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What's new in infectious diseases

What's new in infectious diseases
Authors:
Elinor L Baron, MD, DTMH
Allyson Bloom, MD
Jennifer Mitty, MD, MPH
Sheila Bond, MD
Milana Bogorodskaya, MD
Keri K Hall, MD, MS
Literature review current through: Feb 2022. | This topic last updated: Mar 01, 2022.

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

Omicron variant associated with increased COVID-19 hospitalizations in children (March 2022)

With predominance of the Omicron (B.1.1.529) SARS-CoV-2 variant in the United States, weekly COVID-19 hospitalization rates among children reached an all-time high in January 2022 (7.1 per 100,000 population) [1]. Hospitalization rates were particularly high (15.6 per 100,000 population) in children age 0 to 4 years, who are not eligible for vaccination. Despite increased rates of hospitalization, the proportion of children and adolescents requiring intensive care or invasive mechanical ventilation was lower with Omicron than earlier circulating strains. Greater proportions of unvaccinated than fully vaccinated adolescents had COVID-19 as the primary reason for hospitalization (70 versus 41 percent) and required intensive care (30 versus 16 percent), highlighting the benefits of vaccination. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'How often are children with COVID-19 hospitalized?'.)

Treatment of COVID-19 in outpatients at risk for severe disease (November 2021, Modified February 2022)

Nirmatrelvir-ritonavir, the monoclonal antibody sotrovimab, remdesivir, and high-titer convalescent plasma have all been shown to reduce the risk of hospitalization when given early in the course of COVID-19 [2-5]. For outpatient adults who have mild-to-moderate COVID-19 and are at risk for progression to severe disease (table 1), we recommend treatment with either nirmatrelvir-ritonavir or sotrovimab. When these are not available, we consider remdesivir and convalescent plasma, which may be complicated to administer, as alternatives. If none are feasible options, molnupiravir is an alternative, but it may be less effective and potentially teratogenic [6]. Bebtelovimab is an alternative monoclonal antibody that is active against Omicron, but there are limited data to support its use [7]. When supplies are limited, these treatments should be prioritized for immunocompromised individuals expected to have a suboptimal vaccine response and unvaccinated or incompletely vaccinated individuals at highest risk for severe disease (table 2) [8]. (See "COVID-19: Outpatient evaluation and management of acute illness in adults".)

Booster doses of COVID-19 vaccines for individuals 12 years or older (October 2021, Modified February 2022)

Several countries have introduced booster doses of COVID-19 vaccines because of potentially attenuated vaccine effectiveness due to waning efficacy and variants. The US Food and Drug Administration has authorized and the Centers for Disease Control and Prevention (CDC) recommends a booster dose for all individuals 12 years or older [9-12]. The booster dose is given five months after a primary BNT162b2 (Pfizer) or mRNA-1273 (Moderna) series for most patients (or three months after the primary series for immunocompromised patients) and two months after a primary Ad26.COV2.S (Johnson & Johnson) series. Any vaccine authorized for the patient's age group can be used for the booster dose, regardless of the vaccine used for the primary series; in general, we favor one of the mRNA vaccines over Ad26.COV2.S. We recommend booster doses for eligible individuals, based on trials and observational evidence suggesting improved vaccine efficacy following a booster dose. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations/waning efficacy'.)

Additional COVID-19 vaccine primary series dose for immunocompromised individuals (August 2021, Modified February 2022)

COVID-19 vaccines are less effective among patients with certain immunocompromising conditions than in the general population; additional vaccine doses have been associated with improved effectiveness in this population. We agree with recommendations from the Advisory Committee on Immunization Practices (ACIP) in the United States that individuals with such conditions (table 3) receive an additional mRNA vaccine dose as part of their primary COVID-19 vaccine series (eg, following two doses of an mRNA vaccine or one dose of Ad26.COV2.S vaccine) [13,14]. This additional primary series dose is distinct from the booster dose, which such patients should additionally receive, although at a shorter interval than recommended for the general population. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

ITP after COVID-19 vaccination (January 2022)

Exacerbations of immune thrombocytopenia (ITP) as well as new-onset ITP have been reported after COVID-19 vaccination [15,16]. Individuals with ITP who receive any COVID-19 vaccine should be advised about this risk, and platelet counts should be monitored before and after vaccination. The benefits of vaccination outweigh the risks in almost all patients with ITP. Those in the midst of a flare can delay vaccination until the flare is controlled; flares that occur following vaccination tend to be transient and respond well to standard ITP therapy. ITP is distinct from the exceedingly rare syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT). (See "Initial treatment of immune thrombocytopenia (ITP) in adults", section on 'COVID-19 vaccination'.)

Staff vaccination in nursing homes impacts resident COVID-19 outcomes (January 2022)

Vaccination of nursing home (NH) staff against COVID-19 has lagged behind resident vaccination but impacts resident outcomes when community transmission is high. In a study of over 12,000 NHs, among facilities with the lowest versus highest staff vaccination coverage, there were an estimated 1.6 additional COVID-19 cases and 0.19 COVID-19-related deaths per hundred beds in counties with the highest prevalence of COVID-19 [17]. Efforts to improve staff acceptance of COVID-19 vaccination should continue to be a priority in the NH setting. (See "COVID-19: Management in nursing homes", section on 'Vaccination'.)

COVID-19: Updated CDC recommendations for isolation and quarantine in the community (January 2022)

In December 2021, the United States Centers for Disease Control and Prevention (CDC) updated recommendations on home isolation for individuals with SARS-CoV-2 infection and post-exposure precautions in the community [18]. For select immunocompetent patients with infection (eg, those who are asymptomatic; those with mild, improving infection), the duration of isolation was reduced from 10 to 5 days, followed by strict mask-wearing when around others for another 5 days. Following exposure, people should monitor for symptoms and wear masks when around others for 10 days; those not up-to-date on vaccination should quarantine at home for the first 5 days. Additional details on the role of testing and other restrictions during the post-infection or post-exposure period, as well as updated recommendations for quarantine and isolation for healthcare personnel can be found on the CDC website. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Testing and quarantine' and "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'In the community setting'.)

Fourth dose of COVID mRNA vaccine in solid organ transplant recipients (January 2022)

In solid organ transplant recipients, a third dose of a COVID-19 mRNA vaccine appears to improve the immune response; however, many have a weak response even after three prior doses. Data from three independent case series suggest that a fourth dose of an mRNA vaccine may increase antibody levels in some of these patients [19-21]. In the largest of these studies, approximately half of the 92 kidney transplant recipients who received a fourth dose mounted an appropriate serologic response (antispike IgG titer >143 binding antibody units); however, similarly robust responses were not seen across all studies. Among patients who did not respond to previous doses, the likelihood of response to additional doses was low. Administration of more than three doses of mRNA vaccine is not routinely performed; for patients who are unable to respond to multiple vaccine doses, other strategies may be required to achieve immunity. (See "COVID-19: Issues related to solid organ transplantation", section on 'Vaccination'.)

Neutralization of SARS-CoV-2 variants in transplant recipients after three doses of mRNA vaccine (December 2021)

In transplant recipients, administration of a third COVID-19 mRNA vaccine dose has been shown to improve the immune response without causing short-term adverse events; however, data on vaccine immunogenicity against SARS-CoV-2 variants are limited. In a secondary analysis of a recent randomized trial, sera obtained from participants after receipt of the third vaccine dose had greater ability to neutralize wild-type SARS-CoV-2 and Alpha, Beta, and Delta variants when compared with sera obtained after the second dose and sera from participants who received placebo [22]. The third dose was well tolerated; no cases of rejection were reported, and graft function remained stable in all patients for three months after the third dose. These findings support administering a three-dose primary vaccine series among transplant recipients and other immunocompromised patients. (See "COVID-19: Issues related to solid organ transplantation", section on 'Vaccination'.)

COVID-19 vaccination and hematopoietic cell transplant or CAR-T therapy (November 2021)

Immunocompromised individuals who are recipients of hematopoietic cell transplantation (HCT) or chimeric antigen receptor (CAR)-T-cell therapies are at risk for a suboptimal immune response to COVID-19 vaccination. Updated guidance from the United States Centers for Disease Control and Prevention (CDC) now recommends revaccination with a full primary series for patients who were vaccinated prior to receiving HCT or CAR-T-cell therapy and who are at least three months post-HCT or CAR-T-cell therapy. Our recommendations are in agreement with this guidance [23]. (See 'COVID-19: Considerations in patients with cancer', section on 'COVID-19 vaccination' and 'Immunizations in hematopoietic cell transplant candidates and recipients', section on 'COVID-19 vaccine'.)

No role for aspirin in inpatients with COVID-19 (November 2021)

The RECOVERY trial, which randomly assigned nearly 15,000 individuals hospitalized with COVID-19 to receive standard care with or without aspirin 150 mg, found no benefit of aspirin in reducing mortality or progression to mechanical ventilation [24]. The aspirin group had a small reduction in thrombosis (4.6 versus 5.3 percent) and a small increase in major bleeding (1.6 versus 1.0 percent). We continue to use aspirin for standard indications but do not prescribe aspirin for individuals admitted to the hospital with COVID-19. (See "COVID-19: Hypercoagulability", section on 'Aspirin/antiplatelet agents'.)

COVID-19 vaccination in children 5 years and older (November 2021)

In October 2021, the US Food and Drug Administration authorized BNT162b2 (Pfizer vaccine) for individuals 5 to 11 years old based on data from randomized trials in over 2000 children in this age group, which demonstrated 91 percent vaccine efficacy against symptomatic COVID-19 and immunogenicity similar to that in adolescents and young adults [25]. There were no cases of vaccine-associated myocarditis in the trials; although the precise risk is uncertain, it is expected to be lower than that seen in older individuals. We agree with recommendations from the Centers for Disease Control and Prevention to give BNT162b2 to children ages 5 to 11 years. Clinicians should be aware that the dose and formulation used for children are different than those for adolescents and adults. (See "COVID-19: Vaccines", section on 'Summary and recommendations'.)

Worse outcomes in patients with ST-elevation myocardial infarction infected with COVID-19 (November 2021)

Infection with COVID-19 may complicate the care of patients with ST-elevation myocardial infarction (STEMI), but the magnitude of this effect has not been well described. A new study used a large administrative claims database to assess the impact of COVID-19 on over 76,000 patients with out-of-hospital STEMI (present on admission) and over 4000 patients with in-hospital STEMI (recorded after hospital admission) [26]. In both groups of patients, in-hospital mortality was higher among those infected with COVID-19; while patients with out-of-hospital STEMI infected with COVID-19 were as likely to receive coronary angiography or percutaneous coronary intervention as those without COVID-19, patients with in-hospital STEMI and COVID-19 were less likely to receive these procedures compared with their uninfected counterparts. These results suggest that infection with COVID-19 can alter the management and worsen the prognosis of patients with STEMI. (See "COVID-19: Myocardial infarction and other coronary artery disease issues", section on 'Outcomes in COVID-19 patients'.)

CDC definition of post-acute COVID-19 (October 2021)

The Centers for Disease Control and Prevention (CDC) recently updated their definition of post-acute sequelae of SARS-CoV-2 infection (PASC; "long-COVID") [27]. While it was previously defined as "patients with a broad range of symptoms (physical and mental) that develop during or after COVID-19, continue for ≥4 weeks, and are not explained by an alternate diagnosis," the CDC further specified the duration of symptoms to include only those with symptoms for ≥2 months (ie, 3 months from the onset). (See "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Terminology and stages of recovery'.)

Post-COVID-19 symptoms not affected by vaccination (October 2021)

Some patients with persistent symptoms following COVID-19 are concerned that vaccination could exacerbate them. A recent study of 163 patients who had a heavy burden of post-COVID-19 symptoms at eight months reported that most patients' symptoms had either improved or remained unchanged one month after receiving either the BNT162b2 (Pfizer) or ChAdOx1 nCoV-19/AZD1222 (AstraZeneca) vaccine [28]. We continue to recommend vaccination in patients following COVID-19, regardless of the presence of persistent symptoms. (See "COVID-19: Vaccines", section on 'History of SARS-CoV-2 infection' and "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Persistent symptoms'.)

COVID-19 vaccination does not increase risk for miscarriage (September 2021)

Evidence of the safety of COVID-19 vaccination in pregnancy continues to accrue. In one study involving nearly 2500 pregnancies, the age-standardized cumulative risk of miscarriage was 12.8 percent individuals who received a mRNA COVID-19 vaccine preconception or prior to 20 weeks of gestation, which is similar to the expected miscarriage rate in the general obstetric population [29]. In another study including over 105,000 pregnancies, individuals who experienced miscarriage had similar odds of exposure to a COVID-19 vaccine in the prior 28 days as those with ongoing pregnancies [30]. Results were consistent with either mRNA-1273 or BNT162b2 vaccine exposure; risks specific to Ad26.COV.2.S vaccine could not be assessed due to a small number of exposures. We recommend COVID-19 vaccination regardless of pregnancy status. (See "COVID-19: Overview of pregnancy issues", section on 'Vaccination in people planning pregnancy and pregnant or recently pregnant people'.)

ANTIMICROBIAL AGENTS

Novel microbiome therapeutic for recurrent Clostridioides difficile infection (February 2022)

Oral microbiome therapeutics are being investigated as a safer and less invasive approach than fecal microbiota transplant for preventing Clostridioides difficile infection (CDI) recurrence. In a randomized trial including 182 patients with multiple recurrent CDI who had resolution of symptoms after treatment with standard-of-care antibiotics, an oral capsule composed of live purified Firmicutes spores (SER-109) decreased recurrence rates (12 versus 40 percent with placebo) up to eight weeks after treatment [31]. Although the outcome of CDI recurrence is notable, we await further data and regulatory approval prior to routine use of this agent. (See "Fecal microbiota transplantation for treatment of Clostridioides difficile infection", section on 'Specific bacterial FMT'.)

BACTERIAL INFECTIONS

Mass azithromycin treatment for yaws eradication (January 2022)

Yaws is a potentially eradicable endemic treponematosis; thus far, studies in highly endemic areas suggest a single round of mass treatment is not sufficient for eradication. In a study including more than 56,000 individuals in Papua New Guinea, clusters were randomly assigned to one round of mass azithromycin followed by two rounds of targeted treatment for active cases or three rounds of mass azithromycin at 0, 6, and 12 months [32]. At 18 months, greater reduction in active yaws prevalence was achieved with three rounds (from 0.43 to 0.04 percent) than with one round (from 0.46 to 0.16 percent) of mass treatment. Further evaluation for antimicrobial resistance and re-emergence of infection is needed. (See "Yaws, bejel, and pinta", section on 'Eradication'.)

CDC guidelines for treatment of plague (August 2021)

In the United States, Yersinia pestis is endemic in all western states and has extended north and east over the years; affected areas are rural and largely uninhabited, but cases of plague are sporadically reported. In 2021, the Centers for Disease Control and Prevention (CDC) published guidelines on the treatment of plague, which list aminoglycosides (gentamicin, streptomycin) and fluoroquinolones (levofloxacin, ciprofloxacin, moxifloxacin) as first-line agents for all forms of plague based largely on observational evidence; doxycycline is another first-line agent for bubonic plague [33]. Combination antimicrobial therapy is recommended if bioterrorism is suspected. Our approach is generally consistent with those guidelines. (See "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)", section on 'Preferred antibiotic regimens'.)

FUNGAL INFECTIONS

Surveillance and containment of Candida auris (September 2021)

Candida auris is an emerging multidrug-resistant yeast capable of rapid spread in long-term acute care hospitals; it requires specialized methods for identification. In September 2018, public health authorities in southern California began proactive C. auris surveillance by pursuing species identification for Candida urine isolates from patients in long-term acute care hospitals [34]. The first case of C. auris was identified in February 2019; subsequently, point prevalence surveys at 17 facilities identified a total of 182 cases. Gaps in hand hygiene, transmission-based precautions, and environmental cleaning were identified and addressed; the outbreak was contained to two facilities by October 2019. These findings demonstrate the utility of enhanced laboratory surveillance as well as the importance of public health oversight to reduce the risk for C. auris transmission. (See "Candidemia in adults: Epidemiology, microbiology, and pathogenesis", section on 'C. auris emergence'.)

HIV INFECTION

Tenofovir alafenamide now a preferred NRTI agent for pregnant individuals with HIV (February 2022)

Recommended antiretroviral regimens for individuals with HIV initiating treatment during pregnancy include two nucleoside reverse transcriptase inhibitor (NRTI) agents in conjunction with either an integrase inhibitor or a booster protease inhibitor. Based on accumulating safety and efficacy data in this population, the United States Department of Health and Human Services has added tenofovir alafenamide (TAF) to the list of preferred NRTIs to use for pregnant individuals with HIV [35]. In a recent trial, regimens containing TAF versus tenofovir disoproxil fumarate (TDF) resulted in similar virologic suppression rates, but TAF was associated with fewer adverse pregnancy outcomes. We generally initiate the NRTI combination of TAF-emtricitabine in this patient population unless there is significant concern for excessive gestational weight gain, in which case a TAF-containing regimen can be used. (See "Antiretroviral selection and management in pregnant women with HIV in resource-rich settings", section on 'Selecting the NRTI backbone'.)

Injectable cabotegravir-rilpivirine not recommended during pregnancy (February 2022)

The injectable cabotegravir-rilpivirine regimen is a useful option for individuals with HIV who prefer to avoid oral antiretroviral therapy (ART). However, there are insufficient data on cabotegravir-rilpivirine use during pregnancy. We agree with updated United States Department of Health and Human Services recommendations to transition individuals who become pregnant while taking cabotegravir-rilpivirine to a preferred oral ART regimen for the duration of their pregnancy [35]. Initiation of the oral regimen should occur within four weeks of the last cabotegravir and rilpivirine intramuscular doses. (See "Antiretroviral selection and management in pregnant women with HIV in resource-rich settings", section on 'On ART with viral suppression'.)

Hepatitis B virus revaccination in nonresponders with HIV (November 2021)

People with HIV should be vaccinated against hepatitis B virus (HBV) if they have no evidence of prior HBV infection or immunity. Those who don't seroconvert after vaccination should receive a second complete vaccine series. In a randomized trial of 107 nonresponders with HIV who were undergoing a second HBV vaccine series, the rate of seroconversion was higher when 40 micrograms was used for each vaccine dose rather than the standard 20 micrograms (72 versus 51 percent), and there was no increased risk of adverse events [36]. These results support our suggestion to use a double vaccine dose for repeat HBV vaccination in patients with HIV and nonresponse to an initial series. (See "Prevention of hepatitis B virus infection in adults with HIV", section on 'Anti-HBs <10 milli-international units/mL after initial series'.)

Updated guidelines for cervical cancer screening in patients with HIV (August 2021)

In August 2021, the United States Department of Health and Human Services along with the National Institutes of Health published updated guidelines for the screening of cervical cancer in patients with HIV. In contrast to the previous guideline, cervical cancer screening at the time of HIV diagnosis is now limited to patients age 21 years or older [37]. We also follow these updated guidelines for patients without HIV who are on long-term immunosuppressive therapy (eg, solid organ transplant, allogeneic hematopoietic stem cell transplant, systemic lupus erythematous, and those with inflammatory bowel disease or rheumatologic disease requiring current immunosuppressive treatments). (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'Initial screening' and "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'HIV-negative immunosuppressed patients'.)

IMMUNIZATIONS

ACIP recommendations on dengue vaccination (February 2022)

Dengue is endemic to tropical regions of the world, including the US territories of Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, and the Republic of Palau. In December 2021, the CDC Advisory Committee on Immunization Practices (ACIP) recommended the dengue vaccine CYD-TDV (Dengvaxia) for children aged 9 to 16 who live in those US territories and have serologic evidence of prior infection [38]. Serology for dengue must be performed prior to vaccination. In trials, breakthrough infection after vaccination was more likely to be severe in individuals who were seronegative at baseline, and thus such individuals should not receive the vaccine. It is not approved for travelers visiting dengue-endemic areas. (See "Dengue virus infection: Prevention and treatment", section on 'CYD-TDV (Dengvaxia)'.)

Herpes zoster vaccination for immunocompromised adults ≥19 years old (October 2021, Modified February 2022)

Herpes zoster vaccination is indicated for those ≥50 years of age to reduce the risk of herpes zoster and postherpetic neuralgia. The United States Advisory Committee on Immunization Practices recently expanded the indication for the recombinant zoster vaccine (RZV) to include immunocompromised adults ≥19 years of age [39]; RZV has been shown to reduce the incidence of herpes zoster in immunocompromised adults. Vaccination should ideally be administered prior to immunosuppression, but when this is not possible, it should be administered during periods of lower immunosuppression and stable disease.

Missed opportunities for influenza vaccination (January 2022)

Influenza vaccination rates remain suboptimal. In a retrospective study including more than 31 million Medicare beneficiaries >19 years of age in the United States during the 2018 to 2019 influenza season, vaccination claims were filed for only 50 percent of individuals [40]. Vaccination uptake was higher among White beneficiaries than Black or Hispanic beneficiaries (53, 35, and 30 percent, respectively), and was higher for those with high-risk conditions than for those without (56 versus 27 percent, respectively). Among unvaccinated beneficiaries overall, 77 percent visited a provider during influenza season. A comprehensive strategy leveraging all opportunities for vaccination is needed to improve influenza vaccine uptake. (See "Seasonal influenza vaccination in adults", section on 'Improving vaccination rates'.)

Novel trivalent hepatitis B vaccine (January 2022)

Most available hepatitis B virus vaccines are recombinant vaccines using yeast-derived S protein of the surface antigen. In December 2021, the US Food and Drug Administration approved a trivalent mammalian cell-derived recombinant vaccine that contains two pre-S epitopes in addition to the S antigen [41]. Compared with conventional hepatitis B vaccines, this vaccine is more immunogenic in older adults [42]. However, its role remains uncertain since it causes side effects more frequently than conventional hepatitis B vaccines and requires more doses than the adjuvanted recombinant hepatitis B vaccine (HepB-CpG; three versus two doses). (See "Hepatitis B virus immunization in adults", section on 'Mammalian cell-derived'.)

Vaccination against human papillomavirus, especially at an early age, is associated with greater reductions in cervical cancer (December 2021)

Human papillomavirus (HPV) vaccination has been shown to decrease incidence of HPV infection and cervical intraepithelial neoplasia (CIN), but whether vaccinating females at an earlier age is associated with lower incidence of cervical cancer has not been well established. In a registry-based observational study of 13.7 million years of follow-up of females aged 20 to 30 years, females who received the bivalent HPV vaccine at a younger age had a greater relative reduction in the incidence of cervical cancer and CIN3 (34 percent for vaccination at age 16 to 18 years, 62 percent at age 14 to 16 years, and 87 percent at age 12 to 13 years) compared with the unvaccinated cohort [43]. This lends further support to vaccinating against HPV at a younger age. (See "Human papillomavirus vaccination", section on 'Cervical, vaginal, and vulvar disease'.)

MYCOBACTERIAL INFECTIONS

On-site rapid testing for TB diagnosis in high-burden areas (January 2022)

The Xpert MTB/RIF test can establish a diagnosis of tuberculosis (TB) and detect rifampin resistance within two hours; however, many clinics in high-burden areas refer specimens to centralized laboratories because of infrastructure requirements for on-site testing. In one cluster-randomized trial including 20 community health centers in Uganda, on-site Xpert testing was achieved with infrastructure enhancements (including workflow restructuring and monthly evaluations to address barriers) and improved rates of completed TB testing, same-day diagnosis, and same-day treatment initiation compared with routine centralized testing [44]. These findings highlight the infrastructure modifications that may be needed to support the advantages of on-site rapid testing for diagnosis of TB. (See "Diagnosis of pulmonary tuberculosis in adults", section on 'Xpert MTB/RIF assay'.)

WHO guidelines for treatment of multidrug-resistant tuberculosis (October 2021)

The World Health Organization (WHO) published updated guidelines for treatment of multidrug-resistant tuberculosis (MDR-TB) in June 2021 [45]. For nonpregnant patients with uncomplicated MDR-TB, the WHO supports treatment with an abbreviated bedaquiline-containing regimen rather than a regimen including injectable agents. One preferred regimen in several TB programs is BPaL, an all-oral regimen of bedaquiline, pretomanid, and linezolid for 6 months. In settings where pretomanid and/or linezolid cannot be used, a 9- to 12-month all-oral multidrug regimen that includes bedaquiline for the first 4 to 6 months is another option. Patients who do not meet criteria for an abbreviated bedaquiline-containing regimen should be treated with a longer, individualized regimen. We are in agreement with this guidance. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Regimen selection'.)

PARASITIC INFECTIONS

Persistent benefit of insecticide-treated nets in malaria-endemic areas (February 2022)

Use of insecticide-treated nets (ITNs) is a mainstay of malaria control; however, it is uncertain whether ITN use might delay natural immunity, leading to increased disease incidence at older ages. In a long-term cohort study that enrolled more than 6700 infants and young children in rural Tanzania between 1998 and 2003, follow-up on vital status in 2019 was obtained for 89 percent [46]. Reported use of ITN at more than half of the early-life study visits was associated with a reduced risk of death from early childhood to adulthood (hazard ratio 0.57). Although most deaths occurred prior to age five, that level of ITN use was still associated with a trend towards lower mortality between five years and adulthood (hazard ratio 0.93). These findings suggest that gains in malaria survival from childhood ITN use in a high-transmission setting persist to early adulthood. (See "Malaria: Epidemiology, prevention, and control", section on 'General approach'.)

Artemisinin resistance in sub-Saharan Africa (October 2021)

The artemisinins are the cornerstone of antimalarial therapy. Artemisin resistance in P. falciparum is caused by mutations in the kelch13 gene and is associated with slower clearance of ring stage parasites from the bloodstream after treatment. In a longitudinal study in Northern Uganda, the prevalence of kelch13 mutations increased from 4 to 20 percent from 2015 to 2019, and among 240 patients with P. falciparum infection treated with artesunate, 6 percent had prolonged parasite clearance suggestive of artemisinin resistance [47]. Broader surveys to assess the scope of artemisinin-resistant malaria are needed; in addition, preemptive action in countering drug resistance is needed. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children", section on 'Scope'.)

Combining vaccination with chemoprophylaxis for malaria prevention (September 2021)

Malaria prevention tools include vaccination and chemoprophylaxis; their use in combination may improve protection in endemic areas. A trial in Burkina Faso and Mali randomly assigned more than 6000 children (aged 5 to 17 months) to receive vaccination (primary three-dose series of RTS,S/AS01, followed by two annual boosters), chemoprophylaxis (four monthly doses of sulfadoxine-pyrimethamine and amodiaquine annually), or both [48]. The three-year incidences of uncomplicated malaria, severe malaria, and death from malaria were lower among those who received both interventions (protective efficacy for each of those outcomes ranged from 60 to 75 percent compared with either intervention alone). These findings support a combination approach to reducing seasonal malaria; optimization of delivery to high-burden areas is needed. (See "Malaria: Epidemiology, prevention, and control", section on 'Overview'.)

Monoclonal antibodies for malaria prevention (August 2021)

Monoclonal antibodies may be a useful tool for malaria prevention. CIS43LS is an antibody targeting the P. falciparum circumsporozoite protein, which is required for parasite motility and hepatocyte invasion. In a phase 1 trial among 25 healthy adults with no history of malaria infection or vaccination, CIS43LS was administered intravenously at one of three doses [49]. No safety concerns were identified; dose-dependent increases in serum antibody concentrations were observed with a half-life of 56 days. Among 15 adults who underwent controlled exposure to mosquitoes carrying P. falciparum sporozoites, parasitemia was observed in none of the nine participants who received CIS43LS and in five of six controls. Available data may translate most easily into malaria prevention among travelers; other potential applications within endemic areas include seasonal malaria control and elimination campaigns. (See "Prevention of malaria infection in travelers", section on 'Monoclonal antibodies'.)

SEXUALLY TRANSMITTED DISEASES

Azithromycin as an alternative to doxycycline for LGV proctitis (November 2021)

For patients with lymphogranuloma venereum (LGV) proctitis who cannot take doxycycline, azithromycin (1 g orally once weekly for three weeks) is a reasonable alternative. In a prospective study of 125 men who have sex with men (MSM) with LGV who had been treated empirically for proctitis with ceftriaxone plus either once-weekly azithromycin for three weeks or doxycycline for 21 days based on provider preference, rates of clinical cure (resolution of symptoms at week 6) and microbiologic cure (negative rectal PCR at week 4 if available) were similar with the two regimens [50]. However, azithromycin remains an alternative regimen for LGV, pending further data, in part because studies suggest that doxycycline results in superior microbiologic cure rates to single-dose azithromycin for non-LGV rectal chlamydia. (See "Lymphogranuloma venereum", section on 'Medical therapy for LGV'.)

Updated sexually transmitted infections guidelines from CDC (October 2021)

In 2021, the United States Centers for Disease Control and Prevention (CDC) updated its guidelines on management of sexually transmitted infections [51]. Important changes include preferences for doxycycline over azithromycin for Chlamydia trachomatis infections and nongonococcal urethritis, routine anaerobic coverage for pelvic inflammatory disease, and a moxifloxacin-based regimen for Mycoplasma genitalium. The guidelines also affirmed previous recommendations to use a 500 mg dose of intramuscular ceftriaxone for gonococcal infections. Our approaches to sexually transmitted infections are largely consistent with these updated guidelines. (See "Pelvic inflammatory disease: Treatment in adults and adolescents" and "Mycoplasma genitalium infection in males and females" and "Treatment of uncomplicated Neisseria gonorrhoeae infections" and "Treatment of Chlamydia trachomatis infection", section on 'Doxycycline as preferred agent'.)

VIRAL INFECTIONS, NON-HIV

Updated ACIP guidance on influenza vaccination in the United States (September 2021)

In August 2021, the United States Advisory Committee on Immunization Practices (ACIP) issued recommendations for prevention of seasonal influenza [52]. During the 2021-22 influenza season, the following vaccine types are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) (table 4 and table 5); all vaccines are expected to be quadrivalent. For the IIV4s produced from cell culture, the approved age indication has been expanded from ≥4 years to ≥6 months of age [53,54]. Influenza vaccination may be co-administered with COVID-19 vaccination, at different anatomic sites. We agree with the ACIP guidance. (See "Seasonal influenza vaccination in adults", section on 'Available formulations' and "Seasonal influenza in children: Prevention with vaccines", section on 'Influenza vaccines'.)

Maternal CMV immune globulin not effective for preventing congenital infection (August 2021)

Maternal hyperimmune globulin treatment of primary cytomegalovirus (CMV) infection in early pregnancy is an investigational approach for preventing symptomatic infection in offspring. In the largest trial of this therapy to date, which randomly assigned nearly 400 pregnant women with primary CMV infection before 24 weeks to a monthly infusion of CMV immune globulin or placebo until delivery, the composite outcome (congenital CMV infection or fetal/neonatal death if no CMV testing) was similar in both groups (23 versus 19 percent) [55]. There were no clear differences in individual outcomes (eg, death, preterm birth, birth weight <5th percentile). Given these and previous findings, practitioners should emphasize preventive behavioral measures against maternal CMV acquisition and limit use of hyperimmune globulin therapy to research studies. (See "Cytomegalovirus infection in pregnancy", section on 'CMV immune globulin'.)

REFERENCES

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  40. Cho BH, Weinbaum C, Tsai Y, Koppaka R. Influenza Vaccine Uptake and Missed Opportunities Among the Medicare-Covered Population With High-Risk Conditions During the 2018 to 2019 Influenza Season : A Retrospective Cohort Study. Ann Intern Med 2022; 175:1.
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Topic 8358 Version 10977.0

References

1 : Hospitalizations of Children and Adolescents with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, July 2021-January 2022.

2 : Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab.

3 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

4 : Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

5 : Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

6 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

7 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

8 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

9 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

10 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

11 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

12 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

13 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

14 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

15 : Severe immune thrombocytopenia after COVID-19 vaccination: Report of four cases and review of the literature.

16 : COVID-19 vaccination in patients with immune thrombocytopenia.

17 : Nursing Home Staff Vaccination and Covid-19 Outcomes.

18 : Nursing Home Staff Vaccination and Covid-19 Outcomes.

19 : Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.

20 : Assessment of 4 Doses of SARS-CoV-2 Messenger RNA-Based Vaccine in Recipients of a Solid Organ Transplant.

21 : Antibody Response to a Fourth Messenger RNA COVID-19 Vaccine Dose in Kidney Transplant Recipients: A Case Series.

22 : Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial.

23 : Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial.

24 : Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

25 : Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

26 : Association Between COVID-19 Diagnosis and In-Hospital Mortality in Patients Hospitalized With ST-Segment Elevation Myocardial Infarction.

27 : Association Between COVID-19 Diagnosis and In-Hospital Mortality in Patients Hospitalized With ST-Segment Elevation Myocardial Infarction.

28 : Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series.

29 : Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion.

30 : Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy.

31 : SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection.

32 : Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication.

33 : Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.

34 : Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019.

35 : Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019.

36 : Comparative Efficacy of a High-Dose vs Standard-Dose Hepatitis B Revaccination Schedule Among Patients With HIV: A Randomized Clinical Trial.

37 : Comparative Efficacy of a High-Dose vs Standard-Dose Hepatitis B Revaccination Schedule Among Patients With HIV: A Randomized Clinical Trial.

38 : Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021.

39 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

40 : Influenza Vaccine Uptake and Missed Opportunities Among the Medicare-Covered Population With High-Risk Conditions During the 2018 to 2019 Influenza Season : A Retrospective Cohort Study.

41 : Influenza Vaccine Uptake and Missed Opportunities Among the Medicare-Covered Population With High-Risk Conditions During the 2018 to 2019 Influenza Season : A Retrospective Cohort Study.

42 : Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial.

43 : The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study.

44 : Multicomponent Strategy with Decentralized Molecular Testing for Tuberculosis.

45 : World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update.

46 : Mosquito Net Use in Early Childhood and Survival to Adulthood in Tanzania.

47 : Evidence of Artemisinin-Resistant Malaria in Africa.

48 : Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention.

49 : A Monoclonal Antibody for Malaria Prevention.

50 : Effective Treatment of Lymphogranuloma venereum Proctitis With Azithromycin.

51 : Sexually Transmitted Infections Treatment Guidelines, 2021.

52 : Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

53 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

54 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

55 : A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.