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[Population surveillance and its importance in the study of the effectiveness of primary and secondary prevention of ischemic heart disease among the population].

The results of epidermiologic surveys conducted in the USSR and in other countries are briefly analysed. It is noted that study of the effectiveness of the elaborated measures for primary and secondary prevention of ischemic heart disease is the principal object of long-term surveys among the population. The author believes the term population surveys to be most justified. The general principles of the organization of population surveys are described. Approaches to the evaluation of the effectiveness of intervention among the population are briefly characterized.

Adult

[Participation of the population in mass screening and the role of complete population surveillance for detection of the disease studied (from the experience of the methodical measures for the prevention of ischemic heart disease in Kaunas)].

A comparison of the results of examination of 100 individuals, some of whom had taken part in the survey while the others had refused it and information about them was specially obtained by other means (in some cases by collecting the medical documentation), is presented. Factors conducive to the development of ischemic heart disease predominated among individuals who refused to take part in the survey. The incidence of ischemic heart disease and arterial hypertension was also higher among them. It is concluded that individuals who refuse examination during preventive survey form a group with a high risk of the development of ischemic heart disease; this group should be taken into account when therapeutic and preventive measures are conducted among the population.

Aged

Gestational exposure to rubella vaccinees: a population surveillance study.

Over a two-year period an attempt was made to identify instances of transmission of rubella vaccine virus from rubella vaccinees to pregnant women in Nashville-Davidson County, Tennessee. Approximately 24,000 children were immunized in a mass campaign at the outset of the study. Several prospective surveillance methods of 11,635 women and their new babies were employed. Attempts were made to recover rubella virus from throat swabs of 10,951 newborns. No rubella vaccine virus was recovered. Wild rubella virus was isolated from a single infant with the congenital rubella syndrome whose mother had natural rubella during the first month of pregnancy. Rubella virus was not isolated from the products of 240 abortions. There were no seroconversions among 3990 women who had paired sera available for study. Clinical and serologic follow-ups of infants judged to be a high risk because of intimate maternal exposure to vaccine virus revealed no late manifestations of congenital rubella infection. A history of close maternal contact with vaccinees during the three months before and the three months following conception was not associated with an increased incidence of congenital anomalies or clinical features seen with congenital rubella infection. Thus, no evidence of vaccine virus transmission was found, providing further evidence of the safety of rubella vaccine under field conditions. A seroepidemiologic study of 8824 pregnant women revealed the expected decline in rubella susceptibility with increasing age. When age was controlled, the variables of race, parity, and educational achievement produced no major influence on immunity.

Antibodies, Viral

SARS-CoV-2 genomic diversity and within-host evolution in individuals with persistent infection in the UK: an observational, longitudinal, population-based surveillance study.

BACKGROUND: Persistent SARS-CoV-2 infections in hospitalised immunocompromised individuals are known to facilitate accelerated within-host viral evolution, potentially contributing to the emergence of highly divergent variants. However, little is known about the evolutionary dynamics and transmission risks of persistent infections in the general population. We aimed to characterise the within-host evolution of SARS-CoV-2 during persistent infections identified through a large community surveillance study. METHODS: We used data from the Office for National Statistics COVID-19 Infection Survey (ONS-CIS), a large-scale, longitudinal, population-based surveillance study conducted in the UK from April, 2020, to March, 2023. For this analysis, we focused on infections with high viral load (cycle threshold &#x2264;30) and available genome sequences, from seven major SARS-CoV-2 lineages (alpha, delta, BA.1, BA.2, BA.4, BA.5, and XBB). ONS-CIS participants were randomly selected from the general population and tested regularly by RT-PCR, regardless of symptoms. We defined persistent infections as those with sustained or rebounding high viral RNA titres for 26 days or longer. We examined associated host characteristics and used raw sequence data to identify de novo mutations and estimate within-host synonymous and non-synonymous evolutionary rates across the SARS-CoV-2 genome. FINDINGS: Between Nov 2, 2020, and March 21, 2023, we identified 576 persistent infections with at least two sequences, including 11 alpha, 106 delta, 102 BA.1, 204 BA.2, 16 BA.4, 133 BA.5, and 4 XBB. Persistent infections were more common in males than females (p<0&#xb7;0001) and individuals older than 60 years (p=0&#xb7;0027). The median within-host genome-wide evolutionary rate was 7&#xb7;9&#x2009;&#xd7;&#x2009;10-4 substitutions per site per year (IQR 7&#xb7;0-9&#xb7;0&#x2009;&#xd7;&#x2009;10-4), with high inter-individual variability driven largely by non-synonymous mutations, particularly in the N-terminal and receptor-binding domains of the spike protein. Longer infection duration was associated with higher evolutionary rates, while no associations were found with age, sex, vaccination status, previous infection, or virus lineage. We found no clear evidence of transmission beyond the first month of infection in any of the 84 persistent infections lasting 56 days or longer. In total, we identified 379 recurrent mutations, including many with known or predicted negative fitness effects and low prevalence at the population level, as well as de novo reversions to the Wuhan-Hu-1 reference sequence, which were likely under positive selection within those individuals. INTERPRETATION: This study highlights the heterogeneous nature of within-host SARS-CoV-2 evolution in individuals with persistent infection in the community. Notably, a small subset of persistent infections with high viral loads underwent accelerated viral evolution or recurrently acquired hallmark mutations found in novel variants. In addition, onward transmission from a persistent infection during the later stages of infection is likely to be rare. These insights have important implications for prioritising genomic surveillance and managing patients with persistent infections. FUNDING: Department of Health and Social Care.

Humans

Diagnostic and phylogenetic perspectives of the 2023 Murray Valley encephalitis virus outbreak in Australia: an observational study.

BACKGROUND: An outbreak of Murray Valley encephalitis virus (MVEV), the largest since 1974, was observed in Australia between Jan 1 and July 31, 2023. This study aims to characterise the utility of diagnostic platforms, testing algorithms, and genomic characteristics of MVEV to facilitate a comprehensive framework for MVEV testing and surveillance in the outbreak setting. METHODS: In this observational study, we assessed flavivirus diagnostics for all patients with suspected Murray Valley encephalitis in Australia from Jan 1 to July 31, 2023. We included all patients with confirmed Murray Valley encephalitis, probable Murray Valley encephalitis, or acute unspecified flavivirus infection using the Communicable Diseases Network Australia case definition. Cases were excluded if an alternative diagnosis was identified. We collected blood, serum, cerebrospinal fluid, brain tissue, urine, or a combination of these samples, as appropriate and at the discretion of the treating clinician. We conducted multimodal diagnostic testing, which included flavivirus-specific serological and nucleic acid amplification testing. Metagenomic next-generation sequencing, including next-generation deep sequencing, target-enrichment, and targeted amplification, was conducted on human and representative mosquito-derived samples obtained from established mosquito population surveillance programmes for phylogenetic analysis. FINDINGS: 27 patients with encephalitis were assessed for MVEV between Jan 1, 2023, and July 31, 2023, 23 (85%) of whom fulfilled national case definitions for confirmed Murray Valley encephalitis. Patient ages ranged from 6 weeks to 83 years (median 62&#xb7;0 years [IQR 31&#xb7;0-67&#xb7;5]) and patients were mostly male (21 [78%] male patients and six [22%] female patients). Incidence varied widely by geographical region and was highest in the Northern Territory (32&#xb7;0 per 1&#x2009;000&#x2009;000 population). Diagnostic specimen collection generally occurred promptly (median 6&#xb7;0 days [IQR 4&#xb7;0-14&#xb7;5] from symptom onset to diagnostic specimen collection). In seven patients, case assignation relied on convalescent serum samples to assess for seroconversion or an appropriate rise in antibody titre (to four times the initial value or greater), or both. MVEV-specific IgM was detectable in serum samples of 17 (81%) of 21 patients tested by day 7 and MVEV IgG or total antibody (TAb) were detected in 18 (100%) of 18 patients tested by day 30. MVEV-specific IgM (or TAb) and MVEV RNA were detected in cerebrospinal fluid collected within 14 days of symptom onset in nine (39%) of 23 patients and seven (28%) of 25 patients, respectively. Phylogenetic analysis revealed two circulating MVEV genotypes, G1A and G2, in mosquitoes and humans in 2023. In southeast Australia, only G1A was detected and probably introduced from enzootic foci in northern Australia. INTERPRETATION: This study provides a comprehensive overview of the diagnostic workflows and phylogenetic evaluations used during the 2023 MVEV outbreak in Australia, emphasising the importance of a multimodal approach for accurate and timely confirmation of flavivirus infection. Further One Health surveillance for MVEV and other zoonotic flaviviruses is key, given potential expanded ecological niches in the context of episodic climatic events. FUNDING: None.

Humans

Aspects of the six-month developmental examination in a longitudinal study.

In a longitudinal study concerned with the early detection of delayed and aberrant development, the findings at the six-month examination have been studied in some detail. All births within a given catchment area were included and the results on 1200 babies seen at this age are reported. The findings illustrated that under ordinary clinic conditions not all children achieved the "milestones" expected of them at a particular age. The examinations were carried out in child health clinics by a heterogeneous group of doctors with widely varying training and experience, and this is reflected in the differences between the findings of the more and the less experienced doctors. The problems of follow-up and their implications for total population surveillance programmes are considered. A positive approach to routine developmental examinations is advocated, with the emphasis not only on early detection of developmental problems but also on enabling all children to achieve their optimum potential.

Child Development

Population-level genomic surveillance of human norovirus using wastewater-based whole-genome sequencing.

Wastewater-based surveillance has garnered increasing attention as a valuable approach for capturing community-level infection dynamics that are often difficult to detect through clinical reporting systems alone. In this study, we analyzed human norovirus genotype distributions and whole-genome-level variations in wastewater samples collected in Gwangju, Korea. These results were interpreted in conjunction with a documented foodborne outbreak to evaluate the epidemiological relevance of wastewater-based monitoring. Human norovirus concentrations were quantified using TaqMan Array Card-based RT-qPCR, and whole-genome next-generation sequencing (NGS) was performed to obtain viral read counts and reads per kilobase per million filtered reads values. Overall, strong correlations were observed between RT-qPCR-based concentrations and NGS-derived metrics. Genotype dynamics varied among wastewater treatment plants, reflecting differences in catchment size and local population characteristics. In particular, the relative abundance of GII.17[P17] increased during epidemiological week 50, temporally coinciding with a documented local foodborne outbreak. Variant analysis revealed that wastewater samples exhibited mixed nucleotide patterns, with multiple alleles coexisting at varying relative frequencies rather than fixed substitutions. Notably, some nonsynonymous variants detected in clinical samples were also observed in wastewater samples collected surrounding the outbreak period. Together, these findings demonstrate that wastewater-based whole-genome surveillance can capture both genotype-level shifts and nucleotide-level dynamics at the population scale, highlighting its potential as a complementary tool for monitoring community-level norovirus circulation and outbreak-associated genotype dynamics.IMPORTANCEWastewater-based surveillance is increasingly recognized as a promising approach for capturing community-level infection dynamics that are often missed by clinical surveillance. In this study, we applied whole-genome sequencing to wastewater samples collected in Gwangju, South Korea, to comprehensively characterize human norovirus genotype distributions and genetic variation. Distinct genotype patterns were observed across wastewater treatment plants, reflecting differences in catchment population size and local characteristics. Notably, an increase in the GII.17[P17] genotype detected in wastewater coincided with a foodborne outbreak investigated in Gwangju, demonstrating the potential of wastewater surveillance to reflect ongoing community transmission and emerging outbreak-associated genotypes. In addition, wastewater samples contained diverse and coexisting genetic variants, capturing population-level viral diversity and evolutionary dynamics that are not readily detected through clinical surveillance alone. These findings highlight the value of wastewater-based whole-genome surveillance for monitoring community-level viral circulation and support its integration as a complementary strategy to existing clinical surveillance systems.

genotype dynamics

Geographic correlation between mortality from primary hepatic carcinoma and prevalence of hepatitis B surface antigen in Greece.

Average annual age-adjusted mortality rates per 100,000 from primary hepatic carcinoma (PHC) among males for 1971-1973 in the urban and rural areas of the 9 geographical regions of Greece were estimated. Hepatitis-B surface antigen (HBsAg) prevalence by region and area was evaluated in a sample of 22,844 Greek Air Force recruits from all parts of the country. Mortality from PHC was found significantly higher in urban areas (28-30 vs. 18-81) whereas prevalence of HBsAg was higher in rural areas (5-3% vs. 3-90%). Nevertheless further statistical analysis showed that there is a strong correlation between HBsAg prevalence and mortality from PHC, which is higher in rural (r = + 0-88) than in urban (+ 0-57) areas. The latter findings indicate that hepatitis B infection and PHC may be causally related.

Greece

Arteriosclerotic and other degenerative heart diseases in Finland. II. A death certificate study of the examination of the cause of death from degenerative heart diseases.

A statistical survey of death certificates was made to analyse the ante-mortem and post-mortem medical and medico-legal examinations used in the determination of the cause of death of 12973 decedents who were recorded officially to have died of arteriosclerotic and other degenerative heart diseases in Finland in 1968. The relationship between the regional autopsy rate and the rate of mortality from degenerative heart diseases was studied in particular. The survey indicated that there was no systematic relationship between the type of ante-mortem and post-mortem cause-of-death examinations, including medical and medico-legal autopsies, and the rate of mortality from arteriosclerotic and other degenerative heart diseases in various groups of the Finnish population analysed by age, sex and domicile. This was concluded to be an indication of the reliability of Finnish cause-of-death statistics of degenerative heart diseases which show a generally high rate of mortality and prominent regional differences in the rate of deaths from those diseases among the Finnish male population.

Adult