Characterizing the etiology of recurrent tuberculosis using whole genome sequencing-Alaska, USA, 2008-2020.

BACKGROUND: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods. METHODS: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS. RESULTS: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively. CONCLUSIONS: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities.

MALDI-TOF mass spectrometry misidentification of Cutibacterium namnetense and Cutibacterium modestum: Implications for multiplex PCR phylotyping of Cutibacterium acnes.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can misidentify Cutibacterium namnetense and Cutibacterium modestum as Cutibacterium acnes. We now describe how such MALDI-TOF MS misidentification explains previous reports of C. acnes isolates that could not be characterised using a multiplex PCR phylotyping assay.

Temporally Associated Invasive Pneumococcal Disease and SARS-CoV-2 Infection, Alaska, USA, 2020-2021.

Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations.

Metal-Free Addition of Alkyl Bromides to Access 3,3-Disubstituted Quinoxalinones Enabled by Visible-Light Photoredox Catalysis.

A metal-free addition of unactivated alkyl bromides to quinoxalin-2(1H)-ones is described. This method enables the construction of valuable 3,3-disubstituted dihydroquinoxalin-2(1H)-ones bearing quaternary carbon centers under mild, visible-light photoredox catalysis. High functional group tolerance is observed in both the quinoxalinone and alkyl bromide partners. The ability to scale up this method was demonstrated under photo-flow conditions to enable gram-scale synthesis.

CUTIS-SEQ, a flexible bilocus sequence typing scheme that provides high resolution of Cutibacterium acnes strains across all subspecies.

OBJECTIVES: A 'high resolution' Single Locus Sequence Typing (SLST) scheme has been described for the anaerobic skin bacterium Cutibacterium acnes that seemingly discriminates sequence types (STs) to a level commensurate with previously described Multilocus Sequence Typing (MLST) methods (MLST4; MLST8; MLST9). However, no quantifiable evaluation of SLST versus MLST for differentiation of C. acnes strains, especially in relation to the subspecies of the bacterium, known as C. acnes subsp. acnes (type I), C. acnes subsp. defendens (type II) and C. acnes subsp. elongatum (type III), has been performed which is vital given its increasing use. To address this, we examined the discriminatory power of SLST versus MLST with a large group of isolates representative of all subspecies. METHODS: Simpson's index of diversity (D) was used for quantitative comparison of the resolving power of the SLST and MLST schemes for 186 isolates of C. acnes covering all three subspecies. RESULTS: When strains were considered collectively, SLST and all three MLST approaches had similar D values > 90%. However, at the subspecies level there were significant differences between the methods, most strikingly a reduced discrimination of type II and type III strains (D <80%) by SLST versus MLST8, and to a lesser extent MLST4. The MLST9 method also performed poorly for type II strains (D <70%), but did display the best results for type I (D = 90%). By combining the SLST locus with the camp2 gene sequence to create a novel and flexible high-resolution Bilocus Sequence Typing (BLST) scheme, known as CUTIS-SEQ typing (CUTIbacterium acneS BilocuS sEQuence Typing), we achieved improved resolution at both species and, critically, subspp. levels. CONCLUSIONS: CUTIS-SEQ provides an opportunity to improve differentiation of C. acnes isolates by SLST without significantly impacting laboratory workload, or compromising application to complex biological communities. A CUTIS-SEQ isolate database is now available as part of the C. acnes PubMLST database at https://pubmlst.org.

Genomic Diversity of Haemophilus influenzae Serotype a in an Outbreak Community-Alaska, 2018.

BACKGROUND: Haemophilus influenzae serotype a (Hia) can cause severe invasive disease, especially in young children. In 2018, 4 invasive Hia cases occurred in an Alaska community. We used whole-genome sequencing (WGS) to evaluate the relationship of the bacteria from this community and other Alaska patients with invasive Hia. METHODS: All carriage (n = 15) and invasive (n = 4) Hia isolates from the outbreak community, together with 15 nonoutbreak Alaska invasive Hia surveillance isolates from 2018, were tested for antimicrobial susceptibility and characterized using WGS. RESULTS: Phylogenetic analysis of both invasive and carriage Hia isolates revealed 2 major clades that differed by an average of 300 core single-nucleotide polymorphisms (SNPs). All isolates from the outbreak community were clustered in 1 subclade, within a larger clade containing 3 nonoutbreak invasive Hia isolates. Comparative genomics did not reveal any genetic mutations that distinguished carriage from invasive isolates. Three (20%) community isolates were rifampin resistant and had a previously unreported mutation in the rpoB gene. CONCLUSIONS: In the outbreak community, Hia isolates from carriers were indistinguishable from the invasive Hia isolates. Overall, invasive Hia isolates from Alaska in 2018 were genetically similar. The rifampin resistance mutation is concerning as rifampin is the first-line medication for Hia prophylaxis.

Increased Mortality Among Persons With Symptomatic Coronavirus Disease 2019 (COVID-19) During the Period of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta Variant) Predominance: Alaska, November 2020-October 2021.

We compared the mortality risk in Alaska among persons with symptomatic coronavirus disease 2019 (COVID-19) during the period the Delta variant was predominant to the risk among those with symptomatic COVID-19 before Delta predominance. The Delta period was associated with 2.43-fold higher odds of death. Unvaccinated persons were 4.49 times more likely to die than fully vaccinated persons.

Haemophilus influenzae Serotype a (Hia) Carriage in a Small Alaska Community After a Cluster of Invasive Hia Disease, 2018.

BACKGROUND: Between May and July 2018, 4 Haemophilus influenzae serotype a (Hia) infections occurred in a remote Alaska community. We performed a public health response to prevent further illness and understand Hia carriage. METHODS: We collected oropharyngeal samples community-wide to evaluate baseline carriage. Risk factors were evaluated by interview. We offered prophylactic rifampin to individuals in contact with invasive Hia patients (contacts) and to all children aged <10 years. Oropharyngeal samples were collected again 8 weeks after rifampin distribution. Samples were tested using real-time polymerase chain reaction and culture. RESULTS: At baseline, 4 of 27 (14.8%) contacts and 7 of 364 (1.9%) noncontacts (P < .01) carried Hia. Contacts aged <10 years were more likely to carry Hia at any timepoint (11/18 [61%]) compared to contacts aged ≥10 years (3/34 [8.8%]), noncontacts aged <10 years (2/139 [1.4%]), and noncontacts ≥10 years (6/276 [2.2%]) (P < .001 for all). Hia carriers were clustered in 9 households (7% of total households). At the household level, carriage was associated with households with ≥1 contact (prevalence ratio [PR], 5.6 [95% confidence interval {CI}, 1.3-21.6]), crowding (PR, 7.7 [95% CI, 1.1-199.5]), and ≥3 tobacco users (PR, 5.0 [95% CI, 1.2-19.6]). Elevated carriage prevalence persisted in contacts compared to noncontacts 8 weeks after rifampin distribution (6/25 [24%] contacts, 2/114 [1.8%] noncontacts; P < .001). CONCLUSIONS: Hia carriage prevalence was significantly higher among contacts than noncontacts. Rifampin prophylaxis did not result in a reduction of Hia carriage prevalence in this community.

Vaccination Status of Alaska Native Persons With Hepatitis A Virus Infection-Alaska, 1996-2018.

Following increases in reported cases of hepatitis A, we assessed the impact of hepatitis A vaccine in Alaska Native persons. During 1996-2018, only 6 cases of hepatitis A were identified, all in unvaccinated adults. Populations can be protected against hepatitis A by achieving sufficient vaccination coverage over time.

Epidemiology of Invasive Haemophilus influenzae Serotype a Disease-United States, 2008-2017.

BACKGROUND: Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008-2017. METHODS: Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. RESULTS: From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. CONCLUSIONS: Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development.

COVID-19 Among Workers in the Seafood Processing Industry: Implications for Prevention Measures - Alaska, March-October 2020.

Large COVID-19 outbreaks have occurred in high-density workplaces, such as food processing facilities (1). Alaska's seafood processing industry attracts approximately 18,000 out-of-state workers annually (2). Many of the state's seafood processing facilities are located in remote areas with limited health care capacity. On March 23, 2020, the governor of Alaska issued a COVID-19 health mandate (HM10) to address health concerns related to the impending influx of workers amid the COVID-19 pandemic (3). HM10 required employers bringing critical infrastructure (essential) workers into Alaska to submit a Community Workforce Protective Plan.* On May 15, 2020, Appendix 1 was added to the mandate, which outlined specific requirements for seafood processors, to reduce the risk for transmission of SARS-CoV-2, the virus that causes COVID-19, in these high-density workplaces (4). These requirements included measures to prevent introduction of SARS-CoV-2 into the workplace, including testing of incoming workers and a 14-day entry quarantine before workers could enter nonquarantine residences. After 13 COVID-19 outbreaks in Alaska seafood processing facilities and on processing vessels during summer and early fall 2020, State of Alaska personnel and CDC field assignees reviewed the state's seafood processing-associated cases. Requirements were amended in November 2020 to address gaps in COVID-19 prevention. These revised requirements included restricting quarantine groups to ≤10 persons, pretransfer testing, and serial testing (5). Vaccination of this essential workforce is important (6); until high vaccination coverage rates are achieved, other mitigation strategies are needed in this high-risk setting. Updating industry guidance will be important as more information becomes available.

Airport Traveler Testing Program for SARS-CoV-2 - Alaska, June-November 2020.

Travel can facilitate SARS-CoV-2 introduction. To reduce introduction of SARS-CoV-2 infections, the state of Alaska implemented a program on June 6, 2020, for arriving air, sea, and road travelers that required either molecular testing for SARS-CoV-2, the virus that causes COVID-19, or a 14-day self-quarantine after arrival. The Alaska Department of Health and Social Services (DHSS) used weekly standardized reports submitted by 10 participating Alaska airports to evaluate air traveler choices to undergo testing or self-quarantine, traveler test results, and airport personnel experiences while implementing the program. Among 386,435 air travelers who arrived in Alaska during June 6-November 14, 2020, a total of 184,438 (48%) chose to be tested within 72 hours before arrival, 111,370 (29%) chose to be tested on arrival, and 39,685 (10%) chose to self-quarantine without testing after arrival. An additional 15,112 persons received testing at airport testing sites; these were primarily travelers obtaining a second test 7-14 days after arrival, per state guidance. Of the 126,482 airport tests performed in Alaska, 951 (0.8%) results were positive, or one per 406 arriving travelers. Airport testing program administrators reported that clear communication, preparation, and organization were vital for operational success; challenges included managing travelers' expectations and ensuring that sufficient personnel and physical space were available to conduct testing. Expected mitigation measures such as vaccination, physical distancing, mask wearing, and avoidance of gatherings after arrival might also help limit postarrival transmission. Posttravel self-quarantine and testing programs might reduce travel-associated SARS-CoV-2 transmission and importation, even without enforcement. Traveler education and community and industry partnerships might help ensure success.

Use of Rapid Antigen Testing for SARS-CoV-2 in Remote Communities - Yukon-Kuskokwim Delta Region, Alaska, September 15, 2020-March 1, 2021.

Controlling the spread of SARS-CoV-2, the virus that causes COVID-19, in Alaska is challenging. Alaska includes many remote and isolated villages with small populations (ranging from 15 to >1,000 persons) that are accessible only by air from larger communities. Until rapid point-of-care testing became widely available, a primary challenge in the diagnosis of COVID-19 in rural Alaska was slow turnaround times for SARS-CoV-2 test results, attributable to the need to transport specimens to testing facilities. To provide more timely test results and isolation of cases, the Yukon Kuskokwim Health Corporation (YKHC) introduced Abbott BinaxNOW COVID-19 Ag rapid antigen test (BinaxNOW) on November 9, 2020, in the rural Yukon-Kuskokwim Delta region in southwestern Alaska. To evaluate the impact of implementing antigen testing, YKHC reviewed the results of 54,981 antigen and molecular tests for SARS-CoV-2 performed in the Yukon-Kuskokwim Delta during September 15, 2020-March 1, 2021. Introduction of rapid, point-of-care testing was followed by a more than threefold reduction in daily SARS-CoV-2 case rates during approximately 1 month before the introduction of COVID-19 vaccination. The median turnaround time for SARS-CoV-2 test results decreased by >30%, from 6.4 days during September 15-November 8, 2020, to 4.4 days during November 9, 2020-March 1, 2021 (p<0.001). Daily incidence decreased 65% after the introduction of BinaxNOW, from 342 cases per 100,000 population during the week of November 9 to 119 during the week of December 13 (p<0.001). These findings indicate that point-of-care rapid antigen testing can be a valuable tool in reducing turnaround times in rural communities where local access to laboratory-based nucleic acid amplification testing (NAAT) is not readily available and could thereby reduce transmission by facilitating rapid isolation of infected persons, contact tracing, and implementation of local mitigation strategies.

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing.

OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. METHODS: Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. RESULTS: We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. CONCLUSIONS: Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities.

An Investigation of Early Syphilis Among Men Who have Sex with Men: Alaska, 2018: Findings from a 2018 Rapid Ethnographic Assessment.

The state of Alaska had a sharp increase in cases of primary and secondary syphilis among gay, bisexual, and other men who have sex with men (GBMSM) in 2018, centered in Anchorage. A rapid ethnographic assessment was conducted in October 2018 to examine contextual factors contributing to local increases in syphilis. The assessment team conducted qualitative interviews with 64 (N=49 interviews) key informants in Anchorage and Matanuska-Susitna Valley identified through the STD/HIV program at the Alaska Department of Health and Social Services, Division of Public Health (ADPH):  ADPH staff (n = 11; 22%) Medical Providers (n = 18; 37%), Community-Based Organizations/Partners (n = 9; 18%), and GBMSM Community Members (n = 11; 22%). This project was deemed exempt from IRB review. Primary factors affecting syphilis transmission, care, and treatment among GBMSM were: (1) Low awareness about the current syphilis outbreak and ambivalence about syphilis and other STIs; (2) Aspects of sexual partnering such as travel, tourism, and the use of online sites and apps to facilitate anonymous sex and multiple (both sequential/concurrent) partnering; (3) The synergistic effects of substance use, homelessness, and transactional sex; (4) Choosing condomless sex; and (5) Challenges accessing healthcare, including the ability to find appropriate and culturally competent care. Syphilis increases may have been influenced by factors which spanned multiple sectors of the Anchorage community, including individual behavior, community-level risk and protective factors, and use of and interactions with resources offered by ADPH, community-based organizations, and medical providers.

Characterisation of SiPM Photon Emission in the Dark.

In this paper, we report on the photon emission of Silicon Photomultipliers (SiPMs) from avalanche pulses generated in dark conditions, with the main objective of better understanding the associated systematics for next-generation, large area, SiPM-based physics experiments. A new apparatus for spectral and imaging analysis was developed at TRIUMF and used to measure the light emitted by the two SiPMs considered as photo-sensor candidates for the nEXO neutrinoless double-beta decay experiment: one Fondazione Bruno Kessler (FBK) VUV-HD Low Field (LF) Low After Pulse (Low AP) (VUV-HD3) SiPM and one Hamamatsu Photonics K.K. (HPK) VUV4 Multi-Pixel Photon Counter (MPPC). Spectral measurements of their light emissions were taken with varying over-voltage in the wavelength range of 450-1020 nm. For the FBK VUV-HD3, at an over-voltage of 12.1±1.0 V, we measured a secondary photon yield (number of photons (γ) emitted per charge carrier (e-)) of (4.04±0.02)×10-6γ/e-. The emission spectrum of the FBK VUV-HD3 contains an interference pattern consistent with thin-film interference. Additionally, emission microscopy images (EMMIs) of the FBK VUV-HD3 show a small number of highly localized regions with increased light intensity (hotspots) randomly distributed over the SiPM surface area. For the HPK VUV4 MPPC, at an over-voltage of 10.7±1.0 V, we measured a secondary photon yield of (8.71±0.04)×10-6γ/e-. In contrast to the FBK VUV-HD3, the emission spectra of the HPK VUV4 did not show an interference pattern-likely due to a thinner surface coating. The EMMIs of the HPK VUV4 also revealed a larger number of hotspots compared to the FBK VUV-HD3, especially in one of the corners of the device. The photon yield reported in this paper may be limited if compared with the one reported in previous studies due to the measurement wavelength range, which is only up to 1020 nm.

COVID-19 Mortality Among American Indian and Alaska Native Persons - 14 States, January-June 2020.

American Indian/Alaska Native (AI/AN) persons experienced disproportionate mortality during the 2009 influenza A(H1N1) pandemic (1,2). Concerns of a similar trend during the coronavirus disease 2019 (COVID-19) pandemic led to the formation of a workgroup* to assess the prevalence of COVID-19 deaths in the AI/AN population. As of December 2, 2020, CDC has reported 2,689 COVID-19-associated deaths among non-Hispanic AI/AN persons in the United States.† A recent analysis found that the cumulative incidence of laboratory-confirmed COVID-19 cases among AI/AN persons was 3.5 times that among White persons (3). Among 14 participating states, the age-adjusted AI/AN COVID-19 mortality rate (55.8 deaths per 100,000; 95% confidence interval [CI] = 52.5-59.3) was 1.8 (95% CI = 1.7-2.0) times that among White persons (30.3 deaths per 100,000; 95% CI = 29.9-30.7). Although COVID-19 mortality rates increased with age among both AI/AN and White persons, the disparity was largest among those aged 20-49 years. Among persons aged 20-29 years, 30-39 years, and 40-49 years, the COVID-19 mortality rates among AI/AN were 10.5, 11.6, and 8.2 times, respectively, those among White persons. Evidence that AI/AN communities might be at increased risk for COVID-19 illness and death demonstrates the importance of documenting and understanding the reasons for these disparities while developing collaborative approaches with federal, state, municipal, and tribal agencies to minimize the impact of COVID-19 on AI/AN communities. Together, public health partners can plan for medical countermeasures and prevention activities for AI/AN communities.

COVID-19 in Correctional and Detention Facilities - United States, February-April 2020.

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.

Risk for Invasive Streptococcal Infections among Adults Experiencing Homelessness, Anchorage, Alaska, USA, 2002-2015.

The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002-2015. We used data from the Centers for Disease Control and Prevention's Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.

Exploring the Involvement of NLRP3 and IL-1ß in Osteoarthritis of the Hand: Results from a Pilot Study.

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1ß plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1ß and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1ß and NLRP3, the serum levels of IL-1ß, IL-6, IL-17, and tumor necrosis factor- (TNF-) α, and the protein levels of IL-1ß and NLRP3. We also assessed the relationships between IL-1ß and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1ß and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1ß, IL-6, IL-17, and TNF-α serum levels were determined by ELISA. IL-1ß gene expression was significantly reduced (p = 0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p = 0.0063) and EHOA groups (p = 0.0038). IL-1ß serum levels were not significantly different across the groups; IL-6, IL-17, and TNF-α were not detectable in any sample. IL-1ß concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r = -0.446; p = 0.0008) and in NEHOA (r = -0.608; p = 0.004), while IL-1ß gene expression was positively correlated with the number of joint swellings in the EHOA group (r = 0.512; p = 0.011). Taken together, our results, showing poorly detectable IL-1ß concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level.