11:59 pm Leave a comment

2011 CAMPAÑA NACIONAL VACUNACION ANTIGRPAL

Ministerio de Salud de la Nación Argentina

 Lineamientos Técnicos pag.7 a 26

Manual del Vacunador pag.27 a 52

 Texto Completo

http://www.msal.gov.ar/gripe/5_equipos/info_equipos/lineamientos_tecnicos_gripe_2011.pdf

February 21, 2011 at 4:32 pm Leave a comment

A Randomized Controlled Study of Accelerated Versus Standard Hepatitis B Vaccination in HIV-Positive Patients

Theodora E.M.S. de Vries-Sluijs1, Bettina E. Hansen2,3, Gerard J.J. van Doornum4, Robert H. Kauffmann5, Eliane M.S. Leyten6, Tania Mudrikova7, Kees Brinkman8, Jan G. den Hollander9, Frank P. Kroon10, Harry L.A. Janssen2, Marchina E. van der Ende1 and Robert A. de Man2

1Department of Internal Medicine-Infectious Diseases

2Department of Gastroenterology and Hepatology

3Department of Biostatistics

4Department of Virology, Erasmus MC, Rotterdam

5Department of Internal Medicine, Haga Hospital, location Leyenburg

6Department of Internal Medicine, Medical Center Haaglanden, The Hague

7Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht

8Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam

9Department of Internal Medicine, Maasstad Hospital, location Clara, Rotterdam

10Department of Infectious Diseases, LUMC, Leiden, The Netherlands

Abstract

Background

In human immunodeficiency virus (HIV)−infected patients, the immunogenicity of hepatitis B vaccines is impaired. The primary and secondary aims of our study were to investigate the effectiveness and compliance of 2 different vaccination regimen in an HIV-infected population.

Methods

A noninferiority trial with a 10% response margin was designed. Included were patients ≥18 years old, with negative HBsAg/anti-HBc serology, and not previously vaccinated against hepatitis B. Patients were stratified according to CD4+ cell count: <200, 200–500, >500. Participants received 10 μg HBvaxPRO intramuscularly according to a 0–1–3 week schedule or the standard 0–4–24 week schedule. Anti-HBs levels were measured at week 28, considered protective ≥10 IU/L.

Results

Modified intention to treat analysis in 761 patients was performed. Overall response difference was 50%(standard arm) versus 38.7% (accelerated arm) =11.3% (95% confidence interval [CI], [4.3, 18.3]), close to the 10% response margin. In CD4+ cell count group 200–500 cells/mm3, the response difference was 20.8% (95% CI [10.9, 30.7]). However, the response difference in CD4+cell count group >500 cells/mm3 was -1.8% (95% CI [-13.4,+9.7]). Compliance was significantly superior with the accelerated schedule, 91.8% versus 82.7% (P ≤ .001).

Conclusion

In HIV-infected patients, compliance with an accelerated hepatitis B vaccination schedule is significantly better. The efficacy of an accelerated schedule proved to be non-inferior in CD4+ cell count group >500 cells/mm3.

abstract

http://jid.oxfordjournals.org/content/early/2011/01/25/infdis.jiq137

PDF

http://jid.oxfordjournals.org/content/early/2011/01/25/infdis.jiq137.full.pdf+html

February 19, 2011 at 12:01 pm Leave a comment

Streptococcal Pharyngitis – Clinical Practice

N Engl J of Medicine Feb.17, 2011  V.364 p.648-655

Michael R. Wessels, M.D.

A 10-year-old girl presents with a sore throat and fever that has lasted for 1 day. She appears flushed and moderately ill. Physical examination reveals a temperature of 39°C, tender bilateral anterior cervical lymph nodes that are 1 to 2 cm in the greatest dimension, and erythema and whitish-yellow exudate over enlarged tonsils and the posterior pharynx. A rapid antigen-detection test from a throat-swab specimen is positive for group A streptococcus. How should the patient be evaluated and treated? …

Full Text

http://www.nejm.org/doi/full/10.1056/NEJMcp1009126?query=TOC

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMcp1009126

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February 17, 2011 at 11:34 am Leave a comment

Increasing incidence of ischemic stroke in patients with HIV infection.

Neurology. 2011 Feb 1  V.76 N.5 p.444-50.

Ovbiagele B, Nath A.

Stroke Center and Department of Neuroscience, University of California at San Diego, 200 West Arbor Drive, MC 8466, San Diego, CA 92103-8466 bruce.ovibes@gmail.com.

Abstract

BACKGROUND

Large-scale epidemiologic data on stroke in HIV-infected persons are scarce, especially in an era of combination antiretroviral therapies, which have prolonged patient survival, but may boost stroke risk. We assessed trends in the proportion of HIV infection among patients with stroke in the United States.

METHODS

Data were obtained from all states within the United States that contributed to the Nationwide Inpatient Sample. All patients admitted to hospitals between 1997 and 2006 with a primary discharge diagnosis of stroke (identified by the International Classification of Diseases, Ninth Revision procedure codes) were included. Time trends in the proportion of these patients with HIV diagnosis were computed, and independent predictors of comorbid HIV diagnosis evaluated using multivariable logistic regression.

RESULTS

Of all (ischemic and hemorrhagic) stroke hospitalizations, patients with comorbid HIV infection constituted 0.09% in 1997 vs 0.15% in 2006 (p < 0.0001). Actual numbers of overall US stroke hospitalizations lessened 7% (998,739 to 926,997), while actual numbers of stroke hospitalizations with coexisting HIV infection rose 60% (888 to 1,425). Patients with comorbid HIV infection comprised 0.08% of ischemic strokes in 1997 vs 0.18% in 2006 (p < 0.0001), but their proportion of hemorrhagic strokes did not significantly change. Factors independently associated with higher odds of comorbid HIV diagnosis were Medicaid insurance, urban hospital type, dementia, liver disease, renal disease, and cancer.

CONCLUSION

Over the last decade in the United States, there has been a substantial and significant rise in patients hospitalized for stroke with coexisting HIV infection. This has important public health and socioeconomic consequences.

abstract

http://www.ncbi.nlm.nih.gov/pubmed/21248273?dopt=Abstract

February 16, 2011 at 11:12 am Leave a comment

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