Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 61 Records) |
Query Trace: Hao L [original query] |
---|
Neutralization of rubella vaccine virus and immunodeficiency-related vaccine-derived rubella viruses by intravenous immunoglobulins
Chen MH , Perelygina L , Hao L , Beard RS , Lackner C , Farcet MR , Karbiener M , Icenogle J , Kreil TR . J Infect Dis 2024 The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immune deficiencies (PID) has raised concerns about the ability of immunoglobulin (IG) preparations to neutralize VDRVs. We investigated the capacity of IG to neutralize rubella vaccine virus and four VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by IG preparations; however, the VDRV isolates from patients after intra-host evolution, 2-6 times less so. Diagnosis of immune deficiencies before possible live-virus vaccination is thus of critical importance, while IG replacement therapy can be expected to provide protection from rubella virus infection. | The occurrence of granulomas associated with vaccine derived rubella viruses (VDRV) in people with primary immune deficiencies (PID) challenges immunoglobulin (IG) preparations regarding their rubella neutralizing ability. This study confirmed potent rubella virus neutralization capacity of IG preparations and thus suggests protection of IG-treated PID patients against rubella. The study also highlights the importance of early diagnosis and timely given IG to prevent possible systemic spread of VDRV persisting locally in granulomas. | eng |
Implementing a continuous quality-improvement framework for tuberculosis infection prevention and control in healthcare facilities in China, 2017-2019
Zhang C , O'Connor S , Smith-Jeffcoat SE , Rodriguez DF , Guo H , Hao L , Chen H , Sun Y , Li Y , Xu J , Chen L , Xia L , Yang X , Date A , Cheng J . Infect Control Hosp Epidemiol 2024 1-7 BACKGROUND: Tuberculosis (TB) infection prevention and control (IPC) in healthcare facilities is key to reducing transmission risk. A framework for systematically improving TB IPC through training and mentorship was implemented in 9 healthcare facilities in China from 2017 to 2019. METHODS: Facilities conducted standardized TB IPC assessments at baseline and quarterly thereafter for 18 months. Facility-based performance was assessed using quantifiable indicators for IPC core components and administrative, environmental, and respiratory protection controls, and as a composite of all control types We calculated the percentage changes in scores over time and differences by IPC control type and facility characteristics. RESULTS: Scores for IPC core components increased by 72% during follow-up when averaged across facilities. The percentage changes for administrative, environmental, and respiratory protection controls were 39%, 46%, and 30%, respectively. Composite scores were 45% higher after the intervention. Overall, scores increased most during the first 6 months. There was no association between IPC implementation and provincial economic development or volume of TB services. CONCLUSIONS: TB IPC policies and practices showed most improvement early during implementation and did not differ consistently by facility characteristics. The training component of the project helped increase the capacity of healthcare professionals to manage TB transmission risks. Lessons learned here will inform national TB IPC guidance. |
Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age.
Crider KS , Quinlivan EP , Berry RJ , Hao L , Li Z , Maneval D , Yang TP , Rasmussen SA , Yang Q , Zhu JH , Hu DJ , Bailey LB . PLoS One 2011 6 (12) e28144 Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (-14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation. |
Surveillance for rubella virus in samples obtained from non-immunodeficient individuals
Patel S , Russo P , M HR , Maurer K , Hao L , Beard RS , Perelygina L , Sullivan KE . Pediatr Allergy Immunol 2024 35 (1) e14082 |
Long-term neutralizing antibody levels against measles and rubella viruses among adults with 3 doses of measles-mumps-rubella vaccine
Alonge OD , Marin M , Hickman CJ , Sowers SB , Chen MH , Hao L , Mercader S , El-Badry E , McClure DL , Icenogle JP , Sugerman DE , Crooke SN , Nguyen HQ . Open Forum Infect Dis 2024 11 (1) ofad700 BACKGROUND: A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but data on long-term immunity are limited. We assessed neutralizing antibody levels against measles and rubella among adults up to 11 years after receipt of a third MMR dose. METHODS: In this longitudinal study, healthy adults who received a third MMR dose as young adults (ages 18-28 years) were recalled around 5 years and 9-11 years after the third dose. Measles and rubella antibody levels were assessed by plaque-reduction and immunocolorimetric neutralization assays, respectively. Antibody concentrations <120 mIU/mL and <10 U/mL were considered potentially susceptible to measles and rubella, respectively. Geometric mean concentrations (GMCs) and 95% confidence intervals (CIs) over time were estimated from generalized estimating equation models. RESULTS: Approximately 5 and 9-11 years after receipt of the third dose, 405 and 304 adults were assessed, respectively. Measles GMC was 428 mIU/mL (95% CI, 392-468 mIU/mL) 5 years postvaccination, declining to 381 mIU/mL (95% CI, 339-428 mIU/mL) 11 years postvaccination. At the last follow-up visit (9-11 years postvaccination), 10% of participants were potentially susceptible to measles infection. Rubella GMCs were stable throughout the follow-up period (63 U/mL to 65 U/mL); none of the participants was susceptible to rubella at the last follow-up visit. CONCLUSIONS: Eleven years after receiving a third MMR dose, measles and rubella neutralizing antibody levels remained high in adults. However, on the basis of waning antibody levels, some adults may become susceptible to measles infection over time despite receipt of 3 vaccine doses. |
Rubella virus-associated necrotizing neutrophilic granuloma in a patient with common variable immunodeficiency
Pei S , Khazaeli M , Hao L , Chen MH , Perelygina L , Kuraitis D . J Cutan Pathol 2023 50 (11) 971-976 Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been identified as a novel cell type infected. Here, we present a case of RuV-associated cutaneous granuloma with RuV localized to neutrophils. A 46-year-old female with common variable immunodeficiency presented with verrucous papules and crusted plaques from the right knee to the distal shin of 20 years duration, associated with prior physical trauma. Biopsy specimen showed palisaded granulomas surrounding central necrosis with scattered aggregates of neutrophils. Vaccine-derived RuV was detected by molecular sequencing in lesional skin. Fluorescent immunohistochemistry with CD206, myeloperoxidase (MPO), and RV capsid (RVC) antibodies demonstrated that RuV localized to neutrophils but not macrophages. The clinical presentation, cutaneous findings, and likely presence of RVC-positive granulocytes in bone marrow provide potential support to the evolving hypothesis of persistent RuV within neutrophils contributing to chronic granulomatous inflammation in a milieu of immune dysregulation. |
Use of Public Data to Describe COVID-19 Contact Tracing in China during January 20–February 29, 2020 (preprint)
Dirlikov E , Zhou S , Han L , Li Z , Hao L , Millman AJ , Marston B . medRxiv 2020 2020.12.04.20243972 Objective Although contact tracing is generally not used to control influenza pandemics, China and several countries in the Western Pacific Region employed contact tracing as part of COVID-19 response activities. To improve understanding on the use of contact tracing for COVID-19 emergency public health response activities, we describe reported COVID-19 contacts traced and quarantined in China and a proxy for number of reported contacts traced per reported case.Methods We abstracted publicly available online aggregate data reported from China’s National Health Commission and provincial health commissions’ COVID-19 daily situational reports for January 20–February 29, 2020. The number of new contacts traced by report date was computed as the difference between total contacts traced on consecutive reports. A proxy for the number of contacts traced per case was computed as the number of new contacts traced divided by the number of new cases.Results During January 20–February 29, 2020, China reported 80,968 new COVID-19 cases (Hubei Province = 67,608 [83%]), and 659,899 contacts traced (Hubei Province = 265,617 [40%]). Non-Hubei provinces reported more contacts traced per case than Hubei Province; this difference increased over time.Discussion Along with other NPI used in China, contact tracing likely contributed to reducing SARS-CoV-2 transmission by quarantining a large number of potentially infected contacts. Despite reporting only 15% of total cases, non-Hubei provinces had 1.5 times more reported contacts traced compared to Hubei Province. Contract tracing may have been more complete in areas and periods with lower case counts.Competing Interest StatementThe authors have declared no competing interest.Funding StatementData collection and analysis were conducted as part of COVID-19 emergency response. No external funds were used.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was determined to be non-research, public health emergency response, consistent with applicable U.S. federal law and CDC policy.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData were compiled from Provincial-Level Health Commission Websites Containing Publicly Available Reported Data on COVID-19 National Health Commission http://weekly.chinacdc.cn/news/TrackingtheEpidemic.htm Anhui http://wjw.ah.gov.cn/ Beijing http://wjw.beijing.gov.cn/xwzx_20031/xwfb/ Chongqing http://wsjkw.cq.gov.cn/ Fujian http://wjw.fujian.gov.cn/ Gansu http://wsjk.gansu.gov.cn/ Guangdong http://wsjkw.gd.gov.cn/zwyw_yqxx/index.html Guangxi http://wsjkw.gxzf.gov.cn/gzdt/bt/ Guizhou http://www.gzhfpc.gov.cn/ Hainan http://wst.hainan.gov.cn/swjw/index.html Hebei http://wsjkw.hebei.gov.cn/ Heilongjiang http://wsjkw.hlj.gov.cn/ Henan http://www.hnwsjsw.gov.cn/ Hubei http://wjw.hubei.gov.cn/fbjd/dtyw/ Hunan http://wjw.hunan.gov.cn/ Inner Mongolia http://wjw.nmg.gov.cn/ Jiangsu http://wjw.jiangsu.gov.cn/ Jiangxi http://hc.jiangxi.gov.cn/ Jilin http://wsjkw.jl.gov.cn/ Liaoning http://wsjk.ln.gov.cn/ Ningxia http://wsjkw.nx.gov.cn/ Qinghai https://wsjkw.qinghai.gov.cn/ Shaanxi http://sx jw.shaanxi.gov.cn/ Shandong http://wsjkw.shandong.gov.cn Shanghai http://wsjkw.sh.gov.cn/xwfb/index.html Shanxi http://wjw.shanxi.gov.cn/ Sichuan http://wsjkw.sc.gov.cn/scwsjkw/szyw/tygl.shtml Tianjin http://wsjs.tj.gov.cn/ Tibet http://wjw.xizang.gov.cn Xinjiang http://xjhfpc.gov.cn Yunnan http://ynswsjkw.yn.gov.cn/wjwWebsite/web/index Zhejiang http://www.zjwjw.gov.cn/col/col1202101/index.html |
Comparative genomics of the major parasitic worms (preprint)
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . bioRxiv 2017 236539 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause. |
Comparative genomics of the major parasitic worms
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . Nat Genet 2019 51 (1) 163-174 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms. |
Case report: Persistent shedding of a live vaccine-derived rubella virus in a young man with severe combined immunodeficiency and cutaneous granuloma.
Bonner KE , Sukerman E , Liko J , Lanzieri TM , Sutton M , DeBess E , Leesman C , Icenogle J , Hao L , Chen MH , Faisthalab R , Leman RF , Cieslak PR , DeRavin SS , Perelygina L . Front Immunol 2022 13 1075351 A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts. |
Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo
Knipes AK , Summers A , Sklavounos AA , Lamanna J , de Campos RPS , Narahari T , Dixon C , Fobel R , Ndjakani YD , Lubula L , Magazani A , Muyembe JJ , Lay Y , Pukuta E , Waku-Kouomou D , Hao L , Kayembe JK , Fobel C , Dahmer J , Lee A , Ho M , Valenzuela JGC , Rackus DG , Shih R , Seale B , Chang A , Paluku G , Rota PA , Wheeler AR , Scobie HM . PLoS One 2022 17 (12) e0278749 The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella. |
Association of Persistent Rubella Virus With Idiopathic Skin Granulomas in Clinically Immunocompetent Adults.
Wanat KA , Perelygina L , Chen MH , Hao L , Abernathy E , Bender NR , Shields BE , Wilson BD , Crosby D , Routes J , Samimi SS , Haun PL , Sokumbi O , Icenogle JP , Sullivan KE , Rosenbach M , Drolet BA . JAMA Dermatol 2022 158 (6) 626-633 IMPORTANCE: Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults. OBJECTIVE: To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults. DESIGN, SETTING, AND PARTICIPANTS: This case series, conducted in US academic dermatology clinics from January 2019 to January 2021, investigated the presence of RuV in skin specimens using RuV immunofluorescent staining of paraffin-embedded tissue sections, real-time reverse-transcription polymerase chain reaction, whole-genome sequencing with phylogenetic analyses, and cell culture by the US Centers for Disease Control and Prevention. Rubella immunoglobulin G, immunoglobulin M enzyme-linked immunoassay, and viral neutralization assays were performed for the sera of immunocompetent individuals with treatment refractory cutaneous granulomas and histopathology demonstrating atypical palisaded and necrotizing granulomas. Clinical immune evaluation was performed. MAIN OUTCOMES AND MEASURES: Identification, genotyping, and culture of vaccine-derived and wild-type RuV within granulomatous dermatitis of otherwise clinically immune competent adults. RESULTS: Of the 4 total immunocompetent participants, 3 (75%) were women, and the mean (range) age was 61.5 (49.0-73.0) years. The RuV capsid protein was detected by immunohistochemistry in cutaneous granulomas. The presence of RuV RNA was confirmed by real-time reverse-transcription polymerase chain reaction in fresh-frozen skin biopsies and whole-genome sequencing. Phylogenetic analysis of the RuV sequences showed vaccine-derived RuV in 3 cases and wild-type RuV in 1. Live RuV was recovered from the affected skin in 2 participants. Immunology workup results demonstrated no primary immune deficiencies. CONCLUSIONS AND RELEVANCE: The case series study results suggest that RuV (vaccine derived and wild type) can persist for years in cutaneous granulomas in clinically immunocompetent adults and is associated with atypical (palisaded and necrotizing type) chronic cutaneous granulomas. These findings represent a potential paradigm shift in the evaluation, workup, and management of atypical granulomatous dermatitis and raises questions regarding the potential transmissibility of persistent live RuV. |
Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity.
Perelygina L , Faisthalab R , Abernathy E , Chen MH , Hao L , Bercovitch L , Bayer DK , Noroski LM , Lam MT , Cicalese MP , Al-Herz W , Nanda A , Hajjar J , Vanden Driessche K , Schroven S , Leysen J , Rosenbach M , Peters P , Raedler J , Albert MH , Abraham RS , Rangarjan HG , Buchbinder D , Kobrynski L , Pham-Huy A , Dhossche J , Cunningham Rundles C , Meyer AK , Theos A , Atkinson TP , Musiek A , Adeli M , Derichs U , Walz C , Krüger R , von Bernuth H , Klein C , Icenogle J , Hauck F , Sullivan KE . Front Immunol 2021 12 796065 Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions. |
Use of public data to describe COVID-19 contact tracing in Hubei Province and non-Hubei provinces in China between 20 January and 29 February 2020.
Dirlikov E , Zhou S , Han L , Li Z , Hao L , Millman AJ , Marston B . Western Pac Surveill Response J 2021 12 (3) 82-87 OBJECTIVE: Contact tracing has been used in China and several other countries in the WHO Western Pacific Region as part of the COVID-19 response. We describe COVID-19 cases and the number of contacts traced and quarantined per case as part of COVID-19 emergency public health response activities in China. METHODS: We abstracted publicly available, online aggregated data published in daily COVID-19 situational reports by China's National Health Commission and provincial health commissions between 20 January and 29 February 2020. The number of new contacts traced by report date was computed as the difference between total contacts traced in consecutive reports. A proxy for the number of contacts traced per case was computed as the number of new contacts traced divided by the number of new cases. RESULTS: During the study period, China reported 80 968 new COVID-19 cases and 659 899 contacts. In Hubei Province, there were 67 608 cases and 264 878 contacts, representing 83% and 40% of the total, respectively. Non-Hubei provinces reported tracing 1.5 times more contacts than Hubei Province; the weekly number of contacts traced per case was also higher in non-Hubei provinces than in Hubei Province and increased from 17.2 in epidemiological week 4 to 115.7 in epidemiological week 9. DISCUSSION: More contacts per case were reported from areas and periods with lower COVID-19 case counts. With other non-pharmaceutical interventions used in China, contact tracing and quarantining large numbers of potentially infected contacts probably contributed to reducing SARS-CoV-2 transmission. |
Performance characteristics of the Abbott BinaxNOW SARS-CoV-2 antigen test in comparison to real-time RT-PCR and viral culture in community testing sites during November 2020.
Almendares O , Prince-Guerra JL , Nolen LD , Gunn JKL , Dale AP , Buono SA , Deutsch-Feldman M , Suppiah S , Hao L , Zeng Y , Stevens VA , Knipe K , Pompey J , Atherstone C , Bui DP , Powell T , Tamin A , Harcourt JL , Petway M , Bohannon C , Folster JM , MacNeil A , Salerno R , Kuhnert-Tallman W , Tate JE , Thornburg N , Kirking HL , Villanueva JM , Rose DA , Neatherlin JC , Anderson M , Rota PA , Honein MA , Bower WA . J Clin Microbiol 2021 60 (1) Jcm0174221 Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse-transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease or exposure period and demographic variables are limited. During November 3(rd)-17(th), 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW (BinaxNOW) antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8-10 days post-exposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 hours for BinaxNOW and 26 hours for rRT-PCR. Point-of-care antigen tests have a shorter turn-around time compared to laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program. |
Granulomatous Dermatitis Associated With Rubella Virus Infection in an Adult With Immunodeficiency.
Shields BE , Perelygina L , Samimi S , Haun P , Leung T , Abernathy E , Chen MH , Hao L , Icenogle J , Drolet B , Wilson B , Bryer JS , England R , Blumberg E , Wanat KA , Sullivan K , Rosenbach M . JAMA Dermatol 2021 157 (7) 842-847 IMPORTANCE: Immunodeficiency-related, vaccine-derived rubella virus (RuV) as an antigenic trigger of cutaneous and visceral granulomas is a rare, recently described phenomenon in children and young adults treated with immunosuppressant agents. OBJECTIVE: To perform a comprehensive clinical, histologic, immunologic, molecular, and genomic evaluation to elucidate the potential cause of an adult patient's atypical cutaneous granulomas. DESIGN, SETTING, AND PARTICIPANTS: A prospective evaluation of skin biopsies, nasopharyngeal swabs, and serum samples submitted to the Centers for Disease Control and Prevention was conducted to assess for RuV using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and viral genomic sequencing. The samples were obtained from a man in his 70s with extensive cutaneous granulomas mimicking both cutaneous sarcoidosis (clinically) and CD8+ granulomatous cutaneous T-cell lymphoma (histopathologically). The study was conducted from September 2019 to February 2021. MAIN OUTCOMES AND MEASURES: Identification and genotyping of a novel immunodeficiency-related RuV-associated granulomatous dermatitis. RESULTS: Immunohistochemistry for RuV capsid protein and RT-PCR testing for RuV RNA revealed RuV in 4 discrete skin biopsies from different body sites. In addition, RuV RNA was detected in the patient's nasopharyngeal swabs by RT-PCR. The full viral genome was sequenced from the patient's skin biopsy (RVs/Philadelphia.PA.USA/46.19/GR, GenBank Accession #MT249313). The patient was ultimately diagnosed with a novel RuV-associated granulomatous dermatitis. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that clinicians and pathologists may consider RuV-associated granulomatous dermatitis during evaluation of a patient because it might have implications for the diagnosis of cutaneous sarcoidosis, with RuV serving as a potential antigenic trigger, and for the diagnosis of granulomatous cutaneous T-cell lymphoma, with histopathologic features that may prompt an evaluation for immunodeficiency and/or RuV. |
CATMoS: Collaborative Acute Toxicity Modeling Suite.
Mansouri K , Karmaus AL , Fitzpatrick J , Patlewicz G , Pradeep P , Alberga D , Alepee N , Allen TEH , Allen D , Alves VM , Andrade CH , Auernhammer TR , Ballabio D , Bell S , Benfenati E , Bhattacharya S , Bastos JV , Boyd S , Brown JB , Capuzzi SJ , Chushak Y , Ciallella H , Clark AM , Consonni V , Daga PR , Ekins S , Farag S , Fedorov M , Fourches D , Gadaleta D , Gao F , Gearhart JM , Goh G , Goodman JM , Grisoni F , Grulke CM , Hartung T , Hirn M , Karpov P , Korotcov A , Lavado GJ , Lawless M , Li X , Luechtefeld T , Lunghini F , Mangiatordi GF , Marcou G , Marsh D , Martin T , Mauri A , Muratov EN , Myatt GJ , Nguyen DT , Nicolotti O , Note R , Pande P , Parks AK , Peryea T , Polash AH , Rallo R , Roncaglioni A , Rowlands C , Ruiz P , Russo DP , Sayed A , Sayre R , Sheils T , Siegel C , Silva AC , Simeonov A , Sosnin S , Southall N , Strickland J , Tang Y , Teppen B , Tetko IV , Thomas D , Tkachenko V , Todeschini R , Toma C , Tripodi I , Trisciuzzi D , Tropsha A , Varnek A , Vukovic K , Wang Z , Wang L , Waters KM , Wedlake AJ , Wijeyesakere SJ , Wilson D , Xiao Z , Yang H , Zahoranszky-Kohalmi G , Zakharov AV , Zhang FF , Zhang Z , Zhao T , Zhu H , Zorn KM , Casey W , Kleinstreuer NC . Environ Health Perspect 2021 129 (4) 47013 BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495. |
Risk factors for measles virus infection and susceptibility in persons aged 15 years and older in China: A multi-site case-control study, 2012-2013
Ma C , Hao L , Rodewald L , An Q , Wannemuehler KA , Su Q , An Z , Quick L , Liu Y , Yan R , Liu X , Zhang Y , Yu W , Zhang X , Wang H , Cairns L , Luo H , Gregory CJ . Vaccine 2020 38 (16) 3210-3217 INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. METHODS: Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. RESULTS: 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1-3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6-38.8%). CONCLUSIONS: Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults. |
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. |
Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites - Pima County, Arizona, November 3-17, 2020.
Prince-Guerra JL , Almendares O , Nolen LD , Gunn JKL , Dale AP , Buono SA , Deutsch-Feldman M , Suppiah S , Hao L , Zeng Y , Stevens VA , Knipe K , Pompey J , Atherstone C , Bui DP , Powell T , Tamin A , Harcourt JL , Shewmaker PL , Medrzycki M , Wong P , Jain S , Tejada-Strop A , Rogers S , Emery B , Wang H , Petway M , Bohannon C , Folster JM , MacNeil A , Salerno R , Kuhnert-Tallman W , Tate JE , Thornburg NJ , Kirking HL , Sheiban K , Kudrna J , Cullen T , Komatsu KK , Villanueva JM , Rose DA , Neatherlin JC , Anderson M , Rota PA , Honein MA , Bower WA . MMWR Morb Mortal Wkly Rep 2021 70 (3) 100-105 Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies. |
Durability of humoral immune responses to rubella following MMR vaccination
Crooke SN , Riggenbach MM , Ovsyannikova IG , Warner ND , Chen MH , Hao L , Icenogle JP , Poland GA , Kennedy RB . Vaccine 2020 38 (51) 8185-8193 BACKGROUND: While administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults. METHODS: In this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot. RESULTS: Rubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women. CONCLUSIONS: Collectively, rubella-specific humoral immunity declines following vaccination, although subjects' antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined. |
Building HIV healthcare worker capacity through telehealth in Vietnam
Pollack TM , Nhung VTT , Vinh DTN , Hao DT , Trang LTT , Duc PA , Kinh NV , Dung NTH , Dung DL , Ninh NT , Huyen HTT , Huy VX , Hai DM , Khanh TH , Hien NTT , Khuong PTA , Trong NT , Lam NV , Phinh VN , Phuong DT , Duat ND , Liem NT , Binh NT , Chi NK , Yen LN , Cosimi L . BMJ Glob Health 2020 5 (4) e002166 Development of a robust technical assistance system is an essential component of a sustainable HIV response. Vietnam's National HIV Program is transitioning from a largely donor-funded programme to one primarily supported by domestic resources. Telehealth interventions are increasingly being used for training, mentoring and expert consultation in high-resource settings and hold significant potential for use as a tool to build HIV health worker capacity in low and middle-income countries. We designed, implemented and scaled up a novel HIV telehealth programme for Vietnam, with the goal of building a sustainable training model to support the country's HIV workforce needs. Over a 4-year period, HIV telehealth programmes were initiated in 17 public institutions with participation of nearly 700 clinical sites across 62 of the 63 provinces in the country. The telehealth programme was used to deliver certificate training courses, provide clinical mentoring and case-based learning, support programme implementation, provide coaching in quality improvement and disseminate new guidelines and policies. Programme evaluation demonstrated improved health worker self-reported competence in HIV care and treatment and high satisfaction among the programme participants. Lessons learnt from Vietnam's experience with telehealth can inform country programmes looking to develop a sustainable approach to HIV technical assistance and health worker capacity building. |
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. |
Rubella virus-specific humoral immune responses and their interrelationships before and after a third dose of measles-mumps-rubella vaccine in women of childbearing age
Haralambieva IH , Ovsyannikova IG , Kennedy RB , Goergen KM , Grill DE , Chen MH , Hao L , Icenogle J , Poland GA . Vaccine 2019 38 (5) 1249-1257 In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks). We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT50 (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (>/=4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses. |
Seroprevalence of rubella virus antibodies among pregnant women in the Center and South-West regions of Cameroon
Taku NA , Ndze VN , Abernathy E , Hao L , Waku-Kouomou D , Icenogle JP , Wanji S , Akoachere JKT . PLoS One 2019 14 (11) e0225594 Rubella infection in early pregnancy can lead to miscarriages, fetal death, or birth of an infant with congenital rubella syndrome (CRS). In Cameroon, like in many developing countries, rubella surveillance is not well-established. The aim of this study was to determine the prevalence of rubella virus specific antibodies among pregnant Cameroonians. We conducted a cross-sectional study for rubella infection among pregnant women attending antenatal clinics in the Center and South-West regions of Cameroon. Demographic data and blood were collected and tested for rubella specific antibodies (IgG and IgM), and for the IgM positive cases, IgG avidity and real time PCR was done. From December 2015 to July 2017, 522 serum samples were collected and tested from pregnant women. The seroprevalence of rubella specific IgG was 94.4%, presumably due to immunity induced by wild-type rubella virus. The seroprevalence of rubella specific IgM was 5.0%, possibly indicating rubella infection. However, IgG avidity testing of the IgM positive cases detected high avidity IgGs, ranging from 52.37% to 87.70%, indicating past rubella infection. 5.6% (29/522) of the participants had negative results for IgG to rubella virus, indicating susceptibility to rubella infection. None of the participants had received a rubella containing vaccine (RCV), but 51% (266/522) of the pregnant women lived in a house with a child with records of at least one dose of RCV. Rubella virus RNA was not detected in the urine of any IgM positive case. Findings from this study show that rubella infection is significant in Cameroon. Some pregnant women are still susceptible to rubella infection. For a better management of rubella infection in pregnancy in Cameroon, consideration should be taken to investigate for IgG-avidity test in cases with positive rubella IgM result to distinguish between recent from past rubella infection. |
Burden of viral gastroenteritis in children living in rural China: population-based surveillance.
Wang JX , Zhou HL , Mo ZJ , Wang SM , Hao ZY , Li Y , Zhen SS , Zhang CJ , Zhang XJ , Ma JC , Qiu C , Zhao G , Jiang B , Jiang X , Li RC , Zhao YL , Wang XY . Int J Infect Dis 2019 90 151-160 BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China. |
Distribution of Neisseria meningitidis serogroup B (NmB) vaccine antigens in meningococcal disease causing isolates in the United States during 2009-2014, prior to NmB vaccine licensure.
Chang HY , Vuong J , Hu F , Liberator P , Chen A , Kretz CB , Blain A , Hao L , Retchless AC , Whaley MJ , Anderson AS , Wang X . J Infect 2019 79 (5) 426-434 OBJECTIVES: Two Neisseria meningitidis serogroup B (NmB) vaccines are licensed in the United States. To estimate their potential coverage, we examined the vaccine antigen diversity among meningococcal isolates prior to vaccine licensure. METHODS: NmB vaccine antigen genes of invasive isolates collected in the U.S. from 2009-2014 were characterized by Sanger or whole-genome sequencing. RESULTS: During 2009-2014, the predominant antigen types have remained similar to those reported in 2000-2008 for NmB and 2006-2008 for NmC, NmY, with the emergence of a few new types. FHbp of subfamily B or variant 1 (B/v1) remained prevalent among NmB whereas FHbp of subfamily A or variant 2 and 3 (A/v2-3) were more prevalent among non-NmB. FHbp peptide 1 (B24/1.1) remains the most prevalent type in NmB. Full-length NadA peptide was detected in 26% of isolates, primarily in NmB and NmW. The greatest diversity of NhbA peptides was detected among NmB, with p0005 as the most prevalent type. CONCLUSIONS: The prevalence and diversity of the NmB vaccine antigens have remained stable with common antigen types persisting over time. The data collected prior to NmB vaccine licensure provide the baseline to understand the potential impact of NmB vaccines on antigen diversity and strain coverage. |
Validating the NCBI AMRFinder Tool and Resistance Gene Database Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of NARMS Isolates.
Feldgarden M , Brover V , Haft DH , Prasad AB , Slotta DJ , Tolstoy I , Tyson GH , Zhao S , Hsu CH , McDermott PF , Tadesse DA , Morales C , Simmons M , Tillman G , Wasilenko J , Folster JP , Klimke W . Antimicrob Agents Chemother 2019 63 (11) Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify AMR genes in whole genome sequences, the National Center for Biotechnology Information (NCBI) has produced AMRFinder, a tool that identifies AMR genes using a high-quality curated AMR gene reference database. The Bacterial Antimicrobial Resistance Reference Gene Database consists of up-to-date gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, it contains 4,579 antimicrobial resistance proteins and more than 560 HMMs.Here, we describe AMRFinder and its associated database. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder and resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425 Salmonella enterica, 770 Campylobacter spp., and 47 Escherichia coli phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions.To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene detection system. Most gene calls were identical, but there were 1,229 gene symbol differences (8.8%) between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that Resfinder found, while Resfinder missed 216 loci AMRFinder identified. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system. |
Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation
Chen MY , Rose CE , Qi YP , Williams JL , Yeung LF , Berry RJ , Hao L , Cannon MJ , Crider KS . Am J Clin Nutr 2019 109 (5) 1452-1461 BACKGROUND: For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE: The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS: We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS: Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (+/-3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS: The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558. |
Personal ultraviolet radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children study
Kimlin MG , Fang L , Feng Y , Wang L , Hao L , Fan J , Wang N , Meng F , Yang R , Cong S , Liang X , Wang B , Linet M , Potischman N , Kitahara C , Chao A , Wang Y , Sun J , Brodie A . BMC Public Health 2019 19 (1) 281 BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Apr 22, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure