IDupdateSept2023.pdf

10/10/23, 1:41 PM What's new in infectious diseases - UpToDate Official reprint from UpToDate® www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. What's new in infectious diseases AUTHORS: Elinor L Baron, MD, DTMH, Allyson Bloom, MD, Milana Bogorodskaya, MD, Sheila...

10/10/23, 1:41 PM What's new in infectious diseases - UpToDate Official reprint from UpToDate® www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. What's new in infectious diseases AUTHORS: Elinor L Baron, MD, DTMH, Allyson Bloom, MD, Milana Bogorodskaya, MD, Sheila Bond, MD, Keri K Hall, MD, MS, Jennifer Mitty, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2023. This topic last updated: Oct 06, 2023. 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. COVID-19 Updated COVID-19 mRNA vaccine recommendations (September 2023) The US Food and Drug Administration and Centers for Disease Control and Prevention have updated COVID-19 vaccine authorizations and recommendations [1,2]. Available COVID-19 vaccines have been updated to target Omicron variant XBB.1.5 (Moderna COVID-19 vaccine 2023-2024 formula, Pfizer COVID-19 vaccine 2023-2024 formula, and Novavax 2023-2024 formula); bivalent vaccines are no longer available. An updated mRNA vaccine is recommended for all individuals aged six months and older. Immunocompetent individuals five years and older should receive one updated vaccine, regardless of prior vaccination history. For individuals who are four years or younger or have an immunocompromising condition ( table 1), the number of recommended updated vaccines depends on their vaccination history. Our approach to COVID-19 vaccination is consistent with these recommendations. (See "COVID-19: Vaccines", section on 'Indications and vaccine selection' and "COVID-19: Vaccines", section on 'Benefits of vaccination'.) Adjunctive immunomodulators for severe COVID-19 (August 2023) For patients hospitalized for COVID-19 who require high-flow oxygen or ventilatory support, we suggest adding baricitinib or tocilizumab to dexamethasone to further reduce mortality. Other immunomodulatory agents may also improve outcomes. In a randomized trial of patients with severe COVID-19, most of whom were on remdesivir and glucocorticoids, https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 1/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate infliximab and abatacept each reduced 28-day mortality compared with placebo (10 and 11 versus 15 percent) but did not improve time to clinical improvement [3]. The trial did not detect a benefit with cenicriviroc. Despite their potential efficacy, we do not routinely use infliximab or abatacept for COVID-19, because they do not offer clear advantages over baricitinib or tocilizumab, which have more established benefit and, in the United States, are approved for this indication. (See "COVID-19: Management in hospitalized adults", section on 'Limited roles for alternative immunomodulators'.) Bacille Calmette-Guérin vaccine not effective against COVID-19 (May 2023) It has been hypothesized that the immunomodulatory properties of Bacille Calmette-Guérin (BCG) vaccine might enhance protection against COVID-19 infection. In a trial including more than 3300 health care workers in Australia, Europe, and Brazil (where most individuals receive BCG vaccine at birth), individuals were randomly assigned to receive BCG-Denmark vaccine or placebo [4]. BCG vaccination did not reduce the risk of COVID-19 infection. The development of COVID-19–specific vaccines sooner than expected was as an important limitation for this trial, leading to smaller sample size and shortened observation time. (See "Prevention of tuberculosis: BCG immunization and nutritional supplementation", section on 'Effect on risk of respiratory infection and COVID-19 in adults'.) Ventilatory support of critically ill pregnant patients with COVID-19 (March 2023) Limited data are available in pregnant females who are critically ill with COVID-19. In a cohort study of 91 such patients, lung mechanics and ventilatory parameters during advanced respiratory support were similar to nonpregnant patients with COVID-19 [5]. Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score was the only risk factor for invasive mechanical ventilation. Fetal delivery was induced in nearly two-thirds of patients and mainly for maternal reasons. Delivery did not improve ventilatory parameters other than the arterial oxygen tension to fraction of inspired oxygen ratio. These findings suggest that the approach to advanced respiratory support for critically ill patients with COVID-19 is similar for pregnant and nonpregnant patients. (See "Critical illness during pregnancy and the peripartum period", section on 'COVID-19'.) ANTIMICROBIAL AGENTS No benefit for continuous antibiotic infusion in critically ill patients with sepsis (August 2023) Whether the continuous infusion of antibiotics has improved clinical efficacy compared with traditional intermittent infusion is unclear. In a randomized trial of over 600 patients with sepsis, meropenem, given either as a continuous or intermittent infusion, resulted in similar https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 2/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate rates of the composite outcome of 28-day mortality and emergence of pandrug bacterial resistant (47 versus 49 percent [mortality 30 versus 33 percent]) [6]. Other outcomes were also similar, including 90-day mortality and length of stay. Lack of therapeutic monitoring and common prescription of other antimicrobials may have limited the ability to detect a between-group difference. We continue to prescribe intermittent infusions of antibiotics, unless otherwise indicated. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Dosing'.) BACTERIAL INFECTIONS Revised Duke criteria for diagnosis of infective endocarditis (August 2023) The Duke criteria for diagnosis of infective endocarditis (IE) have been revised to reflect changes in the epidemiology of IE, as well as new imaging and diagnostic tools [7]. The 2023 Duke-International Society for Cardiovascular Infectious Disease criteria classify Enterococcus faecalis as a typical cause of IE regardless of acquisition site (eg, community or healthcare associated) or presence of a primary extracardiac focus; previously E. faecalis was included as a major criterion only if community acquired and in the absence of a primary focus. The criteria also incorporate advances in microbiologic diagnostic testing, such as tissue polymerase chain reaction (such as amplicon or metagenomic sequencing and in situ hybridization). Advances in imaging include improved understanding of the diagnostic utility of cardiac computed tomography (CT) and fluorodeoxyglucose positron emission tomography with CT for detection of IE. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Basis for Duke criteria revision'.) Fecal microbiota oral capsules for preventing recurrent Clostridioides difficile infection (May 2023) In 2023, the US Food and Drug Administration approved a fecal microbiota oral capsule (SER109; Vowst) composed of live, purified Firmicutes spores for the prevention of recurrent Clostridioides difficile infection (CDI) in adults with ≥2 prior episodes [8]. In clinical trials of this product, 79 percent of participants did not have a recurrence up to 24 weeks after their prior CDI. It remains to be seen how this new fecal microbiota oral capsule will compare with traditional methods of fecal microbiota transplantation, the recently approved fecal microbiota rectal suspension, and bezlotoxumab, and whether it is a cost-effective preventive tool for CDI recurrences. (See "Fecal microbiota transplantation for treatment of Clostridioides difficile infection", section on 'Specific bacterial FMT'.) Burden of typhoid fever in India (May 2023) https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 3/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate Vaccine deployment for prevention of typhoid in endemic areas has been limited, in part because of limited epidemiologic data. In a prospective study performed in India between 2017 and 2020, weekly surveillance for acute febrile illness was performed among more than 24,000 children age 6 months to 14 years at three urban sites and one rural site [9]. The risk of culture-confirmed typhoid fever was greater in urban areas (576 to 1173 cases versus 35 cases per 100,000 child-years at the rural site). The risk was greater in larger households with fewer assets and without a sanitary toilet. These findings are important for guiding decisions regarding typhoid vaccine deployment, particularly in endemic urban settings. (See "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis", section on 'Worldwide'.) FUNGAL INFECTIONS Rezafungin for invasive candidiasis (August 2023) Echinocandins are the treatment of choice for initial treatment of invasive candidiasis. A new echinocandin, rezafungin, has been approved by the US Food and Drug Administration and is now available for adults 18 years or older with candidemia or invasive candidiasis who have limited alternative options [10]. Approval was based on two randomized trials that found no difference in overall mortality, clinical cure, or mycological eradication with rezafungin compared with caspofungin [11,12]. Of note, the trials excluded children, patients with severe liver disease, and patients with endocarditis, osteomyelitis, prosthetic joint infection, central nervous system infection, or eye infection. Rezafungin is unique in that it is administered as a once-weekly infusion, which is practical for outpatient echinocandin therapy; however, we continue to favor the other echinocandins for initial inpatient management and oral azole therapy for step-down therapy. (See "Management of candidemia and invasive candidiasis in adults", section on 'Non-neutropenic patients'.) Outbreak of fungal meningitis associated with epidural anesthesia (June 2023) In May 2023, an outbreak of fungal meningitis was reported in the United States among patients who had cosmetic procedures under epidural anesthesia in the city of Matamoros, Tamaulipas, Mexico [13]. The causative agent was identified as Fusarium solani species complex. As of June 14, 2023, 18 suspected, 10 probable, and 6 confirmed cases have been reported; four of these patients died. Persons who received epidural anesthesia at River Side Surgical Center or Clinica K-3 since January 2023 should be evaluated for meningitis, regardless of symptoms. Empiric therapy with liposomal amphotericin B plus voriconazole should be initiated in those with a cerebrospinal fluid (CSF) pleocytosis. Updated information on this outbreak can be found on the CDC website. (See "Aseptic meningitis in adults", section on 'Fusarium outbreaks'.) https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 4/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate HIV INFECTION Statins for primary prevention of cardiovascular disease in persons with HIV (September 2023) HIV infection is associated with an excess risk of cardiovascular disease. A randomized trial evaluated the efficacy of lipid-lowering therapy with pitavastatin for primary prevention in over 7700 persons with HIV ≥40 years of age receiving antiretroviral therapy who had a 10year atherosclerotic cardiovascular disease (ASCVD) risk score <15 percent [14]. Pitavastatin reduced the relative risk of major cardiovascular events (eg, myocardial infarction, stroke) by 35 percent compared with placebo; the trial was stopped early for this apparent benefit. Based on these data, we now advise statins in all persons ≥40 years of age with an ASCVD score ≥5 percent, particularly if the score is ≥7.5 percent; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 years of age, our approach is the same as in persons without HIV. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Indications for statins'.) Updated blood donor deferral criteria related to HIV risk (May 2023) For decades, blood donors have been asked about sexual practices based on their gender, and men who have sex with men (MSM) have been deferred from donating blood. As of May 2023, the US Food and Drug Administration has updated recommendations to genderneutral donor deferrals [15,16]. Individuals are deferred from donating for three months if they have either a new sexual partner or more than one sexual partner and anal sex in the past three months. Other three-month deferrals for HIV risk factors remain in place, including syphilis or gonorrhea, engaging in sex in exchange for money or drugs, new tattoos or piercings, and exposure to blood via transfusion, needlestick, or intravenous recreational drugs. Individuals ever diagnosed with or treated for HIV are deferred indefinitely. (See "Blood donor screening: Medical history", section on 'Deferral criteria related to HIV'.) Severe mpox in persons with advanced HIV (April 2023) In patients with mpox, severe disease can occur in the context of advanced HIV infection. In a multisite study that included 382 patients with HIV and a CD4 count <350 cells/microL, 107 (28 percent) were hospitalized [17]. All 27 deaths occurred in people with CD4 counts of <200 cells/microL. Some developed widespread, large, necrotizing skin lesions and unusual nodular lung lesions. One-quarter of the 85 people who started or restarted antiretroviral therapy (ART) had suspected immune reconstitution inflammatory syndrome (IRIS). Clinicians should be aware of these clinical features so that appropriate treatment can be https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 5/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate initiated. We do not delay ART, despite the potential for IRIS, given the importance of immune recovery. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Complications in people with advanced HIV'.) IMMUNOCOMPROMISED HOSTS Idiopathic CD4 lymphocytopenia (June 2023) Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome of unknown cause defined by CD4+ T cell counts persistently <300 cells/mm3 without evidence of another immunodeficiency, familial linkage, or an infectious cause. In a new cohort from the United States National Institutes of Health, 91 patients were followed from 2006 to 2020 [18]. The majority presented with opportunistic infections caused by viral, encapsulated fungal, and mycobacterial organisms. Autoimmune disorders were present in 35 percent and malignancies in 14 percent. ICL is managed similarly to HIV infection, with careful attention to prophylaxis against opportunistic infections based on CD4 counts. However, unlike HIV, it is usually not progressive, and mortality rates in this cohort were similar to those in the general population. (See "Idiopathic CD4+ lymphocytopenia", section on 'Clinical manifestations'.) IMMUNIZATIONS ACIP recommendations for 2023-24 seasonal influenza vaccination (September 2023) The Advisory Committee on Immunization Practices (ACIP) issued new recommendations for seasonal influenza vaccination in August 2023 ( table 2) [19]. The antigenic composition has been updated. In addition, the ACIP now states that egg allergy alone no longer necessitates additional safety measures for influenza vaccination, including with egg-based vaccines, beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg. All vaccines should be administered in settings where personnel and equipment needed for prompt recognition and treatment of acute hypersensitivity reactions are available. This is consistent with our previous guidance. (See "Seasonal influenza vaccination in adults", section on 'Antigenic composition'.) Investigational live attenuated chikungunya virus vaccine (June 2023) Chikungunya fever is a mosquito-borne viral illness that can cause debilitating polyarthritis in children and adults. In a phase 3 trial that randomly assigned over 4000 healthy adults to a single dose of live-attenuated chikungunya vaccine or placebo, a seroprotective antibody response occurred by 28 days in 99 percent of patients receiving the vaccine and persisted in 96 percent at 180 days [20]. Two serious adverse events (myalgia and syndrome of https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 6/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate inappropriate antidiuretic hormone secretion) were attributed to the vaccine, and both patients fully recovered; adverse effects were otherwise similar to those described with other vaccines. While these results are promising, additional studies on duration of response are needed. The vaccine has not yet been approved by regulatory authorities. (See "Chikungunya fever: Treatment and prevention", section on 'Vaccine development'.) Respiratory syncytial virus vaccines approved for older adults (May 2023) Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults. In 2023, the US Food and Drug Administration approved two recombinant RSV vaccines for the prevention of lower respiratory tract disease in individuals 60 years of age and older [21,22]. Both are subunit vaccines based on prefusion RSV F glycoproteins; however, one includes an AS01E-adjuvant (Arexvy) and the other is nonadjuvanted (Abrysvo). In randomized trials, the efficacy of the adjuvanted and nonadjuvanted vaccines in preventing confirmed RSV-related lower respiratory tract disease were 82 and 67 percent, respectively, compared with placebo [23,24]. Recommendations on the use of these vaccines have been released by the Centers for Disease Control and Prevention [25]. (See "Overview of preventive care in adults", section on 'Immunization'.) Respiratory syncytial virus vaccination in pregnancy (April 2023) Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants. In a phase 3 placebo-controlled randomized trial including almost 7000 pregnant people between 24 and 36 weeks of gestation, a single intramuscular injection of RSV prefusion F protein-based vaccine reduced the rate of severe RSV-associated lower respiratory tract illness in infants up to 180 days after birth [26]. The rate of nonsevere RSV-associated illness also trended lower. Rates of preterm birth trended higher in the vaccinated group, but this was not statistically significant. These data suggest effective passive immunity in infants. In August 2023, the US Food and Drug Administration approved the nonadjuvanted recombinant RSV vaccine for pregnant individuals between 32 and 36 weeks of gestation [27]. Recommendations from the United States Centers Disease Control and Prevention and other expert organizations are pending. (See "Immunizations during pregnancy", section on 'Vaccines under investigation'.) MYCOBACTERIAL INFECTIONS Nutritional supplementation for prevention of tuberculosis (September 2023) Malnutrition is an important risk factor for tuberculosis (TB) disease; the optimal approach to nutritional supplementation for TB prevention is uncertain. In a cluster-randomized trial in Jharkhand, India, over 10,000 household contacts of patients with pulmonary TB were https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 7/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate randomly assigned to receive nutritional intervention (a food basket comprising 750 kcal per day [including 23 g of protein] plus micronutrients) or not [28]. During two-year follow-up, fewer cases of TB, most diagnosed via sputum smear, were observed in the intervention group (1.7 versus 2.1 percent); there were no adverse effects. Those who referred participants for TB evaluation were unblinded to randomization assignment. These findings are important for policy decisions regarding nutritional supplementation as a tool for TB prevention. (See "Prevention of tuberculosis: BCG immunization and nutritional supplementation", section on 'Nutritional supplementation'.) Rifapentine for prevention of leprosy among household contacts (June 2023) Data on the efficacy of postexposure prophylaxis for prevention of leprosy among household contacts have been lacking. In a cluster-randomized trial including 7450 household contacts (≥10 years of age) of patients with newly diagnosed leprosy in China, single-dose rifapentine reduced the cumulative incidence of new leprosy cases over four-year follow-up compared with no intervention (0.09 versus 0.55 percent), but the incidence difference with single dose rifampin compared with no intervention was not statistically significant [29]. The benefit of rifapentine was observed through all four years of follow-up. Based on these findings, we suggest administration of postexposure prophylaxis with rifapentine for household contacts ≥10 years of age of patients with newly diagnosed leprosy. (See "Leprosy: Treatment and prevention", section on 'Prevention'.) USPSTF 2023 recommendations for tuberculosis infection screening (May 2023) In May 2023, the United States Preventive Services Task Force (USPSTF) recommended tuberculosis infection (TBI) screening for all adults at increased risk for TBI; this includes individuals from countries with high TB prevalence and individuals in homeless shelters or correctional facilities [30]. The 2023 recommendation is based on evidence review demonstrating that available screening tools for TBI (tuberculin skin test and interferongamma release assays) are moderately sensitive and highly specific, and that treatment with available regimens confers moderate net benefit [31]. This guidance is in alignment with the prior (2016) USPSTF recommendation but now emphasizes the potential role of primary care clinicians in screening for and treating TBI infection. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)", section on 'United States'.) PARASITIC INFECTIONS Malaria drug resistance in Uganda (September 2023) Artemisinin-based combination therapy is a cornerstone of antimalarial treatment; however, resistance is emerging. In a surveillance study including more than 6500 blood samples https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 8/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate collected from patients with uncomplicated malaria in Uganda between 2016 and 2022, the prevalence of parasites with resistance markers reached more than 20 percent by 2022 in 11 of 16 districts [32]. Mutations in the A675V or C469Y allele of the kelch13 gene (a principal mediator of partial artemisinin resistance in Plasmodium falciparum) reached a combined prevalence of 10 to 54 percent across much of northern Uganda. Possible reasons for these observations include discontinuation of effective malaria control, low level of malaria immunity due to low burden of disease, and use of artemisinin monotherapy. Maintenance of effective malaria control interventions and preemptive action in countering drug resistance are needed. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children", section on 'Scope'.) Emodepside for trichuriasis and hookworm infection (June 2023) Emodepside is an antiparasitic agent used in veterinary medicine that is being evaluated to treat soil-transmitted helminths in humans. In a phase 2a trial in Tanzania, predicted or observed cure rates were higher with emodepside compared with albendazole or placebo among more than 260 adults with trichuriasis (85 versus 17 and 10 percent) and more than 170 adults with hookworm (95 versus 70 and 14 percent) [33]. Adverse events associated with emodepside included headache, blurred vision, and dizziness; there were no serious adverse events. Emodepside could be a promising tool in the ultimate goal to eradicate soiltransmitted helminths, but additional data from larger trials are needed. (See "Hookworm infection", section on 'Treatment' and "Enterobiasis (pinworm) and trichuriasis (whipworm)", section on 'Treatment'.) Malaria prevention regimens and pregnancy outcomes in East Africa (March 2023) Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is important for reducing malaria-associated adverse birth outcomes, but dihydroartemisinin-piperaquine (DP) is a promising alternative in areas with SP resistance. A randomized trial of nearly 4700 pregnant women without human immunodeficiency virus (HIV) infection in East Africa randomly assigned participants to receive IPTp with: SP alone, DP alone, or DP with azithromycin [34]. Compared with SP alone, DP resulted in a 41 percent reduction in clinical malaria but a higher composite rate of adverse pregnancy outcomes (low birth weight, small for gestational age, preterm birth, death: 28 versus 23 percent). Thus, while DP-IPTp may have superior antimalarial effects in areas with SP resistance, SPIPTp may have other benefits on pregnancy outcomes. Further study of malaria prevention tools in areas with SP resistance is needed. (See "Malaria in pregnancy: Prevention and treatment", section on 'Intermittent preventive treatment in pregnancy (IPTp)'.) SEXUALLY TRANSMITTED DISEASES https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2~… 9/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate Doxycycline for post-exposure prophylaxis of sexually transmitted infections (April 2023) Emerging data suggest that post-exposure prophylaxis (PEP) with doxycycline reduces the incidence of certain bacterial sexually transmitted infections (STIs). As an example, in a randomized trial of men who have sex with men (MSM) and transgender women at high risk for STIs, the rate of gonorrhea, chlamydia, and syphilis over three months was approximately one-third lower among those assigned to take 200 mg doxycycline within 72 hours of condomless sex compared with no intervention [35]. Doxycycline was associated with a higher rate of resistance among breakthrough gonococcal infections and colonizing Staphylococcus aureus isolates. For MSM and transgender women who are disproportionately affected by STIs, we individualize the decision to use doxycycline PEP given uncertainties around the long-term effects, including bacterial resistance. (See "Prevention of sexually transmitted infections", section on 'Doxycycline post-exposure prophylaxis for selected individuals'.) VIRAL INFECTIONS, NON-HIV Valacyclovir for prevention of congenital cytomegalovirus infection (October 2023) Emerging evidence suggests that maternal administration of valacyclovir for primary cytomegalovirus (CMV) infection substantially reduces the risk of congenital CMV infection, especially if begun prior to 14 weeks of gestation and within 8 weeks of the maternal infection. In a 2023 individual patient data meta-analysis (one randomized trial, two observational studies), maternal valacyclovir administration upon diagnosis of periconception or first-trimester primary CMV infection was associated with a 66 percent reduction in congenital CMV (11 versus 25 percent) [36]. We suggest high-dose oral valacyclovir for patients with a primary CMV infection in early pregnancy, after a comprehensive discussion of the potential benefits and risks (eg, 2 percent risk of reversible maternal kidney failure). (See "Cytomegalovirus infection in pregnancy", section on 'Antiviral medication'.) Thrombocytopenia and thrombosis syndrome with adenovirus infection (August 2023) Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, autoantibodymediated syndrome of thrombocytopenia and thrombosis (central venous thrombosis is common) that can occur after vaccination with an adenoviral-vectored COVID-19 vaccine. The clinical syndrome is similar to heparin-induced thrombocytopenia. A new report describes two individuals with a similar syndrome and VITT-like autoantibodies following documented adenovirus infection [37]. Neither patient had COVID-19 and neither received a COVID-19 vaccine. This finding suggests that a component of the adenoviral sequence may provide the https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2… 10/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate source of the neoantigen. The inflammatory response to infection could provide the "second hit" that causes the syndrome. (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'Mechanisms/triggers of antibody formation'.) Letermovir for CMV prophylaxis in kidney transplant recipients (July 2023) Valganciclovir is the primary agent for cytomegalovirus (CMV) disease prophylaxis in kidney transplant recipients. Letermovir, an antiviral agent with less myelotoxicity, has been previously shown to prevent CMV disease in hematopoietic cell transplant recipients. Now, in a randomized multicenter trial of over 600 kidney transplant recipients, letermovir resulted in a similar risk of CMV disease at one year compared with valganciclovir (10 versus 12 percent) with less myelotoxicity (26 versus 64 percent) [38]. Letermovir is thus a reasonable alternative for CMV prophylaxis, especially for those who cannot tolerate valganciclovir because of the side effects. However, when using letermovir, a second antiviral agent is required to prevent other herpesviruses such as herpes simplex virus and varicella-zoster virus. (See "Prophylaxis of infections in solid organ transplantation", section on 'Cytomegalovirus'.) Expanded recommendations for hepatitis B virus screening in adults (April 2023) Screening for hepatitis B virus (HBV) in adults has traditionally been recommended for those with risk factors ( table 3). In March 2023, the United States Centers for Disease Control and Prevention expanded their recommendations to include universal screening for persons ≥18 years of age at least once during their lifetime, regardless of risk [39]. The rationale is the prevalence of chronic HBV infection in the general population (0.4 percent), the low vaccination rates in adults, and the harms of missed infection such as fulminant hepatitis and liver cancer. Testing should include hepatitis B surface antigen, hepatitis B surface antibody (anti-HB), and total hepatitis B core antibody. We support universal screening; however, screening is generally not needed if an HBV vaccine series has been completed and there is serologic evidence of immunity (anti-HBs ≥10 milli-international units/mL). (See "Hepatitis B virus: Screening and diagnosis in adults", section on 'Individuals without known risk for HBV infection'.) Marburg outbreaks in Equatorial Guinea and Tanzania (April 2023) Marburg virus causes a rapidly progressive febrile illness that leads to shock and death in a large proportion of infected individuals, similar to Ebola virus disease. In February 2023, an outbreak of Marburg virus disease was confirmed in Equatorial Guinea; the first outbreak of Marburg virus disease in Tanzania was announced several weeks later [40]. There did not appear to be any connection between these outbreaks, which occurred on opposite sides of the continent. By June 2, 2023, both outbreaks were declared over. Strong public health responses are needed to control outbreaks of Marburg virus disease since there are no https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2… 11/12 10/10/23, 1:41 PM What's new in infectious diseases - UpToDate approved vaccines for prevention of Marburg virus disease, and those used to prevent Ebola virus disease are not effective against Marburg virus. (See "Marburg virus", section on 'Endemic areas'.) Use of UpToDate is subject to the Terms of Use. Topic 8358 Version 12239.0  https://www.uptodate.com/contents/whats-new-in-infectious-diseases/print?search=infectious diseases&source=search_result&selectedTitle=2… 12/12