Tecovirimat Resistance in Mpox Patients, United States, 2022-2023.

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.

Monkeypox Case Investigation - Cook County Jail, Chicago, Illinois, July-August 2022.

Knowledge about monkeypox transmission risk in congregate settings is limited. In July 2022, the Chicago Department of Public Health (CDPH) confirmed a case of monkeypox in a person detained in Cook County Jail (CCJ) in Chicago, Illinois. This case was the first identified in a correctional setting in the United States and reported to CDC during the 2022 multinational monkeypox outbreak. CDPH collaborated with CCJ, the Illinois Department of Public Health (IDPH), and CDC to evaluate transmission risk within the facility. Fifty-seven residents were classified as having intermediate-risk exposures to the patient with monkeypox during the 7-day interval between the patient's symptom onset and his isolation. (Intermediate-risk exposure was defined as potentially being within 6 ft of the patient with monkeypox for a total of ≥3 hours cumulatively, without wearing a surgical mask or respirator, or potentially having contact between their own intact skin or clothing and the skin lesions or body fluids from the patient or with materials that were in contact with the patient's skin lesions or body fluids.) No secondary cases were identified among a subset of 62% of these potentially exposed residents who received symptom monitoring, serologic testing, or both. Thirteen residents accepted postexposure prophylaxis (PEP), with higher acceptance among those who were offered counseling individually or in small groups than among those who were offered PEP together in a large group. Monkeypox virus (MPXV) DNA, but no viable virus, was detected on one surface in a dormitory where the patient had been housed with other residents before he was isolated. Although monkeypox transmission might be limited in similar congregate settings in the absence of higher-risk exposures, congregate facilities should maintain recommended infection control practices in response to monkeypox cases, including placing the person with monkeypox in medical isolation and promptly and thoroughly cleaning and disinfecting spaces where the person has spent time. In addition, officials should provide information to residents and staff members about monkeypox symptoms and transmission modes, facilitate confidential monkeypox risk and symptom disclosure and prompt medical evaluation for symptoms that are reported, and provide PEP counseling in a private setting.

Orthopoxvirus Testing Challenges for Persons in Populations at Low Risk or Without Known Epidemiologic Link to Monkeypox - United States, 2022.

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.

Development of a new oral poliovirus vaccine for the eradication end game using codon deoptimization.

Enormous progress has been made in global efforts to eradicate poliovirus, using live-attenuated Sabin oral poliovirus vaccine (OPV). However, as the incidence of disease due to wild poliovirus has declined, vaccine-derived poliovirus (VDPV) has emerged in areas of low-vaccine coverage. Coordinated global cessation of routine, type 2 Sabin OPV (OPV2) use has not resulted in fewer VDPV outbreaks, and continued OPV use in outbreak-response campaigns has seeded new emergences in low-coverage areas. The limitations of existing vaccines and current eradication challenges warranted development of more genetically stable OPV strains, most urgently for OPV2. Here, we report using codon deoptimization to further attenuate Sabin OPV2 by changing preferred codons across the capsid to non-preferred, synonymous codons. Additional modifications to the 5' untranslated region stabilized known virulence determinants. Testing of this codon-deoptimized new OPV2 candidate (nOPV2-CD) in cell and animal models demonstrated that nOPV2-CD is highly attenuated, grows sufficiently for vaccine manufacture, is antigenically indistinguishable from Sabin OPV2, induces neutralizing antibodies as effectively as Sabin OPV2, and unlike Sabin OPV2 is genetically stable and maintains an attenuation phenotype. In-human clinical trials of nOPV2-CD are ongoing, with potential for nOPV strains to serve as critical vaccine tools for achieving and maintaining polio eradication.