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In this feature, a panel of IDSA members reviews important new studies that have a significant impact on the practice of infectious diseases medicine.
For more from Clinical Infectious Diseases and The Journal of Infectious Diseases, see the "In the IDSA Journals" section of IDSA News.
New Studies on Hepatitis B, C Therapies
Prolonged treatment with low-dose peginterferon did not decrease the rate of disease progression in hepatitis C-infected patients who did not respond to initial antiviral therapy, according to a study published in the December 4 issue of The New England Journal of Medicine. In the same issue, a study on patients with hepatitis B infection found that tenofovir achieved viral suppression more often than adefovir.
There has been conflicting data about long-term peginterferon treatment of hepatitis C patients who have failed initial therapy with peginterferon and ribavirin. Some of the earlier nonrandomized observational studies had reported benefit for shorter courses of peginterferon therapy, but long-term outcomes have been uncertain.
More than 1,000 hepatitis C-infected patients with advanced liver fibrosis who had not responded to previous therapy were randomized to receive either 90 µg/week of peginterferon alfa-2a or placebo. Patients were followed every 3 months for 3.5 years and underwent liver biopsy at 1.5 and 3.5 years after randomization. The main outcome measure was progression of liver disease (death, hepatocellular carcinoma, hepatic decompensation, or an increase in pathologic scoring of fibrosis).
Although serum aminotransferases, hepatitis C viral load, and histological scores improved in the treatment arm, there was no difference in the primary outcome between the two groups. Only 60 percent of peginterferon patients tolerated therapy for the entire 3.5 years. Patients in the treatment arm were somewhat—but not significantly—more likely to experience serious adverse events as compared to the placebo group. (Bisceglie et al., N Engl J Med. 2008;359:2429-41.)
Tenofovir vs. Adefovir for Hepatitis B
There are seven drugs licensed for the treatment of hepatitis B infection. The authors of this study compared tenofovir DF to adefovir dipivoxil in 382 HBeAg-negative patients and 272 HBeAg-positive patients. The primary outcome was viral suppression and histologic improvement at 48 weeks.
In both groups, patients randomized to tenofovir DF had better viral suppression than those randomized to adefovir. Both drugs showed a similar improvement in histologic scores. Neither of the two groups developed resistance mutations by 48 weeks, but the investigators are planning a 7 year follow-up. The rates of side effects were similar. Of note, tenofovir was just as effective at suppressing HBV DNA in patients who had previously been treated with lamivudine as those who were treatment-naïve. (Marcellin et al., N Engl J Med. 2008;359:2442-55.)
For those interested, a National Institutes of Health Consensus Development Conference Statement on the management of Heptitis B was recently published. (Sorrell et al., Ann Intern Med.2009;150:104-110.)
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Respiratory Illness? Could Be Human Metapneumovirus
Infection with the newly identified human metapneumovirus (HMPV) occurs commonly in adults and should be considered as a possible diagnosis among patients with respiratory symptoms, according to a study in the December 8 edition of Archives of Internal Medicine.
HMPV was first identified in 2001 as a cause of respiratory tract infections in children. Walsh and colleagues aimed to assess the incidence and clinical manifestations of HMPV over four consecutive winter seasons in four different adult populations: the healthy elderly, young adults, high-risk adults with underlying cardiopulmonary disease, and hospitalized adults.
Most HMPV activity was in the late winter and early spring. HMPV infections occurred in 5.9 percent of healthy elderly subjects, 13.1 percent of young adults, 9.1 percent of high-risk adults, and 8.5 percent of hospitalized patients. Among subjects who tested positive for HMPV, asymptomatic infection was common, occurring in about 40 percent of the elderly and high-risk groups and 71 percent of healthy adults.
The most common symptoms among outpatients were nasal congestion, cough, and rhinorrhea. Most recorded temperatures were normal. Illness duration was long, with a mean of 10 days in young adults, 12 days in healthy elderly, and 16 days in high-risk adults. Physician phone calls, visits, and antibiotic prescription were common, especially among the high-risk adult group. In addition to the symptoms described above, hospitalized patients commonly had wheezing noted on exam (80.2 percent). Twenty-seven percent had an infiltrate noted on admission chest X-ray and 12 percent required intensive care.
This report demonstrates that HMPV contributes significantly to the burden of respiratory illness in the late winter and early spring. Clinicians should consider this diagnosis when assessing patients with respiratory symptoms and encourage local microbiology labs to test for it routinely. (Walsh et al., Arch Intern Med. 2008;168:2489-96.)
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Increasing Incidence of C. difficile in Hospitalized Children
As in adults, the incidence of Clostridium difficile-associated disease (CDAD) in hospitalized children is increasing, according to a report in the December 2008 issue of Pediatrics.
Using a national database that pools inpatient data from many institutions, the authors performed a retrospective cohort study to analyze epidemiological features of CDAD in hospitalized children between 2001 and 2006. Of all patients with ICD-9 codes for C. difficile infection, cases were included only if they had billing codes for a C. difficile toxin assay and documentation of C. difficile-targeted therapy. A total of 4,895 cases were identified.
Similar to the recently reported increases in adult populations, the annual incidence of CDAD increased from 2.6 to 4.0 cases per 1,000 admissions and from 4.4 to 6.5 cases per 100,000 patient days. Unlike recent changes in adult populations, however, there were no increases in colectomy rates or mortality rates in children over the study period.
This study is somewhat limited by its retrospective nature, which did not allow the authors to access clinical data to confirm CDAD cases. This is important to keep in mind when considering the surprisingly high percentage of CDAD cases that were identified in neonates and children less than one year of age – patient populations typically thought to be at very low risk for CDAD. It is difficult to say whether CDAD was incorrectly diagnosed and treated or if the epidemiology of CDAD is substantially changing in these young patients. Despite this caveat, this study successfully highlights overall increases in the incidence of CDAD in children.
(Kim et al., Pediatrics. 2008;122:1266-70.)
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QuantiFERON TB Test for Children?
The QuantiFERON-TB Gold test (QFT) was as sensitive as the tuberculin skin test (TST) for diagnosing latent tuberculosis (LTB) in children over 2 with recent exposure, according to a prospective study of 207 New York children published in the January 2009 issues of Pediatrics. Questions remain regarding the sensitivity of QFT in children less than 2 and among those with unknown exposure histories.
The CDC recommends IFN-g-releasing assays, such as the QFT, for use in diagnosing LTB. While the QFT has been shown to perform well in adults, data are lacking regarding the sensitivity and specificity of these tests among children living in regions of low TB endemicity.
This study indicates that use of the QFT assay should result in fewer false positives and hence fewer children receiving unnecessary prophylaxis. But, the QFT test was less sensitive in young children, who produce lower levels of IFN-g. Furthermore, the sensitivity of QFT appears to decrease with increasing time after initial exposure. The lower sensitivity in these two groups of children suggests that switching from the TST to the QFT may leave some children at risk for active TB; thus, further studies are needed.
(Lighter et al., Pediatrics. 2009;123:30–37.)
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