The Effect of Selective and Mass Immunization Against Pneumococcal Infection on the Morbidity and Mortality due to Community-Acquired Pneumonia in Children Under 5 Years of Age

Background. It is required to perform estimation of epidemiological and cost efficacy (regarding morbidity rate) of mass routine vaccination against pneumococcal infection in Russian children and carried out earlier selective vaccination of children from high-risk groups on the basis of four-year experience. It is also important to estimate the rate of hospital admissions in this patient group, long-term and annual cycles, morbidity age and etiology structure, and mortality due to community-acquired pneumonia as one of the most common form of pneumococcal disease. The aim is to study the effect of selective and mass immunization against pneumococcal infection on the morbidity and mortality due to community-acquired pneumonia in children under 5 years of age. Methods. The analysis of communityacquired pneumonia morbidity (in 2003–2018) and mortality due to pneumonias (in 2003–2018) in children under the 14 years old in Perm was carried out. Serotypes of circulating pneumococcus, etiology of community-acquired pneumonias and immunization cost efficacy (direct expense on health care) were further studied. The analysis of study indexes was carried out following selective (vaccination of at-risk children in 2011–2014) and mass (vaccination of infants in 2015–2018) immunization strategies. Results. The morbidity rate of community-acquired pneumonias decreased by 4.0 times (from 267.0 to 66.7 for 1000) after performing selective vaccination (2011–2014) in at-risk children (frequently and chronically ill children). The morbidity rate of community-acquired pneumonias in non vaccinated children of the same group increased by 2.0 times (from 40.0 to 80.0 for 1000 non-vaccinated). The prophylactic efficacy index was 46.0. Whereby the antibacterial index among vaccinated frequently and chronically ill children was 0.11 on one child. This index has decreased by 2.6 times (from 0.11 to 0.04 on one child) in a year within the framework of prospective controlled randomized clinical study. The antibacterial index among non-vaccinated children of this group remained slightly the same: 0.09 and 0.12 respectively. During the selective vaccination the mortality rate among infants decreased by 2 times: long-term average index was 17.9 (2011–2014) against 35.2 (2003-2010) on 100 thousand children. Mass vaccination of infants against pneumococcal infection has reduced the incidence of community-acquired pneumonias among children under 2 years of age and has led to absence of multiple sites of pneumococcal infection in children’s organizations. It also has reduced the number of hospitalized children and achieved zero mortality due to pneumonias in infants by the third year of this immunization strategy implementation. The obtained results were achieved mainly due to circulation of 7 pneumococcal serotypes (6A, 6B, 9V, 14, 19A, 19F, 23F) in children under 5 years of age. The threshold level of vaccination against pneumococcal infection advancing morbidity and mortality due to pneumonias in children was specified. The strategy of mass vaccination of infants was cost-effective. Conclusion. The new data on epidemiological and cost efficacy of various immunization strategies against pneumococcal infection in children was obtained

Bronchopulmonary Pathology Prevalence Among Premature infants and Estimation of Prophylactic Efficacy and Reactogenicity of 13-Valent Pneumococcal Conjugate Vaccine in Premature infants with Bronchopulmonary Dysplasia

Background. The most frequent chronic lung pathology among infants and especially in premature children with extremely low and very low body weight is bronchopulmonary dysplasia (BPD). The aim of the study is to study the prevalence of bronchopulmonary pathology among premature children and justify the need to vaccinate against pneumococcal disease premature children suffering from BPD. Methods. The official statistics (Form №32) and data from annual reports of the catamnesis department of “the Honourary order” Perm Regional Clinical Hospital were used in order to measure the number of premature children born alive in Perm region in 2015-2017 yy. The estimation of prophylactic efficacy and reactogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) at immunization of premature children with BPD. Results. The study group included vaccinated premature children with BPD (n=29), the experimental group included non-vaccinated premature children with BPD (n=29) and 30 vaccinated term children. Administration of PCV13 in premature children suffering from BPD has revealed its high prophylactic efficacy (no cases of community-acquired pneumonia among vaccinated children during the prospective study for 3 years), high tolerability (no cases of broncho-obstructive syndrome or negative effects on respiratory system such as apnoea or desaturation among vaccinated children). Low reactogenicity (17.2 ± 0.57%) and similar vaccine tolerance with term children (16.5 ± 0.55%) has been revealed as well. The combination of PCV13 with other vaccines from immunisation schedule did not increase the number of vaccine-induced diseases in comparison with administration of PCV13 alone. Conclusion. The scientific necessity of vaccination of premature children with BPD against pneumococcal disease has been proved. The high prophylactic efficacy and low reactogenicity of PCV13 in this children group at tertiary neonatological care (catamnesis department of perinatal center) has been established within the national immunisation schedule

The formation of human populations in South and Central Asia

By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.N.P. carried out this work while a fellow at the Radcliffe Institute for Advanced Study at Harvard University. P.M. was supported by a Burroughs Wellcome Fund CASI award. N.N. is supported by a NIGMS (GM007753) fellowship. T.C. and A.D. were supported by the Russian Science Foundation (project 14-50-00036). T.M.S. was supported by the Russian Foundation for Basic Research (grant 18-09-00779) “Anthropological and archaeological aspects of ethnogenesis of the population of the southern part of Western and Central Siberia in the Neolithic and Early Bronze Age.” D.P., S.S., and D.L. were supported by European Research Council ERC-2011-AdG 295733 grant (Langelin). O.M. was supported by a grant from the Ministry of Education and Sciences of the Russian Federation No. 33.1907, 2017/Π4 “Traditional and innovational models of a development of ancient Volga population”. A.E. was supported by a grant from the Ministry of Education and Sciences of the Russian Federation No. 33.5494, 2017/BP “Borderlands of cultural worlds (Southern Urals from Antiquity to Early Modern period).” Radiocarbon dating work supported by the NSF Archaeometry program BCS-1460369 to D.Ken. and B.J.C. and by the NSF Archaeology program BCS-1725067 to D.Ken. K.Th. was supported by NCP fund (MLP0117) of the Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi. N.Bo., A.N., and M.Z. were supported by the Max Planck Society. D.Re. is an Investigator of the Howard Hughes Medical Institute, and his ancient DNA laboratory work was supported by National Science Foundation HOMINID grant BCS-1032255, by National Institutes of Health grant GM100233, by an Allen Discovery Center grant, and by grant 61220 from the John Templeton Foundation

Population genomics of post-glacial western Eurasia

Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations

Population genomics of post-glacial western Eurasia

Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations