COVID-19 Mortality and Progress Toward Vaccinating Older Adults - World Health Organization, Worldwide, 2020-2022.

After the emergence of SARS-CoV-2 in late 2019, transmission expanded globally, and on January 30, 2020, COVID-19 was declared a public health emergency of international concern.* Analysis of the early Wuhan, China outbreak (1), subsequently confirmed by multiple other studies (2,3), found that 80% of deaths occurred among persons aged ≥60 years. In anticipation of the time needed for the global vaccine supply to meet all needs, the World Health Organization (WHO) published the Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework and a roadmap for prioritizing use of COVID-19 vaccines in late 2020 (4,5), followed by a strategy brief to outline urgent actions in October 2021.† WHO described the general principles, objectives, and priorities needed to support country planning of vaccine rollout to minimize severe disease and death. A July 2022 update to the strategy brief§ prioritized vaccination of populations at increased risk, including older adults,¶ with the goal of 100% coverage with a complete COVID-19 vaccination series** for at-risk populations. Using available public data on COVID-19 mortality (reported deaths and model estimates) for 2020 and 2021 and the most recent reported COVID-19 vaccination coverage data from WHO, investigators performed descriptive analyses to examine age-specific mortality and global vaccination rollout among older adults (as defined by each country), stratified by country World Bank income status. Data quality and COVID-19 death reporting frequency varied by data source; however, persons aged ≥60 years accounted for >80% of the overall COVID-19 mortality across all income groups, with upper- and lower-middle-income countries accounting for 80% of the overall estimated excess mortality. Effective COVID-19 vaccines were authorized for use in December 2020, with global supply scaled up sufficiently to meet country needs by late 2021 (6). COVID-19 vaccines are safe and highly effective in reducing severe COVID-19, hospitalizations, and mortality (7,8); nevertheless, country-reported median completed primary series coverage among adults aged ≥60 years only reached 76% by the end of 2022, substantially below the WHO goal, especially in middle- and low-income countries. Increased efforts are needed to increase primary series and booster dose coverage among all older adults as recommended by WHO and national health authorities.

COVID-19 Mortality and Vaccine Coverage - Hong Kong Special Administrative Region, China, January 6, 2022-March 21, 2022.

What is already known about this topic?: COVID-19 vaccines are important tools to protect populations from severe disease and death. What is added by this report?: Among persons aged ≥60 years in Hong Kong, 49%, had received ≥2 doses of a COVID-19 vaccine, and vaccination coverage declined with age. During January-March 2022, reported COVID-19-associated deaths rose rapidly in Hong Kong. Among these deaths, 96% occurred in persons aged ≥60 years; within this age group, the risk for death was 20 times lower among those who were fully vaccinated compared with those who were unvaccinated. What are the implications for public health practice?: Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially in older adults.

COVID-19 Mortality and Vaccine Coverage - Hong Kong Special Administrative Region, China, January 6, 2022-March 21, 2022.

On January 6, 2022, a cluster of COVID-19 cases* caused by the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, was detected in Hong Kong Special Administrative Region, China (Hong Kong), resulting in the territory's fifth wave of COVID-19 cases (1). This wave peaked on March 4, 2022, with 8,764 COVID-19 cases per million population (2), resulting in a total of 1,049,959 cases and 5,906 COVID-19-associated deaths reported to the Hong Kong Department of Health during January 6-March 21, 2022.† Throughout this period, the COVID-19 mortality rate in Hong Kong (37.7 per million population) was among the highest reported worldwide since the COVID-19 pandemic began (3). Publicly available data on age-specific vaccination coverage in Hong Kong with a 2-dose primary vaccination series (with either Sinovac-CoronaVac [Sinovac], an inactivated COVID-19 viral vaccine, recommended for persons aged ≥3 years or BNT162b2 [Pfizer-BioNTech], an mRNA vaccine, for persons aged ≥5 years), as of December 23, 2021,§,¶ and COVID-19 mortality during January 6-March 21, 2022, were analyzed. By December 23, 2021, 67% of vaccine-eligible persons in Hong Kong had received ≥1 dose of a COVID-19 vaccine, 64% had received ≥2 doses, and 5% had received a booster dose. Among persons aged ≥60 years, these proportions were 52%, 49%, and 7%, respectively. Among those aged ≥60 years, vaccination coverage declined with age: 48% of persons aged 70-79 years had received ≥1 dose, 45% received ≥2 doses, and 7% had received a booster, and among those aged ≥80 years, 20%, 18%, and 2% had received ≥1 dose, ≥2 doses, and a booster dose, respectively. Among 5,906 COVID-19 deaths reported, 5,655 (96%) occurred in persons aged ≥60 years**; among these decedents, 3,970 (70%) were unvaccinated, 18% (1,023) had received 1 vaccine dose, and 12% (662) had received ≥2 doses. The overall rates of COVID-19-associated mortality among persons aged ≥60 years who were unvaccinated, who had received 1 COVID-19 vaccine dose, and who had received ≥2 vaccine doses were 10,076, 1,099, and 473 per million population, respectively; the risk for COVID-19-associated death among unvaccinated persons was 21.3 times that among recipients of 2-3 doses in this age group. The high overall mortality rate during the ongoing 2022 Hong Kong Omicron COVID-19 outbreak is being driven by deaths among unvaccinated persons aged ≥60 years. Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially among persons aged ≥60 years.

Students' Perceptions of FSBio 201, A CURE-Based Course that Scaffolds Research and Scientific Communication, Align with Learning Outcomes.

Incorporating active research opportunities into undergraduate curricula is one of the most cited elements demonstrated to improve inclusive excellence and retention in all STEM fields. Allegheny College has a long and nationally-recognized tradition of collaborative student-faculty research within the academic curriculum and as co-curricular opportunities. We present an example of the former, a Course-based Undergraduate Research Experience (CURE), FSBio 201, that has been central to Allegheny's biology curriculum for over two decades. The course emphasizes biological research design, execution, and communication. We have coded and analyzed feedback from student evaluations and from the national CURE project database, both of which measure students' perceptions and attitudes toward the course. The majority of the student feedback related to the course learning outcomes of fostering independent research and communication skills was positive. However, we also see areas for improvement, such as how we employ peer-to-peer mentoring and how we teach quantitative and computer-based skills. We conclude that students' self-reported data are in line with our learning outcomes and provide FSBio 201 as a model for introducing college undergraduates to biological research.

Virus Innexins induce alterations in insect cell and tissue function.

Polydnaviruses are dsDNA viruses that induce immune and developmental alterations in their caterpillar hosts. Characterization of polydnavirus gene families and family members is necessary to understand mechanisms of pathology and evolution of these viruses, and may aid to elucidate the role of host homologues if present. For example, the polydnavirus vinnexin gene family encodes homologues of insect gap junction genes (innexins) that are expressed in host immune cells (hemocytes). While the roles of Innexin proteins and gap junctions in insect immunity are largely unclear, we previously demonstrated that Vinnexins form functional gap junctions and alter the junctional characteristics of a host Innexin when co-expressed in paired Xenopus oocytes. Here, we test the effect of ectopic vinnexin expression on host cell physiology using both a lepidopteran cell culture model and a dipteran whole organism model. Vinnexin expression in the cell culture system resulted in gene-specific alterations in cell morphology and a slight, but non-statistically significant, reduction in gap junction activity as measured by dye transfer, while ectopic expression of a lepidopteran innexin2 gene led to morphological alterations and increase in gap junction activity. Global ectopic expression in the model dipteran, Drosophila melanogaster, of one vinnexin (vinnexinG) or D. melanogaster innexin2 (Dm-inx2) resulted in embryonic lethality, while expression of the other vinnexin genes had no effect. Furthermore, ectopic expression of vinnexinG, but not other vinnexin genes or Dm-inx2, in D. melanogaster larval gut resulted in developmental arrest in the pupal stage. These data indicate the vinnexins likely have gene-specific roles in host manipulation. They also support the use of Drosophila in further analysis of the role of Vinnexins and other polydnavirus genes in modifying host physiological processes. Finally, our findings suggest the vinnexin genes may be useful to perturb and characterize the physiological functions of insect Innexins.

More than Meets the Eye: A Primer for "Timing of Locomotor Recovery from Anoxia Modulated by the white Gene in Drosophila melanogaster".

SummaryA single gene might have several functions within an organism, and so mutational loss of that gene has multiple effects across different physiological systems in the organism. Though the white gene in Drosophila melanogaster was identified originally for its effect on fly eye color, an article by Xiao and Robertson in the June 2016 issue of GENETICS describes a function for the white gene in the response of Drosophila to oxygen deprivation. This Primer article provides background information on the white gene, the phenomenon of pleiotropy, and the molecular and genetic approaches used in the study to demonstrate a new behavioral function for the white gene.

Trends in AIDS Deaths, New Infections and ART Coverage in the Top 30 Countries with the Highest AIDS Mortality Burden; 1990-2013.

BACKGROUND: Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV) disease progression, mortality and transmission. We assess the impact of expanded HIV treatment for the prevention of Acquired Immunodeficiency Syndrome (AIDS)-related deaths and simulate four treatment scenarios for Nigeria and South Africa. METHODS: For 1990-2013, we used the Joint United Nations Programme on HIV/AIDS (UNAIDS) database to examine trends in AIDS deaths, HIV incidence and prevalence, ART coverage, annual AIDS death rate, AIDS death-to-treatment and HIV infections to treatment ratios for the top 30 countries with the highest AIDS mortality burden and compare them with data from high-income countries. We projected the 1990-2020 AIDS deaths for Nigeria and South Africa using four treatment scenarios: 1) no ART; 2) maintaining current ART coverage; 3) 90% ART coverage based on 2013 World Health Organization (WHO) ART guidelines by 2020; and 4) reaching the United Nations 90-90-90 Target by 2020. FINDINGS: In 2013, there were 1.3 million (1.1 million-1.6 million) AIDS deaths in the top 30 countries representing 87% of global AIDS deaths. Eight countries accounted for 58% of the global AIDS deaths; Nigeria and South Africa accounted for 27% of global AIDS deaths. The highest death rates per 1000 people living with HIV were in Central African Republic (91), South Sudan (82), Côte d'Ivoire (75), Cameroon (72) and Chad (71), nearly 8-10 times higher than the high-income countries. ART access in 2013 has averted as estimated 1,051,354 and 422,448 deaths in South Africa and Nigeria, respectively. Increasing ART coverage in these two countries to meet the proposed UN 90-90-90 Target by 2020 could avert 2.2 and 1.2 million deaths, respectively. INTERPRETATION: Over the past decade the expansion of access to ART averted millions of deaths. Reaching the proposed UN 90-90-90 Target by 2020 will prevent additional morbidity, mortality and HIV transmission. Despite progress, high-burden countries will need to accelerate access to ART treatment to avert millions of premature AIDS deaths and new HIV infections.

Global Policy Review of Recommendations on Cotrimoxazole Prophylaxis among People Living with HIV.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) Treatment 2015 calls for expanded access to HIV care and treatment, including cotrimoxazole preventive therapy (CPT), for prevention of HIV-related morbidity and mortality. We review 115 national guidelines from 92 countries for recommendations on CPT for adults and adolescents and determine the level of consistency with the World Health Organization (WHO) guidelines. Of the 66 countries with recommendations, 5 (8%) countries recommend lifelong CPT for people living with HIV; 19 (29%) countries recommend a CD4 count threshold of ≤350 cells/mm(3) or WHO clinical stages III and IV or II, III, and IV; and 19 (29%) countries recommend a CD4 count threshold of ≤200 cells/mm(3). Of the 48 countries with recommendations on discontinuing CPT, 25 (52%) countries recommend discontinuation of cotrimoxazole when the CD4 count is >200 cells/mm(3). World Health Organization guidelines offer countries flexibility on the use of CPT, and countries are recommending a wide range of CD4 counts and WHO clinical stage criteria for prophylaxis initiation and discontinuation.

Hox en provence.

In the nearly 25 years since the cloning of the first Hox genes, the broad brushstrokes of their functions in axial patterning have become familiar motifs in developmental biology. The October 2007 Fondation des Treilles workshop on "Hox Genes in Development and Evolution" in Les Treilles, France, highlighted some of the finer details regarding the function of these genes in shaping animal morphology.

Has the 2005 measles mortality reduction goal been achieved? A natural history modelling study.

BACKGROUND: In 2002, the UN General Assembly Special Session on Children adopted a goal to reduce deaths owing to measles by half by the end of 2005, compared with 1999 estimates. We describe efforts and progress made towards this goal. METHODS: We assessed trends in immunisation against measles on the basis of national implementation of the WHO/UNICEF comprehensive strategy for measles mortality reduction, and the provision of a second opportunity for measles immunisation. We used a natural history model to evaluate trends in mortality due to measles. RESULTS: Between 1999 and 2005, according to our model mortality owing to measles was reduced by 60%, from an estimated 873,000 deaths (uncertainty bounds 634,000-1,140,000) in 1999 to 345,000 deaths (247,000-458,000) in 2005. The largest percentage reduction in estimated measles mortality during this period was in the western Pacific region (81%), followed by Africa (75%) and the eastern Mediterranean region (62%). Africa achieved the largest total reduction, contributing 72% of the global reduction in measles mortality. Nearly 7.5 million deaths from measles were prevented through immunisation between 1999 and 2005, with supplemental immunisation activities and improved routine immunisation accounting for 2.3 million of these prevented deaths. INTERPRETATION: The achievement of the 2005 global measles mortality reduction goal is evidence of what can be accomplished for child survival in countries with high childhood mortality when safe, cost-effective, and affordable interventions are backed by country-level political commitment and an effective international partnership.

The UBX-regulated network in the haltere imaginal disc of D. melanogaster.

Hox proteins have been proposed to act at multiple levels within regulatory hierarchies and to directly control the expression of a plethora of target genes. However, for any specific Hox protein or tissue, very few direct in vivo-regulated target genes have been identified. Here, we have identified target genes of the Hox protein Ultrabithorax (UBX), which modifies the genetic regulatory network of the wing to generate the haltere, a modified hindwing. We used whole-genome microarrays and custom arrays including all predicted transcription factors and signaling molecules in the Drosophila melanogaster genome to identify differentially expressed genes in wing and haltere imaginal discs. To elucidate the regulation of selected genes in more detail, we isolated cis-regulatory elements (CREs) for genes that were specifically expressed in either the wing disc or haltere disc. We demonstrate that UBX binds directly to sites in one element, and these sites are critical for activation in the haltere disc. These results indicate that haltere and metathoracic segment morphology is not achieved merely by turning off the wing and mesothoracic development programs, but rather specific genes must also be activated to form these structures. The evolution of haltere morphology involved changes in UBX-regulated target genes, both positive and negative, throughout the wing genetic regulatory network.

Efforts at rubella elimination in the United States: the impact of hemispheric rubella control.

We examined rubella vaccination trends, rubella surveillance, and disease patterns for the Americas, Mexico, and the United States, to evaluate the impact of hemispheric rubella control on rubella elimination in the United States during 1997-2004. In 1997, 130,375 rubella cases were reported in the Americas, with 38,042 reported in Mexico. Over the next 7 years, a rubella control initiative resulted in the administration of approximately 110 million rubella-containing vaccine doses in Latin America, with 77.7 million doses administered within Mexico. By 2004, the number of reported rubella cases had declined to 3103 in the Americas and 698 in Mexico. Concurrently, the number of rubella cases in the United States fell from 817 during 1997-1999 to <25 cases/year from 2001 onward, with loss of seasonality and geographic clustering, despite no change in vaccination rates. Implementation of rubella control strategies in the Americas, particularly in Mexico, appears to have facilitated rubella elimination in the United States.

Direct regulation of knot gene expression by Ultrabithorax and the evolution of cis-regulatory elements in Drosophila.

The regulation of development by Hox proteins is important in the evolution of animal morphology, but how the regulatory sequences of Hox-regulated target genes function and evolve is unclear. To understand the regulatory organization and evolution of a Hox target gene, we have identified a wing-specific cis-regulatory element controlling the knot gene, which is expressed in the developing Drosophila wing but not the haltere. This regulatory element contains a single binding site that is crucial for activation by the transcription factor Cubitus interruptus (Ci), and a cluster of binding sites for repression by the Hox protein Ultrabithorax (UBX). The negative and positive control regions are physically separable, demonstrating that UBX does not repress by competing for occupancy of Ci-binding sites. Although knot expression is conserved among Drosophila species, this cluster of UBX binding sites is not. We isolated the knot wing cis-regulatory element from D. pseudoobscura, which contains a cluster of UBX-binding sites that is not homologous to the functionally defined D. melanogaster cluster. It is, however, homologous to a second D. melanogaster region containing a cluster of UBX sites that can also function as a repressor element. Thus, the knot regulatory region in D. melanogaster has two apparently functionally redundant blocks of sequences for repression by UBX, both of which are widely separated from activator sequences. This redundancy suggests that the complete evolutionary unit of regulatory control is larger than the minimal experimentally defined control element. The span of regulatory sequences upon which selection acts may, in general, be more expansive and less modular than functional studies of these elements have previously indicated.

Migration as a risk factor for measles after a mass vaccination campaign, Burkina Faso, 2002.

BACKGROUND: Shortly after a measles supplementary immunization activity (SIA) targeting children from 9 months to 14 years of age that achieved high coverage, Burkina Faso had a large, serologically confirmed measles outbreak. To investigate the causes of this first reported failure of a widely successful measles control strategy we conducted a case-control study. METHODS: Serologically confirmed measles cases aged > or =9 months at the time of the SIA in 6 heavily affected districts were frequency matched on age to 3 controls recruited from people frequenting health centres in the same districts. RESULTS: Between January and July 2002, 1287 measles cases were reported throughout Burkina Faso. Of the 707 cases that were serologically confirmed, 358 (51%) were from 9 months to 14 years of age and 265 (37%) were > or =15 years of age. Among cases and controls from 9 months to 14 years of age significant risk factors for measles were lack of measles vaccination and, in the unvaccinated, recent travel to Cote d'Ivoire. Of the recent measles cases in Cote d'Ivoire 54% were there when exposed to measles. Among adults, risk factors included non-vaccination and the lack of school attendance during childhood. Vaccine effectiveness was estimated to be 98%. CONCLUSIONS: Migration of children between Cote d'Ivoire and Burkina Faso played a major role in the failure of the SIA to interrupt measles transmission. Synchronization of measles control activities should be a high priority in countries with regions where much migration occurs.

The regulatory content of intergenic DNA shapes genome architecture.

BACKGROUND: Factors affecting the organization and spacing of functionally unrelated genes in metazoan genomes are not well understood. Because of the vast size of a typical metazoan genome compared to known regulatory and protein-coding regions, functional DNA is generally considered to have a negligible impact on gene spacing and genome organization. In particular, it has been impossible to estimate the global impact, if any, of regulatory elements on genome architecture. RESULTS: To investigate this, we examined the relationship between regulatory complexity and gene spacing in Caenorhabditis elegans and Drosophila melanogaster. We found that gene density directly reflects local regulatory complexity, such that the amount of noncoding DNA between a gene and its nearest neighbors correlates positively with that gene's regulatory complexity. Genes with complex functions are flanked by significantly more noncoding DNA than genes with simple or housekeeping functions. Genes of low regulatory complexity are associated with approximately the same amount of noncoding DNA in D. melanogaster and C. elegans, while loci of high regulatory complexity are significantly larger in the more complex animal. Complex genes in C. elegans have larger 5' than 3' noncoding intervals, whereas those in D. melanogaster have roughly equivalent 5' and 3' noncoding intervals. CONCLUSIONS: Intergenic distance, and hence genome architecture, is highly nonrandom. Rather, it is shaped by regulatory information contained in noncoding DNA. Our findings suggest that in compact genomes, the species-specific loss of nonfunctional DNA reveals a landscape of regulatory information by leaving a profile of functional DNA in its wake.

Rubella and congenital rubella syndrome: global update

Se calcula que cada año nacen en el mundo más de 100 000 niños con síndrome de rubéola congénita (SRC). La Organización Mundial de la Salud (OMS) estandarizó en 1998 las definiciones de casos para la vigilancia del SRC y de la rubéola. En 2001, 123 países o territorios notificaron 836 356 casos de rubéola y se espera que el número de países se incremente a medida que se desarrolla, bajo la coordinación de la OMS, una red mundial de laboratorios para la detección del sarampión y la rubéola. Se están realizando investigaciones para mejorar la vigilancia de esta última enfermedad, entre ellas algunos proyectos encaminados a echar a andar la vigilancia y a comparan métodos diagnósticos, así como estudios de epidemiología molecular para lograr entender más a fondo los patrones de circulación del virus de la rubéola en el mundo. En 1996 una encuesta efectuada por la OMS reveló que 78 (36 per ciento) de los 214 países o territorios que habían notificado casos de la enfermedad aplicaban la vacuna contra la rubéola como parte de su régimen de vacunación estándar. Para fines de 2002 un total de 124 de esos 214 (58 per ciento) países o territorios aplicaban la vacuna antirrubeólica cuyo uso depende del nivel de desarrollo económico: 100 per ciento en países industrializados, 71 per ciento en países con economías en transición y 48 per ciento en países en desarrollo. Se dispone de una vacuna inocua y eficaz y se ha demostrado la eficacia de algunas estrategias de vacunación para la prevención de la rubeóla y el SRC. En un trabajo de posición de la OMS se ofrece orientación acerca de lo que entraña, desde el punto de vista programático, emprender la vacunación antirrubeólica. Se trata de una medida cuya efectividad y beneficios superan su costo, pero que exige un continuo fortalecimiento de los servicios de vacunación y sistemas de vigilancia habituales.

The unfinished measles immunization agenda.

Despite achieving and sustaining global measles vaccination coverage of about 80% over the past decade, worldwide measles remains the fifth leading cause of mortality among children aged <5 years. In May 2002, the United Nations Special Session on Children endorsed the goal of reducing measles deaths by half by 2005. Countries and World Health Organization (WHO) regions that adopted aggressive measles control or elimination strategies have shown excellent results. In 2001, countries in the Americas reported an all time low of 537 confirmed measles cases. Substantial progress in measles control has also been achieved in the WHO Western Pacific Region, in seven southern African countries, and in selected countries in WHO European, Eastern Mediterranean, and Southeast Asian regions. The ongoing measles disease burden and availability of safe and effective measles mortality reduction strategies make a compelling case to complete the unfinished agenda of measles immunization.

Ensuring injection safety during measles immunization campaigns: more than auto-disable syringes and safety boxes.

Measles immunization campaigns are effective elements of a comprehensive strategy for preventing measles cases and deaths. However, if immunizations are not properly administered or if immunization waste products are not safely managed, there is the potential to transmit bloodborne pathogens (e.g., human immunodeficiency virus and hepatitis B and hepatitis C). A safe injection can be defined as one that results in no harm to the recipient, the vaccinator, and the surrounding community. Proper equipment, such as the exclusive use of auto-disable syringes and safety boxes, is necessary, but these alone are not sufficient to ensure injection safety in immunization campaigns. Equally important are careful planning and managerial activities that include policy and strategy development, financing, budgeting, logistics, training, supervision, and monitoring. The key elements that must be in place to ensure injection safety in measles immunization campaigns are outlined.

Rubella and congenital rubella syndrome: global update.

Worldwide, it is estimated that there are more than 100.000 infants born with congenital rubella syndrome (CRS) each year. In 1998, standard case definitions for surveillance of CRS and rubella were developed by the World Health Organization (WHO). In 2001, 123 countries/territories reported a total of 836.356 rubella cases. In the future more countries are expected to report on rubella as a global measles/rubella laboratory network is further developed under the coordination of WHO. Operational research is being conducted to improve rubella surveillance. This includes projects on initiating CRS surveillance, comparative studies on diagnostic laboratory methods, and molecular epidemiology research to expand the global understanding of patterns of rubella virus circulation. In 1996 a WHO survey found that 78 od 214 reporting countries/territories (36%) were using rubella vaccine in their routine immunization services. By the en of 2002 a total of 124 of the 214 counties/territories (58%) were using rubella vaccine. Rubella vaccine use varies by stage of economic development: 100% for industrialized countries, 71% for countries with economies in transition, and 48% for developing countries. A safe effective rubella vaccine is available, and there are proven vaccination strategies for preventing rubella and CRS. A WHO position paper provides guidance on programmatic aspects of rubella vaccine introduction. The introduction of rubella vaccine is cost-effective and cost-beneficial but requires ongoing strengthening of routine immunization services and surveillance systems.