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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: Aug 2014. | This topic last updated: Sep 15, 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.

ANTIMICROBIAL AGENTS

Safety of fluoroquinolones in children (June 2014)

Fluoroquinolones are not recommended for routine use in children <18 years of age because studies in immature animals have demonstrated the development of arthropathy with erosions of the cartilage in weight-bearing joints. A study evaluated the risk of musculoskeletal toxicity during five years of follow-up in children who received levofloxacin or a comparator for acute otitis media or community-acquired pneumonia [1]. Of children identified with a musculoskeletal adverse event, the number that were considered “possibly related” to drug therapy was equally low in both groups. No musculoskeletal adverse event was considered “likely related” to levofloxacin. Nevertheless, until further data are available to confirm these findings, the use of fluoroquinolones in children should be limited to the treatment of infections for which no safe and effective alternative exists. (See "Fluoroquinolones", section on 'Use in children'.)

Cardiovascular outcomes and azithromycin use for pneumonia (June 2014)

Large observational studies have shown conflicting results with regards to a possible increase in cardiovascular mortality associated with azithromycin use. A more recent large cohort study evaluated the association between azithromycin use and all-cause mortality and cardiovascular events in more than 60,000 United States veterans ≥65 years of age who were hospitalized with pneumonia [2]. Ninety-day mortality was significantly lower in those who were treated with an azithromycin-containing regimen versus those who received other guideline-concordant antibiotics. Compared with patients who did not receive azithromycin, those who received azithromycin were slightly more likely to have a myocardial infarction, but not arrhythmias, heart failure, or any cardiac event. An analysis of these data suggested that seven deaths were averted for each non-fatal myocardial infarction associated with azithromycin use, reflecting a net benefit of azithromycin for patients ≥65 years of age with pneumonia. (See "Azithromycin, clarithromycin, and telithromycin", section on 'QT interval prolongation and cardiovascular events'.)

New antibiotics with activity against MRSA for skin and skin structure infections (June 2014, MODIFIED June 2014)

Antibiotic options for the treatment of skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are growing. Dalbavancin and oritavancin have a similar mechanism of action and spectrum of activity to vancomycin, but can be administered as once-weekly intravenous doses because of long half-lives. Tedizolid is from the same antibiotic class as linezolid and can be administered intravenously or orally once daily. In several large randomized trials of adults with acute cellulitis, wound infections, and abscesses, including infections caused by MRSA, these new agents had efficacy and safety profiles similar to vancomycin and/or linezolid with more convenient dosing [3-5]. Dalbavancin, tedizolid, and oritavancin have been approved for skin and skin structure infections by the U.S. Food and Drug Administration in 2014. (See "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults", section on 'Dalbavancin' and "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults", section on 'Oritavancin'.)

Influenza vaccine administration by needle-free jet injector (June 2014)

Needle-free vaccine technology could be useful for immunizing needle-phobic patients and reducing the risk of needlestick injuries. In August 2014, the US Food and Drug Administration (FDA) approved an intramuscular inactivated influenza vaccine (Afluria) for use with a jet injector device (PharmaJet Stratis needle-free injection system) for adults between 18 and 64 years of age [6]. The jet injector uses a high-pressure narrow jet of liquid vaccine to penetrate tissue [7]. In a randomized trial in healthy adults, the immune response to influenza vaccine was comparable when administered by jet injector device or needle and syringe. The jet injector device was associated with a higher frequency of local injection site reactions. (See "Seasonal influenza vaccination in adults", section on 'Needle-free jet injector'.)

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 [8]. 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'.)

BACTERIAL INFECTIONS

Perioperative asymptomatic bacteriuria and prosthetic joint infection (August 2014)

Some clinicians screen and treat for asymptomatic bacteriuria prior to joint arthroplasty, but evidence to support this practice is lacking. Although asymptomatic bacteriuria was associated with subsequent prosthetic joint infection in a prospective study of nearly 2500 patients undergoing total hip or knee arthroplasty, treatment of the bacteriuria, which was at the discretion of the clinician, was not associated with a decreased risk of infection [9]. Furthermore, the organisms isolated from the urine were not the same as those from the surgical site infection in any patient. Although asymptomatic bacteriuria may be a marker for individuals at higher risk for subsequent prosthetic joint infection, it appears unlikely to be causative. We do not routinely perform urinalysis or culture in patients without urinary symptoms prior to or following joint arthroplasty. (See "Approach to the adult with asymptomatic bacteriuria", section on 'Patients undergoing joint arthroplasty'.)

Next-generation DNA sequencing for pathogen identification (June 2014)

Next-generation sequencing (NGS) is a method for determining DNA sequence by analyzing multiple DNA fragments in parallel; it allows sequencing of an exponentially greater number of genes than conventional DNA sequencing. Although NGS has been applied to the diagnosis of complex genetic disorders, a new report suggests it may also be helpful in identifying an infectious pathogen when microbial or serologic testing is unrevealing [10]. NGS was performed on the cerebrospinal fluid of a 14-year-old boy with unexplained fever and progressive neurologic deterioration in whom an extensive infectious disease evaluation had been negative. A species of Leptospira was identified, and antibiotic therapy was initiated with rapid clinical improvement. Subsequent testing confirmed the diagnosis. (See "Principles and clinical applications of next-generation DNA sequencing", section on 'Indications for next-generation sequencing'.)

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) [11]. 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 [12]. 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 healthcare 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 [13]. 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 [14]. 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 [15]. 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'.)

GLOBAL HEALTH

Outbreak of Ebola virus in West Africa (August 2014)

The largest outbreak of Ebola virus infection reported to date is occurring in West Africa. This outbreak started in Guinea and Liberia and has subsequently spread to Sierra Leone and Nigeria [16]. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have provided information to help clinicians evaluate and manage patients with suspected Ebola virus disease [17,18]. The decision to test an individual who may have been exposed to Ebola virus depends upon when the exposure occurred, if the exposure was high or low risk, and whether or not the individual is displaying signs and symptoms consistent with Ebola virus disease (for most patients fever plus symptoms such as severe headache, myalgias, gastrointestinal symptoms, or unexplained hemorrhage). If testing is indicated, patients should be should be placed on standard, contact, and droplet isolation precautions, and other special infection control measures should be implemented (table 1) [19,20]. Clinicians can refer to the CDC and WHO websites for additional information. (See "Diagnosis and treatment of Ebola and Marburg virus disease" and "Epidemiology, pathogenesis, and clinical manifestations of Ebola and Marburg virus disease".)

Efficacy of oral cholera vaccine in an epidemic setting (May 2014)

Shanchol, one of two internationally-available oral cholera vaccines, has been demonstrated in trials to provide protection against cholera several years after vaccination. However, its efficacy in the first few months after administration, and thus its utility in response to an epidemic, was previously unknown. After a 2012 cholera outbreak in Guinea, a nonselective mass vaccination campaign with Shanchol was undertaken. A small study that compared vaccination rates through this campaign between individuals who developed cholera within six months after the outbreak onset and individuals who did not develop cholera estimated vaccine efficacy at 87 percent [21]. (See "Overview of cholera", section on 'Vaccines'.)

HIV INFECTION

Efficacy of second-line antiretroviral regimens in resource-limited settings (September 2014)

In resource-limited settings, the choice of an antiretroviral regimen for HIV infection following virologic failure with an initial regimen must often be made without knowledge of the presence of resistance mutations. There has been concern that drug resistance following failure of a nucleoside reverse transcriptase inhibitor (NRTI) based regimen would render subsequent NRTI-based regimens less effective. However, in a trial from sub-Saharan Africa that included 1277 HIV-infected individuals who had failed treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs, rates of virologic suppression were similar with a boosted protease inhibitor plus two to three NRTIs or plus an integrase inhibitor (88 and 87 percent, respectively) [22]. Virologic suppression rates with boosted protease inhibitor monotherapy were lower. These data support the World Health Organization recommendations to use a boosted protease inhibitor with at least two NRTIs as a second line regimen in resource limited settings. (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Drug resistance'.)

Treatment guidelines for adults with HIV infection (July 2014)

The 2014 International Antiviral Society-USA panel (IAS-USA) has published antiretroviral treatment guidelines for adults with HIV infection [23]. These guidelines are generally in agreement with the 2014 Department of Health and Human Services panel recommendations [24]. ART should be initiated for virtually all treatment-naïve HIV-infected individuals. Recommended regimens contain a backbone of two different nucleoside/nucleotide reverse transcriptase inhibitors, and a third drug, which may be an integrase inhibitor, a non-nucleoside reverse transcriptase inhibitor, or a boosted protease inhibitor. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'RECOMMENDATIONS OF OTHERS'.)

Suicidality among HIV-infected individuals receiving efavirenz (July 2014)

Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is often included as part of a first-line antiretroviral regimen for treatment-naïve HIV-infected individuals. Recent data suggest that efavirenz is associated with long-term mental health consequences, including suicidality. In an analysis of 5332 HIV-infected individuals who had participated in four antiretroviral treatment trials, receipt of an efavirenz-containing regimen was associated with a twofold increase in suicidality (a combined measure of suicidal ideation, suicide attempts, and completed suicides) compared with regimens that did not contain efavirenz [25]. We do not use efavirenz-based regimens for treatment naïve patients with mental health disorders given the many other available treatment options. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Efavirenz'.)

Testing algorithms to diagnose HIV infection (July 2014)

We agree with new recommendations from the United States Centers for Disease Control and Prevention (CDC) to use a combination assay that detects HIV antigen and antibodies as the initial test for laboratory-based HIV screening and diagnosis for patients two years and older (algorithm 1) [26]. If the initial test is reactive, an HIV-1/HIV-2 differentiation assay should be performed as a confirmatory test. Testing with an antibody-only assay followed by a confirmatory Western blot is no longer recommended. In comparison, the new algorithm is better able to diagnose acute infection when antibody may not yet be detectable (eg, "window period of acute HIV infection") and can provide information as to whether the patient is infected with HIV-1, HIV-2, or both. Reactive rapid antibody tests performed in community-based settings should be confirmed using this new algorithm as well. (See "Screening and diagnostic testing for HIV infection", section on 'Testing algorithm'.)

Timing of antiretroviral initiation in HIV-infected patients with cryptococcal meningitis (July 2014)

HIV-infected individuals with cryptococcal meningitis can develop paradoxical worsening of cryptococcal disease following initiation of antiretroviral therapy (ART) because immune reconstitution can result in a local inflammatory reaction at sites of a pre-existing infection. Thus, the timing of ART initiation must weigh this risk against the potential advantage of early immune recovery in severely immunosuppressed patients. In a randomized trial of 177 HIV-infected patients with cryptococcal meningitis in Uganda and South Africa, mortality was higher when ART was initiated within one or two weeks after starting antifungal therapy compared with five weeks after starting antifungal therapy [27]. Most excess deaths associated with early ART initiation occurred two to five weeks after initiation of antifungal therapy. Based on results from this and other trials, we suggest that initiation of ART be delayed for at least four weeks after antifungal therapy has been started. For patients with access to close medical follow-up and preventative therapy, we typically start ART 10 weeks after the initiation of antifungal therapy to minimize the risks of immune reconstitution inflammatory syndrome (IRIS) and drug interactions. (See "Clinical management and monitoring during antifungal therapy of the HIV-infected patient with cryptococcal meningoencephalitis", section on 'Timing of antiretroviral therapy'.)

Guidelines on pre-exposure prophylaxis for HIV prevention (June 2014)

Pre-exposure prophylaxis (PrEP) with daily use of tenofovir-emtricitabine, a combination antiretroviral agent, can reduce the risk of HIV acquisition in uninfected individuals who are at high risk of infection. In 2014, the US Public Health Service formally released clinical practice guidelines to help providers decide which patients may benefit from PrEP [28]. The guidelines also advise on the evaluation and monitoring of patients who decide to initiate PrEP. To optimize the efficacy of PrEP, they stress the importance of a comprehensive approach to care that includes HIV testing prior to and during treatment, as well as adherence and risk reduction counseling. UpToDate recommendations are largely consistent with these guidelines. (See "Pre-exposure prophylaxis against HIV infection", section on 'Approach to pre-exposure prophylaxis against HIV'.)

Antiretroviral use in HIV-infected pregnant women (May 2014)

Earlier initiation of an antiretroviral regimen in HIV-infected pregnant women is associated with increased likelihood of viral suppression by the time of delivery and thus decreased risk of transmission, but must be weighed against potential fetal effects of first trimester drug exposure in women who do not warrant prompt treatment for their own health. Women who present to care later in pregnancy should initiate an antiretroviral regimen without delay. In 2014, the Department of Health and Human Services in the United States published updated guidelines on the evaluation and management of HIV-infected pregnant women [29]. Given increasing experience with certain antiretroviral agents during pregnancy, the list of preferred agents has grown. This now includes tenofovir-emtricitabine, tenofovir with lamivudine, abacavir-lamivudine, and efavirenz. Zidovudine-lamivudine, lopinavir-ritonavir, and ritonavir-boosted atazanavir remain preferred agents. We agree with the guidelines’ recommendation that antiretroviral regimens for treatment-naïve pregnant women be constructed from these agents as long as there are no issues with drug resistance. (See "Use of antiretroviral medications in pregnant HIV-infected patients and their infants in resource-rich settings".)

CD4 cell count monitoring for well-controlled HIV-infected patients (May 2014)

For HIV-infected individuals, CD4 cell count monitoring informs prognosis and the need for continued prophylaxis to prevent opportunistic infections. Among patients on stable antiretroviral therapy (ART) whose CD4 cell count has stabilized at a level well above the threshold for developing an opportunistic infection, CD4 cell count monitoring has traditionally been performed every 6 to 12 months. In 2014, the Department of Health and Human Services of the United States and the International Antiviral Society-USA panel issued new recommendations for less frequent monitoring in patients who have achieved consistent viral suppression and CD4 cell counts well above the threshold for opportunistic infections (eg, >300 cells/microL) on at least two years of ART [23,24]. In such patients, we monitor the CD4 cell count every 12 months if the CD4 cell count is between 300 and 500 cells/microL. If the CD4 cell count is >500 cells/microL, CD4 cell count monitoring is optional. More frequent testing is warranted for changes in clinical status (ie, receipt of immunosuppressive therapy or virologic failure). (See "Patient monitoring during HIV antiretroviral therapy", section on 'CD4 cell count monitoring'.)

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 [30]. 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 [31]. The risk of decompensation in HIV/HCV coinfected patients is even greater in the absence of antiretroviral therapy [32]. 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 [33]. 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'.)

IMMUNOCOMPROMISED HOSTS

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 [34]. 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'.)

IMMUNIZATIONS

ACIP recommendations for the 2014-2015 influenza season (August 2014)

In August 2014 the United States Advisory Committee on Immunization Practices (ACIP) released updated recommendations for the prevention of seasonal influenza with vaccines [35]. Important changes from previous recommendations include:

A preferential recommendation for the nasal spray vaccine (live attenuated influenza vaccine, LAIV) over the intramuscular injection (inactivated influenza vaccine, IIV) for children two through eight years of age who do not have specific contraindications to the nasal vaccine (eg, asthma, egg allergy, diabetes, immunosuppression). UpToDate agrees with this recommendation, but also prefers LAIV for children older than eight years. If LAIV is not immediately available, IIV should be administered to avoid missing an opportunity for influenza immunization. (See "Seasonal influenza in children: Prevention with vaccines", section on 'LAIV compared with IIV'.)

Changes to the dosing schedule for children six months through eight years of age (algorithm 2). (See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule'.)

Recommendations for adults are largely unchanged. (See "Seasonal influenza vaccination in adults", section on 'Overview'.)

Efficacy of high-dose influenza vaccine in elderly adults (August 2014)

Due to concern that standard-dose influenza vaccines may be less effective in elderly adults than in younger adults, a high-dose influenza vaccine, Fluzone high-dose, has been developed. In a trial that included more than 30,000 adults ≥65 years of age, Fluzone high-dose was modestly more effective than standard-dose Fluzone [36]. Among individuals in the high-dose group, 1.4 percent had laboratory-confirmed influenza associated with an influenza-like illness compared with 1.9 percent in the standard-dose group (relative efficacy 24.2 percent). The rates of serious adverse events were similar with the high-dose and standard-dose vaccines. For individuals ≥65 years of age, we prefer Fluzone high-dose when available rather than a standard-dose inactivated vaccine. However, the United States Advisory Committee on Immunization Practices has not stated a preference for Fluzone high-dose over the standard-dose inactivated influenza vaccine in older adults [35,37]. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

WHO poliovirus vaccination recommendations for travelers exiting 10 countries (June 2014)

In May 2014, the World Health Organization issued poliovirus vaccination recommendations for all residents and long-term visitors (>4 weeks) exiting 10 poliovirus-affected countries in order to prevent further spread of the disease [38]. The recommendations apply to Afghanistan, Cameroon, Equatorial Guinea, Ethiopia, Iraq, Israel, Nigeria, Pakistan, Somalia, and Syria. A dose of a poliovirus vaccine should be given within the year prior to exit from those countries. The burden for implementation of these recommendations lies with the poliovirus-affected countries. Although these recommendations are for vaccination on exit from the listed countries, travel health practitioners should be aware of individual country requirements in order to discuss whether vaccination prior to travel to the listed countries might be advisable. In the United States, the Centers for Disease Control and Prevention recommends that travelers to poliovirus-affected areas be fully vaccinated against poliovirus, including a one-time booster dose for adults [39]. (See "Poliovirus vaccination", section on 'Recommendations for travelers'.)

Influenza vaccine administration by needle-free jet injector (June 2014)

Needle-free vaccine technology could be useful for immunizing needle-phobic patients and reducing the risk of needlestick injuries. In August 2014, the US Food and Drug Administration (FDA) approved an intramuscular inactivated influenza vaccine (Afluria) for use with a jet injector device (PharmaJet Stratis needle-free injection system) for adults between 18 and 64 years of age [6]. The jet injector uses a high-pressure narrow jet of liquid vaccine to penetrate tissue [7]. In a randomized trial in healthy adults, the immune response to influenza vaccine was comparable when administered by jet injector device or needle and syringe. The jet injector device was associated with a higher frequency of local injection site reactions. (See "Seasonal influenza vaccination in adults", section on 'Needle-free jet injector'.)

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 [40]. 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) [41,42]. 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) [43]. 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'.)

MYCOBACTERIAL INFECTIONS

Corticosteroids of limited benefit in tuberculous pericarditis (September 2014)

Whether corticosteroids are beneficial for patients with tuberculous pericarditis has been controversial. A randomized trial including 1400 adults initiating antimicrobial treatment for definite or probable tuberculous pericarditis in South Africa (approximately two-thirds of patients had concomitant HIV infection) demonstrated no effect of adjunctive corticosteroids on the primary composite efficacy outcome of death, cardiac tamponade requiring pericardiocentesis, or development of constrictive pericarditis [44]. Corticosteroid use did reduce the incidence of constrictive pericarditis alone (4.4 versus 7.8 percent). The overall lack of benefit may have reflected harm from corticosteroid treatment in patients with HIV, and it remains possible that patients without HIV could benefit from corticosteroids. Based on the totality of the evidence, we do not routinely use adjunctive corticosteroids in the absence of constrictive disease or high risk for constrictive disease. This approach is in disagreement with prior guidelines favoring routine use of corticosteroids for all patients with tuberculous pericarditis.

We continue to suggest administration of corticosteroids for patients with constrictive tuberculous pericarditis and for those felt to be at high risk of developing the condition (ie, large effusion, high level of pericardial fluid inflammatory cells, or early signs of constriction). (See "Tuberculous pericarditis", section on 'Role of corticosteroids'.)

PARASITIC INFECTIONS

Posaconazole ineffective for chronic Chagas disease (May 2014)

There has been interest in evaluating posaconazole for the treatment of chronic Chagas disease (Trypanosoma cruzi infection) because it has shown promise in animal models. However, in a randomized open-label trial of 78 patients with chronic Chagas disease, approximately 85 percent of patients who received posaconazole had treatment failure, defined as detectable T. cruzi DNA during the 10-month follow-up period after the end of treatment, compared with 38 percent of those who received benznidazole [45]. (See "Chagas disease: Management of acute disease, early chronic disease, and disease in immunocompromised hosts", section on 'Antitrypanosomal therapy'.)

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 [46]. 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'.)

VIRAL INFECTIONS, NON-HIV

Clusters of enterovirus D68 infections in the United States (September 2014)

Since August 2014, clusters of severe respiratory infections due to enterovirus D68 have been reported in several states in the United States [47,48]. These have occurred predominantly in children with a prior history of asthma and have been characterized by low-grade or absent fever with wheezing, dyspnea, hypoxia, and perihilar infiltrates. The possibility of enterovirus D68 should thus be suspected in cases of severe respiratory illnesses without alternative explanation, particularly in young children. Treatment is supportive and prevention relies on basic hygienic measures, including handwashing with soap and water. Enterovirus D68 had previously been implicated in smaller clusters of respiratory infections but was otherwise rarely reported. Additional surveillance information can be found on the CDC website. (See "Virus-induced wheezing and asthma: An overview", section on 'Enterovirus D68 infection' and "Clinical manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Respiratory disease' and "Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections", section on 'Serotypes and disease'.)

Chikungunya fever in the Caribbean and the Americas (July 2014)

Chikungunya is an arthropod-borne virus (arbovirus) endemic to West Africa that causes acute febrile polyarthralgia and arthritis. In December 2013, the first cases of chikungunya fever in the western hemisphere were reported in the Caribbean Island of Saint Martin [49,50]. Since then, local transmission has been confirmed in many countries and territories in the Caribbean, North America, Central America, and South America [49,51-54]. The first two cases of local transmission in the continental United States were reported in Florida in mid-July 2014 [53,54]; local transmission has been reported more widely in Puerto Rico [55]. (See "Chikungunya fever", section on 'Americas'.)

Risk of perinatal transmission of HBV in the United States (June 2014)

Administration of hepatitis B virus (HBV) vaccination and hepatitis B immune globulin (HBIG) to newborns of women with chronic HBV infection significantly reduces the risk of perinatal HBV transmission but does not eradicate it. In an observational study of over 4000 infants born to HBV-infected mothers in the United States between 1997 and 2010, over 95 percent received HBV vaccination and HBIG [56]. Perinatal transmission occurred in 3.40 percent of births to hepatitis B e antigen (HBeAg) positive mothers and 0.04 percent of births to HBeAg negative mothers. Among women whose HBV DNA results and HBeAg status were known, no HBV transmission occurred with a viral load less than 5 x107 IU/mL, regardless of the HBeAg status. (See "Hepatitis B and pregnancy", section on 'HBV DNA level'.)

Screening for Hepatitis B virus infection in the United States (June 2014)

Infection with Hepatitis B virus (HBV) can lead to chronic liver disease and is preventable with vaccination. The US Preventive Services Task Force (USPSTF) has updated its statement on screening for HBV infection in nonpregnant adolescents and adults to recommend that individuals at high-risk for HBV infection be screened if they have not been vaccinated or if they were vaccinated without prior screening [57]. High-risk populations include persons born in regions with a prevalence of HBV ≥2 percent, US–born persons whose parents were born in regions with a prevalence ≥8 percent, injection drug users, men who have sex with men, household contacts of persons with HBV infection, and individuals with HIV infection. Existing guidelines from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease also support screening of high-risk individuals in the US. (See "Diagnosis of hepatitis B virus infection", section on 'Who should be tested or screened'.)

Increase in Middle East respiratory syndrome coronavirus cases and evidence of camel-to-human transmission (May 2014, MODIFIED May 2014)

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged to cause severe pneumonia in humans in the Arabian Peninsula in 2012. A sharp increase in cases, including hospital-associated clusters, was reported in Saudi Arabia and the United Arab Emirates in March and April 2014 [58,59]. The majority of cases of MERS-CoV occurred in Jeddah and Riyadh, Saudi Arabia, and in Abu Dhabi, United Arab Emirates. Isolated cases have also been reported in Greece, Malaysia, the Philippines, Jordan, Egypt, the United States, and the Netherlands in individuals who had traveled from Saudi Arabia or the United Arab Emirates to these countries [60-62]. A case has also been reported in Yemen in a man with no recent travel outside of Yemen [60]. There has been no clear evidence of sustained transmission of MERS-CoV in community settings. (See "Middle East respiratory syndrome coronavirus", section on 'Cases and clusters'.)

The virus is thought to be of animal origin and several studies have suggested that camels serve as an intermediate host. The strongest evidence of camel-to-human transmission comes from a study in which the MERS-CoV strains isolated from a man in Saudi Arabia with fatal infection and from one of his camels were demonstrated by full-genome sequencing to be identical [63]. (See "Middle East respiratory syndrome coronavirus", section on 'Camels'.)

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 [64]. 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 [65,66]. 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 [67]. Patients with confirmed anti-NMDA receptor encephalitis may respond favorably to immunosuppression. (See "Paraneoplastic and autoimmune encephalitis", section on 'Anti-NMDA receptor encephalitis'.)

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 [68]. 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 [69]. 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'.)

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