Background Emerging COVID-19 pandemic caused extensive lockdowns in a number of countries, but yet unknown number of cases positive to SARS-CoV-2 escapes surveillance systems. Methods Mothers participating in an Italian NINFEA birth cohort were invited to complete an online questionnaire on COVID-19-like symptoms in the household. We estimated the population prevalence of COVID-19-like symptoms in children and adults, assessed their geographical correlation with the cumulative number of COVID-19 cases by province, analysed their clustering within families, and estimated their sensitivity, positive (PPV) and negative predictive values (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2. Results Information was collected on 3184 households, 6133 adults, and 5751 children. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing di culties in adults (Spearman's rho ≥0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5 o C; prevalence ratio 5.27; 95% con dence intervals: 2.37 to 11.74) and anosmia/dysgeusia in children. Among adults with COVID-19, fatigue, muscle pain, and fever had a sensitivity ≥70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing di culties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%. Among tested Piedmont residents, with a COVID-19 prevalence of 18.5%, breathing di culties and anosmia/disguesia reached PPVs above 80%. Conclusion Geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of con rmed COVID-19 cases could help identi cation of the intra-familial spread of the virus and its further propagation in the community. Lowgrade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection. geographical correlation between the symptoms' prevalence and the cumulative number of new SARS-CoV-2 positive cases reported by the Surveillance System, (iii) analyse the clustering of symptoms within families with or without a member who tested negative for SARS-CoV-2 or was diagnosed with COVID-19 and, nally, (iv) estimate the sensitivity, positive and negative predictive values for COVID-19-like symptoms in tested individuals of the NINFEA population. Methods Study design and population The NINFEA study is an Italian internet-based mother-child cohort (www.progettoninfea.it) set up to investigate the in uence of early-life exposures on later childhood and adulthood health. Between 2005 and 2016, approximately 7,500 pregnant women were recruited by completing the baseline questionnaire, and the children are currently followed up with questionnaires complete...
Eligible participants were born during January 2001-February 2007. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) represents coverage with ≥1 Tdap dose at age ≥10 years. Meningococcal conjugate vaccine (MenACWY) represents coverage with the quadrivalent meningococcal conjugate vaccine or meningococcal-unknown type vaccine. Human papillomavirus (HPV) vaccination coverage includes receipt of any HPV vaccine and does not distinguish between nine-valent (9vHPV), quadrivalent (4vHPV), or bivalent (2vHPV) vaccines. Some adolescents might have received more than the two or three recommended HPV vaccine doses. Estimates for hepatitis A, hepatitis B, and measles, mumps, and rubella vaccines represent coverage based on the catch-up schedule for adolescents who are not up to date with these vaccinations. Except as noted, coverage estimates for ≥1 and ≥2 varicella vaccine doses were obtained among adolescents with no history of varicella disease. Influenza vaccination coverage data are not included in this report but are available online at https:// www.cdc.gov/flu/fluvaxview/index.htm. † Adolescents were considered to be up to date with HPV vaccination if they had received ≥3 doses, or if each of the following applied: 1) they had received 2 doses; 2) the first dose was received before their 15th birthday; and 3) the difference between dates of first and second doses was ≥5 months minus 4 days, the absolute minimum interval between the first and second doses. https:// www.cdc.gov/vaccines/programs/iis/cdsi.html. in 2019. Both HPV vaccination coverage measures improved among females and males. An increase in adolescent coverage with ≥1 dose of MenACWY (from 86.6% in 2018 to 88.9% in 2019) also was observed. Among adolescents aged 17 years, 53.7% received the booster dose of MenACWY in 2019, not statistically different from 50.8% in 2018; 21.8% received ≥1 dose of MenB, a 4.6 percentage point increase from 17.2% in 2018. Among adolescents living at or above the poverty level, § INSIDE
HIV causes a chronic infection characterized by depletion of CD4+ T lymphocytes and development of opportunistic infections. Despite drugs that inhibit viral spread, HIV has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy and the immune response. Here we used CD34+ cells from infected people as well as in vitro studies of wild type HIV to demonstrate infection and killing of CD34+ multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A novel reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have important implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.
The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) vaccines. Catch-up vaccination is recommended for hepatitis B (HepB); hepatitis A (HepA); measles, mumps, and rubella (MMR); and varicella (VAR) vaccines for adolescents whose childhood vaccinations are not current. Adolescents are also recommended to receive a booster dose of MenACWY vaccine at age 16 years, and shared clinical decision-making is recommended for the serogroup B meningococcal vaccine (MenB) for persons aged 16-23 years (1). To estimate coverage with recommended vaccines, CDC analyzed data from the 2020 National Immunization Survey-Teen (NIS-Teen) for 20,163 adolescents aged 13-17 years.* Coverage with ≥1 dose of HPV vaccine increased from 71.5% in 2019 to 75.1% in 2020. The percentage of adolescents * Eligible participants were born during January 2002-January 2008. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine represents coverage with ≥1 Tdap dose at age ≥10 years. Meningococcal conjugate vaccine represents coverage with the quadrivalent meningococcal conjugate vaccine or meningococcal-unknown type vaccine. HPV vaccination coverage includes receipt of any HPV vaccine and does not distinguish between nine-valent (9vHPV), quadrivalent (4vHPV), or bivalent (2vHPV) vaccines. Some adolescents might have received more than the 2 or 3 recommended HPV vaccine doses. Hepatitis A, hepatitis B, varicella, and measles, mumps, and rubella vaccines are considered childhood vaccinations and are recommended for adolescents who are not up to date with these vaccinations. Estimates in this report include those who might have received vaccinations on-time or as catch-up. Except as noted, coverage estimates for ≥1 and ≥2 varicella vaccine doses were obtained among adolescents with no history of varicella disease.
APOBEC3G (A3G) is an intrinsic antiviral factor that inhibits HIV replication by deaminating cytidine residues to uridine. This causes G-to-A hypermutation in the opposite strand and results in viral inactivation. HIV counteracts A3G through the activity of viral infectivity factor (Vif), which promotes A3G degradation. We report that viral protein R (Vpr), which interacts with a uracil glycosylase, also counteracts A3G by reducing uridine incorporation. However, this process results in activation of the DNA damage response pathway and expression of NK cell activating ligands. Our results reveal that pathogen-induced cytidine deamination and the DNA damage response to viral-mediated repair of uridine incorporation enhance recognition of HIV-infected cells by NK cells.
SUMMARY HIV infection is characterized by gradual immune system collapse and hematopoietic dysfunction. We recently showed that HIV enters multipotent hematopoietic progenitor cells and establishes both active cytotoxic and latent infections that can be reactivated by myeloid differentiation. However, whether these multipotent progenitors include long-lived hematopoietic stem cells (HSCs) that could establish viral reservoirs for the life of the infected person remains unknown. Here we provide direct evidence that HIV targets long-lived HSCs and show that infected HSCs yield stable, multilineage engraftment in a xenograft model. Furthermore, we establish that the capacity to use the chemokine receptor CXCR4 for entry determines whether a virus will enter multipotent versus differentiated progenitor cells. Because HSCs live for the lifespan of the infected person and are crucial for hematopoietic health, these data may explain the poor prognosis associated with CXCR4-tropic HIV infection and suggest HSCs as long-lived cellular reservoirs of latent HIV.
Background In 2013–2014, an outbreak of serogroup B meningococcal disease occurred among persons linked to a New Jersey university (University A). In the absence of a licensed serogroup B meningococcal (MenB) vaccine in the US, the Food and Drug Administration authorized use of an investigational MenB vaccine to control the outbreak. An investigation of the outbreak and response was undertaken to determine the population at risk and assess vaccination coverage. Methods The epidemiologic investigation relied on compilation and review of case and population data, laboratory typing of meningococcal isolates, and unstructured interviews with university staff. Vaccination coverage data were collected during the vaccination campaign held under an expanded access Investigational New Drug protocol. Results Between March 25, 2013 and March 10, 2014, 9 cases of serogroup B meningococcal disease occurred in persons linked to University A. Laboratory typing results were identical for all 8 isolates available. Through May 14, 2014, 89.1% coverage with the two-dose vaccination series was achieved in the target population. From the initiation of MenB vaccination through February 1, 2015, no additional cases of serogroup B meningococcal disease occurred in University A students. However, the 9th case occurred in March 2014 in an unvaccinated close contact of University A students. Conclusions No serogroup B meningococcal disease cases occurred in persons who received 1 or more doses of 4CMenB vaccine, suggesting 4CMenB may have protected vaccinated individuals from disease. However, the 9th case demonstrates that carriage of serogroup B Nesisseria meningitidis among vaccinated persons was not eliminated.
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