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Background: The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible tuberculosis (TB), is the main driver of incident MDR-TB in these countries.Methods and Findings: We conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of Mycobacterium tuberculosis. Of 2,236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. Moreover, 92% of multidrug-resistant M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified 3 large clades that were comprised nearly uniformly of MDR-TB: 2 of these clades were of Beijing lineage, and 1 of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity. Our study lasted for only 2 years, a relatively short duration compared with the natural history of TB, and, thus, the ability to infer the full extent of transmission is limited.Conclusions: The MDR-TB epidemic in Moldova is associated with the local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To define geographic variations in emergency general surgery (EGS) care, we sought to determine how much variability exists in the rates of EGS operations and subsequent mortality in the Northeastern and Southeastern United States (US). Summary Background Data: While some geographic variations in healthcare are normal, unwarranted variations raise questions about the quality, appropriateness, and cost-effectiveness of care in different areas. Methods: Patients ≥18 years who underwent 1 of 10 common EGS operations were identified using the State Inpatient Databases (2011–2012) for 6 states, representing Northeastern (New York) and Southeastern (Florida, Georgia, Kentucky, North Carolina, Mississippi) US. Geographic unit of analysis was the hospital service area (HSA). Age-standardized rates of operations and in-hospital mortality were calculated and mapped. Differences in rates across geographic areas were compared using the Kruskal–Wallis test, and variance quantified using linear random-effects models. Variation profiles were tabulated via standardized rates of utilization and mortality to compare geographically heterogenous areas. Results: 227,109 EGS operations were geospatially analyzed across the 6 states. Age-standardized EGS operation rates varied significantly by region (Northeast rate of 22.7 EGS operations per 10,000 in population versus Southeast 21.9; P < 0.001), state (ranging from 9.9 to 29.1; P < 0.001), and HSA (1.9–56.7; P < 0.001). The geographic variability in age-standardized EGS mortality rates was also significant at the region level (Northeast mortality rate 7.2 per 1000 operations vs Southeast 7.4; P < 0.001), state-level (ranging from 5.9 to 9.0 deaths per 1000 EGS operations; P < 0.001), and HSA-level (0.0–77.3; P < 0.001). Maps and variation profiles visually exhibited widespread and substantial differences in EGS use and morality. Conclusions: Wide geographic variations exist across 6 Northeastern and Southeastern US states in the rates of EGS operations and subsequent mortality. More detailed geographic analyses are needed to determine the basis of these variations and how they can be minimized. [ABSTRACT FROM AUTHOR]

Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate less than 1). Genetic identity (identity by state, IBS) was established using a 24-single nucleotide polymorphism molecular barcode, identity by descent was calculated from whole genome sequence data, and a hierarchical Bayesian regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts. [ABSTRACT FROM AUTHOR]

Background Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children < 5 years of age. Methods We obtained national-level mortality data between 2000 and 2016 from 10 Latin American and Caribbean countries, using the standardized protocol. Time series models were used to evaluate the decline in all-cause pneumonia deaths during the postvaccination period while controlling for unrelated temporal trends using control causes of death. Results The estimated declines in pneumonia mortality following the introduction of PCVs ranged from 11% to 35% among children aged 2–59 months in 5 countries: Colombia (24% [95% credible interval {CrI}, 3%–35%]), Ecuador (25% [95% CrI, 4%–41%]), Mexico (11% [95% CrI, 3%–18%]), Nicaragua (19% [95% CrI, 0–34%]), and Peru (35% [95% CrI, 20%–47%]). In Argentina, Brazil, and the Dominican Republic, the declines were not detected in the aggregated age group but were detected in certain age strata. In Guyana and Honduras, the estimates had large uncertainty, and no declines were detected. Across the 10 countries, most of which have low to moderate incidence of pneumonia mortality, PCVs have prevented nearly 4500 all-cause pneumonia deaths in children 2–59 months since introduction. Conclusions Although the data quality was variable between countries, and the patterns varied across countries and age groups, the balance of evidence suggests that mortality due to all-cause pneumonia in children declined after PCV introduction. The impact could be greater in populations with a higher prevaccine burden of pneumonia. [ABSTRACT FROM AUTHOR]

Background The importance of specific serotypes causing invasive pneumococcal disease (IPD) differs by age. Data on pneumococcal carriage in different age groups, along with data on serotype-specific invasiveness, could help explain these age-related patterns and their implications for vaccination. Methods Using pneumococcal carriage and disease data from Israel, we evaluated the association between serotype-specific IPD in adults and serotype-specific carriage prevalence among children in different age categories, while adjusting for serotype-specific invasiveness. We estimated carriage prevalence using different age groupings that were selected a priori. The Deviance Information Criterion was used to determine which age groupings of carriage data best fit the adult IPD data. Serotype-specific disease patterns were further evaluated by stratifying IPD data by comorbidity status. Results The relative frequency of serotypes causing IPD differed between adults and children, and also differed between older and younger adults and between adults with and without comorbidities. Serotypes overrepresented as causes of IPD in adults were more commonly carried in older children compared with younger children. In line with this, the serotype-specific frequency of carriage in older children, rather than infants, best correlated with serotype-specific IPD in adults. Conclusions These analyses demonstrate that the serotype patterns in carriage in older children, rather than infants, are best correlated with disease patterns in adults. This might suggest these older children are more influential for disease patterns in adults. These insights could help in optimizing vaccination strategies to reduce disease burden across all ages. [ABSTRACT FROM AUTHOR]