Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Subvariant Neutralization Following a Primary Vaccine Series of NVX-CoV2373 and BNT162b2 Monovalent Booster Vaccine.

We evaluated the immunologic response to a novel vaccine regimen that included 2 doses of NVX-CoV2373 (Novavax) followed by 1 dose of BNT162b2 (Pfizer-BioNTech) monovalent booster vaccine. A durable neutralizing antibody response to Omicron BA.4/BA.5 and BA.1 variants was observed at month 6 after the booster, while immune escape was noted for the XBB.1.5 variant.

Use of rapid genomic deletion typing to monitor a tuberculosis outbreak within an urban homeless population.

Beginning in mid-2002, a large tuberculosis outbreak occurred among homeless persons in King County, Washington. In order to further monitor the outbreak following its peak in 2003, Mycobacterium tuberculosis isolates from all new King County tuberculosis (TB) patients in 2004 and the first half of 2005 (n = 220) were genotyped by using a rapid comparative genomics-based (genomic deletion-typing) approach, with confirmation by mycobacterial interspersed repetitive units and repetitive-sequence-based PCR (rep-PCR). Results were compared to retrospective genotypic data from 1995 to 2003. The outbreak strain SBRI9, which was not seen among King County homeless persons prior to 2002, accounted for 16 out of 30 TB cases (53%) within this population in 2002. This trend continued with 27 out of 35 cases (77%) caused by the outbreak strain in 2003, 11 out of 13 cases (85%) caused by the outbreak strain in 2004, and 4 out of 10 cases (40%) caused by the outbreak strain in the first 5 months of 2005. Thus, the outbreak strain remained well established within this homeless population throughout the study period. At least four SBRI9 cases were in people who had previously been infected by other strains. The novel PCR-based strain-typing approach used in this investigation proved to be cost-effective and very rapid. In most cases, it was possible to analyze DNA extracted directly from primary isolation (Mycobacterium growth indicator tube) cultures submitted by clinical laboratories, a feature that markedly reduced the delay between diagnosis and strain typing results. This rapid turnaround facilitated public health efforts to prevent new outbreaks involving this strain.

Genes required for intrinsic multidrug resistance in Mycobacterium avium.

Genes required for intrinsic multidrug resistance by Mycobacterium avium were identified by screening a library of transposon insertion mutants for the inability to grow in the presence of ciprofloxacin, clarithromycin, and penicillin at subinhibitory concentrations. Two genes, pks12 and Maa2520, were disrupted in multiple drug-susceptible mutants. The pks12 gene (Maa1979), which may be cotranscribed with a downstream gene (Maa1980), is widely conserved in the actinomycetes. Its ortholog in Mycobacterium tuberculosis is a polyketide synthase required for the synthesis of dimycocerosyl phthiocerol, a major cell wall lipid. Mutants of M. avium with insertions into pks12 exhibited altered colony morphology and were drug susceptible, but they grew as well as the wild type did in vitro and intracellularly within THP-1 cells. A pks12 mutant of M. tuberculosis was moderately more susceptible to clarithromycin than was its parent strain; however, susceptibility to ciprofloxacin and penicillin was not altered. M. avium complex (MAC) and M. tuberculosis appear to have different genetic mechanisms for resisting the effects of these antibiotics, with pks12 playing a relatively more significant role in MAC. The second genetic locus identified in this study, Maa2520, is a conserved hypothetical gene with orthologs in M. tuberculosis and Mycobacterium leprae. It is immediately upstream of Maa2521, which may code for an exported protein. Mutants with insertions at this locus were susceptible to multiple antibiotics and slow growing in vitro and were unable to survive intracellularly within THP-1 cells. Like pks12 mutants, they exhibited increased Congo red binding, an indirect indication of cell wall modifications. Maa2520 and pks12 are the first genes to be linked by mutation to intrinsic drug resistance in MAC.

Expanded geographical distribution of the N family of Mycobacterium tuberculosis strains within the United States.

The N and W-Beijing families of Mycobacterium tuberculosis are phylogenetically closely related. The ability of the W-Beijing family to rapidly cause widespread disease is well described; however, few outbreaks involving the N family have been reported outside the New York City, N.Y., area. During 2002 to 2003, Seattle, Wash., experienced a rapidly expanding tuberculosis outbreak involving 38 persons in a 23-month period. The outbreak strain, SBRI9, exhibited the genotypic properties of the N family. Its IS6110 restriction fragment length polymorphism pattern was identical or nearly identical to those of two N family strains that were responsible for clusters of tuberculosis cases, including a large nosocomial outbreak, in New York City and New Jersey from 1989 to 1990. It was also identical to strains involved in late 1990s tuberculosis cases in Michigan, Maryland, and Arkansas. Further monitoring of the N family may show that it shares with the W-Beijing family the propensity to spread rapidly, suggesting that this characteristic evolved prior to the divergence of the two genetic lineages.