Mucormycosis: update on clinical presentation, diagnosis, and treatment.

PURPOSE OF REVIEW: Mucormycosis (MCR) is a common opportunistic mold infection, and Mucorales were recently designated by WHO as priority pathogens. The interest in this infection has risen significantly since the major outbreak of MCR in the context of the COVID-19 pandemic, particularly in India. Herein, we summarize recently (last 24 months) published information regarding clinical aspects of MCR. RECENT FINDINGS: The disease remains protean in its clinical presentation, difficult to diagnose, and challenging to treat. In 2021, cases of COVID-19-associated mucormycosis (CAM) exploded in India during COVID-19 and manifested primarily as sino-orbital or sino-cerebral disease. Its classic risk factors included the triad of COVID-19, uncontrolled diabetes mellitus and use of corticosteroids. Despite difficulties in the timely diagnosis of MCR, significant progress has been made with the use of molecular techniques in blood to assist with earlier diagnosis, which can facilitate earlier appropriate therapy and improve outcomes. In addition, advances have been made in the use of imaging to stage the disease, determining what types of multimodal therapy are required depending on staging, and tissue-based identification of Mucorales. SUMMARY: Although the outlook for MCR has improved, effective new antifungals, risk stratification, and the optimal multimodality approaches remain an unmet need.

Correction: Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.

[This corrects the article DOI: 10.1371/journal.pntd.0009427.].

Improving the safety of outpatient parenteral antimicrobial therapy for patients with solid tumors.

BACKGROUND AND OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. METHODS: We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. RESULTS: Completeness of ID provider notes improved from a baseline of 77 to 100% (p < .0001) for antimicrobial recommendations, 75 to 97% (p < .0001) for follow-up recommendations, and 19 to 98% (p < .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% (p = .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. CONCLUSIONS: Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.

Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases through mosquito control has been used, it has not been entirely successful. There are currently no licensed vaccines or treatments specific for CHIKV disease, thus more work is needed to develop effective countermeasures. Current animal research on CHIKV is often not representative of human disease. Most models use CHIKV needle inoculation via unnatural routes to create immediate viremia and localized clinical signs; these methods neglect the natural route of transmission (the mosquito vector bite) and the associated human immune response. Since mosquito saliva has been shown to have a profound effect on viral pathogenesis, we evaluated a novel model of infection that included the natural vector, Aedes species mosquitoes, transmitting CHIKV to mice containing components of the human immune system. Humanized mice infected by 3-6 mosquito bites showed signs of systemic infection, with demonstrable viremia (by qRT-PCR and immunofluorescent antibody assay), mild to moderate clinical signs (by observation, histology, and immunohistochemistry), and immune responses consistent with human infection (by flow cytometry and IgM ELISA). This model should give a better understanding of human CHIKV disease and allow for more realistic evaluations of mechanisms of pathogenesis, prophylaxis, and treatments.

Adenovirus infection and disease in recipients of hematopoietic cell transplantation.

PURPOSE OF REVIEW: To provide an update on risk factors associated with adenovirus (ADV) infection in patients after hematopoietic cell transplant (HCT) and on options for ADV monitoring and treatment in the setting of HCT. RECENT FINDINGS: Among patients undergoing HCT, ADV infection continues to be more common amongst those receiving a T-cell-depleted or graft other than from a matched-related donor. Among children undergoing HCT, reactivation in the gastrointestinal tract appears to be the most common source, and the virus is detectable by quantitative PCR in the stool before it is detectable in the blood. Thus, screening for the virus in the stool of these children may allow for preemptive therapy to reduce mortality. Brincidofovir, although still not approved by any regulatory agency, remains a potential agent for preemptive therapy and for salvage in cases not responding to cidofovir. Rapidly generated off-the-shelf virus-specific T cells may facilitate adoptive cell therapy in populations with a special need and previously not eligible for adoptive cell therapy, such as cord blood recipients. SUMMARY: ADV infection continues to adversely affect survival in HCT recipients. Screening stool in children and preemptive therapy may reduce mortality. Brincidofovir and adoptive T-cell therapy remain potential options for treatment.

Characterization of a Zika Virus Isolate from Colombia.

BACKGROUND: Zika virus (Flavivirus genus) is the first mosquito-borne virus known to cause high rates of microcephaly and abortion in humans. Typically, Zika virus causes a self-limiting, systemic illness; however, the current outbreak of Zika virus in the Americas has been associated with increased rates of fetal malformations and Guillain-Barré syndrome. Very few Zika virus isolates have been described in the literature, and live viruses are needed to perform studies of pathogenesis and to develop vaccines and treatments. METHODOLOGY/CLINICAL FINDINGS: We isolated Zika virus, strain FLR, directly from the serum of an individual infected in Barranquilla, Colombia (December, 2015). Here, we describe the patient's clinical course and characterize strain FLR by its growth characteristics in mosquito and mammalian cells and its partial resistance to UV-inactivation. The full genome sequence of FLR was also analyzed (including the 3' un-translated region), to determine its probable geographic origin, and to pinpoint structural differences from other Zika virus strains. CONCLUSIONS/SIGNIFICANCE: We anticipate that the study of this low passage, clinical isolate of Zika virus, which is available for worldwide distribution, will help uncover the mechanisms of viral replication and host immune responses contributing to the varied and sometimes severe clinical presentations seen during the current epidemic in the Americas.

Previously undiagnosed HIV infections identified through cluster investigation, North Carolina, 2002-2007.

During cluster investigation, index patients name social contacts that are not sex or drug-sharing partners. The likelihood of identifying new HIV infections among social contacts is unknown. We hypothesized greater odds of identifying new infections among social contacts identified by men who report sex with men (MSM). We reviewed North Carolina HIV diagnoses during 2002-2005 and used logistic regression to compare testing results among social contacts of MSM, men who report sex with women only (MSW) and women. HIV was newly diagnosed among 54/601 (9.0 %) social contacts tested named by MSM, 16/522 (3.1 %) named by MSW, and 23/639 (3.6 %) named by women. Compared with those named by MSW, odds of new HIV diagnosis were greater among MSM social contacts (adjusted odds ratio: 2.5; 95 % confidence interval: 1.3-4.7). Testing social contacts identified previously undiagnosed HIV infections and could provide an opportunity to interrupt transmission.