Simplified Model to Survey Tuberculosis Transmission in Countries Without Systematic Molecular Epidemiology Programs

Systematic molecular/genomic epidemiology studies for tuberculosis surveillance cannot be implemented in many countries. We selected Panama as a model for an alternative strategy. Mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis revealed a high proportion (50%) of Mycobacterium tuberculosis isolates included in 6 clusters (A–F) in 2 provinces (Panama and Colon). Cluster A corresponded to the Beijing sublineage. Whole-genome sequencing (WGS) differentiated clusters due to active recent transmission, with low single-nucleotide polymorphism–based diversity (cluster C), from clusters involving long-term prevalent strains with higher diversity (clusters A, B). Prospective application in Panama of 3 tailored strain–specific PCRs targeting marker single-nucleotide polymorphisms identified from WGS data revealed that 31.4% of incident cases involved strains A–C and that the Beijing strain was highly represented and restricted mainly to Colon. Rational integration of MIRU-VNTR, WGS, and tailored strain–specific PCRs could be a new model for tuberculosis surveillance in countries without molecular/genomic epidemiology programsSystematic molecular/genomic epidemiology studies for tuberculosis surveillance cannot be implemented in many countries. We selected Panama as a model for an alternative strategy. Mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis revealed a high proportion (50%) of Mycobacterium tuberculosis isolates included in 6 clusters (A–F) in 2 provinces (Panama and Colon). Cluster A corresponded to the Beijing sublineage. Whole-genome sequencing (WGS) differentiated clusters due to active recent transmission, with low single-nucleotide polymorphism–based diversity (cluster C), from clusters involving long-term prevalent strains with higher diversity (clusters A, B). Prospective application in Panama of 3 tailored strain–specific PCRs targeting marker single-nucleotide polymorphisms identified from WGS data revealed that 31.4% of incident cases involved strains A–C and that the Beijing strain was highly represented and restricted mainly to Colon. Rational integration of MIRU-VNTR, WGS, and tailored strain–specific PCRs could be a new model for tuberculosis surveillance in countries without molecular/genomic epidemiology program

Simplified Model to Survey Tuberculosis Transmission in Countries Without Systematic Molecular Epidemiology Programs

Systematic molecular/genomic epidemiology studies for tuberculosis surveillance cannot be implemented in many countries. We selected Panama as a model for an alternative strategy. Mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis revealed a high proportion (50%) of Mycobacterium tuberculosis isolates included in 6 clusters (A–F) in 2 provinces (Panama and Colon). Cluster A corresponded to the Beijing sublineage. Whole-genome sequencing (WGS) differentiated clusters due to active recent transmission, with low single-nucleotide polymorphism–based diversity (cluster C), from clusters involving long-term prevalent strains with higher diversity (clusters A, B). Prospective application in Panama of 3 tailored strain–specific PCRs targeting marker single-nucleotide polymorphisms identified from WGS data revealed that 31.4% of incident cases involved strains A–C and that the Beijing strain was highly represented and restricted mainly to Colon. Rational integration of MIRU-VNTR, WGS, and tailored strain–specific PCRs could be a new model for tuberculosis surveillance in countries without molecular/genomic epidemiology programs.Systematic molecular/genomic epidemiology studies for tuberculosis surveillance cannot be implemented in many countries. We selected Panama as a model for an alternative strategy. Mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis revealed a high proportion (50%) of Mycobacterium tuberculosis isolates included in 6 clusters (A–F) in 2 provinces (Panama and Colon). Cluster A corresponded to the Beijing sublineage. Whole-genome sequencing (WGS) differentiated clusters due to active recent transmission, with low single-nucleotide polymorphism–based diversity (cluster C), from clusters involving long-term prevalent strains with higher diversity (clusters A, B). Prospective application in Panama of 3 tailored strain–specific PCRs targeting marker single-nucleotide polymorphisms identified from WGS data revealed that 31.4% of incident cases involved strains A–C and that the Beijing strain was highly represented and restricted mainly to Colon. Rational integration of MIRU-VNTR, WGS, and tailored strain–specific PCRs could be a new model for tuberculosis surveillance in countries without molecular/genomic epidemiology programs

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Reduced Food Intake Among Tuberculosis Patients Within an Urban Setting in Panama (P10-023-19).

Objectives The aim of our study is to characterize the dietary factors and food items intake of people living with pulmonary tuberculosis in an urban and high disease incidence city in Panama. Methods We recruited 41 participants newly diagnosed with pulmonary tuberculosis. We applied a culturally adapted version of the NHANES Food Screener to estimate dietary median intakes and to evaluate daily and weekly frequencies of consumption. All frequencies reported were converted to daily frequency to describe the dietary patterns and make estimations. Direct observed anti-tuberculosis therapy was provided to all participants. Results Among the participants, 20% were female, the average age was 38.9 years old, the average body mass index was 20.4 and 16% were patients living with HIV. When comparing the consumption frequency reported by the TB patients with the Panamanian Dietary recommendations, these patients did not meet the minimal frequency intake of fruit and whole grain. Only 30% of participants achieved the recommended fruit frequency intake. We also found that only 37% of participants meet the recommended consumption of at least 3 times a week of beans and legumes. In contrast, a high number of these TB patients (34/41) reported a daily vegetable intake frequency and a mean of 25 teaspoons of added sugar daily intake. For sugar-sweetened beverages intake, we found a mean frequency intake of twice a day and 73% of our participants had a daily consumption of any dairy product. A total of 63% of our participants reported consumption of processed meat more than twice a week. Conclusions The food intake pattern in patients suffering tuberculosis includes daily consumption of vegetables, frequent consumption of dairy products and sport or fruit drinks, but a low frequency of fruits, beans, and legumes. These findings suggest that the protective dietary factors including fruits and whole grain are not consumed at the minimum requirement intake to improve general health in our patient group. We recommend decreasing processed meat intake among patients suffering tuberculosis. Also, we recommend the use of diet supplementation programs to improve anti-tuberculosis treatment success rates. Food security investigations to determine the extent of limitations to access healthy food remain key for improving disease control.Objectives The aim of our study is to characterize the dietary factors and food items intake of people living with pulmonary tuberculosis in an urban and high disease incidence city in Panama. Methods We recruited 41 participants newly diagnosed with pulmonary tuberculosis. We applied a culturally adapted version of the NHANES Food Screener to estimate dietary median intakes and to evaluate daily and weekly frequencies of consumption. All frequencies reported were converted to daily frequency to describe the dietary patterns and make estimations. Direct observed anti-tuberculosis therapy was provided to all participants. Results Among the participants, 20% were female, the average age was 38.9 years old, the average body mass index was 20.4 and 16% were patients living with HIV. When comparing the consumption frequency reported by the TB patients with the Panamanian Dietary recommendations, these patients did not meet the minimal frequency intake of fruit and whole grain. Only 30% of participants achieved the recommended fruit frequency intake. We also found that only 37% of participants meet the recommended consumption of at least 3 times a week of beans and legumes. In contrast, a high number of these TB patients (34/41) reported a daily vegetable intake frequency and a mean of 25 teaspoons of added sugar daily intake. For sugar-sweetened beverages intake, we found a mean frequency intake of twice a day and 73% of our participants had a daily consumption of any dairy product. A total of 63% of our participants reported consumption of processed meat more than twice a week. Conclusions The food intake pattern in patients suffering tuberculosis includes daily consumption of vegetables, frequent consumption of dairy products and sport or fruit drinks, but a low frequency of fruits, beans, and legumes. These findings suggest that the protective dietary factors including fruits and whole grain are not consumed at the minimum requirement intake to improve general health in our patient group. We recommend decreasing processed meat intake among patients suffering tuberculosis. Also, we recommend the use of diet supplementation programs to improve anti-tuberculosis treatment success rates. Food security investigations to determine the extent of limitations to access healthy food remain key for improving disease control

Preferential Cleavage of Degradative Intermediates of rpsT mRNA by the Escherichia coli RNA Degradosome

RNase E, the principal RNase capable of initiating mRNA decay, preferentially attacks 5′-monophosphorylated over 5′-triphosphorylated substrates. Site-specific cleavage in vitro of the rpsT mRNA by RNase H directed by chimeric 2′-O-methyl oligonucleotides was employed to create truncated RNAs which are identical to authentic degradative intermediates. The rates of cleavage of two such intermediates by RNase E in the RNA degradosome are significantly faster (2.5- to 8-fold) than that of intact RNA. This verifies the preference of RNase E for degradative intermediates and can explain the frequent “all-or-none” behavior of mRNAs during the decay process