Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 31 Records) |
Query Trace: Kamal N[original query] |
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Health-related quality of life among prostate cancer survivors with metastatic disease and non-metastatic disease and men without a cancer history in the USA
Zheng Z , Shi KS , Kamal A , Howard DH , Horný M , Richards TB , Ekwueme DU , Yabroff KR . J Cancer Surviv 2023 BACKGROUND: Few studies have comprehensively compared health-related quality of life (HRQoL) between metastatic prostate cancer survivors, survivors with non-metastatic disease, and men without a cancer history. METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) data linkage to identify men aged ≥ 65 years enrolled in Medicare Advantage (MA) plans. Prostate cancer survivors were diagnosed between 1988 and 2017 and completed MHOS surveys between 1998 and 2019. We analyzed data from 752 metastatic prostate cancer survivors (1040 survey records), 19,583 localized or regional prostate cancer survivors (non-metastatic; 30,121 survey records), and 784,305 men aged ≥ 65 years without a cancer history in the same SEER regions (1.15 million survey records). We used clustered linear regressions to compare HRQoL measures at the person-level using the Veterans RAND 12 Item Health Survey (VR-12) T-scores for general health and physical and mental component summaries. RESULTS: Compared to men without a cancer history, prostate cancer survivors were older, more likely to be married, and had higher socioeconomic status. Compared to men without a cancer history, metastatic prostate cancer survivors reported lower general health (T-score differences [95% confidence interval]: - 6.26, [- 7.14, - 5.38], p < .001), physical health (- 4.33, [- 5.18, - 3.48], p < .001), and mental health (- 2.64, [- 3.40, - 1.88], p < .001) component summaries. Results were similar for other VR-12 T-scores. In contrast, non-metastatic prostate cancer survivors reported similar VR-12 T-scores as men without a cancer history. Further analyses comparing metastatic and non-metastatic prostate cancer survivors support these findings. CONCLUSION: Interventions to improve health-related quality of life for men diagnosed with metastatic prostate cancer merit additional investigation. IMPLICATIONS FOR CANCER SURVIVORS: Interventions to improve health-related quality of life for metastatic prostate cancer survivors merit additional investigation. |
Progress toward measles and rubella elimination - Indonesia, 2013-2022
Chacko S , Kamal M , Hastuti EB , Mildya F , Kelyombar C , Voronika V , Yosephine P , Tandy G , Anisiska D , Karolina S , Dewi LA , Khanal S , Bahl S , Wijayanti F , Merrill RD , Hsu CH , Morales M . MMWR Morb Mortal Wkly Rep 2023 72 (42) 1134-1139 In 2019, Indonesia and the other countries in the World Health Organization South-East Asia Region adopted the goal of measles and rubella elimination by 2023. This report describes Indonesia's progress toward measles and rubella elimination during 2013-2022. During this period, coverage with a first dose of measles-containing vaccine (MCV) decreased from 87% to 84%, and coverage with a second MCV dose decreased from 76% to 67%. After rubella vaccine was introduced in 2017, coverage with the first dose of rubella-containing vaccine increased approximately fivefold, from 15% in 2017 to 84% in 2022. During 2013-2021, annual reported measles incidence decreased by 95%, from 33.2 to 1.4 cases per million population; reported rubella incidence decreased 89%, from 9.3 to 1.0 cases per million population. However, a large surge in measles and rubella cases occurred in 2022, with a reported measles incidence of 29 cases per million and a reported rubella incidence of 3 per million, primarily related to disruption in immunization services caused by the COVID-19 pandemic. In 2022, approximately 26 million children (an estimated 73% of the target population) received a combined measles- and rubella-containing vaccine during supplementary immunization activities completed in 32 provinces. Progress toward measles and rubella elimination in Indonesia has been made; however, continued and urgent efforts are needed to restore routine immunization services that were adversely affected by the COVID-19 pandemic and close immunity gaps to accelerate progress toward measles and rubella elimination. |
Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period
Sternberg MR , Johnson A , King J , Ali AR , Linde L , Awofeso AO , Baker JS , Bayoumi NS , Broadway S , Busen K , Chang C , Cheng I , Cima M , Collingwood A , Dorabawila V , Drenzek C , Fleischauer A , Gent A , Hartley A , Hicks L , Hoskins M , Jara A , Jones A , Khan SI , Kamal-Ahmed I , Kangas S , Kanishka F , Kleppinger A , Kocharian A , León TM , Link-Gelles R , Lyons BC , Masarik J , May A , McCormick D , Meyer S , Milroy L , Morris KJ , Nelson L , Omoike E , Patel K , Pietrowski M , Pike MA , Pilishvili T , Peterson Pompa X , Powell C , Praetorius K , Rosenberg E , Schiller A , Smith-Coronado ML , Stanislawski E , Strand K , Tilakaratne BP , Vest H , Wiedeman C , Zaldivar A , Silk B , Scobie HM . PLoS One 2023 18 (9) e0291678 ![]() BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future. |
Quail rearing practices and potential for avian influenza virus transmission, Bangladesh
Hasan SMM , Sturm-Ramirez K , Kamal AM , Islam MA , Rahman M , Kile JC , Kennedy ED , Gurley ES , Islam MS . Ecohealth 2023 20 (2) 167-177 In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission. |
Characteristics of Nursing Home Residents and Healthcare Personnel with Repeat Positive SARS-CoV-2 Tests ≥ 90 Days After Initial Infection: 4 U.S. Jurisdictions, July 2020 - March 2021.
Wilson WW , Hatfield KM , Tressler S , BickingKinsey C , Parra G , Zell R , Denson A , Williams C , Spicer KB , Kamal-Ahmed I , Abdalhamid B , Gemechu M , Folster J , Thornburg NJ , Tamin A , Harcourt JL , Queen K , Tong S , Jernigan JA , Crist M , Perkins KM , Reddy SC . Infect Control Hosp Epidemiol 2023 44 (5) 809-812 One in six nursing home residents and staff with positive SARS-CoV-2 tests 90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data. |
Outbreaks of SARS-CoV-2 infections in nursing homes during periods of Delta and Omicron predominance, United States, July 2021-March 2022
Wilson WW , Keaton AA , Ochoa LG , Hatfield KM , Gable P , Walblay KA , Teran RA , Shea M , Khan U , Stringer G , Ganesan M , Gilbert J , Colletti JG , Grogan EM , Calabrese C , Hennenfent A , Perlmutter R , Janiszewski KA , Brandeburg C , Kamal-Ahmed I , Strand K , Donahue M , Ashraf MS , Berns E , MacFarquhar J , Linder ML , Tran DJ , Kopp P , Walker RM , Ess R , Baggs J , Jernigan JA , Kallen A , Hunter JC . Emerg Infect Dis 2023 29 (4) 761-770 ![]() SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents. |
Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreaks in nursing homes involving residents who had completed a primary coronavirus disease 2019 (COVID-19) vaccine series-13 US jurisdictions, July-November 2021.
Wyatt Wilson W , Keaton AA , Ochoa LG , Hatfield KM , Gable P , Walblay KA , Teran RA , Shea M , Khan U , Stringer G , Colletti JG , Grogan EM , Calabrese C , Hennenfent A , Perlmutter R , Janiszewski KA , Kamal-Ahmed I , Strand K , Berns E , MacFarquhar J , Linder M , Tran DJ , Kopp P , Walker RM , Ess R , Read JS , Yingst C , Baggs J , Jernigan JA , Kallen A , Hunter JC . Infect Control Hosp Epidemiol 2023 44 (6) 1-5 ![]() Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents. |
Covid-19 Rates by Time since Vaccination during Delta Variant Predominance
Paz-Bailey G , Sternberg M , Kugeler K , Hoots B , Amin AB , Johnson AG , Barbeau B , Bayoumi NS , Bertolino D , Boulton R , Brown CM , Busen K , Cima M , Drenzek C , Gent A , Haney G , Hicks L , Hook S , Jara A , Jones A , Kamal-Ahmed I , Kangas S , Kanishka FNU , Khan SI , Kirkendall SK , Kocharian A , Lyons BC , Lauro P , McCormick D , McMullen C , Milroy L , Reese HE , Sell J , Sierocki A , Smith E , Sosin D , Stanislawski E , Strand K , Troelstrup T , Turner KA , Vest H , Warner S , Wiedeman C , Silk B , Scobie HM . NEJM Evid 2022 1 (3) BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.). |
The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis
Walker TM , Fowler PW , Knaggs J , Hunt M , Peto TE , Walker AS , Crook DW , Walker TM , Miotto P , Cirillo DM , Kser CU , Knaggs J , Iqbal Z , Hunt M , Chindelevitch L , Farhat MR , Comas I , Comas I , Posey J , Omar SV , Peto TE , Walker AS , Crook DW , Suresh A , Uplekar S , Laurent S , Colman RE , Rodwell TC , Nathanson CM , Zignol M , Ismail N , Rodwell TC , Walker AS , Steyn AJC , Lalvani A , Baulard A , Christoffels A , Mendoza-Ticona A , Trovato A , Skrahina A , Lachapelle AS , Brankin A , Piatek A , GibertoniCruz A , Koch A , Cabibbe AM , Spitaleri A , Brandao AP , Chaiprasert A , Suresh A , Barbova A , VanRie A , Ghodousi A , Bainomugisa A , Mandal A , Roohi A , Javid B , Zhu B , Letcher B , Rodrigues C , Nimmo C , Nathanson CM , Duncan C , Coulter C , Utpatel C , Liu C , Grazian C , Kong C , Kser CU , Wilson DJ , Cirillo DM , Matias D , Jorgensen D , Zimenkov D , Chetty D , Moore DA , Clifton DA , Crook DW , vanSoolingen D , Liu D , Kohlerschmidt D , Barreira D , Ngcamu D , SantosLazaro ED , Kelly E , Borroni E , Roycroft E , Andre E , Bttger EC , Robinson E , Menardo F , Mendes FF , Jamieson FB , Coll F , Gao GF , Kasule GW , Rossolini GM , Rodger G , Smith EG , Meintjes G , Thwaites G , Hoffmann H , Albert H , Cox H , Laurenson IF , Comas I , Arandjelovic I , Barilar I , Robledo J , Millard J , Johnston J , Posey J , Andrews JR , Knaggs J , Gardy J , Guthrie J , Taylor J , Werngren J , Metcalfe J , Coronel J , Shea J , Carter J , Pinhata JM , Kus JV , Todt K , Holt K , Nilgiriwala KS , Ghisi KT , Malone KM , Faksri K , Musser KA , Joseph L , Rigouts L , Chindelevitch L , Jarrett L , Grandjean L , Ferrazoli L , Rodrigues M , Farhat M , Schito M , Fitzgibbon MM , Loemb MM , Wijkander M , Ballif M , Rabodoarivelo MS , Mihalic M , Wilcox M , Hunt M , Zignol M , Merker M , Egger M , O'Donnell M , Caws M , Wu MH , Whitfield MG , Inouye M , Mansj M , DangThi MH , Joloba M , Kamal SM , Okozi N , Ismail N , Mistry N , Hoang NN , Rakotosamimanana N , Paton NI , Rancoita PMV , Miotto P , Lapierre P , Hall PJ , Tang P , Claxton P , Wintringer P , Keller PM , Thai PVK , Fowler PW , Supply P , Srilohasin P , Suriyaphol P , Rathod P , Kambli P , Groenheit R , Colman RE , Ong RTH , Warren RM , Wilkinson RJ , Diel R , Oliveira RS , Khot R , Jou R , Tahseen S , Laurent S , Gharbia S , Kouchaki S , Shah S , Plesnik S , Earle SG , Dunstan S , Hoosdally SJ , Mitarai S , Gagneux S , Omar SV , Yao SY , GrandjeanLapierre S , Battaglia S , Niemann S , Pandey S , Uplekar S , Halse TA , Cohen T , Cortes T , Prammananan T , Kohl TA , Thuong NTT , Teo TY , Peto TEA , Rodwell TC , William T , Walker TM , Rogers TR , Surve U , Mathys V , Furi V , Cook V , Vijay S , Escuyer V , Dreyer V , Sintchenko V , Saphonn V , Solano W , Lin WH , vanGemert W , He W , Yang Y , Zhao Y , Qin Y , Xiao YX , Hasan Z , Iqbal Z , Puyen ZM , CryPticConsortium theSeq , Treat Consortium . Lancet Microbe 2022 3 (4) e265-e273 Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome.
Alymova IV , Cipollo JF , Parsons LM , Music N , Kamal RP , Tzeng WP , Goldsmith CS , Contessa JN , Hartshorn KL , Wilson JR , Zeng H , Gansebom S , York IA . mBio 2022 13 (2) e0298321 ![]() Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. |
COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.
Johnson AG , Amin AB , Ali AR , Hoots B , Cadwell BL , Arora S , Avoundjian T , Awofeso AO , Barnes J , Bayoumi NS , Busen K , Chang C , Cima M , Crockett M , Cronquist A , Davidson S , Davis E , Delgadillo J , Dorabawila V , Drenzek C , Eisenstein L , Fast HE , Gent A , Hand J , Hoefer D , Holtzman C , Jara A , Jones A , Kamal-Ahmed I , Kangas S , Kanishka F , Kaur R , Khan S , King J , Kirkendall S , Klioueva A , Kocharian A , Kwon FY , Logan J , Lyons BC , Lyons S , May A , McCormick D , Mendoza E , Milroy L , O'Donnell A , Pike M , Pogosjans S , Saupe A , Sell J , Smith E , Sosin DM , Stanislawski E , Steele MK , Stephenson M , Stout A , Strand K , Tilakaratne BP , Turner K , Vest H , Warner S , Wiedeman C , Zaldivar A , Silk BJ , Scobie HM . MMWR Morb Mortal Wkly Rep 2022 71 (4) 132-138 Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status() indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended() additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged 18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),() case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and 65 years. Eligible persons should stay up to date with COVID-19 vaccinations. |
Multiple Variants of SARS-CoV-2 in a University Outbreak After Spring Break - Chicago, Illinois, March-May 2021.
Doyle K , Teran RA , Reefhuis J , Kerins JL , Qiu X , Green SJ , Choi H , Madni SA , Kamal N , Landon E , Albert RC , Pacilli M , Furtado LE , Hayden MK , Kunstman KJ , Bethel C , Megger L , Fricchione MJ , Ghinai I . MMWR Morb Mortal Wkly Rep 2021 70 (35) 1195-1200 ![]() ![]() To prevent transmission of SARS-CoV-2, the virus that causes COVID-19, colleges and universities have implemented multiple strategies including testing, isolation, quarantine, contact tracing, masking, and vaccination. In April 2021, the Chicago Department of Public Health (CDPH) was notified of a large cluster of students with COVID-19 at an urban university after spring break. A total of 158 cases of COVID-19 were diagnosed among undergraduate students during March 15-May 3, 2021; the majority (114; 72.2%) lived in on-campus dormitories. CDPH evaluated the role of travel and social connections, as well as the potential impact of SARS-CoV-2 variants, on transmission. Among 140 infected students who were interviewed, 89 (63.6%) reported recent travel outside Chicago during spring break, and 57 (40.7%) reported indoor social exposures. At the time of the outbreak, undergraduate-aged persons were largely ineligible for vaccination in Chicago; only three of the students with COVID-19 (1.9%) were fully vaccinated. Whole genome sequencing (WGS) of 104 specimens revealed multiple distinct SARS-CoV-2 lineages, suggesting several nearly simultaneous introductions. Most specimens (66; 63.5%) were B.1.1.222, a lineage not widely detected in Chicago before or after this outbreak. These results demonstrate the potential for COVID-19 outbreaks on university campuses after widespread student travel during breaks, at the beginning of new school terms, and when students participate in indoor social gatherings. To prevent SARS-CoV-2 transmission, colleges and universities should encourage COVID-19 vaccination; discourage unvaccinated students from travel, including during university breaks; implement serial COVID-19 screening among unvaccinated persons after university breaks; encourage masking; and implement universal serial testing for students based on community transmission levels. |
Effects of Patient Characteristics on Diagnostic Performance of Self-Collected Samples for SARS-CoV-2 Testing.
Smith-Jeffcoat SE , Koh M , Hoffman A , Rebolledo PA , Schechter MC , Miller HK , Sleweon S , Rossetti R , Kasinathan V , Shragai T , O'Laughlin K , Espinosa CC , Khalil GM , Adeyemo AO , Moorman A , Bauman BL , Joseph K , O'Hegarty M , Kamal N , Atallah H , Moore BL , Bohannon CD , Bankamp B , Hartloge C , Bowen MD , Paulick A , Gargis AS , Elkins C , Stewart RJ , da Silva J , Biedron C , Tate JE , Wang YF , Kirking HL . Emerg Infect Dis 2021 27 (8) 2081-2089 We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2. |
Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization.
Patel MK , Bergeri I , Bresee JS , Cowling BJ , Crowcroft NS , Fahmy K , Hirve S , Kang G , Katz MA , Lanata CF , L'Azou Jackson M , Joshi S , Lipsitch M , Mwenda JM , Nogareda F , Orenstein WA , Ortiz JR , Pebody R , Schrag SJ , Smith PG , Srikantiah P , Subissi L , Valenciano M , Vaughn DW , Verani JR , Wilder-Smith A , Feikin DR . Vaccine 2021 39 (30) 4013-4024 ![]() Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results. |
The COVID-19 Pandemic: Effects on Civil Registration of Births and Deaths and on Availability and Utility of Vital Events Data.
AbouZahr C , Bratschi MW , Cercone E , Mangharam A , Savigny D , Dincu I , Forsingdal AB , Joos O , Kamal M , Fat DM , Mathenge G , Marinho F , Mitra RG , Montgomery J , Muhwava W , Mwamba R , Mwanza J , Onaka A , Sejersen TB , Tuoane-Nkhasi M , Sferrazza L , Setel P . Am J Public Health 2021 111 (6) e1-e9 The complex and evolving picture of COVID-19-related mortality highlights the need for data to guide the response. Yet many countries are struggling to maintain their data systems, including the civil registration system, which is the foundation for detailed and continuously available mortality statistics. We conducted a search of country and development agency Web sites and partner and media reports describing disruptions to the civil registration of births and deaths associated with COVID-19 related restrictions.We found considerable intercountry variation and grouped countries according to the level of disruption to birth and particularly death registration. Only a minority of the 66 countries were able to maintain service continuity during the COVID-19 restrictions. In the majority, a combination of legal and operational challenges resulted in declines in birth and death registration. Few countries established business continuity plans or developed strategies to deal with the backlog when restrictions are lifted.Civil registration systems and the vital statistics they generate must be strengthened as essential services during health emergencies and as core components of the response to COVID-19. (Am J Public Health. Published online ahead of print April 15, 2021: e1-e9. https://doi.org/10.2105/AJPH.2021.306203). |
Zika virus detection in amniotic fluid and Zika-associated birth defects
Reyes MM , Ailes EC , Daza M , Tong VT , Osorio J , Valencia D , Turca AR , Galang RR , Gonzalez Duarte M , Ricaldi JN , Anderson KN , Kamal N , Thomas JD , Villanueva J , Burkel VK , Meaney-Delman D , Gilboa SM , Honein MA , Jamieson DJ , Martinez MO . Am J Obstet Gynecol 2020 222 (6) 610 e1-610 e13 BACKGROUND: Zika virus (ZIKV) infection during pregnancy can cause serious birth defects, including brain and eye abnormalities. The clinical importance of detection of ZIKV ribonucleic acid (RNA) in amniotic fluid is unknown. OBJECTIVES: To describe patterns of ZIKV RNA testing of amniotic fluid relative to other clinical specimens and to examine the association between ZIKV detection in amniotic fluid and Zika-associated birth defects. Our null hypothesis was that ZIKV detection in amniotic fluid was not associated with Zika-associated birth defects. STUDY DESIGN: We conducted a retrospective cohort analysis of women with amniotic fluid specimens submitted to Colombia's National Institute of Health as part of national ZIKV surveillance from January 2016 to January 2017. Specimens (maternal serum, amniotic fluid, cord blood, umbilical cord tissue, and placental tissue) were tested for the presence of ZIKV RNA using a singleplex or multiplex real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay. Birth defect information was abstracted from maternal prenatal and infant birth records and reviewed by expert clinicians. Chi-square and Fisher's exact tests were used to compare the frequency of Zika-associated birth defects (defined as brain abnormalities [with or without microcephaly, but excluding neural tube defects and their associated findings] or eye abnormalities) by frequency of detection of ZIKV RNA in amniotic fluid. RESULTS: Our analysis included 128 women with amniotic fluid specimens. Seventy-five women (58%) had prenatally-collected amniotic fluid, 42 (33%) at delivery, and 11 (9%) had missing collection dates. Ninety-one women had both amniotic fluid and other clinical specimens submitted for testing, allowing for comparison across specimen types. Of those 91 women, 68 had evidence of ZIKV infection based on detection of ZIKV RNA (ZIKV+) in >1 specimen. Testing of amniotic fluid collected prenatally or at delivery identified 39 (57%) of these ZIKV infections (15 [22%] identified only in amniotic fluid), and 29 (43%) infections were identified in other specimen types and not amniotic fluid. Among women included in the analysis, 89 had pregnancy outcome information available, allowing for assessment of the presence of Zika-associated birth defects. Zika-associated birth defects were significantly (p<0.05) more common among pregnancies with ZIKV+ amniotic fluid specimens collected prenatally (19/32, 59%) than for those with no laboratory evidence of ZIKV infection in any specimen (6/23, 26%), but the proportion was similar in pregnancies with only ZIKV+ specimens other than amniotic fluid (10/23, 43%). Though Zika-associated birth defects were more common among women with any ZIKV+ amniotic fluid specimen (i.e., collected prenatally or at delivery; 21/43, 49%) than those with no laboratory evidence of ZIKV infection (6/23, 26%), this comparison did not reach statistical significance (p=0.07). CONCLUSIONS: Testing of amniotic fluid provided additional evidence for maternal diagnosis of ZIKV infection. Zika-associated birth defects were more common among women with ZIKV RNA detected in prenatal amniotic fluid specimens than women with no laboratory evidence of ZIKV infection, but similar to women with ZIKV RNA detected in other, non-amniotic fluid specimen types. |
Pathology and telepathology methods in the Child Health and Mortality Prevention Surveillance Network
Martines RB , Ritter JM , Gary J , Shieh WJ , Ordi J , Hale M , Carrilho C , Ismail M , Traore CB , Ndibile BE , Sava S , Arjuman F , Kamal M , Rahman MM , Blau DM , Zaki SR . Clin Infect Dis 2019 69 S322-s332 This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations. |
Both immune priming and egg-adaptation in the vaccine influence antibody responses to circulating A(H1N1)pdm09 viruses following influenza vaccination in adults
Liu F , Tzeng WP , Horner L , Kamal RP , Tatum HR , Blanchard EG , Xu X , York I , Tumpey TM , Katz JM , Lu X , Levine MZ . J Infect Dis 2018 218 (10) 1571-1581 Background: Although ferret antisera used in influenza surveillance did not detect antigenic drift of A(H1N1)pdm09 viruses during 2015-16 season, low vaccine effectiveness was reported in adults. We investigated the immune basis of low responses to circulating A(H1N1)pdm09 viruses following vaccination. Methods: Over 300 paired adult (18-49 yrs) pre and post-vaccination sera collected in 6 seasons (2010-11 to 2015-16) were analyzed by hemagglutination inhibition assays to evaluate the antibody responses to thirteen A(H1N1) viruses circulated from 1977 to 2016. Microneutralization and serum adsorption assays were used to verify 163K- and 223R-specificity of antibodies. Results: Individual antibody profiles to A(H1N1) viruses revealed three priming patterns: USSR/77-, TW/86- or NC/99-priming. Over 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared to the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was only observed in USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts. Conclusion: Both 163K-specificity driven by immune priming and 223R-specificity from egg-adapted changes in the vaccine contributed to low responses to circulating A(H1N1)pdm09 viruses following vaccination. Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection. |
Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
Alymova IV , McCullers JA , Kamal RP , Vogel P , Green AM , Gansebom S , York IA . Sci Rep 2018 8 (1) 7474 Specific residues of influenza A virus (IAV) PB1-F2 proteins may enhance inflammation or cytotoxicity. In a series of studies, we evaluated the function of these virulence-associated residues in the context of different IAV subtypes in mice. Here, we demonstrate that, as with the previously assessed pandemic 1968 (H3N2) IAV, PB1-F2 inflammatory residues increase the virulence of H1N1 IAV, suggesting that this effect might be a universal feature. Combining both inflammatory and cytotoxic residues in PB1-F2 enhanced virulence further, compared to either motif alone. Residues from these virulent motifs have been present in natural isolates from human seasonal IAV of all subtypes, but there has been a trend toward a gradual reduction in the number of virulent residues over time. However, human IAV of swine and avian origin tend to have more virulent residues than do the human-adapted seasonal strains, raising the possibility that donation of PB1 segments from these zoonotic viruses may increase the severity of some seasonal human strains. Our data suggest the value of surveillance of virulent residues in both human and animal IAV to predict the severity of influenza season. |
Evolution and Virulence of Influenza A Virus Protein PB1-F2.
Kamal RP , Alymova IV , York IA . Int J Mol Sci 2017 19 (1) ![]() PB1-F2 is an accessory protein of most human, avian, swine, equine, and canine influenza A viruses (IAVs). Although it is dispensable for virus replication and growth, it plays significant roles in pathogenesis by interfering with the host innate immune response, inducing death in immune and epithelial cells, altering inflammatory responses, and promoting secondary bacterial pneumonia. The effects of PB1-F2 differ between virus strains and host species. This can at least partially be explained by the presence of multiple PB1-F2 sequence variants, including premature stop codons that lead to the expression of truncated PB1-F2 proteins of different lengths and specific virulence-associated residues that enhance susceptibility to bacterial superinfection. Although there has been a tendency for human seasonal IAV to gradually reduce the number of virulence-associated residues, zoonotic IAVs contain a reservoir of PB1-F2 proteins with full length, virulence-associated sequences. Here, we review the molecular mechanisms by which PB1-F2 may affect influenza virulence, and factors associated with the evolution and selection of this protein. |
Structural and immunochemical relatedness suggests a conserved pathogenicity motif for secondary cell wall polysaccharides in Bacillus anthracis and infection-associated Bacillus cereus
Kamal N , Ganguly J , Saile E , Klee SR , Hoffmaster A , Carlson RW , Forsberg LS , Kannenberg EL , Quinn CP . PLoS One 2017 12 (8) e0183115 Bacillus anthracis (Ba) and human infection-associated Bacillus cereus (Bc) strains Bc G9241 and Bc 03BB87 have secondary cell wall polysaccharides (SCWPs) comprising an aminoglycosyl trisaccharide repeat: -->4)-beta-d-ManpNAc-(1-->4)-beta-d-GlcpNAc-(1-->6)-alpha-d-GlcpNAc-(1-->, substituted at GlcNAc residues with both alpha- and beta-Galp. In Bc G9241 and Bc 03BB87, an additional alpha-Galp is attached to O-3 of ManNAc. Using NMR spectroscopy, mass spectrometry and immunochemical methods, we compared these structures to SCWPs from Bc biovar anthracis strains isolated from great apes displaying "anthrax-like" symptoms in Cameroon (Bc CA) and Cote d'Ivoire (Bc CI). The SCWPs of Bc CA/CI contained the identical HexNAc trisaccharide backbone and Gal modifications found in Ba, together with the alpha-Gal-(1-->3) substitution observed previously at ManNAc residues only in Bc G9241/03BB87. Interestingly, the great ape derived strains displayed a unique alpha-Gal-(1-->3)-alpha-Gal-(1-->3) disaccharide substitution at some ManNAc residues, a modification not found in any previously examined Ba or Bc strain. Immuno-analysis with specific polyclonal anti-Ba SCWP antiserum demonstrated a reactivity hierarchy: high reactivity with SCWPs from Ba 7702 and Ba Sterne 34F2, and Bc G9241 and Bc 03BB87; intermediate reactivity with SCWPs from Bc CI/CA; and low reactivity with the SCWPs from structurally distinct Ba CDC684 (a unique strain producing an SCWP lacking all Gal substitutions) and non-infection-associated Bc ATCC10987 and Bc 14579 SCWPs. Ba-specific monoclonal antibody EAII-6G6-2-3 demonstrated a 10-20 fold reduced reactivity to Bc G9241 and Bc 03BB87 SCWPs compared to Ba 7702/34F2, and low/undetectable reactivity to SCWPs from Bc CI, Bc CA, Ba CDC684, and non-infection-associated Bc strains. Our data indicate that the HexNAc motif is conserved among infection-associated Ba and Bc isolates (regardless of human or great ape origin), and that the number, positions and structures of Gal substitutions confer unique antigenic properties. The conservation of this structural motif could open a new diagnostic route in detection of pathogenic Bc strains. |
Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies
Kamal RP , Blanchfield K , Belser JA , Music N , Tzeng WP , Holiday C , Burroughs A , Sun X , Maines TR , Levine MZ , York IA . J Virol 2017 91 (20) Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutinin inhibition (HI) and micro-neutralization (MN) assays, H7 viruses and vaccines induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate pre-pandemic vaccines. We have previously shown that purified recombinant H7 hemagglutinin (HA) appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. Here, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and NA from 3 different H7 viruses [A/Shanghai/2/2013 (H7N9), A/Netherlands/219/2003 (H7N7) and A/New York/107/2003 (H7N2)], or with human A(H1N1)pdm09 [A/California/07/2009-like] or A(H3N2) [A/Perth16/2009] viruses. Mice produced equivalent titers of antibodies to all viruses as measured by ELISA. However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for pre-pandemic vaccines.IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of pre-pandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody titers measured by hemagglutination inhibition (HI) and virus microneutralization (MN) assays. Since H7 vaccines typically induce low HI and MN titers, they have been considered to be poorly immunogenic. We show that in mice H7 whole inactivated virus (WIV) vaccines were as immunogenic as seasonal WIVs, as they induced similar levels of overall serum antibodies. However, a larger fraction of the antibodies induced by H7 WIV was non-neutralizing in vitro. Nevertheless, the H7 WIV completely protected mice against homologous viral challenge, and antibodies directed against the HA-head were the major contributor toward immune protection. Vaccines against H7 avian influenza viruses may be more effective than HI and virus neutralization assays suggest, and such vaccines may need other methods for evaluation. |
An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo
Wilson JR , Guo Z , Reber A , Kamal RP , Music N , Gansebom S , Bai Y , Levine M , Carney P , Tzeng WP , Stevens J , York IA . Antiviral Res 2016 135 48-55 Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. Treatment options for people infected with A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other influenza viruses, A(H7N9) can become resistant to these drugs. The use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed against the NA of A(H7N9) and show that prophylactic systemic administration of 3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013 (H7N9). Further, post-infection treatment with a single systemic dose of 3c10-3 at either 24, 48 or 72 h post A(H7N9) challenge resulted in both dose- and time-dependent protection of up to 100% of mice, demonstrating therapeutic potential for 3c10-3. Epitope mapping revealed that 3c10-3 binds near the enzyme active site of NA, and functional characterization showed that 3c10-3 inhibits the enzyme activity of NA and restricts the cell-to-cell spread of the virus in cultured cells. Affinity analysis also revealed that 3c10-3 binds equally well to recombinant NA of wild-type A/Anhui/1/2013 and to a variant NA carrying a R289K mutation known to infer NAI resistance. These results suggest that 3c10-3 has the potential to be used as a therapeutic to treat A(H7N9) infections either as an alternative to, or in combination with, current NA antiviral inhibitors. |
A Novel Rapidly Growing Mycobacterium Species Causing an Abdominal Cerebrospinal Fluid Pseudocyst Infection.
Hussain CK , de Man TJ , Toney NC , Kamboj K , Balada-Llasat JM , Wang SH . Open Forum Infect Dis 2016 3 (3) ofw146 ![]() Nontuberculous mycobacteria (NTM) are a rare cause of ventriculoperitoneal shunt infections. We describe the isolation and identification of a novel, rapidly growing, nonpigmented NTM from an abdominal cerebrospinal fluid pseudocyst. The patient presented with fevers, nausea, and abdominal pain and clinically improved after shunt removal. NTM identification was performed by amplicon and whole-genome sequencing. |
RIG-I ligand enhances the immunogenicity of recombinant H7HA protein
Cao W , Liepkalns JS , Kamal RP , Reber AJ , Kim JH , Hofstetter AR , Amoah S , Stevens J , Ranjan P , Gangappa S , York IA , Sambhara S . Cell Immunol 2016 304-305 55-8 Avian H7N9 influenza virus infection with fatal outcomes continues to pose a pandemic threat and highly immunogenic vaccines are urgently needed. In this report we show that baculovirus-derived recombinant H7 hemagglutinin protein, when delivered with RIG-I ligand, induced enhanced antibody and T cell responses and conferred protection against lethal challenge with a homologous H7N9 virus. These findings indicate the potential utility of RIG-I ligands as vaccine adjuvants to increase the immunogenicity of recombinant H7 hemagglutinin. |
A highly immunogenic vaccine against A(H7N9) influenza virus
Cao W , Liepkalns J , Hassan AO , Kamal R , Hofstetter AR , Amoah S , Kim JH , Reber A , Stevens J , Katz JM , Gangappa S , York I , Mittal SK , Sambhara S . Vaccine 2016 34 (6) 744-9 Since the first case of human infection in March 2013, continued reports of H7N9 cases highlight a potential pandemic threat. Highly immunogenic vaccines to this virus are urgently needed to protect vulnerable populations who lack protective immunity. In this study, an egg- and adjuvant-independent adenoviral vector-based, hemagglutinin H7 subtype influenza vaccine (HAd-H7HA) demonstrated enhanced cell-mediated immunity as well as serum antibody responses in a mouse model. Most importantly, this vaccine provided complete protection against homologous A/(H7N9) viral challenge suggesting its potential utility as a pandemic vaccine. |
Qualitative interviews with non-national tuberculosis patients in Cairo, Egypt: understanding the financial and social cost of treatment adherence
Lohiniva AL , Mokhtar A , Azer A , Elmoghazy E , Kamal E , Benkirane M , Dueger E . Health Soc Care Community 2015 24 (6) e164-e172 Limited data are available about the challenges of non-national TB patients undergoing long-term treatment courses in an urban setting. This study aimed to understand the financial and social cost of adherence of non-national TB patients in Cairo, Egypt as a means to inform the development of context-specific interventions to support treatment adherence. In 2011, 22 in-depth interviews were conducted with TB patients from Sudan, Ethiopia, Eritrea, Somalia and Djibouti to obtain qualitative data. Analysis was based on thematic analysis that aimed to identify recurrent themes and codes from the narratives. The study identified a number of factors that influence TB treatment adherence. Uncertain financial status due to limited or no employment was frequently discussed in interviews, which resulted in fear of not being able to support family, loss of pride, dependence on family and friends, fear of losing housing, food insecurity and limited food options. Respondents also feared infecting other household members and longed for opportunities to discuss their illness and treatment experiences with other individuals but their social networks were often limited. TB-related stigma was driven by shame and blame of infection. Respondents also believed stigma was based on their foreign origin. Stigma manifested in distancing and exclusion in various ways, resulting in isolation, psychological distress and reluctance to disclose TB status to others. Poverty-related factors and social context with a special focus on stigma should be considered when developing strategies for supporting long-term treatment courses for non-national patients in Cairo and other similar urban settings. |
Emergence of Highly Pathogenic Avian Influenza A(H5N1) Virus PB1-F2 Variants and Their Virulence in BALB/c Mice.
Kamal RP , Kumar A , Davis CT , Tzeng WP , Nguyen T , Donis RO , Katz JM , York IA . J Virol 2015 89 (11) 5835-46 ![]() Influenza A viruses (IAV) express the PB1-F2 protein from an alternate reading frame within the PB1 gene segment. The roles of PB1-F2 are not well understood, but appear to involve modulation of host cell responses. As shown in previous studies, we find that PB1-F2 of mammalian IAV frequently have premature stop codons that are expected to cause truncations of the protein, whereas avian IAV usually express a full-length 90 amino acid PB1-F2. However, in contrast to other avian IAV, recent isolates of highly pathogenic H5N1 influenza viruses had a high proportion of PB1-F2 truncations (15% since 2010; 61% of isolates in 2013) due to several independent mutations that have persisted and expanded in circulating viruses. One natural H5N1 IAV containing a mutated PB1-F2 start codon (i.e., lacking ATG) was 1000-fold more virulent for BALB/c mice than a closely-related H5N1 containing intact PB1-F2. In vitro, we detected expression of an in-frame protein (C-terminal PB1-F2) from downstream ATGs in PB1-F2 plasmids lacking the well-conserved ATG start codon. Transient expression of full-length, truncated (25 amino acids), and PB1-F2 lacking the initiating ATG in mammalian and avian cells had no effect on cell apoptosis or interferon expression in human lung epithelial cells. Full length and C-terminal PB1-F2 mutants co-localized with mitochondria in A549 cells. Close monitoring of alterations of PB1-F2 and their frequency in contemporary avian H5N1 viruses should continue, as such changes may be markers for mammalian virulence. IMPORTANCE: Although most avian influenza viruses are harmless for humans, some (such as highly pathogenic H5N1 avian influenza viruses) are capable of infecting humans and causing severe disease with a high mortality rate. A number of risk factors potentially associated with adaptation to mammalian infection have been noted. Here we demonstrate that the protein PB1-F2 is frequently truncated in recent isolates of highly pathogenic H5N1 viruses. Truncation of PB1-F2 has been proposed to act as an adaptation to mammalian infection. We show that some forms of truncation of PB1-F2 may be associated with increased virulence in mammals. Our data support the assessment of PB1-F2 truncations for genomic surveillance of influenza viruses. |
Recombinant influenza H7 hemagglutinins induce lower neutralizing antibody titers in mice than do seasonal hemagglutinins
Blanchfield K , Kamal RP , Tzeng WP , Music N , Wilson JR , Stevens J , Lipatov AS , Katz JM , York IA . Influenza Other Respir Viruses 2014 8 (6) 628-35 BACKGROUND: Vaccines against avian influenza viruses often require high hemagglutinin (HA) doses or adjuvants to achieve serological titers associated with protection against disease. In particular, viruses of the H7 subtype frequently do not induce strong antibody responses following immunization. OBJECTIVES: To evaluate whether poor immunogenicity of H7 viruses is an intrinsic property of the H7 hemagglutinin. METHODS: We compared the immunogenicity, in naive mice, of purified recombinant HA from two H7 viruses [A/Netherlands/219/2003(H7N7) and A/New York/107/2003(H7N2)] to that of HA from human pandemic [A/California/07/2009(H1N1pdm09)] and seasonal [A/Perth16/2009(H3N2)] viruses. RESULTS: After two intramuscular injections with purified hemagglutinin, mice produced antibodies to all HAs, but the response to the human virus HAs was greater than to H7 HAs. The difference was relatively minor when measured by ELISA, greater when measured by hemagglutination inhibition assays, and more marked still by microneutralization assays. H7 HAs induced little or no neutralizing antibody response in mice at either dose tested. Antibodies induced by H7 were of significantly lower avidity than for H3 or H1N1pdm09. CONCLUSIONS: We conclude that H7 HAs may be intrinsically less immunogenic than HA from seasonal human influenza viruses. |
Molecular determinants of influenza virus pathogenesis in mice.
Kamal RP , Katz JM , York IA . Curr Top Microbiol Immunol 2014 385 243-74 ![]() Mice are widely used for studying influenza virus pathogenesis and immunology because of their low cost, the wide availability of mouse-specific reagents, and the large number of mouse strains available, including knockout and transgenic strains. However, mice do not fully recapitulate the signs of influenza infection of humans: transmission of influenza between mice is much less efficient than in humans, and influenza viruses often require adaptation before they are able to efficiently replicate in mice. In the process of mouse adaptation, influenza viruses acquire mutations that enhance their ability to attach to mouse cells, replicate within the cells, and suppress immunity, among other functions. Many such mouse-adaptive mutations have been identified, covering all 8 genomic segments of the virus. Identification and analysis of these mutations have provided insight into the molecular determinants of influenza virulence and pathogenesis, not only in mice but also in humans and other species. In particular, several mouse-adaptive mutations of avian influenza viruses have proved to be general mammalian-adaptive changes that are potential markers of pre-pandemic viruses. As well as evaluating influenza pathogenesis, mice have also been used as models for evaluation of novel vaccines and anti-viral therapies. Mice can be a useful animal model for studying influenza biology as long as differences between human and mice infections are taken into account. |
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