Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.

BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Use of serial testing to interrupt a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreak on a hospital medical floor-Minnesota, October-December 2020.

OBJECTIVE: Describe a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) hospital outbreak and the role of serial testing of patients and healthcare personnel (HCP) in interrupting SARS-CoV-2 transmission. DESIGN: Outbreak investigation. SETTING: Medical floor of a tertiary-care center in Minnesota. METHODS: Serial testing for SARS-CoV-2 and whole-genome sequencing (WGS) of positive specimens from HCP and patients were used. An outbreak-associated case was defined as a positive SARS-CoV-2 molecular test in an HCP who worked on the floor prior to testing positive or in a patient who was hospitalized on the medical floor bewteen October 27 and December 1, 2020. WGS was used to determine potential routes of transmission. RESULTS: The outbreak was detected after a patient hospitalized for 12 days tested positive for SARS-CoV-2. Serial testing of patients and HCP was conducted in response. Overall, 247 HCP and 41 patients participated in serial SARS-CoV-2 testing; 52 HCP (21%) and 19 hospitalized patients (46%) tested positive. One additional HCP tested positive outside serial testing. The WGS of specimens from 27 (51%) HCP and 15 (79%) patients identified 3 distinct transmission clusters. WGS and epidemiologic evidence suggested intrafacility transmission. The proportions of asymptomatic and presymptomatic patients who tested positive (63%) and HCP who worked during their infectious period (75%) highlight the need for serial testing of asymptomatic patients and HCP during outbreaks. CONCLUSIONS: Coupled with preventive measures such as personal protective equipment use and physical distancing, serial testing of HCP and patients could help detect and prevent transmission within healthcare facilities during outbreaks and when nosocomial transmission is suspected.

Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole.

A 31-year-old Jamaican man with disseminated nonmeningeal coccidioidomycosis that involved the spine, ribs, pelvis, liver, and spleen did not clinically respond to a prolonged course of both amphotericin B deoxycholate and liposomal amphotericin B therapy. After institution of voriconazole monotherapy, the patient had a favorable (albeit slow) radiological and clinical response without adjunctive surgical intervention.

Avian influenza: a new pandemic threat?

In December 2003, the largest outbreak of highly pathogenic avian influenza H5N1 occurred among poultry in 8 Asian countries. A limited number of human H5N1 infections have been reported from Vietnam and Thailand, with a mortality rate approaching 70%. Deaths have occurred in otherwise healthy young individuals, which is reminiscent of the 1918 Spanish influenza pandemic. The main presenting features were fever, pneumonitis, lymphopenia, and diarrhea. Notably, sore throat, conjunctivitis, and coryza were absent. The H5N1 strains are resistant to amantadine and rimantadine but are susceptible to neuraminidase inhibitors, which can be used for treatment and prophylaxis. The widespread epidemic of avian influenza in domestic birds increases the likelihood for mutational events and genetic reassortment. The threat of a future pandemic from avian influenza is real. Adequate surveillance, development of vaccines, outbreak preparedness, and pandemic influenza planning are important. This article summarizes the current knowledge on avian influenza, including the virology, epidemiology, diagnosis, and management of this emerging disease.

Clinical review: Severe malaria.

Malaria represents a medical emergency because it may rapidly progress to complications and death without prompt and appropriate treatment. Severe malaria is almost exclusively caused by Plasmodium falciparum. The incidence of imported malaria is increasing and the case fatality rate remains high despite progress in intensive care and antimalarial treatment. Clinical deterioration usually appears 3-7 days after onset of fever. Complications involve the nervous, respiratory, renal, and/or hematopoietic systems. Metabolic acidosis and hypoglycemia are common systemic complications. Intravenous quinine and quinidine are the most widely used drugs in the initial treatment of severe falciparum malaria, whereas artemisinin derivatives are currently recommended for quinine-resistant cases. As soon as the patient is clinically stable and able to swallow, oral treatment should be given. The intravascular volume should be maintained at the lowest level sufficient for adequate systemic perfusion to prevent development of acute respiratory distress syndrome. Renal replacement therapy should be initiated early. Exchange blood transfusion has been suggested for the treatment of patients with severe malaria and high parasitemia. For early diagnosis, it is paramount to consider malaria in every febrile patient with a history of travel in an area endemic for malaria.

Antimicrobial susceptibility patterns among viridans group streptococcal isolates from infective endocarditis patients from 1971 to 1986 and 1994 to 2002.

To determine whether changes in antimicrobial resistance have occurred among viridans group streptococci, we retrospectively examined 50 viridans group streptococcal isolates recovered from patients with infective endocarditis over 3 decades. Resistance rates (percent resistant isolates 1971 to 1986 and 1994 to 2002) were as follows: levofloxacin, 0 and 9; penicillin and clindamycin, 0 and 4; and erythromycin and azithromycin, 11 and 26, respectively.