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December 2011/January 2012
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IDSA Journal Club
December 2011/January 2012

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.

Environmental Factors that Impact HCV Transmission
Reviewed by Jonathan Li, MD

As many as 170 million people are infected with hepatitis C virus (HCV) worldwide, and HCV incidence in injection drug users (IDUs) may be as high as 40 infections per 100 person-years, according to estimates. Harm reduction strategies have significantly reduced rates of HIV infection among IDUs but have had a far smaller impact on HCV. In addition, a number of HCV outbreaks have been reported in health-care settings linked to either contaminated products or equipment. The high prevalence of HCV is thought to be due to the higher transmissibility of the virus and its durability in the environment. Two recent studies in The Journal of Infectious Diseases shed more light on environmental factors that may decrease HCV transmission.

In the first study, 620 pieces of used IDU equipment (needles, syringes, filters, cups, water, alcohol swabs, and cotton pads) were collected from a cohort of HCV infected individuals and a separate validation cohort of IDUs in the community with unknown HCV serostatus. Items were pooled in groups of 10 for HCV RNA testing. In both groups, HCV RNA was detected in more than 80 percent of pooled compress material (alcohol swabs and cotton pads) and in more than 30 percent of pooled syringe washes. In addition, HCV viral loads were much higher within the compress material than the syringes.

In the second study, researchers used a recently developed HCV cell culture system to test the ability of various disinfectants and environmental conditions in decreasing the infectivity of dried HCV. They found that in the presence of serum, infectious HCV could be reconstituted for up to five days after drying but could be inactivated by all six of the commercially available disinfectants that were tested. Finally, the authors found that heating dried HCV to ≥65oC in a spoon cooker (80-95 seconds using a tea light until small bubbles began appearing) was required to inactivate the virus.

These studies provide valuable insight into mechanisms of HCV transmission and also provide specific targets for prevention efforts, namely emphasizing the need to avoid sharing compression material (including alcohol swabs) and the prolonged heating of injected material. The effectiveness of commercially available disinfectants to inactivate HCV highlights the need to strictly adhere to hospital infection control measures to prevent transmission in the health-care setting.

(Thibault et al. J Infect Dis. 2011;204(12):1839-42 and Doerrbecker et al. J Infect Dis. 2011;204(12):1830-8.)

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Long-Term Follow-Up of PFAPA Patients
Reviewed by Jason B. Weinberg, MD

Long-term outcomes are good in patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, according to an article in the December 2011 issue of the Journal of Pediatrics.

Children with PFAPA are often evaluated in infectious diseases clinics because of the fevers, which are accompanied by other characteristic features and typically recur at regular intervals in the absence of documented infections. This study details up to 21 years of follow-up of a cohort of 94 patients with PFAPA that was assembled beginning in 1988 using strict diagnostic criteria.

Fever episodes ended at a median age of 9.2 years in the majority of 59 patients who could be surveyed. Episodes were shorter and less frequent in the nine patients who continued to have episodes of fever. Glucocorticoid therapy was deemed effective in 37 of 44 (84 percent) patients, while cimetidine was effective in six of 25 (24 percent) patients. Only 12 patients underwent tonsillectomy or adenotonsillectomy, but nine of these patients (75 percent) reported very effective results, with complete remission of episodes occurring in six patients at some point following surgery. Only three patients from the cohort ultimately received alternative diagnoses, none of which included infections.

Although the pathogenesis of PFAPA remains unclear, this valuable study helps to define its natural history. In doing so, it will help practitioners reassure patients with PFAPA and their families of the likelihood that the episodes spontaneously resolve as well as the patients’ very good long-term prognosis.

(Wurster et al. J Pediatr 2011; 159:958-64.)

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Short-Course Combination Therapy for Latent TB
Reviewed by Jason B. Weinberg, MD

Three months of therapy with rifapentine and isoniazid was as effective as nine months of isoniazid in preventing tuberculosis (TB), according to a study published in the Dec. 8, 2011 edition of The New England Journal of Medicine.

In an open-label, randomized, noninferiority trial, 8,053 subjects over 2 years of age who were at high risk for developing TB received either three months of once-weekly rifapentine and isoniazid or nine months of daily isoniazid. Treatment was given under direct observation for the combination group and self-administered for the isoniazid-only group. Combination therapy was noninferior to the isoniazid-only regimen in preventing tuberculosis, with cumulative proportions of subjects developing tuberculosis of 0.19 percent in the combination-therapy group and 0.43 percent in the isoniazid-only group. Subjects in the combination group were more likely to complete treatment than subjects receiving only isoniazid. Combination-therapy subjects were more likely to discontinue treatment due to an adverse event, although they were less likely to develop adverse events overall and hepatotoxicity in particular.

Treatment of latent TB is a mainstay of TB-control programs, but overall success is limited by poor compliance and side effects associated with long-term, daily medication regimens. This study was limited by the small number of patients in each group who developed TB. Additional data are needed to confirm efficacy and safety of the combined regimen in HIV-infected patients and children, who represented only a small proportion of the subjects in this study. However, the results of this study provide additional evidence that short-term combination regimens can be effective in preventing TB. 

(Sterling et al. N Engl J Med. 2011; 365:2155-66.)

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Weekly Atovaquone-Proguanil for Malaria Prevention
Reviewed by Kathryn E. Stephenson, MD, MPH

Malaria is the primary cause of febrile illness in returning travelers, but adherence to daily malaria chemoprophylaxis can be difficult for many patients. The use of weekly chemoprophylaxis with chloroquine or hydroxychloroquine is limited by widespread malaria resistance to these agents, and weekly mefloquine is associated with neuropsychiatric side effects. Thus, an additional weekly chemoprophylaxis regimen for prevention would greatly benefit the field of travel medicine.

A Jan. 15, 2012, report in Clinical Infectious Diseases describes a randomized, placebo-controlled, double-blind trial of once-weekly atovaquone-proguanil (A-P) for the prevention of Plasmodium falciparum using a human P. falciparum challenge model. Thirty volunteers were randomly assigned to receive either A-P 250/100 mg one day prior to malaria challenge, A-P 250/100 mg four days after challenge, A-P 250/100 mg seven days prior to challenge, A-P 500/200 mg seven days prior to challenge, or A-P 1000/400 mg seven days prior to challenge. All volunteers were exposed to P. falciparum sporozoites by having five infected mosquitoes feed on their forearms for five minutes. Infection was determined through serial microscopy and clinical monitoring.

After sporozoite challenge, three volunteers developed parasitemia: two volunteers who received A-P 250/100 seven days prior to challenge, and one who received A-P 1000/400 mg seven days prior to challenge. All volunteers who received A-P 250/100 four days after sporozoite exposure were protected from parasitemia. The authors conclude that a single dose of A-P provides significant chemoprophylaxis against P. falciparum challenge and argue that weekly dosing would likely be 100 percent effective.

Follow-up clinical trials involving more patients in the field are needed to establish efficacy of a weekly A-P regimen for the prevention of malaria. However, this study provides evidence that a few missed doses of A-P per week should not greatly impact prophylactic efficacy.

(Deye et al. Clin Infect Dis. 2012;54(2):232-239.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

January 15

  • Antibiotic Resistance—It’s Not All Our Fault
  • “Slingshotting” Through Biofilm
  • Daptomcin and Cationic Antimicrobial Peptides

January 1

  • Genomic Variability of Cytomegalovirus is Comparable to That Seen in HIV
  • DRACOnian Antivirals or the “Greatest Discovery Since Penicillin: A Cure for Everything—From Colds to HIV”
  • Controlling Dengue

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