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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.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2015. | This topic last updated: May 26, 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.


Enhanced gram-negative activity of novel beta-lactam/beta-lactamase inhibitor combinations (January 2015, MODIFIED March 2015)

The US Food and Drug Administration recently approved two novel cephalosporin-beta-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolazone-tazobactam, which were developed to treat highly resistant gram-negative infections. These agents have broad-spectrum in vitro activity against aerobic gram-negative rods, including Pseudomonas aeruginosa and most extended-spectrum beta-lactamase-producing gram-negative organisms. Ceftazidime-avibactam also has in vitro activity against some carbapenemase-producing organisms. In clinical trials, some of which have not been published yet, clinical cure rates with these new agents alone or in combination with metronidazole were similar to those with comparator antibiotics for complicated urinary tract and intra-abdominal infections [1-4]. (See "Combination beta-lactamase inhibitors, carbapenems, and monobactams", section on 'Ceftolozane-tazobactam' and "Combination beta-lactamase inhibitors, carbapenems, and monobactams", section on 'Ceftazidime-avibactam'.)

Trimethoprim-sulfamethoxazole and sudden death (December 2014)

While trimethoprim-sulfamethoxazole (TMP-SMX) has generally been felt to be well tolerated, a case-control study found an association between sudden death, possibly due to hyperkalemia, and prescription of TMP-SMX among older patients who were also receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) [5].Those who received TMP-SMX had an increased seven-day risk of sudden death compared with those who received amoxicillin (adjusted odds ratio 1.38, 95% CI 1.09-1.76). However, other factors that affected the choice of antibiotic may have confounded these results, and higher quality evidence is needed to determine whether this association is causal. (See "Trimethoprim-sulfamethoxazole: An overview", section on 'Life threatening effects'.)


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 [6]. 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'.)

Beta-lactam monotherapy for community-acquired pneumonia (April 2015, MODIFIED April 2015)

CAP-START, a large randomized trial performed in the Netherlands, compared empiric therapy for community-acquired pneumonia (CAP) using beta-lactam monotherapy, beta-lactam-macrolide combination therapy, or fluoroquinolone monotherapy in patients admitted to inpatient wards [7]. The risk of death by 90 days was 1.9 percent higher with the beta-lactam-macrolide strategy and 0.6 percent lower with the fluoroquinolone monotherapy strategy than with the beta-lactam strategy. These results reflect noninferiority of the beta-lactam strategy. The median length of hospital stay was similar for all strategies. It is important to note that only 2 percent of patients were found to have infections caused by atypical bacteria, such as Mycoplasma pneumoniae; beta-lactams do not have activity against these pathogens. In other studies from different regions of the world, atypical pathogens have accounted for ≥10 percent of cases of CAP in hospitalized patients, so it is uncertain whether the results of this trial are widely generalizable. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Combination therapy'.)

Increased mortality with delayed treatment for spontaneous bacterial peritonitis (April 2015)

Patients with spontaneous bacterial peritonitis (SBP) who develop septic shock have high mortality rates, but early initiation of antimicrobial therapy may result in improved outcomes. In a retrospective study of patients with cirrhosis and SBP-associated septic shock, the risk of mortality nearly doubled (1.9-fold increase) with every hour delay in administering antimicrobial therapy [8]. In patients with suspected SBP-associated sepsis, ascitic fluid cultures should be obtained immediately and empiric antimicrobial therapy initiated to maximize the patient's chance of survival. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Prognosis'.)

Pneumonia and long-term cardiovascular risk (February 2015)

Community-acquired pneumonia has been associated with increased short-term risk of cardiac events. In two cohorts of community-dwelling adults, hospitalization for pneumonia was also associated with increased long-term risk of new-onset cardiovascular disease (myocardial infarction, cerebrovascular accident, or fatal coronary heart disease), even after adjusting for traditional cardiovascular risk factors [9]. In one of the cohorts, the risk of cardiovascular events among patients with pneumonia was highest during the first year after hospitalization and remained higher than among controls through 10 years. In the other cohort, the risk of cardiovascular events was elevated during the first two years following pneumonia hospitalization, but not thereafter. (See "Prognosis of community-acquired pneumonia in adults", section on 'Association with cardiovascular events'.)

Infection associated with contaminated endoscopes (October 2014, MODIFIED February 2015)

In January 2014, the Centers for Disease Control and Prevention (CDC) reported that 69 cases of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) had been identified in the United States (44 from northeastern Illinois) in the previous year [10]. Further investigation identified 39 cases from one hospital [11]. Sporadic cases have been subsequently reported to the US Food and Drug Administration (FDA) [12]. The source of infection has been traced to the elevator channel of a single duodenoscope (the endoscopes used for endoscopic retrograde cholangiopancreatography [ERCP]). No lapses in the cleaning protocol were identified. It is theorized that the complex design of the elevator mechanism makes it more difficult to clean than other parts of endoscopes [11,13]. After changing duodenoscope reprocessing from high-level disinfection to gas sterilization with ethylene oxide, no new cases have been identified. Duodenoscopes should be considered as possible sources for CRE outbreaks in healthcare facilities and facilities should adhere to reprocessing and surveillance guidelines issued by the Centers for Disease Control and Prevention, the US Food and Drug Administration, and professional societies, such as the American Gastroenterological Association. If a patient is diagnosed with a multidrug-resistant organism following ERCP, the duodenoscope that was used for the procedure should be removed from service until it is verified to be free of pathogens [14,15]. (See "Endoscope disinfection", section on 'Carbapenem-resistant Enterobacteriaceae'.)

Adjunctive glucocorticoids for hospitalized patients with community-acquired pneumonia (January 2015)

There has been interest in using glucocorticoids as adjunctive therapy to antibiotics in hospitalized patients with community-acquired pneumonia (CAP) in an attempt to reduce the inflammatory response, which is likely to contribute to the morbidity of the disease. There are conflicting data on this approach, but the largest randomized trial suggests a modest benefit. In the trial, which included 785 hospitalized adults with CAP, prednisone 50 mg daily for seven days shortened the time to clinical stability by approximately one day compared with placebo, without an increase in complications [16]. In another randomized trial that included 120 patients in Spain with severe CAP and a high inflammatory response, there was less treatment failure among patients who received methylprednisolone 0.5 mg/kg every 12 hours for five days than in those who received placebo, but no difference in the rate of in-hospital mortality [17]. Pending the results of a larger trial evaluating mortality rates in severe CAP, we do not favor the routine use of adjunctive glucocorticoids in adults with CAP. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)

Multistate outbreak of listeriosis associated with caramel apples (December 2014)

A multistate outbreak of listeriosis associated with commercially produced prepackaged caramel apples was reported in the United States in December 2014 [18]. Updated case counts, a list of states in which cases have been reported, and guidance from the United States Centers for Disease Control and Prevention (CDC) can be found on the CDC’s website. (See "Epidemiology and pathogenesis of Listeria monocytogenes infection", section on 'Food epidemiology and outbreaks'.)


FDA approval of isavuconazole for invasive aspergillosis and mucormycosis (March 2015)

Isavuconazole was approved by the US Food and Drug Administration in March 2015 for the treatment of invasive aspergillosis and mucormycosis [19]. It is formulated as the prodrug, isavuconazonium sulfate, and it is available as an IV formulation and an oral formulation [20]. For patients with invasive aspergillosis who do not tolerate the first-line antifungal agent, voriconazole, we use either a lipid formulation of amphotericin B or isavuconazole in place of voriconazole. For patients with mucormycosis, isavuconazole can be used as an alternative to posaconazole for step-down therapy or salvage therapy in patients who do not tolerate posaconazole. (See "Pharmacology of azoles", section on 'Isavuconazole' and "Treatment and prevention of invasive aspergillosis" and "Treatment and prevention of invasive aspergillosis", section on 'Initial therapy' and "Mucormycosis (zygomycosis)", section on 'Approach to treatment'.)

Voriconazole plus anidulafungin for invasive aspergillosis (January 2015)

Voriconazole has been the first-line therapy for invasive aspergillosis for several years, but mortality remains substantial. A randomized trial assessed voriconazole with or without a second antifungal agent, anidulafungin (an echinocandin), for the treatment of invasive aspergillosis in patients with hematologic malignancy and/or hematopoietic cell transplant [21]. Results showed a non-significant trend toward improved six-week survival with the combination of voriconazole and anidulafungin compared with voriconazole monotherapy. A post-hoc analysis suggested that the survival benefit was statistically significant among a major subset of patients with probable invasive aspergillosis, defined as radiographic abnormalities and a positive galactomannan antigen. Based on these results, we favor the use of a combination regimen of voriconazole plus an echinocandin for the first one to two weeks of therapy of confirmed invasive aspergillosis. However, some experts remain uncertain about these data and prefer monotherapy with voriconazole. (See "Treatment and prevention of invasive aspergillosis", section on 'Voriconazole and an echinocandin'.)


Yaws eradication (February 2015)

Yaws is a treponemal infection that can cause destructive skin and bone lesions and is endemic to rural, equatorial regions in the Eastern Hemisphere. The approach to eradication of yaws consists of a single dose of oral azithromycin (30 mg/kg, maximum 2 g) to be given to the entire population in areas known to harbor yaws [22]. The efficacy of this approach was demonstrated in a study of mass treatment performed in rural villages on Lihir Island, Papua New Guinea [23]. Of 16,092 residents, 83 percent received mass treatment with single dose azithromycin and were monitored for one year; the prevalence of active yaws decreased from 2.4 to 0.3 percent, and the prevalence of latent yaws with high-titer seroreactivity decreased from 18.3 to 6.5 percent. There was a near-absence of high-titer seroreactivity among children 1 to 5 years of age. No evidence of macrolide resistance was observed. (See "Yaws, bejel, and pinta", section on 'Eradication'.)


Kidney transplantation from HIV-positive deceased donors into HIV-positive recipients (February 2015)

As is the case for most other patients with end stage renal disease (ESRD), kidney transplantation is superior to other forms of renal replacement therapy for HIV-positive patients with ESRD. In countries where dialysis is a limited resource, kidney transplantation is life-saving. However, kidney transplantation is limited by a shortage of available organs. In a case series from South Africa, 27 carefully selected and treated HIV-positive patients underwent transplantation with kidneys from HIV-positive deceased donors [24]. Patient and allograft survival at 1, 3 and 5 years was comparable to reported patient and allograft survival of HIV-positive patients who received kidneys from HIV-negative donors. (See "Solid organ transplantation in HIV-infected individuals", section on 'Renal transplantation'.)

HIV infection and chronic kidney disease (February 2015)

The HIV Medicine Association of the Infectious Diseases Society of America has updated its guidelines for the management of chronic kidney disease in patients infected with HIV [25]. They recommend screening for kidney disease with serum creatinine measurement and urinalysis at baseline and during use of antiretroviral therapy. The guidelines also discuss indications for nephrology referral and selection of antiretroviral regimens in the setting of renal impairment. The discussion in UpToDate is generally consistent with these guidelines. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Tenofovir-emtricitabine' and "Overview of kidney disease in HIV-positive patients" and "Primary care of the HIV-infected adult".)

Timing of antiretroviral initiation during pregnancy (January 2015)

The risk of HIV transmission from an infected mother to her infant is proportional to the level of maternal viremia at delivery. Among women not already taking an antiretroviral regimen, viral suppression at delivery is more likely when a regimen is initiated earlier during gestation. In a large US cohort of antiretroviral-naïve HIV-infected women who initiated a combination antiretroviral regimen during pregnancy, a detectable viral load at delivery was documented in 13 percent overall, but in 24 percent of those who initiated the regimen during the third trimester [26]. This supports our recommendation to initiate antiretroviral therapy promptly in treatment-naïve pregnant women with advanced HIV disease or CD4 cell count th week of gestation for HIV-infected pregnant women with higher CD4 cell counts. (See "Use of antiretroviral medications in pregnant HIV-infected patients and their infants in resource-rich settings", section on 'When to initiate antiretroviral medications during pregnancy'.)


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 [27]. 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: Risk of bacterial, viral, and fungal infections", section on 'Assessing infectious risk'.)


Effectiveness of pertussis vaccine in infants (May 2015)

Infants younger than 12 months have the highest incidence of pertussis and pertussis-related complications, including death. In a large case-control study, having received ≥1 dose of pertussis vaccine was associated with a 72 percent reduction in the risk of death and a 31 percent reduction in the risk of hospitalization in infants ≥6 weeks of age (the minimum age for the first dose of pertussis vaccine) [28]. However, 64 percent of the deaths occurred in infants younger than six weeks. These findings highlight the importance of timely pertussis immunization for infants, as well as maternal immunization during pregnancy and immunization of the infant’s close contacts, as recommended by the Global Pertussis Initiative [29]. (See "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age", section on 'Efficacy and effectiveness' and "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination' and "Bordetella pertussis infection in adolescents and adults: Treatment and prevention", section on 'Tdap booster'.)

The efficacy of an inactivated vaccine to prevent zoster (April 2015)

The live attenuated zoster vaccine reduces the risk of herpes zoster with a reported vaccine efficacy of 60 to 70 percent in adults 50 years and older, but it cannot be used in immunocompromised individuals and may have decreased efficacy in adults 70 years and older. A randomized, placebo-controlled trial evaluated the efficacy of HZ/su, an experimental recombinant inactivated zoster vaccine administered in two doses two months apart, among 15,411 adults 50 years and older [30]. After three years of follow-up, the overall vaccine efficacy against herpes zoster was 97.2 percent (95% CI 93.7-99.0), and efficacy among adults 70 years and older was similar to that seen in adults between 50 and 69 years of age. (See "Prevention of varicella-zoster virus infection: Herpes zoster", section on 'Inactivated vaccines'.)

Aerosolized measles vaccine inferior to subcutaneous vaccine with respect to seropositivity rate (April 2015)

Measles vaccine is usually given by subcutaneous injection; an aerosolized vaccine could be administered by individuals with less training and would not require sterile needles or syringes. In a study including 2004 infants aged 9.0 to 11.9 months in India randomized to receive measles vaccine either by aerosol inhalation or subcutaneous injection, aerosolized vaccine was found to be immunogenic but inferior to the subcutaneous vaccine with respect to seropositivity rate [31]. Follow-up was completed for 1560 children (775 children in the aerosolized vaccine group and 785 children in the subcutaneous vaccine group); seropositivity rates at day 91 were 85.4 and 94.6 percent, respectively. Subcutaneous administration of the measles vaccine remains the standard of care. (See "Prevention and treatment of measles", section on 'Types of vaccines'.)

Circulating influenza A H3N2 viruses and influenza vaccine effectiveness in the United States (December 2014, MODIFIED March 2015)

In December 2014, the United States Centers for Disease Control and Prevention (CDC) released a health advisory stating that more than half of influenza A H3N2 viruses collected and analyzed in the United States in October and November 2014 were antigenically different (drifted) from the H3N2 antigen included in this season's influenza vaccines [32]. Most isolated influenza viruses to date have been H3N2 strains. During previous seasons in which influenza A H3N2 viruses have predominated, higher hospitalization and mortality rates have been reported among older people, very young children, and individuals with certain medical conditions. In seasons where predominant circulating influenza viruses have antigenically drifted, decreased vaccine effectiveness has been observed. Nevertheless, vaccination typically provides some cross-protection against drifted viruses and should still reduce hospitalization and death. As of late February 2015, overall vaccine effectiveness was only 19 percent and vaccine effectiveness against influenza A H3N2 was only 18 percent [33]. Influenza vaccination is still highly recommended [32]. The CDC health advisory was issued to reemphasize the importance of the use of neuraminidase inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and prevention of influenza infection as an adjunct to vaccination. (See "Seasonal influenza vaccination in adults", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season' and "Seasonal influenza in children: Prevention with vaccines", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season'.)

Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014, MODIFIED March 2015)

The CAPiTA trial, which is the largest trial to assess the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13) in adults, compared PCV13 to placebo in approximately 85,000 immunocompetent adults ≥65 years of age in the Netherlands who had not received a pneumococcal vaccine previously [34]. The trial demonstrated 46 percent efficacy of PCV13 against vaccine-type pneumococcal pneumonia, 45 percent efficacy against vaccine-type nonbacteremic pneumococcal pneumonia, and 75 percent efficacy against vaccine-type invasive pneumococcal disease. Efficacy persisted for the duration of the trial (mean follow-up four years). However, some concern has been raised that since this trial began before PCV13 was used routinely in infants in the Netherlands, it might not answer the question of whether its use in adults is efficacious in countries that routinely vaccinate infants. (See "Pneumococcal vaccination in adults", section on 'Efficacy'.)

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 September 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending PCV13 for all adults ≥65 years of age [35]. The ACIP revision was prompted by results from the CAPiTA trial. Current recommendations for individuals ≥65 years of age who have not previously received either PCV13 or PPSV23 are to administer PCV13 followed 6 to 12 months later by PPSV23 (algorithm 1). In patients who have already received PPSV23, at least one year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Indications'.)

New human papillomavirus (HPV) vaccine targets nine HPV types (February 2015)

Infection with human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58 is implicated in approximately 90 percent of invasive cervical cancers. The US Food and Drug Administration has approved Gardasil 9, a 9-valent HPV vaccine that targets those seven HPV types in addition to the two types associated with genital warts (6 and 11), for the prevention of HPV-related disease [36]. In a trial that included approximately 14,000 females randomly assigned to receive the 9-valent or quadrivalent HPV vaccine, immune responses with the two vaccines were comparable for the HPV types targeted by both (6, 11, 16, and 18). Additionally, the 9-valent HPV vaccine was 97 percent effective for preventing precancerous and cancerous lesions of the cervix, vagina, and vulva associated with the other targeted HPV types (31, 33, 45, 52, and 58). Safety profiles were overall similar. We favor the 9-valent HPV vaccine for its broader HPV type coverage.

Routine immunization should be offered to boys and girls aged 11 to 12, but can be administered as early as nine years of age. Catch-up vaccination should be offered for males between the ages of 13 to 21 and females between 13 to 26 years who have not been previously vaccinated. Repeat vaccination with the 9-valent vaccine is likely not warranted for individuals who have completed a series with a different HPV vaccine.

(See "Recommendations for the use of human papillomavirus vaccines", section on 'Available vaccines'.)

No association between HPV vaccination and multiple sclerosis (January 2015)

Although anecdotal and sporadic case reports had fueled concerns about a potential causal relationship between human papillomavirus (HPV) vaccination and development of multiple sclerosis and other demyelinating disorders, larger studies have refuted this. In a study of nearly four million Swedish and Danish females aged 10 to 44 years, receipt of the quadrivalent HPV vaccine was not associated with demyelinating diseases, including multiple sclerosis, optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis [37]. This study adds to the abundance of data demonstrating the overall safety of HPV vaccination. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Postlicensure data'.)


Sputum Xpert MTB/RIF for discontinuation of TB airborne isolation (February 2015)

Serial acid-fast bacilli (AFB) sputum smears are traditionally used to assess the need for continued airborne infection isolation for patients with suspected tuberculosis, and airborne precautions can generally be discontinued if three serial AFB smear are negative. In February 2015, the US FDA approved the use of the Xpert MTB/RIF assay, a nucleic acid amplification test that detects Mycobacterium tuberculosis (MTB), as an alternative to serial AFB smears for this purpose [38,39]. This approval was based on a study demonstrating that sputum Xpert MTB/RIF results are highly predictive of AFB smear results and may require fewer sputum samples [40]. Xpert MTB/RIF assay testing on a single sputum sample detected MTB in approximately 97 percent of patients who had at least one positive result on two or three serial fluorescent-stained AFB sputum smears and were subsequently culture-confirmed as infected with MTB. Xpert MTB/RIF assay testing on two serial sputum samples detected 100 percent of AFB smear–positive/MTB culture-positive patients. (See "Diagnosis of pulmonary tuberculosis in HIV-negative patients", section on 'Xpert MTB/RIF assay' and "Tuberculosis transmission and control".)

Isoniazid and rifapentine for treatment of latent tuberculosis infection in children (February 2015)

Isoniazid (INH) is the regimen of choice for the treatment of latent tuberculosis infection in children, but full adherence throughout the nine-month course can be challenging. A study among 1058 children ages 2 to 17 years demonstrated that directly observed treatment with three months of INH and rifapentine (RPT) was as effective as nine months of unsupervised INH alone for prevention of tuberculosis [41]. Treatment related adverse events were uncommon and similar with the two regimens. Directly observed treatment with INH-RPT is a reasonable regimen for children aged 2 to 17 years when the circumstances make completion of nine months of daily INH difficult. (See "Latent tuberculosis infection in children", section on 'Isoniazid and rifapentine'.)


RTS,S/AS01 malaria vaccine in children (April 2015)

A successful malaria vaccine used in conjunction with other control interventions could reduce the global disease burden of malaria. Phase 3 trial results of RTS,S/AS01 vaccine demonstrated that the vaccine induced partial protection against clinical malaria among children ages 5 to 17 months over the follow-up period of the trial (median 48 months), and showed benefit of the 18-month booster [42]. In the intention-to-treat population, vaccine efficacy among children ages 5 to 17 months who received three doses plus a booster (months 0, 1, 2 and 20) was 36 percent. Formal recommendations from advisory groups for clinical use of this vaccine are forthcoming. (See "Epidemiology, prevention, and control of malaria in endemic areas", section on 'Vaccine development'.)

Cerebral malaria and elevated intracranial pressure (March 2015)

Cerebral malaria is an encephalopathy that presents with impaired consciousness, delirium, and/or seizures. Cerebral edema and elevated intracranial pressure may contribute to a fatal outcome. In one study that included 168 children with cerebral malaria, approximately 84 percent of deaths occurred among individuals with evidence of severe brain swelling on MRI at admission; such swelling was noted among 27 percent of survivors [43]. (See "Clinical manifestations of malaria", section on 'Cerebral malaria'.)


Ocular syphilis in the United States (April 2015)

Ocular syphilis, a potentially sight-threatening form of neurosyphilis, has been reported more frequently among HIV-infected patients compared with those without HIV. It can occur at any time after initial infection and may be associated with rash. Ocular findings typically include uveitis or optic neuritis, and the diagnosis is supported by a reactive serologic test. In the United States, an outbreak of ocular syphilis has been reported in California and Washington since December 2014; the majority of cases were among HIV-infected men who have sex with men, and several cases resulted in blindness [44]. (See "Epidemiology, clinical presentation, and diagnosis of syphilis in the HIV-infected patient", section on 'Neurosyphilis'.)


Investigational fixed-dose combination therapies for chronic HCV infection (May 2015)

Drug development for chronic hepatitis C virus (HCV) infection continues at a rapid pace and is yielding new, simple, and highly effective regimens that are both interferon- and ribavirin-free. Recent studies of such regimens have demonstrated the following:

A once-daily, single-pill combination of the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir given for 12 weeks resulted in sustained virological response (SVR) rates greater than 90 percent among treatment-naïve and experienced genotype 1-infected patients with and without cirrhosis [45-47]. The addition of ribavirin to the regimen did not appear to substantially improve outcomes. Data on this regimen in patients with HIV coinfection, Child-Pugh Class B cirrhosis, severe renal impairment, and genotype 4 or 6 infection are also very promising [48-50]. This regimen is not expected to be available until 2016. (See "Investigational therapies for hepatitis C virus infection", section on 'Grazoprevir and elbasvir'.)

A single-pill combination of the NS5A inhibitor daclatasvir, the NS3/4A protease inhibitor asunaprevir, and the non-nucleoside NS5B inhibitor beclasvir given twice daily for 12 weeks resulted in SVR rates of 92 and 89 percent among treatment-naïve and experienced genotype 1-infected patients without cirrhosis [51]. A trial among patients with cirrhosis suggested that response rates are even higher when this regimen is combined with ribavirin [52]. (See "Investigational therapies for hepatitis C virus infection", section on 'Daclatasvir and asunaprevir combinations'.)

Measles outbreak in United States (April 2015, MODIFIED April 2015)

The United States has experienced a record number of measles cases during 2014 to 2015. In 2014, 644 cases were reported from 27 states [53]. Between January 1 and May 1, 2015, 169 cases have been reported. Most cases have occurred among individuals who were unvaccinated. Children living in or traveling to areas where there is a measles outbreak (defined as ≥3 cases linked in time and space) and children traveling outside the United States should receive measles-mumps-rubella vaccine earlier than it is routinely recommended. (See "Epidemiology and transmission of measles", section on 'United States'.)

Avian H5N1 outbreak in Egypt (March 2015)

Highly pathogenic avian H5N1 influenza viruses have caused disease in >780 people since 2003 [54]. The largest outbreak of H5N1 influenza in humans to date began in Egypt in late 2014 and has continued into 2015; 116 cases and 36 deaths were reported between January and late March 2015 [55,56].  (See "Epidemiology, transmission, and pathogenesis of avian influenza", section on 'Avian influenza H5N1'.)

Possible association of giant cell arteritis with varicella zoster virus (March 2015)

The etiology of giant cell arteritis (GCA) remains unknown, although various infectious causes have been considered as triggering events. One of the largest studies to evaluate the relationship between varicella zoster virus (VZV) and GCA included temporal artery (TA) biopsies from 82 pathologically-confirmed GCA patients and 13 TA biopsies from healthy controls [57]. VZV antigen was found in 74 percent of pathologically-confirmed GCA TAs versus 8 percent of normal TAs. The majority of biopsies showing GCA contained VZV antigen in skip areas that correlated with adjacent GCA pathology. However, direct pathogenetic evidence of a causal role of VZV in GCA is lacking. (See "Pathogenesis of giant cell (temporal) arteritis", section on 'Etiology and pathogenesis'.)

Interferon-free regimens to treat HCV in HIV/HCV coinfected patients (February 2015)

Patients coinfected with HIV and hepatitis C virus (HCV) traditionally had lower response rates to HCV treatment with peginterferon and ribavirin compared with individuals without HIV infection. However, with the use of direct-acting antiviral (DAA) agents in HCV treatment, HIV infection is no longer a negative predictor of response. In two studies of HIV/HCV genotype 1 coinfected individuals, sustained virological response rates to two interferon-free DAA regimens (ledipasvir-sofosbuvir or ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin) were greater than 90 percent, comparable to rates in populations infected with HCV alone [58,59]. The major consideration in HCV antiviral regimen selection for HIV/HCV coinfected patients is the potential for drug interactions between antiretroviral and HCV antiviral agents. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)

Preventing hepatitis B virus reactivation in patients receiving chemotherapy (February 2015)

When patients with serologic evidence of hepatitis B virus (HBV) infection need immunosuppressive therapy for other reasons, antiviral therapy may be warranted to decrease the risk of HBV reactivation. We favor prophylaxis with entecavir or tenofovir over lamivudine in such cases because these agents have more potent antiviral activity and are less likely to select for drug resistant virus. This preference is supported by results of a trial in which 121 HBV surface antigen (HBsAg) positive patients were randomly assigned to prophylactic antiviral therapy with entecavir or lamivudine prior to receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for diffuse large B-cell lymphoma [60]. The rates of HBV-related hepatitis and HBV reactivation were lower among those who received entecavir. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy", section on 'Which agents to use'.)

Oseltamivir for the treatment of influenza in adults (January 2015)

Oseltamivir has been demonstrated to shorten the duration of influenza symptoms and to reduce the duration of viral shedding. However, studies and meta-analyses have provided contradictory results regarding the effect of oseltamivir on influenza-related lower respiratory tract complications in healthy adults. A 2015 meta-analysis evaluated all manufacturer-sponsored randomized trials, published and unpublished, of oseltamivir for the treatment of influenza in adults [61]. Among those with documented influenza, oseltamivir reduced the time to alleviation of all symptoms (median time 98 versus 123 hours), reduced lower respiratory tract complications requiring antibiotics, and reduced hospital admissions for any cause compared with placebo. In contrast to an earlier meta-analysis that aggregated study results and did not demonstrate a benefit with regards to complications, this meta-analysis pooled individual patient data from the trials, which is generally considered a more rigorous method [62]. These results support our recommendations to use an antiviral agent such as oseltamivir in patients with confirmed or suspected influenza and severe illness or at high risk of complications. (See "Treatment of seasonal influenza in adults", section on 'Efficacy of oseltamivir'.)

Rapid nucleic acid amplification test for seasonal influenza (January 2015)

A rapid nucleic acid amplification test for influenza, the Alere i influenza A & B test, is available in several countries in Europe. In January 2015, the US Food and Drug Administration allowed use of the test in non-traditional laboratory sites, including physicians' offices, emergency rooms, health department clinics, and other healthcare facilities [63]. This test uses a nasal swab sample and provides results (reports influenza A or B, but not subtypes) in as few as 15 minutes. It is performed on a small proprietary machine. Nucleic acid amplification tests are generally more sensitive than antigen and immunofluorescence techniques, which most other rapid influenza tests utilize. (See "Diagnosis of seasonal influenza in adults", section on 'Nucleic acid tests' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)

Late cytomegalovirus prophylaxis versus preemptive therapy following hematopoietic cell transplantation (January 2015)

During the early postengraftment period following allogeneic hematopoietic cell transplantation (HCT), preemptive strategies are employed more commonly than prophylactic strategies to prevent cytomegalovirus (CMV) disease. Optimal preventive strategies during the late postengraftment period (days 100 to 270) have been uncertain. In a multicenter trial, allogeneic HCT recipients at high risk for late CMV disease were randomly assigned to receive six months of valganciclovir prophylaxis or placebo at a median of approximately 97 days after HCT [64]. Plasma CMV levels were monitored weekly and the study drug was replaced by preemptive antiviral therapy if the CMV viral load increased above a certain threshold. Although fewer patients receiving valganciclovir prophylaxis warranted preemptive therapy (11 versus 36 percent of placebo recipients), the primary composite endpoint (death, CMV disease, or other invasive bacterial or fungal infections by 270 days after HCT) occurred at similar frequencies in both groups (20 and 21 percent). These results suggest that routine prophylaxis during the late postengraftment period is not warranted; however, it is prudent to monitor the CMV load in the blood in high-risk patients and initiate preemptive therapy if it becomes positive. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Late postengraftment'.)

Interferon-free regimens for chronic genotype 1 HCV infection (December 2013, MODIFIED January 2015)

Several highly effective and well tolerated interferon-free options are now available for chronic genotype 1 hepatitis C virus (HCV) infection. Ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir plus dasabuvir, and simeprevir plus sofosbuvir all achieve sustained virologic response (SVR) rates, and thus effective cure, in excess of 90 percent in genotype 1 infected patients [65-73]. The duration of the regimen and the decision of whether to add weight-based ribavirin depend on the treatment history, presence of cirrhosis, and, for the ombitasvir-paritaprevir-ritonavir plus dasabuvir regimen, the infecting subtype (1a or 1b) (algorithm 2). The choice between the regimens depends primarily on the potential for drug interactions and drug toxicity. Additionally, in the United States, options will be limited by the individual's insurance provider. If cost or insurance coverage is not an issue, we generally favor the regimen of ledipasvir-sofosbuvir for its favorable adverse effect profile, its minimal drug interactions, and its ease of administration (a single pill once daily). (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Selection of treatment regimens'.)

Intravenous peramivir for influenza (December 2014)

Peramivir was approved by the US Food and Drug Administration (FDA) in December 2014 for treating uncomplicated influenza infection in adults who have been ill for ≤2 days [74,75]. Peramivir is the first IV neuraminidase inhibitor to be approved by the FDA, although it has been in use in Japan and South Korea for several years. It is administered as a single intravenous dose of 600 mg. In a randomized trial, those who received peramivir had their influenza symptoms alleviated an average of 21 hours sooner and became afebrile approximately 12 hours sooner than those who received placebo. Patients who cannot receive zanamivir or oseltamivir (eg, those who cannot tolerate inhaled or enteral agents) should receive IV peramivir. Although the FDA has only approved IV peramivir for patients with uncomplicated influenza, we think it is also reasonable to use it for patients with severe influenza who cannot receive oral oseltamivir or inhaled zanamivir; in such patients, we would use either oseltamivir by a nasogastric tube or IV peramivir. (See "Treatment of seasonal influenza in adults", section on 'Efficacy of peramivir' and "Treatment of seasonal influenza in adults".)

Direct-acting antiviral agents for post-transplantation hepatitis C recurrence (November 2014)

Recurrence of hepatitis C virus (HCV) following liver transplantation occurs in more than 95 percent of patients who fail to have the virus eradicated prior to transplantation. Current treatment regimens using direct-acting antiviral agents such as sofosbuvir and simeprevir are based largely on studies in patients with HCV who have not undergone liver transplantation. Treatment of patients with HCV recurrence after liver transplantation with direct-acting antiviral agents was recently examined in a study with 34 patients [76]. The patients were given ombitasvir (an NS5A inhibitor), ritonavir-boosted paritaprevir (a protease inhibitor), dasabuvir (a nonnucleoside NS5B polymerase inhibitor), and ribavirin for 24 weeks. A sustained virologic response at 24 weeks was achieved by 97 percent of patients, with no episodes of graft rejection. This study supports the use of direct-acting antiviral agents in patients with HCV recurrence following liver transplantation. (See "Liver transplantation for hepatitis C virus infection", section on 'Other regimens'.)


Revised name and diagnostic criteria for chronic fatigue syndrome (February 2015)

Diagnostic criteria for chronic fatigue syndrome have been revised (table 1) by the Institute of Medicine (IOM), which has also suggested renaming the condition as systemic exertion intolerance disease (SEID) [77]. The IOM diagnostic criteria focus on the most specific features of the disease. Symptoms should be present for at least six months and have moderate, substantial, or severe intensity at least one-half of the time. Other criteria include post-exertional malaise, sleep problems, cognitive impairment, and orthostatic-related symptoms. (See "Clinical features and diagnosis of chronic fatigue syndrome (systemic exertion intolerance disease)", section on 'Definition'.)

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