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.

Interim Clinical Treatment Considerations for Severe Manifestations of Mpox - United States, February 2023.

Monkeypox (mpox) is a disease caused by infection with Monkeypox virus (MPXV), an Orthopoxvirus (OPXV) in the same genus as Variola virus, which causes smallpox. During 2022, a global outbreak involving mpox clade IIb was recognized, primarily among gay, bisexual, and other men who have sex with men.* Most affected patients have been immunocompetent and experienced ≤10 rash lesions (1). CDC has recommended supportive care including pain control.† However, some patients have experienced severe mpox manifestations, including ocular lesions, neurologic complications, myopericarditis, complications associated with mucosal (oral, rectal, genital, and urethral) lesions, and uncontrolled viral spread due to moderate or severe immunocompromise, particularly advanced HIV infection (2). Therapeutic medical countermeasures (MCMs) are Food and Drug Administration (FDA)-regulated drugs and biologics that are predominantly stockpiled by the U.S. government; MCMs developed for smallpox preparedness or shown to be effective against other OPXVs (i.e., tecovirimat, brincidofovir, cidofovir, trifluridine ophthalmic solution, and vaccinia immune globulin intravenous [VIGIV]) have been used to treat severe mpox. During May 2022-January 2023, CDC provided more than 250 U.S. mpox consultations. This report synthesizes data from animal models, MCM use for human cases of related OPXV, unpublished data, input from clinician experts, and experience during consultations (including follow-up) to provide interim clinical treatment considerations. Randomized controlled trials and other carefully controlled research studies are needed to evaluate the effectiveness of MCMs for treating human mpox. Until data gaps are filled, the information presented in this report represents the best available information concerning the effective use of MCMs and should be used to guide decisions about MCM use for mpox patients.

Monkeypox in a Traveler Returning from Nigeria - Dallas, Texas, July 2021.

Monkeypox is a rare, sometimes life-threatening zoonotic infection that occurs in west and central Africa. It is caused by Monkeypox virus, an orthopoxvirus similar to Variola virus (the causative agent of smallpox) and Vaccinia virus (the live virus component of orthopoxvirus vaccines) and can spread to humans. After 39 years without detection of human disease in Nigeria, an outbreak involving 118 confirmed cases was identified during 2017-2018 (1); sporadic cases continue to occur. During September 2018-May 2021, six unrelated persons traveling from Nigeria received diagnoses of monkeypox in non-African countries: four in the United Kingdom and one each in Israel and Singapore. In July 2021, a man who traveled from Lagos, Nigeria, to Dallas, Texas, became the seventh traveler to a non-African country with diagnosed monkeypox. Among 194 monitored contacts, 144 (74%) were flight contacts. The patient received tecovirimat, an antiviral for treatment of orthopoxvirus infections, and his home required large-scale decontamination. Whole genome sequencing showed that the virus was consistent with a strain of Monkeypox virus known to circulate in Nigeria, but the specific source of the patient's infection was not identified. No epidemiologically linked cases were reported in Nigeria; no contact received postexposure prophylaxis (PEP) with the orthopoxvirus vaccine ACAM2000.

Ocular Monkeypox - United States, July-September 2022.

As of October 11, 2022, a total of 26,577 monkeypox cases had been reported in the United States.* Although most cases of monkeypox are self-limited, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox can occur when Monkeypox virus (MPXV) is introduced into the eye (e.g., from autoinoculation), potentially causing conjunctivitis, blepharitis, keratitis, and loss of vision (1). This report describes five patients who acquired ocular monkeypox during July-September 2022. All patients received treatment with tecovirimat (Tpoxx)†; four also received topical trifluridine (Viroptic).§ Two patients had HIV-associated immunocompromise and experienced delays between clinical presentation with monkeypox and initiation of monkeypox-directed treatment. Four patients were hospitalized, and one experienced marked vision impairment. To decrease the risk for autoinoculation, persons with monkeypox should be advised to practice hand hygiene and to avoid touching their eyes, which includes refraining from using contact lenses (2). Health care providers and public health practitioners should be aware that ocular monkeypox, although rare, is a sight-threatening condition. Patients with signs and symptoms compatible with ocular monkeypox should be considered for urgent ophthalmologic evaluation and initiation of monkeypox-directed treatment. Public health officials should be promptly notified of cases of ocular monkeypox. Increased clinician awareness of ocular monkeypox and of approaches to prevention, diagnosis, and treatment might reduce associated morbidity.

Severe Monkeypox in Hospitalized Patients - United States, August 10-October 10, 2022.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy†† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.

Investigation of a Suspect Severe Acute Respiratory Syndrome Coronavirus-2 and Influenza A Mixed Outbreak: Lessons Learned for Long-Term Care Facilities Nationwide.

A suspected outbreak of influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a long-term care facility in Los Angeles County was, months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow Centers for Disease Control and Prevention (CDC) guidelines that specifically address infection control challenges.

Characteristics Associated with Hospitalization Among Patients with COVID-19 - Metropolitan Atlanta, Georgia, March-April 2020.

The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged ≥18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age ≥65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.

Electronic application for rabies management improves surveillance, data quality, and investigator experience in Haiti.

Background: Integrated bite case management (IBCM) is a multi-sectoral response to animal-bites which reduces human and canine rabies mortality through animal quarantine, bite-victim counseling, and vaccination tracking. Haiti's national rabies surveillance program was established in 2013 using paper-based IBCM (pIBCM) with adoption of an electronic smartphone application (eIBCM) in 2018. Methods: We evaluated the feasibility of implementing the electronic app in Haiti and compared pIBCM and eIBCM data quality collected January 2013-August 2019. Deaths prevented, cost-per-death averted, and cost-per-investigation during use of pIBCM and eIBCM were estimated using a previously validated rabies cost-effectiveness tool that accounted for bite-victim demographics; probability of acquiring rabies; post-exposure prophylaxis; and costs including training, supplies, and salaries. We compared pIBCM and eIBCM based on data comprehensiveness, completeness, and reporting efficiency. Surveys were administered to IBCM staff to evaluate the usefulness, simplicity, flexibility, and acceptability of eIBCM. Results: Of 15,526 investigations, 79% were paper-based and 21% electronic. IBCM prevented 241 (estimated) human rabies deaths. Using pIBCM, cost-per-death averted was $2,692 and the cost-per-investigation was $21.02; up to 55 data variables were collected per investigation; data transmission took 26 days to reach national staff, and 180 days until analysis. Using eIBCM, the cost-per-death averted was $1,247 and the cost-per-investigation was $22.70; up to 174 data variables were collected per investigation; data transmission took 3 days to reach national staff, and 30 days until analysis. Among 12,194 pIBCM investigations, 55% were mappable by commune, compared to 100% of eIBCM investigations mappable by GPS. Animal case definitions were incorrectly ascribed by investigators in 5.5% of pIBCM investigations and zero for eIBCM; typically, errors were in determining probable vs. suspect case assignments. Overall, eIBCM was well-accepted by staff, who reported the app is easy-to-use, facilitates investigations, and compared to pIBCM hastens data reporting. Discussion: In Haiti, eIBCM showed improved data completeness, data quality, and shorter notification times with minimal increase in operational cost. The electronic app is simple-to-use and facilitates IBCM investigations. Rabies endemic countries could refer to eIBCM in Haiti as a cost-effective means to reduce human rabies mortality and improve surveillance capacity.

Corrigendum: Electronic application for rabies management improves surveillance, data quality, and investigator experience in Haiti.

[This corrects the article DOI: 10.3389/fvets.2023.1052349.].

Welder's Anthrax: A Review of an Occupational Disease.

Since 1997, nine cases of severe pneumonia, caused by species within the B. cereus group and with a presentation similar to that of inhalation anthrax, were reported in seemingly immunocompetent metalworkers, with most being welders. In seven of the cases, isolates were found to harbor a plasmid similar to the B. anthracis pXO1 that encodes anthrax toxins. In this paper, we review the literature on the B. cereus group spp. pneumonia among welders and other metalworkers, which we term welder's anthrax. We describe the epidemiology, including more information on two cases of welder's anthrax in 2020. We also describe the health risks associated with welding, potential mechanisms of infection and pathological damage, prevention measures according to the hierarchy of controls, and clinical and public health considerations. Considering occupational risk factors and controlling exposure to welding fumes and gases among workers, according to the hierarchy of controls, should help prevent disease transmission in the workplace.

Epidemiologic Investigation of Two Welder's Anthrax Cases Caused by Bacillus Cereus Group Bacteria: Occupational Link Established by Environmental Detection.

Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax.