Phase I Evaluation of STA-1474, a Prodrug of the Novel HSP90 Inhibitor Ganetespib, in Dogs with Spontaneous Cancer

The novel water soluble compound STA-1474 is metabolized to ganetespib (formerly STA-9090), a potent HSP90 inhibitor previously shown to kill canine tumor cell lines in vitro and inhibit tumor growth in the setting of murine xenografts. The purpose of the following study was to extend these observations and investigate the safety and efficacy of STA-1474 in dogs with spontaneous tumors.This was a Phase 1 trial in which dogs with spontaneous tumors received STA-1474 under one of three different dosing schemes. Pharmacokinetics, toxicities, biomarker changes, and tumor responses were assessed. Twenty-five dogs with a variety of cancers were enrolled. Toxicities were primarily gastrointestinal in nature consisting of diarrhea, vomiting, inappetence and lethargy. Upregulation of HSP70 protein expression was noted in both tumor specimens and PBMCs within 7 hours following drug administration. Measurable objective responses were observed in dogs with malignant mast cell disease (n = 3), osteosarcoma (n = 1), melanoma (n = 1) and thyroid carcinoma (n = 1), for a response rate of 24% (6/25). Stable disease (>10 weeks) was seen in 3 dogs, for a resultant overall biological activity of 36% (9/25).This study provides evidence that STA-1474 exhibits biologic activity in a relevant large animal model of cancer. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 activation, it is likely that STA-1474 and ganetespib will demonstrate comparable anti-cancer activity in human patients

Bat rabies in Washington State: Temporal-spatial trends and risk factors for zoonotic transmission (2000–2017)

Background: Rabies is a zoonotic viral disease that can affect all mammals. In the United States, the majority of human rabies cases are caused by bats, which are the only known reservoirs for rabies virus (RABV) in Washington State. We sought to characterize bat RABV epidemiology in Washington among bats submitted by the public for RABV testing. Methods: We examined temporal and spatial trends in RABV positivity (% positive) for taxonomically identified bats submitted to diagnostic laboratories during 2006–2017. For a subset of Myotis species, we evaluated sensitivity and predictive value positive (PPV) of morphological identification keys, using mitochondrial markers (cytochrome b) as a reference. For bats tested during 2000–2016, we analyzed RABV positivity by circumstances of encounters with humans, cats, and dogs. Results: During 2006–2017, RABV positivity for all bat species was 6.0% (176/2,928). Among species with ≥100 submissions, RABV positivity was 2.0%–11.7% and highest among big brown bats (Eptesicus fuscus). An increasing trend in annual positivity was significant only for big brown bats (P = 0.02), and was circumstantially linked to a geographic cluster. Sensitivity and PPV of morphological identification keys was high for M. evotis but varied for M. lucifugus, M. californicus, M. yumanensis, and M. septentrionalis. A positive RABV result was significantly associated with nonsynanthropic species, abnormal behavior, abnormal hiding, injury, biting, found in a body of water, found alive, found outdoors, and caught by a dog. Conclusion: Monitoring passive RABV surveillance trends enables public health authorities to perform more accurate risk assessments. Differences in temporal and spatial trends in RABV positivity by bat species indicate the importance of collecting taxonomic data, although morphological identification can be unreliable for certain Myotis species. Current public health practices for RABV exposures should be maintained as RABV infection in bats can never be excluded without diagnostic testing

Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4–38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19