Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-20 (of 20 Records) |
Query Trace: Basu M[original query] |
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Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine
Bhatla N , Muwonge R , Malvi SG , Joshi S , Poli URR , Lucas E , Esmy PO , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Vashist S , Mishra G , Jadhav R , Siddiqi M , Anantharaman D , Panicker G , Butt J , Sankaran S , Kannan Tpra , Varghese R , Kartha P , Pillai MR , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Hum Vaccin Immunother 2023 19 (3) 2289242 Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier. |
Ferrets as a mammalian model to study influenza virus-bacteria interactions
Basu Thakur P , Mrotz VJ , Maines TR , Belser JA . J Infect Dis 2023 Ferrets represent an invaluable model for the study of influenza virus pathogenicity and transmissibility due to the ability of this species to recapitulate clinical symptoms of influenza infection present in humans. Ferrets are also employed for the study of bacterial pathogens that naturally infect humans at different anatomical sites, including the respiratory and gastrointestinal tracts. While viral and bacterial infection studies in isolation using animal models are important for furthering our understanding of pathogen biology and for the development of improved therapeutics, it is also critical to extend our knowledge to pathogen coinfections in vivo, to more closely examine interkingdom dynamics that may contribute to overall disease outcomes. Despite the increasing use of ferrets for studies with influenza virus, few reports have investigated influenza and bacterial coinfection challenges in ferrets. In this review, we discuss how ferrets have been employed to study a diverse range of both influenza viruses and bacterial species and summarize key studies that have utilized the ferret model for primary influenza virus challenge followed by secondary bacterial infection. These co-pathogenesis studies have provided critical insight into the dynamic interplay between these pathogens, underscoring the utility of ferrets as a model system for investigating influenza virus-bacteria interactions. |
Cost analysis of the WHO-HEARTS program for hypertension control and CVD prevention in primary health facilities in Ethiopia
Beshah SA , Husain MJ , Dessie GA , Worku A , Negeri MG , Banigbe B , Moran AE , Basu S , Kostova D . Public Health Pract (Oxf) 2023 6 100423 BACKGROUND: In 2020, Ethiopia launched the Ethiopia Hypertension Control Initiative (EHCI) program to improve hypertension care using the approach described in the WHO HEARTS technical package. OBJECTIVE: To estimate the costs of implementing the HEARTS program for hypertension control and cardiovascular disease (CVD) prevention in the primary care setting in Ethiopia for adult primary care users in the catchment area of five examined facilities. STUDY DESIGN: This study entails a program cost analysis using cross-sectional primary and secondary data. METHODS: Micro-costing facility surveys were used to assess activity costs related to training, counselling, screening, lab diagnosis, medications, monitoring, and start-up costs at five selected health facilities. Cost data were obtained from primary and secondary sources, and expert opinion. Annual costs from the health system perspective were estimated using the Excel-based HEARTS costing tool under two intervention scenarios - hypertension-only control and a CVD risk management program, which addresses diabetes and hypercholesterolemia in addition to hypertension. RESULTS: The estimated cost per adult primary care user was USD 5.3 for hypertension control and USD 19.3 for integrated CVD risk management. The estimated medication cost per person treated for hypertension was USD 9.0, whereas treating diabetes and high cholesterol would cost USD 15.4 and USD 15.3 per person treated, respectively. Medications were the major cost driver, accounting for 37% of the total cost in the hypertension control program. In the CVD risk management scenario, the proportions of medication and lab diagnostics of total costs were 18% and 64%, respectively. CONCLUSIONS: The results from this study can inform planning and budgeting for HEARTS scale-up to prevent CVD across Ethiopia. |
Memory CD4 T cell subset organization in the female reproductive tract is regulated via the menstrual cycle through CCR5 signaling (preprint)
Swaims-Kohlmeier A , Wein AN , Hardnett FP , Sheth AN , Li ZRT , Williams ME , Radzio-Basu J , Zheng H , Dinh C , Haddad LB , Collins EMB , Lobby JL , Kost K , Hayward SL , Ofotokun I , Antia R , Scharer CD , Lowen AC , Garcia-Lerma JG , Kohlmeier JE . bioRxiv 2022 03 Despite their importance for immunity against sexually transmitted infections (STIs), the composition of the female reproductive tract (FRT) memory CD4 T cell population in response to changes in the local tissue environment during the menstrual cycle remains poorly defined. Here we show that across humans, non-human primates (NHP), and mice, FRT CD4 T cells comprise distinct subsets corresponding to migratory memory (TMM) and resident memory (TRM) cells. TMM display tissue-itinerant trafficking characteristics, restricted FRT tissue distribution, with distinct transcriptional properties and effector responses to infection. CD4 T cell subset fluctuations synchronized with cycle-driven proinflammatory changes within the local tissue environment and oral administration of a CCR5 antagonist inhibited cycle phase-specific migratory T cell surveillance. This study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of memory T cell defense at the site of STI exposure. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Enhanced fitness of SARS-CoV-2 B.1.617.2 Delta variant in ferrets.
Sun X , Belser JA , Kieran TJ , Brock N , Pulit-Penaloza JA , Pappas C , Basu Thakur P , Jones J , Wentworth DE , Zhou B , Tumpey TM , Maines TR . Virology 2023 582 57-61 Competition assays were conducted in vitro and in vivo to examine how the Delta (B.1.617.2) variant displaced the prototype Washington/1/2020 (WA/1) strain. While WA/1 virus exhibited a moderately increased proportion compared to that in the inoculum following co-infection in human respiratory cells, Delta variant possessed a substantial in vivo fitness advantage as this virus becoming predominant in both inoculated and contact animals. This work identifies critical traits of the Delta variant that likely played a role in it becoming a dominant variant and highlights the necessities of employing multiple model systems to assess the fitness of newly emerged SARS-CoV-2 variants. |
Attitudes and beliefs about HIV treatment as prevention among people who are not engaged in HIV care, 2018-2019
Padilla M , Gutierrez M , Basu M , Fagan J . AIDS Behav 2023 27 (9) 3122-3132 Treatment as prevention (TasP) is an effective HIV prevention strategy. Our objectives were to explore TasP attitudes and beliefs among people with HIV (PWH) who are not engaged in care and to examine attitudes and beliefs by selected characteristics. We sampled PWH who had participated in the Medical Monitoring Project (MMP), a structured interview survey, from June 2018-May 2019 to participate in 60-minute semi-structured telephone interviews. We obtained sociodemographic and behavioral quantitative data from the MMP structured interview. We used applied thematic analysis to analyze the qualitative data and integrated the qualitative and quantitative data during analysis. Negative attitudes and beliefs, especially skepticism and mistrust, about TasP were pervasive. Only one participant who identified as female, was not sexually active, and had not heard of TasP held positive attitudes and beliefs about TasP. TasP messages should use clear and unambiguous language, address mistrust, and reach people who are not engaged in medical care. |
Refractory, fatal autoimmune hemolytic anemia due to ineffective thymic-derived T-cell reconstitution following allogeneic hematopoietic cell transplantation for hypomorphic RAG1 deficiency
Yonkof JR , Basu A , Redmond MT , Dobbs AK , Perelygina L , Notarangelo LD , Abraham RS , Rangarajan HG . Pediatr Blood Cancer 2022 70 (5) e30183 Pathogenic recombination-activating gene 1 (RAG1) variants cause a phenotypic spectrum ranging from severe combined immunodeficiency (SCID) to combined immunodeficiency with granulomas and autoimmunity (CID-G/A), depending on residual recombinase activity.1-4 Our patient, a 12-year-old African American female with hypogammaglobulinemia and T-, B-cell lymphopenia, was diagnosed with CID at 5 years of age, with a history of recurrent herpes simplex virus (HSV) gingivostomatitis, bacterial pneumonia, and cutaneous abscess. She tolerated two doses of live measles–mumps–rubella (MMR) vaccine. She was referred to our facility for steroid-refractory sterile non-caseating cutaneous granulomas (Figure S1) affecting posterior thigh and midface, appearing at 9 years and with progressive lymphopenia (Figure 1A) concerning for a CID. Next-generation sequencing identified compound heterozygous pathogenic RAG1 variants, c.1187G>A, p.Arg396His and c.1566G>T, p.Trp522Cys (NM_000448.2). Residual recombinase activity is estimated at 40%–50% for RAG1-Trp522Cys and less than 5%–30% for RAG1-Arg396His.2, 5, 6 |
Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination
Joshi S , Anantharaman D , Muwonge R , Bhatla N , Panicker G , Butt J , Rani Reddy Poli U , Malvi SG , Esmy PO , Lucas E , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Divate U , Vashist S , Mishra G , Jadhav R , Siddiqi M , Sankaran S , Pillai Rameshwari Ammal Kannan T , Kartha P , Shastri SS , Sauvaget C , Radhakrishna Pillai M , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Vaccine 2022 41 (1) 236-245 BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination. |
Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster
Laing KJ , Ouwendijk WJD , Campbell VL , McClurkan CL , Mortazavi S , Elder Waters M , Krist MP , Tu R , Nguyen N , Basu K , Miao C , Schmid DS , Johnston C , Verjans Gmgm , Koelle DM . Nat Commun 2022 13 (1) 6957 Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin. |
A sub-group evaluation of the multi-month dispensing strategy for differentiated HIV care: is personalization of care guidelines warranted in Haiti
Parrish C , Basu A , Fishman P , Koama JB , Robin E , Francois K , Honoré JG , Van Onacker JD , Puttkammer N . BMC Health Serv Res 2022 22 (1) 80 BACKGROUND: Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. METHODS: This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. RESULTS: There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. CONCLUSIONS: All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines. |
Estimating the effect of increasing dispensing intervals on retention in care for people with HIV in Haiti
Parrish C , Basu A , Fishman P , Koama JB , Robin E , Francois K , Honore JG , Van Onacker JD , Puttkammer N . EClinicalMedicine 2021 38 101039 Background: Multi-month dispensing (MMD) for antiretroviral therapy (ART) is a promising care strategy to improve HIV treatment adherence. The effectiveness of MMD in routine settings has not yet been evaluated within a causal inference framework. We analyzed data from a robust clinical data system to evaluate MMD in Haiti. Method(s): We assessed 1-year retention in care among 21,880 ART-naive HIV-positive persons who started ART on or after January 1, 2017, up until November 1, 2018. We used an instrumental variable analysis to estimate the causal impact of MMD. This approach was used to address potential selection into specific dispensing intervals because MMD is not randomly applied to individuals. Finding(s): We found that extending ART dispensing intervals increased the probability of retention at 12 months after ART initiation, with up to a 24.2%-point increase (95%CI: 21.9, 26.5) in the likelihood of retention with extending dispenses by 30 days for those receiving one-month dispenses. We observed statistically significant gains to retention with MMD with up to an approximately 4-month supply of ART; +5.1%-points (95%CI: 2.4,7.8). Increasing dispensing lengths for those already receiving >=5-month supply of ART had a potentially negative effect on retention. Interpretation(s): MMD for ART is an effective service delivery strategy that improves care retention for new ART recipients. There is a potentially negative effect of increasing prescription lengths for those new ART recipients already receiving longer ART supplies, though more research is needed to characterize this effect given medication supplies of this length are not common for newer ART recipients. Copyright © 2021 The Author(s) |
Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment
Buck WC , Nguyen H , Siapka M , Basu L , Greenberg Cowan J , De Deus MI , Gleason M , Ferreira F , Xavier C , Jose B , Muthemba C , Simione B , Kerndt P . AIDS Res Ther 2021 18 (1) 3 BACKGROUND: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. METHODS: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0-14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. RESULTS: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). CONCLUSIONS: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed. |
Evaluation of serological assays to monitor antibody responses to single-dose HPV vaccines
Tsang SH , Basu P , Bender N , Herrero R , Kemp TJ , Kreimer AR , Muller M , Panicker G , Pawlita M , Pinto LA , Sampson JN , Sankaranarayanan R , Schussler J , Sehr P , Sierra MS , Unger ER , Waterboer T , Hildesheim A . Vaccine 2020 38 (38) 5997-6006 INTRODUCTION: Whether existing serological assays are sufficiently robust to measure the lower antibody levels expected following single-dose HPV vaccination is unknown. METHODS: We evaluated seven assays measuring HPV-16/18 immunological responses overall and by number of doses in 530 serum samples from participants receiving varying doses of Cervarix or Gardasil up to 36-months post-vaccination. Serum was evaluated by simplex (HPV-16 ELISA, HPV-18 ELISA), multiplex (LIA-4, VLP-MIA, M9ELISA, GST-L1), and high-throughput pseudovirion-based neutralization assays (HT-PBNA), and results were compared to the gold standard HPV-16/18 secreted alkaline phosphatase neutralization assay (SEAP-NA). Reproducibility was assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Percent agreement, Pearson correlation, and weighted-kappa were used to assess validity. Determinants of seronegativity were evaluated by chi-squared test. RESULTS: HPV-16: Seropositivity range was 97.1-99.5% for single dose and 98.8-99.8% overall. CV range was 4.0-18.0% for single dose and 2.9-19.5% overall. ICC range was 0.77-0.99 for single dose and 0.74-0.99 overall. Correlation with SEAP-NA range was 0.43-0.85 for single dose and 0.51-0.90 overall. Weighted-kappa range was 0.34-0.82 for single dose and 0.45-0.84 overall. HPV-18: Seropositivity range was 63.9-94.7% for single dose and 86.2-97.9% overall. CV range was 8.1-18.2% for single dose and 4.6-18.6% overall. ICC range was 0.75-0.99 for single dose and 0.83-0.99 overall. Correlation with SEAP-NA range was 0.31-0.99 for single dose and 0.27-0.96 overall. Weighted-kappa range was 0.35-0.83 for single dose and 0.45-0.84 overall. HPV-16 seronegativity was <5% for all assays. HPV-18 seronegativity range was 5.5-17.3%. For LIA-4 and GST-L1 where the proportion of seronegativity was >10%, the strongest correlates of seronegativity were receiving a single vaccine dose and receiving Gardasil. CONCLUSIONS: These results support the utility of existing serological assays to monitor antibody responses following single-dose HPV vaccination. |
Cancer Informatics for Cancer Centers (CI4CC): Building a Community Focused on Sharing Ideas and Best Practices to Improve Cancer Care and Patient Outcomes.
Barnholtz-Sloan JS , Rollison DE , Basu A , Borowsky AD , Bui A , DiGiovanna J , Garcia-Closas M , Genkinger JM , Gerke T , Induni M , Lacey JVJr , Mirel L , Permuth JB , Saltz J , Shenkman EA , Ulrich CM , Zheng WJ , Nadaf S , Kibbe WA . JCO Clin Cancer Inform 2020 4 108-116 Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. Although each of the participating cancer centers is structured differently, and leaders' titles vary, we know firsthand there are similarities in both the issues we face and the solutions we achieve. As a consortium, we have initiated a dedicated listserv, an open-initiatives program, and targeted biannual face-to-face meetings. These meetings are a place to review our priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues we, as informatics leaders, individually face at our respective institutions and cancer centers. Here we provide a brief history of the CI4CC organization and meeting highlights from the latest CI4CC meeting that took place in Napa, California from October 14-16, 2019. The focus of this meeting was "intersections between informatics, data science, and population science." We conclude with a discussion on "hot topics" on the horizon for cancer informatics. |
Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection
Radzio-Basu J , Council O , Cong ME , Ruone S , Newton A , Wei X , Mitchell J , Ellis S , Petropoulos CJ , Huang W , Spreen W , Heneine W , Garcia-Lerma JG . Nat Commun 2019 10 (1) 2005 A long-acting injectable formulation of the HIV integrase inhibitor cabotegravir (CAB-LA) is currently in clinical development for PrEP. Although the long plasma half-life of CAB-LA is an important attribute for PrEP, it also raises concerns about drug resistance emergence if someone becomes infected with HIV, or if PrEP is initiated during undiagnosed acute infection. Here we use a macaque model of SHIV infection to model risks of drug resistance to CAB-LA PrEP. Six macaques infected with SHIV received CAB-LA before seroconversion. We show integrase mutations G118R, E92G/Q, or G140R in plasma from 3/6 macaques as early as day 57, and identify G118R and E92Q in viruses from vaginal and rectal fluids. G118R and G140R confer > 800-fold resistance to CAB and cross-resistance to all licensed integrase inhibitors. Our results emphasize the need for appropriate HIV testing strategies before and possibly shortly after initiating CAB LA PrEP to exclude acute infection. |
Development of a Manikin-Based Performance Evaluation Method for Loose-Fitting Powered Air-Purifying Respirators
Bergman M , Basu R , Lei Z , Niezgoda G , Zhuang Z . J Int Soc Respir Prot 2017 34 (1) 40-57 OBJECTIVE: Loose-fitting powered air-purifying respirators (PAPRs) are increasingly being used in healthcare. NIOSH has previously used advanced manikin headforms to develop methods to evaluate filtering facepiece respirator fit; research has now begun to develop methods to evaluate PAPR performance using headforms. This preliminary study investigated the performance of PAPRs at different work rates to support development of a manikin-based test method. METHODS: Manikin penetration factors (mPF) of three models of loose-fitting PAPRs were measured at four different work rates (REST: 11 Lpm, LOW: 25 Lpm, MODERATE: 48 Lpm, and HIGH: 88 Lpm) using a medium-sized NIOSH static advanced headform mounted onto a torso. In-mask differential pressure was monitored throughout each test. Two condensation particle counters were used to measure the sodium chloride aerosol concentrations in the test chamber and also inside the PAPR facepiece over a 2-minute sample period. Two test system configurations were evaluated for returning air to the headform in the exhalation cycle (filtered and unfiltered). Geometric mean (GM) and 5th percentile mPFs for each model/work rate combination were computed. Analysis of variance tests were used to assess the variables affecting mPF. RESULTS: PAPR model, work rate, and test configuration significantly affected PAPR performance. PAPR airflow rates for the three models were approximately 185, 210, and 235 Lpm. All models achieved GM mPFs and 5(th) percentile mPFs greater than their designated Occupational Safety and Health Administration assigned protection factors despite negative minimum pressures observed for some work rate/model combinations. CONCLUSIONS: PAPR model, work rate, and test configuration affect PAPR performance. Advanced headforms have potential for assessing PAPR performance once test methods can be matured. A manikin-based inward leakage test method for PAPRs can be further developed using the knowledge gained from this study. Future studies should vary PAPR airflow rate to better understand the effects on performance. Additional future research is needed to evaluate the correlation of PAPR performance using advanced headforms to the performance measured with human subjects. |
A Zika vaccine targeting NS1 protein protects immunocompetent adult mice in a lethal challenge model
Brault AC , Domi A , McDonald EM , Talmi-Frank D , McCurley N , Basu R , Robinson HL , Hellerstein M , Duggal NK , Bowen RA , Guirakhoo F . Sci Rep 2017 7 (1) 14769 Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model. |
Second worldwide proficiency study on variable number of tandem repeats typing of Mycobacterium tuberculosis complex
De Beer JL , Kodmon C , Van Ingen J , Jamieson FB , Bidovec-Stojkovic U , Brown T , Cirillo DM , Cruz L , Miranda A , Dou HY , Fauville-Dufaux M , Fitzgibbon MM , Garcia De Viedma D , Groenheit R , Haanpera-Heikkinen M , Indra A , Kam KM , Kramer R , Jiang GL , Niemann S , Obrovac M , Rasmussen EM , Refregier G , Realpe T , Samper S , Sharma MK , Sougakoff W , Stakenas P , Stavrum R , Trenkler J , Wada T , Siame KK , Tafaj S , Cowan L , Sng LH , Seagar AL , Basu I , Rastogi N , Ferro BE , De Matos F , Kipnis A , Van Soolingen D , Supply P . Int J Tuberc Lung Dis 2014 18 (5) 594-600+i BACKGROUND: The quality of variable number of tandem repeats (VNTR) typing of Mycobacterium tuberculosis was first investigated in 2009 in 37 laboratories worldwide. The results revealed an inter- and intra-laboratory reproducibility of respectively 60% and 72%. These data spurred an improvement in laboratory-specific assays and global standardisation of VNTR typing. OBJECTIVE: To measure the effects of the technical improvements and increased standardisation, a test panel consisting of 30 M. tuberculosis complex DNA samples was distributed for VNTR typing in 41 participating laboratories from 36 countries. RESULTS: The inter- and intra-laboratory reproducibility increased overall to respectively 78% and 88%. The 33 laboratories that participated in both the first and second proficiency studies improved their inter- and intra-laboratory reproducibility from 62% and 72% to respectively 79% and 88%. The largest improvement in reproducibility was detected in 10 laboratories that use an in-house polymerase chain reaction technique and perform amplicon sizing using gel electrophoresis. Detailed error analysis revealed a reduction in the number of systematic errors, sample exchange events and non-amplifiable loci. CONCLUSION: This second worldwide proficiency study indicates a substantial increase in the reproducibility of VNTR typing of M. tuberculosis. This will contribute to a more meaningful interpretation of molecular epidemiological and phylogenetic studies on the M. tuberculosis complex. |
Increased early RNA replication by chimeric West Nile Virus W956IC Leads to IPS-1-mediated activation of NF-kappaB and insufficient virus-mediated counteraction of the resulting canonical type I interferon signaling
Scherbik SV , Pulit-Penaloza JA , Basu M , Courtney SC , Brinton MA . J Virol 2013 87 (14) 7952-65 Although infections with "natural" West Nile virus (WNV) and the chimeric W956IC WNV infectious clone virus produce comparable peak virus yields in type I interferon (IFN) response-deficient BHK cells, W956IC infection produces higher levels of "unprotected" viral RNA at early times after infection. Analysis of infections with these two viruses in IFN-competent cells showed that W956IC activated NF-kappaB, induced higher levels of IFN-beta, and produced lower virus yields than WNV strain Eg101. IPS-1 was required for both increased induction of IFN-beta and decreased yields of W956IC. In Eg101-infected cells, phospho-STAT1/STAT2 nuclear translocation was blocked at all times analyzed, while some phospho-STAT1/STAT2 nuclear translocation was still detected at 8 h after infection in W956IC-infected mouse embryonic fibroblasts (MEFs), and early viral protein levels were lower in these cells. A set of additional chimeras was made by replacing various W956IC gene regions with the Eg101 equivalents. As reported previously, for three of these chimeras, the low early RNA phenotype of Eg101 was restored in BHK cells. Analysis of infections with two of these chimeric viruses in MEFs detected lower early viral RNA levels, higher early viral protein levels, lower early IFN-beta levels, and higher virus yields similar to those seen after Eg101 infection. The data suggest that replicase protein interactions directly or indirectly regulate genome switching between replication and translation at early times in favor of translation to minimize NF-kappaB activation and IFN induction by decreasing the amount of unprotected viral RNA, to produce sufficient viral protein to block canonical type I IFN signaling, and to efficiently remodel cell membranes for exponential genome amplification. |
Emergence and characterization of serotype G9 rotavirus strains from Africa
Page N , Esona M , Armah G , Nyangao J , Mwenda J , Sebunya T , Basu G , Pyndiah N , Potgieter N , Geyer A , Steele AD . J Infect Dis 2010 202 Suppl S55-63 Serotype G9 strains have been detected sporadically and in localized outbreaks in various African countries, including South Africa, Botswana, Malawi, Kenya, Cameroon, Nigeria, Ghana, Guinea-Bissau, Libya, and Mauritius. Serotype G9 strains were analyzed to investigate genogroup characteristics, including subgroup specificity, electropherotype, and P and G genotypes. In addition, the antigenic composition of the South African G9 strains was assessed. African G9 strains were associated with both DS-1-like characteristics and Wa-like characteristics, indicating the predisposition of G9 strains to frequently reassort. Despite these reassortment events, serotype G9 strains appear to maintain antigenic character in the outer capsid protein, as evident with the reaction of the South African G9 strains with the G9-specific monoclonal antibody F45:1. Phylogenetic analysis clustered African G9 strains geographically, regardless of genogroup characteristics, into 1 lineage (IIId). Two groups of G9 strains, originating in India and Japan, were identified in this lineage. Continuous surveillance of circulating rotavirus strains in Africa is vital to prepare for future vaccine implementation on a continent that clearly needs such preventative medicines. |
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