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Background Breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization). Methods In total, 89 762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively. Results The incidence was 0.45 (95% confidence interval [CI], .38–.50) during pre-Delta, 2.80 (95% CI, 2.25–3.14) during Delta, and 11.2 (95% CI, 8.80–12.95) during Omicron, per 10 000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic white, OR = 1.243; 95% CI, 1.073–1.441), larger household size (OR = 1.251 [95% CI, 1.048–1.494] for 3–5 vs 1 and OR = 1.726 [95% CI, 1.317–2.262] for more than 5 vs 1 person), rural versus urban living (OR = 1.383; 95% CI, 1.122–1.704), receiving Pfizer or Johnson & Johnson versus Moderna, and multiple comorbidities. Of the 1700 breakthrough infections, 1665 reported on severity; 112 (6.73%) were severe. Higher body mass index, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs. Conclusions Breakthrough infection was 4–25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.

To better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant lineage distribution in a college campus population, we carried out viral genome surveillance over a 7-week period from January to March 2021. Among the sequences were three novel viral variants: BV-1 with a B.1.1.7/20I genetic background and an additional spike mutation Q493R, associated with a mild but longer-than-usual COVID-19 case in a college-age person, BV-2 with a T478K mutation on a 20B genetic background, and BV-3, an apparent recombinant lineage. This work highlights the potential of an undervaccinated younger population as a reservoir for the spread and generation of novel variants. This also demonstrates the value of whole genome sequencing as a routine disease surveillance tool.

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).

Background. Recent data suggest the SARS-CoV-2 Delta (B.1.617.2) variant is more transmissible among children compared to the Alpha (B.1.1.7) variant. The true incidence and longitudinal presence of antibody response to SARS-CoV-2 infection is not known, however. We provided estimates of antibody response using Texas Coronavirus Antibody REsponse Survey (Texas CARES) data, a prospective population-based seroprevalence project designed to assess antibody status over time among the general population throughout the state. Methods. In October 2020 Texas CARES began enrolling adults (aged 20-80 years) and children (aged 5-19 years). Participants were offered a series of three SARS-CoV-2 antibody tests over 6-8 months, or every 2-3 months that includes the immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Descriptive characteristics and COVID-19 infection-related symptom status was determined by questionnaire at the time of enrollment and prior to each successive blood draw. This analysis included participants ages 5-to-19 years old who have completed all three antibody assessments. Results. From our sample (n=159; mean age 12.5 years, SD 3.6), 96% of those with evidence of nucleocapsid antibodies at baseline assessment continued to have antibodies > six months later (mean 7.0 months, SD 0.97). There was no difference in the presence of antibodies by symptom status (asymptotic versus symptomatic) or severity (mild-moderate versus severe), sex, age group, or body mass index group (underweight, healthy weight, overweight, obesity) over the three antibody measurement timepoints. Conclusions. These results suggest that infection-induced antibodies persist and thus may provide some protection against future infection for at least half a year. 57.9% of the sample were negative for infection-induced antibodies at their third measurement point, suggesting a significant proportion of children have still not acquired natural infection.

In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons.

As COVID-19 continues to spread rapidly and vaccine uptake stagnates, questions remain about the amount of SARS-CoV-2 antibodies present in the population induced by either SARS-CoV-2 infection, by a COVID-19 vaccine, or both.The TEXAS Coronavirus Antibody REsponse Survey (CARES) is a statewide seroprevalence program which utilizes the Roche S-test to detect antibodies to the SARS-CoV-2 spike protein and the Roche N-test to detect antibodies to the SARS-CoV-2 nucleocapsid protein, to monitor the combined impact of prior infection and the COVID-19 vaccine. The current sample size having both S- and N-test data and reported vaccination status is 8,846.Participants with prior infection (i.e. N+) and with either partial or full vaccination have the highest proportion of those showing the maximum value of the S-test (80.95% and 83.07%, respectively). Using a permutation test, there is no statistically significant difference between the median S-test value for those that have had prior infection and are partially vaccinated versus those that have had prior infection and are fully vaccinated. These groups both show significantly higher median amount compared to the other three groups: N+/not vaccinated, N-/partially vaccinated, and N-/fully vaccinated (all p-values < 0.0001).Unvaccinated individuals with prior infection have one of the lowest median S-test values. For participants with previous SARS-CoV-2 infection and a COVID-19 vaccine, the median S-test value is high and is not statistically different between those who are partially vaccinated and those who are fully vaccinated.

Given the underestimate of seroprevalence in the US due to insufficient testing, accurate estimates of population immunity to SARS-CoV-2 or vaccinations do not exist. Although model-based estimates have been proposed, they require inputting unknown parameters such as viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach for estimating population immunity, or simplistic summing of natural- and vaccine-induced immunity, the current study presents a data-driven statistical procedure for estimating the total immunity rate in a region using prospectively collected serological data along with state-level vaccination data. We present a detailed procedure so that efforts can be replicated regionally to inform policy-making decisions relevant to SARS-CoV-2. Specifically, we conducted a prospective longitudinal statewide cohort serological survey with 10,482 participants and more than 14,000 blood samples beginning on September 30, 2020. Along with Department of State Health Services vaccination data, as of July 4, 2021, the estimated percentage of those with naturally occurring antibodies to SARS-CoV-2 in Texas is 35.3% (95% CI = (33.7%, 36.9%) and total estimated immunity is 69.1%. We conclude the seroprevalence of SARS-CoV-2 is 4 times higher than the state-confirmed COVID-19 cases (8.8%). This methodology is integral to pandemic preparedness.

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunity remains uncertain in populations. The state of Texas ranks 2ndin infection with over 2.71 million cases and has seen a disproportionate rate of death across the state. The TX CARES project was funded by the state of Texas to estimate the prevalence of SARS-CoV-2 antibody status in children and adults.Materials and MethodsThe TX CARES (Texas Coronavirus Antibody Response Survey) is an ongoing prospective population-based convenience sample from the Texas general population that commenced in October 2020. Volunteer participants are recruited across the state to participate in a 3-time point data collection TX CARES to assess antibody response over time. We use the Roche Elecsys® Anti-SARS-CoV-2 Immunoassay to determine SARS-CoV-2 antibody status.ResultsThe crude antibody positivity prevalence in Phase I was 26.1% (80/307). The fully adjusted seroprevalence of the sample was 31.5%. Specifically, 41.1% of males and 21.9% of females were seropositive. For age categories, 33.5% of those 18-34; 24.4% of those 35-44; 33.2% of those 45-54; and 32.8% of those 55+ were seropositive. In this sample,42.2% (89/211) of those negative for the antibody test reported having had a COVID-19 test.ConclusionsIn this survey we enrolled and analyzed data for 319 participants, demonstrating a high survey and antibody test completion rate, and ability to implement a questionnaire and SARS-CoV-2 antibody testing within FQHC clinical settings. We were also able to determine our capability to estimate the cross-sectional seroprevalence within Texas’s FQHC clinical settings. The crude positivity prevalence for SARS-CoV-2 antibodies in this sample was 26.1% indicating potentially high exposure to COVID-19 for FQHC clinic employees and patients. These methods are being used to guide the completion of a large longitudinal survey in the state of Texas with implications for practice and population health.

Background: The extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents at a population level in 2021 remains unclear. Children and adolescents have been considered to play an important role in transmission regardless of presence of symptoms. The objective of this study was to estimate the prevalence of SARS-CoV-2 antibody status in children ages 5-to-19 years in a sample from the State of Texas in the presence and absence of symptoms. Methods: The TX CARES (Texas Coronavirus Antibody Response Survey) is an ongoing prospective population-based sample from the Texas general population (~29·8 million) that commenced in October 2020. For the current analysis, volunteers ages 5-to-19 years were recruited throughout the state from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural pediatric and family medicine practices, health insurance providers, and a social media campaign. SARS-CoV-2 antibody status measured via the Roche Elecsys® Anti-SARS-CoV-2 Immunoassay. Prevalence of IgM, IgA, or IgG antibodies were adjusted using sampling weights and post-stratification of age and sex. We report here findings from January 1-June 1, 2021. Findings: This analysis that included 503 children ages 5-to-19 years showed 38·7% (95% CI, 34·5-43·1) of the sample was SARS-CoV-2 antibody positive in fully adjusted estimates. A total of 30·1% (95% CI, 29·4-31·5) of adults (N=6992) in the sample were antibody positive. Over half (55·8%) of those with positive antibody status were reportedly asymptomatic. Headache (25·4%), congestion/runny nose (20·8%), and fatigue (20·3%) and were the most frequently reported symptoms among those with a positive antibody result. The odds of having a positive antibody status was 37% higher in 15-to-19 year olds versus adults (OR 1·37, 95% CI, 1·03-1·83). Interpretation: These results highlight that a majority of the pediatric population remains immunologically naive to SARS-CoV-2, emphasizing the important role vaccines may play in reaching whole population herd immunity. Funding: Texas Department of State Health Services. Declaration of Interest: We declare no competing interests. Ethical Approval: All protocols were reviewed and approved by the University of Texas Health Science Center at Houston Institutional Review Board (IRB), but also deemed public health practice by the Texas Department of State Health Services IRB.

Cases of seroconversion on pre-exposure prophylaxis (PrEP) should be carefully investigated, given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.

In December 2020, the B.1.1.7 genetic variant of SARS-CoV-2, the virus that causes COVID-19, was first reported after emergence and rapid circulation in the United Kingdom (1). Evidence suggests that the B.1.1.7 variant is more efficiently transmitted than are other SARS-CoV-2 variants, and widespread circulation could thereby increase SARS-CoV-2 infection and hospitalization rates (1,2). The first reported SARS-CoV-2 B.1.1.7 variant case in the United States was confirmed by sequencing in Colorado on December 29, 2020.* This report describes a person who traveled from the United Kingdom to the United States after experiencing COVID-19-compatible symptoms† and was eventually confirmed to be infected with the B.1.1.7 variant.

Background Murine (also known as flea-borne) typhus is uncommon in the United States, but it is considered endemic in certain parts of Texas, especially the southernmost region. It is caused by Rickettsia typhi, which is transmitted to humans by rat and cat fleas. Murine typhus is often a mild illness with nonspecific clinical findings, though delayed treatment may result in severe disease and increased risk of complications. Diagnostic tests have low sensitivity in early disease. Therefore, correctly diagnosing patients with murine typhus is challenging unless clinical suspicion is high. In endemic regions, physicians are aware of the disease and diagnose it readily. However, in areas that have not historically been affected, physicians may be less familiar with the presentation of this rickettsial infection, impacting their ability to diagnose and treat it effectively. Methods Probable and confirmed murine typhus cases reported in Texas were collected for 1944–2017. Cases were mapped by county for each of the last 5 years. Cases reported over the last 5 years were also geocoded by residence for spatial cluster analysis by year. Results There has been an overall rise in the number of murine typhus cases reported per year over the last 13 years (Figure 1). The distribution of reported cases throughout Texas has changed over the last 5 years. There continues to be a high number of reported cases in South Texas and Central Texas, while reported cases are increasing in the Harris County/Houston area, Tarrant County/Ft. Worth area, and Dallas County/Dallas area. Spatial cluster (hot spot) analysis of typhus cases in Texas over the last 5 years shows areas of increased risk of murine typhus in South Texas that have persisted over time, while other areas of increased risk have appeared more recently in North Texas and Central Texas (Figures 2 and 3). Conclusion Murine typhus can be a difficult diagnosis to make based on clinical presentation, and physician awareness of its epidemiology is important. The gradual increase in case counts and the changing distribution of cases within Texas may put patients at risk of missed diagnoses. Recognizing the changing epidemiology of typhus in Texas may help inform public health education and control efforts. Disclosures All authors: No reported disclosures.

Thirty clinical isolates of Candida albicans were collected from blood or other sterile site infections. Biofilm dry weight and metabolic activity were measured for each isolate. Planktonic and sessile antifungal susceptibilities of each isolate were determined for amphotericin B deoxycholate, caspofungin, and voriconazole. Sessile susceptibilities were determined for the combination of caspofungin/voriconazole. No significant differences in biofilm dry weight or metabolic activity were found between bloodstream and other invasive isolates. Planktonic MIC 90 values and sessile MIC 90 (SMIC 90 ) values were 0.25 and 2, 0.06 and >256, and 0.5 and 2 μg/mL for amphotericin, voriconazole, and caspofungin, respectively. The SMIC 90 of the combination of caspofungin/voriconazole against sessile isolates was 0.5/2 μg/mL. Therefore, the source of invasive C. albicans clinical isolates did not affect in vitro biofilm formation. Susceptibility to antifungal agents decreased when C. albicans was associated with biofilm, and the combination of caspofungin/voriconazole did not appear to provide enhanced activity compared with caspofungin alone.

Medical therapy of chronic osteomyelitis is largely based on experimental models, historical observational or non-randomized studies, and expert opinions. A minimum of 4-6 weeks of intravenous antimicrobial therapy targeting the causative organism, given in conjunction with surgery, has become the standard for chronic long-bone osteomyelitis in adults. Given the expense, inconvenience, and potential complications inherent to such a treatment program, alternative strategies including effective oral antimicrobial regimens are desirable.Several oral antimicrobial agents have undergone evaluation for the treatment of acute and chronic osteomyelitis recently. These include fluoroquinolones, clindamycin, and linezolid. For the treatment of atypical causes of Gram-positive osteomyelitis, other oral therapies have been evaluated with reported success in small numbers of patients.The standard of care for chronic osteomyelitis in adults remains intravenous antimicrobial therapy, in combination with surgery, for at least 4-6 weeks. Acute osteomyelitis in the pediatric population as well as osteomyelitis caused by atypical Gram-positive organisms and some Gram-negative organisms may be treated successfully with oral antibiotics. Some antimicrobials have equivalent concentration in serum whether administered orally or parenterally. When therapy with these antimicrobials is indicated, the oral route is preferred in compliant patients. As research continues in this area and as new drug formulations are developed, oral therapy may become an accepted alternative in additional selected patients.

Candida albicans biofilms complicate the treatment of infected implanted intravascular devices because of decreased antifungal susceptibility. In our investigation, 48 rabbits with experimental central venous catheter C. albicans infection were equally allocated to a control arm or to receive amphotericin B deoxycholate or caspofungin treatment while undergoing systemic and intraluminal lock therapy for 7 days. C. albicans was cultured from catheters from all control rabbits, from 3 that received amphotericin B, and from 0 that received caspofungin. Differences in colony counts were detected between the control and amphotericin (P

Association of cefazolin treatment failure with type A beta-lactamase-producing Staphylococcus aureus has been suggested. The prevalence of beta-lactamase gene types among 23 methicillin-susceptible S. aureus (MSSA) isolates associated with prosthetic joint infection (PJI) treated with cefazolin was determined using polymerase chain reaction (PCR), and clinical and microbiologic outcomes were assessed. PCR revealed 4 isolates without blaZ, and 12 with type A, 2 with type B, and 5 with type C blaZ. Of 13 patients undergoing resection arthroplasty with subsequent reimplantation, all received antimicrobial spacer placement at resection with or without antimicrobial-impregnated polymethylmethacrylate at reimplantation. All 13 cases had tissue cultures at time of reimplantation that were negative for S. aureus and 11 had histopathology specimens showing no acute inflammation. Of 8 type A cases undergoing reimplantation, all prostheses remained in place at follow-up (median, 798 days; range, 32-927 days). We conclude that type A blaZ is common in MSSA PJI and that cefazolin therapy for blaZ MSSA PJI can be successful when combined with 2-stage reimplantation and local antimicrobial therapy.

The use of pacemakers and implantable cardioverterdefibrillators continues to increase for the management of cardiac dysrhythmias and, more recently, heart failure. Long-term complications associated with their use include infection, lead failure, and spurious shocks. Although the risk of infection with intracardiac devices is well known, the clinical presentation of this complication can be insidious, delayed in onset, and difficult to diagnose. We report a case of Aspergillus fumigatus infection of an implantable cardioverter-defibrillator with right-sided endocarditis in a 55-year-old man. The infection presented as persistent pulmonary infiltrates (due to recurrent septic pulmonary embolism) and anemia more than 2 years after implantation of the device. Clinicians should be aware of the variable manifestations resulting from infection of intracardiac devices.

The effects of fresh garlic extract (FGE) against planktonic Candida spp. have been demonstrated in vitro and have been attributed to the action of allicin (3), a sulfur-containing compound that is formed at levels of approximately 3 to 5 mg/g of fresh clove (8). Biofilm-associated, or sessile, Candida albicans organisms demonstrate increased resistance to traditional antifungal agents that have activity against their planktonic counterparts (5). Therefore, we investigated the activity of FGE against both planktonic and sessile forms of C. albicans. (This data was presented in part at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, D.C., 30 October to 2 November 2004.) FGE was prepared as previously described by Lemar and colleagues (7). Briefly, fresh garlic cloves were crushed in sterile saline at a concentration of 40 mg/ml. FGE was filter sterilized and stored at −70°C until use. We utilized C. albicans GDH 2346, a strain isolated from a denture stomatitis patient that is known to produce an extracellular matrix containing a mannoprotein adhesin, with a previously described method of C. albicans biofilm formation (2, 4). Sterile silicone elastomer disks were immersed in 1 × 107 CFU of C. albicans, incubated at 37°C on an orbital shaker for 90 min, and then rinsed. One-third of the disks were placed in 0, 0.5, or 1.0 mg of FGE/ml in yeast nitrogen base and incubated at 37°C for 48 h prior to evaluation. The other disks were incubated in yeast nitrogen base for 48 h to form mature biofilms. The untreated, mature biofilms were incubated with 0, 2, or 4 mg of FGE/ml in saline for 1 or 48 h prior to evaluation. All biofilms were evaluated with XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay, a semiquantitative, colorimetric assay of metabolic activity (2). MICs for planktonic organisms were measured using the NCCLS macrodilution method. All experiments were performed in triplicate on three different days. Comparisons between groups were performed by analysis of variance (ANOVA). P values of