Effectiveness of two and three mRNA COVID-19 vaccine doses against Omicron- and Delta-Related outpatient illness among adults, October 2021-February 2022.

Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose.

Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736 Enterococcus faecium and Multiple Mechanisms of Linezolid Resistance in Enterococci in the United States.

Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013-2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA-encoding multiresistance plasmids of animal origin. The optrA-encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance.

One-step PCR: A novel protocol for determination of pfhrp2 deletion status in Plasmodium falciparum.

Histidine-rich protein 2 (HRP2) detecting rapid diagnostic tests (RDTs) have played an important role in enabling prompt malaria diagnosis in remote locations. However, emergence of pfhrp2 deleted parasites is threatening the efficacy of RDTs, and the World Health Organization (WHO) has highlighted surveillance of these deletions as a priority. Nested PCR is used to confirm pfhrp2 deletion but is costly and laborious. Due to spurious amplification of paralogue pfhrp3, the identity of nested exon 1 PCR product must be confirmed by sequencing. Here we describe a new one-step PCR method for detection of pfhrp2. To determine sensitivity and specificity, all PCRs were performed in triplicate. Using photo-induced electron transfer (PET) PCR detecting 18srRNA as true positive, one-step had comparable sensitivity of 95.0% (88.7-98.4%) to nested exon 1, 99.0% (94.6-99.9%) and nested exon 2, 98.0% (93.0-99.8%), and comparable specificity 93.8% (69.8-99.8%) to nested exon 1 100.0% (79.4-100.0%) and nested exon 2, 100.0% (74.4-100.0%). Sequencing revealed that one step PCR does not amplify pfhrp3. Logistic regression models applied to measure the 95% level of detection of the one-step PCR in clinical isolates provided estimates of 133p/µL (95% confidence interval (CI): 3-793p/µL) for whole blood (WB) samples and 385p/µL (95% CI: 31-2133 p/µL) for dried blood spots (DBSs). When considering protocol attributes, the one-step PCR is less expensive, faster and more suitable for high throughput. In summary, we have developed a more accurate PCR method that may be ideal for the application of the WHO protocol for investigating pfhrp2 deletions in symptomatic individuals presenting to health care facilities.