Last data update: Jun 24, 2024. (Total: 47078 publications since 2009)
Records 1-30 (of 40 Records) |
Query Trace: Denison A [original query] |
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Second nationwide tuberculosis outbreak caused by bone allografts containing live cells - United States, 2023
Wortham JM , Haddad MB , Stewart RJ , Annambhotla P , Basavaraju SV , Nabity SA , Griffin IS , McDonald E , Beshearse EM , Grossman MK , Schildknecht KR , Calvet HM , Keh CE , Percak JM , Coloma M , Shaw T , Davidson PJ , Smith SR , Dickson RP , Kaul DR , Gonzalez AR , Rai S , Rodriguez G , Morris S , Armitige LY , Stapleton J , Lacassagne M , Young LR , Ariail K , Behm H , Jordan HT , Spencer M , Nilsen DM , Denison BM , Burgos M , Leonard JM , Cortes E , Thacker TC , Lehman KA , Langer AJ , Cowan LS , Starks AM , LoBue PA . MMWR Morb Mortal Wkly Rep 2024 72 (5253) 1385-1389 ![]() ![]() During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed. |
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus (preprint)
Sheahan TP , Sims AC , Zhou S , Graham RL , Hill CS , Leist SR , Schafer A , Dinnon KH 3rd , Montgomery SA , Agostini ML , Pruijssers AJ , Chappell JD , Brown AJ , Bluemling GR , Natchus MG , Saindane M , Kolykhalov AA , Painter G , Harcourt J , Tamin A , Thornburg NJ , Swanstrom R , Denison MR , Baric RS . bioRxiv 2020 2020.03.19.997890 Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
Detection of coxsackievirus A6 in formalin-fixed, paraffin-embedded skin biopsy specimens using immunohistochemistry and real-time reverse-transcriptase PCR
Denison AM , Bhatnagar J , Jahan-Tigh RR , Fair P , Hale GL . J Clin Virol Plus 2021 1(1-2) (no pagination) Background: Hand, foot, and mouth disease (HFMD), classically a childhood viral infection, has an atypical and severe clinical presentation in adults. Coxsackievirus A6 is a leading cause of atypical HFMD, but current diagnostic methods utilizing formalin-fixed, paraffin-embedded skin biopsy specimens often lack sensitivity and specificity. Method(s): Formalin-fixed, paraffin-embedded skin biopsies from seven case patients with clinical and histopathological suspicion of atypical HFMD were evaluated by coxsackievirus A6 (CVA6) immunohistochemistry, enterovirus-specific conventional reverse transcriptase-PCR with subsequent Sanger sequencing targeting the 5'UTR, and CVA6-specific real-time PCR targeting the VP1 gene. Result(s): The CVA6-specific antibody demonstrated appropriate antigen distribution and staining intensity in keratinocytes in all cases. Conventional RT-PCR and sequencing also detected the presence of enterovirus, and CVA6-specific real-time RT-PCR analysis identified CVA6. Conclusion(s): Applying these immunohistochemistry and molecular techniques to formalin-fixed, paraffin-embedded tissues, CVA6 was determined to be the causative infectious agent in seven cases of atypical hand, foot, and mouth disease. Copyright © 2021 |
Identifying Cases of Shoulder Injury Related to Vaccine Administration (SIRVA) in the United States: Development and Validation of a Natural Language Processing Method.
Zheng C , Duffy J , Liu IA , Sy LS , Navarro RA , Kim SS , Ryan DS , Chen W , Qian L , Mercado C , Jacobsen SJ . JMIR Public Health Surveill 2022 8 (5) e30426 ![]() ![]() BACKGROUND: Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce. OBJECTIVE: The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes. METHODS: We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases. RESULTS: In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively. CONCLUSIONS: The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation. |
Rickettsia honei infection in a traveler returning from India
Denison AM , Leitgeb B , Obadiah JM , Schwindt A , Ladd-Wilson SG , Paddock CD , Matkovic E . Open Forum Infect Dis 2021 8 (2) ofaa636 We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses. |
Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients with Fatal COVID-19: An Autopsy Case-Series.
Bhatnagar J , Gary J , Reagan-Steiner S , Estetter LB , Tong S , Tao Y , Denison AM , Lee E , DeLeon-Carnes M , Li Y , Uehara A , Paden CR , Leitgeb B , Uyeki TM , Martines RB , Ritter JM , Paddock CD , Shieh WJ , Zaki SR . J Infect Dis 2021 223 (5) 752-764 ![]() ![]() BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes. |
A fatal case of Powassan virus encephalitis
Yu Q , Matkovic E , Reagan-Steiner S , Denison AM , Osborn R , Salamat SM . J Neuropathol Exp Neurol 2020 79 (11) 1239-1243 Powassan virus (POWV) is a flavivirus of the tick-borne encephalitis serogroup that causes a rare and potentially life-threatening neuroinvasive disease. Viral transmission occurs during zoonotic spillover from mammals by the bite of an infected tick in endemic regions of North America. The number of reported POWV cases has recently increased in the United States. We report a fatal case of POWV meningoencephalomyelitis in Northern Wisconsin following a documented tick bite. Histologic examination of the brain demonstrated widespread intraparenchymal and perivascular lymphohistocytic infiltration, microglial nodule formation, and marked neuronal degeneration, most severely involving the substantia nigra, anterior horn of spinal cord and cerebellum. Although no viral inclusions were seen in routine light microscopy, electron microscopy identified multiple neurons containing cytoplasmic clusters of virus particles ∼50 nm in diameter. POWV infection was confirmed using immunohistochemical analysis and reverse transcription-polymerase chain reaction. This report demonstrates in detail regional central nervous system involvement and ultrastructural characteristics of Powassan viral particles by transmission electron microscopy, while highlighting the utility of evaluating fixed autopsy tissues in cases of unexplained meningoencephalomyelitis. |
SARS-CoV-2 Infection Among Hospitalized Pregnant Women: Reasons for Admission and Pregnancy Characteristics - Eight U.S. Health Care Centers, March 1-May 30, 2020.
Panagiotakopoulos L , Myers TR , Gee J , Lipkind HS , Kharbanda EO , Ryan DS , Williams JTB , Naleway AL , Klein NP , Hambidge SJ , Jacobsen SJ , Glanz JM , Jackson LA , Shimabukuro TT , Weintraub ES . MMWR Morb Mortal Wkly Rep 2020 69 (38) 1355-1359 Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19), possibly related to changes in their immune system and respiratory physiology* (1). Further, adverse birth outcomes, such as preterm delivery and stillbirth, might be more common among pregnant women infected with SARS-CoV-2, the virus that causes COVID-19 (2,3). Information about SARS-CoV-2 infection during pregnancy is rapidly growing; however, data on reasons for hospital admission, pregnancy-specific characteristics, and birth outcomes among pregnant women hospitalized with SARS-CoV-2 infections are limited. During March 1-May 30, 2020, as part of Vaccine Safety Datalink (VSD)(†) surveillance of COVID-19 hospitalizations, 105 hospitalized pregnant women with SARS-CoV-2 infection were identified, including 62 (59%) hospitalized for obstetric reasons (i.e., labor and delivery or another pregnancy-related indication) and 43 (41%) hospitalized for COVID-19 illness without an obstetric reason. Overall, 50 (81%) of 62 pregnant women with SARS-CoV-2 infection who were admitted for obstetric reasons were asymptomatic. Among 43 pregnant women hospitalized for COVID-19, 13 (30%) required intensive care unit (ICU) admission, six (14%) required mechanical ventilation, and one died from COVID-19. Prepregnancy obesity was more common (44%) among pregnant women hospitalized for COVID-19 than that among asymptomatic pregnant women hospitalized for obstetric reasons (31%). Likewise, the rate of gestational diabetes (26%) among pregnant women hospitalized for COVID-19 was higher than it was among women hospitalized for obstetric reasons (8%). Preterm delivery occurred in 15% of pregnancies among 93 women who delivered, and stillbirths (fetal death at ≥20 weeks' gestation) occurred in 3%. Antenatal counseling emphasizing preventive measures (e.g., use of masks, frequent hand washing, and social distancing) might help prevent COVID-19 among pregnant women,(§) especially those with prepregnancy obesity and gestational diabetes, which might reduce adverse pregnancy outcomes. |
Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case series
Reagan-Steiner S , Gary J , Matkovic E , Ritter JM , Shieh WJ , Martines RB , Werner AK , Lynfield R , Holzbauer S , Bullock H , Denison AM , Bhatnagar J , Bollweg BC , Patel M , Evans ME , King BA , Rose DA , Baldwin GT , Jones CM , Krishnasamy V , Briss PA , Weissman DN , Meaney-Delman D , Zaki SR . Lancet Respir Med 2020 8 (12) 1219-1232 BACKGROUND: Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. METHODS: Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. FINDINGS: 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. INTERPRETATION: Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. FUNDING: US Centers for Disease Control and Prevention. |
Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.
Martines RB , Ritter JM , Matkovic E , Gary J , Bollweg BC , Bullock H , Goldsmith CS , Silva-Flannery L , Seixas JN , Reagan-Steiner S , Uyeki T , Denison A , Bhatnagar J , Shieh WJ , Zaki SR , Covid-Pathology Working Group . Emerg Infect Dis 2020 26 (9) 2005-2015 An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection. |
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.
Sheahan TP , Sims AC , Zhou S , Graham RL , Pruijssers AJ , Agostini ML , Leist SR , Schafer A , Dinnon KH 3rd , Stevens LJ , Chappell JD , Lu X , Hughes TM , George AS , Hill CS , Montgomery SA , Brown AJ , Bluemling GR , Natchus MG , Saindane M , Kolykhalov AA , Painter G , Harcourt J , Tamin A , Thornburg NJ , Swanstrom R , Denison MR , Baric RS . Sci Transl Med 2020 12 (541) Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (beta-D-N(4)-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
Identification of an Emergent Pathogen, Bartonella vinsonii, Using Next-Generation Sequencing in a Patient With Culture-Negative Endocarditis.
Downey RD , Russo SM , Hauger SB , Murphey DK , Marx G , Huynh T , Denison AM , Quirt R , Bailey A , Fernandez M . J Pediatric Infect Dis Soc 2020 10 (2) 213-216 ![]() Diagnosis and treatment of culture negative endocarditis remains a challenge. This report describes a rare cause of endocarditis in humans, Bartonella vinsonii, identified through next generation sequencing of plasma microbial cell-free DNA with confirmation of cardiac valve tissue infection through immunohistochemical staining and polymerase chain reaction. |
Diagnosis of spotted fever group rickettsioses in U.S. travelers returning from Africa, 2007-2016
Cherry CC , Denison AM , Kato CY , Thornton K , Paddock CD . Am J Trop Med Hyg 2018 99 (1) 136-142 Spotted fever group rickettsioses (SFGRs), such as African tick bite fever (ATBF), are among the most commonly diagnosed diseases for ill travelers returning from southern Africa. We summarized demographic, clinical, and diagnostic features of imported SFGR cases in U.S. travelers returning from Africa who had laboratory specimens submitted to the Centers for Disease Control and Prevention. Diagnosis of SFGR was performed by indirect immunofluorescence antibody assay, immunohistochemical staining, polymerase chain reaction (PCR), or culture. Cases were defined as probable SFGR, confirmed SFGR, or confirmed ATBF. Clinical and epidemiological categorical variables were described as counts and proportions; continuous variables were described using geometric mean titers, median, and range. One hundred and twenty-seven patients satisfied laboratory criteria for confirmed or probable SFGR. Fever was the most common symptom (N = 88; 69%), followed by >/= 1 eschars (N = 70; 55%). Paired serums were submitted for 36 patients (28%); 12 patients (33%) had nonreactive initial serum sample but converted to a titer >/= 64 with the convalescent sample. Twenty-seven patients (21%) had infection with Rickettsia africae based on PCR analysis of eschar swab (N = 8) or biopsy (N = 23). Fifteen patients had eschar biopsy or swab samples and serum sample(s) submitted together; 9 (60%) had PCR-positive eschar results and nonreactive acute serology. Health-care providers should consider SFGR when evaluating patients for a febrile illness with eschar and compatible foreign travel history. Polymerase chain reaction testing of eschar biopsies or swabs provides a confirmed diagnosis in early stages of disease; eschar swabs or biopsies are an underutilized diagnostic technique. |
Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on MERS-CoV Spike to avoid neutralization escape
Wang L , Shi W , Chappell JD , Joyce MG , Zhang Y , Kanekiyo M , Becker MM , van Doremalen N , Fischer R , Wang N , Corbett KS , Choe M , Mason RD , Van Galen JG , Zhou T , Saunders KO , Tatti KM , Haynes LM , Kwong PD , Modjarrad K , Kong WP , McLellan JS , Denison MR , Munster VJ , Mascola JR , Graham BS . J Virol 2018 92 (10) Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with approximately 35% mortality. The potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell-cloning strategy, we have identified and characterized multiple neutralizing mAbs specifically binding to the receptor binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific mAbs tended to have greater neutralizing potency than non-RBD S1-specific mAbs. Six RBD-specific and five S1-specific mAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined co-crystal structures for two mAbs targeting RBD from different angles and show they can only bind RBD in the "out" position. We then showed that selected RBD-specific, non-RBD S1, and S2-specific mAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD mAbs delayed the emergence of escape mutations in a cell-based virus-escape assay. These studies identify mAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization, and for developing more effective interventions to prevent or treat MERS-CoV infections.IMPORTANCE: MERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally-defined probes for the MERS-CoV Spike (S) glycoprotein, the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized non-human primates (NHPs). mAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining mAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed mAbs. These data suggest that antibody responses to multiple domains on CoV Spike may improve immunity and will guide future vaccine and therapeutic development efforts. |
Evaluation of placental and fetal tissue specimens for Zika virus infection - 50 states and District of Columbia, January-December, 2016
Reagan-Steiner S , Simeone R , Simon E , Bhatnagar J , Oduyebo T , Free R , Denison AM , Rabeneck DB , Ellington S , Petersen E , Gary J , Hale G , Keating MK , Martines RB , Muehlenbachs A , Ritter J , Lee E , Davidson A , Conners E , Scotland S , Sandhu K , Bingham A , Kassens E , Smith L , St George K , Ahmad N , Tanner M , Beavers S , Miers B , VanMaldeghem K , Khan S , Rabe I , Gould C , Meaney-Delman D , Honein MA , Shieh WJ , Jamieson DJ , Fischer M , Zaki SR . MMWR Morb Mortal Wkly Rep 2017 66 (24) 636-643 Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection. |
Trends in prevalence of advanced HIV disease at antiretroviral therapy enrollment - 10 countries, 2004-2015
Auld AF , Shiraishi RW , Oboho I , Ross C , Bateganya M , Pelletier V , Dee J , Francois K , Duval N , Antoine M , Delcher C , Desforges G , Griswold M , Domercant JW , Joseph N , Deyde V , Desir Y , Van Onacker JD , Robin E , Chun H , Zulu I , Pathmanathan I , Dokubo EK , Lloyd S , Pati R , Kaplan J , Raizes E , Spira T , Mitruka K , Couto A , Gudo ES , Mbofana F , Briggs M , Alfredo C , Xavier C , Vergara A , Hamunime N , Agolory S , Mutandi G , Shoopala NN , Sawadogo S , Baughman AL , Bashorun A , Dalhatu I , Swaminathan M , Onotu D , Odafe S , Abiri OO , Debem HH , Tomlinson H , Okello V , Preko P , Ao T , Ryan C , Bicego G , Ehrenkranz P , Kamiru H , Nuwagaba-Biribonwoha H , Kwesigabo G , Ramadhani AA , Ng'wangu K , Swai P , Mfaume M , Gongo R , Carpenter D , Mastro TD , Hamilton C , Denison J , Wabwire-Mangen F , Koole O , Torpey K , Williams SG , Colebunders R , Kalamya JN , Namale A , Adler MR , Mugisa B , Gupta S , Tsui S , van Praag E , Nguyen DB , Lyss S , Le Y , Abdul-Quader AS , Do NT , Mulenga M , Hachizovu S , Mugurungi O , Barr BAT , Gonese E , Mutasa-Apollo T , Balachandra S , Behel S , Bingham T , Mackellar D , Lowrance D , Ellerbrock TV . MMWR Morb Mortal Wkly Rep 2017 66 (21) 558-563 Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/muL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,dagger, section sign To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence. |
Genotypic analysis of Tropheryma whipplei from patients with Whipple disease in the Americas.
Rollin DC , Paddock CD , Pritt BS , Cunningham SA , Denison AM . J Clin Pathol 2017 70 (10) 891-895 ![]() Tropheryma whipplei, the agent of Whipple disease, causes a rare bacterial disease that may be fatal if not treated. The classical form of the disease includes diarrhoea, weight loss, arthritis, endocarditis and neurological manifestations. Genotyping studies done in Europe, Africa and Asia showed high genetic diversity with no correlation between genotypes and clinical features, but contributed to a better understanding of the epidemiology of the disease. More than 70 genotypes have been described. No similar assessment of T. whipplei in the USA and the Caribbean has been performed. In this study, we describe genetic analysis of DNA from histopathological samples obtained from 30 patients from the Americas with Whipple disease and compare the genotypes with those previously identified. Complete genotypes were obtained from 18 patients (60%). Only 4 genotypes were previously described, and 14 were newly reported, confirming the diversity of T. whipplei strains. |
Routine argyrophil techniques detect Rickettsia rickettsii in tissues of patients with fatal Rocky Mountain spotted fever
Paddock CD , Sanders JH , Denison AM , Muehlenbachs A , Zaki SR . J Histotechnol 2016 39 (4) 116-122 Rickettsia rickettsii, a bacterial tickborne pathogen that causes Rocky Mountain spotted fever (RMSF), stains poorly or not at all with conventional tissue Gram techniques, and contemporary visualization of the pathogen in formalin-fixed, paraffin-embedded tissues has relied almost entirely on immunohistochemical staining methods that are generally limited to specialized research laboratories or national reference centers. To our knowledge, previously described argyrophil-based histochemical techniques have not successfully detected rickettsiae in formalin-fixed, paraffin-embedded tissues. To investigate the ability of standard silver impregnation techniques to demonstrate the occurrence and distribution of R. rickettsii in tissues of patients with RMSF confirmed by molecular and immunohistochemical methods, three widely recognized and commercially available silver impregnation methods (Warthin–Starry, Steiner, and Dieterle’s) were applied to various tissues obtained at autopsy from 10 patients with fatal RMSF. R. rickettsii bacteria were demonstrated in one or more tissues of all patients, using each of the argyrophil-based methods, and appeared as small, dark brown-to-black lanceolate rods, often in pairs and occasionally surrounded by a faint halo. Rickettsiae were identified most consistently in small arteries and arterioles of liver, kidney, and leptomeninges, and were localized predominantly to the cytoplasm of endothelial cells and less often within the internal elastic lamella and smooth muscle of the media. This validation of argyrophilic techniques to detect R. rickettsii demonstrates the utility of inexpensive core histochemical methods in the diagnosis of infectious agents in pathology specimens and may have utility in certain resource-limited settings where RMSF is endemic. |
Placental massive perivillous fibrinoid deposition associated with coxsackievirus A16-report of a case, and review of the literature
Heller DS , Tellier R , Pabbaraju K , Wong S , Faye-Petersen OM , Muehlenbachs A , Goldsmith C , Denison A , Zaki SR . Pediatr Dev Pathol 2016 19 (5) 421-423 Massive placental perivillous fibrinoid deposition in the placenta is thought to be an immune-related condition associated with poor perinatal outcomes, including growth restriction and intrauterine fetal demise, with a high risk of recurrence. Rare cases have been associated with Coxsackievirus infection. We present such a case and review the literature. |
Notes from the field: Rickettsia parkeri rickettsiosis - Georgia, 2012-2014
Straily A , Feldpausch A , Ulbrich C , Schell K , Casillas S , Zaki SR , Denison AM , Condit M , Gabel J , Paddock CD . MMWR Morb Mortal Wkly Rep 2016 65 (28) 718-719 During 2012-2014, five cases of Rickettsia parkeri rickettsiosis were identified by a single urgent care practice in Georgia, located approximately 40 miles southwest of Atlanta. Symptom onset occurred during June-October, and all patients had a known tick bite. Patients ranged in age from 27 to 72 years (median = 53 years), and all were male. The most commonly reported initial signs were erythema (n = 3) and swelling (n = 2) at the site of the bite. Two patients reported fever and a third patient reported a rash and lymphadenopathy without fever. Other symptoms included myalgia (n = 3), chills (n = 3), fatigue (n = 2), arthralgia (n = 2), and headache (n = 2). Eschar biopsy specimens were collected from each patient using a 4-mm or 5-mm punch and placed in 10% neutral buffered formalin or sterile saline. These specimens were tested by immunohistochemical (IHC) stains, quantitative polymerase chain reaction (qPCR) assays, or cell culture isolation to determine if there was evidence of infection with a Rickettsia species (1). IHC evidence of spotted fever group rickettsiae was found in the eschar biopsy specimens in all five cases. In four cases, the biopsy specimens were also positive for R. parkeri by qPCR. The fifth case (specimen positive only by IHC testing) was considered a probable R. parkeri case based on clinical signs and symptoms. R. parkeri was grown in cell culture from one specimen from which isolation was attempted. All patients were treated with oral doxycycline (100 mg twice daily) for a minimum of 10 days, and all recovered. |
Rickettsia parkeri Rickettsiosis, Arizona, USA
Herrick KL , Pena SA , Yaglom HD , Layton BJ , Moors A , Loftis AD , Condit ME , Singleton J , Kato CY , Denison AM , Ng D , Mertins JW , Paddock CD . Emerg Infect Dis 2016 22 (5) 780-5 In the United States, all previously reported cases of Rickettsia parkeri rickettsiosis have been linked to transmission by the Gulf Coast tick (Amblyomma maculatum). Here we describe 1 confirmed and 1 probable case of R. parkeri rickettsiosis acquired in a mountainous region of southern Arizona, well beyond the recognized geographic range of A. maculatum ticks. The likely vector for these 2 infections was identified as the Amblyomma triste tick, a Neotropical species only recently recognized in the United States. Identification of R. parkeri rickettsiosis in southern Arizona demonstrates a need for local ecologic and epidemiologic assessments to better understand geographic distribution and define public health risk. Education and outreach aimed at persons recreating or working in this region of southern Arizona would improve awareness and promote prevention of tickborne rickettsioses. |
Reasons for missing antiretroviral therapy: results from a multi-country study in Tanzania, Uganda, and Zambia
Koole O , Denison JA , Menten J , Tsui S , Wabwire-Mangen F , Kwesigabo G , Mulenga M , Auld A , Agolory S , Mukadi YD , van Praag E , Torpey K , Williams S , Kaplan J , Zee A , Bangsberg DR , Colebunders R . PLoS One 2016 11 (1) e0147309 OBJECTIVES: To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence. METHODS: Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients' medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months. RESULTS: Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2-7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1-1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms. CONCLUSIONS: Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes. |
Lower levels of antiretroviral therapy enrollment among men with HIV compared with women - 12 countries, 2002-2013
Auld AF , Shiraishi RW , Mbofana F , Couto A , Fetogang EB , El-Halabi S , Lebelonyane R , Pilatwe PT , Hamunime N , Okello V , Mutasa-Apollo T , Mugurungi O , Murungu J , Dzangare J , Kwesigabo G , Wabwire-Mangen F , Mulenga M , Hachizovu S , Ettiegne-Traore V , Mohamed F , Bashorun A , Nhan do T , Hai NH , Quang TH , Van Onacker JD , Francois K , Robin EG , Desforges G , Farahani M , Kamiru H , Nuwagaba-Biribonwoha H , Ehrenkranz P , Denison JA , Koole O , Tsui S , Torpey K , Mukadi YD , van Praag E , Menten J , Mastro TD , Hamilton CD , Abiri OO , Griswold M , Pierre E , Xavier C , Alfredo C , Jobarteh K , Letebele M , Agolory S , Baughman AL , Mutandi G , Preko P , Ryan C , Ao T , Gonese E , Herman-Roloff A , Ekra KA , Kouakou JS , Odafe S , Onotu D , Dalhatu I , Debem HH , Nguyen DB , Yen le N , Abdul-Quader AS , Pelletier V , Williams SG , Behel S , Bicego G , Swaminathan M , Dokubo EK , Adjorlolo-Johnson G , Marlink R , Lowrance D , Spira T , Colebunders R , Bangsberg D , Zee A , Kaplan J , Ellerbrock TV . MMWR Morb Mortal Wkly Rep 2015 64 (46) 1281-6 Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(dagger) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage. |
High prevalence of "Candidatus Rickettsia andeanae" and apparent exclusion of Rickettsia parkeri in adult Amblyomma maculatum (Acari: Ixodidae) from Kansas and Oklahoma.
Paddock CD , Denison AM , Dryden MW , Noden BH , Lash RR , Abdelghani SS , Evans AE , Kelly AR , Hecht JA , Karpathy SE , Ganta RR , Little SE . Ticks Tick Borne Dis 2015 6 (3) 297-302 ![]() Amblyomma maculatum (the Gulf Coast tick), an aggressive, human-biting, Nearctic and Neotropical tick, is the principal vector of Rickettsia parkeri in the United States. This pathogenic spotted fever group Rickettsia species has been identified in 8-52% of questing adult Gulf Coast ticks in the southeastern United States. To our knowledge, R. parkeri has not been reported previously from adult specimens of A. maculatum collected in Kansas or Oklahoma. A total of 216 adult A. maculatum ticks were collected from 18 counties in Kansas and Oklahoma during 2011-2014 and evaluated by molecular methods for evidence of infection with R. parkeri. No infections with this agent were identified; however, 47% of 94 ticks collected from Kansas and 73% of 122 ticks from Oklahoma were infected with "Candidatus Rickettsia andeanae" a spotted fever group Rickettsia species of undetermined pathogenicity. These preliminary data suggest that "Ca. R. andeanae" is well-adapted to survival in populations of A. maculatum in Kansas and Oklahoma, and that its ubiquity in Gulf Coast ticks in these states may effectively exclude R. parkeri from their shared arthropod host, which could diminish markedly or preclude entirely the occurrence of R. parkeri rickettsiosis in this region of the United States. |
Antiretroviral therapy enrollment characteristics and outcomes among HIV-infected adolescents and young adults compared with older adults - seven African countries, 2004-2013
Auld AF , Agolory SG , Shiraishi RW , Wabwire-Mangen F , Kwesigabo G , Mulenga M , Hachizovu S , Asadu E , Tuho MZ , Ettiegne-Traore V , Mbofana F , Okello V , Azih C , Denison JA , Tsui S , Koole O , Kamiru H , Nuwagaba-Biribonwoha H , Alfredo C , Jobarteh K , Odafe S , Onotu D , Ekra KA , Kouakou JS , Ehrenkranz P , Bicego G , Torpey K , Mukadi YD , Praag Ev , Menten J , Mastro T , Hamilton CD , Swaminathan M , Dokubo EK , Baughman AL , Spira T , Colebunders R , Bangsberg D , Marlink R , Zee A , Kaplan J , Ellerbrock TV . MMWR Morb Mortal Wkly Rep 2014 63 (47) 1097-103 Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group. |
Rickettsia parkeri rickettsiosis in different ecological regions of Argentina and its association with Amblyomma tigrinum as a potential vector
Romer Y , Nava S , Govedic F , Cicuttin G , Denison AM , Singleton J , Kelly AJ , Kato CY , Paddock CD . Am J Trop Med Hyg 2014 91 (6) 1156-60 Rickettsia parkeri, a newly recognized tick-borne pathogen of humans in the Americas, is a confirmed cause of spotted fever rickettsiosis in Argentina. Until recently, almost all cases of R. parkeri rickettsiosis in Argentina have originated from the Parana River Delta, where entomological surveys have identified populations of R. parkeri-infected Amblyomma triste ticks. In this report, we describe confirmed cases of R. parkeri rickettsiosis in patients from Cordoba and La Rioja provinces, which are located several hundred kilometers inland, and patients from a more arid ecological region, where A. triste ticks do not occur. Additionally, we identified questing A. tigrinum ticks naturally infected with R. parkeri in Cordoba province. These data provide evidence that another human-biting tick species serves as a potential vector of R. parkeri in Argentina and possibly, other countries of South America. |
Novel poxvirus infection in two patients from the United States
Osadebe LU , Manthiram K , McCollum AM , Li Y , Emerson GL , Gallardo-Romero NF , Doty JB , Wilkins K , Zhao H , Drew CP , Metcalfe MG , Goldsmith CS , Muehlenbachs A , Googe P , Dunn J , Duenckel T , Henderson H , Carroll DS , Zaki SR , Denison M , Reynolds MG , Damon IK . Clin Infect Dis 2014 60 (2) 195-202 BACKGROUND: Some human poxvirus infections can be acquired through zoonotic transmission. We report a previously unknown poxvirus infection in two patients, one of whom was immunocompromised, and both patients had known equine contact. METHODS: The patients were interviewed and clinical information was abstracted from the patients' medical files. Biopsies of the skin lesions were collected from both patients for histopathology, immunohistochemistry, and transmission electron microscopy analysis. Oral and skin swabs were collected from animals with frequent contact with the patients and environmental sampling including rodent trapping was performed on the farm where the immunosuppressed patient was employed. 'Pan-pox and high GC' PCR assays were performed on patient, animal, and environmental isolates. Amplicon sequences of the viral DNA were used for agent identification and phylogenetic analysis. RESULTS: Specimens from both human cases revealed a novel poxvirus. The agent shares 88% similarity to viruses in the Parapoxvirus genus and 78% to those in the Molluscipoxvirus genus but is sufficiently divergent to resist classification as either. All animal and environmental specimens were negative for poxvirus and both patients had complete resolution of lesions. CONCLUSION: This report serves as a reminder that poxviruses should be considered in cutaneous human infections especially in individuals with known barnyard exposures. The clinical course of the patients was similar to that of parapoxvirus infections and the source of this virus is currently unknown but is presumed to be zoonotic. This report also demonstrates the importance of a comprehensive approach to diagnosis of human infections caused by previously unknown pathogens. |
Transmission of methicillin-resistant Staphylococcus aureus infection through solid organ transplantation: confirmation via whole genome sequencing.
Wendt JM , Kaul D , Limbago BM , Ramesh M , Cohle S , Denison AM , Driebe EM , Rasheed JK , Zaki SR , Blau DM , Paddock CD , McDougal LK , Engelthaler DM , Keim PS , Roe CC , Akselrod H , Kuehnert MJ , Basavaraju SV . Am J Transplant 2014 14 (11) 2633-9 ![]() We describe two cases of donor-derived methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that developed after transplantation of organs from a common donor who died from acute MRSA endocarditis. Both recipients developed recurrent MRSA infection despite appropriate antibiotic therapy, and required prolonged hospitalization and hospital readmission. Comparison of S. aureus whole genome sequence of DNA extracted from fixed donor tissue and recipients' isolates confirmed donor-derived transmission. Current guidelines emphasize the risk posed by donors with bacteremia from multidrug-resistant organisms. This investigation suggests that, particularly in the setting of donor endocarditis, even a standard course of prophylactic antibiotics may not be sufficient to prevent donor-derived infection. |
Middle East respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to September 2012
Khuri-Bulos N , Payne DC , Lu X , Erdman D , Wang L , Faouri S , Shehabi A , Johnson M , Becker MM , Denison MR , Williams JV , Halasa NB . Clin Microbiol Infect 2014 20 (7) 678-82 Hospitalized children < 2 years of age in Amman, Jordan, admitted for fever and/or respiratory symptoms, were tested for Middle East respiratory syndrome coronavirus (MERS-CoV): MERS-CoV by real-time RT-PCR (rRT-PCR). This was a prospective year-round viral surveillance study in children <2 years of age admitted with acute respiratory symptoms and/or fever from March 2010 to September 2012 and enrolled from a government-run hospital, Al-Bashir in Amman, Jordan. Clinical and demographic data, including antibiotic use, were collected. Combined nasal/throat swabs were collected, aliquoted, and frozen at -80 degrees C. Specimen aliquots were shipped to Vanderbilt University and the Centers for Disease Control and Prevention (CDC), and tested by rRT-PCR for MERS-CoV. Of the 2433 subjects enrolled from 16 March 2010 to 10 September 2012, 2427 subjects had viral testing and clinical data. Of 1898 specimens prospectively tested for other viruses between 16 March 2010 and 18 March 2012, 474 samples did not have other common respiratory viruses detected. These samples were tested at CDC for MERS-CoV and all were negative by rRT-PCR for MERS-CoV. Of the remaining 531 samples, collected from 19 March 2012 to 10 September 2012 and tested at Vanderbilt, none were positive for MERS-CoV. Our negative findings from a large sample of young Jordanian children hospitalized with fever and/or respiratory symptoms suggest that MERS-CoV was not widely circulating in Amman, Jordan, during the 30-month period of prospective, active surveillance occurring before and after the first documented MERS-CoV outbreak in the Middle East region. |
Phylogeography of Rickettsia rickettsii genotypes associated with fatal Rocky Mountain spotted fever.
Paddock CD , Denison AM , Lash RR , Liu L , Batten BC , Dahlgren FS , Kanamura CT , Angerami RN , Pereira Dos Santos FC , Brasil Martines R , Karpathy SE . Am J Trop Med Hyg 2014 91 (3) 589-97 ![]() Rocky Mountain spotted fever (RMSF), a tick-borne zoonosis caused by Rickettsia rickettsii, is among the deadliest of all infectious diseases. To identify the distribution of various genotypes of R. rickettsii associated with fatal RMSF, we applied molecular typing methods to samples of DNA extracted from formalin-fixed, paraffin-embedded tissue specimens obtained at autopsy from 103 case-patients from seven countries who died of RMSF. Complete sequences of one or more intergenic regions were amplified from tissues of 30 (29%) case-patients and revealed a distribution of genotypes consisting of four distinct clades, including the Hlp clade, regarded previously as a non-pathogenic strain of R. rickettsii. Distinct phylogeographic patterns were identified when composite case-patient and reference strain data were mapped to the state and country of origin. The phylogeography of R. rickettsii is likely determined by ecological and environmental factors that exist independently of the distribution of a particular tick vector. |
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