IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. OBJECTIVE: To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. EXPOSURE: Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. RESULTS: From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection(1,2), yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

We determined the in vitro minimum lethal concentration (MLC) of secnidazole (SEC) and assessed correlation with clinical susceptibility among T. vaginalis isolates obtained from 71 women, of whom 66 were successfully treated with this medication. An MLC ≤12.5 μg/ml correlated with clinical susceptibility in this study.

In December 2021 the U.S. Government announced a new, whole-of-government $1.8 billion effort, the Initiative for Global Vaccine Access (Global VAX) in response to the global COVID-19 pandemic. Using the foundation of decades of U.S. government investments in global health and working in close partnership with local governments and key global and multilateral organizations, Global VAX enabled the rapid acceleration of the global COVID-19 vaccine rollout in selected countries, contributing to increased COVID-19 vaccine coverage in some of the world's most vulnerable communities. Through Global VAX, the U.S. Government has supported 125 countries to scale up COVID-19 vaccine delivery and administration while strengthening primary health care systems to respond to future health crises. The progress made by Global VAX has paved the way for a stronger global recovery and improved global health security.

During January 28-May 5, 2019, a meningitis outbreak caused by Neisseria meningitidis serogroup C (NmC) occurred in Burkina Faso. Demographic and laboratory data for meningitis cases were collected through national case-based surveillance. Cerebrospinal fluid was collected and tested by culture and real-time PCR. Among 301 suspected cases reported in 6 districts, N. meningitidis was the primary pathogen detected; 103 cases were serogroup C and 13 were serogroup X. Whole-genome sequencing revealed that 18 cerebrospinal fluid specimens tested positive for NmC sequence type (ST) 10217 within clonal complex 10217, an ST responsible for large epidemics in Niger and Nigeria. Expansion of NmC ST10217 into Burkina Faso, continued NmC outbreaks in the meningitis belt of Africa since 2019, and ongoing circulation of N. meningitidis serogroup X in the region underscore the urgent need to use multivalent conjugate vaccines in regional mass vaccination campaigns to reduce further spread of those serogroups.

Current U.S. guidelines recommend integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as initial treatment for people with HIV (PWH). We assessed long-term effects of INSTI use on lipid profiles in routine HIV care. We analyzed medical record data from the HIV Outpatient Study's participants in care from 2007 to 2021. Hyperlipidemia was defined based on clinical diagnoses, treatments, and laboratory results. We calculated hyperlipidemia incidence rates and rate ratios (RRs) during initial ART and assessed predictors of incident hyperlipidemia by using Poisson regression. Among 349 eligible ART-naïve PWH, 168 were prescribed INSTI-based ART (36 raltegravir (RAL), 51 dolutegravir (DTG), and 81 INSTI-others (elvitegravir and bictegravir)) and 181 non-INSTI-based ART, including 68 protease inhibitor (PI)-based ART. During a median follow-up of 1.4 years, hyperlipidemia rates were 12.8, 22.3, 22.7, 17.4, and 12.6 per 100 person years for RAL-, DTG-, INSTI-others-, non-INSTI-PI-, and non-INSTI-non-PI-based ART, respectively. In multivariable analysis, compared with the RAL group, hyperlipidemia rates were higher in INSTI-others (RR = 2.25; 95% confidence interval (CI): 1.29-3.93) and non-INSTI-PI groups (RR = 1.89; CI: 1.12-3.19) but not statistically higher for the DTG (RR = 1.73; CI: 0.95-3.17) and non-INSTI-non-PI groups (RR = 1.55; CI: 0.92-2.62). Other factors independently associated with hyperlipidemia included older age, non-Hispanic White race/ethnicity, and ART without tenofovir disoproxil fumarate. PWH using RAL-based regimens had lower rates of incident hyperlipidemia than PWH receiving non-INSTI-PI-based ART but had similar rates as those receiving DTG-based ART, supporting federal recommendations for using DTG-based regimens as the initial therapy for ART-naïve PWH.

Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats.

In “Pneumococcal Meningitis Outbreaks in Africa, 2000–2018: | Systematic Literature Review and Meningitis Surveillance | Database Analyses” by Franklin et al reference #27 was incorrect but is now updated. | We have added the middle initial to the name of author, Jason | M. Mwenda.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.

Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for T. vaginalis isolates obtained from women who had failed treatment (n = 4) or were successfully cured (n = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive T. vaginalis isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more T. vaginalis isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains.

After the emergence of SARS-CoV-2 in late 2019, transmission expanded globally, and on January 30, 2020, COVID-19 was declared a public health emergency of international concern.* Analysis of the early Wuhan, China outbreak (1), subsequently confirmed by multiple other studies (2,3), found that 80% of deaths occurred among persons aged ≥60 years. In anticipation of the time needed for the global vaccine supply to meet all needs, the World Health Organization (WHO) published the Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework and a roadmap for prioritizing use of COVID-19 vaccines in late 2020 (4,5), followed by a strategy brief to outline urgent actions in October 2021.(†) WHO described the general principles, objectives, and priorities needed to support country planning of vaccine rollout to minimize severe disease and death. A July 2022 update to the strategy brief(§) prioritized vaccination of populations at increased risk, including older adults,(¶) with the goal of 100% coverage with a complete COVID-19 vaccination series** for at-risk populations. Using available public data on COVID-19 mortality (reported deaths and model estimates) for 2020 and 2021 and the most recent reported COVID-19 vaccination coverage data from WHO, investigators performed descriptive analyses to examine age-specific mortality and global vaccination rollout among older adults (as defined by each country), stratified by country World Bank income status. Data quality and COVID-19 death reporting frequency varied by data source; however, persons aged ≥60 years accounted for >80% of the overall COVID-19 mortality across all income groups, with upper- and lower-middle-income countries accounting for 80% of the overall estimated excess mortality. Effective COVID-19 vaccines were authorized for use in December 2020, with global supply scaled up sufficiently to meet country needs by late 2021 (6). COVID-19 vaccines are safe and highly effective in reducing severe COVID-19, hospitalizations, and mortality (7,8); nevertheless, country-reported median completed primary series coverage among adults aged ≥60 years only reached 76% by the end of 2022, substantially below the WHO goal, especially in middle- and low-income countries. Increased efforts are needed to increase primary series and booster dose coverage among all older adults as recommended by WHO and national health authorities.

BACKGROUND: Early in the pandemic, cruise travel exacerbated the global spread of SARS-CoV-2. We report epidemiologic and molecular findings from an investigation of a cluster of travelers with confirmed COVID-19 returning to the U.S. from Nile River cruises in Egypt. METHODS: State health departments reported data on real-time reverse transcription-polymerase chain reaction-confirmed COVID-19 cases with a history of Nile River cruise travel during February-March 2020 to the Centers for Disease Control and Prevention (CDC). Demographic and epidemiologic data were collected through routine surveillance channels. Sequences were obtained from either state health departments or from the Global Initiative on Sharing Avian Flu Data (GISAID). We conducted descriptive analyses of epidemiologic data and explored phylogenetic relationships between sequences. RESULTS: We identified 149 Nile River cruise travelers with confirmed COVID-19 who returned to 67 different U.S. counties in 27 states: among those with complete data, 4.7% (6/128) died and 28.1% (38/135) were hospitalized. These individuals traveled on 20 different Nile River cruise voyages (12 unique vessels). Fifteen community transmission events were identified in four states, with 73.3% (11/15) of these occurring in Wisconsin (as the result of a more detailed contact investigation in that state). Phylogenetic analyses supported the hypothesis that travelers were most likely infected in Egypt, with most sequences in Nextstrain clade 20A 93% (87/94). We observed genetic clustering by Nile River cruise voyage and vessel. CONCLUSIONS: Nile River cruise travelers with COVID-19 introduced SARS-CoV-2 over a very large geographic range, facilitating transmission across the United States early in the pandemic. Travelers who participate in cruises, even on small river vessels as investigated in this study, are at increased risk of SARS-CoV-2 exposure. Therefore, history of river cruise travel should be considered in contact tracing and outbreak investigations.

BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.

BACKGROUND: In the United States, the rates of primary and secondary syphilis have increased more rapidly among men who have sex with men (MSM) than among any other subpopulation. Rising syphilis rates among MSM reflect changes in both individual behaviors and the role of sexual networks (eg, persons linked directly or indirectly by sexual contact) in the spread of the infection. Decades of research examined how sexual networks influence sexually transmitted infections (STIs) among MSM; however, few longitudinal data sources focusing on syphilis have collected network characteristics. The Centers for Disease Control and Prevention, in collaboration with 3 sites, enrolled a prospective cohort of MSM in 3 US cities to longitudinally study sexual behaviors and STIs, including HIV, for up to 24 months. OBJECTIVE: The Network Epidemiology of Syphilis Transmission (NEST) study aimed to collect data on the factors related to syphilis transmission and acquisition among MSM. METHODS: The NEST study was a prospective cohort study that enrolled 748 MSM in Baltimore, Maryland; Chicago, Illinois; and Columbus, Ohio. NEST recruitment used a combination of convenience sampling, venue-based recruitment, and respondent-driven sampling approaches. At quarterly visits, participants completed a behavioral questionnaire and were tested for syphilis, HIV, gonorrhea, and chlamydia. The participants also provided a list of their sexual partners and described their 3 most recent partners in greater detail. RESULTS: The NEST participants were enrolled in the study from July 2018 to December 2021. At baseline, the mean age of the participants was 31.5 (SD 9.1) years. More than half (396/727. 54.5%) of the participants were non-Hispanic Black, 29.8% (217/727) were non-Hispanic White, and 8.8% (64/727) were Hispanic or Latino. Multiple recruitment strategies across the 3 study locations, including respondent-driven sampling, clinic referrals, flyers, and social media advertisements, strengthened NEST participation. Upon the completion of follow-up visits in March 2022, the mean number of visits per participant was 5.1 (SD 3.2; range 1-9) in Baltimore, 2.2 (SD 1.6; range 1-8) in Chicago, and 7.2 (SD 2.9; range 1-9) in Columbus. Using a community-based participatory research approach, site-specific staff were able to draw upon collaborations with local communities to address stigma concerning STIs, particularly syphilis, among potential NEST participants. Community-led efforts also provided a forum for staff to describe the NEST study objectives and plans for research dissemination to the target audience. Strategies to bolster data collection during the COVID-19 pandemic included telehealth visits (all sites) and adaptation to self-collection of STI specimens (Baltimore only). CONCLUSIONS: Data from NEST will be used to address important questions regarding individual and partnership-based sexual risk behaviors among MSM, with the goal of informing interventions to prevent syphilis in high-burden areas. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/40095.

BACKGROUND: The timing and magnitude of antiretroviral therapy-associated weight change attributions are unclear. SETTING: HIV Outpatient Study participants. METHODS: We analyzed 2007-2018 records of virally suppressed (VS) persons without integrase inhibitor (INSTI) experience who switched to either INSTI- or another non-INSTI-based ART, and remained VS. We analyzed BMI changes using linear mixed models (LMM), INSTI-and tenofovir alafenamide (TAF) contributions to BMI change by LMM-estimated slopes, and BMI inflection points. RESULTS: Among 736 participants (5,316 person-years), 441 (60%) switched to INSTI-based ART; the remainder to non-INSTI-based ART. Mean follow-up was 7.15 years for INSTI recipients, 7.35 years for non-INSTI. Pre-switch, INSTI and non-INSTI groups had similar median BMI (26.3 versus 25.9 kg/m2, p=0.41). INSTI regimens included raltegravir (178), elvitegravir (112) and dolutegravir (143). Monthly BMI increases post-switch were greater with INSTI than non-INSTI (0.0525 versus 0.006, p<0.001). A BMI inflection point occurred eight months after switch among INSTI users; slopes were similar regardless of TAF use immediately post-switch. Among INSTI+TAF users, during eight months post-switch, 87% of BMI slope change was associated with INSTI use, 13% with TAF use; after eight months, estimated contributions were 27% and 73%, respectively. For non-INSTI+TAF, 84% of BMI gain was TAF-associated consistently post switch. Persons switching from TDF to TAF had greater BMI increases than others (p<0.001). CONCLUSION: Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During eight months post-switch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated.

Purpose of Review: In 2020, the Appropriations Committee for the U.S. House of Representatives directed the CDC to develop a national One Health framework to combat zoonotic diseases, including sylvatic plague, which is caused by the flea-borne bacterium Yersinia pestis. This review builds upon that multisectoral objective. We aim to increase awareness of Y. pestis and to highlight examples of plague mitigation for One Health purposes (i.e., to achieve optimal health outcomes for people, animals, plants, and their shared environment). We draw primarily upon examples from the USA, but also discuss research from Madagascar and Uganda where relevant, as Y. pestis has emerged as a zoonotic threat in those foci. Recent Findings: Historically, the bulk of plague research has been directed at the disease in humans. This is not surprising, given that Y. pestis is a scourge of human history. Nevertheless, the ecology of Y. pestis is inextricably linked to other mammals and fleas under natural conditions. Accumulating evidence demonstrates Y. pestis is an unrelenting threat to multiple ecosystems, where the bacterium is capable of significantly reducing native species abundance and diversity while altering competitive and trophic relationships, food web connections, and nutrient cycles. In doing so, Y. pestis transforms ecosystems, causing “shifting baselines syndrome” in humans, where there is a gradual shift in the accepted norms for the condition of the natural environment. Eradication of Y. pestis in nature is difficult to impossible, but effective mitigation is achievable; we discuss flea vector control and One Health implications in this context. Summary: There is an acute need to rapidly expand research on Y. pestis, across multiple host and flea species and varied ecosystems of the Western US and abroad, for human and environmental health purposes. The fate of many wildlife species hangs in the balance, and the implications for humans are profound in some regions. Collaborative multisectoral research is needed to define the scope of the problem in each epidemiological context and to identify, refine, and implement appropriate and effective mitigation practices. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

In the past few decades, reported human cases of Colorado tick fever in the western United States have decreased dramatically. The goal of this study was to conduct surveillance for Colorado tick fever virus (CTFV) in Dermacentor ticks in recreational sites in Colorado, Wyoming, and California to determine whether the virus is still present in Dermacentor ticks from these states. Surveillance focused on regions where surveys had been conducted in the 1950s, 1960s, and 1970s. Adult Rocky Mountain wood ticks (Dermacentor andersoni), Pacific Coast ticks (Dermacentor occidentalis), and winter ticks (Dermacentor albipictus) were tested by PCR. A subset of PCR-positive D. andersoni ticks (n=7) were cultured in Vero cells. CTFV-positive Rocky Mountain wood ticks were found in all states: Colorado (58% prevalence), Wyoming (21%), and California (4%). Although no winter ticks tested positive, Pacific Coast ticks tested positive in one county (Siskiyou County, 15% prevalence) and were positive only in a location that also maintained Rocky Mountain wood ticks and golden mantled ground squirrels, a known CTFV host. In summary, CTFV is prevalent in D. andersoni and D. occidentalis in regions where they are sympatric in California and in D. andersoni in Colorado and Wyoming. Although the number of human CTFV cases has declined dramatically, this decrease in reported disease does not appear to be due to the disappearance or even the decline in prevalence of this virus in ticks in historically endemic regions of the country.

On January 6, 2022, a cluster of COVID-19 cases* caused by the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, was detected in Hong Kong Special Administrative Region, China (Hong Kong), resulting in the territory's fifth wave of COVID-19 cases (1). This wave peaked on March 4, 2022, with 8,764 COVID-19 cases per million population (2), resulting in a total of 1,049,959 cases and 5,906 COVID-19-associated deaths reported to the Hong Kong Department of Health during January 6-March 21, 2022.() Throughout this period, the COVID-19 mortality rate in Hong Kong (37.7 per million population) was among the highest reported worldwide since the COVID-19 pandemic began (3). Publicly available data on age-specific vaccination coverage in Hong Kong with a 2-dose primary vaccination series (with either Sinovac-CoronaVac [Sinovac], an inactivated COVID-19 viral vaccine, recommended for persons aged 3 years or BNT162b2 [Pfizer-BioNTech], an mRNA vaccine, for persons aged 5 years), as of December 23, 2021,()(,)() and COVID-19 mortality during January 6-March 21, 2022, were analyzed. By December 23, 2021, 67% of vaccine-eligible persons in Hong Kong had received 1 dose of a COVID-19 vaccine, 64% had received 2 doses, and 5% had received a booster dose. Among persons aged 60 years, these proportions were 52%, 49%, and 7%, respectively. Among those aged 60 years, vaccination coverage declined with age: 48% of persons aged 70-79 years had received 1 dose, 45% received 2 doses, and 7% had received a booster, and among those aged 80 years, 20%, 18%, and 2% had received 1 dose, 2 doses, and a booster dose, respectively. Among 5,906 COVID-19 deaths reported, 5,655 (96%) occurred in persons aged 60 years**; among these decedents, 3,970 (70%) were unvaccinated, 18% (1,023) had received 1 vaccine dose, and 12% (662) had received 2 doses. The overall rates of COVID-19-associated mortality among persons aged 60 years who were unvaccinated, who had received 1 COVID-19 vaccine dose, and who had received 2 vaccine doses were 10,076, 1,099, and 473 per million population, respectively; the risk for COVID-19-associated death among unvaccinated persons was 21.3 times that among recipients of 2-3 doses in this age group. The high overall mortality rate during the ongoing 2022 Hong Kong Omicron COVID-19 outbreak is being driven by deaths among unvaccinated persons aged 60 years. Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially among persons aged 60 years.

During 2007-2019, the percentage of HIV Outpatient Study participants reporting anal or vaginal condomless sex in the past 6 months ranged from a low of 17% among heterosexual males to 59% for men who have sex with men (MSM). MSM reported having had condomless sex more frequently than heterosexual males and females and were the only group in which an increase in condomless sex was observed during the study period (from 39 to 59%). Although persons with undetectable HIV viral load have effectively no risk of transmitting HIV sexually (U = U), there is still the potential risk of transmission or acquisition of other sexually transmitted infections (STIs) when engaging in condomless sex. Continuing education about risks of HIV and STI transmission as well as ongoing screening for and treatment of STIs, retention in HIV treatment, and support for sexual health are critical components of care for people living with HIV.

COVID-19 vaccines are important tools to protect populations from severe disease and death.Among persons aged ≥60 years in Hong Kong, 49%, had received ≥2 doses of a COVID-19 vaccine, and vaccination coverage declined with age. During January-March 2022, reported COVID-19-associated deaths rose rapidly in Hong Kong. Among these deaths, 96% occurred in persons aged ≥60 years; within this age group, the risk for death was 20 times lower among those who were fully vaccinated compared with those who were unvaccinated.Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially in older adults.Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.

Togo has reported seasonal meningitis outbreaks caused by non-Neisseria meningitidis serogroup A (NmA) pathogens since the introduction of meningococcal serogroup A conjugate vaccine (MACV, MenAfriVac) in 2014. From 2016 to 2017, NmW caused several outbreaks. In early 2019, a NmC outbreak was detected in the Savanes region of Togo and its investigation is described here. Under case-based surveillance, epidemiological and clinical data, and cerebrospinal fluid specimens were collected for every suspected case of meningitis. Specimens were tested for meningitis pathogens using confirmatory microbiological and molecular methods. During epidemic weeks 9 to 15, 199 cases were reported, with 179 specimens being available for testing and 174 specimens (97.2%) were tested by at least one confirmatory method. The NmC was the predominant pathogen confirmed (93.9%), belonging to sequence type (ST)-9367 of clonal complex (CC) 10217. All NmC cases were localized to the West Kpendjal district of the Savanes region with attack rates ranging from 4.1 to 18.8 per 100,000 population and case fatality rates ranging up to 2.2% during weeks 9 to 15. Of the 93 NmC confirmed cases, 63.4% were males and 88.2% were in the 5 to 29 age group. This is the first report of a NmC meningitis outbreak in Togo. The changing epidemiology of bacterial meningitis in the meningitis belt post-MACV highlights the importance of monitoring of emerging strain and country preparedness for outbreaks in the region. IMPORTANCE The recent emergence of an invasive NmC strain in Togo is an example of the changing bacterial meningitis epidemiology in the meningitis belt post-MACV. The current epidemiology includes the regional circulation of various non-NmA serogroups, which emphasizes the need for effective molecular surveillance, laboratory diagnosis, and a multivalent vaccine that is effective against all serogroups in circulation.

BACKGROUND: Predominance of 2 antigenically drifted influenza viruses during the 2019-2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States. METHODS: We enrolled children aged <18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation. RESULTS: We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, -21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses. CONCLUSIONS: During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children.

BACKGROUND: Age blunts CD4+ lymphocyte cell count/mm3 (CD4) improvements observed with antiretroviral therapy (ART)-induced viral suppression among people with HIV (PWH). Prolonged viral suppression reduces immune dysregulation, reflected by rising CD4/CD8 ratios (CD4/CD8). We studied CD4/CD8 over time to determine whether it predicts risk for select comorbidities and mortality among aging PWH with viral suppression. METHODS: We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000-2018 who achieved a VL<200copies/mL on or after January 1, 2000, and remained virally suppressed at least one year thereafter. We modeled associations of CD4/CD8 with select incident comorbidities and all-cause mortality using Cox regression and controlling for demographic and clinical factors. RESULTS: Of 2,480 eligible participants,1,145 (46%) were aged<40years, 835 (34%) 40-49years, and 500 (20%) 50years. At baseline, median CD4/CD8 was 0.53 (interquartile range: 0.30-0.84) and similar among all age groups (P=0.18). CD4/CD8 values and percent of participants with CD4/CD8 0.70 increased within each age group (P<0.001 for all). CD4/CD8 increase was greatest for PWH aged<40years at baseline. In adjusted models, most recent CD4/CD8<1.00 and<0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively. CONCLUSIONS: Pre-treatment immune dysregulation may persist as indicated by CD4/CD8<0.70. Persistent viral suppression can improve immune dysregulation over time, reducing comorbidity and mortality risk. Monitoring CD4/CD8 among ART-treated PWH with lower values provide a means to assess for mortality and co-morbidity risk.

BACKGROUND: In March 2017, Burkina Faso introduced meningococcal serogroup A conjugate vaccine (MACV) into the Expanded Programme on Immunization. MACV is administered to children aged 15-18 months, concomitantly with the second dose of measles-containing vaccine (MCV2). One year after MACV introduction, we assessed the sources and content of immunization information available to caregivers and explored motivations and barriers that influence their decision to seek MACV for their children. METHODS: Twenty-four focus group discussions (FGDs) were conducted with caregivers of children eligible for MACV and MCV2. Data collection occurred in February-March 2018 in four purposively selected districts, each from a separate geographic region; within each district, caregivers were stratified into groups based on whether their children were unvaccinated or vaccinated with MACV. FGDs were recorded and transcribed. Transcripts were coded and analyzed using qualitative content analysis. RESULTS: We identified many different sources and content of information about MACV and MCV2 available to caregivers. Healthcare workers were most commonly cited as the main sources of information; caregivers also received information from other caregivers in the community. Caregivers' motivations to seek MACV for their children were driven by personal awareness, engagements with trusted messengers, and perceived protective benefits of MACV against meningitis. Barriers to MACV and MCV2 uptake were linked to the unavailability of vaccines, immunization personnel not providing doses, knowledge gaps about the 15-18 month visit, practical constraints, past negative experiences, sociocultural influences, and misinformation, including misunderstanding about the need for MCV2. CONCLUSIONS: MACV and MCV2 uptake may be enhanced by addressing vaccination barriers and effectively communicating vaccination information and benefits through trusted messengers such as healthcare workers and other caregivers in the community. Educating healthcare workers to avoid withholding vaccines, likely due to fear of wastage, may help reduce missed opportunities for vaccination.

BACKGROUND: The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. METHODS: Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. RESULTS: A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. CONCLUSIONS: Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.

Since 2010, the introduction of an effective serogroup A meningococcal conjugate vaccine has led to the near-elimination of invasive Neisseria meningitidis serogroup A disease in Africa's meningitis belt. However, a significant burden of disease and epidemics due to other bacterial meningitis pathogens remain in the region. High-quality surveillance data with laboratory confirmation is important to monitor circulating bacterial meningitis pathogens and design appropriate interventions, but complete testing of all reported cases is often infeasible. Here, we use case-based surveillance data from 5 countries in the meningitis belt to determine how accurately estimates of the distribution of causative pathogens would represent the true distribution under different laboratory testing strategies. Detailed case-based surveillance data was collected by the MenAfriNet surveillance consortium in up to 3 seasons from participating districts in 5 countries. For each unique country-season pair, we simulated the accuracy of laboratory surveillance by repeatedly drawing subsets of tested cases and calculating the margin of error of the estimated proportion of cases caused by each pathogen (the greatest pathogen-specific absolute error in proportions between the subset and the full set of cases). Across the 12 country-season pairs analyzed, the 95% credible intervals around estimates of the proportion of cases caused by each pathogen had median widths of ±0.13, ±0.07, and ±0.05, respectively, when random samples of 25%, 50%, and 75% of cases were selected for testing. The level of geographic stratification in the sampling process did not meaningfully affect accuracy estimates. These findings can inform testing thresholds for laboratory surveillance programs in the meningitis belt.

We evaluated the association of bone fracture with mortality among persons with HIV, controlling for sociodemographic, behavioral, and clinical factors. Incident fracture was associated with 48% greater risk of all-cause mortality, underscoring the need for bone mineral density screening and fracture prevention. PURPOSE/INTRODUCTION: Low bone mineral density (BMD) and fracture are more common among persons with HIV (PWH) than those without HIV infection. We evaluated the association of bone fracture with mortality among PWH, controlling for sociodemographic, behavioral, and clinical factors. METHODS: We analyzed data from HIV Outpatient Study (HOPS) participants seen at nine US HIV clinics during January 1, 2000, through September 30, 2017. Incident fracture rates and post-fracture mortality were compared across four calendar periods. Cox proportional hazards analyses determined factors associated with all-cause mortality among all participants and those with incident fracture. RESULTS: Among 6763 HOPS participants, 504 (7.5%) had incident fracture (median age = 47 years) and 719 (10.6%) died. Of fractures, 135 (26.8%) were major osteoporotic (hip/pelvis, wrist, spine, arm/shoulder). During observation, 27 participants with major osteoporotic fractures died (crude mortality 2.97/100 person-years [PY]), and 48 with other site fractures died (crude mortality 2.51/100 PY). Post-fracture, age- and sex-adjusted all-cause mortality rates per 100 PY decreased from 8.5 during 2000-2004 to 1.9 during 2013-2017 (P<0.001 for trend). In multivariable analysis, incident fracture was significantly associated with all-cause mortality (Hazard Ratio 1.48, 95% confidence interval 1.15-1.91). Among 504 participants followed post-fracture, pulmonary, kidney, and cardiovascular disease, hepatitis C virus co-infection, and non-AIDS cancer, remained independently associated with all-cause mortality. CONCLUSIONS: Incident fracture was associated with 48% greater risk of all-cause mortality among US PWH in care, underscoring the need for BMD screening and fracture prevention. Although fracture rates among PWH increased during follow-up, post-fracture death rates decreased, likely reflecting advances in HIV care.

The aim of this study was to identify viral exposure (VE) measures and their relationship to mortality risk among persons with HIV.Prospective multicenter observational study to compare VE formulae.Eligible participants initiated first combination antiretroviral therapy (cART) between March 1, 1995 and June 30, 2015. We included 1645 participants followed for ≥6 months after starting first cART, with cART prescribed ≥75% of time, who underwent ≥2 plasma viral load (VL) and ≥1 CD4+ T-lymphocyte cell (CD4) measurement during observation. We evaluated all-cause mortality from 6 months after cART initiation until June 30, 2016. VE was quantified using 2 time-updated variables: viremia copy-years and percent of person-years (%PY) spent >200 or 50 copies/mL. Cox models were fit to estimate associations between VE and mortality.Participants contributed 10,453 person years [py], with median 14 VLs per patient. Median %PY >200 or >50 were 10% (interquartile range: 1%-47%) and 26% (interquartile range: 6%-72%), respectively. There were 115 deaths, for an overall mortality rate of 1.19 per 100 person years. In univariate models, each measure of VE was significantly associated with mortality risk, as were older age, public insurance, injection drug use HIV risk history, and lower pre-cART CD4. Based on model fit, most recent viral load and %PY >200 copies/mL provided the best combination of VE factors to predict mortality, although all VE combinations evaluated performed well.The combination of most recent VL and %PY >200 copies/mL best predicted mortality, although all evaluated VE measures performed well.

BACKGROUND: We evaluated treatment duration and viral suppression (VS) outcomes with integrase strand transfer inhibitor (INSTI)-based regimens versus other contemporary regimens among adults in routine HIV care. METHODS: Eligible participants were seen during January 1, 2007 to June 30, 2018 at nine U.S. HIV clinics, initiated antiretroviral therapy (ART) (baseline date), and had ≥2 clinic visits thereafter. We assessed the probability of remaining on a regimen and achieving HIV RNA < 200 copies/mL on initial INSTI versus non-INSTI ART by Kaplan-Meier analyses and their correlates by Cox regression. RESULTS: Among 1005 patients, 335 (33.3%) were prescribed an INSTI-containing regimen and 670 (66.7%) a non-INSTI regimen, which may have included non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and other agents. In both groups, most patients were male, non-white, and aged <50 years. Comparing the INSTI with non-INSTI group, the median baseline log10 HIV viral load (copies/mL) was 4.6 vs. 4.5 and the median CD4+ cell count (cells/mm3) was 352 vs. 314. In Kaplan-Meier analysis, the estimated probabilities of remaining on initial regimens at 2 and 4 years were 58% and 40% for INSTI and 51% and 33% for non-INSTI group, respectively (log-rank test p = 0.003. In multivariable models, treatment with an INSTI (vs. non-INSTI) ART was negatively associated with a regimen switch (Hazard Ratio [HR], 0.67, 95% Confidence Interval [CI] 0.56, 0.81, p < 0.001), and was positively associated with achieving viral suppression (HR 1.52; CI 1.29, 1.79, p < 0.001), both irrespective of baseline viral load levels. CONCLUSIONS: Initial INSTI-based regimens were associated with longer durations and better viral suppression than non-INSTI regimens. Results support INSTI regimens as the initial therapy in U.S. treatment guidelines.

BACKGROUND: Cruise travel contributed to SARS-CoV-2 transmission when there were relatively few cases in the United States. By March 14, 2020, the Centers for Disease Control and Prevention (CDC) issued a No Sail Order suspending U.S. cruise operations; the last U.S. passenger ship docked on April 16. METHODS: We analyzed SARS-CoV-2 outbreaks on cruises in U.S. waters or carrying U.S. citizens and used regression models to compare voyage characteristics. We used compartmental models to simulate the potential impact of four interventions (screening for COVID-19 symptoms; viral testing on two days and isolation of positive persons; reduction of passengers by 40%, crew by 20%, and port visits to one) for 7-day and 14-day voyages. RESULTS: During January 19-April 16, 2020, 89 voyages on 70 ships had known SARS-CoV-2 outbreaks; 16 ships had recurrent outbreaks. There were 1,669 RT-PCR-confirmed SARS-CoV-2 infections and 29 confirmed deaths. Longer voyages were associated with more cases (adjusted incidence rate ratio, 1.10, 95% CI: 1.03-1.17, p < 0.0001). Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43-49% reduction in total infections) and testing passengers and crew (42-43% reduction in total infections). All four interventions reduced transmission by 80%, but no single intervention or combination eliminated transmission. Results were similar for 14-day voyages. CONCLUSIONS: SARS-CoV-2 outbreaks on cruises were common during January-April 2020. Despite all interventions modeled, cruise travel still poses a significant SARS-CoV-2 transmission risk.