Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-11 (of 11 Records) |
Query Trace: Hacker JK[original query] |
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Treatment of Mpox with suspected tecovirimat resistance in immunocompromised patient, United States, 2022
Contag CA , Mische L , Fong I , Karan A , Vaidya A , McCormick DW , Bower W , Hacker JK , Johnson K , SanJuan P , Crebbin L , Temmins C , Sahni H , Bogler Y , Cooper JD , Narasimhan S . Emerg Infect Dis 2023 29 (12) 2520-2523 Reports of tecovirimat-resistant mpox have emerged after widespread use of antiviral therapy during the 2022 mpox outbreak. Optimal management of patients with persistent infection with or without suspected resistance is yet to be established. We report a successfully treated case of severe mpox in California, USA, that had suspected tecovirimat resistance. |
Community spread of a human monkeypox virus variant with a tecovirimat resistance-associated mutation
Garrigues JM , Hemarajata P , Espinosa A , Hacker JK , Wynn NT , Smith TG , Gigante CM , Davidson W , Vega J , Edmondson H , Karan A , Marutani AN , Kim M , Terashita D , Balter SE , Hutson CL , Green NM . Antimicrob Agents Chemother 2023 67 (11) e0097223 Tecovirimat, also known as TPOXX or ST-246, is a drug available for the treatment of mpox. Tecovirimat targets the conserved orthopoxvirus VP37 protein (also known as F13) required for extracellular virus particle generation (1, 2). Multiple VP37 mutations associated with tecovirimat resistance have been reported within the current global mpox outbreak in immunocompromised individuals with advanced HIV infection (3 – 5). In many of these cases, resistance mutation heterogeneity was observed following tecovirimat exposure, suggesting resistance emerged under selective pressure during treatment. | To monitor circulating monkeypox virus (MPXV) within California, a genomic surveillance network was established whereby clinical and commercial laboratories provided positive specimens for whole-genome sequencing using an amplicon-based protocol and subsequent analysis (6 – 9). Through this surveillance, 11 mpox cases were identified in southern California with the same tecovirimat resistance-associated mutation (Table 1): a three-nucleotide deletion in the vaccinia virus Copenhagen F13L gene homolog (OPG057) resulting in asparagine removed from position 267 in the VP37 protein (VP37:N267del) (5) (https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/fda-mpox-response#therapeutics). VP37:N267del was the only tecovirimat resistance-associated mutation detected in identified specimens and had allele frequencies greater than 89% in all instances, suggesting infections may have occurred with predominantly mutant virus. Phenotypic testing in vitro (3 – 5) confirmed tecovirimat resistance in ten identified specimens with EC50 values ranging from 1.488 to 3.977 µM, corresponding to an 85- to 230-fold change compared to wild-type isolates. |
Fleaborne typhus-associated deaths - Los Angeles County, California, 2022
Alarcón J , Sanosyan A , Contreras ZA , Ngo VP , Carpenter A , Hacker JK , Probert WS , Terashita D , Balter S , Halai UA . MMWR Morb Mortal Wkly Rep 2023 72 (31) 838-843 Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts. |
A forty-year review of Rocky Mountain spotted fever cases in California shows clinical and epidemiologic changes
Kjemtrup AM , Padgett K , Paddock CD , Messenger S , Hacker JK , Feiszli T , Melgar M , Metzger ME , Hu R , Kramer VL . PLoS Negl Trop Dis 2022 16 (9) e0010738 Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease documented in North, Central, and South America. In California, RMSF is rare; nonetheless, recent fatal cases highlight ecological cycles of the two genera of ticks, Dermacentor and Rhipicephalus, known to transmit the disease. These ticks occur in completely different habitats (sylvatic and peridomestic, respectively) resulting in different exposure risks for humans. This study summarizes the demographic, exposure, and clinical aspects associated with the last 40 years of reported RMSF cases to the California Department of Public Health (CDPH). Seventy-eight RMSF cases with onsets from 1980 to 2019 were reviewed. The incidence of RMSF has risen in the last 20 years from 0.04 cases per million to 0.07 cases per million (a two-fold increase in reports), though the percentage of cases that were confirmed dropped significantly from 72% to 25% of all reported cases. Notably, Hispanic/Latino populations saw the greatest rise in incidence. Cases of RMSF in California result from autochthonous and out-of-state exposures. During the last 20 years, more cases reported exposure in Southern California or Mexico than in the previous 20 years. The driver of these epidemiologic changes is likely the establishment and expansion of Rhipicephalus sanguineus sensu lato ticks in Southern California and on-going outbreaks of RMSF in northern Mexico. Analysis of available electronically reported clinical data from 2011 to 2019 showed that 57% of reported cases presented with serious illness requiring hospitalization with a 7% mortality. The difficulty in recognizing RMSF is due to a non-specific clinical presentation; however, querying patients on the potential of tick exposure in both sylvatic and peridomestic environments may facilitate appropriate testing and treatment. |
Genetic Characterization of Mumps Viruses Associated with the Resurgence of Mumps in the United States: 2015-2017.
McNall RJ , Wharton AK , Anderson R , Clemmons N , Lopareva EN , Gonzalez C , Espinosa A , Probert WS , Hacker JK , Liu G , Garfin J , Strain A , Boxrud D , Bryant PW , George KS , Davis T , Griesser RH , Shult P , Bankamp B , Hickman CJ , Wroblewski K , Rota PA . Virus Res 2020 281 197935 Despite high coverage with measles, mumps, and rubella vaccine in the United States, outbreaks of mumps occur in close contact settings such as schools, colleges, and camps. Starting in late 2015, outbreaks were reported from several universities, and by the end of 2017, greater than 13,800 cases had been reported nation-wide. In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. Twelve genotypes of mumps virus are currently recognized by the World Health Organization, and the standard protocol for genotyping requires sequencing the entire gene coding for the small hydrophobic (SH) protein. Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was low. Only 0.8% of the sequences were identified as genotypes C, H, J, or K, and 0.5% were identified as vaccine strains in genotypes A or N, while most sequences (98.7%) were genotype G. The majority of the genotype G sequences could be included into one of two large groups with identical SH sequences. Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. These results demonstrate that molecular and epidemiologic data can be used to track transmission pathways of mumps virus; however, the limited diversity of the SH sequences may be insufficient for resolving transmission in all outbreaks. |
A novel TaqMan assay to detect Rickettsia 364D, the etiologic agent of Pacific Coast tick fever.
Karpathy SE , Espinosa A , Yoshimizu MH , Hacker JK , Padgett KA , Paddock CD . J Clin Microbiol 2019 58 (1) Pacific Coast tick fever is a febrile illness associated with the bite of Dermacentor occidentalis and results from an infection due to the intracellular pathogen Rickettsia 364D (also known by the proposed name "Rickettsia philipii"). Current molecular methods for the detection of this pathogen rely on the amplification of a conserved spotted fever group rickettsial gene (ompA) followed by DNA sequencing of the amplicon to identify the species. This work describes the development of a Rickettsia 364D-specific TaqMan assay to simplify and accelerate the detection and identification processes. The assay demonstrated a sensitivity of 1 genomic copy per 4 mul sample and is highly specific for Rickettsia 364D. The utility of this assay for ecological and diagnostic samples was evaluated using single-blinded banked specimens and yielded a clinical sensitivity and specificity of 100%. In conclusion, we describe the development and evaluation of a novel TaqMan real-time PCR assay for the detection and identification of Rickettsia 364D suitable for ecological and diagnostic applications. |
Patients with laboratory evidence of West Nile virus disease without reported fever
Landry K , Rabe IB , Messenger SL , Hacker JK , Salas ML , Scott-Waldron C , Haydel D , Rider E , Simonson S , Brown CM , Smole SC , Neitzel DF , Schiffman EK , Strain AK , Vetter S , Fischer M , Lindsey NP . Epidemiol Infect 2019 147 e219 In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013. |
Expanded Molecular Testing on Patients with Suspected West Nile Virus Disease.
Lindsey NP , Messenger SL , Hacker JK , Salas ML , Scott-Waldron C , Haydel D , Rider E , Simonson S , Brown CM , Patel P , Smole SC , Neitzel DF , Schiffman EK , Palm J , Strain AK , Vetter SM , Nefzger B , Fischer M , Rabe IB . Vector Borne Zoonotic Dis 2019 19 (9) 690-693 Most diagnostic testing for West Nile virus (WNV) disease is accomplished using serologic testing, which is subject to cross-reactivity, may require cumbersome confirmatory testing, and may fail to detect infection in specimens collected early in the course of illness. The objective of this project was to determine whether a combination of molecular and serologic testing would increase detection of WNV disease cases in acute serum samples. A total of 380 serum specimens collected </=7 days after onset of symptoms and submitted to four state public health laboratories for WNV diagnostic testing in 2014 and 2015 were tested. WNV immunoglobulin M (IgM) antibody and RT-PCR tests were performed on specimens collected </=3 days after symptom onset. WNV IgM antibody testing was performed on specimens collected 4-7 days after onset and RT-PCR was performed on IgM-positive specimens. A patient was considered to have laboratory evidence of WNV infection if they had detectable WNV IgM antibodies or WNV RNA in the submitted serum specimen. Of specimens collected </=3 days after symptom onset, 19/158 (12%) had laboratory evidence of WNV infection, including 16 positive for only WNV IgM antibodies, 1 positive for only WNV RNA, and 2 positive for both. Of specimens collected 4-7 days after onset, 21/222 (9%) were positive for WNV IgM antibodies; none had detectable WNV RNA. These findings suggest that routinely performing WNV RT-PCR on acute serum specimens submitted for WNV diagnostic testing is unlikely to identify a substantial number of additional cases beyond IgM antibody testing alone. |
Rickettsia species isolated from Dermacentor occidentalis (Acari: Ixodidae) from California
Paddock CD , Yoshimizu MH , Zambrano ML , Lane RS , Ryan BM , Espinosa A , Hacker JK , Karpathy SE , Padgett KA . J Med Entomol 2018 55 (6) 1555-1560 The Pacific Coast tick (Dermacentor occidentalis Marx, 1892) is one of the most widely distributed and frequently encountered tick species in California. This tick is the primary vector of an unclassified spotted fever group rickettsial pathogen, designated currently as Rickettsia 364D, the etiologic agent of a recently recognized tick-borne rickettsiosis known as Pacific Coast tick fever. Despite intensified interest in this pathogen, important questions remain regarding its taxonomic status and possible variations in genotype among different strains that could influence its pathogenicity. Only the extensively passaged prototypical isolate (strain 364-D) is widely available to rickettsiologists and public health scientists worldwide. To achieve a larger, more geographically diverse, and contemporary collection of strains, 1,060 questing adult D. occidentalis ticks were collected from 18 sites across six counties in northern and southern California in 2016 and 2017. Fourteen ticks (1.3%) yielded DNA of Rickettsia 364D and from these, 10 unique isolates from Lake and Orange counties were obtained. Additionally, Rickettsia rhipicephali was detected in 108 (10.2%) ticks, from which eight isolates were obtained, and Rickettsia bellii in six (0.6%), from which three isolates were obtained. The panel of recently acquired, low-passage strains of Rickettsia 364D derived from this study could enhance opportunities for investigators to accurately determine the taxonomic standing of this agent and to develop specific diagnostic assays for detecting infections with Rickettsia 364D in ticks and humans. |
Complete Genome Sequences of Mumps and Measles Virus Isolates from Three States in the United States.
Magana LC , Espinosa A , Marine RL , Ng TFF , Castro CJ , Montmayeur AM , Hacker JK , Scott S , Whyte T , Bankamp B , Oberste MS , Rota PA . Genome Announc 2017 5 (33) We report here the full coding sequence of nine paramyxovirus genomes, including two full-length mumps virus genomes (genotypes G and H) and seven measles virus genomes (genotypes B3 and D4, D8, and D9), from respiratory samples of patients from California, Virginia, and Alabama obtained between 2010 and 2014. |
Undiagnosed cases of fatal clostridium-associated toxic shock in Californian women of childbearing age
Ho CS , Bhatnagar J , Cohen AL , Hacker JK , Zane SB , Reagan S , Fischer M , Shieh WJ , Guarner J , Ahmad S , Zaki SR , McDonald LC . Am J Obstet Gynecol 2009 201 (5) 459 e1-7 OBJECTIVE: In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Californian women after medical abortions. The true incidence of this rare disease is unknown, and a population-based study has never been performed. Additional clostridia-associated deaths were sought to describe associated clinical characteristics. STUDY DESIGN: Population-based death certificate review and a clinical case definition for clostridial-associated toxic shock identified women with likelihood of dying from a Clostridium infection. Formalin-fixed autopsy tissues underwent immunohistochemical and polymerase chain reaction assays. RESULTS: Thirty-eight women were suspected of having C sordellii-associated death. Five tested positive for Clostridium species: 3 for Clostridium perfringens, 1 for C sordellii, and 1 for both. Deaths occurred after the medical procedures for cervical dysplasia (n = 2), surgical abortion (n = 1), stillborn delivery (n = 1), and term live birth (n = 1). None had a medical abortion. CONCLUSION: C sordellii and C perfringens are associated with undiagnosed catastrophic infectious gynecologic illnesses among women of childbearing age. |
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