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What's new in infectious diseases
Official reprint from UpToDate® ©2016 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: Jan 2016. | This topic last updated: Feb 08, 2016.

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.


Frozen fecal microbiota transplantation for Clostridium difficile infection (January 2016)

Treatment with fecal microbiota transplantation (FMT) has been hampered by logistic difficulties in preparation and administration of the fecal suspension. In a randomized non-inferiority trial, 219 patients with recurrent Clostridium difficile infection (CDI) or refractory CDI were assigned to receive frozen-and-thawed or fresh FMT via rectal enema [1]. In the modified intention-to-treat population, rates of clinical resolution in the frozen FMT group were non-inferior to fresh FMT, and there were no differences in adverse events between the two groups. The use of frozen FMT also has the potential advantage of immediate availability. Frozen FMT is currently an investigational technique for the treatment of C. difficile. (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection", section on 'Suggested protocol'.)

Time to return to school following treatment for streptococcal pharyngitis (December 2015)

Traditionally, patients with streptococcal pharyngitis have been considered contagious until 24 hours following antibiotic therapy and so have not been allowed to return to daycare, school, or camp until this interval has passed. In a recent study including 111 children with a sore throat and positive streptococcal rapid antigen detection test (RADT) who were treated with single-dose amoxicillin, 91 percent had a negative follow-up RADT and throat culture the following morning (12 to 23 hours later) [2]. Based on these findings, children treated with amoxicillin for streptococcal pharyngitis by 5:00 pm are unlikely to be contagious by the next morning. When consistent with local policies, it would be reasonable to permit such children to attend school the following day if afebrile and clinically improved. (See "Treatment and prevention of streptococcal tonsillopharyngitis", section on 'Follow-up'.)

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 [3]. 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 [4,5]; 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 [6,7]. 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) [8]. 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) [9]. 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) [10]. 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'.)


IDSA guidelines on the management of candidiasis (January 2016)

The Infectious Diseases Society of America released updated guidelines for the management of patients with candidiasis [11]. A substantial change compared with previous versions is the preference for echinocandins (anidulafungin, caspofungin, micafungin) as first-line therapy for candidemia and invasive candidiasis. As an example, for both nonneutropenic and neutropenic patients with candidemia, an echinocandin is the preferred choice for initial therapy (table 1). This change is due to an increase in fluconazole-resistant Candida infections, the favorable safety profile of the echinocandins, and accumulating efficacy data and clinical experience to support the echinocandins. Important exceptions include Candida central nervous system, eye, and urinary tract infections, for which other antifungals are preferred. (See "Treatment of candidemia and invasive candidiasis in adults", section on 'Nonneutropenic patients'.)

Miscarriage risk with oral fluconazole (January 2016)

The pregnancy effects of oral azoles for treatment of vulvovaginal candidiasis is unclear. Studies have reported an increased risk of birth defects after exposure to high-dose azole therapy (400 to 800 mg/day), but not for the low dose therapy used to treat vulvovaginal infections (eg, fluconazole 150 mg). Prior studies have not reported an increased risk of miscarriage with oral fluconazole. However, a recent cohort study of over 3300 women who received 150 to 300 mg of oral fluconazole between 7 and 22 weeks of pregnancy reported an approximately 50 percent increased risk of miscarriage in exposed women compared with either unexposed women or with women treated with vaginal azole therapy [12]. We continue to offer topical azole treatment during pregnancy and prefer to avoid oral therapy until more data on reproductive outcomes are available. (See "Candida vulvovaginitis", section on 'Pregnancy'.)

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 [13]. 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 [14]. 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 [15]. 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'.)


New guidance on blood donation deferral for men who have sex with men in the United States (December 2015)

The US Food and Drug Administration has updated its guidance on blood donation for men who have sex with men (MSM). The new guidance specifies a deferral period of 12 months since the last MSM sexual contact rather than indefinite deferral [16]. Prospective donors are instructed not to donate if they have other risk factors for human immunodeficiency virus (HIV) infection such as a recent needle stick injury or blood splash, and permanent deferral remains in place for individuals who have tested positive for HIV, used non-prescription injection drugs, or engaged in sex in exchange for money or drugs. The 12-month deferral has already been in place for other donors who have sex with at-risk individuals, and it aligns the US policy with that of Australia and the United Kingdom. Other countries have deferral periods ranging from six months to indefinite. (See "Blood donor screening: Medical history", section on 'Human immunodeficiency virus'.)

Tenofovir alafenamide as part of a coformulated antiretroviral regimen (November 2015)

Tenofovir is a preferred nucleoside to use in a combination antiretroviral regimen for the treatment of HIV infection. Until recently, tenofovir was available only as tenofovir-disoproxil fumarate (TDF), which has been associated with renal toxicity and decreased bone mineral density. As of November 2015, a newer formulation, tenofovir alafenamide (TAF), is available in the United States as part of a single tablet co-formulation, elvitegravir-cobicistat-emtricitabine-TAF (ECF-TAF) [17]. This combination agent is as effective as elvitegravir-cobicistat-emtricitabine-TDF (ECF-TDF) in suppressing HIV RNA with fewer adverse renal and bone effects [18]. ECF-TAF can be used for patients with reduced kidney function (estimated glomerular filtration rate [eGFR] ≥30 mL/min/m2), unlike ECF-TDF, which should only be used in patients with an eGFR >70 mL/min/m2. ECF-TAF is considered a recommended regimen by the United States Department of Health and Human Services [19]. TAF is not yet available as a single agent or in other combinations. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Preferred regimens'.)

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 [20]. 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'.)


Updated adult immunization schedule in the United States (February 2016)

Updates to the adult immunization schedule for 2016 have been issued by the United States Advisory Committee on Immunization Practices (ACIP) (figure 1 and figure 2) [21]. Changes from the 2015 schedule include updates to the recommendations for pneumococcal vaccine, serogroup B meningococcal (MenB) vaccine, and human papillomavirus (HPV) vaccine. The interval between administration of the 23-valent pneumococcal polysaccharide (PPSV23) and the 13-valent pneumococcal conjugate (PCV13) vaccines has been changed from '6 to 12 months' to 'at least one year' for immunocompetent adults aged ≥65 years. In addition, the MenB vaccine series should be administered to individuals age ≥10 years who are at increased risk for serogroup B meningococcal disease. Finally, the nine-valent HPV vaccine has been added to the schedule as an option for routine HPV vaccination for females and males. (See "Approach to immunizations in healthy adults", section on 'Immunization schedule for healthy adults'.)

Adjuvanted influenza vaccine approved for elderly adults in the United States (November 2015)

There has been interest in using adjuvants in influenza vaccines in elderly individuals, who have reduced immune responses to influenza vaccines; adjuvants are substances that amplify the immune response to an antigen. In November 2015, an adjuvanted trivalent inactivated influenza vaccine (Fluad) was approved for use in individuals ≥65 years of age in the United States [22]. It is the first adjuvanted seasonal influenza vaccine to be approved in the United States, but it has been approved already in >35 other countries. The vaccine is formulated with the adjuvant MF59, an oil-in-water emulsion of squalene oil. Studies have shown that the MF59-adjuvanted vaccine has comparable [22] or higher immunogenicity compared with unadjuvanted vaccines [23-25]. Until further data are available, we continue to suggest the non-adjuvanted high-dose inactivated vaccine for individuals ≥65 years of age. (See "Seasonal influenza vaccination in adults", section on 'Adjuvanted vaccine' and "Seasonal influenza vaccination in adults", section on 'Vaccine formulations'.)

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 [26]. 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 [27]. 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 [28]. The estimated vaccine effectiveness for preventing influenza-associated pneumonia was 57 percent. (See "Seasonal influenza vaccination in adults", section on 'Trivalent inactivated vaccines' and "Seasonal influenza in children: Prevention with vaccines", section on 'Indications'.)

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 [29]. 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 [30]. 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) [31]. 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 [32]. 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 2)

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


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 [33]. 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'.)


Azithromycin versus doxycycline for uncomplicated chlamydia (January 2016)

The first-line regimens for uncomplicated urogenital chlamydial infection are azithromycin administered as a single dose or a seven-day course of doxycycline administered twice daily. There is emerging evidence that the efficacy of doxycycline may be marginally greater than that of azithromycin, although the reasons for this are unknown. In a trial of 310 adolescents and young adults who screened positive for urogenital Chlamydia trachomatis upon entrance into a correctional facility, microbial cure rates at 28 days were high for both doxycycline and azithromycin (each administered as directly-observed therapy), but were numerically higher for doxycycline (100 versus 97 percent) [34]. Adherence is the main challenge with the doxycycline regimen, and direct observation of the full course is unrealistic in most situations; thus, it is uncertain that doxycycline would achieve a similarly superior cure rate in the community. Given the very high efficacy of azithromycin, we continue to favor directly-observed single-dose azithromycin for treatment of uncomplicated urogenital C. trachomatis infection. (See "Treatment of Chlamydia trachomatis infection", section on 'First-line agents'.)


Elbasvir-grazoprevir for chronic HCV infection (February 2016)

Despite the proliferation of interferon-free regimens for the treatment of chronic hepatitis C (HCV) infection, safety concerns have limited options for patients with severe renal impairment, who have been excluded from trials of most available regimens. In January 2016, the US Food and Drug Administration approved the new combination regimen elbasvir-grazoprevir for the treatment of patients with genotypes 1 and 4 HCV infection, including those with any degree of renal impairment (including dialysis dependence) [35]. In a randomized, placebo-controlled trial of genotype 1-infected patients with estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2, the sustained virologic response (SVR) rate was 94 percent among the 122 patients who received elbasvir-grazoprevir for 12 weeks, and adverse event rates were similar between treatment and placebo groups [36]. These results were comparable to those among patients with normal renal function. Elbasvir-grazoprevir is given for 12 to 16 weeks with or without ribavirin, depending on the presence of pre-existing resistance-associated variants in the NS5A protein and prior exposure to HCV protease inhibitors. (See "Treatment of chronic hepatitis C infection in adults with renal impairment".)

Hepatitis B virus reactivation in patients undergoing chemotherapy for solid tumors (January 2016)

Patients with serologic evidence of hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg]-positive or hepatitis B core antibody [anti-HBc]-positive) are at risk for HBV reactivation if they receive immunosuppressive therapy. However, the magnitude of risk for patients receiving chemotherapy for solid tumors has not been well established. In a systematic review of such patients, the risk of reactivation among those who were HBsAg-positive ranged from 4 to 68 percent, with most studies reporting a reactivation risk greater than 10 percent [37]. Antiviral therapy administered during chemotherapy was associated with an approximately 90 percent reduction in HBV reactivation risk as well as reductions in HBV-related hepatitis and the need for chemotherapy interruption. Although some expert groups disagree, we check HBV serologies before initiating therapy with any potentially immunosuppressive chemotherapy. Our recommendations for prophylactic antiviral therapy depend upon the HBsAg status of the patient and the type of chemotherapy used. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy", section on 'Who is at risk for HBV reactivation'.)

Zika virus infection in the Americas (January 2016)

Zika virus is a member of the flavivirus family that is spread via mosquito bites. Outbreaks have occurred in Africa, Southeast Asia, and the Pacific Islands; more recently Zika virus has spread to the Americas. More than 20 countries in Latin America have confirmed circulation; cases of Zika virus infection in the United States have occurred among returning travelers. The illness is usually mild; typical symptoms include fever, rash, joint pain, and conjunctivitis. However, Zika virus infection has also been associated with perinatal complications (congenital microcephaly and fetal losses) and Guillain-Barre syndrome [38]. In 2015, more than 3500 cases of microcephaly were reported among newborns in Brazil; this represents a 20-fold increase in the number of cases compared with years prior to the circulation of Zika virus [39]. In January 2016, the United States and European Centers for Disease Control advised that pregnant women consider postponing travel to any area where Zika virus transmission is ongoing and also advised that healthcare providers ask all pregnant women about recent travel, with follow-up testing (ultrasound, laboratory testing, or both) depending on clinical circumstances [40]. Anecdotal reports of apparent sexual transmission have been described [41]. Although this appears to be an infrequent mechanism for Zika virus transmission, it may be prudent for men with symptoms of Zika virus infection who have female sexual partners of childbearing age to defer unprotected sex for at least a few weeks following resolution of symptoms. Zika virus is also transmissible via blood products; outside of areas with local mosquito-borne Zika virus transmission, self-deferral of blood donation for 28 days following potential Zika virus exposure has been advised [42]. (See "Zika virus infection", section on 'Geographic distribution'.)

Investigational combination of sofosbuvir plus velpatasvir for chronic HCV infection (November 2015)

The selection of all-oral antiviral regimens for patients with chronic hepatitis C virus (HCV) infection currently depends on the infecting genotype, treatment history, and the presence of cirrhosis. The investigational agent sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, appears extremely effective across viral genotypes and patient characteristics, and thus offers the possibility of a streamlined approach to regimen selection. In a randomized, placebo-controlled trial of patients with genotypes 1, 2, 4, 5, and 6 infection, including those with cirrhosis and prior treatment failure with interferon-containing regimens, the sustained virologic response (SVR) rate among the 624 patients who were assigned to receive sofosbuvir-velpatasvir for 12 weeks was 99 percent [43]. In another study, the regimen resulted in an SVR rate of 98 percent among 163 treatment-naïve genotype 3-infected patients without cirrhosis [44]. SVR rates were somewhat lower, but still high (89 to 93 percent), in the setting of genotype 3 infection with cirrhosis and/or prior treatment failure. (See "Investigational therapies for hepatitis C virus infection", section on 'Sofosbuvir and velpatasvir'.)

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 [45]. 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 [46]. 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 [47]. 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 'Investigational approaches'.)

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 [48]. 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 [49,50]. 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'.)

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