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What's new in infectious diseases
Official reprint from UpToDate® ©2015 UpToDate®
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What's new in infectious diseases

Disclosures: Elinor L Baron, MD, DTMH Nothing to disclose. Allyson Bloom, MD Nothing to disclose. Anna R Thorner, MD Nothing to disclose. Jennifer Mitty, MD, MPH Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2015. | This topic last updated: Nov 19, 2015.

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.


Eosinophilia during prolonged antibiotic therapy (June 2015)

Eosinophilia is not uncommon in patients receiving prolonged intravenous (IV) antibiotics, but the prevalence and significance has not been extensively studied. In a prospective cohort study of 824 patients receiving prolonged intravenous antibiotic therapy, eosinophilia developed in 25 percent, appearing at a median of 15 days of therapy and peaking at a median absolute count of 726/mL (500 to 8610/mL) [1]. Although most patients with eosinophilia completed their courses without complications, one-third developed a hypersensitivity reaction involving rash or hepatic or renal involvement. Medication-associated eosinophilia does not mandate discontinuation of therapy but warrants close monitoring for evidence of hypersensitivity and consideration of alternative medications that could be substituted without compromising care. (See "Approach to the patient with unexplained eosinophilia", section on 'Medications and over the counter remedies'.)


Adjunctive glucocorticoids for adults with severe community-acquired pneumonia (August 2015, Modified November 2015)

For hospitalized patients with community-acquired pneumonia (CAP), glucocorticoids as adjunctive therapy to antibiotics have the potential to reduce the inflammatory response and decrease morbidity. A 2015 meta-analysis of randomized trials that included hospitalized patients with CAP suggested a modest mortality benefit for adjunctive glucocorticoids [2]. A reduction in all-cause mortality was of borderline statistical significance (relative risk [RR] 0.67, 95% CI 0.45-1.01; risk difference 2.8 percent). Rates of mechanical ventilation and acute respiratory distress syndrome were decreased, as were time to clinical stability and duration of hospitalization; rates of hyperglycemia requiring treatment increased.

For hospitalized patients with CAP who require intensive care unit admission, we recommend adjunctive glucocorticoids. For other hospitalized patients with CAP, we suggest adjunctive glucocorticoids. Clinicians should make the decision whether or not to give glucocorticoids on a case-by-case basis, especially in patients with an elevated risk of adverse effects. Limited evidence suggests that infections caused by certain pathogens (eg, influenza virus, Aspergillus spp) may be associated with worse outcomes in the setting of glucocorticoid use [3,4]; given these concerns, we avoid adjunctive glucocorticoids if one of these pathogens is detected. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)

New American and European guidelines on endocarditis (October 2015)

The American Heart Association (AHA) and European Society of Cardiology (ESC) have each issued new guidelines on management of infective endocarditis (IE) that provide updated information on antimicrobial therapy for IE [5,6]. Daptomycin has been added as an alternative agent for treatment of staphylococcal IE, and gentamicin is no longer recommended for treatment of staphylococcal native valve IE. Regimens for treatment of enterococcal IE now include double beta-lactam therapy with ampicillin and high-dose ceftriaxone. In addition, high-dose daptomycin (with or without a beta-lactam) and linezolid are included as potential alternative regimens for managing IE caused by enterococci resistant to penicillin, aminoglycosides, and vancomycin. (See "Antimicrobial therapy of native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis".)

Discretionary ICU admission and mortality in older adults with pneumonia (October 2015)

A retrospective cohort study of over one million Medicare beneficiaries (aged >64 years) admitted with pneumonia to hospitals in the United States evaluated the relationship between intensive care unit (ICU) admission and outcomes among patients whose ICU admissions appeared to be discretionary (ie, based predominantly on proximity to a hospital with high ICU admission rates) [7]. In an adjusted analysis, among patients whose ICU admission was potentially discretionary, ICU admission was associated with lower mortality than general ward admission. There were no differences in Medicare spending or hospitalization costs between discretionary ICU and general ward patients. These results suggest a potential benefit for broader ICU admission criteria for older adults with pneumonia without substantially increased costs, but should be confirmed in a randomized trial. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Indications for hospitalization and ICU admission'.)

Chlorhexidine-alcohol for site preparation before intravascular catheter insertion (October 2015)

Skin antiseptic preparation with chlorhexidine-alcohol prior to intravascular catheter insertion provides greater protection against short-term catheter-related infection than povidone iodine-alcohol. In a large randomized trial including 2349 patients (5159 catheters), use of chlorhexidine–alcohol resulted in a lower incidence of catheter-related infections than povidone iodine-alcohol (0.28 versus 1.77 per 1000 catheter-days) [8]. We continue to recommend use of chlorhexidine-alcohol prior to catheter insertion, in conjunction with other measures for prevention of intravascular catheter-related infections. (See "Prevention of intravascular catheter-related infections", section on 'Insertion site preparation'.)

IDSA guidelines on vertebral osteomyelitis (August 2015)

Guidelines on diagnosis and treatment of vertebral osteomyelitis in adults have been issued by the Infectious Disease Society of America (IDSA) [9]. These guidelines highlight the use of magnetic resonance imaging as the diagnostic imaging method of choice, withholding empiric antibiotics in patients without sepsis or progressive neurological complications until the microbiological etiology is identified, and the importance of biopsy for microbiologic diagnosis when blood cultures and serology are uninformative. In addition to prolonged antibiotic therapy, they recommend surgical intervention for individuals with progressive neurologic deficits or deformity, spinal instability, or clinical deterioration despite appropriate medical therapy. Our approach to vertebral osteomyelitis is generally consistent with these guidelines. (See "Vertebral osteomyelitis and discitis in adults", section on 'Introduction'.)

Uncertain benefit of routine S. aureus decolonization for prevention of surgical site infection (June 2015)

Routine preoperative Staphylococcus aureus screening and decolonization to prevent surgical site infection (SSI) has not been definitively proven to be beneficial or cost-effective. A large multicenter study of patients undergoing cardiac or orthopedic surgical procedures compared the rates of S. aureus SSI prior to and after the implementation of a preventive intervention bundle, which included S. aureus screening, decolonization, and targeted preoperative antimicrobial prophylaxis [10]. The mean rate of deep incisional or organ space S. aureus infection was lower during the intervention compared with the preintervention period (21 versus 36 cases per 10,000 operations). However, the adherence rate to the full bundle was only 39 percent and several patient characteristics (including age and comorbidities) differed between the two periods. Because of these and other limitations, we continue to suggest not using routine preoperative S. aureus screening and decolonization for patients undergoing surgery. (See "Adjunctive measures for prevention of surgical site infection in adults", section on 'S. aureus decolonization'.)

Antimicrobial-resistant Shigella infections in the United States (June 2015)

Antimicrobial resistance in Shigella is an increasing problem in the United States. Fluoroquinolones are typically the antibiotic class of choice in adults, and azithromycin is often used if fluoroquinolone resistance is suspected or documented. Clusters of ciprofloxacin-resistant cases, likely introduced by international travelers with subsequent domestic spread, have been reported throughout the country, and isolates with decreased susceptibility to azithromycin have caused outbreaks and sporadic cases, predominantly among men who have sex with men (MSM) [11,12]. Scattered infections with extremely drug-resistant isolates that are ciprofloxacin-resistant and have decreased susceptibility to azithromycin have also been reported [13]. These reports highlight the importance of obtaining susceptibility testing to ensure adequate efficacy of the chosen antimicrobial when managing shigellosis and emphasizing prevention measures, primarily hygiene practices around food preparation or consumption and oral or anal sex. (See "Shigella infection: Treatment and prevention in adults", section on 'Antimicrobial resistance' and "Shigella infection: Treatment and prevention in children", section on 'Antibiotic resistance'.)

Trends in infective endocarditis incidence in the United States (May 2015)

The epidemiology of infective endocarditis (IE) has changed over time because of changes in the prevalence of risk factors, as well as improved diagnostic tools and management. A study using the Nationwide Inpatient Sample database, which included 457,052 hospitalizations for IE in the United States between 2000 and 2011, found a steady increase in IE incidence over this time [14]. The trends in hospitalization rates overall from 2000 to 2007 and from 2008 to 2011 were not significantly different, but there was a steeper increase in hospitalization rates for streptococcal IE, specifically, after 2007. It has been postulated that this reflects reduced antimicrobial IE prophylaxis after the American College of Cardiology/American Heart Association (ACC/AHA) recommended a narrower range of indications for prophylaxis in 2007. However, in the absence of controlled data, a causal connection is uncertain. Given the available evidence, we continue to recommend an approach to IE prophylaxis consistent with the ACC/AHA guidelines. (See "Epidemiology, risk factors, and microbiology of infective endocarditis", section on 'Epidemiology' and "Antimicrobial prophylaxis for bacterial endocarditis", section on 'Trends in endocarditis incidence'.)

Short-course antibiotic therapy for intraabdominal infection (May 2015)

Short courses of antibiotics have been advocated for patients with intraabdominal infection once source control has been achieved, but many clinicians give longer courses due to concerns about relapsing infection. The efficacy of short-course antimicrobial therapy was demonstrated in a trial in which patients with complicated intraabdominal infection and adequate source control were randomly assigned to receive either a fixed course of antibiotics for 4±1 days or antibiotics until two days after resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of antimicrobial therapy [15]. The median duration of antibiotics was four days in the experimental group versus eight days in the control group. The composite primary outcome of surgical site infection, recurrent intraabdominal infection, or death occurred in a similar percentage of patients in both groups (22 percent). (See "Anaerobic bacterial infections", section on 'Antibiotic treatment'.)


Outbreak of fungal CNS infection and septic arthritis in the United States: Long-term follow-up (November 2015)

A multistate outbreak of fungal central nervous system infection and septic arthritis associated with injections with contaminated methylprednisolone was detected in the United States in 2012 and involved >750 cases. In a long-term follow-up study, by 12 months after the initial diagnosis, 42 percent of 455 patients followed in the study were considered cured, 41 percent were no longer receiving antifungal therapy but did not meet the definition of cure, 7 percent were still receiving antifungal therapy, 8 percent had died (with 24 of 36 fatalities attributed to outbreak-associated infections), and 2 percent had incomplete follow-up data [16]. One patient developed probable fungal meningitis 26 months after receiving an injection of contaminated methylprednisolone. In addition, eight cases of relapsed fungal infection were reported. Median time to relapse was 90 days, but one relapse occurred 21 months after cessation of therapy. (See "Outbreak of fungal central nervous system and osteoarticular infections in the United States: Epidemiology, clinical manifestations, and diagnosis", section on 'Incubation period' and "Outbreak of fungal central nervous system and osteoarticular infections in the United States: Treatment", section on 'Outcomes'.)


Adverse pregnancy effects of improved control of malaria (November 2015)

Improvements in malaria control in some endemic areas have led to declines in malaria transmission and, in turn, immunity. A recent study from Mozambique illustrated an adverse consequence of a less immune population. In this study, a large reduction in malaria transmission in recent years was associated with a large reduction in maternal levels of antimalarial IgG antibodies against both pregnancy-specific parasite lines and more general parasite lines [17]. In addition, women who developed a malaria infection during pregnancy in recent years had greater reductions in hemoglobin level and newborn birth weight compared with pregnant women infected prior to the overall decline in malaria prevalence and reduced immunity. (See "Overview of malaria in pregnancy", section on 'Immunity'.)

Antitrypanosomal therapy for Chagas heart disease (September 2015)

Limited evidence is available on the efficacy of antitrypanosomal therapy in patients with established Chagas heart disease. The multicenter, double-blind BENEFIT trial randomly assigned 2854 patients with chronic Chagas cardiomyopathy to receive either benznidazole or placebo for up to 80 days with mean 5.4-year follow-up [18]. Although benznidazole reduced serum parasite detection compared with placebo, it did not reduce the primary outcome (the first of the following events: death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event). Despite the neutral overall result, all components of the composite end point were nominally less frequent in the treated group than in the placebo group, and the number of hospitalizations for cardiovascular causes in the benznidazole group was significantly reduced. We suggest antitrypanosomal therapy to treat patients with early chronic CD including those with mild cardiomyopathy, but not in those with more advanced stages of Chagas cardiomyopathy. (See "Chagas heart disease: Treatment and prognosis", section on 'T. cruzi infection'.)

Persistence of Ebola virus in bodily fluids (May 2015)

Among survivors of the 2014-2015 Ebola outbreak in West Africa, infectious virus or viral RNA has been detected from several sites (eg, urine, semen, and aqueous humor) even after it is no longer detected in blood [19-21]. Although transmission from persistent virus at these sites is possible, the risk of transmission is not well established. As an example, a patient in West Africa had detectable viral RNA in his semen 199 days after symptom onset. There was apparent transmission of Ebola virus to one, but not another, of his sexual contacts. To prevent sexual transmission of Ebola virus, the Centers for Disease Control and World Health Organization suggest Ebola survivors refrain from all sexual activity (oral, anal, vaginal) until more information on the persistence of infectious virus in convalescent patients becomes available; condoms should be used if abstinence is not possible [22,23]. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Risk of transmission through different body fluids'.)


WHO recommendations on HIV treatment and prevention (October 2015)

In 2015, the World Health Organization (WHO) updated its guidelines for the prevention and treatment of HIV infection to recommend initiation of lifelong antiretroviral (ART) for all HIV-infected patients, regardless of CD4 cell count or clinical stage [24]. This recommendation was based, in part, on mounting evidence that the clinical benefit of ART extends to those with very high CD4 cell counts and data demonstrating a dramatic reduction in sexual HIV transmission to uninfected partners with successful ART. The updated guidelines also recommend pre-exposure prophylaxis (PrEP) with a tenofovir-containing regimen as part of the HIV prevention strategy for individuals at substantial risk of HIV infection (ie, those for whom the predicted incidence of infection would be >3 per 100 person years). (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Initiation of antiretroviral therapy' and "Pre-exposure prophylaxis against HIV infection" and "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Recommended antiretroviral management'.)

Benefit of early antiretroviral therapy and isoniazid preventive therapy in endemic areas (July 2015)

In certain resource-limited settings, the epidemics of HIV and tuberculosis (TB) have converged to result in substantial morbidity and mortality, which can be reduced by antiretroviral therapy (ART) and treatment of latent TB infection. In a trial from Ivory Coast, over 2000 HIV-infected patients with a CD4 cell count <800 cells/microL were randomly assigned to receive early ART at the time of enrollment or to defer ART until meeting contemporaneous World Health Organization (WHO) criteria (which ranged from a CD4 cell threshold of 200 to 500 cells/microL over the course of the trial) [25]. Participants in each group were also randomly assigned to receive six months of isoniazid preventive therapy or not. Early ART and isoniazid each reduced the combined endpoint of all-cause death or severe HIV-related illness by approximately 45 and 35 percent, respectively. The effect of ART was similar among those with baseline CD4 cell counts >500 cells/microL. The benefit of isoniazid was statistically significant among participants who were interferon-gamma release assay (IGRA) test positive at baseline but not in those with a negative IGRA test. These findings demonstrate that the benefit of ART extends to those with CD4 cell counts >500 cells/microL, as seen in resource-rich settings, and reinforce the importance of therapy for the prevention of active TB disease among HIV-infected patients with evidence of latent TB infection. (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Optimal timing of antiretroviral therapy' and "Treatment of latent tuberculosis infection in HIV-infected patients", section on 'Antiretroviral therapy'.)

Direct-acting antiviral therapy for HCV in HIV-infected patients (July 2015)

Although HIV-infected patients had lower response rates to chronic hepatitis C virus (HCV) treatment with peginterferon and ribavirin compared with HIV-uninfected patients, a growing number of studies have demonstrated that HIV/HCV coinfection is not associated with worse response to direct-acting antiviral-based regimens. Most recently, the regimen of ledpasvir-sofosbuvir for 12 weeks and the regimen of the investigational NS5A inhibitor daclatasvir with sofosbuvir for 12 weeks were each reported to result in sustained virologic response (SVR) rates exceeding 90 percent among HIV/HCV coinfected patients, including those who had failed prior HCV treatment and those with cirrhosis [26,27]. The efficacy and safety in these studies are comparable to those observed among HCV monoinfected patients. Potential drug interactions with antiretroviral agents remain a major consideration when selecting HCV treatment regimens in HIV-infected patients. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)

Early versus deferred antiretroviral therapy in treatment-naive HIV-infected individuals (May 2015)

Trials have demonstrated that antiretroviral therapy (ART) improves morbidity and mortality in HIV-infected individuals with CD4 cell counts <350 cells/microL. The benefit of ART for those with higher CD4 cell counts had been suggested by observational data but had not previously been demonstrated in a randomized trial. In the START trial, 4685 HIV-infected adults who had not previously received ART and had a CD4 cell count >500 cells/microL were randomly assigned to initiate ART immediately or when the CD4 cell count declined to <350 cells/microL [28]. After approximately three years of follow-up, an interim analysis found that the risk of the combined outcome of AIDS-related events, serious non-AIDS events (eg, major cardiovascular, renal and liver disease, and cancer), or death was reduced by 57 percent with immediate compared with deferred treatment (42 versus 96 events). These data support guidelines in the United States that recommend ART initiation in all HIV-infected patients, regardless of CD4 cell count. (See "When to initiate antiretroviral therapy in HIV-infected patients", section on 'Introduction'.)


Outcomes with viral respiratory illness before allogeneic hematopoietic cell transplantation (July 2015)

Hematopoietic cell transplant (HCT) candidates with upper respiratory tract symptoms at the time that the conditioning regimen is due to begin should postpone transplantation until the illness has resolved, when feasible. This recommendation is supported by a prospective study that showed that patients with a respiratory virus detected prior to allogeneic HCT had fewer days alive and out of the hospital and lower survival at day 100 compared with patients with negative samples [29]. Among symptomatic patients, those with respiratory viruses detected had increased overall mortality compared with patients without viruses detected; among asymptomatic patients, detection of respiratory viruses was not associated with increased mortality. (See "Evaluation for infection before hematopoietic cell transplantation", section on 'Community respiratory viruses'.)

Updated ASCO guidelines for use of WBC growth factors (July 2015)

Updated guidelines from the American Society of Clinical Oncology (ASCO) are available for the use of white blood cell growth factors (colony stimulating factors, CSFs) [30]. The new guidelines specify several clinical situations in which primary prophylaxis with CSFs is appropriate to prevent febrile neutropenia during chemotherapy: Patients receiving a drug regimen that carries a baseline risk of febrile neutropenia of ≥20 percent, patients 65 years and older with diffuse aggressive lymphoma who are being treated with curative chemotherapy (particularly in the presence of comorbidities), and patients receiving dose-dense chemotherapy regimens that are supported by convincing efficacy data (eg, adjuvant treatment of high-risk breast cancer and high-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin for urothelial cancer). (See "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation".)

Risk of serious infections with biologic drugs for rheumatoid arthritis (May 2015)

Postmarketing surveillance and observational studies provided the first indications that the tumor necrosis factor (TNF)-alpha inhibitors are associated with an increased risk of serious infections. Data from individual randomized trials and large observational studies have been inconsistent on this issue. A meta-analysis of randomized trials of patients with rheumatoid arthritis who received biologic drugs including TNF-alpha inhibitors found that standard-dose biologic drugs and high-dose biologic drugs were associated with an increased risk of serious infections compared with traditional disease-modifying antirheumatic drugs (DMARDs), but low-dose biologic drugs were not [31]. The risk was lower in patients who were methotrexate-naive compared with those who had previously received a traditional DMARD or a TNF-alpha inhibitor. (See "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections", section on 'Assessing the risk of serious infection'.)


Statins and influenza vaccine immunogenicity and effectiveness (November 2015)

Statins are used commonly in older adults with hyperlipidemia and are known to have immunomodulatory effects, which could affect vaccine responses. In an observational study conducted in the context of a randomized trial that evaluated influenza vaccines in individuals >65 years of age, hemagglutination inhibition (HAI) geometric mean titers to various influenza strains were substantially lower in those receiving chronic statin therapy than in those not receiving it [32]. In addition, in the adjusted analysis of a large retrospective cohort study, statin use was associated with reduced influenza vaccine effectiveness against medically attended acute respiratory illness [33]. The observed associations between statin use and vaccine effectiveness could be due to confounding, as patients receiving statins are likely to be at differing baseline risk of influenza from those not receiving statins. Although these studies raise the possibility that older patients receiving statins are less likely to be protected by the influenza vaccine, such individuals should still receive statins, when indicated, as well as an influenza vaccine annually. (See "Seasonal influenza vaccination in adults", section on 'Efficacy'.)

Influenza vaccination and influenza-associated pneumonia (October 2015)

Many studies have demonstrated that influenza vaccination decreases the incidence of laboratory-confirmed influenza infection, but few have evaluated the effect on the serious complications of influenza. Recent data suggest that vaccination is associated with a reduced risk of influenza pneumonia. In a case-control study of adult and pediatric patients hospitalized for community-acquired pneumonia (CAP), those with laboratory-confirmed influenza-associated pneumonia had lower odds of having received an influenza vaccine during the same influenza season compared with those with CAP not associated with influenza [34]. The estimated vaccine effectiveness for preventing influenza-associated pneumonia was 57 percent. (See "Seasonal influenza vaccination in adults", section on 'Trivalent inactivated vaccines'.)

Oral recombinant H. pylori vaccine (October 2015)

In a randomized phase 3 trial, 4464 H. pylori uninfected children (ages 6 to 15 years) were assigned to a three-dose oral recombinant H. pylori vaccine or placebo [35]. At one year, the incidence of H. pylori infection was significantly lower in the vaccine group. Among patients who completed extended follow-up, H. pylori acquisition continued to be lower in vaccinated as compared with unvaccinated children, but protection levels were lower in the second and third year. There were no serious adverse events related to the vaccine. Additional studies with long-term follow-up are needed to validate these results. (See "Pathophysiology of and immune response to Helicobacter pylori infection", section on 'Vaccination'.)

Revised schedule for pneumococcal vaccination in older adults (September 2015)

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the 13-valent pneumococcal conjugate vaccine (PCV13) for adults ≥65 years of age [36]. In September 2015, the ACIP changed the recommended interval between administration of PCV13 and PPSV23 for immunocompetent adults ≥65 years of age from 6-12 months to ≥1 year to simplify the administration schedule (algorithm 1) [37]. In patients who have already received PPSV23, at least 1 year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Schedule for dual vaccination'.)

Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)

In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age [38]. Changes for the 2015-2016 season include:

Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines

A simplified dosing algorithm for children six months through eight years (algorithm 2)

Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 1)

(See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule' and "Seasonal influenza vaccination in adults", section on 'Overview'.)

Yellow fever vaccine booster doses (June 2015)

Immunity after a single dose of yellow fever vaccine is long lasting. In June 2015, the United States Advisory Committee on Immunization Practices (ACIP) issued recommendations stating that a single primary dose of yellow fever vaccine is adequate for most travelers, with additional doses reserved for certain at-risk individuals [39]. However, the World Health Organization (WHO) international certificate of yellow fever immunization for international travel is valid for only 10 years; a booster dose is required every 10 years for the certificate to be reissued. The World Health Assembly adopted the recommendation to remove the 10-year booster dose requirement from the International Health Regulations by June 2016; until this time, travelers to countries with a yellow fever vaccination entry requirement must have received a dose of yellow fever vaccine within the past 10 years. (See "Yellow fever", section on 'Whom to vaccinate'.)

US ACIP recommendations for serogroup B meningococcal vaccination (June 2015)

In late 2014 and early 2015, the US Food and Drug Administration approved two serogroup B meningococcal vaccines (Trumenba, MenB-FHbp and Bexsero, MenB-4C). In June 2015, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for serogroup B meningococcal vaccine for high-risk individuals aged 10 years or older; these include individuals with persistent complement component deficiencies, individuals with anatomic or functional asplenia, microbiologists routinely exposed to N. meningitidis isolates, and individuals at increased risk because of a serogroup B meningococcal disease outbreak [40]. These indications overlap with those for the quadrivalent meningococcal conjugate vaccine and are summarized in the table (table 2). Among patients with none of the above risk factors, the ACIP advises discussion between doctors and patients regarding vaccination against serogroup B meningococcus; routine vaccination has not been recommended [41]. (See "Meningococcal vaccines", section on 'Use in United States'.)


Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy (October 2015)

For pregnant women who live in areas with medium and high malaria transmission, we agree with the World Health Organization (WHO) strategy to provide intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). The optimal approach to IPTp is uncertain in areas of high SP resistance and malaria transmission, such as Kenya. In a recent trial including over 1500 Kenyan women randomly assigned to receive IPT with SP or dihydroartemisinin-piperaquine (DP), IPT with DP resulted in a lower prevalence of malaria infection at delivery (3 versus 10 percent) and fewer episodes of clinical malaria during pregnancy (38 versus 6 episodes) compared with IPT with SP [42]. The trial was not powered to detect small differences in neonatal outcomes. Before changing to IPT with DP, more data are needed to compare the effects of the two therapies on these outcomes. (See "Prevention and treatment of malaria in pregnant women", section on 'Intermittent preventive treatment during pregnancy'.)


Repeat testing for women treated for trichomoniasis (July 2015)

The risk of repeat infection following treatment for a sexually transmitted infection (STI) is high. In the United States, reinfection with Trichomonas vaginalis has been reported to occur in up to 17 percent of women following treatment for an initial infection. The 2015 Centers for Disease Control and Prevention (CDC) guidelines on the management of STIs recommend that women treated for confirmed T. vaginalis infection undergo repeat testing within three months of treatment, regardless of partner treatment status [43]. Prior guidelines had only listed retesting as a consideration. The preferred diagnostic test for repeat testing is a nucleic acid amplification test (NAAT) on a vaginal swab, which can be performed as soon as two weeks after treatment. Data are insufficient to support retesting men. (See "Trichomoniasis", section on 'Follow-up'.)

Updated CDC guidelines on the management of sexually transmitted infections (June 2015)

The US Centers for Disease Control and Prevention (CDC) updated its guidelines on the management of sexually transmitted infections in June 2015 [44]. Major revisions include a lower threshold for the diagnosis of urethritis based on microscopy of a urethral specimen, a new emphasis on the role of Mycoplasma genitalium in persistent urethritis and cervicitis, preference for nucleic acid amplification-based testing for the diagnosis of Trichomonas vaginalis, and a recommendation to retest women after treatment for T. vaginalis to evaluate for reinfection. New screening recommendations include annual hepatitis C virus (HCV) testing for HIV-infected men who have sex with men and T. vaginalis testing for HIV-infected women annually and when pregnant. (See "Urethritis in adult men", section on 'Diagnostic criteria' and "Mycoplasma genitalium infection in men and women", section on 'Nongonococcal urethritis' and "Trichomoniasis", section on 'Follow-up' and "Primary care of the HIV-infected adult", section on 'Sexually transmitted infections'.)


Prevalence and clinical presentation of Borrelia miyamotoi infection (June 2015)

Borrelia miyamotoi is an emerging zoonotic pathogen that is transmitted by the same genus of ticks (eg, Ixodes scapularis, Ixodes pacificus) that transmits Borrelia burgdorferi (the agent of Lyme disease), Anaplasma phagocytophilum, and Babesia species. In one case series, B. miyamotoi was identified using polymerase chain reaction (PCR) in approximately 1 percent of specimens from 11,515 patients in the northeastern United States who presented with an acute febrile episode from April through November in 2013 and 2014 [45]. Clinical information was available for 51 patients with B. miyamotoi infection; the majority had marked headache, myalgia, arthralgia, malaise, and/or fatigue, and 24 percent were hospitalized. Diagnostic testing is not widely available, but doxycycline, which is used to treat many other tick-borne infections, is also effective against B. miyamotoi. (See "Borrelia miyamotoi infection", section on 'Clinical manifestations'.)


Hepatic decompensation associated with ombitasvir-paritaprevir-ritonavir for chronic HCV infection (November 2015)

With more widespread use of ombitasvir-paritaprevir-ritonavir with or without dasabuvir for patients with chronic hepatitis C virus (HCV) genotypes 1 and 4 infection, reports of associated hepatic injury and decompensation have emerged [46]. Most cases occurred in patients with existing cirrhosis and within one to four weeks of drug initiation; some cases resulted in death or need for liver transplantation. Patients with compensated cirrhosis who use this regimen should be monitored closely for signs of decompensation and undergo interval transaminase and bilirubin testing after initiation. The regimen is contraindicated in individuals with Child B and C class cirrhosis. (See "Direct-acting antivirals for the treatment of hepatitis C virus infection", section on 'Ombitasvir-paritaprevir-ritonavir with or without dasabuvir'.)

Topical microbicides to reduce genital herpes acquisition (August 2015)

Preventive measures to reduce the transmission of genital herpes virus infections include the use of barrier protection and chronic suppressive antiviral therapy in infected individuals. The use of novel approaches, such as topical microbicides, is under investigation. The effect of vaginally administered tenofovir gel on herpes simplex virus type 2 (HSV-2) acquisition was evaluated in a study of seronegative women from South Africa who participated in a clinical trial designed to assess the efficacy of this agent in reducing HIV acquisition [47]. The incidence of HSV-2 infection was lower among those who received tenofovir gel (10 versus 21 cases per 100 person-years with placebo). In contrast, vaginal tenofovir did not reduce viral shedding among HSV-2-infected women in a separate study [48]. Topical tenofovir is not clinically available, and further longer-term study is warranted to clarify its overall effect on HSV-2 transmission. (See "Prevention of genital herpes virus infections", section on 'Topical microbicides'.)

Daclatasvir-based regimens for genotype 3 HCV infection (August 2015)

In the era of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, patients with genotype 3 infection have emerged as a difficult-to-treat population, with suboptimal sustained virologic response (SVR) rates with short courses of previously available regimens. In July 2015, the US Food and Drug Administration approved the use of the novel NS5A inhibitor daclatasvir in combination with sofosbuvir for genotype 3 HCV infection. This agent has been available in Europe and elsewhere. Daclatasvir plus sofosbuvir for 12 weeks is now our preferred regimen for genotype 3-infected patients without cirrhosis. In an open-label study that included 120 such patients, SVR rates were 96 percent with that regimen [49]. SVR rates were only 63 percent in the 32 patients with cirrhosis included in the study, although limited evidence suggests that efficacy is enhanced with the addition of ribavirin to the regimen [50,51]. Thus, daclatasvir plus sofosbuvir plus weight-based ribavirin is our preferred regimen for genotype 3-infected patients with cirrhosis; the regimen is given for 24 weeks, although the optimal duration is uncertain. Sofosbuvir plus peginterferon plus ribavirin for 12 weeks is an effective alternative for patients willing to take interferon and has more established efficacy data. Sofosbuvir plus ribavirin for 24 weeks can also result in acceptably high SVR rates for treatment-naïve patients with cirrhosis. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3", section on 'Genotype 3'.)

Hospitalization risk in children <9 years old with dengue vaccine CYD-TDV (July 2015)

No licensed vaccine is available for preventing dengue. The vaccine that is most advanced in development is CYD-TDV, a formulation of four chimeric yellow fever 17D vaccine viruses, each engineered to express the surface envelope and membrane proteins from one of the four dengue virus serotypes. The safety and efficacy of CYD-TDV after the administration of three doses over a 12-month period has been studied in three large pediatric trials. In an analysis of the long-term results from those trials, the pooled efficacy for preventing symptomatic dengue infection in the first 25 months was 60 percent for all ages [52]. However, the vaccine was associated with an elevated risk of hospitalization for dengue among children younger than nine years in the setting of natural infection in the third year after vaccination. Further follow-up of participants in these trials will be important to assess the durability of vaccine-induced protective immunity. (See "Prevention and treatment of dengue virus infection", section on 'Vaccination'.)

Causes of community-acquired pneumonia in adults in the United States (July 2015)

As molecular tests have become more widely available, viruses are being detected with increasing frequency in patients with community-acquired pneumonia (CAP). In the Etiology of Pneumonia in the Community (EPIC) study, an active Centers for Disease Control and Prevention (CDC) surveillance study of adults requiring hospitalization for CAP, one or more viruses were detected in 23 percent of cases, bacteria in 11 percent, bacteria and viruses in 3 percent, and fungi or mycobacteria in 1 percent; an etiology was not identified in 62 percent of cases [53]. The most commonly identified organisms were rhinovirus (in 9 percent), influenza virus (in 6 percent), and S. pneumoniae (in 5 percent). In a related study, detection of rhinovirus was associated with CAP in adults, but not in children [54]. These results add to accumulating evidence that rhinovirus is likely to play a role in CAP in adults. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Rhinovirus' and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiologic diagnosis'.)

Middle East respiratory syndrome coronavirus in South Korea and other Asian countries (June 2015)

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 to cause severe pneumonia in patients in the Arabian Peninsula. Cases continue to occur. A large outbreak occurred in South Korea between May and early July 2015; the index case was a man who had recently traveled to Bahrain, the United Arab Emirates, Saudi Arabia, and Qatar [55]. By early July 2015, 185 secondary and tertiary cases had been reported among household and hospital contacts in South Korea; 36 deaths were reported [56-60]. One case occurred in a man who traveled to China following exposure to two relatives with MERS-CoV infection; this patient is the first reported case in China [59]. The first case of MERS-CoV in Thailand was reported in June 2015 in a man who traveled from Oman to Bangkok [61]. (See "Middle East respiratory syndrome coronavirus", section on 'Cases and clusters'.)

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