Lifelong Protection Research Articles

Duration of post-vaccination immunity to yellow fever in volunteers ten years after a dose-response study – A complementary study

A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose–response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses.Clinical trial registry: NCT04416477.

Systemic and local regulation of hematopoietic homeostasis in health and disease.

Hematopoietic stem cells (HSCs) generate all blood cell lineages responsible for tissue oxygenation, life-long hematopoietic homeostasis and immune protection. In adulthood, HSCs primarily reside in the bone marrow (BM) microenvironment, consisting of diverse cell types that constitute the stem cell 'niche'. The adaptability of the hematopoietic system is required to respond to the needs of the host, whether to maintain normal physiology or during periods of physical, psychosocial or environmental stress. Hematopoietic homeostasis is achieved by intricate coordination of systemic and local factors that orchestrate the function of HSCs throughout life. However, homeostasis is not a static process; it modulates HSC and progenitor activity in response to circadian rhythms coordinated by the central and peripheral nervous systems, inflammatory cues, metabolites and pathologic conditions. Here, we review local and systemic factors that impact hematopoiesis, focusing on the implications of aging, stress and cardiovascular disease.

Seroprotection against tetanus in the Italian general population

BackgroundTetanus is a non-communicable disease, preventable with vaccination. Despite the implemented vaccination strategy, a certain number of tetanus cases per year continue to occur. The aim of the study was to evaluate the seroprevalence of anti-tetanus antibodies in the Italian population by age, sex and geographical area. MethodsTo determine the level of tetanus-specific antibodies, an immunoenzymatic assay was used. ResultsA total of 3,821 serum samples were collected in the years 2019–20 from healthy subjects aged 6–90 years residing in 13 Italian regions. Overall, 85 % of the tested subjects resulted positive. The rate of subjects protected against tetanus showed a gradual decrease from the younger age groups to the older ones (6–12 years: 93.6 %, 13–24 years: 91.8 %, 25–39 years: 91.0 %, 40–64 years: 78.2 %, ≥ 65 years: 45.3 %); this is particularly evident in the Southern regions and Islands. Moreover, the prevalence of subjects with low protection (<0.1 IU/ml) was significantly higher in the ≥ 65 age group (10.3 %). Males and females’ prevalence showed a significant difference only in the oldest age group (M: 60.8 %, F: 30.4 %). In general, a higher prevalence was observed for Northern (90.8 %) and Central regions (87.3 %) than Southern regions and Islands (80.0 %). ConclusionThese data, compared with epidemiological ones which showed a high number of cases in the elderly, confirmed that the population with lower protection has a greater risk of contracting the disease, demonstrating the need for adequate immunization through both primary vaccination and boosters for all ages and both sexes, in order to provide lifelong protection.

Progress Toward Rubella and Congenital Rubella Syndrome Elimination - Worldwide, 2012-2022.

Rubella virus is a leading cause of vaccine-preventable birth defects. Infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects, including cataracts, deafness, heart defects, and developmental delay, known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine can provide lifelong protection against rubella. The Global Vaccine Action Plan 2011-2020 included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions by 2020, and rubella elimination is a critical goal of the Immunization Agenda 2030. This report updates a previous report and describes progress toward rubella and CRS elimination during 2012-2022. During 2012-2022, among 194 WHO countries, the number that included rubella-containing vaccine (RCV) in their immunization schedules increased from 132 (68%) to 175 (90%) and the percentage of the world's infants vaccinated against rubella increased from 40% to 68%. Reported rubella cases declined 81%, from 93,816 in 2012 to 17,407 in 2022. Verification of rubella elimination was achieved in 98 (51%) of 194 countries by 2022, an increase from 84 (43%) countries in 2019. Despite significant progress in the introduction of RCV into routine immunization programs worldwide, approximately 25 million infants annually still do not have access to RCV. Nevertheless, even in complex settings, the increasing number of countries that have achieved and sustained rubella elimination demonstrates progress toward global rubella elimination.

New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells.

Plasma cells are unique immune effectors, capable of producing large amounts of high-affinity antibodies that protect against pathogenic infections. Although most plasma cells have short lifespans, certain conditions or vaccinations can give rise to long-lived plasma cells (LLPCs) that provide individuals with lifelong protection against pathogen exposure. The nature of these LLPCs is poorly understood; however, recent studies have shed new light on the ontogeny, diversity, maturation and survival of these unique cells. Whereas LLPCs had been thought to arise preferentially from germinal centres, novel genetic tools have revealed that they can originate from various stages throughout the humoral response. Furthermore, new single-cell analyses have shown that mouse and human plasma cells are heterogeneous and may undergo further maturation in situ in the bone marrow niche. Finally, plasma cells were previously considered to be sessile cells maintained in fixed survival niches, but new data show that plasma cell subsets can differentially migrate and organize into clusters that may be associated with survival niches. These descriptive findings provide new insights into how cell-intrinsic programmes and extrinsic factors may regulate the longevity of plasma cells in various contexts, which suggest new research avenues for their functional validation.

B Cell Therapeutics

Plasma cells are specialized immune cells that can survive in the bone marrow for decades and continually secrete large amounts of antibodies, thus providing long-term, often lifelong protection from repeated exposures to a pathogen. The long-term survival and the capability to secrete high amounts of protein make plasma cells a potential candidate for stable delivery of therapeutic proteins and antibodies. However, engineering plasma cells or B cells has been challenging due to low lentiviral transduction efficiency, incompatibility with plasmid transfection and loss of episomal DNA expression over time. We have previously shown that human plasma cells can be engineered to secrete antibodies and proteins in in vitro culture systems via gene editing. In the current study, we have generated engineered murine plasma cells that can secrete the clotting factor IX (FIX). We hypothesize that the FIX-secreting plasma cells will engraft long-term in FIX-deficient immunocompetent mice and secrete therapeutic levels of FIX leading to protection from Hemophilia B. The standard of care for Hemophilia B is repeated intravenous infusion of recombinant FIX or AAV-based gene therapy. However, 30-60% humans have pre-existing immunity to AAV-based gene therapy and gene therapy can induce an immune response in people lacking pre-existing antibodies. Moreover, gene therapy is unsuitable for pediatric patients due to their rapid growth and proportional loss of AAV. Plasma cell-based therapy is lowly immunogenic and can be used for redosing in pediatric patients that require more product with age. Here, we will describe proof-of-concept studies showing that engineered murine plasma cells can engraft into immunocompetent mice without the need for conditioning and produce stable levels of protein for &amp;gt;10 weeks. We developed a three-step in vitro co-culture system that can be used to engineer and differentiate naïve B cells into plasma cells. These in vitro generated murine plasma cells had a comparable gene expression profile and phenotype to natural plasma cells and can engraft stably, in the absence of conditioning, into immunocompetent mice whereupon they secreted antibodies (Figure 1). Moreover, we show that plasma cells can be re-dosed to increase antibody levels without triggering a secondary immune response (Figure 1). For delivery of therapeutic proteins, we have developed adeno-associated virus-based homology directed repair reagents to edit murine B cells at several loci, including beta-2 microglobulin, Rosa-26, and the antibody heavy chain. By co-delivery of cis-linked fluorescent markers, we were able to sort and expand only edited cells, enabling enrichment of cells expressing a therapeutic protein. In proof-of-concept studies, we have used this approach to generate a human FIX-secreting plasma cell product with close to 90% edited cells at the end of the B cell culture. The enriched plasma cells generated 0.28 pg FIX/cell/day compared to 0.19 pg FIX/cell/day generated by the bulk edited cells (figure 2). We estimate that engraftment of 1 million edited plasma cells is sufficient to generate therapeutic levels of FIX upon (figure 2). We have developed reagents for a novel cell-based therapeutic tool with protein secretion capabilities and far-reaching applications. Out studies will provide insights into the feasibility and efficacy of a B cell based therapeutic product.

Attitudes towards hearing, hearing loss, and hearing protection in university students

Objective Young adults are at risk for hearing loss caused by exposure to loud music. Intervention at this stage provides opportunities to support lifelong hearing protection use. This study explores attitudes related to hearing, hearing loss, and hearing protection among university students. Design Qualitative interview design, supplemented by quantitative questionnaire data. Study sample 18 university students, aged 18–24 years. Results Students were uncertain about mechanisms of noise-induced hearing loss, did not feel vulnerable to permanent hearing damage from loud music, were unconvinced of hearing protection efficacy, and reported barriers to hearing protection use. Students emphasised the positive effects of loud music and reported an increased likelihood of using hearing protection were it used by peers. Music students appeared more aware of the negative effects of loud music exposure. Students reported conflicting attitudes regarding government regulation of hearing protection use. Conclusion Young adults require education about hearing protection from multiple, credible sources and need to understand the mechanisms behind noise-induced hearing loss in a way that makes it of high personal relevance.

Health and economic effects of introducing single-dose or two-dose human papillomavirus vaccination in India

BackgroundCervical cancer is a major public health problem in India, where access to prevention programmes is low. The WHO-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus...

Identifying physiological tissue niches that support the HIV reservoir in T cells.

Successful antiretroviral therapy (ART) can efficiently suppress Human Immunodeficiency Virus-1 (HIV-1) replication to undetectable levels, but rare populations of infected memory CD4+ T cells continue to persist, complicating viral eradication efforts. Memory T cells utilize distinct homing and adhesion molecules to enter, exit, or establish residence at diverse tissue sites, integrating cellular and environmental cues that maintain homeostasis and life-long protection against pathogens. Critical roles for T cell receptor and cytokine signals driving clonal expansion and memory generation during immunity generation are well established, but whether HIV-infected T cells can utilize similar mechanisms for their own long-term survival is unclear. How infected, but transcriptionally silent T cells maintain their recirculation potential through blood and peripheral tissues, or whether they acquire new capabilities to establish unique peripheral tissue niches, is also not well understood. In this review, we will discuss the cellular and molecular cues that are important for memory T cell homeostasis and highlight opportunities for HIV to hijack normal immunological processes to establish long-term viral persistence.

"Big Data" Analyses Underlie Clinical Discoveries at the Aortic Institute.

This issue of the Yale Journal of Biology and Medicine (YJBM) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets). 1. Ascending aortic aneurysms should be resected at 5 cm to prevent dissection and rupture. 2. Indexing aortic size to height improves aortic risk prognostication. 3. Aortic root dilatation is more malignant than mid-ascending aortic dilatation. 4. Ascending aortic aneurysm patients with bicuspid aortic valves do not carry the poorer prognosis previously postulated. 5. The descending and thoracoabdominal aorta are capable of rupture without dissection. 6. Female patients with TAA do more poorly than male patients. 7. Ascending aortic length is even better than aortic diameter at predicting dissection. 8. A "silver lining" of TAA disease is the profound, lifelong protection from atherosclerosis. From Modern "Big Data" Machine Learning/Artificial Intelligence analysis: 1. Machine learning models for TAA: outperforming traditional anatomic criteria. 2. Genetic testing for TAA and dissection and discovery of novel causative genes. 3. Phenotypic genetic characterization by Artificial Intelligence. 4. Panel of RNAs "detects" TAA. Such findings, based on (a) long-standing application of advanced conventional statistical analysis to large clinical data sets, and (b) recent application of advanced machine learning/artificial intelligence to large genetic data sets at the Yale Aortic Institute have advanced the diagnosis and medical and surgical treatment of TAA.

Microban launches Ascera™: a patent-pending antimicrobial technology inspired by nature

On September 13, Microban International announced it had introduced its latest technology – Ascera™. This patent-pending antimicrobial technology uses an active ingredient inspired by nature*, and is designed for use in olefinic polymers and solvent-based coatings. The Microban technology used in this product is similar to acids found in nature and is used in multiple consumer product applications. Ascera reportedly is sustainable, metal free and less toxic than alternative technologies, and should provide lifelong antimicrobial product protection.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis

BackgroundTo eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme.MethodsUsing three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021–2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme.ResultsOver the years 2021–2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1–130.4) and 146.8 million (114.1–161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6–169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14–3.82) USD in low-income countries to 44.83 (3.75–85.64) USD in high-income countries, assuming one dose confers 30-year protection.ConclusionsResults were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge.

Vaccines are among the most cost-effective public health measures for controlling infectious diseases. Coxiella burnetii is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX® contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the C. burnetii proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without C. burnetii lipopolysaccharide (LPS) in immunogenicity studies in vivo in mice and in a Hartley guinea pig intratracheal aerosol challenge model using C. burnetii strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. C. burnetii LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.

Multi-Strain Epidemic Models of Mutating Viruses with Airborne Transmission Based on Cellular Automata and Ordinary Differential Equations

The emergence of SARS-CoV-2 virus mutations is a pressing concern in the context of the COVID-19 pandemic. In this paper, a Susceptible–Infected–Recovered (SIR) compartmental model has been formulated in terms of cellular automata and ordinary differential equations to simulate the transmission dynamics of a virus. This model accounts for the potential of new virus mutations to create additional infections of a multi-strain disease while also considering the impact of vaccination on disease control within a population. The basic reproduction number of the disease is derived, and the effect of virus mutations and vaccination rates is evaluated on a population over five years. The results of numerical simulations demonstrate the significant role of maintaining high vaccination rates in controlling the spread of the virus, even when assuming that all variants have similar illness characteristics and that a single shot of vaccine provides complete and lifelong protection against all strains. The findings underscore the necessity for countries to implement a consistent and high-level vaccination plan as soon as vaccines become available in order to mitigate the impact of a pandemic effectively. In conclusion, this study highlights the importance of taking into account the potential impact of virus mutations for controlling the COVID-19 pandemic. Furthermore, it emphasizes the critical role of vaccination in limiting the spread of the virus, and emphasizes the need to implement and maintain high vaccination rates as part of a comprehensive approach to managing the ongoing pandemic.

Incidence of Recurrent SARS-CoV-2 Infections during the COVID19 Pandemic in Madina, Saudi Arabia

Background: SARS-CoV-2 infections emerged in China and spread globally causing the Corona virus disease 2019 (COVID19) pandemic. Dispersed reports from different countries reported the possibility of the incidence of SARS-CoV-2 reinfection in individual reported cases. The aim of this report was, therefore, to document several recurrent infection cases in Saudi Arabia to furtherly augment this body of evidence.&#x0D; Methods: The study was conducted retrospectively from October 2020 to October 2021. The study included patients who had experienced multiple COVID-19 infections, which were confirmed through qPCR tests. There was a minimum gap of three months between each infection, and the patients had tested negative after each infection. Personal or phone interviews were conducted with the patients.&#x0D; Results: In total, 10 cases (7 males and 3 females) of COVID19 recurrent infections were reported with an average age of 34.1 years. The most common symptoms included fever, headache, body aches, sore throat, cough, diarrhea. With the exception of one case that required hospitalization during the third infection and one case of miscarriage during the first infection, all reported cases were mild. The average duration of illness for the first infection was 13.9 days, while for the second infection, it was 12.9 days. Only one patient reported being vaccinated before his second course of infection.&#x0D; Conclusion: Infection with COVID-19 does not provide life-long protection. The possibility of recurrent and repeated reinfection with COVID-19 was presented in several cases especially in healthcare workers, indicating that screening of COVID19 infection in hospitals and healthcare centers is essential.

Breastfeeding and ApoB in late adolescence: a Hong Kong birth cohort study.

Breastfeeding may provide some population-level lifelong protection against cardiovascular disease. This study supports policies promoting breastfeeding as a modifiable exposure that contributes to a healthy start in life as an investment for lifelong cardiovascular disease prevention. • Apolipoprotein B (ApoB) is a recognizedrisk factor forcardiovascular disease, but whether breastfeeding affects ApoB in later life overall and by sex is unknown. • Exclusive breastfeeding in the first 3 months of life was associated with lower ApoB in late adolescence, with similar estimates for both sexes. • The inverse association of breastfeeding with ApoB suggests that breastfeeding could reduce cardiovascular disease and overall mortality over the lifespan.

Tetanus and Diphtheria Seroprotection among Children Younger Than 15 Years in Nigeria, 2018: Who Are the Unprotected Children?

Serological surveys provide an objective biological measure of population immunity, and tetanus serological surveys can also assess vaccination coverage. We undertook a national assessment of immunity to tetanus and diphtheria among Nigerian children aged <15 years using stored specimens collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey, a national cross-sectional household-based survey. We used a validated multiplex bead assay to test for tetanus and diphtheria toxoid-antibodies. In total, 31,456 specimens were tested. Overall, 70.9% and 84.3% of children aged <15 years had at least minimal seroprotection (≥0.01 IU/mL) against tetanus and diphtheria, respectively. Seroprotection was lowest in the north west and north east zones. Factors associated with increased tetanus seroprotection included living in the southern geopolitical zones, urban residence, and higher wealth quintiles (p < 0.001). Full seroprotection (≥0.1 IU/mL) was the same for tetanus (42.2%) and diphtheria (41.7%), while long-term seroprotection (≥1 IU/mL) was 15.1% for tetanus and 6.0% for diphtheria. Full- and long-term seroprotection were higher in boys compared to girls (p < 0.001). Achieving high infant vaccination coverage by targeting specific geographic areas and socio-economic groups and introducing tetanus and diphtheria booster doses in childhood and adolescence are needed to achieve lifelong protection against tetanus and diphtheria and prevent maternal and neonatal tetanus.

Vaccination-Based Immunoprevention of Colorectal Tumors: A Primer for the Clinician.

Colorectal cancer (CRC) continues to be a significant public health problem worldwide. CRC screening programs have reduced the incidence rates of CRCs but still suffer from the problems of missed lesions and interval cancers. Chemopreventive strategies against CRC would benefit high-risk populations but trials testing synthetic and naturally occurring compounds have not yielded a front runner. Immune mechanisms promoting cancer have been modulated to develop immunotherapy for cancer treatment that has revolutionized cancer management, but could also be applied to cancer interception, that is, cancer immunoprevention. Cancer immunoprevention refers to approaches that can enhance the immune system, either directly or by removing natural breaks such as immune checkpoints, to survey and destroy tumor cells. In this primer, we aim to explain the concepts behind vaccine-based cancer immunoprevention. Multiple cancer vaccines have been tried in advanced cancer populations, but most have failed primarily because of an immunosuppressive environment that accompanies advanced cancers. Preventive vaccines in immunocompetent hosts may have a better clinical response compared with therapeutic vaccines in immunosuppressed hosts. The first randomized controlled trial testing the mucin1 vaccine against CRC in the prevention setting has been successfully completed. For the benefit of the clinician, we briefly discuss important concepts related to the workings of preventive vaccines. Prevention with vaccines is a highly attractive approach because of the potential for highly targeted therapy with minimal side effects that could theoretically provide lifelong protection.

Knowledge and Uptake Of Tetanus Toxoid Vaccine and Associated Factors Among Reproductive Age Group Women in Hayk Town South Wollo, Ethiopia, CrossSectional Study

Background Tetanus is an acute, often fatal, disease caused by an exotoxin and highly potent neurotoxin, tetanospasm, Tetanus is a preventable disease by tetanus toxoid immunization, which is usually given to the reproductive women at the age between (15- 44) years in order to protect both mother and newborn in order to prevent maternal and neonatal tetanus For lifelong protection from tetanus a woman needs a total of five tetanus toxoid doses. Objective: To assess the level of knowledge uptake and associated factors of completing tetanus toxoid vaccine among reproductive age women in Hayk town, SouthWollo, Amhara, Ethiopia in 2020. Methods and materials: A community based cross-sectional study conducted in Hayk town, South Wollo Amhara, Ethiopia, from November to December on 2020. Data collected using structured and pretested questionnaire, entered in to Epi Data version 3.1 and exported to statistical package for social science version 25.0 for analysis. Result: Magnitude of uptake of TT2 immunization at Hayk town was 71.2%, have taken at least two doses of TT. But only 35(8.5%) had completed 5 doses of TT according to EPI schedule. Nearly half of 182(44%) of women in the reproductive age group had knowledge on complete TT5 immunization. Educational status, having sort of info on TT5 and knowledge about TT are significantly associated factors for full dose of TT according to EPI schedule. Conclusion: Fair proportions of women had uptake of TT2, but very low proportion for complete dose of TT5 according to expanded program on Immunization. Most of study participants have inadequate knowledge on TT vaccine. Educational status, having sort of info on TT5 and knowledge about TT are significantly associated factors for completing full dose of TT according to EPI schedule.

Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study.

Despite the high burden of cervical cancer, access to preventive measures remains low in India. A single-dose immunisation schedule could facilitate the scale-up of human papillomavirus (HPV) vaccination, contributing to global elimination of cervical cancer. We projected the effect of single-dose quadrivalent HPV vaccination in India in comparison with no vaccination or to a two-dose schedule. In this modelling study, we adapted an HPV transmission model (EpiMetHeos) to Indian data on sexual behaviour (from the Demographic and Health Survey and the Indian National AIDS Control Organisation), HPV prevalence data (from two local surveys, from the states of Tamil Nadu and West Bengal), and cervical cancer incidence data (from Cancer Incidence in Five Continents for the period 2008-12 [volume XI], and the Indian National Centre for Disease Informatics and Research for the period 2012-16). Using the model, we projected the nationwide and state-specific effect of HPV vaccination on HPV prevalence and cervical cancer incidence, and lifetime risk of cervical cancer, for 100 years after the introduction of vaccination or in the first 50 vaccinated birth cohorts. Projections were derived under a two-dose vaccination scenario assuming life-long protection and under a single-dose vaccination scenario with protection duration assumptions derived from International Agency for Research on Cancer (IARC) India vaccine trial data, in combination with different vaccination coverages and catch-up vaccination age ranges. We used two thresholds to define cervical cancer elimination: an age-standardised incidence rate of less than 4 cases per 100 000 woman-years, and standardised lifetime risk of less than 250 cases per 100 000 women born. Assuming vaccination in girls aged 10 years, with 90% coverage, and life-long protection by two-dose or single-dose schedule, HPV vaccination could reduce the prevalence of HPV16 and HPV18 infection by 97% (80% UI 96-99) in 50 years, and the lifetime risk of cervical cancer by 71-78% from 1067 cases per 100 000 women born under a no vaccination scenario to 311 (80% UI 284-339) cases per 100 000 women born in the short term and 233 (219-252) cases per 100 000 women born in the long term in vaccinated cohorts. Under this scenario, we projected that the age-standardised incidence rate threshold for elimination could be met across India (range across Indian states: 1·6 cases [80% UI 1·5-1·7] to 4·0 cases [3·8-4·4] per 100 000 woman-years), while the complementary threshold based on standardised lifetime risk was attainable in 17 (68%) of 25 states, but not nationwide (range across Indian states: 207 cases [80% UI 194-223] to 477 cases [447-514] per 100 000 women born). Under the considered assumptions of waning vaccine protection, single-dose vaccination was projected to have a 21-100% higher per-dose efficiency than two-dose vaccination. Single-dose vaccination with catch-up for girls and women aged 11-20 years was more impactful than two-dose vaccination without catch-up, with reduction of 39-65% versus 38% in lifetime risk of cervical cancer across the ten catch-up birth cohorts and the first ten routine vaccination birth cohorts. Our evidence-based projections suggest that scaling up cervical cancer prevention through single-dose HPV vaccination could substantially reduce cervical cancer burden in India. The Bill &amp; Melinda Gates Foundation.