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We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose.
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BACKGROUND: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people. METHODS: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18). RESULTS: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age. CONCLUSIONS: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination.
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Nativos do Alasca , Anticorpos Antivirais , Imunogenicidade da Vacina , Infecções por Papillomavirus , Humanos , Criança , Adolescente , Feminino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/imunologia , Anticorpos Antivirais/sangue , Masculino , Nativos do Alasca/estatística & dados numéricos , Alaska , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Vacinação , Imunoglobulina G/sangue , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagemRESUMO
The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories. IMPORTANCE: Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.
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Antibacterianos , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas , Controle de Qualidade , Streptococcus pneumoniae , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana/normas , Infecções Pneumocócicas/microbiologia , Regiões Árticas , Antibacterianos/farmacologia , Laboratórios/normas , Sorotipagem , Alaska/epidemiologia , Sorogrupo , Monitoramento EpidemiológicoRESUMO
Background: Evidence suggests an increased risk of new-onset diabetes following COVID-19 infection. American Indian/Alaska Native (AI/AN) people were disparately impacted by the COVID-19 pandemic and historically have had higher diabetes incidence than other racial/ethnic groups in the US. We measured the association between COVID-19 infection and incident diabetes in AI/AN people. Methods: We conducted a retrospective cohort study using de-identified patient data from the Indian Health Service's (IHS) National Patient Information Reporting System. We estimated age-adjusted diabetes incidence rates, incidence rate ratios, and adjusted hazard ratios among three cohorts spanning pre-pandemic (1/1/2018-2/28/2020) and pandemic (3/1/2020-12/31/2021) timeframes: 1) pre-pandemic cohort (1,503,085 individuals); 2) no-COVID-19 pandemic cohort (1,344,339 individuals); and 3) COVID-19 cohort (176,483 individuals). Findings: The COVID-19 cohort had an increased hazard of diabetes compared to the no-COVID-19 group (adjusted hazard ratio (aHR) = 1.56; 95% CI: 1.50-1.62) and the pre-pandemic group (aHR = 1.27; 95% CI: 1.22-1.32). The association between COVID-19 infection and new-onset diabetes was stronger in those with severe COVID-19 illness. A sensitivity analysis comparing the COVID-19 cohort to members of other cohorts that had acute upper respiratory infections showed an attenuated but higher risk of new-onset diabetes in those with COVID-19. Interpretation: AI/AN people diagnosed with COVID-19 had an elevated risk of a new diabetes diagnosis when compared to the no-COVID-19 group and the pre-pandemic group. The increased diabetes risk in the COVID-19 group remained in a sensitivity analysis that limited the comparator groups to individuals with an AURI diagnosis. Funding: US National Institute of Diabetes and Digestive and Kidney Diseases.
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BACKGROUND: Haemophilus influenzae (Hi) can cause severe disease in children. This study aimed to identify risk factors related to invasive Hi disease in Alaska children and evaluate carriage in people around them. METHODS: From 2005 to 2011, we investigated episodes of invasive, typeable Hi disease in Alaska children <10 years old. Three age-matched control children were enrolled for each case-patient. We evaluated oropharyngeal Hi carriage in people in close contact with Hi case-patients (contacts) as well as control children and their household members. Individual and household risk factors for illness and carriage were evaluated using questionnaires and chart reviews. RESULTS: Thirty-eight of 44 (86%) children with invasive, typeable Hi disease were recruited: 20 Hi serotype a (53%), 13 serotype b (Hib) (34%) and 5 serotype f (13%). Children with the invasive Hi disease were more likely than controls to have underlying health problems (67% vs. 24%, P = 0.001), other carriers of any Hi in their household (61% vs. 15%, P < 0.001), and inadequate Hib vaccination (26% vs. 9%, P = 0.005). People who carried Hi were younger than noncarriers (mean 12.7 vs. 18.0 years, P = 0.008). The carriage was clustered within case-patient households, with carriage in 19% of household contacts, while only 6.3% of nonhousehold contacts and 5.5% of noncontacts carried the Hi serotype of interest ( P < 0.001). CONCLUSIONS: Factors associated with invasive Hi disease in children included underlying health problems, household carriage and inadequate Hib vaccination. The high level of carriage in case-patient households is important to consider when evaluating treatment and prophylaxis strategies.
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Portador Sadio , Infecções por Haemophilus , Haemophilus influenzae , Humanos , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/classificação , Pré-Escolar , Masculino , Feminino , Lactente , Alaska/epidemiologia , Criança , Estudos de Casos e Controles , Fatores de Risco , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in US adults. We describe the epidemiology of IPD among Alaska adults and estimate the proportion of IPD cases potentially preventable by new vaccines. METHODS: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CIs) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. RESULTS: During 2011-2020, 1164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100 000 adults per year (95% CI, 20.1-22.5). Incidence increased significantly during the study period (P < .01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI, 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than in the general adult population (95% CI, 59-89). Overall, 1032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.
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Pessoas Mal Alojadas , Infecções Pneumocócicas , Adulto , Humanos , Lactente , Adolescente , Streptococcus pneumoniae , Vacinas Conjugadas , Alaska/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , IncidênciaRESUMO
BACKGROUND AND AIMS: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH AND RESULTS: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up. CONCLUSIONS: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion.
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Activating parathyroid hormone (PTH)/PTH-related Peptide (PTHrP) receptor (PTH1R) mutations causes Jansen's metaphyseal chondrodysplasia (JMC), a rare disease characterized by growth plate abnormalities, short stature, and PTH-independent hypercalcemia. Previously generated transgenic JMC mouse models, in which the human PTH1R allele with the H223R mutation (H223R-PTH1R) is expressed in osteoblasts via type Ia1 collagen or DMP1 promoters cause excess bone mass, while expression of the mutant allele via the type IIa1 collagen promoter results in only minor growth plate changes. Thus, neither transgenic JMC model adequately recapitulates the human disease. We therefore generated "humanized" JMC mice in which the H223R-PTH1R allele was expressed via the endogenous mouse Pth1r promoter and, thus, in all relevant target tissues. Founders with the H223R allele typically died within 2 months without reproducing; several mosaic male founders, however, lived longer and produced F1 H223R-PTH1R offspring, which were small and exhibited marked growth plate abnormalities. Serum calcium and phosphate levels of the mutant mice were not different from wild-type littermates, but serum PTH and P1NP were reduced significantly, while CTX-1 and CTX-2 were slightly increased. Histological and RNAscope analyses of the mutant tibial growth plates revealed markedly expanded zones of type II collagen-positive, proliferating/prehypertrophic chondrocytes, abundant apoptotic cells in the growth plate center and a progressive reduction of type X collagen-positive hypertrophic chondrocytes and primary spongiosa. The "humanized" H223R-PTH1R mice are likely to provide a more suitable model for defining the JMC phenotype and for assessing potential treatment options for this debilitating disease of skeletal development and mineral ion homeostasis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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The population in rural southwest Alaska has been disproportionately affected by COVID-19. To assess the benefit of COVID-19 vaccines, we analyzed data from the regional health system. We estimated vaccine effectiveness (VE) during January 16-December 3, 2021, against symptomatic SARS-CoV-2 infection after a primary series or booster dose, and overall VE against hospitalization. VE of a primary series against symptomatic infection among adult residents was 91.3% (95% CI: 85.7, 95.2) during January 16-May 7, 2021, 50.3% (95% CI, 41.1%-58.8%) during July 17-September 24, and 37.0% (95% CI, 27.8-45.0) during September 25-December 3, 2021; VE of a booster dose during September 25-December 3, 2021, was 92.1% (95% CI: 87.2-95.2). During the overall study period, VE against hospitalization was 91.9% (95% CI: 85.4-95.5). COVID-19 vaccination offered strong protection against hospitalization and a booster dose restored protection against symptomatic infection.
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Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Alaska/epidemiologia , SARS-CoV-2 , HospitalizaçãoRESUMO
The combination of denosumab and teriparatide is an effective treatment strategy in postmenopausal osteoporosis, though skeletal gains are promptly lost when these agents are discontinued. In the DATA-HD study, we reported that a single dose of zoledronic acid (ZOL) maintains the increases in areal spine and hip bone mineral density (BMD) achieved with this combination for at least 12 months. The capacity of ZOL to maintain corresponding improvements in peripheral volumetric BMD and microarchitecture, however, has not been reported. In the 15-month DATA-HD study, 76 postmenopausal osteoporotic women were randomized to receive 9 months of teriparatide (20-µg or 40-µg daily) overlapped with denosumab (60 mg at months 3 and 9). In the Extension study, 53 participants received a single dose of ZOL (5 mg intravenously) 24-35 weeks after the last denosumab dose. We measured volumetric BMD and microarchitecture at the distal radius and tibia using high-resolution peripheral quantitative computed tomography at months 27 and 42. Despite ZOL administration, total and cortical BMD gradually decreased over 27 months resulting in values similar to baseline at the radius but still significantly above baseline at the tibia. At both sites, cortical porosity decreased to values below pretreatment baseline at month 27 but then increased from month 27 to 42. There were no significant changes in trabecular parameters throughout the 27-month post-ZOL observation period. Stiffness and failure load, at both sites, decreased progressively from month 15 42 though remained above baseline at the tibia. These findings suggest that in contrast to the largely maintained gains in dual-energy X-ray absorptiometry (DXA)-derived spine and hip BMD, a single dose of ZOL was not as effective in maintaining the gains in volumetric peripheral bone density and microarchitecture produced by 15 months of overlapping treatment with denosumab and teriparatide. Alternative therapeutic approaches that can fully maintain improvements in peripheral bone parameters require further study. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Feminino , Humanos , Teriparatida/uso terapêutico , Denosumab/farmacologia , Denosumab/uso terapêutico , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Densidade ÓsseaRESUMO
BACKGROUND: Peptide YY (PYY) is an anorexigenic gut hormone that also has anti-osteogenic effects, inhibiting osteoblastic activity and inducing catabolic effects. It has been postulated that increases in PYY after Roux-en-Y gastric bypass (RYGB) contribute to declines in bone mineral density (BMD) and increases in bone turnover. The aim of this study is to determine the role of the PYY Y2-receptor in mediating bone loss post-RYGB in mice. METHODS: We compared adult male wildtype (WT) and PYY Y2 receptor-deficient (KO) C57BL/6 mice that received RYGB (WT: n = 8; KO: n = 9), with sham-operated mice (Sham; WT: n = 9; KO: n = 10) and mice that were food-restricted to match the weights of the RYGB-treated group (Weight-Matched, WM; WT: n = 7; KO: n = 5). RYGB or sham surgery was performed at 15-16 weeks of age, and mice sacrificed 21 weeks later. We characterized bone microarchitecture with micro-computed tomography (µCT) at the distal femur (trabecular) and femoral midshaft (cortical). Differences in body weight, bone microarchitecture and biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) were compared using 2-factor ANOVA with Tukey's adjustments for multiple comparisons. RESULTS: Body weights were similar in the WT-RYGB, WT-WM, KO-RYGB, and KO-WM: 41-44 g; these groups weighed significantly less than the Sham surgery groups: 55-57 g. Trabecular BMD was 31-43 % lower in RYGB mice than either Sham or WM in WT and KO groups. This deficiency in trabecular bone was accompanied by a lower trabecular number (19 %-23 %), thickness (22 %-30 %) and increased trabecular spacing (25 %-34 %) in WT and KO groups (p < 0.001 for all comparisons vs. RYGB). RYGB led to lower cortical thickness, cortical tissue mineral density, and cortical bone area fraction as compared to Sham and WM in WT and KO groups (p ≤ 0.004 for all). There were no interactions between genotype and bone microarchitecture, with patterns of response to RYGB similar in both WT and KO groups. CTX and P1NP were significantly higher in RYGB mice than WM in WT and KO groups. PTH did not differ among groups. CONCLUSIONS: RYGB induced greater trabecular and cortical deficits and high bone turnover than observed in weight-matched mice, with a similar pattern in the WT and Y2RKO mice. Thus, skeletal effects of RYGB are independent of weight loss, and furthermore, PYY signaling through Y2R is not a key mediator of bone loss post-RYGB.
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Doenças Ósseas Metabólicas , Derivação Gástrica , Animais , Masculino , Camundongos , Densidade Óssea/fisiologia , Camundongos Endogâmicos C57BL , Peptídeo YY , Microtomografia por Raio-XRESUMO
Invasive Haemophilus influenzae type a (iHia) disease was detected in Alaska and Northern Canada in 2002 and 2000, respectively. From 2006 to 2017, 164 iHia cases (Alaska=53, Northern Canada=111) were reported. Rates of iHia disease per 100,000 persons were higher in Northern Canada compared to Alaska and were significantly higher in Indigenous (Alaska 2.8, Northern Canada 9.5) compared to non-Indigenous populations (Alaska 0.1, Northern Canada=0.4). Disease rates were highest in Indigenous children <2 years of age (Alaska 56.2, Northern Canada=144.1) and significantly higher than in non-Indigenous children <2 (Alaska 0.1, Northern Canada 0.4). The most common clinical presentation in children <5 years was meningitis of age and pneumonia in persons ≥5 years old. Most patients were hospitalised (Alaska=87%, Northern Canada=89%) and fatality was similar (Alaska=11%, Northern Canada=10%). MLST testing showed sequence types ST23 and ST576 in Northern Canada and ST576, ST23 and ST56 in Alaska. Alaska and Northern Canada have high rates of iHia disease. A vaccine is needed in these regions to protect young children.
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Haemophilus influenzae , Grupos Raciais , Criança , Humanos , Pré-Escolar , Tipagem de Sequências Multilocus , Sorogrupo , Alaska/epidemiologiaRESUMO
Glucocorticoid excess suppresses osteocyte remodeling of surrounding bone minerals, causes apoptosis of osteoblasts and osteocytes, and disrupts bone remodeling, eventually, leading to glucocorticoid-induced osteoporosis and bone fragility. Preventing apoptosis and preserving osteocyte morphology could be an effective means of preventing bone loss during glucocorticoid treatment. We hypothesized that osteocrin, which preserves osteocyte viability and morphology in Sp7-deficient mice, could prevent osteocyte death and dysfunction in a glucocorticoid excess model. We used adeno-associated virus (AAV8) to induce osteocrin overexpression in mice one week before implantation with prednisolone or placebo pellets. After 28 days, prednisolone caused the expected reduction in cortical bone thickness and osteocyte canalicular length in control AAV8-treated mice, and these effects were blunted in mice receiving AAV8-osteocrin. Glucocorticoid-induced changes in cortical porosity, trabecular bone mass, and gene expression were not prevented by osteocrin. These findings support a modest therapeutic potential for AAV8-osteocrin in preserving osteocyte morphology during disease.
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Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism. Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. This introduces an element of uncertainty in the accuracy of rodent models for performing such preclinical evaluations. To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach to generate a mouse (in-host strain C57Bl/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein is expressed. Expression is directed by the endogenous mouse promoter and hence occurs in all biologically relevant cells and tissues and at appropriate levels. The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed functional responses to injected PTH analog peptides that are consistent with a fully functional human PTH1R in target bone and kidney cells. The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues in humans is reported here.
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Proteína Relacionada ao Hormônio Paratireóideo , Hormônio Paratireóideo , Receptor Tipo 1 de Hormônio Paratireóideo , Sequência de Aminoácidos , Animais , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Hormônio Paratireóideo/genética , Hormônio Paratireóideo/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/genética , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Ratos , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Receptores de Hormônios Paratireóideos/genética , Receptores de Hormônios Paratireóideos/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years. METHODS: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I2. FINDINGS: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I2=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I2=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I2=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I2=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I2=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I2=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I2=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I2=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I2=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I2=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I2=54%; two studies). INTERPRETATION: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS. FUNDING: Wellcome Trust.
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Gestantes , Infecções Estreptocócicas , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus pyogenesRESUMO
BACKGROUND AND AIMS: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were ≥6 months old. APPROACH AND RESULTS: We tested persons for antibody to hepatitis B surface antigen (anti-HBs) levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received one booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days postbooster. Among the 320 recruited, 112 persons had not participated in the 22- or 30-year follow-up study (group 1), and 208 persons had participated but were not given an HBV booster dose (group 2). Among the 112 persons in group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28 of 38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for antibody to hepatitis B core antigen, none tested positive for HBsAg or HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate that 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time.
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Vacinas contra Hepatite B , Hepatite B , Adulto , Criança , DNA Viral , Seguimentos , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Humanos , Imunização Secundária , LactenteRESUMO
Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for ≥24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR] = 6.39) or after symptomatic infection (aOR = 9.63), and less likely after previous infection (aOR = 0.30), receipt of a primary COVID-19 vaccination series (aOR = 0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR = 0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days.
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Teste Sorológico para COVID-19 , COVID-19/diagnóstico , Quarentena , SARS-CoV-2 , Adolescente , Adulto , Alaska/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Criança , Pré-Escolar , Feminino , Diretrizes para o Planejamento em Saúde , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death. METHODS: This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations. RESULTS: The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate. CONCLUSIONS: Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States.
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Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Adulto , Alaska/epidemiologia , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Estados UnidosRESUMO
BACKGROUND: Haemophilus influenzae serotype a (Hia) can cause severe invasive disease, especially in young children. In 2018, 4 invasive Hia cases occurred in an Alaska community. We used whole-genome sequencing (WGS) to evaluate the relationship of the bacteria from this community and other Alaska patients with invasive Hia. METHODS: All carriage (n = 15) and invasive (n = 4) Hia isolates from the outbreak community, together with 15 nonoutbreak Alaska invasive Hia surveillance isolates from 2018, were tested for antimicrobial susceptibility and characterized using WGS. RESULTS: Phylogenetic analysis of both invasive and carriage Hia isolates revealed 2 major clades that differed by an average of 300 core single-nucleotide polymorphisms (SNPs). All isolates from the outbreak community were clustered in 1 subclade, within a larger clade containing 3 nonoutbreak invasive Hia isolates. Comparative genomics did not reveal any genetic mutations that distinguished carriage from invasive isolates. Three (20%) community isolates were rifampin resistant and had a previously unreported mutation in the rpoB gene. CONCLUSIONS: In the outbreak community, Hia isolates from carriers were indistinguishable from the invasive Hia isolates. Overall, invasive Hia isolates from Alaska in 2018 were genetically similar. The rifampin resistance mutation is concerning as rifampin is the first-line medication for Hia prophylaxis.
Assuntos
Infecções por Haemophilus , Alaska/epidemiologia , Criança , Pré-Escolar , Surtos de Doenças , Genômica , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/genética , Humanos , Filogenia , Rifampina , SorogrupoRESUMO
Some osteoblasts embed within bone matrix, change shape, and become dendrite-bearing osteocytes. The circuitry that drives dendrite formation during "osteocytogenesis" is poorly understood. Here we show that deletion of Sp7 in osteoblasts and osteocytes causes defects in osteocyte dendrites. Profiling of Sp7 target genes and binding sites reveals unexpected repurposing of this transcription factor to drive dendrite formation. Osteocrin is a Sp7 target gene that promotes osteocyte dendrite formation and rescues defects in Sp7-deficient mice. Single-cell RNA-sequencing demonstrates defects in osteocyte maturation in the absence of Sp7. Sp7-dependent osteocyte gene networks are associated with human skeletal diseases. Moreover, humans with a SP7R316C mutation show defective osteocyte morphology. Sp7-dependent genes that mark osteocytes are enriched in neurons, highlighting shared features between osteocytic and neuronal connectivity. These findings reveal a role for Sp7 and its target gene Osteocrin in osteocytogenesis, revealing that pathways that control osteocyte development influence human bone diseases.