Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-30 (of 67 Records) |
Query Trace: Wen W[original query] |
---|
A diverse group of small circular ssDNA viral genomes in human and non-human primate stools.
Ng TF , Zhang W , Sachsenröder J , Kondov NO , da Costa AC , Vega E , Holtz LR , Wu G , Wang D , Stine CO , Antonio M , Mulvaney US , Muench MO , Deng X , Ambert-Balay K , Pothier P , Vinjé J , Delwart E . Virus Evol 2015 1 (1) vev017 Viral metagenomics sequencing of fecal samples from outbreaks of acute gastroenteritis from the US revealed the presence of small circular ssDNA viral genomes encoding a replication initiator protein (Rep). Viral genomes were ∼2.5 kb in length, with bi-directionally oriented Rep and capsid (Cap) encoding genes and a stem loop structure downstream of Rep. Several genomes showed evidence of recombination. By digital screening of an in-house virome database (1.04 billion reads) using BLAST, we identified closely related sequences from cases of unexplained diarrhea in France. Deep sequencing and PCR detected such genomes in 7 of 25 US (28 percent) and 14 of 21 French outbreaks (67 percent). One of eighty-five sporadic diarrhea cases in the Gambia was positive by PCR. Twenty-two complete genomes were characterized showing that viruses from patients in the same outbreaks were closely related suggesting common origins. Similar genomes were also characterized from the stools of captive chimpanzees, a gorilla, a black howler monkey, and a lemur that were more diverse than the human stool-associated genomes. The name smacovirus is proposed for this monophyletic viral clade. Possible tropism include mammalian enteric cells or ingested food components such as infected plants. No evidence of viral amplification was found in immunodeficient mice orally inoculated with smacovirus-positive stool supernatants. A role for smacoviruses in diarrhea, if any, remains to be demonstrated. |
First Case of Covid-19 in the United States. Reply.
Uyeki TM , Holshue ML , Diaz G . N Engl J Med 2020 382 (21) e53 The authors reply: Weng et al. question the clinical benefit of remdesivir treatment. In our article, we noted that the decision to administer remdesivir for compassionate use was based on the patient’s worsening clinical status. No inferences are possible from the uncontrolled treatment of one patient, and we stated, “randomized, controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.” | | Tsung notes that an increase in lymphocyte counts and subsequent clinical improvement are consistent with activation of the adaptive immune response and resolution of SARS-CoV-2 infection. IgM and IgA antibodies may be detectable early in the clinical course, and IgG antibodies can be detected a median of 14 days after the onset of illness.1 We agree that the adaptive immune response contributes to clinical recovery and clearance of SARS-CoV-2, although one study showed that seroconversion was not correlated with a rapid decline in the SARS-CoV-2 load.2 In another study that showed a good correlation between IgG and neutralizing antibody titers, an increase in IgG antibody levels was correlated with a decrease in the viral load between 1 and 3 weeks after the onset of illness, but SARS-CoV-2 RNA was still detectable for prolonged periods.3 | | Zhang inquires about detection of SARS-CoV-2 in stool and urine specimens after remdesivir treatment. In our patient, although a stool specimen collected on day 7 of illness was positive with high cycle threshold values (36 to 38) that were consistent with detection of viral RNA and probably not infectious virus, a stool specimen obtained from the patient on day 14 of illness was negative. SARS-CoV-2 RNA was not detected in urine specimens; these findings are consistent with those in a larger study.4 | | Wen et al. and Link and Hold raise the issue of fecal–oral transmission of SARS-CoV-2. Diarrhea has been reported to occur in patients with Covid-19, and it can precede the development of respiratory symptoms and progression to pneumonia. SARS-CoV-2 RNA has been detected in stool specimens, and recovery of live infectious virus from stool has been reported.4 Further studies are needed to understand the implications of SARS-CoV-2 detected in stool for transmission of the virus. | | Ren et al. argue that high-resolution low-dose chest CT should be performed instead of chest radiography in persons with fever and suspected Covid-19. The Centers for Disease Control and Prevention recommends collection of nasopharyngeal swab specimens and lower respiratory specimens, if available, for SARS-CoV-2 testing and prioritizes testing of hospitalized patients and symptomatic health care workers. Furthermore, the American College of Radiology has noted concerns regarding prevention and control of SARS-CoV-2 transmission in health care facilities, including transmission that may occur with the use of CT scanners, and has recommended that CT should not be used to screen for or diagnose Covid-19.5 |
Using a One Health approach to prioritize zoonotic diseases in China, 2019.
Wang X , Rainey JJ , Goryoka GW , Liang Z , Wu S , Wen L , Duan R , Qin S , Huang H , Kharod G , Rao CY , Salyer SJ , Behravesh CB , Jing H . PLoS One 2021 16 (11) e0259706 BACKGROUND: China is vulnerable to zoonotic disease transmission due to a large agricultural work force, sizable domestic livestock population, and a highly biodiverse ecology. To better address this threat, representatives from the human, animal, and environmental health sectors in China held a One Health Zoonotic Disease Prioritization (OHZDP) workshop in May 2019 to develop a list of priority zoonotic diseases for multisectoral, One Health collaboration. METHODS: Representatives used the OHZDP Process, developed by the US Centers for Disease Control and Prevention (US CDC), to prioritize zoonotic diseases for China. Representatives defined the criteria used for prioritization and determined questions and weights for each individual criterion. A review of English and Chinese literature was conducted prior to the workshop to collect disease specific information on prevalence, morbidity, mortality, and Disability-Adjusted Life Years (DALYs) from China and the Western Pacific Region for zoonotic diseases considered for prioritization. RESULTS: Thirty zoonotic diseases were evaluated for prioritization. Criteria selected included: 1) disease hazard/severity (case fatality rate) in humans, 2) epidemic scale and intensity (in humans and animals) in China, 3) economic impact, 4) prevention and control, and 5) social impact. Disease specific information was obtained from 792 articles (637 in English and 155 in Chinese) and subject matter experts for the prioritization process. Following discussion of the OHZDP Tool output among disease experts, five priority zoonotic diseases were identified for China: avian influenza, echinococcosis, rabies, plague, and brucellosis. CONCLUSION: Representatives agreed on a list of five priority zoonotic diseases that can serve as a foundation to strengthen One Health collaboration for disease prevention and control in China; this list was developed prior to the emergence of SARS-CoV-2 and the COVID-19 pandemic. Next steps focused on establishing a multisectoral, One Health coordination mechanism, improving multisectoral linkages in laboratory testing and surveillance platforms, creating multisectoral preparedness and response plans, and increasing workforce capacity. |
Costs and Consequences of Eliminating a Routine, Point-Of-Care HIV Screening Program in a High-Prevalence Jail
Hutchinson AB , MacGowan RJ , Margolis AD , Adee MG , Wen W , Bowden CJ , Spaulding AC . Am J Prev Med 2021 61 S32-s38 INTRODUCTION: This study aims to assess the public health impact of eliminating a longstanding routine HIV screening program and replacing it with targeted testing. In addition, costs, outcomes, and cost effectiveness of routine screening are compared with those of targeted testing in the Fulton County Jail, Atlanta, Georgia. METHODS: A published mathematical model was used to assess the cost effectiveness and public health impact of routine screening (March 2013-February 2014) compared with those of targeted testing (January 2018-December 2018) from a health system perspective. Costs, outcomes, and other model inputs were derived from the testing programs and the published literature, and the cost effectiveness analysis was conducted from 2019 to 2020. RESULTS: Routine screening identified 74 more new HIV infections over 1 year than targeted testing, resulting in an estimated 10 HIV transmissions averted and 45 quality-adjusted life-years saved, and was cost saving. The missed opportunity to diagnose infections because routine screening was eliminated resulted in an estimated 8.4 additional HIV transmissions and $3.7 million in additional costs to the healthcare system. CONCLUSIONS: Routine HIV screening in high-prevalence jails is cost effective and has a larger impact on public health than targeted testing. Prioritizing sustained funding for routine, jail-based HIV screening programs in high-prevalence areas may be important to realizing the national HIV prevention goals. |
2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
Kuhn JH , Adkins S , Agwanda BR , Al Kubrusli R , Alkhovsky Aльxoвcкий Cepгeй Bлaдимиpoвич SV , Amarasinghe GK , Avšič-Županc T , Ayllón MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Basler CF , Bavari S , Beer M , Bejerman N , Bennett AJ , Bente DA , Bergeron É , Bird BH , Blair CD , Blasdell KR , Blystad DR , Bojko J , Borth WB , Bradfute S , Breyta R , Briese T , Brown PA , Brown JK , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Büttner C , Calisher CH , Cao 曹孟籍 M , Casas I , Chandran K , Charrel RN , Cheng Q , Chiaki 千秋祐也 Y , Chiapello M , Choi IR , Ciuffo M , Clegg JCS , Crozier I , Dal Bó E , de la Torre JC , de Lamballerie X , de Swart RL , Debat H , Dheilly NM , Di Cicco E , Di Paola N , Di Serio F , Dietzgen RG , Digiaro M , Dolnik O , Drebot MA , Drexler JF , Dundon WG , Duprex WP , Dürrwald R , Dye JM , Easton AJ , Ebihara 海老原秀喜 H , Elbeaino T , Ergünay K , Ferguson HW , Fooks AR , Forgia M , Formenty PBH , Fránová J , Freitas-Astúa J , Fu 付晶晶 J , Fürl S , Gago-Zachert S , Gāo 高福 GF , García ML , García-Sastre A , Garrison AR , Gaskin T , Gonzalez JJ , Griffiths A , Goldberg TL , Groschup MH , Günther S , Hall RA , Hammond J , Han 韩彤 T , Hepojoki J , Hewson R , Hong 洪健 J , Hong 洪霓 N , Hongo 本郷誠治 S , Horie 堀江真行 M , Hu JS , Hu T , Hughes HR , Hüttner F , Hyndman TH , Ilyas M , Jalkanen R , Jiāng 姜道宏 D , Jonson GB , Junglen S , Kadono 上遠野冨士夫 F , Kaukinen KH , Kawate M , Klempa B , Klingström J , Kobinger G , Koloniuk I , Kondō 近藤秀樹 H , Koonin EV , Krupovic M , Kubota 久保田健嗣 K , Kurath G , Laenen L , Lambert AJ , Langevin SL , Lee B , Lefkowitz EJ , Leroy EM , Li 李邵蓉 S , Li 李龙辉 L , Lǐ 李建荣 J , Liu 刘华珍 H , Lukashevich IS , Maes P , de Souza WM , Marklewitz M , Marshall SH , Marzano SL , Massart S , McCauley JW , Melzer M , Mielke-Ehret N , Miller KM , Ming TJ , Mirazimi A , Mordecai GJ , Mühlbach HP , Mühlberger E , Naidu R , Natsuaki 夏秋知英 T , Navarro JA , Netesov Heтёcoв Cepгeй Bиктopoвич SV , Neumann G , Nowotny N , Nunes MRT , Olmedo-Velarde A , Palacios G , Pallás V , Pályi B , Papa Άννα Παπά A , Paraskevopoulou Σοφία Παρασκευοπούλου S , Park AC , Parrish CR , Patterson DA , Pauvolid-Corrêa A , Pawęska JT , Payne S , Peracchio C , Pérez DR , Postler TS , Qi 亓立莹 L , Radoshitzky SR , Resende RO , Reyes CA , Rima BK , Luna GR , Romanowski V , Rota P , Rubbenstroth D , Rubino L , Runstadler JA , Sabanadzovic S , Sall AA , Salvato MS , Sang R , Sasaya 笹谷孝英 T , Schulze AD , Schwemmle M , Shi 施莽 M , Shí 石晓宏 X , Shí 石正丽 Z , Shimomoto 下元祥史 Y , Shirako Y , Siddell SG , Simmonds P , Sironi M , Smagghe G , Smither S , Song 송진원 JW , Spann K , Spengler JR , Stenglein MD , Stone DM , Sugano J , Suttle CA , Tabata A , Takada 高田礼人 A , Takeuchi 竹内繁治 S , Tchouassi DP , Teffer A , Tesh RB , Thornburg NJ , Tomitaka 冨高保弘 Y , Tomonaga 朝長啓造 K , Tordo N , Torto B , Towner JS , Tsuda 津田新哉 S , Tu 涂长春 C , Turina M , Tzanetakis IE , Uchida J , Usugi 宇杉富雄 T , Vaira AM , Vallino M , van den Hoogen B , Varsani A , Vasilakis Νίκος Βασιλάκης N , Verbeek M , von Bargen S , Wada 和田治郎 J , Wahl V , Walker PJ , Wang 王林发 LF , Wang 王国平 G , Wang 王雁翔 Y , Wang 王亚琴 Y , Waqas M , Wèi 魏太云 T , Wen 温少华 S , Whitfield AE , Williams JV , Wolf YI , Wu 吴建祥 J , Xu 徐雷 L , Yanagisawa 栁澤広宣 H , Yang 杨彩霞 C , Yang 杨作坤 Z , Zerbini FM , Zhai 翟立峰 L , Zhang 张永振 YZ , Zhang 张松 S , Zhang 张靖国 J , Zhang 张哲 Z , Zhou 周雪平 X . Arch Virol 2021 166 (12) 3513-3566 In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
Epidemiologic Findings from Case Investigations and Contact Tracing for First 200 Cases of Coronavirus Disease, Santa Clara County, California, USA.
Ortiz N , Villarino E , Lee JT , Bajema KL , Ricaldi JN , Smith S , Lin W , Cortese M , Barskey AE , Da Silva JF , Bonin BJ , Rudman S , Han GS , Fischer M , Chai SJ , Cody SH . Emerg Infect Dis 2021 27 (5) 1301-1308 In January 2020, Santa Clara County, California, USA, began identifying laboratory-confirmed coronavirus disease among residents. County staff conducted case and contact investigations focused on households and collected detailed case demographic, occupation, exposure, and outcome information. We describe the first 200 test-positive cases during January 31-March 20, 2020, to inform future case and contact investigations. Probable infection sources included community transmission (104 cases), known close contact with a confirmed case-patient (66 cases), and travel (30 cases). Disease patterns across race and ethnicity, occupational, and household factors suggested multiple infection risk factors. Disproportionately high percentages of case-patients from racial and ethnic subgroups worked outside the home (Hispanic [86%] and Filipino [100%]); household transmission was more common among persons from Vietnam (53%). Even with the few initial cases, detailed case and contact investigations of household contacts capturing occupational and disaggregated race and ethnicity data helped identify at-risk groups and focused solutions for disease control. |
Racial and Ethnic Disparities in Incidence of SARS-CoV-2 Infection, 22 US States and DC, January 1-October 1, 2020.
Hollis ND , Li W , Van Dyke ME , Njie GJ , Scobie HM , Parker EM , Penman-Aguilar A , Clarke KEN . Emerg Infect Dis 2021 27 (5) 1477-1481 We examined disparities in cumulative incidence of severe acute respiratory syndrome coronavirus 2 by race/ethnicity, age, and sex in the United States during January 1-October 1, 2020. Hispanic/Latino and non-Hispanic Black, American Indian/Alaskan Native, and Native Hawaiian/other Pacific Islander persons had a substantially higher incidence of infection than non-Hispanic White persons. |
Introduction, Transmission Dynamics, and Fate of Early SARS-CoV-2 Lineages in Santa Clara County, California.
Villarino E , Deng X , Kemper CA , Jorden MA , Bonin B , Rudman SL , Han GS , Yu G , Wang C , Federman S , Bushnell B , Wadford DA , Lin W , Tao Y , Paden CR , Bhatnagar J , MacCannell T , Tong S , Batson J , Chiu CY . J Infect Dis 2021 224 (2) 207-217 We combined viral genome sequencing with contact tracing to investigate introduction and evolution of SARS-CoV-2 lineages in Santa Clara County, California from January 27 to March 21, 2020. Of 558 persons with COVID-19, 101 genomes from 143 available clinical samples comprised 17 different lineages including SCC1 (n=41), WA1 (n=9, including the first 2 reported deaths in the United States, diagnosed post-mortem), D614G (n=4), ancestral Wuhan Hu-1 (n=21), and 13 others (n=26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February-March. By August, only D614G lineages introduced after March 21 were circulating in SCC. |
Racial and Ethnic Disparities in COVID-19 Incidence by Age, Sex, and Period Among Persons Aged <25 Years - 16 U.S. Jurisdictions, January 1-December 31, 2020.
Van Dyke ME , Mendoza MCB , Li W , Parker EM , Belay B , Davis EM , Quint JJ , Penman-Aguilar A , Clarke KEN . MMWR Morb Mortal Wkly Rep 2021 70 (11) 382-388 The COVID-19 pandemic has disproportionately affected racial and ethnic minority groups in the United States. Whereas racial and ethnic disparities in severe COVID-19-associated outcomes, including mortality, have been documented (1-3), less is known about population-based disparities in infection with SARS-CoV-2, the virus that causes COVID-19. In addition, although persons aged <30 years account for approximately one third of reported infections,(§) there is limited information on racial and ethnic disparities in infection among young persons over time and by sex and age. Based on 689,672 U.S. COVID-19 cases reported to CDC's case-based surveillance system by jurisdictional health departments, racial and ethnic disparities in COVID-19 incidence among persons aged <25 years in 16 U.S. jurisdictions(¶) were described by age group and sex and across three periods during January 1-December 31, 2020. During January-April, COVID-19 incidence was substantially higher among most racial and ethnic minority groups compared with that among non-Hispanic White (White) persons (rate ratio [RR] range = 1.09-4.62). During May-August, the RR increased from 2.49 to 4.57 among non-Hispanic Native Hawaiian and Pacific Islander (NH/PI) persons but decreased among other racial and ethnic minority groups (RR range = 0.52-2.82). Decreases in disparities were observed during September-December (RR range = 0.37-1.69); these decreases were largely because of a greater increase in incidence among White persons, rather than a decline in incidence among racial and ethnic minority groups. NH/PI, non-Hispanic American Indian or Alaska Native (AI/AN), and Hispanic or Latino (Hispanic) persons experienced the largest persistent disparities over the entire period. Ensuring equitable and timely access to preventive measures, including testing, safe work and education settings, and vaccination when eligible is important to address racial/ethnic disparities. |
Population-based geospatial and molecular epidemiologic study of tuberculosis transmission dynamics, Botswana, 2012-2016
Zetola NM , Moonan PK , Click E , Oeltmann JE , Basotli J , Wen XJ , Boyd R , Tobias JL , Finlay A , Modongo C . Emerg Infect Dis 2021 27 (3) 835-844 Tuberculosis (TB) elimination requires interrupting transmission of Mycobacterium tuberculosis. We used a multidisciplinary approach to describe TB transmission in 2 sociodemographically distinct districts in Botswana (Kopanyo Study). During August 2012-March 2016, all patients who had TB were enrolled, their sputum samples were cultured, and M. tuberculosis isolates were genotyped by using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats. Of 5,515 TB patients, 4,331 (79%) were enrolled. Annualized TB incidence varied by geography (range 66-1,140 TB patients/100,000 persons). A total of 1,796 patient isolates had valid genotyping results and residential geocoordinates; 780 (41%) patients were involved in a localized TB transmission event. Residence in areas with a high burden of TB, age <24 years, being a current smoker, and unemployment were factors associated with localized transmission events. Patients with known HIV-positive status had lower odds of being involved in localized transmission. |
Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors
Wu BC , Olivia NA , Tembo JM , He YX , Zhang YM , Xue Y , Ye CL , Lv Y , Li WJ , Jiang LY , Huo XX , Sun ZY , Chen ZJ , Qin JC , Li AY , Park CG , Klena JD , Ding HH , Chen T . J Med Microbiol 2021 70 (3) Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors. |
Assessing the burden of congenital rubella syndrome in China and evaluating mitigation strategies: a metapopulation modelling study
Su Q , Feng Z , Hao L , Ma C , Hagan JE , Grant GB , Wen N , Fan C , Yang H , Rodewald LE , Wang H , Glasser JW . Lancet Infect Dis 2021 21 (7) 1004-1013 BACKGROUND: A rubella vaccine was licensed in China in 1993 and added to the Expanded Programme on Immunization in 2008, but a national cross-sectional serological survey during 2014 indicates that many adolescents remain susceptible. Maternal infections during the first trimester often cause miscarriages, stillbirths, and, among livebirths, congenital rubella syndrome. We aimed to evaluate possible supplemental immunisation activities (SIAs) to accelerate elimination of rubella and congenital rubella syndrome. METHODS: We analysed residual samples from the national serological survey done in 2014, data from monthly rubella surveillance reports from 2005 and 2016, and additional publications through a systematic review. Using an age-structured population model with provincial strata, we calculated the reproduction numbers and evaluated the gradient of the metapopulation effective reproduction number with respect to potential supplemental immunisation rates. We corroborated these analytical results and estimated times-to-elimination by simulating SIAs among adolescents (ages 10-19 years) and young adults (ages 20-29 years) using a model with regional strata. We estimated the incidence of rubella and burden of congenital rubella syndrome by simulating transmission in a relatively small population lacking only spatial structure. FINDINGS: By 2014, childhood immunisation had reduced rubella's reproduction number from 7·6 to 1·2 and SIAs among adolescents were the optimal elimination strategy. We found that less than 10% of rubella infections were reported; that although some women with symptomatic first-trimester infections might have elected to terminate their pregnancies, 700 children could have been born with congenital rubella syndrome during 2014; and that timely SIAs would avert outbreaks that, as susceptible adolescents reached reproductive age, could greatly increase the burden of this syndrome. INTERPRETATION: Our findings suggest that SIAs among adolescents would most effectively reduce congenital rubella syndrome as well as eliminate rubella, owing both to fewer infections in the immunised population and absence of infections that those immunised would otherwise have caused. Metapopulation models with realistic mixing are uniquely capable of assessing such indirect effects. FUNDING: WHO and National Science Foundation. |
Performance of Xpert MTB/RIF and Determine TB-LAM Ag in HIV-infected adults in peri-urban sites in Zambia
Kasaro MP , Chilyabanyama ON , Shah NS , Muluka B , Kapata N , Krüüner A , Mwaba I , Kaunda K , Coggin WL , Wen XJ , Henostroza G , Reid S . Public Health Action 2020 10 (4) 134-140 SETTING: Peri-urban health facilities providing HIV and TB care in Zambia. OBJECTIVE: To evaluate 1) the impact of Xpert(®) MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. DESIGN: Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. RESULTS: Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm(3) vs. 31.7% overall. CONCLUSION: Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease. |
Characterizations of Enterocytozoon bieneusi at new genetic loci reveal a lack of strict host specificity among common genotypes and the existence of a canine-adapted Enterocytozoon species.
Ou Y , Jiang W , Roellig DM , Wan Z , Li N , Guo Y , Feng Y , Xiao L . Int J Parasitol 2020 51 215-223 Molecular characterizations of the microsporidian pathogen Enterocytozoon bieneusi at the ribosomal internal transcribed spacer (ITS) locus have identified nearly 500 genotypes in 11 phylogenetic groups with different host ranges. Among those, one unique group of genotypes, Group 11, is commonly found in dogs. Genetic characterizations of those and many divergent E. bieneusi genotypes at other genetic loci are thus far impossible. In this study, we sequenced 151 E. bieneusi isolates from several ITS genotype groups at the 16S rRNA locus and two new semi-conservative genetic markers (casein kinase 1 (ck1) and spore wall protein 1 (swp1)). Comparison of the near full (~1,200 bp) 16S rRNA sequences showed mostly two to three nucleotide substitutions between Group 1 and Group 2 genotypes, while Group 11 isolates differed from those by 26 (2.2%) nucleotides. Sequence analyses of the ck1 and swp1 loci confirmed the genetic uniqueness of Group 11 genotypes, which produced sequences very divergent from other groups. In contrast, genotypes in Groups 1 and 2 produced similar nucleotide sequences at these genetic loci, and there was discordant placement of ITS genotypes among loci in phylogenetic analyses of sequences. These results suggest that the canine-adapted Group 11 genotypes are genetically divergent from other genotype groups of E. bieneusi, possibly representing a different Enterocytozoon sp. They also indicate that there is no clear genetic differentiation of ITS Groups 1 and 2 at other genetic loci, supporting the conclusion on the lack of strict host specificity in both groups. Data and genetic markers from the study should facilitate population genetic characterizations of E. bieneusi isolates and improve our understanding of the zoonotic potential of E. bieneusi in domestic animals. |
Development of a Subtyping Tool for Zoonotic Pathogen Cryptosporidium Canis .
Jiang W , Roellig DM , Guo Y , Li N , Feng Y , Xiao L . J Clin Microbiol 2020 59 (3) Cryptosporidium canis is an important cause of cryptosporidiosis in canines and humans. Studies of the transmission characteristics of C. canis are currently hampered by lack of suitable subtyping tools. In this study, we conducted a genomic survey of the pathogen and developed a subtyping tool targeting the partial 60-kDa glycoprotein (gp60) gene. Seventy-six isolates previously identified as C. canis were analyzed using the new subtyping tool. Amplicons of expected size were obtained from 49 isolates, and phylogenetic analysis identified 10 subtypes clustered in five distinct groups (XXa-XXe). The largest group XXa contained 43 isolates from four subtypes that differed slightly from each other at the nucleotide level, while groups XXb-XXe contain one to three isolates each. The similar distribution of subtypes in humans and canines suggests that zoonotic transmission might play an important role in the epidemiology of C. canis In addition, a suspected zoonotic transmission of C. canis between dogs and humans in a household was confirmed using the subtyping tool. The subtyping tool and data generated in this study might improve our understanding of the transmission of this zoonotic pathogen. |
Subtype distribution of zoonotic pathogen Cryptosporidium felis in humans and animals in several countries.
Jiang W , Roellig DM , Lebbad M , Beser J , Troell K , Guo Y , Li N , Xiao L , Feng Y . Emerg Microbes Infect 2020 9 (1) 1-22 Cryptosporidium felis is the major etiologic agent of cryptosporidiosis in felines and has been reported in numerous human cryptosporidiosis cases. Sequence analysis of the 60-kDa glycoprotein (gp60) gene has been developed for subtyping C. felis recently. In this study, 66 C. felis isolates from the United States, Jamaica, Peru, Portugal, Slovakia, Nigeria, Ethiopia, Kenya, China, India and Australia were subtyped using the newly established tool. Forty-four specimens yielded gp60 sequences, generating 23 subtypes clustered in 4 subtype families (XIXa, XIXc, XIXd and XIXe) with high bootstrap support in a phylogenetic analysis of sequence data. Among them, XIXa showed high genetic diversity at the nucleotide level, with the formation of 18 subtypes from both cats and humans with different geographic distribution. In contrast, all 11 XIXd isolates derived from humans from various countries had identical sequences. Results of this study improve our understanding of the genetic diversity, host specificity and transmission dynamics of C. felis. |
Limited tryptic digestion-isotope dilution mass spectrometry (LTD-IDMS): A reagent-free analytical assay to quantify hemagglutinin of A(H5N1) vaccine material
Cooper HC , Xie Y , Palladino G , Barr JR , Settembre EC , Wen Y , Williams TL . Anal Chem 2020 92 (17) 11879-11887 Avian influenza viruses, such as A(H5N1) and A(H7N9), are primary public health concerns due to their pandemic potential. Influenza vaccines represent the most effective response to this threat especially with timely provision. The current pandemic response timelines require a substantial period for strain-specific reference antigen and sera preparation for use with single-radial immunodiffusion (SRID), the accepted vaccine potency assay. To address this time lag, the isotope dilution mass spectrometry (IDMS) method was developed to quantify the absolute hemagglutinin (HA, the main influenza antigen) amount in the vaccine without the need for purified, inactivated, and calibrated virus reference antigens. However, an additional challenge in determining potency is to differentiate between vaccine antigens in their most potent form from other less potent, stressed antigen forms. The limited trypsin digestion (LTD) method has been developed and does not require strain-specific full-length reference antigens or antibodies; instead, stressed HA is selectively degraded, leaving the more potent form to be measured. LTD, followed by precipitation and IDMS, allows for efficient differentiation between potent and significantly less potent HA for vaccine release and potency testing across the vaccine's shelf life. In this study, we tested the LTD-IDMS assay on A(H5N1) vaccine material that had been stressed by low pH, heat, and multiple freeze-thaw cycles. The results showed that the LTD-IDMS method effectively quantified the potent HA in A(H5N1) vaccine material with results comparable to SRID. As such, it shows great promise to complement and potentially replace SRID in a pandemic when strain-specific reagents may not be readily available. |
Contribution of hospitals to the occurrence of enteric protists in urban wastewater.
Jiang W , Roellig DM , Li N , Wang L , Guo Y , Feng Y , Xiao L . Parasitol Res 2020 119 (9) 3033-3040 We assessed the potential contribution of hospitals to contaminations of wastewater by enteric protists, including Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in raw wastewater. Wastewater samples were collected from storage tanks in two hospitals and one associated wastewater treatment plant in Shanghai, China, from March to November 2009. Enteric pathogens were detected and identified using PCR and DNA sequencing techniques. Among a total of 164 samples analyzed, 31 (18.9%), 45 (27.4%), and 122 (74.4%) were positive for Cryptosporidium spp., G. duodenalis, and E. bieneusi, respectively. Altogether, three Cryptosporidium species, four G. duodenalis assemblages, and 12 E. bieneusi genotypes were detected. Cryptosporidium hominis, G. duodenalis sub-assemblage AII, and E. bieneusi genotype D were the dominant ones in wastewater from both hospitals and the wastewater treatment plant. A similar distribution in genotypes of enteric pathogens was seen between samples from hospitals and the wastewater treatment plant, suggesting that humans are one of the major sources for these pathogens and hospitals are important contributors of enteric parasites in urban wastewater. Data from this study might be useful in the formulation of preventive measures against environmental contamination of waterborne pathogens. |
A neighbor-based approach to identify tuberculosis exposure, the Kopanyo Study
Moonan PK , Zetola NM , Tobias JL , Basotli J , Boyd R , Click ES , Dima M , Fane O , Finlay AM , Ogopotse M , Wen XJ , Modongo C , Oeltmann JE . Emerg Infect Dis 2020 26 (5) 1010-1013 Contact investigation is one public health measure used to prevent tuberculosis by identifying and treating persons exposed to Mycobacterium tuberculosis. Contact investigations are a major tenet of global tuberculosis elimination efforts, but for many reasons remain ineffective. We describe a novel neighbor-based approach to reframe contact investigations. |
Geographic Differences in COVID-19 Cases, Deaths, and Incidence - United States, February 12-April 7, 2020.
CDC COVID-19 Response Team , Bialek Stephanie , Bowen Virginia , Chow Nancy , Curns Aaron , Gierke Ryan , Hall Aron , Hughes Michelle , Pilishvili Tamara , Ritchey Matthew , Roguski Katherine , Silk Benjamin , Skoff Tami , Sundararaman Preethi , Ussery Emily , Vasser Michael , Whitham Hilary , Wen John . MMWR Morb Mortal Wkly Rep 2020 69 (15) 465-471 Community transmission of coronavirus disease 2019 (COVID-19) was first detected in the United States in February 2020. By mid-March, all 50 states, the District of Columbia (DC), New York City (NYC), and four U.S. territories had reported cases of COVID-19. This report describes the geographic distribution of laboratory-confirmed COVID-19 cases and related deaths reported by each U.S. state, each territory and freely associated state,* DC, and NYC during February 12-April 7, 2020, and estimates cumulative incidence for each jurisdiction. In addition, it projects the jurisdiction-level trajectory of this pandemic by estimating case doubling times on April 7 and changes in cumulative incidence during the most recent 7-day period (March 31-April 7). As of April 7, 2020, a total of 395,926 cases of COVID-19, including 12,757 related deaths, were reported in the United States. Cumulative COVID-19 incidence varied substantially by jurisdiction, ranging from 20.6 cases per 100,000 in Minnesota to 915.3 in NYC. On April 7, national case doubling time was approximately 6.5 days, although this ranged from 5.5 to 8.0 days in the 10 jurisdictions reporting the most cases. Absolute change in cumulative incidence during March 31-April 7 also varied widely, ranging from an increase of 8.3 cases per 100,000 in Minnesota to 418.0 in NYC. Geographic differences in numbers of COVID-19 cases and deaths, cumulative incidence, and changes in incidence likely reflect a combination of jurisdiction-specific epidemiologic and population-level factors, including 1) the timing of COVID-19 introductions; 2) population density; 3) age distribution and prevalence of underlying medical conditions among COVID-19 patients (1-3); 4) the timing and extent of community mitigation measures; 5) diagnostic testing capacity; and 6) public health reporting practices. Monitoring jurisdiction-level numbers of COVID-19 cases, deaths, and changes in incidence is critical for understanding community risk and making decisions about community mitigation, including social distancing, and strategic health care resource allocation. |
Rapid Sentinel Surveillance for COVID-19 - Santa Clara County, California, March 2020.
Zwald ML , Lin W , Sondermeyer Cooksey GL , Weiss C , Suarez A , Fischer M , Bonin BJ , Jain S , Langley GE , Park BJ , Moulia D , Benedict R , Nguyen N , Han GS . MMWR Morb Mortal Wkly Rep 2020 69 (14) 419-421 On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19. |
Phylogenetic diversity of Mycobacterium tuberculosis in two geographically distinct locations in Botswana - The Kopanyo Study.
Click ES , Finlay A , Oeltmann JE , Basotli J , Modongo C , Boyd R , Wen XJ , Shepard J , Moonan PK , Zetola N . Infect Genet Evol 2020 81 104232 Mycobacterium tuberculosis complex (MTBC) is divided into several major phylogenetic lineages, with differential distribution globally. Using population-based data collected over a three year period, we performed 24-locus Mycobacterial Interspersed Repeat Unit - Variable Number Tandem Repeat (MIRU-VNTR) genotyping on all culture isolates from two districts of the country that differ in tuberculosis (TB) incidence (Gaborone, the capital, and Ghanzi in the Western Kalahari). The study objective was to characterize the molecular epidemiology of TB in these districts. Overall phylogenetic diversity mirrored that reported from neighboring Republic of South Africa, but differences in the two districts were marked. All four major lineages of M. tuberculosis were found in Gaborone, but only three of the four major lineages were found in Ghanzi. Strain diversity was lower in Ghanzi, with a large proportion (38%) of all isolates having an identical MIRU-VNTR result, compared to 6% of all isolates in Gaborone with the same MIRU-VNTR result. This study demonstrates localized differences in strain diversity by two districts in Botswana, and contributes to a growing characterization of MTBC diversity globally. |
Progress toward measles elimination - China, January 2013-June 2019
Ma C , Rodewald L , Hao L , Su Q , Zhang Y , Wen N , Fan C , Yang H , Luo H , Wang H , Goodson JL , Yin Z , Feng Z . MMWR Morb Mortal Wkly Rep 2019 68 (48) 1112-1116 In 2005, the World Health Organization (WHO) Western Pacific Region countries, including China, resolved to eliminate measles by 2012 or as soon as feasible thereafter (1). As of 2018, nine* of the 37 Western Pacific Region countries or areas(dagger) had eliminated( section sign) measles. China's Measles Elimination Action Plan 2006-2012 included strengthening routine immunization; conducting measles risk assessments, followed by supplementary immunization activities (SIAs) with measles-containing vaccine (MCV) at national and subnational levels; strengthening surveillance and laboratory capacity; and investigating and responding to measles outbreaks. Most recently, progress toward measles elimination in China was described in a 2014 report documenting measles elimination efforts in China during 2008-2012 and a resurgence in 2013 (2). This report describes progress toward measles elimination in China during January 2013-June 2019.( paragraph sign) Measles incidence per million persons decreased from 20.4 in 2013 to 2.8 in 2018; reported measles-related deaths decreased from 32 in 2015 to one in 2018 and no deaths in 2019 through June. Measles elimination in China can be achieved through strengthening the immunization program's existing strategy by ensuring sufficient vaccine supply; continuing to improve laboratory-supported surveillance, outbreak investigation and response; strengthening school entry vaccination record checks; vaccinating students who do not have documentation of receipt of 2 doses of measles-rubella vaccine; and vaccinating health care professionals and other adults at risk for measles. |
Development and characterization of a reverse genetics system for influenza D virus.
Yu J , Liu R , Zhou B , Chou TW , Ghedin E , Sheng Z , Gao R , Zhai SL , Wang D , Li F . J Virol 2019 93 (21) Influenza D virus (IDV) of the Orthomyxoviridae family has a wide host range and a broad geographical distribution. Recent IDV outbreaks in swine along with serological and genetic evidence of IDV infection in humans have raised concerns regarding the zoonotic potential of this virus. To better study IDV at the molecular level, a reverse-genetics system (RGS) is urgently needed, but to date, no RGS had been described for IDV. In this study, we rescued the recombinant influenza D/swine/Oklahoma/1314/2011 (D/OK) virus by using a bidirectional seven-plasmid-based system and further characterized rescued viruses in terms of growth kinetics, replication stability, and receptor-binding capacity. Our results collectively demonstrated that RGS-derived viruses resembled the parental viruses for these properties, thereby supporting the utility of this RGS to study IDV infection biology. In addition, we developed an IDV minigenome replication assay and identified the E697K mutation in PB1 and the L462F mutation in PB2 that directly affected the activity of the IDV ribonucleoprotein (RNP) complex, resulting in either attenuated or replication-incompetent viruses. Finally, by using the minigenome replication assay, we demonstrated that a single nucleotide polymorphism at position 5 of the 3' conserved noncoding region in IDV and influenza C virus (ICV) resulted in the inefficient cross-recognition of the heterotypic promoter by the viral RNP complex. In conclusion, we successfully developed a minigenome replication assay and a robust reverse-genetics system that can be used to further study replication, tropism, and pathogenesis of IDV.IMPORTANCE Influenza D virus (IDV) is a new type of influenza virus that uses cattle as the primary reservoir and infects multiple agricultural animals. Increased outbreaks in pigs and serological and genetic evidence of human infection have raised concerns about potential IDV adaptation in humans. Here, we have developed a plasmid-based IDV reverse-genetics system that can generate infectious viruses with replication kinetics similar to those of wild-type viruses following transfection of cultured cells. Further characterization demonstrated that viruses rescued from the described RGS resembled the parental viruses in biological and receptor-binding properties. We also developed and validated an IDV minireplicon reporter system that specifically measures viral RNA polymerase activity. In summary, the reverse-genetics system and minireplicon reporter assay described in this study should be of value in identifying viral determinants of cross-species transmission and pathogenicity of novel influenza D viruses. |
Substrate stiffness-dependent carbon nanotube-induced lung fibrogenesis
Wang K , Shi L , Linthicum W , Man K , He X , Wen Q , Rojanasakul LW , Rojanasakul Y , Yang Y . Nano Lett 2019 19 (8) 5443-5451 Most living tissues exhibit the specific stiffness, which has been known to have profound influence on cell behaviors, yet how the stiffness affects cellular responses to engineered nanomaterials has not been elucidated. Particularly, discrepancies exist between in vitro and in vivo nanotoxicological studies. Here, we investigated the effects of substrate stiffness on the fibrogenic responses of normal human lung fibroblasts (NHLFs) to multiwalled carbon nanotubes (MWCNTs). NHLFs were grown on polyacrylamide (PAAm) hydrogels with the stiffness comparable to that of human normal and fibrotic lung tissues, and treated with MWCNTs for various time. The fibrogenic responses, including cell proliferation, reactive oxygen species production, and collagen I expression, of NHLFs to MWCNTs were observed to be regulated by substrate stiffness in a time-dependent manner. NHLFs generally were rounded on soft hydrogels and required a long treatment time to exhibit fibrogenic responses, while on stiff hydrogels the cells were well-spread with defined stress fibers and short-time MWCNTs treatment sufficiently induced the fibrogenic responses. Mechanistic studies showed that MWCNTs induced fibrogenesis of NHLFs through promoting expression and phosphorylation of focal adhesion kinase (FAK), while attenuating intracellular tension in the cells on stiff gels could increase MWCNTs uptake and thus elevate the induced fibrogenic responses. Moreover, we proposed a time-stiffness superposition principle to describe the equivalent effects of treatment time and substrate stiffness on nanomaterials-induced fibrogenesis, which suggested that increasing substrate stiffness expedited fibrogenesis and shed light on the rational design of in vitro models for nanotoxicological study. |
Development of a World Health Organization International Reference Panel for different genotypes of hepatitis E virus for nucleic acid amplification testing.
Baylis SA , Hanschmann KO , Matsubayashi K , Sakata H , Roque-Afonso AM , Kaiser M , Corman VM , Kamili S , Aggarwal R , Trehanpati N , Gartner T , Thomson EC , Davis CA , da Silva Filipe A , Abdelrahman TT , Blumel J , Terao E . J Clin Virol 2019 119 60-67 BACKGROUND: Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. OBJECTIVES: The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. STUDY DESIGN: The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1(st) World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. RESULTS: The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. CONCLUSIONS: Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV. |
One hypervirulent clone, sequence type 283, accounts for a large proportion of invasive Streptococcus agalactiae isolated from humans and diseased tilapia in Southeast Asia.
Barkham T , Zadoks RN , Azmai MNA , Baker S , Bich VTN , Chalker V , Chau ML , Dance D , Deepak RN , van Doorn HR , Gutierrez RA , Holmes MA , Huong LNP , Koh TH , Martins E , Mehershahi K , Newton P , Ng LC , Phuoc NN , Sangwichian O , Sawatwong P , Surin U , Tan TY , Tang WY , Thuy NV , Turner P , Vongsouvath M , Zhang D , Whistler T , Chen SL . PLoS Negl Trop Dis 2019 13 (6) e0007421 BACKGROUND: In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence. Before 2015 ST283 had only been reported from twenty humans in Hong Kong and two in France, and from one fish in Thailand. We hypothesised that ST283 was causing region-wide infection in Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: We performed a literature review, whole genome sequencing on 145 GBS isolates collected from six Southeast Asian countries, and phylogenetic analysis on 7,468 GBS sequences including 227 variants of ST283 from humans and animals. Although almost absent outside Asia, ST283 was found in all invasive Asian collections analysed, from 1995 to 2017. It accounted for 29/38 (76%) human isolates in Lao PDR, 102/139 (73%) in Thailand, 4/13 (31%) in Vietnam, and 167/739 (23%) in Singapore. ST283 and its variants were found in 62/62 (100%) tilapia from 14 outbreak sites in Malaysia and Vietnam, in seven fish species in Singapore markets, and a diseased frog in China. CONCLUSIONS: GBS ST283 is widespread in Southeast Asia, where it accounts for a large proportion of bacteraemic GBS, and causes disease and economic loss in aquaculture. If human ST283 is fishborne, as in the Singapore outbreak, then GBS sepsis in Thailand and Lao PDR is predominantly a foodborne disease. However, whether transmission is from aquaculture to humans, or vice versa, or involves an unidentified reservoir remains unknown. Creation of cross-border collaborations in human and animal health are needed to complete the epidemiological picture. |
Evaluating vaccination policies to accelerate measles elimination in China: a meta-population modelling study
Hao L , Glasser JW , Su Q , Ma C , Feng Z , Yin Z , Goodson JL , Wen N , Fan C , Yang H , Rodewald LE , Feng Z , Wang H . Int J Epidemiol 2019 48 (4) 1240-1251 BACKGROUND: Measles is among the most highly infectious human diseases. By virtue of increasingly effective childhood vaccination, together with targeted supplemental immunization activities (SIAs), health authorities in the People's Republic of China have reduced measles' reproduction number from about 18 to 2.3. Despite substantial residual susceptibility among young adults, more in some locales than others, sustained routine childhood immunization likely would eliminate measles eventually. To support global eradication efforts, as well as expedite morbidity and mortality reductions in China, we evaluated alternative SIAs via mechanistic mathematical modelling. METHODS: Our model Chinese population is stratified by immune status (susceptible to measles infection; infected, but not yet infectious; infectious; and recovered or immunized), age (0, 1-4, 5-9, ..., 65+ years) and location (31 provinces). Contacts between sub-populations are either empirical or a mixture of preferential and proportionate with respect to age and decline exponentially with distance between locations at age-dependent rates. We estimated initial conditions and most parameters from recent cross-sectional serological surveys, disease surveillance and demographic observations. Then we calculated the reproduction numbers and gradient of the effective number with respect to age- and location-specific immunization rates. We corroborated these analytical results by simulating adolescent and young adult SIAs using a version of our model in which the age-specific contact rates vary seasonally. RESULTS: Whereas the gradient indicates that vaccinating young adults generally is the optimal strategy, simulations indicate that a catch-up campaign among susceptible adolescent schoolchildren would accelerate elimination, with timing dependent on uptake. CONCLUSIONS: These results are largely due to indirect effects (i.e. fewer infections than immunized people might otherwise cause), which meta-population models with realistic mixing are uniquely capable of reproducing accurately. |
Inter- and intra-host sequence diversity reveal the emergence of viral variants during an overwintering epidemic caused by dengue virus serotype 2 in southern Taiwan
Ko HY , Li YT , Chao DY , Chang YC , Li ZT , Wang M , Kao CL , Wen TH , Shu PY , Chang GJ , King CC . PLoS Negl Trop Dis 2018 12 (10) e0006827 Purifying selection during dengue viral infection has been suggested as the driving force of viral evolution and the higher complexity of the intra-host quasi-species is thought to offer an adaptive advantage for arboviruses as they cycle between arthropod and vertebrate hosts. However, very few studies have been performed to investigate the viral genetic changes within (intra-host) and between (inter-host) humans in a spatio-temporal scale. Viruses of different serotypes from various countries imported to Taiwan cause annual outbreaks. During 2001-2003, two consecutive outbreaks were caused by dengue virus serotype 2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases in the following year. Phylogenetic analyses showed that the viruses from both events were similar and related to the 2001 DENV-2 isolate from the Philippines. We comprehensively analyzed viral sequences from representative dengue patients and identified three consensus genetic variants, group Ia, Ib and II, with different spatio-temporal population dynamics. The phylodynamic analysis suggested group Ib variants, characterized by lower genetic diversity, transmission rate, and intra-host variant numbers, might play the role of maintenance variants. The residential locations among the patients infected by group Ib variants were in the outer rim of case clusters throughout the 2001-2003 period whereas group Ia and II variants were located in the centers of case clusters, suggesting that group Ib viruses might serve as "sheltered overwintering" variants in an undefined ecological niche. Further deep sequencing of the viral envelope (E) gene directly from individual patient serum samples confirmed the emergence of variants belonging to three quasi-species (group Ia, Ib, and II) and the ancestral role of the viral variants in the latter phase of the 2001 outbreak contributed to the later, larger-scale epidemic beginning in 2002. These findings enhanced our understanding of increasing epidemic severity over time in the same epidemic area. It also highlights the importance of combining phylodynamic and deep sequencing analysis as surveillance tools for detecting dynamic changes in viral variants, particularly searching for and monitoring any specific viral subpopulation. Such subpopulations might have selection advantages in both fitness and transmissibility leading to increased epidemic severity. |
Reference antigen-free and antibody-free LTD-IDMS assay for influenza H7N9 vaccine in vitro potency determination
Morgenstern K , Xie Y , Palladino G , Barr JR , Settembre EC , Williams TL , Wen Y . Vaccine 2018 36 (41) 6144-6151 Influenza vaccines are the most effective intervention to prevent the substantial public health burden of seasonal and pandemic influenza. Hemagglutinin (HA), as the main antigen in inactivated influenza vaccines (IIVs), elicits functional neutralizing antibodies and largely determines IIV effectiveness. HA potency has been evaluated by single-radial immunodiffusion (SRID), the standard in vitro potency assay for IIVs, to predict vaccine immunogenicity with a correlation to protective efficacy. We previously reported that limited trypsin digestion (LTD) selectively degraded stressed HA, so that an otherwise conformationally insensitive biophysical quantification technique could specifically quantify trypsin-resistant, immunologically active HA. Here, we demonstrate that isotope dilution mass spectrometry (IDMS), a method capable of quantifying the absolute HA concentration without reference antigen use, can be further expanded by adding LTD followed with precipitation to selectively quantify the active HA. We test the LTD-IDMS assay on H7N9 vaccines stressed by low pH, raised temperature, or freeze/thaw cycles. This method, unlike SRID, has no requirement for strain-specific reference antigens or antibodies and can generate potency values that correlate with SRID. Thus, LTD-IDMS is a promising alternative in vitro potency assay for influenza vaccines to complement and potentially replace SRID in a pandemic when strain specific reagents may not be readily available. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 20, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure