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PURPOSE OF REVIEW: Despite the availability of safe and effective oral combination antiretroviral therapy, barriers to maintaining viral suppression remain a challenge to ending the HIV epidemic. Long-acting injectable antiretroviral therapy was developed as an alternative to daily oral therapy. This review summarizes the current literature on the efficacy of long-acting cabotegravir plus rilpivirine for the treatment of HIV-1, reasons to switch to injectable therapy, and barriers to switching. RECENT FINDINGS: Long-acting cabotegravir plus rilpivirine is safe and effective in maintaining HIV-1 virologic suppression. Ideal candidates for switching to long-acting cabotegravir plus rilpivirine are virologically suppressed on oral regimens with good adherence and no history of virologic failure or baseline resistance. Indications to switch to injectable therapy include patient preference, the potential for improved adherence, and avoidance of adverse effects. Implementation research is needed to assess and overcome system barriers. Long-acting cabotegravir plus rilpivirine is a novel alternative to oral antiretrovirals, with the potential to improve adherence and quality of life in people with HIV.
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BACKGROUND: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes. CONCLUSIONS: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression. CLINICAL TRIALS REGISTRATION: NCT04333953.
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COVID-19 , Infecções por HIV , Idoso , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Pessoa de Meia-Idade , Sistema de Registros , SARS-CoV-2RESUMO
Background: There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. Methods: In 5 returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Results: Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for >44 and >26 days. Three days after symptom onset, transient increases in proinflammatory monocytes began followed at 5 days by transient decreases in myeloid dendritic cells. Anti-Zika virus immunoglobulin M was detected at day 7 after symptom onset, persisted beyond 103 days, and remained equivocal through day 172. Zika virus-specific plasmablasts and neutralizing antibodies developed quickly; dengue virus-specific plasmablasts and neutralizing antibodies at high titers developed only in flavivirus-experienced patients. Zika virus- and dengue virus-specific memory B cells developed in both flavivirus-naive and -experienced patients. CD4+ T cells were moderately activated and produced antiviral cytokines after stimulation with Zika virus C, prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were massively activated, but virus-specific cells that produced cytokines were present in only 2/4 patients assessed. Conclusions: Acute infections with Zika virus modulated antigen-presenting cell populations early. Flavivirus-experienced patients quickly recalled cross-reactive MBCs to secrete antibodies. Dengue virus-naive patients made little dengue-specific antibody but developed MBCs that cross-reacted against dengue virus. Zika virus-specific functional CD4+ T cells were readily detected, but few CD8+ T cells specific for the tested peptides were found.
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Imunidade Adaptativa , Linfócitos B/imunologia , Imunidade Inata , Subpopulações de Linfócitos T/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/patologia , Zika virus/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Gravidez , RNA Viral/sangue , Fatores de Tempo , Carga Viral , Infecção por Zika virus/virologiaRESUMO
Infection with Zika virus is an emerging public health crisis. We observed prolonged detection of virus RNA in vaginal mucosal swab specimens and whole blood for a US traveler with acute Zika virus infection who had visited Honduras. These findings advance understanding of Zika virus infection and provide data for additional testing strategies.
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RNA Viral/sangue , Vagina/virologia , Infecção por Zika virus/virologia , Adulto , Animais , Chlorocebus aethiops , Meios de Cultivo Condicionados/química , Feminino , Honduras , Humanos , RNA Viral/urina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saliva/virologia , Fatores de Tempo , Viagem , Estados Unidos , Vagina/metabolismo , Células Vero , Zika virus/genética , Zika virus/crescimento & desenvolvimento , Infecção por Zika virus/sangue , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/urinaRESUMO
BACKGROUND: Influenza A(H5N1) virus and other avian influenza virus strains represent major pandemic threats. Like all influenza A virus strains, A(H5N1) viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity. METHODS: Subjects primed with clade 1 H5 antigen, with or without adjuvant, and H5-naive individuals were boosted with clade 2 H5 antigen. The impact of priming on T cells capable of both proliferation and cytokine production after antigen restimulation was assessed. RESULTS: Subjects previously vaccinated with clade 1 H5 antigen developed significantly enhanced clade 2 H5 cross-reactive T cell responses detectable 6 months after vaccination with clade 2 H5 antigen. Priming dose (15 µg vs 45 or 90 µg) had no effect on magnitude of heterotypic H5 T cell responses. In contrast, age at priming negatively modulated both the magnitude and duration of heterotypic H5 T cell responses. Elderly subjects developed significantly less heterotypic H5 T cell boosting, predominantly for T cells capable of cytokine production. Adjuvant had a positive albeit weaker effect than age. The magnitude of CD4(+) interferon-γ producing T cells correlated with H5 antibody responses. CONCLUSIONS: H5 heterotypic priming prior to onset of an A(H5N1) pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus.
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Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunidade Heteróloga , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Linfócitos T/imunologia , Vacinação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Humanos , Vacinas contra Influenza/administração & dosagem , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-µg or 90-µg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens. Clade 2 titers were unaffected by the previous dose of clade 1 vaccine. Low-dose priming with a mismatched pandemic influenza A(H5N1) vaccine would improve the rapidity, magnitude, and cross-reactivity of the immunological response following a single high-dose, unadjuvanted, pandemic vaccine.
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Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adulto , Idoso , Anticorpos Antivirais/sangue , Reações Cruzadas , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Feminino , Humanos , Imunização Secundária , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Vacinas contra Influenza/administração & dosagem , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Adulto JovemRESUMO
BACKGROUND: Variant influenza A(H3N2) viruses (H3N2v) have transmitted recently from pigs to humans in the United States. Vaccines strategies are needed. METHODS: Healthy adults received 2 doses of subvirion H3N2v vaccine (15 µg of hemagglutinin/dose) 21 days apart in this open-label trial. Serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody (Ab) titers were measured before and 8 and 21 days after each dose. Memory B-cell (MBC) responses were assessed. RESULTS: Vaccine was well tolerated. A total of 40% of subjects had an HAI Ab titer of ≥40 before vaccination. Eight-seven percent (95% confidence interval [CI], 79%-93%) and 73% (95% CI, 63%-81%) of subjects 18-64 years old (98 subjects) and ≥65 years old (90 subjects), respectively, had an HAI titer of ≥40 21 days after dose 1 (P = .01); 51% (95% CI, 41%-61%) and 52% (95% CI, 41%-62%) of younger and older subjects, respectively, developed ≥4-fold rises in titer (P = not significant). Neut Ab response patterns were similar. Geometric mean titers were higher in younger subjects. Dose 2 provided no significant enhancement in responses. Cross-reactive MBCs were detected before vaccination and expanded after vaccination. Preexisting H3N2v-specific MBCs positively correlated with early increases in vaccine-induced Ab. CONCLUSIONS: In most healthy adults, one 15-µg dose of vaccine elicited levels of HAI Abs associated with protection. Studies in children and elderly individuals are indicated to define the immunization needs of these groups. CLINICAL TRIALS REGISTRATION: NCT01746082.
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Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Linfócitos B/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
IMPORTANCE: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continue to occur. Hemagglutinin H7 administered alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines. OBJECTIVE: To evaluate the immunogenicity and safety of an inactivated H7N9 vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that included sequential administration of AS03- and MF59-containing formulations and of adjuvanted and unadjuvanted formulations. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, phase 2 trial at 5 US sites enrolled 980 adults aged 19 through 64 years from September 2013 through November 2013; safety follow-up was completed in January 2015. INTERVENTIONS: The H7N9 vaccine was given on days 0 and 21 at nominal doses of 3.75 µg, 7.5 µg, 15 µg, and 45 µg of hemagglutinin with or without AS03 or MF59 adjuvant mixed on site. MAIN OUTCOMES AND MEASURES: Proportions achieving a hemagglutination inhibition antibody (HIA) titer of 40 or higher at 21 days after the second vaccination; vaccine-related serious adverse events through 12 months after the first vaccination; and solicited signs and symptoms after vaccination through day 7. RESULTS: Two doses of vaccine were required to induce detectable antibody titers in most participants. After 2 doses of an H7N9 formulation containing 15 µg of hemagglutinin given without adjuvant, with AS03 adjuvant, or with MF59 adjuvant, the proportion achieving an HIA titer of 40 or higher was 2% (95% CI, 0%-7%) without adjuvant (n = 94), 84% (95% CI, 76%-91%) with AS03 adjuvant (n = 96), and 57% (95% CI, 47%-68%) with MF59 adjuvant (n = 92) (P < .001 for comparison of the AS03 and MF59 schedules). The 2 schedules alternating AS03-and MF59-adjuvanted formulations led to lower geometric mean titers (GMTs) of (41.5 [95% CI, 31.7-54.4]; n = 92) and (58.6 [95% CI, 44.3-77.6]; n = 96) than the group induced by 2 AS03-adjuvanted formulations (n = 96) (103.4 [95% CI, 78.7-135.9]; P < .001) but higher GMTs than 2 doses of MF59-adjuvanted formulation (n = 94) (29.0 [95% CI, 22.4-37.6]; P < .001). CONCLUSIONS AND RELEVANCE: The AS03 and MF59 adjuvants augmented the immune responses to 2 doses of an inactivated H7N9 influenza vaccine, with AS03-adjuvanted formulations inducing the highest titers. This study of 2 adjuvants used in influenza vaccine formulations with adjuvant mixed on site provides immunogenicity information that may be informative to influenza pandemic preparedness programs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01942265.
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Adjuvantes Imunológicos/administração & dosagem , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologia , Adulto , Fatores Etários , Anticorpos Antivirais/sangue , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Testes de Inibição da Hemaglutinação , Hemaglutinação por Vírus/imunologia , Humanos , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Polissorbatos/administração & dosagem , Esqualeno/administração & dosagem , alfa-Tocoferol/administração & dosagemRESUMO
Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization.
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Controle de Doenças Transmissíveis , Imunização , Complicações Infecciosas na Gravidez/prevenção & controle , Vacinas , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunidade Materno-Adquirida , Programas de Imunização , Lactente , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Gravidez , Tétano/prevenção & controle , Estados Unidos , Vacinas/administração & dosagem , Vacinas/efeitos adversos , Vacinas/imunologia , Coqueluche/prevenção & controleRESUMO
BACKGROUND: Direct comparisons of similar doses of a novel influenza virus antigen administered by the intradermal route and the intramuscular route have not been reported. METHODS: A total of 227 healthy adults aged 18-49 years were randomized to receive 2 doses 1 month apart of a subvirion inactivated influenza A virus subtype H5N1 (rgA/Vietnam/1203/2004) vaccine containing 38.7 µg of H5N1 hemagglutinin (HA), by the intramuscular route or by the intradermal route using the Mantoux technique. Clinical and serologic responses were assessed. RESULTS: Injection site reactions were more frequent in the intradermal group. Immune responses and the geometric mean titer of serum hemagglutination inhibition and neutralizing antibodies 1 month after receipt of the first dose were similar and low but were significantly higher after 2 doses of vaccine in both groups. CONCLUSIONS: Intramuscular and intradermal delivery of vaccine were both well tolerated. Immune responses after 2 doses of this influenza A/H5N1 HA (38.7 µg) were low and not significantly different when given by the intradermal or intramuscular route. Evaluation of higher dosages, alternative intradermal delivery methods, and the addition of adjuvants will be needed to enhance the immunogenicity of inactivated influenza A/H5N1 vaccines by the intradermal route. CLINICAL TRIALS REGISTRATION: NCT00439335.
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Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Método Duplo-Cego , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/efeitos adversos , Influenza Humana/sangue , Influenza Humana/imunologia , Injeções Intradérmicas , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge. METHODS: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 µg, 30 µg, and 100 µg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit. RESULTS: Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered Sm-TSP-2/Alhydrogel with AP 10-701. Peak anti-Sm-TSP-2 IgG levels were observed approximately 2 weeks following the third dose, regardless of Sm-TSP-2 formulation. IgG levels fell to low levels by Day 478 in all groups except the 100 µg with AP 10-701 group, in which 57% of subjects (4 of 7) still had IgG levels that were ≥4-fold higher than baseline. IgG subclass levels mirrored those of total IgG, with IgG1 being the predominant subclass response. CONCLUSIONS: Vaccination of adults with Sm-TSP-2/Alhydrogel in an area of ongoing S. mansoni transmission was safe, minimally reactogenic, and elicited significant IgG and IgG subclass responses against the vaccine antigen. These promising results have led to initiation of a Phase 2 clinical trial of this vaccine in an endemic region of Uganda. TRIAL REGISTRATION: NCT03110757.
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Esquistossomose mansoni , Animais , Humanos , Camundongos , Adjuvantes Imunológicos , Hidróxido de Alumínio , Brasil , Imunoglobulina G , Schistosoma mansoni , Vacinas ProtozoáriasRESUMO
We evaluated the prevalence of respiratory virus infection (RVI) in 403 illnesses of 364 persons hospitalized over a 2-year period with acute respiratory conditions using virus-specific reverse transcription-PCR (RT-PCR) assays in addition to cell culture and serology. RVIs were identified in >75% of children under 5 years of age and 25 to 37% of adults. The molecular assays doubled the number of infections identified; picornaviruses were the most frequent in patients of all ages, followed by respiratory syncytial virus and influenza viruses.
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Hospitalização/estatística & dados numéricos , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/virologia , Picornaviridae/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções por Picornaviridae/patologia , Prevalência , Infecções Respiratórias/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testes Sorológicos , Cultura de Vírus , Vírus , Adulto JovemRESUMO
BACKGROUND: Although pregnant women are at increased risk of severe illness following influenza infection, there is relatively little information on the immunogenicity of influenza vaccines administered during pregnancy. METHODS: We conducted a clinical trial that enrolled 120 pregnant women in which participants were randomly assigned to receive an inactivated 2009 H1N1 influenza vaccine containing either 25 µg or 49 µg of hemagglutinin (HA) in a 2-dose series with a 21-day period between administration of the first and second doses. RESULTS: Following the first vaccination, HA inhibition (HAI) titers of ≥1:40 were detected in 93% (95% confidence interval [CI], 82%-98%) of subjects who received the 25-µg dose and 97% (95% CI, 88%-100%) of subjects receiving the 49-µg dose. In cord blood samples, HAI titers of ≥1:40 were found in 87% (95% CI, 73%-96%) of samples from the 25-µg dose group and in 89% (95% CI, 76%-96%) from the 49-µg dose group. Microneutralization titers tended to be higher than HAI titers, but the patterns of response were similar. CONCLUSIONS: In pregnant women, 1 dose of an inactivated 2009 H1N1 influenza vaccine containing 25 µg of HA elicited an antibody response typically associated with protection against influenza infection. Efficient transplacental transfer of antibody was also documented.
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Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Anticorpos Antivirais/sangue , Feminino , Humanos , Imunização Secundária/métodos , Vacinas contra Influenza/administração & dosagem , Gravidez , Vacinação/métodos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Adulto JovemRESUMO
Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally.
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Intravascular lymphoma is an uncommon subtype of B-cell lymphoma with neoplastic cells limited to the lumen of small blood vessels. We report a case of a 52-year-old man who presented with constitutional symptoms and rapidly progressive dementia. He was found to have diffuse leptomeningeal and faint parenchymal enhancement on magnetic resonance imaging and was subsequently diagnosed with intravascular lymphoma following a brain biopsy. He responded remarkably well to systemic and intrathecal chemotherapy. The diagnosis and treatment of intravascular lymphoma have been guided by a few case reports and are largely based on expert opinion.
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OBJECTIVE: Inactivated influenza virus vaccines (IIVs) are recommended for all pregnant women in the United States. We conducted a prospective, randomized, double blind study of three licensed seasonal trivalent IIVs (IIV3s) to assess their safety and immunogenicity in pregnant women and determine the level and persistence of passively transferred maternal antibody in infants. STUDY DESIGN: 139 pregnant women ages 18-39 years and 14-33 weeks' gestation, and 44 non-pregnant women, were randomized 1:1:1 to receive a single intramuscular dose of one of three licensed IIV3s (Agriflu®, Fluzone®, or Fluarix®) prior to the 2010-2011 influenza season. Reactogenicity, adverse events (AEs) and pregnancy outcomes were documented. Serum samples for hemagglutination inhibition (HAI) and neutralization antibody assays were collected prior to and 28 and 180 days after immunization. Maternal sera and cord blood were collected at the time of delivery and sera were obtained from 44 infants at 6 weeks of age. RESULTS: Pregnant and non-pregnant women experienced similar frequency of injection site (92% and 86%, respectively) and systemic (95% and 87%, respectively) reactions, the majority of which were mild. There were no vaccine-associated maternal or infant serious AEs. Antibody responses to the three vaccine antigens were not different between pregnant and non-pregnant women. The ratios of cord blood (infant) to maternal HAI antibody titers at delivery ranged between 1.1 and 1.7 for each of the vaccine antigens. Influenza antibody concentrations in infants were 70-40% of the birth titer by 6 weeks of age. CONCLUSIONS: The three IIV3s were well tolerated in pregnant women. Antibody responses were comparable in pregnant and non-pregnant women, and after second or third trimester vaccination. Transplacental transfer of maternal antibodies to the infant was efficient. However, antibody titers decline rapidly in the first 6 weeks of life.
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Vacinas contra Influenza , Influenza Humana , Adolescente , Adulto , Anticorpos Antivirais , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Lactente , Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Gravidez , Gestantes , Estudos Prospectivos , Estações do Ano , Vacinas de Produtos Inativados/efeitos adversos , Adulto JovemRESUMO
Current diagnostic protocols of acute Zika virus (ZIKV) infection focus on detection of viral RNA in serum or urine using reverse transcription quantitative polymerase chain reaction (RT-qPCR); however, detecting infection can be a challenge, given that 80% of people with acute ZIKV infection are asymptomatic, and the window to detect viremia in serum is short. The ability to extend that window is needed to detect ZIKV at later time points after infection, particularly in high-risk individuals such as pregnant women. We evaluated RNA extraction methods to optimize detection of ZIKV in various body fluids using RT-qPCR as a means of improving the analytical sensitivity of detection. We optimized methods for ZIKV RNA recovery from a number of body fluids by spiking with three varying concentrations of virus, then comparing recovery with that of spiked buffer control. RNA extraction protocols were adjusted as necessary for maximum RNA recovery. Adjustment of the elution step was essential for improved ZIKV RNA recovery from whole blood, saliva, vaginal secretions, and breast milk. Optimal recovery from urine samples required the addition of Urine Conditioning Buffer, and the use of RLT Plus buffer and RNeasy Mini Spin Columns was necessary for RNA extractions from semen samples. Optimized QIAamp MinElute Virus Spin Kit (QIAGEN, Valencia, CA) protocol followed by the singleplex ZIKV RT-qPCR assay provided a reliable method for detection of ZIKV RNA in a variety of biological samples. Improved diagnostics are crucial for timely detection and diagnosis, particularly during pregnancy when the consequences of ZIKV infection can greatly impact the developing fetus.
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Líquidos Corporais/virologia , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Feminino , Humanos , Masculino , Leite Humano/virologia , Gravidez , RNA Viral/sangue , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Saliva/virologia , Sêmen/virologia , Vagina/virologia , Zika virus/genética , Infecção por Zika virus/sangue , Infecção por Zika virus/urina , Infecção por Zika virus/virologiaRESUMO
HIV medical care providers need a wide range of evidence-based clinical information resources to manage their patients' health. We determined whether providers' choice of information sources for HIV care and treatment are associated with their demographic and medical practice characteristics. Data used for this study were obtained from a probability sample of HIV medical care providers in 13 outpatient HIV facilities in Houston/Harris County, Texas, surveyed between June and September 2009. The mean number of information sources used by HIV medical care providers for HIV care and treatment was 5.83 (95% confidence interval: 4.90-6.75). Antiretroviral therapy guidelines (95.6%), medical journals and textbooks (82.6%), and Internet sources (69.5%) were ranked first, second, and third as sources of clinical information. At least one of the providers' demographic or medical practice characteristics was significantly (p ⩽ 0.05) associated with six of the clinical information sources. Integration of these information resources into clinicians' workflow may enhance efficiency of HIV care and treatment and facilitate improved patients' care and health outcomes.
Assuntos
Infecções por HIV/terapia , Pessoal de Saúde/psicologia , Serviços de Informação/normas , Adulto , Atitude do Pessoal de Saúde , Demografia/estatística & dados numéricos , Feminino , Pessoal de Saúde/normas , Pessoal de Saúde/estatística & dados numéricos , Humanos , Serviços de Informação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , TexasRESUMO
BACKGROUND: Influenza A/H7N9 viruses are undergoing antigenic drift since their emergence in 2013, and vaccination strategies are needed for pandemic preparedness. Two doses of adjuvanted monovalent inactivated influenza A/H7N9 vaccine (IIV1 A/H7N9) are needed for optimal serological responses. However, administering 2 doses in a pandemic setting might be challenging. We evaluated the immunogenicity of "boosting" with IIV1 A/H7N9 in subjects "primed" 8â¯years previously with IIV1 A/H7N7. METHODS: We administered 1 booster dose containing 45â¯mcg of IIV1 A/H7N9 hemagglutinin to 17 recipients of 2 prior doses of IIV1 A/H7N7, and to 10 influenza A/H7-naïve subjects. We tested their post-boosting sera for antibodies (Ab) against homologous influenza A/H7N9 using a hemagglutination inhibition assay; and compared their Ab titers to those in stored sera from recipients of AS03-adjuvanted IIV1 A/H7N9 against 9 strains of influenza A/H7N9 viruses. RESULTS: The percentage of subjects with Ab titers ≥40 on Days 9 and 29 post boosting, respectively, was 65% and 41% in primed subjects and 10% and 0% in unprimed subjects. The Ab titers in recipients of AS03-adjuvanted IIV1 A/H7N9 were higher than those in the prime-boost group against a panel of influenza A/H7N9 viruses, except for 2 highly pathogenic strains. CONCLUSIONS: Priming with IIV1 A/H7 results in serological responses following a delayed boost with 1 dose of unadjuvanted IIV1 A/H7N9, despite lack of antibody response after the prime. Optimizing prime-boost approaches would benefit pandemic preparedness. ClinicalTrials.gov identifier: NCT02586792.
Assuntos
Imunização Secundária , Imunogenicidade da Vacina , Vírus da Influenza A Subtipo H7N7/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Vacinação , Fluxo de TrabalhoRESUMO
BACKGROUND: Seasonal influenza results in significant morbidity and mortality worldwide, but the currently licensed inactivated vaccines generally have low vaccine efficacies and could be improved. In this phase 1 clinical trial, we compared seasonal influenza vaccine regimens with different priming strategies, prime-boost intervals, and administration routes to determine the impact of these variables on the resulting antibody response. METHODS: Between August 17, 2012 and January 25, 2013, four sites enrolled healthy adults 18-70 years of age. Subjects were randomized to receive one of the following vaccination regimens: trivalent hemagglutinin (HA) DNA prime followed by trivalent inactivated influenza vaccine (IIV3) boost with a 3.5 month interval (DNA-IIV3), IIV3 prime followed by IIV3 boost with a 10 month interval (IIV3-IIV3), or concurrent DNA and IIV3 prime followed by IIV3 boost with a 10 month interval (DNA/IIV3-IIV3). Each regimen was additionally stratified by an IIV3 administration route of either intramuscular (IM) or intradermal (ID). DNA vaccines were administered by a needle-free jet injector (Biojector). Study objectives included evaluating the safety and tolerability of each regimen and measuring the antibody response by hemagglutination inhibition (HAI). RESULTS: Three hundred and sixteen subjects enrolled. Local reactogenicity was mild to moderate in severity, with higher frequencies recorded following DNA vaccine administered by Biojector compared to IIV3 by either route (p <0.02 for pain, swelling, and redness) and following IIV3 by ID route compared to IM route (p <0.001 for swelling and redness). Systemic reactogenicity was similar between regimens. Though no overall differences were observed between regimens, the highest titers post boost were observed in the DNA-IIV3 group by ID route and in the IIV3-IIV3 group by IM route. CONCLUSIONS: All vaccination regimens were found to be safe and tolerable. While there were no overall differences between regimens, the DNA-IIV3 group by ID route, and the IIV3-IIV3 group by IM route, showed higher responses compared to the other same-route regimens.