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BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95%â¯CI:â¯5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95%â¯CI:â¯0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95%â¯CI:â¯17.8-42.5). Work during illness occurred in 92% (95%â¯CI:â¯91-93) of ARI episodes, absence from work in 38% (95%â¯CI:â¯36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.
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Absenteísmo , Pessoal de Saúde , Influenza Humana , Presenteísmo , Infecções por Vírus Respiratório Sincicial , Estações do Ano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/diagnóstico , Influenza Humana/prevenção & controle , Feminino , Incidência , Masculino , Pessoal de Saúde/estatística & dados numéricos , Israel/epidemiologia , Adulto , Presenteísmo/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/genética , Exposição Ocupacional/estatística & dados numéricos , Testes de Inibição da HemaglutinaçãoRESUMO
The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.
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Anticorpos Antivirais , Testes de Inibição da Hemaglutinação , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Vacinas de Produtos Inativados , Vacinas Sintéticas , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Adulto , Anticorpos Antivirais/sangue , Adulto Jovem , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Adolescente , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vírus da Influenza A Subtipo H3N2/imunologia , Wisconsin , Vacinação/métodos , Vírus da Influenza B/imunologia , Imunogenicidade da Vacina , Técnicas de Cultura de Células , Estados Unidos , Formação de Anticorpos/imunologia , Imunização Secundária/métodos , OvosRESUMO
Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.
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Anticorpos Antivirais , Reações Cruzadas , Vírus da Influenza A Subtipo H3N2 , Influenza Humana , Neuraminidase , Pandemias , Neuraminidase/imunologia , Neuraminidase/genética , Animais , Humanos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H3N2/imunologia , Feminino , Reações Cruzadas/imunologia , Camundongos , Influenza Humana/imunologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Idoso , Vírus da Influenza A Subtipo H2N2/imunologia , Vírus da Influenza A Subtipo H2N2/genética , Masculino , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Aves/virologia , Pessoa de Meia-Idade , Influenza Aviária/epidemiologia , Influenza Aviária/imunologia , Influenza Aviária/virologia , Vírus da Influenza A Subtipo H9N2/imunologia , Adulto , Proteínas Virais/imunologia , Proteínas Virais/genéticaRESUMO
Objective: To establish biological exposure index (BEI) of occupational exposure to arsenic and its inorganic compounds through occupational epidemiology and the regression analysis of internal and external exposure of workers. Methods: In November 2021, 125 workers with occupational exposure to arsenic and its inorganic compounds and 49 office administrators in a non-ferrous metal smelter in Yunnan Province were selected as the exposure group and control group, respectively. Air samples from the workplace of the study subjects on weekdays were collected and arsenic concentrations were determined. Urine samples were collected in end-of-work weekend and high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect the levels of trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , monomethyl arsenic (MMA) and dimethyl arsenic (DMA) in urine. The correlations between arsenic concentration in the workplace air and arsenic species in urine of workers were analyzed. Arsenic exposure concentration and the level of urinary arsenic (ΣiAs+MMA+DMA) of workers was analyzed by linear regression and the BEI of arsenic and its inorganic compounds in the workplace was proposed based on the results of micronucleus test. Results: The median of time-weighted average concentration (C(TWA)) of arsenic in the workplace air of the exposure group was 0.0116 mg/m(3), and the over-standard rate was 71.2% (89/125) . The concentrations of iAs(3+), iAs(5+), inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) ãMMAãDMA and urinary arsenic in the exposure group were higher than those in the control group at the end of shift, and the differences were statistically significant (P<0.05) . The concentration of arsenic in the workplace air had the strongest correlation with the concentration of urinary arsenic at the end of the shift (r(s)=0.909, P<0.001) . The regression equation was lg (y) =7.662+2.968lg (x) (r=0.821, P<0.05) . According to the occupational exposure limit (OEL) of arsenic in China, the concentration of urinary arsenic in the end-of-work weekend was calculated to be 53.2 µg/L. Combined with the results of micronucleus test, the BEI of occupational exposure to arsenic and its inorganic compounds in the workplace was proposed to be 50 µg/L. Conclusion: The urinary arsenic in the end-of-work weekend can be used as a biomarker of occupational exposure to arsenic, and its BEI is recommended to be 50 µg/L.
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Arsênio , Arsenicais , Exposição Ocupacional , Humanos , Arsênio/urina , China , Exposição Ocupacional/análiseRESUMO
Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.
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Arsênio , Arsenicais , Exposição Ocupacional , Humanos , Arsênio/urina , China , Arsenicais/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Biomarcadores TumoraisRESUMO
Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018-19 (N = 723) and 2019-20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Anticorpos Antivirais , Formação de Anticorpos , Técnicas de Cultura de Células , Epitopos , Testes de Inibição da Hemaglutinação , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/prevenção & controle , Vacinação , Vacinas de Produtos InativadosRESUMO
BACKGROUND: Preexisting immunity, including memory B cells and preexisting antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether preexisting hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163 antibodies) could affect antibody responses following vaccination with A/California/07/2009-like A(H1N1)pdm09 influenza viruses in humans. METHODS: Pre- and postvaccination sera collected from 300 adults (birth years, 1961-1998) in 6 seasons (2010-2016) were analyzed by HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the preexisting K163 antibody-mediated suppression effect. RESULTS: Preexisting K163 antibody titers ≥80 affected HAI antibody responses following influenza vaccination containing A/California/07/2009-like antigens. At high K163 antibody concentrations (HAI antibody titers ≥160), all HAI antibody responses were suppressed. However, at moderate K163 antibody concentrations (HAI antibody titer, 80), only K163 epitope-specific antibody responses were suppressed, and novel HAI antibody responses targeting the non-K163 epitopes were induced by vaccination. Novel antibodies targeting non-K163 epitopes cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation rather than historic 1977-2007 A(H1N1) viruses. CONCLUSIONS: K163 antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how preexisting antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adulto , Humanos , Imunidade Humoral , Anticorpos Antivirais , Vacinação , Testes de Inibição da Hemaglutinação , EpitoposRESUMO
Background: Uncertainty about risk of illness and the value of influenza vaccines negatively affects vaccine uptake among persons targeted for influenza vaccination. Methods: During 2016-2019, we followed a cohort of healthcare personnel (HCP) targeted for free-of-charge influenza vaccination in five Lima hospitals to quantify risk of influenza, workplace presenteeism (coming to work despite illness), and absenteeism (taking time off from work because of illness). The HCP who developed acute respiratory illnesses (ARI) (≥1 of acute cough, runny nose, body aches, or feverishness) were tested for influenza using reverse-transcription polymerase chain reaction (rt-PCR). Findings: The cohort (2968 HCP) contributed 950,888 person-days. Only 36 (6%) of 605 HCP who participated every year were vaccinated. The HCP had 5750 ARI and 147 rt-PCR-confirmed influenza illnesses. The weighted incidence of laboratory-confirmed influenza was 10.0/100 person-years; 37% used antibiotics, and 0.7% used antivirals to treat these illnesses. The HCP with laboratory-confirmed influenza were present at work while ill for a cumulative 1187 hours. Interpretation: HCP were frequently ill and often worked rather than stayed at home while ill. Our findings suggest the need for continuing medical education about the risk of influenza and benefits of vaccination and stay-at-home-while-ill policies.
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Vacinas contra Influenza , Influenza Humana , Viroses , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Antivirais/uso terapêutico , Estudos Prospectivos , Antibacterianos , Atenção à SaúdeRESUMO
The globular head domain of influenza virus surface protein hemagglutinin (HA1) is the major target of neutralizing antibodies elicited by vaccines. As little as one amino acid substitution in the HA1 can result in an antigenic drift of influenza viruses, indicating the dominance of some epitopes in the binding of HA to polyclonal serum antibodies. Therefore, identifying dominant binding epitopes of HA is critical for selecting seasonal influenza vaccine viruses. In this study, we have developed a biolayer interferometry (BLI)-based assay to determine dominant binding epitopes of the HA1 in antibody response to influenza vaccines using a panel of recombinant HA1 proteins of A(H1N1)pdm09 virus with each carrying a single amino acid substitution. Sera from individuals vaccinated with the 2010-2011 influenza trivalent vaccines were analyzed for their binding to the HA1 panel and hemagglutination inhibition (HI) activity against influenza viruses with cognate mutations. Results revealed an over 50% reduction in the BLI binding of several mutated HA1 compared to the wild type and a strong correlation between dominant residues identified by the BLI and HI assays. Our study demonstrates a method to systemically analyze antibody immunodominance in the humoral response to influenza vaccines.
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OBJECTIVES: Interpreting real-time reverse transcription-polymerase chain reaction (rRT-PCR) results for human avian influenza A virus (AIV) detection in contaminated settings like live bird markets (LBMs) without serology or viral culture poses a challenge. METHODS: During February-March 2012 and November 2012-February 2013, we screened workers at nine LBMs in Dhaka, Bangladesh, to confirm molecular detections of AIV RNA in respiratory specimens with serology. We tested nasopharyngeal (NP) and throat swabs from workers with influenza-like illness (ILI) and NP, throat, and arm swabs from asymptomatic workers for influenza virus by rRT-PCR and sera for seroconversion and antibodies against HPAI A(H5N1) and A(H9N2) viruses. RESULTS: Among 1273 ILI cases, 34 (2.6%) had A(H5), 56 (4%) had A(H9), and six (0.4%) had both A(H5) and A(H9) detected by rRT-PCR. Of 192 asymptomatic workers, A(H5) was detected in eight (4%) NP and 38 (20%) arm swabs. Of 28 ILI cases with A(H5) or A(H9) detected, none had evidence of seroconversion, but one (3.5%) and 12 (43%) were seropositive for A(H5) and A(H9), respectively. CONCLUSION: Detection of AIV RNA in respiratory specimens from symptomatic and asymptomatic LBM workers without evidence of seroconversion or virus isolation suggests environmental contamination, emphasizing caution in interpreting rRT-PCR results in high viral load settings.
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Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Animais , Humanos , Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/diagnóstico , Virus da Influenza A Subtipo H5N1/genética , Bangladesh/epidemiologia , Galinhas , RNARESUMO
Background: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020). Methods: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4. Results: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes. Conclusions: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.
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BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adulto Jovem , Humanos , Criança , Influenza Humana/prevenção & controle , Influenza Humana/tratamento farmacológico , Anticorpos Antivirais , Vacinas Atenuadas , Vacinas de Produtos Inativados , Testes de Inibição da Hemaglutinação , Imunoglobulina GRESUMO
During February 7âSeptember 3, 2022, a total of 39 US states experienced outbreaks of highly pathogenic avian influenza A(H5N1) virus in birds from commercial poultry farms and backyard flocks. Among persons exposed to infected birds, highly pathogenic avian influenza A(H5) viral RNA was detected in 1 respiratory specimen from 1 person.
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Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Influenza Humana , Animais , Humanos , Estados Unidos/epidemiologia , Influenza Aviária/epidemiologia , Virus da Influenza A Subtipo H5N1/genética , Aves , Influenza Humana/epidemiologia , Aves Domésticas , Surtos de DoençasRESUMO
Introduction: External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods. Methods: We invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays. Results: Within run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization. Discussion: This study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.
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Influenza Humana , Humanos , Hemaglutinação , Laboratórios , Estudos de Viabilidade , Estações do AnoRESUMO
BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.
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Vacina Antirrábica , Raiva , Masculino , Humanos , Idoso de 80 Anos ou mais , Raiva/prevenção & controle , Minnesota , Profilaxia Pós-Exposição/métodos , Anticorpos AntiviraisRESUMO
BACKGROUND: Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. METHODS: Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018-2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. RESULTS: Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). CONCLUSION: Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Idoso , Influenza Humana/prevenção & controle , Imunidade Humoral , Vírus da Influenza A Subtipo H3N2 , Estudos Prospectivos , Anticorpos Antivirais , Vacinas de Produtos Inativados , Testes de Inibição da Hemaglutinação , Vacinas CombinadasRESUMO
BACKGROUND: We estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication. METHODS: We collected residue sera from multiple antenatal-care blood draws during October 2016-April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance. RESULTS: Among all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness. CONCLUSIONS: The incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission.
Assuntos
Infecções por Herpesviridae , Vacinas contra Influenza , Influenza Humana , Humanos , Feminino , Gravidez , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , VacinaçãoRESUMO
BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers. RESULTS: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons. CLINICAL TRIALS REGISTRATION: NCT03722589.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Vacina Antivariólica , Adulto , Humanos , Anticorpos Antivirais , Técnicas de Cultura de Células , Atenção à Saúde , Testes de Inibição da Hemaglutinação , Vírus da Influenza A Subtipo H3N2 , Estados Unidos , Vacinação , Vacinas Combinadas , Vacinas de Produtos Inativados , Vacinas SintéticasRESUMO
Arsenic is a common metal-like element. Drinking arsenic-containing water and occupational exposure to arsenic are the main ways exposure to arsenic for population. Long-term exposure to arsenic can cause various organs dysfunction and cancer. After entering the body, inorganic arsenic is mainly methylated into monomethyl arsenic and dimethyl arsenic in the liver. Only a small part of inorganic arsenic is metabolized in the kidneys and lungs, and finally the metabolites of arsenic are excreted in the urine. understanding the biological characteristics of arsenic absorption, metabolism, and distribution in the body and formulating biological indicators related to occupational exposure to arsenic and can provide a scientific basis for the prevention and treatment of arsenic-related diseases. This article will review the biological monitoring indicators of occupational exposure to arsenic and the metabolic process of arsenic in the body.