BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

BACKGROUND: Syphilis in Florida increased 49% from 2016-2020. Moreover, many serological tests for syphilis (STS) do not indicate current infection. Traditionally, syphilis surveillance systems used reactor grids, a method for prioritizing STS for investigation based on age, non-treponemal titer, and/or sex. In 2022, Florida's STD surveillance system implemented an automated method for processing electronically reported STS (eSTS), expanding upon the reactor grid, using an individual's current STS (treponemal and non-treponemal), treatment history, and historical STS results aiming for more efficiently processing eSTS. We compared the new method of processing eSTS results against the reactor grid and determined potential value in time/cost savings of this change. METHODS: All eSTS (n = 4,144) from 1/2/2023-1/8/2023 were compared by how the logic-based method processed test results vs. how the reactor grid processed test results. Each method was compared using measurements of accuracy (e.g., sensitivity/specificity). Time and cost savings in eSTS processing were estimated. RESULTS: Using the surveillance case definition as reference, the accuracy of the logic-based method for processing eSTS was nearly double (82.3% vs. 43.6%), had greater specificity (79.0% vs. 33.0%), and increased positive predictive value (47.5% vs. 22.0%) when compared to the reactor grid method. Sensitivity (99.5% vs. 98.6%) and negative predictive value (99.9% vs. 99.2%) remained similar. The logic-based method is estimated to save 7,783 hours annually (~$185,000). CONCLUSIONS: Processing eSTS based on current and historical STS results is significantly more accurate than using a reactor grid. Moreover, these improvements save time and resources that can be better allocated to other program prevention activities.

BACKGROUND: Each year, Florida Department of Health staff process hundreds of thousands of electronically received laboratory results for chlamydia (CT) and gonorrhea (GC). These processing steps are currently performed manually in Florida's surveillance system and divert from other sexually transmitted disease prevention efforts. We developed processes that would automate these procedures and evaluated the impact on potential programmatic time savings. METHODS: We evaluated 575,952 electronic CT/GC laboratory results from January 2019 to December 2021. Laboratory results were processed through the newly automated procedures and algorithms. Expected time savings were projected using conservative estimates of 1 minute saved every time an automated process replaced a current manual procedure: profile matching, profile creation, event record creation, case review, and case reporting. Exceptions to automatic case reporting applied to certain higher-priority populations needing intervention. RESULTS: During this period, 297,348 electronic CT/GC laboratory results were received for people with no previous recorded history of sexually transmitted diseases and required profile creation. In total, 386,763 new surveillance infection records were created for reporting. Of reported cases, 127,345 were from higher-priority groups. The proposed automations would have saved an estimated 33,121 hours of staff time, about 11,040 hours or the work of 5.3 full-time staff annually. CONCLUSIONS: Automating current CT/GC laboratory processing would save thousands of personnel hours that could be redirected to higher-priority activities. Flexibility in prioritization criteria for automated case reporting allows programs to adjust automation to disease prevention priorities and resources. Similar automation procedures could be developed by other jurisdictions or health programs.

BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

OBJECTIVES: As, cases of congenital syphilis (CS) and infectious syphilis among women more than doubled in Florida and across the nation during 2013-2019, we sought to understand what may be contributing to these increases in Florida. DESIGN: A two time-period observational study. SETTING: Pregnant women with reported syphilis infections and their pregnancy outcomes (2013-2014 and 2018-2019) in Florida. PARTICIPANTS: 1213 pregnant women with reported syphilis infections living in Florida and 341 infants meeting the CS case definition. OUTCOME MEASURES: We assessed what proportion of the increase in CS was from increases in maternal syphilis infections. We examined maternal demographics, infection characteristics and timing of diagnoses that could explain the increase in CS. Finally, we reviewed if changes in presentation or severity of CS cases occurred. RESULTS: During 2013-2014, 83 (21%) of 404 pregnant women with syphilis delivered babies with CS. During 2018-2019, 258 (32%) of 809 pregnant women with syphilis delivered babies with CS. Comparing CS prevention rates, it was determined that 65% of the increase in CS was due to the increases in maternal syphilis infections. The proportion of maternal cases staged as primary or secondary increased over time (7%-13%) (p<0.01) and reports of drug use became slightly more common (6%-10%) (p=0.02). During 2018-2019, women delivering CS infants were more likely to be reinfected during the same pregnancy (27 (10%) vs 5 (6%) p=0.23) and more had negative third trimester screening tests (43 (17%) vs 7 (8% p=0.07)). The percentage of infants with CS who had ≥1 sign or symptom increased from 35% to 40%, and the combined total of stillbirths and infant deaths increased from 5 to 26. CONCLUSIONS: Recently, more pregnant women are being infected with syphilis and a higher per cent are not being treated to prevent CS. The reasons for this finding are unclear.

BACKGROUND: Shigella species, which cause acute diarrheal disease, are transmitted via fecal-oral and sexual contact. To better understand the overlapping populations affected by Shigella infections and sexually transmitted infections (STIs) in the United States, we examined the occurrence of reported STIs within 24 months among shigellosis case-patients. METHODS: Culture-confirmed Shigella cases diagnosed during 2007-2016 among residents of six U.S. jurisdictions were matched to reports of STIs (chlamydia, gonorrhea, and all stages of syphilis) diagnosed 12 months before or after the shigellosis case. We examined epidemiologic characteristics and reported temporal trends of Shigella cases by sex and species. RESULTS: During 2007-2016, 10,430 shigellosis cases were reported. The annual number of reported shigellosis cases across jurisdictions increased 70%, from 821 cases in 2007 to 1,398 cases in 2016; males saw a larger increase compared to females. Twenty percent of male shigellosis case-patients had an STI reported in the reference period, versus 4% of female case-patients. The percentage of male shigellosis case-patients with an STI increased from 11% (2007) to 28% (2016); the overall percentage among females remained low. CONCLUSIONS: We highlight the substantial proportion of males with shigellosis who were diagnosed with STIs within 24 months and the benefit of matching data across programs. STI screening may be warranted for male shigellosis case-patients.

Syphilis rates have continued to rise in the United States. Florida and Louisiana consistently report high numbers of cases. We evaluated rates of reinfection to see if frequent rescreening might lead to earlier treatment and prevent infections. All syphilis records of all stages for males and females aged 15-70 years from the Florida and Louisiana Departments of Health surveillance databases 2000-2018 were evaluated. The first episode of syphilis during this period was considered the initial diagnosis for each person. Demographics of cases and repeaters (individuals reported with two or more cases of syphilis) were examined. Percentages of syphilis cases from repeaters by year were calculated as were percentages from HIV+ males. During 2000-2018, 124,827 syphilis cases were reported from 107,405 individuals: 73,811 (68.7%) males; 33,594 (31.3%) females. There were 12,545 individuals (repeaters) with two or more syphilis diagnoses (n = 17,422 cases; range, 2-10). From 2010 to 2018, repeaters accounted for steadily increasing percentage of all syphilis reported: 2010 (11%), 2013 (16%), 2015 (20%), and 2018 (26%). Among HIV+ male cases the percentage from repeaters also increased: 2010 (28%), 2013 (35%), 2015 (42%), and 2018 (50%). In 2018, 19% of all cases (n = 2455) were from HIV+ males who had a previous syphilis diagnosis. Among HIV+ males diagnosed with syphilis in 2015, 34% had a repeat syphilis diagnosis within 3 years. Most syphilis diagnosed in Florida and Louisiana was among persons infected for the first time. However, some subgroups could possibly benefit from more frequent screening. Males living with HIV who had a prior syphilis diagnosis were at very high risk of repeat infection.

On June 30, 2021, the Illinois Department of Public Health (IDPH) contacted CDC concerning COVID-19 outbreaks at two events sponsored by the same organization: a 5-day overnight church camp for persons aged 14-18 years and a 2-day men's conference. Neither COVID-19 vaccination nor COVID-19 testing was required before either event. As of August 13, a total of 180 confirmed and probable cases had been identified among attendees at the two events and their close contacts. Among the 122 cases associated with the camp or the conference (primary cases), 18 were in persons who were fully vaccinated, with 38 close contacts. Eight of these 38 close contacts subsequently became infected with SARS-CoV-2, the virus that causes COVID-19 (secondary cases); among the eight close contacts with secondary cases, one half (four) were fully vaccinated. Among the 180 total persons with outbreak-associated cases, five (2.8%) were hospitalized; no deaths occurred. None of the vaccinated persons with cases were hospitalized. Approximately 1,000 persons across at least four states were exposed to SARS-CoV-2 through attendance at these events or through close contact with a person who had a primary case. This investigation underscores the impact of secondary SARS-CoV-2 transmission during large events, such as camps and conferences, when COVID-19 prevention strategies are not implemented. In Los Angeles County, California, during July 2021, when the SARS-CoV-2 B.1.617.2 (Delta) variant was predominant, unvaccinated residents were five times more likely to be infected and 29 times more likely to be hospitalized from infection than were vaccinated residents (1). Implementation of multiple prevention strategies, including vaccination and nonpharmaceutical interventions such as masking, physical distancing, and screening testing, are critical to preventing SARS-CoV-2 transmission and serious complications from COVID-19.

INTRODUCTION: Disease intervention specialists (DIS) prevent syphilis by assuring treatment for patients' sex partners through partner notification (PN). Different interpretations of how to measure partners treated due to DIS efforts complicates PN evaluation. We measured PN impact by counting partners treated for syphilis after DIS interviewed the patient. METHODS: We reviewed data from early syphilis cases reported during 2015-2017 in seven jurisdictions. We compared infected partners brought to treatment using: 1) DIS-assigned disposition codes or 2) all infected partners treated 0-90 days after the patient's interview (adjusted treatment estimate). Stratified analyses assessed patient characteristics associated with the adjusted treatment estimate. RESULTS: DIS interviewed 23,613 patients who reported 20,890 partners with locating information. Many of the 3,569 (17.1%) partners classified by DIS as brought to treatment were treated before the patient was interviewed. There were 2,359 (11.3%) partners treated 0-90 days after the patient's interview. Treatment estimates were more consistent between programs when measured using our adjusted estimates (range 6.1%-14.8% per patient interviewed) compared to DIS-assigned disposition (range 6.1%-28.3%). Treatment of >1 partner occurred after 9.0% of interviews and was more likely if the patient was a woman (17.9%), aged <25 years (12.6%), interviewed ≤7 days from diagnosis (13.9%), HIV negative (12.6%), or had no reported history of syphilis (9.8%). CONCLUSIONS: Counting infected partners treated 0-90 days after interview reduced variability in reporting and facilitates quality assurance. Identifying programs and DIS who are particularly good at finding and treating partners could improve program impact.

Primary amebic meningoencephalitis is a rare, usually fatal disease, caused by Naegleria fowleri. This case highlights the challenging clinicopathologic diagnosis in a 13-year-old boy who swam in freshwater in northern Florida where a previous case had exposure to a body of water on the same property in 2009. © 2021

BACKGROUND: Reactive syphilis serologies are investigated by health departments to determine if they represent new infection, reinfection, or treatment failure. Serologies prioritized for investigation based on nontreponemal test titer and age (using a 'reactor grid') undergo manual record search and review. We developed a computerized algorithm that automates the record search and review. METHODS: We developed and tested the algorithm using a Florida Department of Health dataset containing serologies reported January 2016-December 2018 and previous records linked to each individual. The algorithm was based on the syphilis case definition, which requires (except primary cases with signs and symptoms) 1) a positive treponemal test and a newly positive nontreponemal test or, 2) a 4-fold increase in nontreponemal test titer. Two additional steps were added to avoid missing cases. New York City Department of Health and Mental Hygiene validated this algorithm. RESULTS: The algorithm closed more investigations (49.9%) than the reactor grid (27.0%). The algorithm opened 99.4% of the individuals investigated and labeled as cases by the health department; it missed 75 cases. Many investigations opened by the algorithm were closed by the 'reactor grid'; we could not assess how many would have been cases. In New York City, the algorithm closed 70.9% of investigations, likely because more individuals had previous test in the database (88.2%) compared to Florida (56.5%). CONCLUSIONS: The automated algorithm successfully searched and reviewed records to help identify cases of syphilis. We estimate the algorithm would have saved Florida 590 workdays over 3 years.

BACKGROUND: The SARS-CoV-2 virus responsible for severe respiratory infection associated with coronavirus disease 2019 (COVID-19) was first confirmed in Florida on March 1, 2020. Responding to the pandemic, multi-agency collaborative partnerships put in place actions integrating point-of-care antibody testing at established large-scale COVID-19 testing sites where the baseline seropositivity of COVID-19 in health care workers and first responders in Florida at the start of the pandemic was established. PURPOSE: Determine the seropositivity of healthcare workers and first responders at five drive thru testing sites using a rapid SARS-CoV-2 antibody test in Florida from May 6 through June 3, 2020. METHODS: The first drive-thru SARS-CoV-2 antibody test site was opened at Miami Hard Rock Stadium, May 6, 2020. Testing expanded to three additional sites on May 9, 2020: Jacksonville, Orlando, and Palm Beach. The fifth and final site, Miami Beach, began testing on May 21, 2020. Healthcare workers and first responder's self-seeking SARS-CoV-2 testing were designated for antibody testing and completed a laboratory collection form onsite for the point-of-care test. All testing was performed on whole blood specimens (obtained by venipuncture) using the Cellex Inc. qSARS-CoV-2 IgG/IgM Rapid Test. Seropositivity was assessed by univariate analysis and by logistic regression including the covariates age, sex, race/ethnicity, and testing location. RESULTS AND DISCUSSION: As of June 3, 2020, of 5,779 healthcare workers and first responders tested, 4.1% were seropositive (range 2.6-8.2%). SARS-COV-2 antibody tests had higher odds of being positive for persons testing at the Miami Hard Rock Stadium (aOR 2.24 [95% C.I. 1.48-3.39]), persons of Haitian/Creole ethnicity (aOR 3.28 [95% C.I. 1.23-8.72]), Hispanic/Latino(a) ethnicity (aOR 2.17 [95% C.I. 1.50-3.13], and Black non-Hispanic persons (aOR 1.63 [95% C.I. 1.08-2.46]). SARS-COV-2 antibody prevalence among first responders and healthcare workers in five sites in Florida varied by race and ethnicity and by testing location.

In late September 2020, the incidence of confirmed COVID-19* in North Dakota began increasing rapidly, from approximately 300 new cases per day to approximately 2,260 cases on November 13, 2020 (1). On October 20, the North Dakota Department of Health reported that contact tracing notification efforts were delayed. Because of the delay, COVID-19 patients were asked to notify their own contacts about potential exposure and encourage them to seek testing for SARS-CoV-2, the virus that causes COVID-19 (2). The Spirit Lake sovereign nation in east central North Dakota is home to approximately 7,500 members of the Spirit Lake Tribe. In response to increasing incidence of COVID-19 on the Spirit Lake Reservation, CDC assisted the Spirit Lake Tribe in building a tribally managed program for comprehensive COVID-19 case investigations, case notification, contact tracing, contact testing, and contact management to ensure timely implementation of these critical epidemic control measures.

In 2018, an estimated 1.8 million persons living in Nigeria had HIV infection (1.3% of the total population), including 1.1 million (64%) who were receiving antiretroviral therapy (ART) (1). Effective ART reduces morbidity and mortality rates among persons with HIV infection and prevents HIV transmission once viral load is suppressed to undetectable levels (2,3). In April 2019, through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR),* CDC launched an 18-month ART Surge program in nine Nigerian states to rapidly increase the number of persons with HIV infection receiving ART. CDC analyzed programmatic data gathered during March 31, 2019-September 30, 2020, to describe the ART Surge program's progress on case finding, ART initiation, patient retention, and ART Surge program growth. Overall, the weekly number of newly identified persons with HIV infection who initiated ART increased approximately eightfold, from 587 (week ending May 4, 2019) to 5,329 (week ending September 26, 2020). The ART Surge program resulted in 208,202 more HIV-infected persons receiving PEPFAR-supported ART despite the COVID-19 pandemic (97,387 more persons during March 31, 2019-March 31, 2020 and an additional 110,815 persons during April 2020-September 2020). Comprehensive, data-guided, locally adapted interventions and the use of incident command structures can help increase the number of persons with HIV infection who receive ART, reducing HIV-related morbidity and mortality as well as decreasing HIV transmission.

The novel coronavirus disease 2019, COVID-19, which is caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) [1] was first reported in December 2019 by Chinese Health Authorities following an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province [2,3]. SARS-CoV-2 is likely of zoonotic origin, similar to SARS and Middle East Respiratory Syndrome (MERS), and transmitted between humans through respiratory droplets and fomites. Since its emergence, it has rapidly spread globally [4].

Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention's Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted.

The objective of this study was to describe the epidemiology of COVID-19 in Nigeria with a view of generating evidence to enhance planning and response strategies. A national surveillance dataset between 27 February and 6 June 2020 was retrospectively analysed, with confirmatory testing for COVID-19 done by real-time polymerase chain reaction (RT-PCR). The primary outcomes were cumulative incidence (CI) and case fatality (CF). A total of 40 926 persons (67% of total 60 839) had complete records of RT-PCR test across 35 states and the Federal Capital Territory, 12 289 (30.0%) of whom were confirmed COVID-19 cases. Of those confirmed cases, 3467 (28.2%) had complete records of clinical outcome (alive or dead), 342 (9.9%) of which died. The overall CI and CF were 5.6 per 100 000 population and 2.8%, respectively. The highest proportion of COVID-19 cases and deaths were recorded in persons aged 31-40 years (25.5%) and 61-70 years (26.6%), respectively; and males accounted for a higher proportion of confirmed cases (65.8%) and deaths (79.0%). Sixty-six per cent of confirmed COVID-19 cases were asymptomatic at diagnosis. In conclusion, this paper has provided an insight into the early epidemiology of COVID-19 in Nigeria, which could be useful for contextualising public health planning.

BACKGROUND: Reducing transmission depends on the percentage of infected partners treated; if many are missed, impact on transmission will be low. Traditional partner services metrics evaluate the number of partners found and treated. We estimated the proportion of partners of syphilis patients not locatable for intervention. METHODS: We reviewed records of early syphilis cases (primary, secondary, early latent) reported during 2015-2017 in seven jurisdictions (Florida, Louisiana, Michigan, North Carolina, Virginia, New York City, and San Francisco). Among interviewed syphilis patients, we determined the proportion who reported named partners (with locating information), reported unnamed partners (no locating information), and did not report partners. For patients with no reported partners, we estimated their range of unreported partners to be between one and the average number of partners for patients who reported partners. RESULTS: Among 29,719 syphilis patients, 23,613 (80%) were interviewed and 18,581 (63%) reported 84,224 sex partners (average=4.5; 20,853 (25%) named and 63,371 (75%) unnamed). An estimated 11,138 to 54,521 partners were unreported. Thus, 74,509 to 117,892 (of 95,362 to 138,745) partners were not reached by partner services (78-85%). Among interviewed patients, 71% reported ≥1 unnamed partner or reported no partners; this proportion was higher for men who reported sex with men [MSM] (75%), compared to men who reported sex with women only (65%), and women (44%). CONCLUSION: Approximately 80% of sex partners were either unnamed or unreported. Partner services may be less successful at interrupting transmission in MSM networks where a higher proportion of partners are unnamed or unreported.

We reviewed all cases of syphilis reported among pregnant women in Florida during 2018 for syphilitic reinfection. Nineteen (7.3%) of 261 pregnant women with syphilis were reported as reinfected during the same pregnancy. Timely rescreening and treatment prevented six (31.6%) of nineteen reinfected women from delivering infants with congenital syphilis.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV and MOKV Gs in mice. Immune sera also neutralize a range of wild-type lyssaviruses across the major phylogroups. LyssaVax-immunized mice are protected against challenge with recombinant RABV and MOKV. Altogether, LyssaVax demonstrates the utility of structural modeling in vaccine design and constitutes a broadened lyssavirus vaccine candidate.

BACKGROUND: Neonatal herpes simplex virus infection (nHSV) leads to severe morbidity and mortality, but national incidence is uncertain. Florida regulations require that healthcare providers report cases, and clinical laboratories report test results when herpes simplex virus (HSV) is detected. We estimated nHSV incidence using laboratory-confirmed provider-reported cases and electronic laboratory reports (ELR) stored separately from provider-reported cases. Mortality was estimated using provider-reported cases, ELR, and vital statistics death records. METHODS: For 2011-2017, we reviewed: provider-reported cases (infants <60 days of age with HSV infection confirmed by culture or polymerase chain reaction (PCR)), ELR of HSV-positive culture or PCR results in the same age group, and death certificates containing International Classification of Disease, Tenth Revision, codes for herpes infection: P35.2, B00.0-B00.9, and A60.0-A60.9. Provider-reported cases were matched against ELR reports. Death certificates were matched with provider and ELR reports. Chapman's capture-recapture method was used to estimate nHSV incidence and mortality. Mortality from all three sources was estimated using log-linear modelling. RESULTS: Providers reported 114 nHSV cases and ELR identified 197 nHSV cases. Forty-six cases were common to both datasets, leaving 265 unique nHSV reports. Chapman's estimate suggests 483 (95% C.I. 383-634) nHSV cases occurred (31.5 infections per 100,000 live births). nHSV deaths were reported by providers (n=9), ELR (n=18), and vital statistics (n=31), totaling 34 unique reports. Log-linear modeling estimates 35.8 fatal cases occurred (95% CI 34-40). CONCLUSIONS: Chapman's estimates using data collected over 7 years in Florida, conclude nHSV infections occurred at a rate of 1 per 3000 live births.

Reports are emerging at a rapid pace that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the nervous system in various ways. Preliminary data from Wuhan, China, suggest that neurological manifestations are present in more than 30% of patients presenting with coronavirus disease 2019 (COVID-19).1 Neurological features range from quite diffuse neurological signs and symptoms like headache, dizziness, reduced level of consciousness, confusion, diffuse corticospinal tract signs, and paraesthesia, to more specific manifestations, such as seizures, stroke, encephalitis, or meningoencephalitis, and myopathy.1, 2 To date, SARS-CoV-2 has not been detected in the neural tissue directly, although it has been isolated from the CSF of some patients.3 The hypothesis of neurotropism with subsequent neuronal injury, either directly or indirectly (through immune mechanisms), is supported by previous findings from other infections with severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV.3

BACKGROUND: Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project. METHODS: Persons diagnosed with ES were selected for interviews based on current health department protocols in five participating SSuN jurisdictions from November 2016-October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers. RESULTS: Among 9,123 patients with ES who were interviewed, 151 (1.7%, 95% CI: 1.4-1.9) reported >/=1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture (LP), 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented LP (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis. CONCLUSIONS: We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis.

BACKGROUND: Atypical Beijing genotype Mycobacterium tuberculosis strains are widespread in South Africa and have acquired resistance to up to 13 drugs on multiple occasions. It is puzzling that these strains have retained fitness and transmissibility despite the potential fitness cost associated with drug resistance mutations. METHODS: We conducted Illumina sequencing of 211 Beijing genotype M. tuberculosis isolates to facilitate the detection of genomic features that may promote acquisition of drug resistance and restore fitness in highly resistant atypical Beijing forms. Phylogenetic and comparative genomic analysis was done to determine changes that are unique to the resistant strains that also transmit well. Minimum inhibitory concentration (MIC) determination for streptomycin and bedaquiline was done for a limited number of isolates to demonstrate a difference in MIC between isolates with and without certain variants. RESULTS: Phylogenetic analysis confirmed that two clades of atypical Beijing strains have independently developed resistance to virtually all the potent drugs included in standard (pre-bedaquiline) drug-resistant TB treatment regimens. We show that undetected drug resistance in a progenitor strain was likely instrumental in this resistance acquisition. In this cohort, ethionamide (ethA A381P) resistance would be missed in first-line drug-susceptible isolates, and streptomycin (gidB L79S) resistance may be missed due to an MIC close to the critical concentration. Subsequent inadequate treatment historically led to amplification of resistance and facilitated spread of the strains. Bedaquiline resistance was found in a small number of isolates, despite lack of exposure to the drug. The highly resistant clades also carry inhA promoter mutations, which arose after ethA and katG mutations. In these isolates, inhA promoter mutations do not alter drug resistance, suggesting a possible alternative role. CONCLUSION: The presence of the ethA mutation in otherwise susceptible isolates from ethionamide-naive patients demonstrates that known exposure is not an adequate indicator of drug susceptibility. Similarly, it is demonstrated that bedaquiline resistance can occur without exposure to the drug. Inappropriate treatment regimens, due to missed resistance, leads to amplification of resistance, and transmission. We put these results into the context of current WHO treatment regimens, underscoring the risks of treatment without knowledge of the full drug resistance profile.

The Syphilis Health Check (SHC) had low estimated specificity (91.5%) in one Florida county. We investigated use of SHC by a range of Florida publicly-funded programs between 2015 and 2016 to estimate specificity, positive predictive value (PPV), field staff acceptance, and impacts on programmatic outcomes. All reported SHC results were extracted from routinely collected program data. Field staff were surveyed about SHC's utility. Analyses investigated differences between SHC and traditional syphilis testing outcomes. Of 3,630 SHC results reported, 442 were reactive; 92 (20.8%) had prior diagnoses of syphilis; 7 (1.6%) had no further testing. Of the remaining 343; 158 (46.0%) were confirmed cases, 168 (49.0%) were considered false-positive, and 17 (5.0%) were not cases but not clearly false-positive. Estimated specificity of SHC was 95.0%. Overall, 48.5% of positives became confirmed cases (PPV). PPV varied according to prevalence of syphilis in populations tested. Staff (90%) thought SHC helped identify new cases but expressed concern regarding discordance between reactive SHC and lab-based testing. Programmatic outcomes assessment showed shorter time to treatment and increased numbers of partners tested for the SHC group; these enhanced outcomes may better mitigate the spread of syphilis compared to traditional syphilis testing alone, but more research is needed.

Prevention of HIV outbreaks among people who inject drugs remains a challenge to ending the HIV epidemic in the United States. The first legal syringe services program (SSP) in Florida implemented routine screening in 2018 leading to the identification of ten anonymous HIV seroconversions. The SSP collaborated with the Department of Health to conduct an epidemiologic investigation. All seven acute HIV seroconversions were linked to care (86% within 30 days) and achieved viral suppression (mean 70 days). Six of the seven individuals are epidemiologically and/or socially linked to at least two other seroconversions. Analysis of the HIV genotypes revealed that two individuals are connected molecularly at 0.5% genetic distance. We identified a risk network with complex transmission dynamics that could not be explained by epidemiological methods or molecular analyses alone. Providing wrap-around services through the SSP, including routine screening, intensive linkage and patient navigation, could be an effective model for achieving viral suppression for people who inject drugs.

BACKGROUND: Discordant syphilis test results, with a reactive non-treponemal test and non-reactive treponemal test are usually considered biological false positive test results (BFP), which can be attributed to other conditions. Syphilis surveillance laws mandate laboratory reporting of reactive syphilis tests which include many BFPs. We describe the frequency of BFP, titer distributions, and titer increases from reported test results in Florida and New York City (NYC). METHODS: Reactive non-treponemal tests for individuals with at least one non-reactive treponemal test and no reactive treponemal test, were extracted from STD surveillance systems in Florida and NYC from 2013 through 2017. Characteristics of individuals with BFPs were analyzed after selecting the observation with the highest titer from each individual. We next considered all results from individuals to characterize persons who had a four-fold titer increase between successive non-treponemal tests. RESULTS: Among 526,540 reactive non-treponemal tests, there were 57,580 BFPs (11%) from 39,920 individuals. Over 90% (n=52,330) of BFPs were low titer (</=1:4), but 654 (1%) were high-titer BFPs (>/=1:32). Very high-titer (>/=1:128) BFPs were more common among individuals over 60 years of age (OR 2.68 95%CI 1.22-5.91). A four-fold increase in titer was observed among 1,863 (14%) individuals with more than one reported BFP. CONCLUSIONS: Most BFPs detected by surveillance were low-titer but some were high-titer and some had a four-fold increase in titer. Review of patient histories might identify underlying conditions contributing to these high and rising titers.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.