Global-, Regional-, and National-Level Impacts of the COVID-19 Pandemic on Tuberculosis Diagnoses, 2020-2021.

Evaluating cross-country variability on the impact of the COVID-19 pandemic on tuberculosis (TB) may provide urgent inputs to control programs as countries recover from the pandemic. We compared expected TB notifications, modeled using trends in annual TB notifications from 2013-2019, with observed TB notifications to compute the observed to expected (OE) ratios for 170 countries. We applied the least absolute shrinkage and selection operator (LASSO) method to identify the covariates, out of 27 pandemic- and tuberculosis-relevant variables, that had the strongest explanatory power for log OE ratios. The COVID-19 pandemic was associated with a 1.55 million (95% CI: 1.26-1.85, 21.0% [17.5-24.6%]) decrease in TB diagnoses in 2020 and a 1.28 million (0.90-1.76, 16.6% [12.1-21.2%]) decrease in 2021 at a global level. India, Indonesia, the Philippines, and China contributed the most to the global declines for both years, while sub-Saharan Africa achieved pre-pandemic levels by 2021 (OE ratio = 1.02 [0.99-1.05]). Age-stratified analyses revealed that the ≥ 65-year-old age group experienced greater relative declines in TB diagnoses compared with the under 65-year-old age group in 2020 (RR = 0.88 [0.81-0.96]) and 2021 (RR = 0.88 [0.79-0.98]) globally. Covariates found to be associated with all-age OE ratios in 2020 were age-standardized smoking prevalence in 2019 (ß = 0.973 [0.957-990]), school closures (ß = 0.988 [0.977-0.998]), stay-at-home orders (ß = 0.993 [0.985-1.00]), SARS-CoV-2 infection rate (ß = 0.991 [0.987-0.996]), and proportion of population ≥65 years (ß = 0.971 [0.944-0.999]). Further research is needed to clarify the extent to which the observed declines in TB diagnoses were attributable to disruptions in health services, decreases in TB transmission, and COVID-19 mortality among TB patients.

Effectiveness of Monoclonal Antibody Therapy for Preventing COVID-19 Hospitalization and Mortality in a Statewide Population.

BACKGROUND: Monoclonal antibody (MAB) treatments for COVID-19 received Emergency Use Authorization in the United States. METHODS: We used surveillance data from Rhode Island to conduct a retrospective, statewide cohort study to estimate the effectiveness of MABs for preventing hospitalization and death during periods when Alpha and Delta variants were predominant. RESULTS: From 1/17/2021-10/26/2021, 285 long-term congregate care (LTCC) residents and 3,113 non-congregate patients met our eligibility criteria and received MAB; they were matched to 285 and 6,226 controls, respectively. Among LTCC residents, 8.8% (25/285) of patients who received MAB were hospitalized or died compared to 25.3% (72/285) of those who did not receive MAB (adjusted difference=16.7%, 95% confidence interval CI=11.0-22.3%). Among non-congregate patients, 4.5% (140/3,113) of patients who received MAB were hospitalized or died compared to 11.8% (737/6,226) of those who did not receive MAB (adjusted difference=7.2%, 95% CI=6.0-8.4%). CONCLUSIONS: Administration of MABs led to an absolute reduction in hospitalization or death during periods when Alpha and Delta variants were predominant.

Viral synergism suppresses R gene-mediated resistance by impairing downstream defense mechanisms in soybean.

Viral synergism occurs when mixed infection of a susceptible plant by 2 or more viruses leads to increased susceptibility to at least 1 of the viruses. However, the ability of 1 virus to suppress R gene-controlled resistance against another virus has never been reported. In soybean (Glycine max), extreme resistance (ER) against soybean mosaic virus (SMV), governed by the Rsv3 R-protein, manifests a swift asymptomatic resistance against the avirulent strain SMV-G5H. Still, the mechanism by which Rsv3 confers ER is not fully understood. Here, we show that viral synergism broke this resistance by impairing downstream defense mechanisms triggered by Rsv3 activation. We found that activation of the antiviral RNA-silencing pathway and the proimmune mitogen-activated protein kinase 3 (MAPK3), along with the suppression of the proviral MAPK6, are hallmarks of Rsv3-mediated ER against SMV-G5H. Surprisingly, infection with bean pod mottle virus (BPMV) disrupted this ER, allowing SMV-G5H to accumulate in Rsv3-containing plants. BPMV subverted downstream defenses by impairing the RNA-silencing pathway and activating MAPK6. Further, BPMV reduced the accumulation of virus-related siRNAs and increased the virus-activated siRNA that targeted several defense-related nucleotide-binding leucine-rich repeat receptor (NLR) genes through the action of the suppression of RNA-silencing activities encoded in its large and small coat protein subunits. These results illustrate that viral synergism can result from abolishing highly specific R gene resistance by impairing active mechanisms downstream of the R gene.

Effectiveness Associated With Vaccination After COVID-19 Recovery in Preventing Reinfection.

Importance: The benefit of vaccination for preventing reinfection among individuals who have been previously infected with SARS-CoV-2 is largely unknown. Objective: To obtain population-based estimates of the probability of SARS-CoV-2 reinfection and the effectiveness associated with vaccination after recovery from COVID-19. Design, Setting, and Participants: This cohort study used Rhode Island statewide surveillance data from March 1, 2020, to December 9, 2021, on COVID-19 vaccinations, laboratory-confirmed cases, hospitalizations, and fatalities to conduct a population-based, retrospective study during periods when wild type, Alpha, and Delta strains of SARS-CoV-2 were predominant. Participants included Rhode Island residents aged 12 years and older who were previously diagnosed with COVID-19 and unvaccinated at the time of first infection, stratified into 3 subpopulations: long-term congregate care (LTCC) residents, LTCC employees, and the general population (ie, individuals not associated with congregate settings). Data were analyzed from October 2021 to January 2022. Exposures: Completion of the primary vaccination series, defined as 14 days after the second dose of an mRNA vaccine or 1 dose of vector virus vaccine. Main Outcomes and Measures: The main outcome was SARS-CoV-2 reinfection, defined as a laboratory-confirmed positive result on a polymerase chain reaction (PCR) or antigen test at least 90 days after the first laboratory-confirmed positive result on a PCR or antigen test. Results: Overall, 3124 LTCC residents (median [IQR] age, 81 [71-89]; 1675 [53.6%] females), 2877 LTCC employees (median [IQR] age, 41 [30-53]; 2186 [76.0%] females), and 94 516 members of the general population (median [IQR] age, 35 [24-52] years; 45 030 [47.6%] females) met eligibility criteria. Probability of reinfection at 9 months for those who remained unvaccinated after recovery from prior COVID-19 was 13.0% (95% CI, 12.0%-14.0%) among LTCC residents, 10.0% (95% CI, 8.8%-11.5%) among LTCC employees, and 1.9% (95% CI, 1.8%-2.0%) among the general population. Completion of the primary vaccination series after infection was associated with 49% (95% CI, 27%-65%) protection among LTCC residents, 47% (95% CI, 19%-65%) protection among LTCC employees, and 62% (95% CI, 56%-68%) protection in the general population against reinfection, adjusting for potential sociodemographic and clinical confounders and temporal variation in infection rates. Conclusions and Relevance: These findings suggest that risk of SARS-CoV-2 reinfection after recovery from COVID-19 was relatively high among individuals who remained unvaccinated. Vaccination after recovery from COVID-19 was associated with reducing risk of reinfection by approximately half.

A newly emerging alphasatellite affects banana bunchy top virus replication, transcription, siRNA production and transmission by aphids.

Banana bunchy top virus (BBTV) is a six-component ssDNA virus (genus Babuvirus, family Nanoviridae) transmitted by aphids, infecting monocots (mainly species in the family Musaceae) and likely originating from South-East Asia where it is frequently associated with self-replicating alphasatellites. Illumina sequencing analysis of banana aphids and leaf samples from Africa revealed an alphasatellite that should be classified in a new genus, phylogenetically related to alphasatellites of nanoviruses infecting dicots. Alphasatellite DNA was encapsidated by BBTV coat protein and accumulated at high levels in plants and aphids, thereby reducing helper virus loads, altering relative abundance (formula) of viral genome components and interfering with virus transmission by aphids. BBTV and alphasatellite clones infected dicot Nicotiana benthamiana, followed by recovery and symptomless persistence of alphasatellite, and BBTV replication protein (Rep), but not alphasatellite Rep, induced leaf chlorosis. Transcriptome sequencing revealed 21, 22 and 24 nucleotide small interfering (si)RNAs covering both strands of the entire viral genome, monodirectional Pol II transcription units of viral mRNAs and pervasive transcription of each component and alphasatellite in both directions, likely generating double-stranded precursors of viral siRNAs. Consistent with the latter hypothesis, viral DNA formulas with and without alphasatellite resembled viral siRNA formulas but not mRNA formulas. Alphasatellite decreased transcription efficiency of DNA-N encoding a putative aphid transmission factor and increased relative siRNA production rates from Rep- and movement protein-encoding components. Alphasatellite itself spawned the most abundant siRNAs and had the lowest mRNA transcription rate. Collectively, following African invasion, BBTV got associated with an alphasatellite likely originating from a dicot plant and interfering with BBTV replication and transmission. Molecular analysis of virus-infected banana plants revealed new features of viral DNA transcription and siRNA biogenesis, both affected by alphasatellite. Costs and benefits of alphasatellite association with helper viruses are discussed.

The impact of an educational forum intervention on East African mothers' HPV vaccine-related knowledge, attitudes, and intentions to vaccinate their adolescent children.

OBJECTIVE: HPV vaccine uptake in U.S. East African adolescents is low. We developed and evaluated a culturally-targeted interactive educational intervention for East African immigrant mothers to increase HPV-vaccine-related knowledge, attitudes, and intentions to vaccinate adolescent children. METHODS: Eligible mothers had ≥ 1 11-17-year-old child and reported all children's HPV vaccination status as unvaccinated or unknown. The intervention was delivered via 10 dinners in the Seattle metropolitan area (8 with the Somali community, 2 with the Ethiopian community). Educational presentations and pre/post-tests on knowledge, attitudes, and intentions were conducted in the participants' native language by a co-ethnic physician. Pre/post differences in responses were evaluated with McNemar's tests and GEE models. HPV vaccination uptake 6-months post-intervention was evaluated using state immunization registry data. RESULTS: Of 115 participating mothers, most (84%) were Somali and < 40 years of age (60%). Median years of formal education was 8 (range 0-16), and 61% reported a household income <$25,000. Knowledge of HPV/HPV-vaccines was low pre-intervention, with correct responses ranging from 4% to 39% (61%-91% of responses were "not sure"); correct post-intervention responses ranged from 29% to 97%. Pre-intervention, only 12% of mothers thought they had enough information to make a decision about vaccination, compared to 90% post-intervention. Pre-intervention, only 16% of mothers reported that they were somewhat or very likely to vaccinate their child, compared to 83% post-intervention. All pre/post comparisons were statistically significantly different (p < 0.0001). Although mothers were more likely to report correct HPV-related knowledge and positive vaccine attitudes and intentions post-intervention, only two mothers' children initiated HPV vaccination within 6 months after the intervention. CONCLUSIONS: Results illustrate that a culturally targeted educational intervention effectively increased East African mothers' HPV vaccine-related knowledge, attitudes, and intentions to vaccinate their adolescent children. Future research should identify additional intervention components that can bridge the gap between intention and behavior to facilitate HPV vaccine uptake.

Role of the central junction in folding topology of the protein-free human U2-U6 snRNA complex.

U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies have shown that the protein-free U2-U6 snRNA complex adopts two conformations in equilibrium, characterized by four and three helices surrounding a central junction. The four-helix conformer is strongly favored in the in vitro protein-free state, but the three-helix conformer predominates in spliceosomes. To analyze the role of the central junction in positioning elements forming the active site, we derived three-dimensional models of the two conformations from distances measured between fluorophores at selected locations in constructs representing the protein-free human U2-U6 snRNA complex by time-resolved fluorescence resonance energy transfer. Data describing four angles in the four-helix conformer suggest tetrahedral geometry; addition of Mg2+ results in shortening of the distances between neighboring helices, indicating compaction of the complex around the junction. In contrast, the three-helix conformer shows a closer approach between helices bearing critical elements, but the addition of Mg2+ widens the distance between them; thus in neither conformer are the critical helices positioned to favor the proposed triplex interaction. The presence of Mg2+ also enhances the fraction of the three-helix conformer, as does incubation with the Prp19-related protein RBM22, which has been implicated in the remodeling of the U2-U6 snRNA complex to render it catalytically active. These data suggest that although the central junction assumes a significant role in orienting helices, spliceosomal proteins and Mg2+ facilitate formation of the catalytically active conformer.

Facile synthesis of chlorin bioconjugates by a series of click reactions.

A multifunctional chlorin platform appended with four short polyethylene glycols and a carboxylate-linker allows rapid conjugation to biotargeting motifs such as proteins and oligonucleotides. The stability and photophysical properties of the chlorin enable development of diagnostics, imaging, molecular tracking, and theranostics.

Impact of medicated feed on the development of antimicrobial resistance in bacteria at integrated pig-fish farms in Vietnam.

Integrated livestock-fish aquaculture utilizes animal excreta, urine, and feed leftovers as pond fertilizers to enhance the growth of plankton and other microorganisms eaten by the fish. However, antimicrobial-resistant bacteria may be transferred and develop in the pond due to selective pressure from antimicrobials present in animal feed, urine, and feces. In an experimental pig-fish farm located in periurban Hanoi, Vietnam, nine piglets were provided feed containing 5 µg of tetracycline (TET)/kg pig weight/day and 0.45 µg of enrofloxacin (ENR)/kg pig weight/day during the second and fourth (last) months of the experiment. The aim of this study was to determine the association between the provision of pig feed with antimicrobials and the development of antimicrobial resistance, as measured in a total of 520 Escherichia coli and 634 Enterococcus strains isolated from pig manure and water-sediment pond samples. MIC values for nalidixic acid (NAL) and ENR showed that E. coli and Enterococcus spp. overall exhibited significant higher frequencies of resistance toward NAL and ENR during the 2 months when pigs were administered feed with antimicrobials, with frequencies reaching 60 to 80% in both water-sediment and manure samples. TET resistance for both indicators was high (>80%) throughout the study period, which indicates that TET-resistant E. coli and Enterococcus spp. were present in the piglets before the initiation of the experiment. PCR-based identification showed similar relative occurrences of Enterococcus faecium, Enterococcus faecalis, and other Enterococcus spp. in the water-sediment and manure samples, suggesting that Enterococcus spp. isolated in the ponds originated mainly from the pig manure. The development of antimicrobial resistance in integrated animal husbandry-fish farms and possible transfers and the impact of such resistance on food safety and human health should be further assessed.