Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-19 (of 19 Records) |
Query Trace: Subbarao S[original query] |
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Robustness of the ferret model for influenza risk assessment studies: a cross-laboratory exercise (preprint)
Belser JA , Lau EHY , Barclay W , Barr IG , Chen H , Fouchier RAM , Hatta M , Herfst S , Kawaoka Y , Lakdawala SS , Lee LYY , Neumann G , Peiris M , Perez DR , Russell C , Subbarao K , Sutton TC , Webby RJ , Yang H , Yen HL . bioRxiv 2022 2022.04.02.486825 Ferrets represent the preferred animal model for assessing the transmission potential of newly emerged zoonotic influenza viruses. However, heterogeneity among established experimental protocols and facilities across different laboratories may lead to variable results, complicating interpretation of transmission experimental data. Between 2018-2020, a global exercise was conducted by 11 participating laboratories to assess the range of variation in ferret transmission experiments using two common stock H1N1 influenza viruses that possess different transmission characteristics in ferrets. Inoculation route, dose, and volume were standardized, and all participating laboratories followed the same experimental conditions for respiratory droplet transmission, including a strict 1:1 donor:contact ratio. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored throughout. Overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. To attain high confidence in identifying zoonotic influenza viruses with moderate-to-high or low transmissibility, our analyses support that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.Competing Interest StatementThe authors have declared no competing interest. |
Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution (preprint)
Huddleston J , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Whittaker L , Ermetal B , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Barr I , Subbarao K , Neher RA , Bedford T . bioRxiv 2020 2020.06.12.145151 Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.Competing Interest StatementThe authors have declared no competing interest. |
When to update COVID-19 vaccine composition.
Grant R , Sacks JA , Abraham P , Chunsuttiwat S , Cohen C , Figueroa JP , Fleming T , Fine P , Goldblatt D , Hasegawa H , MacIntrye CR , Memish ZA , Miller E , Nishioka S , Sall AA , Sow S , Tomori O , Wang Y , Van Kerkhove MD , Wambo MA , Cohen HA , Mesfin S , Otieno JR , Subissi L , Briand S , Wentworth DE , Subbarao K . Nat Med 2023 29 (4) 776-780 Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy. | | Entering the fourth year of the COVID-19 pandemic, index virus-based1 vaccines across several different platforms continue to provide high levels of protection against severe disease caused by all variants of SARS-CoV-2, including Omicron2. However, there has been continuous and substantial evolution of SARS-CoV-2 since the virus emerged, posing challenges to the ongoing public health response, including ensuring that vaccines continue to provide protection. In September 2021, the World Health Organization (WHO) established the Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC)3 to assess the public health implications of emerging SARS-CoV-2 variants of concern (VOC) on the performance of COVID-19 vaccines and to issue timely recommendations on proposed modifications to vaccine antigen composition. The TAG-CO-VAC has evaluated evidence to inform its advice on COVID-19 vaccine composition so far, but there remain challenges and evidence gaps that the scientific community needs to address to enable future, timely decisions on modifications to COVID-19 vaccine antigen composition. |
Robustness of the ferret model for influenza risk assessment studies: A cross-laboratory exercise
Belser JA , Lau EHY , Barclay W , Barr IG , Chen H , Fouchier RAM , Hatta M , Herfst S , Kawaoka Y , Lakdawala SS , Lee LYY , Neumann G , Peiris M , Perez DR , Russell C , Subbarao K , Sutton TC , Webby RJ , Yang H , Yen HL . mBio 2022 13 (4) e0117422 Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment. IMPORTANCE Following detection of a novel virus, rapid characterization efforts (both in vitro and in vivo) are undertaken at numerous laboratories worldwide to evaluate the relative risk posed to human health. Aggregation of these data are critical, but the use of nonstandardized protocols can make interpretation of divergent results a challenge. For evaluation of virus transmissibility, a multifactorial trait which can only be evaluated in vivo, identifying intrinsic levels of variability between groups can improve the utility of these data, as well as ensure that experiments are performed with sufficient replication to ensure high confidence in compiled results. Using the ferret transmission model and two influenza A viruses, we conducted a multicenter standardization exercise to improve the interpretation of transmission data generated during risk assessment activities; this exercise serves as a model for future efforts employing both in vitro and in vivo models against possible pandemic pathogens. |
Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020.
Govorkova EA , Takashita E , Daniels RS , Fujisaki S , Presser LD , Patel MC , Huang W , Lackenby A , Nguyen HT , Pereyaslov D , Rattigan A , Brown SK , Samaan M , Subbarao K , Wong S , Wang D , Webby RJ , Yen HL , Zhang W , Meijer A , Gubareva LV . Antiviral Res 2022 200 105281 Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.6% (159/26010) for the 2018-2019 and 2019-2020 periods, respectively. The most common amino acid substitution was NA-H275Y (N1 numbering) conferring HRI by oseltamivir and peramivir in A(H1N1)pdm09 viruses. Combined phenotypic and PA sequence-based analysis showed that the global frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low, 0.5% (72/15906) and 0.1% (18/15692) for the 2018-2019 and 2019-2020 periods, respectively. Most (n = 61) of these viruses had I38→T/F/M/S/L/V PA amino acid substitutions. In Japan, where baloxavir use was highest, the rate was 4.5% (41/919) in the 2018-2019 period and most of the viruses (n = 32) had PA-I38T. Zoonotic viruses isolated from humans (n = 32) in different countries did not contain substitutions in NA associated with NAI RI/HRI phenotypes. One A(H5N6) virus had a dual substitution PA-I38V + PA-E199G, which may reduce susceptibility to baloxavir. Therefore, NAIs and baloxavir remain appropriate choices for the treatment of influenza virus infections, but close monitoring of antiviral susceptibility is warranted. |
Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution.
Huddleston J , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Whittaker L , Ermetal B , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Barr I , Subbarao K , Barrat-Charlaix P , Neher RA , Bedford T . Elife 2020 9 Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence- only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth. |
Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017-2018.
Takashita E , Daniels RS , Fujisaki S , Gregory , Gubareva LV , Huang W , Hurt AC , Lackenby A , Nguyen HT , Pereyaslov D , Roe M , Samaan M , Subbarao K , Tse H , Wang D , Yen H-L , Zhang W , Meijer A . Antiviral Res 2020 175 104718-104718 The global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012-13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for the treatment of influenza virus infection in Japan and the United States. For this annual report, the susceptibilities of influenza viruses to NAIs and baloxavir were analyzed. A total of 15409 viruses, collected by World Health Organization (WHO) recognized National Influenza Centers and other laboratories between May 2017 and May 2018, were assessed for phenotypic NAI susceptibility by five WHO Collaborating Centers (CCs). The 50% inhibitory concentration (IC(50)) was determined for oseltamivir, zanamivir, peramivir and laninamivir. Reduced inhibition (RI) or highly reduced inhibition (HRI) by one or more NAIs was exhibited by 0.8% of viruses tested (n = 122). The frequency of viruses with RI or HRI has remained low since this global analysis began (2012-13: 0.6%; 2013-14: 1.9%; 2014-15: 0.5%; 2015-16: 0.8%; 2016-17: 0.2%). PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23G/K/R, PA A36V, PA A37T, PA I38F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions. Five of them were included in phenotypic baloxavir susceptibility analysis by two WHO CCs and IC(50) values were determined. The PA variant viruses showed 6-17-fold reduced susceptibility to baloxavir. Overall, in the 2017-18 period the frequency of circulating influenza viruses with reduced susceptibility to NAIs or baloxavir was low, but continued monitoring is important. |
Safety, immunogenicity and protection of A(H3N2) live attenuated influenza vaccines containing wild-type nucleoprotein in a ferret model.
Korenkov DA , Laurie KL , Reading PC , Carolan LA , Chan KF , Isakova Sivak II , Smolonogina TA , Subbarao K , Barr IG , Villanueva J , Shcherbik S , Bousse T , Rudenko LG . Infect Genet Evol 2018 64 95-104 Live attenuated influenza vaccines (LAIVs) are promising tools for the induction of broad protection from influenza due to their ability to stimulate cross-reactive T cells against influenza pathogens. One of the major targets for cytotoxic T-cell immunity is viral nucleoprotein (NP), which is relatively conserved among antigenically distant influenza viruses. Nevertheless, a diversity of epitope composition has been found in the NP protein of different lineages of influenza A viruses. The H2N2 master donor virus which is currently used as a backbone for the LAIV and donor of the six genomic segments encoding the internal proteins, A/Leningrad/134/17/57 (MDV Len/17), was isolated 60years ago. As such, NP-specific T-cell immunity induced upon vaccination with classical LAIVs with a 6:2 genome composition containing this older NP might be suboptimal against currently circulating influenza viruses. In this study, a panel of H3N2 LAIV candidates with wild-type NP genes derived from circulating viruses were generated by reverse genetics (5:3 genome composition). These viruses displayed the cold adaptation and temperature sensitivity phenotypes of MDV Len/17 in vitro. LAIVs with both 6:2 and 5:3 genome compositions were attenuated and replicated to a similar extent in the upper respiratory tract of ferrets. LAIVs were immunogenic as high neutralizing and hemagglutination inhibition serum antibody titers were detected 21days after infection. All vaccinated animals were protected against infection with heterologous H3N2 influenza A viruses. Thus, LAIV with a 5:3 genome composition is safe, immunogenic and can induce cross-protective immunity. |
Ferrets as models for influenza virus transmission studies and pandemic risk assessments
Belser JA , Barclay W , Barr I , Fouchier RAM , Matsuyama R , Nishiura H , Peiris M , Russell CJ , Subbarao K , Zhu H , Yen HL . Emerg Infect Dis 2018 24 (6) 965-971 The ferret transmission model is extensively used to assess the pandemic potential of emerging influenza viruses, yet experimental conditions and reported results vary among laboratories. Such variation can be a critical consideration when contextualizing results from independent risk-assessment studies of novel and emerging influenza viruses. To streamline interpretation of data generated in different laboratories, we provide a consensus on experimental parameters that define risk-assessment experiments of influenza virus transmissibility, including disclosure of variables known or suspected to contribute to experimental variability in this model, and advocate adoption of more standardized practices. We also discuss current limitations of the ferret transmission model and highlight continued refinements and advances to this model ongoing in laboratories. Understanding, disclosing, and standardizing the critical parameters of ferret transmission studies will improve the comparability and reproducibility of pandemic influenza risk assessment and increase the statistical power and, perhaps, accuracy of this model. |
Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine
Babu TM , Levine M , Fitzgerald T , Luke C , Sangster MY , Jin H , Topham D , Katz J , Treanor J , Subbarao K . Vaccine 2014 32 (50) 6798-804 BACKGROUND: H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV). METHODS: Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04 (H7N3) pLAIV all given as 10(7.5) 50% tissue culture infective doses (TCID50) intranasally. A subset of subjects received one 45mug dose of H7N7 pIIV containing the A/Mallard/Netherlands/12/2000 HA intramuscularly 18-24 months after pLAIV. Viral shedding was assessed by culture and real-time polymerase chain reaction (rRT-PCR), B cell responses following pLAIV were evaluated by ELISPOT and flow cytometry. Serum antibody was assessed by hemagglutination-inhibition (HAI), microneutralization (MN) and ELISA assays after each vaccine. RESULTS: Serum HAI or MN responses were not detected in any subject following one or two doses of either H7 pLAIV, although some subjects had detectable H7 specific B cells after vaccination. However, 10/13 subjects primed with two doses of H7N7 pLAIV responded to a subsequent dose of the homologous H7N7 pIIV with high titer HAI and MN antibody that cross-reacted with both North American and Eurasian lineage H7 viruses, including H7N9. In contrast, naive subjects and recipients of a single dose of the mismatched H7N3 pLAIV did not develop HAI or MN antibody after pIIV. CONCLUSIONS: While pLAIVs did not elicit detectable serum MN or HAI antibody, strain-specific pLAIV priming established long term immune memory that was cross-reactive with other H7 influenza strains. Understanding the mechanisms underlying priming by pLAIV may aid in pandemic vaccine development. |
Impact of proficiency testing program for laboratories conducting early infant diagnosis of HIV-1 in low to middle-income countries
Garcia A , Subbarao S , Zhang G , Parsons L , Nkengasong J , Ou CY , Ellenberger D . J Clin Microbiol 2013 52 (3) 773-80 A voluntary, cost-free external quality assessment (EQA) program established by the U.S. Centers for Disease Control and Prevention (CDC) was implemented to primarily monitor the performance of laboratories conducting HIV Early Infant Diagnosis (EID) from dried blood spots (DBS) in low to middle-income countries since 2006. Ten blinded DBS proficiency test (PT) specimens and 100 known HIV-positive and negative DBS specimens (to be used as internal controls) were shipped tri-annually to participating laboratories with reports for the PT specimens due within 30 days. The participant's results and summary of the performance of all participating laboratories and each diagnostic method were provided after each test cycle. Enrollment in the CDC PT program expanded progressively from 17 laboratories from 11 countries in 2006 to include 136 laboratories from 41 countries at the end of 2012. Despite external pressures to test and treat more children while expanding EID programs, mean PT test scores significantly improved over time as demonstrated by the upward trend from mid-2006 to end of 2012 (P = 0.001) and increase in the percentage of laboratories scoring 100% (P =0.003). The mean test scores plateaued over the past 10 testing cycles, ranging between 98.2 and 99.7% and discordant test results still occur, but at a rate no higher than 2.6%. Analysis of these test results suggests a positive impact of proficiency testing on the testing performance of the participating laboratories and a continuous training program and proficiency testing participation may translate into laboratories improving their testing accuracy. |
Transmission studies resume for avian flu
Fouchier RA , Garcia-Sastre A , Kawaoka Y , Barclay WS , Bouvier NM , Brown IH , Capua I , Chen H , Compans RW , Couch RB , Cox NJ , Doherty PC , Donis RO , Feldmann H , Guan Y , Katz JM , Kiselev OI , Klenk HD , Kobinger G , Liu J , Liu X , Lowen A , Mettenleiter TC , Osterhaus AD , Palese P , Peiris JS , Perez DR , Richt JA , Schultz-Cherry S , Steel J , Subbarao K , Swayne DE , Takimoto T , Tashiro M , Taubenberger JK , Thomas PG , Tripp RA , Tumpey TM , Webby RJ , Webster RG . Science 2013 339 (6119) 520-1 In January 2012, influenza virus researchers from around the world announced a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals (1). We declared a pause to this important research to provide time to explain the public health benefits of this work, to describe the measures in place to minimize possible risks, and to enable organizations and governments around the world to review their policies (for example, on biosafety, biosecurity, oversight, and communication) regarding these experiments. | During the past year, the benefits of this important research have been explained clearly in publications (2-7) and meetings (8-10). Measures to mitigate possible risks of the work have been detailed (11-13). The World Health Organization has released recommendations on laboratory biosafety for those conducting this research (14), and relevant authorities in several countries have reviewed the biosafety, biosecurity, and funding conditions under which further research would be conducted on the laboratory-modified H5N1 viruses (10, 15-17). Thus, acknowledging that the aims of the voluntary moratorium have been met in some countries and are close to being met in others, we declare an end to the voluntary moratorium on avian flu transmission studies. |
Generation of dried tube specimen for HIV-1 viral load proficiency test panels: a cost-effective alternative for external quality assessment programs
Ramos A , Nguyen S , Garcia A , Subbarao S , Nkengasong JN , Ellenberger D . J Virol Methods 2012 188 1-5 Participation in external quality assessment programs is critical to ensure quality clinical laboratory testing. Commercially available proficiency test panels for HIV-1 virus load testing that are used commonly in external quality assessment programs remain a financial obstacle to resource-limited countries. Maintaining cold-chain transportation largely contributes to the cost of traditional liquid proficiency test panels. Therefore, we developed and evaluated a proficiency test panel using dried tube specimens that can be shipped and stored at ambient temperature. This dried tube specimens panel consisted of 20mcl aliquots of a HIV-1 stock that were added to 2ml tubes and left uncapped for drying, as a preservation method. The stability of dried tube specimens at concentrations ranging from 10(2) to 10(6.5) RNA copies/ml was tested at different temperatures over time, showing no viral load reduction at 37 degrees C and a decrease in viral load smaller than 0.5 Log(10) at 45 degrees C for up to eight weeks when compared to initial results. Eight cycles of freezing-thawing had no effect on the stability of the dried tube specimens. Comparable viral load results were observed when dried tube specimen panels were tested on Roche CAPTAQ, Abbott m2000, and Biomerieux easyMAG viral load systems. Preliminary test results of dried proficiency test panels shipped to four African countries at ambient temperature demonstrated a low inter assay variation (SD range: 0.29-0.41 Log(10) RNA copies/ml). These results indicated that HIV-1 proficiency test panels generated by this methodology might be an acceptable alternative for laboratories in resource-limited countries to participate in external quality assessment programs. |
Evaluation of blood collection filter papers for HIV-1 DNA PCR.
Masciotra S , Khamadi S , Bile E , Puren A , Fonjungo P , Nguyen S , Girma M , Downing R , Ramos A , Subbarao S , Ellenberger D . J Clin Virol 2012 55 (2) 101-6 BACKGROUND: The collection of dried blood spots (DBS) on Whatman 903 cards has facilitated for years the detection of HIV-1 in infants by DNA PCR as early as 4-6 weeks after birth in resource-limited settings (RLS), but alternate blood collection devices are proving to be necessary. OBJECTIVES: The qualitative detection of HIV-1 DNA by PCR from DBS prepared on three commercially available blood collection cards was evaluated at the Centers for Disease Control and Prevention (CDC) and in four laboratories in Africa. STUDY DESIGN: DBS were prepared on Ahlstrom grade 226, Munktell TFN and Whatman 903, and stored under a variety of conditions. DBS were stored at ambient temperature (RT), 37 degrees C with high humidity, and -20 degrees C for varying lengths of time. The presence of HIV-1 DNA was tested using Roche Amplicor HIV-1 DNA (v 1.5) weekly for 4 weeks and at weeks 8 and 12 (RT and 37 degrees C), at weeks 4, 8, and 18 (-20 degrees C) of storage. DBS specimens were also tested after international shipment at RT. In addition, after nearly 3 years storage at -20 degrees C, DBS were also evaluated independently using the COBAS Ampliprep/TaqMan HIV-1 Qual and Abbott RealTime HIV-1 Qualitative tests. RESULTS: HIV-1 DNA was detected equally well on the three blood collection cards regardless of storage conditions and PCR assay. CONCLUSIONS: Ahlstrom 226 and Munktell TFN papers were comparable to Whatman 903 for HIV-1 DNA detection and may be considered as optional blood collection devices in resource-limited countries. |
Evaluation of a high-throughput diagnostic system for detection of HIV-1 in dried blood spot samples from infants in Mozambique.
Jani IV , Sabatier J , Vubil A , Subbarao S , Bila D , de Sousa A , Mabunda N , Garcia A , Skaggs B , Ellenberger D , Ramos A . J Clin Microbiol 2012 50 (4) 1458-60 We performed a comparative analysis between Roche Amplicor HIV-1 DNA test and CAPTAQ assay for the detection of HIV in 830 dried blood spot (DBS) pediatric samples collected in Mozambique. Our results demonstrated no statistical difference between these assays. The CAPTAQ assay approached nearly 100% repeatability/accuracy. The increased throughput of testing with minimal operator interference in performing the CAPTAQ assay clearly demonstrated that this method is an improvement over the Roche Amplicor HIV-1 DNA test, version 1.5. |
Pause on avian flu transmission research
Fouchier RA , Garcia-Sastre A , Kawaoka Y , Barclay WS , Bouvier NM , Brown IH , Capua I , Chen H , Compans RW , Couch RB , Cox NJ , Doherty PC , Donis RO , Feldmann H , Guan Y , Katz J , Klenk HD , Kobinger G , Liu J , Liu X , Lowen A , Mettenleiter TC , Osterhaus AD , Palese P , Peiris JS , Perez DR , Richt JA , Schultz-Cherry S , Steel J , Subbarao K , Swayne DE , Takimoto T , Tashiro M , Taubenberger JK , Thomas PG , Tripp RA , Tumpey TM , Webby RJ , Webster RG . Science 2012 335 (6067) 400-1 THE CONTINUOUS THREAT OF AN INFLUENZA PANDEMIC REPRESENTS ONE OF THE BIGGEST CHALlenges in public health. Influenza pandemics are known to be caused by viruses that evolve from animal reservoirs, such as in birds and pigs, and can acquire genetic changes that increase their ability to transmit in humans. Pandemic preparedness plans have been implemented worldwide to mitigate the impact of influenza pandemics. A major obstacle in preventing influenza pandemics is that little is known regarding what makes an influenza virus transmissible in humans. As a consequence, the potential pandemic risk associated with the many different influenza viruses of animals cannot be assessed with any certainty. | Recent research breakthroughs identified specific determinants of transmission of H5N1 influenza viruses in ferrets. Responsible research on influenza virus transmission using different animal models is conducted by multiple laboratories in the world using the highest international standards of biosafety and biosecurity practices that effectively prevent the release of transmissible viruses from the laboratory. These standards are regulated and monitored closely by the relevant authorities. This statement is being made by the principal investigators of these laboratories. |
Mass casualty response in the 2008 Mumbai terrorist attacks
Roy N , Kapil V , Subbarao I , Ashkenazi I . Disaster Med Public Health Prep 2011 5 (4) 273-9 OBJECTIVES: The November 26-29, 2008, terrorist attacks on Mumbai were unique in its international media attention, multiple strategies of attack, and the disproportionate national fear they triggered. Everyone was a target: random members of the general population, iconic targets, and foreigners alike were under attack by the terrorists. METHODS: A retrospective, descriptive study of the distribution of terror victims to various city hospitals, critical radius, surge capacity, and the nature of specialized medical interventions was gathered through police, legal reports, and interviews with key informants. RESULTS: Among the 172 killed and 304 injured people, about four-fifths were men (average age, 33 years) and 12% were foreign nationals. The case-fatality ratio for this event was 2.75:1, and the mortality rate among those who were critically injured was 12%. A total of 38.5% of patients arriving at the hospitals required major surgical intervention. Emergency surgical operations were mainly orthopedic (external fixation for compound fractures) and general surgical interventions (abdominal explorations for penetrating bullet/shrapnel injuries). CONCLUSIONS: The use of heavy-duty automatic weapons, explosives, hostages, and arson in these terrorist attacks alerts us to new challenges to medical counterterrorism response. The need for building central medical control for a coordinated response and for strengthening public hospital capacity are lessons learned for future attacks. These particular terrorist attacks had global consequences, in terms of increased security checks and alerts for and fears of further similar "Mumbai-style" attacks. The resilience of the citizens of Mumbai is a critical measure of the long-term effects of terror attacks. |
The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus
Suguitan AL Jr , Marino MP , Desai PD , Chen LM , Matsuoka Y , Donis RO , Jin H , Swayne DE , Kemble G , Subbarao K . Virology 2009 395 (2) 280-8 A recombinant live attenuated influenza virus DeltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the DeltaH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the DeltaH5N1 vaccine in mice. |
Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection
Chen J , Lau YF , Lamirande EW , Paddock CD , Bartlett JH , Zaki SR , Subbarao K . J Virol 2009 84 (3) 1289-301 We characterized the cellular immune response to SARS coronavirus (SARS-CoV) infection in 12-14 month old (m/o) BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs with peak titers on day (d) 2 post-infection. Enhanced production of cytokines (TNFalpha, IL-6) and chemokines (CXCL10, CCL2, CCL3, CCL5) correlated with migration of NK cells, macrophages and plasmacytoid DC (pDC) into the lungs. By d 7, histopathologic evidence of pneumonitis was seen in the lungs when viral clearance occurred. At this time, a second wave of enhanced production of cytokines (TNFalpha, IL-6, IFNgamma, IL-2, IL-5), chemokines (CXCL9, CXCL10, CCL2, CCL3, CCL5) and receptors (CXCR3, CCR2, CCR5), was detected in the lungs associated with an influx of T lymphocytes. Depletion of CD8(+) T cells at the time of infection did not affect viral replication or clearance. However, depletion of CD4(+) T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed clearance of SARS-CoV from the lungs, associated with reduced neutralizing antibody and cytokine production and reduced pulmonary recruitment of lymphocytes. Innate defense mechanisms are able to control SARS-CoV infection in the absence of CD4(+) and CD8(+) T cells and antibodies. Our findings provide new insights into the pathogenesis of SARS, demonstrating the important role of CD4(+) but not CD8(+) T cells in primary SARS-CoV infection in this model. |
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