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What's new in infectious diseases

Disclosures: Elinor L Baron, MD, DTMH Employee of UpToDate, Inc. Allyson Bloom, MD Employee of UpToDate, Inc. Anna R Thorner, MD Employee of UpToDate, Inc. Jennifer Mitty, MD, MPH Employee of UpToDate, Inc.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2014. | This topic last updated: Apr 16, 2014.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


New formulations of posaconazole for antifungal prophylaxis (March 2014)

Posaconazole, an azole antifungal agent with activity against yeasts and molds, was previously available only as a suspension requiring oral intake, optimally with a high-fat meal, for effective absorption. The US Food and Drug Administration approved two new formulations, a delayed-release tablet and an IV formulation, for the prophylaxis of invasive Aspergillus and Candida infections in patients at high risk for these infections, such as those with hematologic malignancies with prolonged chemotherapy-induced neutropenia and hematopoietic cell transplant recipients with graft-versus-host disease [1]. The delayed release tablets are useful in patients who cannot eat a full meal, since they result in higher plasma drug concentrations than the oral suspension regardless of food intake. The IV formulation is useful for patients who are unable to take medications orally or who are expected not to absorb oral medications, but should generally be avoided in patients with moderate or severe renal impairment (CrCl <50 mL/min) due to the potential for toxic accumulation of the cyclodextrin vehicle. (See "Pharmacology of azoles", section on 'Posaconazole'.)

Fluoroquinolones and retinal detachment (December 2013)

Two observational studies report conflicting findings regarding an association between fluoroquinolone use and retinal detachment. A previously published case-control study of patients in Canada who visited an ophthalmologist found a small increased rate of retinal detachment in patients receiving an oral fluoroquinolone [2]. In contrast, a cohort study from a nationwide registry in Denmark that more comprehensively controlled for potential confounders did not find an association between fluoroquinolone use and risk of retinal detachment [3]. Additional studies are required to determine whether fluoroquinolones are associated with retinal detachment. (See "Fluoroquinolones", section on 'Retinal detachment'.)

Coprescription of clarithromycin and calcium channel blockers (November 2013)

In a population-based study of older adults, coprescribing clarithromycin with a calcium channel blocker (compared with azithromycin plus a calcium channel blocker) was associated with a small but statistically significant increase in risk of hospitalization with acute kidney injury [4]. Coprescription with clarithromycin was also associated with a higher risk of hospitalization with hypotension and all-cause mortality. Although the risks associated with the combined use of clarithromycin and calcium channel blockers appear to be small, they should be considered when deciding whether to use these agents in combination in older patients or other patients at risk for acute kidney injury. (See "Azithromycin, clarithromycin, and telithromycin", section on 'Drug interactions'.)

FDA boxed warning regarding tigecycline (October 2013)

Tigecycline is a broad-spectrum antibiotic, which has been approved by the US Food and Drug administration (FDA) for community-acquired pneumonia, but not for hospital-acquired pneumonia. In September 2010, the FDA issued a safety announcement regarding increased mortality with use of tigecycline in patients with hospital-acquired pneumonia (HAP); tigecycline is not FDA-approved for HAP [5]. A recent analysis of 10 clinical trials showing an increased risk of death in patients receiving tigecycline for FDA-approved uses, including community-acquired bacterial pneumonia, complicated skin and skin structure infections, and complicated intraabdominal infections (2.5 versus 1.8 percent, adjusted risk difference 0.6 percent) [6]. In 2013, the FDA added a boxed warning stating that tigecycline should be reserved for use in situations when alternative agents are not suitable. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Tigecycline' and "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Other agents'.)

FDA approval of telavancin for HAP and VAP (October 2013)

Telavancin is an antibiotic with activity against methicillin-resistant Staphylococcus aureus. In 2013, telavancin was approved by the US Food and Drug Administration (FDA) for the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus, but not for other bacterial causes of HAP or VAP; it is recommended only when alternative agents cannot be used [7]. The FDA has included several boxed warnings for telavancin, which must be considered before choosing it [8]. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Telavancin'.)


Vancomycin dose for intrapartum GBS chemoprophylaxis (April 2014)

A study has found that vancomycin dosing recommendations from a 2010 guideline from the US Centers for Disease Control (CDC) regarding intrapartum chemoprophylaxis of neonatal early-onset Group B Streptococcus may provide subtherapeutic levels in neonates. The CDC guidelines recommend vancomycin 1 gram every 12 hours for penicillin allergic women if GBS isolates are resistant to clindamycin or susceptibility results are not available. However, a 2014 study of vancomycin levels in neonatal cord blood noted that therapeutic levels were infrequently achieved in neonates whose mothers received this dose, but usually were achieved with maternal weight-based dosing (20 mg/kg every 8 hours; maximum dose 2 grams) [9]. We now suggest weight-based dosing for vancomycin intrapartum GBS chemoprophylaxis. (See "Neonatal group B streptococcal disease: Prevention", section on 'Patients with penicillin allergy'.)

Healthcare-associated infections in the United States (April 2014)

A study retrospectively reviewed records of over 11,000 randomly selected patients admitted to general or pediatric acute care hospitals in the US and found that 4 percent had a healthcare-associated infection [10]. Pneumonia and surgical-site infections were the most common, each accounting for 22 percent of all infections. Based on these results and data on national hospital admissions rates, an estimated 648,000 patients in the US experienced a healthcare-associated infection in 2011. These findings highlight the substantial burden of such infections and the importance of infection control measures designed to prevent them. (See "General principles of infection control", section on 'Burden of health care associated infections'.)

Decreased mortality from sepsis (March 2014)

Several studies have suggested that mortality from sepsis is decreasing, although most have been limited by size or other factors and did not constitute high-quality evidence. Using an internationally-accepted, standardized definition of sepsis, a 12-year multicenter study of over 100,000 patients in Australia and New Zealand with severe sepsis and septic shock reported a 50 percent risk reduction (35 to 18 percent) in in-hospital mortality between 2000 and 2012 [11]. This study, together with reports of improved compliance with treatment guidelines, suggests that the reduction in mortality is authentic and possibly due to improved therapeutic strategies for sepsis recognition and management. (See "Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis", section on 'Mortality and prognosis'.)

FDA warning about doripenem for ventilator-associated pneumonia (March 2014)

In 2014, the US Food and Drug Administration (FDA) approved revisions to the doripenem label warning clinicians about increased mortality rates in patients who received doripenem rather than imipenem for ventilator-associated bacterial pneumonia, based on results of a randomized trial that was stopped early due to safety concerns [12]. In the intention-to-treat population of the trial, 28-day all-cause mortality was higher and clinical response rates were lower among patients receiving doripenem than in those receiving imipenem, although different dosing regimens and use of adjunctive aminoglycosides may have influenced these results [13]. Doripenem is not approved by the FDA for the treatment of pneumonia. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Gram-negative pathogens'.)

Guidelines on healthcare personnel attire (February 2014)

Clothing and paraphernalia of healthcare personnel quickly become contaminated during the course of patient care with bacterial pathogens, but no studies clearly demonstrate that strategies to minimize this contamination have any impact on hospital infection rates. Despite the limited data, the Society for Healthcare Epidemiology of America (SHEA) released guidelines on healthcare personnel attire, emphasizing the balance of maintaining professionalism, comfort, and practicality against the possible risk of pathogen transmission through clothing [14]. Their suggestions include frequent laundering of attire, disinfection of all items (including pagers and cell phones) that come into direct contact with the patient or patient's environment, and avoiding ties and jewelry on the hands or wrists. (See "General principles of infection control", section on 'Healthcare personnel attire'.)

Statins in patients with ventilator-associated pneumonia (October 2013)

Some, but not all, studies have suggested that statin use might reduce the risk of infection, including pneumonia, and infection-related mortality. In a multicenter randomized trial to evaluate statin therapy in patients with ventilator-associated pneumonia, patients were assigned to either simvastatin or placebo, to be continued through intensive care unit (ICU) discharge or up to 28 days [15]. The trial was stopped early for futility. After enrollment of 300 patients, day 28 mortality was not lower in the statin group compared with the placebo group (21 versus 15 percent). There were also no significant differences in day 14, ICU, or in-hospital mortality rates; duration of mechanical ventilation; or changes in Sequential Organ Failure Assessment (SOFA) score. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Lack of benefit of statins'.)

Universal contact precautions in the intensive care unit (October 2013)

The issue of whether to use universal contact precautions for every patient in the intensive care unit (ICU), regardless of colonization history, is a matter of ongoing debate. Although this may be a reasonable practice in outbreak settings or institutions that have a high rate of colonization or infection with drug resistant bacteria, routine use of universal contact precautions is not yet supported by strong scientific evidence. In a large cluster randomized trial, universal gown and glove use did not reduce the primary combined endpoint of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin resistant enterococcus (VRE) acquisition more than gown and glove use only for known colonization or infection with drug resistant bacteria [16]. There were no excess adverse events with the use of universal contact precautions. (See "Epidemiology and prevention of infections and antimicrobial resistance in the intensive care unit", section on 'Contact precautions'.)


Donor PTX3 deficiency and invasive aspergillosis in hematopoietic cell transplant recipients (January 2014)

Invasive aspergillosis occurs most frequently in immunocompromised hosts, such as hematopoietic cell transplant (HCT) recipients, and results in significant morbidity and mortality. Certain genetic polymorphisms in donors or recipients have been associated with an increased risk for invasive aspergillosis in HCT recipients. HCT from a donor with a homozygous haplotype for a single nucleotide polymorphism in the soluble pattern recognition receptor, long pentraxin 3 (PTX3), is associated with defective expression of PTX3 and with an increased risk of invasive aspergillosis [17]. PTX3 deficiency in neutrophils leads to impaired phagocytosis and clearance of the fungus, likely due to messenger RNA instability. (See "Epidemiology and clinical manifestations of invasive aspergillosis", section on 'Risk factors'.)

Beta-D-glucan assay for outbreak-associated fungal meningitis (February 2014)

1,3-Beta-D-glucan is a cell wall component of many fungi. The beta-D-glucan assay may be positive in patients with a variety of invasive fungal infections, including those caused by Exserohilum (the most common fungus identified in patients with fungal meningitis during the 2012 outbreak associated with injections of contaminated methylprednisolone in the United States). In a study of fungal meningitis cases that occurred during the outbreak, the beta-D-glucan assay had a sensitivity of 100 percent and a specificity of 98 percent for the diagnosis of fungal meningitis [18]. Among 20 patients with serially collected samples (over months), most patients with a decline in beta-D-glucan concentrations had clinical improvement, but all four patients with continually elevated beta-D-glucan concentrations or concentrations that initially declined but later increased had poor clinical outcomes, such as stroke or relapse of meningitis or soft tissue phlegmon. (See "Outbreak of fungal central nervous system and osteoarticular infections in the United States: Epidemiology, clinical manifestations, and diagnosis", section on 'Evaluation and diagnosis'.)

CARD9 deficiency and idiopathic deep dermatophytosis (October 2013)

Caspase recruitment domain-containing protein 9 (CARD9) plays a role in antifungal immunity, and manifestations of CARD9 deficiency include chronic mucocutaneous candidiasis, superficial dermatophytosis, and Candida meningitis. Using the candidate-gene approach, CARD9 deficiency has now been associated with deep dermatophytosis (invasive dermatophyte infection of the skin, scalp, nails, lymph nodes, and brain) in several affected kindreds with no previously identified immunodeficiency [19]. Further studies are needed to elucidate the specific mechanisms underlying increased susceptibility to fungal disease in these patients. (See "Primary disorders of phagocytic function: An overview", section on 'CARD9 deficiency'.)


Coronary artery plaque and HIV infection (April 2014)

Cardiovascular disease has emerged as an important cause of death in HIV-infected patients. In an observational study of 450 HIV-infected and 309 HIV-uninfected men between the ages of 40 and 70 years who have sex with men, HIV-infection was associated with a greater prevalence and extent of non-calcified coronary artery plaque, as detected by computed tomography angiography, even after adjustment for traditional cardiovascular risk factors [20]. These results add to the growing evidence that HIV-specific factors contribute to cardiovascular risk beyond the excess of traditional risk factors observed in the HIV-infected population, although the precise mechanism for this remains unknown. (See "Pathogenesis and biomarkers of cardiovascular disease in HIV-infected patients", section on 'Coronary artery calcification and plaque'.)

Risk of hepatic decompensation in HIV/HCV coinfected patients (April 2014)

In patients with chronic hepatitis C virus (HCV) infection, concomitant HIV infection is associated with higher rates of liver-related morbidity and mortality. In a retrospective study of over 10,000 HCV-infected male US veterans, the estimated 10-year incidence of hepatic decompensation was 7.4 percent among antiretroviral treated HIV/HCV coinfected men compared with 4.8 percent among HCV monoinfected men [21]. The risk of decompensation in HIV/HCV coinfected patients is even greater in the absence of antiretroviral therapy [22]. These findings argue for early treatment of chronic HCV, which can prevent liver complications if successful, in HIV infected patients. (See "Epidemiology, natural history, and diagnosis of hepatitis C in the HIV-infected patient", section on 'Hepatic decompensation'.)

Infusion of genetically engineered CD4 cells to control HIV infection (March 2014)

Interaction with the CCR5 receptor is essential for HIV entry into the CD4 cell, and mutations in the gene encoding this protein are associated with decreased susceptibility to HIV infection and a more favorable natural history if infected. In a preliminary study, 12 HIV-infected patients with viral suppression on antiretroviral therapy (ART) underwent a single infusion of autologous CD4 cells in which the CCR5 gene had been functionally knocked out through genetic engineering [23]. The infusion resulted in one transient, but severe, febrile reaction. The median half life of the modified CD4 cells was 48 weeks, and among the four patients who subsequently discontinued ART, the median decline of modified CD4 cells was lower than that of unmodified cells. Whether such an intervention can alter the natural history of HIV infection is yet to be determined. (See "Factors affecting HIV progression", section on 'Effect of CCR5 delta32 genetic background'.)

Prognosis of HIV-related Kaposi sarcoma in the era of antiretroviral therapy (January 2014)

The widespread use of combination antiretroviral therapy (ART) has led to a striking decrease in the incidence of HIV-related Kaposi sarcoma (KS). The prognosis for HIV infected individuals who develop KS is favorable. In a consecutive series of 469 patients, those with T0 (table 1) disease were generally treated with ART alone, while those with the more advanced T1 disease were treated with ART plus chemotherapy. For those with T0 disease, the five-year overall survival rate was 92 percent and for those with T1 disease the five-year overall survival rate was 83 percent [24]. (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Prognosis'.)

Early treatment of HIV infection (November 2013)

In a highly publicized case, an infant diagnosed with HIV infection and initiated on antiretroviral therapy (ART) at 30 hours of age maintained an undetectable HIV viral load one year following the discontinuation of ART at 18 months of age [25]. Although some experts remain unconvinced that the infant was truly infected, the case report joins other small observational studies that demonstrate very low viral reservoirs or persistent control of viral replication in some patients who initiated ART at the earliest time points after HIV infection [26-28]. Discontinuation of ART, regardless of when it is initiated, is not recommended because of poor clinical outcomes associated with treatment interruption in the setting of chronic HIV infection. Nevertheless, this possibility of an alteration in disease course with its potential implications for future cure strategies, in addition to the known benefits of early treatment, overall support the initiation of ART during acute or early HIV infection. (See "Acute and early HIV infection: Treatment", section on 'Can ART in early infection alter disease course?'.)


Ribavirin for chronic hepatitis E infection in transplant recipients (March 2014)

Transplant recipients are at increased risk for chronic hepatitis E virus (HEV) and there is currently no established therapy. A multicenter retrospective case series included 59 patients with a solid organ transplant who had received ribavirin for a median of three months, beginning a median of nine months after the diagnosis of HEV infection [29]. At the end of therapy, HEV clearance was observed in 95 percent of patients. A sustained virologic response, defined as undetectable serum HEV RNA at least six months after cessation of ribavirin, was observed in 78 percent of patients. Anemia was the most common side effect. Prospective studies are needed to confirm these findings and to determine the dose, duration, and timing of ribavirin therapy. (See "Hepatitis E virus infection", section on 'Treatment'.)


World Health Organization recommendations on polio vaccination (March 2014)

Some national polio vaccine programs utilize live attenuated oral polio vaccine (OPV) only. In 2014, the World Health Organization (WHO) recommended the addition of at least one dose of inactivated polio vaccine (IPV), to be given at ≥14 weeks of age, to the OPV series in such countries [30]. IPV and OPV can be given concurrently. The purpose of the added IPV dose is to maintain immunity against type 2 poliovirus during and after the planned global switch in 2016 from trivalent OPV to bivalent OPV for routine immunization. (See "Poliovirus vaccination", section on 'Recommendations of the World Health Organization (WHO)'.)

ACIP immunization recommendations (March 2014)

New immunization recommendations for 2014 for adults in the United States have been issued by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) (figure 1 and figure 2) [31,32]. Changes to the updated schedule include the addition of Haemophilus influenza b (Hib) vaccine recommendations for adults with asplenia, sickle cell disease, stem cell transplant, or planned splenectomy. HIV infection is not an indication for Hib vaccination. (See "Approach to immunizations in healthy adults", section on 'Immunization schedule for healthy adults'.)

Menveo for infants at increased risk for meningococcal disease (March 2014)

In 2014, the United States Advisory Committee on Immunization Practices began recommending Menveo, a quadrivalent conjugate vaccine against meningococcus serogroups A, C, Y, and W135 conjugated to a mutant diphtheria toxin, CRM197, for infants ≥2 months of age at increased risk for meningococcal disease (table 2) [33]. The minimum age for Menveo was previously two years. Menveo was approved by the US Food and Drug Administration in 2013. (See "Meningococcal vaccines", section on 'In infants and toddlers'.)

IDSA guidelines for vaccination of immunocompromised hosts (January 2014)

The Infectious Diseases Society of America has published new guidelines for vaccination of immunocompromised hosts, including hematopoietic cell transplant recipients, solid organ transplant recipients, as well as patients with cancer, asplenia, primary immunodeficiency disorders, chronic inflammatory conditions, HIV infection, and chronic inflammatory diseases receiving immunosuppressive agents [34]. The document includes recommendations about the appropriate use (and avoidance) of specific vaccines in immunocompromised hosts. (See "Immunizations in hematopoietic cell transplant candidates and recipients" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in patients with cancer" and "Prevention of sepsis in the asplenic patient".)

Japanese encephalitis vaccine for children (November 2013)

Japanese encephalitis (JE) is the most important cause of viral encephalitis in Asia. One JE vaccine is available in the United States: an inactivated Vero cell culture-derived vaccine (JE-VC; IXIARO). This vaccine, originally licensed in 2009 for use in individuals ≥17 years, was subsequently licensed in 2013 for use in children 2 months through 16 years of age [35]. Recommendations for use of JE vaccine in travelers are summarized in a table (table 3). (See "Japanese encephalitis: Epidemiology, diagnosis, treatment and prevention", section on 'Vaccination'.)


Miltefosine for treatment of leishmaniasis (March 2014)

In March 2014, the US Food and Drug Administration approved the oral antiparasitic agent miltefosine for treatment of cutaneous, mucosal, and visceral leishmaniasis in patients ≥12 years of age [36]. Leishmaniasis is a parasitic infection transmitted via sand fly bites in tropical and subtropical regions. Because of its potential for fetal toxicity, miltefosine is contraindicated in pregnant women. Women of child-bearing potential should use effective contraception during and for four months following treatment with miltefosine. (See "Treatment of cutaneous leishmaniasis", section on 'Miltefosine' and "Treatment of visceral leishmaniasis", section on 'Miltefosine'.)


Efficacy of counseling to prevent sexually transmitted infections (October 2013)

High-intensity behavioral counseling with multiple sessions over several hours is effective in reducing the incidence of sexually transmitted infections (STIs). However, the benefit of less intense counseling is unclear. In a trial of 5012 individuals presenting to several STI clinics across the United States, there was no difference in cumulative STI incidence (HIV, HSV-2, chlamydia, gonorrhea, trichomoniasis, and syphilis) at six months between those randomly assigned to receive one-time counseling on STI risk reduction (median of 35 minutes total) and those who received only basic information (median of six minutes total); both groups received rapid HIV testing [37]. We continue to advise risk-reduction counseling in general, but screening for STIs, and HIV testing in particular, should occur even in settings where there is only time to provide basic risk-reduction information. (See "Prevention of sexually transmitted infections", section on 'Risk reduction counseling'.)


Hyperimmune globulin does not prevent congenital CMV infection (April 2014)

Although prospective observational studies have reported that administration of hyperimmune globulin to pregnant women with primary cytomegalovirus (CMV) infection reduced maternal-to-fetal transmission and the severity of congenital infection, a recent randomized trial did not demonstrate a significant benefit. The Congenital Human CMV Infection Prevention (CHIP) trial randomly assigned pregnant women at 5 to 26 weeks of gestation with recent onset primary CMV infection to receive hyperimmune globulin or placebo every four weeks [38]. The overall rate of congenital infection and the proportion of infected infants symptomatic at birth was similar for both groups. (See "Cytomegalovirus infection in pregnancy", section on 'Hyperimmunoglobulin'.)

Anti-NMDA receptor encephalitis after herpes simplex virus encephalitis (March 2014)

Accumulating evidence suggests that herpes simplex virus (HSV) encephalitis may be a trigger for anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. In reported cases, patients have presented with relapsing neurologic symptoms two to six weeks after HSV encephalitis; most have exhibited prominent choreoathetosis or facial dyskinesias [39,40]. In five patients, negative anti-NMDA receptor antibody status was documented at the time of primary HSV infection, with later seroconversion at the time of relapsing symptoms [41]. Patients with confirmed anti-NMDA receptor encephalitis may respond favorably to immunosuppression. (See "Paraneoplastic and autoimmune encephalitis", section on 'Anti-NMDA receptor encephalitis'.)

Polio-like illness in California (March 2014)

A rare polio-like illness of unknown etiology has affected five children in California since 2012, and at least 20 more cases are under investigation [42]. Cases with full clinical information were characterized by sudden onset of flaccid paralysis in one or more limbs, usually preceded by a respiratory illness. None of the children had a history of travel to Asia or Australia, where similar illnesses have been reported recently. Nasal swabs of two children were positive for enterovirus 68, but the virus was not isolated from the cerebrospinal fluid. Its role in the pathogenesis of the illness is therefore speculative. Affected children did not respond to immune-modulating treatment and had limited neurologic recovery up to six months after onset. (See "Polio and infectious diseases of the anterior horn", section on 'California polio-like illness'.)

Chronic hepatitis C virus infection in the United States (March 2014)

An estimated 1 percent of the United States population, or approximately 2.7 million individuals, has chronic hepatitis C virus (HCV) infection, based on an analysis of the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2010 [43]. Peak prevalence was observed among those born between 1945 and 1965, who accounted for 80 percent of all chronically infected individuals. One-time screening for HCV infection is recommended by UpToDate, consistent with recommendations from the Centers for Disease Control and Prevention, for all US adults in this birth cohort, regardless of risk factors. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'United States' and "Screening for chronic hepatitis C virus infection".)

HPV vaccine dosing and genital warts (March 2014)

Three doses of HPV vaccine are recommended in the United States, but missed doses and suboptimal adherence to the schedule are frequent. In a Swedish cohort study of over one million females, aged 10 to 24 years, followed for four years, receipt of two quadrivalent HPV vaccine doses was associated with substantial protection against genital warts, although completion of three doses was slightly superior [44]. The study did not assess other important outcomes such as cervical intraepithelial neoplasia or cervical cancer. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Missed doses/alternate schedules'.)

Vaccines to protect against enteroviral infection (March 2014)

In east and southeast Asia, enterovirus 71 is a notable cause of epidemics of hand, foot, and mouth syndrome, with outcomes including fatality and severe central nervous system disease. Effective vaccines against enteroviruses other than poliovirus are not yet clinically available. In randomized trials in China of three distinct inactivated genotype C4 enterovirus 71 vaccines, vaccine efficacy in children ranged from 90 to 97 percent for laboratory confirmed hand, foot, and mouth disease caused by enterovirus 71 [45-47]. The vaccines did not cause excess serious adverse reactions. There was no assessment of cross-protection against other enterovirus 71 genotypes, which limits the application of these results to other parts of Asia, where genotypes other than C4 predominate. (See "Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections", section on 'Prevention'.)

Potential for interferon-free regimens in chronic HCV genotype 1 infection (January 2014)

Rapid progress is being made towards developing all-oral, interferon-free regimens that achieve excellent rates of sustained virologic response (SVR), and thus effective cure, for genotype 1 hepatitis C virus (HCV) infection, even among patients who had not previously responded to peginterferon and ribavirin. Genotype 1 infection is the most common in North America and Europe and has traditionally been difficult to treat. In two trials of different interferon-free regimens in genotype 1 infected patients without cirrhosis, including both treatment-naive and experienced individuals, SVR was achieved in 83 to 98 percent, depending on the specific regimen [48,49]. Although most of the agents in these regimens are not currently available, these results highlight the feasibility of cure of genotype 1 HCV infection without the need for interferon and should thus inform the decision on whether to defer antiviral treatment to wait for these new agents. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Deciding when to treat' and "Investigational therapies for hepatitis C virus infection", section on 'Interferon-free DAA combinations'.)

Fatal case of H5N1 avian influenza in North America (January 2014)

The first case of H5N1 avian influenza in North America was reported in January 2014 in a woman who had returned to Canada from a trip to Beijing, China [50,51]. The patient was a previously healthy young woman who developed pneumonia and encephalitis, resulting in intracranial hypertension and brain death [52]. H5N1 influenza was detected from respiratory samples and cerebrospinal fluid using the polymerase chain reaction and sequencing. (See "Clinical manifestations and diagnosis of avian influenza", section on 'Clinical manifestations'.)

2013-2014 seasonal influenza surveillance (January 2014)

The United States Centers for Disease Control and Prevention and the World Health Organization track influenza virus isolates worldwide. Surveillance between September 29 and December 7, 2013 found that approximately 90 percent of isolates in the United States were influenza A viruses [53]. Among influenza A isolates, 90 percent were 2009 pandemic H1N1 viruses, which have been associated with severe respiratory illness in young and middle-aged adults early in the 2013-2014 influenza season [54]. Although it is not possible to predict whether this pattern will continue throughout the season, if it does, young and middle-aged adults may be disproportionately affected. This influenza strain is included in the 2013-2014 seasonal influenza vaccine, but vaccine efficacy remains to be determined. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Influenza activity' and "Epidemiology of influenza", section on 'Influenza activity'.)

Rise in cases of novel avian influenza H7N9 infection (January 2014)

In late March and April 2013, human cases of novel avian influenza H7N9 infection in China were reported to the World Health Organization. During the initial wave from February to May 2013, 133 cases were detected [55]. The number of new cases initially peaked in April 2013 and then declined; it is likely that the reduction in cases was related, at least in part, to implementation of control strategies including closure of live poultry markets and increased public awareness. A rise in the number of cases occurred in late 2013 and early 2014, coinciding with influenza season. Over 200 cases have been detected during the second wave wave [55,56]. Approximately one-third of patients have died [57]. (See "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis" and "Avian influenza A H7N9: Treatment and prevention", section on 'Outcomes'.)

Chikungunya fever in the Caribbean (January 2014)

Chikungunya is an arthropod-borne virus (arbovirus) endemic to West Africa that causes acute febrile polyarthralgia and arthritis. In December 2013, several cases of chikungunya fever were reported in the Caribbean [58]. This is the first time that local transmission of chikungunya has been reported in the Americas. (See "Chikungunya fever", section on 'Americas'.)

First human infections with avian influenza H10N8 and H6N1 (December 2013)

The first human infections with the avian influenza viruses, H10N8 and H6N1, have been reported in China and Taiwan, respectively. A case of avian influenza H10N8 infection was detected in December 2013 in a 73-year-old woman in China who had visited a live bird market four days before the onset of illness [59]. She developed severe pneumonia and died several days after being hospitalized. A second case was subsequently reported in China, involving a 55-year-old woman who also visited a live bird market and developed severe pneumonia [60]. In May 2013, avian influenza H6N1 was detected in a 20-year-old woman in Taiwan who presented with pneumonia [61]. She was treated with oseltamivir and recovered. (See "Epidemiology, transmission, and pathogenesis of avian influenza", section on 'Avian influenza H10N8 and H10N7' and "Epidemiology, transmission, and pathogenesis of avian influenza", section on 'Avian influenza H6N1'.)

Sofosbuvir and simeprevir for genotype 1 chronic hepatitis C infection (December 2013)

Sofosbuvir, a hepatitis C virus (HCV) polymerase inhibitor, and simeprevir, a HCV protease inhibitor, are currently becoming available in the United States and elsewhere for treatment of chronic genotype 1 HCV infection. Regimens that include these agents offer high sustained virological response (SVR) rates, more favorable adverse effect profiles than earlier regimens, ease of administration, and relatively short treatment durations [62-65]. However, regimens for genotype 1 infection generally continue to include interferon. Interferon-free regimens are expected in the near future, and it is reasonable for many patients to defer treatment while awaiting newer therapies. Most patients with chronic genotype 1 HCV infection who are candidates for and desire therapy at this time should be treated with peginterferon, weight-based ribavirin, and a direct-acting antiviral (DAA). If available, we recommend the DAAs sofosbuvir or simeprevir rather than telaprevir or boceprevir. Choice of regimens for specific populations of patients are further discussed in the topic. A joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America has also released guidelines on the use of these agents for the treatment of chronic hepatitis C infection [66]. (See "Treatment regimens for chronic hepatitis C virus genotype 1".)

Sofosbuvir for genotype 2 and 3 chronic hepatitis C infection (December 2013)

Sofosbuvir, a hepatitis C virus (HCV) polymerase inhibitor, is becoming available in the United States and elsewhere for the treatment of genotype 2 and genotype 3 chronic HCV infection. Despite relatively high sustained virologic response (SVR) rates with only 24 weeks of peginterferon and ribavirin among most patients with genotype 2 or 3 infection, the many contraindications and side effects associated with interferon have precluded therapy for many patients. Thus, the introduction of sofosbuvir, which offers the possibility of an effective, well-tolerated, all-oral, interferon-free regimen for most genotype 2 and 3 infected patients [62,67,68], represents a major milestone in the management of chronic HCV infection. Where available, for most patients with genotype 2 and 3 chronic HCV infection, we recommend the combination of sofosbuvir and ribavirin, rather than peginterferon and ribavirin. Choice of regimens for specific populations of patients are further discussed in the topic. A joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America has also released guidelines on the use of these agents for the treatment of chronic hepatitis C infection [66]. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3".)

Antidepressants as prophylaxis for interferon alfa induced depression (November 2013)

For patients who are treated with interferon, the common side effect of depression can be prevented with antidepressants. Randomized trials have previously yielded conflicting results about the benefits of prophylactic antidepressants, but meta-analyses have found that prophylaxis is beneficial. A new analysis of eight trials including nearly 600 patients compared antidepressants (selective serotonin reuptake inhibitors) with placebo for preventing depression in patients who were about to start interferon for hepatitis C or malignant melanoma [69]. Major depression was less likely to occur during interferon treatment in patients who received antidepressants (odds ratio 0.4). (See "Neuropsychiatric side effects associated with interferon-alfa plus ribavirin therapy: Treatment and prevention", section on 'When to treat for interferon psychiatric side effects'.)

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