Fleaborne typhus (FBT) is reemerging as a significant cause of febrile illness in southern California, USA. We performed enhanced testing on low-titer Rickettsia typhi antibody-positive specimens from patients with FBT-compatible illness reported in Los Angeles County, California, during 2022-2024. We tested 114 specimens by repeat serology and 113 by real-time PCR; 81 (71%) were PCR-positive, and 95 (83%) had higher antibody titers by repeat serology. Most PCR-positive specimens were collected 8-10 days after illness onset, but some were collected up to 15 days after illness onset. All PCR-positive specimens were R. typhi-specific. After additional testing, 113 (99%) suspected cases were reclassified as probable or confirmed FBT cases. Our findings indicate that many low-titer seropositive results represent true infections and that use of minimum serology thresholds for public health investigation underestimates surveillance case counts. Expanding commercial molecular testing capacity will improve clinical FBT diagnosis and enhance surveillance accuracy.

In California, public health disease surveillance data for flea-borne typhus (FBT) are generated by healthcare providers and laboratories who are responsible for notifying local health jurisdictions when the disease is detected. When accounting for the associations between socioeconomic status (SES) factors (age, race and ethnicity, poverty, unemployment, housing status and land use), R. typhi reservoir host presence (e.g., rats, cats, opossums), and healthcare-seeking behaviours, it is reasonable to consider whether these factors also lead to under-reporting of FBT surveillance and distorted estimations of incidence. This study aimed to evaluate population-level associations between SES factors and FBT surveillance reporting using a Bayesian hierarchical model including a spatially autocorrelated random effect. Census tract-level covariates were sourced from the American Community Survey and Healthy Places Index (HPI). Specifying a zero-inflated Poisson distribution to FBT surveillance report counts, we estimated spatially smoothed, census tract-level estimates of FBT surveillance report rates and attributed variability in report rates to census tract characteristics. Socioeconomic advantage, as measured by the HPI, had the largest effect (IRR = 1.34 [1.07, 1.69]), corresponding to a 34% increase in FBT surveillance reporting for every point increase in HPI score for census tracts. The results herein suggest that FBT surveillance may be biased in its ascertainment of surveillance data, which may be helpful in contextualising and interpreting current trends in FBT epidemiology.

Background While primarily a disease of tropical and subtropical regions, dengue outbreaks are increasing in non-endemic regions due to environmental change and increasing travel and trade. For these non-endemic regions, estimating the risk of dengue is challenging as transmission is driven by both local environmental conditions and the introduction of viremic travelers. In this study, we aimed to estimate current and future dengue risk in California, USA—a region that has recently experienced its first cases of locally-acquired dengue. Methods We modeled dengue risk as the product of three key components needed for local transmission—vector presence, temperature-suitability for pathogen transmission, and viral introductions via travel-associated cases—estimated using vector and case surveillance, sociodemographic, and environmental data. We estimated risk for locations and months where local transmission was reported in 2023-2024 to define a ‘threshold’ level of risk. We then projected monthly, census tract-level risk under both current conditions and future scenarios of climate warming and urban expansion. Findings Approximately 18.2 million (95% CI: 17.9-18.3) California residents—primarily in the Central Valley and the Los Angeles and San Diego metropolitan areas—currently live in areas where peak monthly dengue risk exceeds levels estimated during observed local transmission. Under moderate scenarios of climate warming and urban expansion, an additional 4.1 million (95% CI: 3.7-4.6) California residents may be at risk by mid-century, with the largest increase in risk estimated for September and for the Sacramento Valley and coastal southern California regions. Outside the summer months and beyond the Central Valley and southern California, current and future risk remains low due to one or more major bottlenecks to transmission. Interpretation Our study identifies the specific regions and months conducive to dengue transmission in the non-endemic setting of California. At present, this covers a substantial portion of the state and is projected to expand under on-going climate warming and urbanization. Our results underscore the need for sustained vector control, and timely detection and management of travel-associated cases. Evidence before this study Dengue is considered endemic in over 125 countries and rapidly expanding its range, aided by climate warming, urbanization, and global travel and trade. Estimating transmission risk in newly emerging regions is critical for public health preparedness and depends on both local environmental conditions and the introduction of viremic travelers. We searched PubMed from database inception to May 8, 2025, for articles published in English using search terms “dengue”, “model”, “non-endemic”, and their common textual variants. We identified 75 relevant studies modeling dengue transmission risk in non-endemic settings. However, nearly all were focused on one or two major determinants of transmission (eg, climate, vector population dynamics, or case importations) and/or did not include future projections. We found no studies that developed and validated a model of dengue transmission risk in non-endemic settings that incorporated vector, pathogen, and human suitability factors, and applied this model to project future risk. Added value of this study This study provides a novel approach to model dengue transmission risk in emerging regions that integrates the major factors driving transmission—vector presence, temperature suitability, and travel-associated cases. We apply this model to California—an emerging center of transmission risk in the continental USA—to identify the times and regions where risk exceeds levels observed during recent local transmission. We found that approximately 18.2 million California residents may be at risk based on this threshold, with an additional 4.1 million potentially at risk by mid-century under a moderate scenario of warming and urban expansion. Implications of all the available evidence Our study identifies the hotspots of dengue transmission risk at a fine spatial and temporal resolution (census tract, month) in a highly populous and globally-connected region of emerging dengue risk. These risk estimates, and the regionally-specific bottlenecks to transmission that we identify can inform targeted disease surveillance and prevention strategies. Further, our findings have implications for other emerging regions including the southern USA and southern Europe, suggesting that the risk of local dengue transmission may increase under ongoing climate warming, urbanization, and global travel. ### Competing Interest Statement The authors have declared no competing interest. United States Department of Agriculture National Institute of Food and Agriculture, 2023-68016-40683 National Science Foundation Postdoctoral Research Fellowship in Biology

Flea-borne typhus (FBT), also referred to as murine typhus, is an acute febrile disease in humans caused by the bacteria Rickettsia typhi. Currently, cases of FBT are reported for public health surveillance purposes (i.e., to detect incidence and outbreaks) in a few U.S. states. In California, healthcare providers and testing laboratories are mandated to report to their respective local public health jurisdictions whenever R. typhi or antibodies reactive to R. typhi are detected in a patient, who then report cases to state health department. In this study, we characterize the epidemiology of flea-borne typhus cases in California from 2011 to 2019. A total of 881 cases were reported during this period, with most cases reported among residents of Los Angeles and Orange Counties (97%). Demographics, animal exposures, and clinical courses for case patients were summarized. Additionally, spatiotemporal cluster analyses pointed to five areas in southern California with persistent FBT transmission.

Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts.

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases.† Among cases with available data, 44% occurred in cisgender women who were non-Hispanic Black or African American (Black), 25% who were non-Hispanic White (White), and 23% who were Hispanic or Latino (Hispanic). Among cisgender women with available data, 73% reported sexual activity or close intimate contact as the likely route of exposure, with mpox lesions most frequently reported on the legs, arms, and genitals. Twenty-three mpox cases were reported in persons who were pregnant or recently pregnant§; all identified as cisgender women based on the mpox case report form. Four pregnant persons required hospitalization for mpox. Eleven pregnant persons received tecovirimat, and no adverse reactions were reported. Continued studies on mpox transmission risks in populations less commonly affected during the outbreak, including cisgender women and pregnant persons, are important to assess and understand the impact of mpox on sexual, reproductive, and overall health.

BACKGROUND:It is well established that pregnant persons with SARS-CoV-2 are at an increased risk for preterm birth, however, less is known about perinatal outcomes for neonates with intrauterine exposure to SARS-CoV-2.METHODS:Characteristics of 50 SARS-CoV-2 positive neonates born to SARS-CoV-2 pregnant persons positive between May 22, 2020, and February 22, 2021, in Los Angeles County, CA, were assessed. Pattern of neonate SARS-CoV-2 test results and time to positive test was analyzed. Objective clinical severity criteria were applied to assess neonatal disease severity.RESULTS:Median gestational age was 39 weeks with 8 (16%) neonates born preterm. Most (74%) were asymptomatic, while 13 (26%) were symptomatic from any cause. Four (8%) symptomatic neonates met criteria for severe disease, of which 2 (4%) were likely secondary to COVID-19. The other 2 with severe disease had more likely alternate diagnoses, and 1 of these neonates subsequently died at 7 months of life. Among 12 (24%) that were positive within 24 hours after birth, one was persistently positive and represented likely intrauterine transmission. Sixteen (32%) were admitted to the neonatal intensive care unit.CONCLUSION:In this case series of 50 SARS-CoV-2 positive mother-neonate pairs, we found that most neonates were asymptomatic regardless of when they tested positive during the 14 days after birth, that there was relatively low risk of COVID-19 associated severe disease, and that intrauterine transmission can occur in rare cases. Although short-term outcomes are mostly promising, more research is needed to study long-term consequences of SARS-CoV-2 infection in neonates born to positive pregnant persons.

Abstract Background Human herpesvirus 6 (HHV-6) is ubiquitous and a known central nervous system (CNS) pathogen. However, HHV-6 in cerebrospinal fluid (CSF) without clinical findings of meningoencephalitis (ME) may not represent true infection, but rather, asymptomatic viral reactivation, chromosomal integration, or latent activation. With the introduction in 2015 of a rapid polymerase chain reaction (PCR) multiplex panel that simultaneously tests for 14 CNS pathogens, reports of HHV-6 PCR positive ME have increased. We sought to understand the epidemiology of HHV-6 ME by evaluating reported cases in Los Angeles County (LAC) between 2016-2020. Methods ME is a reportable condition in LAC. We reviewed clinical, laboratory, and radiologic data for all HHV-6 PCR positive cases reported in LAC between 2016-2020. We developed case classification categories, “unlikely,” “possible,” and “likely”, based on symptoms, CSF profile, and alternative diagnoses (see Table 1). Results A total of 67 HHV-6 ME cases were reported (see Table 2). Reports increased over time, with one in 2016, 12 in 2017, 17 in 2018, 20 in 2019, and 17 in 2020. Median age was 9 months (range 0d-78y), and 47 (70%) were < three years old. Forty-four (66%) were male. Six (9%) were immunocompromised, including one hematopoietic stem cell transplant recipient. Nineteen (28%) had abnormal CSF, and eight (12%) received therapy for HHV-6. Five cases (7%) were classified as “likely” HHV-6 ME, 12 (18%) “possible,” and 50 (75%) “unlikely”. The “likely” cases ranged in age from 7 months to 12 years old, and none were immunocompromised. One received antiviral therapy and was discharged to a rehabilitation facility, the other four were discharged home with full recovery. Conclusion The significance of HHV-6 in CSF remains challenging to determine both clinically and epidemiologically. In the setting of increased testing, increasing detection of HHV-6 in CSF may not reflect increasing rates of HHV-6 ME. The majority of reported HHV-6 ME cases were “unlikely” based on our classification. Classifying cases with alternative diagnoses as ‘unlikely” may miss cases with multiple true infections, particularly in the immunocompromised. It is important to consider clinical presentation, CSF profile and other diagnoses to understand the true burden of HHV-6 ME. Disclosures All Authors: No reported disclosures.

The Surveillance for Emerging Threats to Mothers and Babies Network conducts longitudinal surveillance of pregnant persons in the United States with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection during pregnancy. Of 6,551 infected pregnant persons in this analysis, 142 (2.2%) had positive RNA tests >90 days and up to 416 days after infection.

OBJECTIVE:We examined the relationship between trimester of SARS-CoV-2 infection, illness severity, and risk for preterm birth. STUDY DESIGN:We analyzed data for 6336 pregnant persons with SARS-CoV-2 infection in 2020 in the United States. Risk ratios for preterm birth were calculated for illness severity, trimester of infection, and illness severity stratified by trimester of infection adjusted for age, selected underlying medical conditions, and pregnancy complications. RESULT:Pregnant persons with critical COVID-19 or asymptomatic infection, compared to mild COVID-19, in the second or third trimester were at increased risk of preterm birth. Pregnant persons with moderate-to-severe COVID-19 did not show increased risk of preterm birth in any trimester. CONCLUSION:Critical COVID-19 in the second or third trimester was associated with increased risk of preterm birth. This finding can be used to guide prevention strategies, including vaccination, and inform clinical practices for pregnant persons.

Maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the second and third trimesters of pregnancy may impact fetal development via vertical transmission, complications of coronavirus disease 2019 (COVID-19), or placental injury. However, potential associations between prenatal SARS-CoV-2 infection and fetal loss are not well understood. This case series of thirteen second and third trimester fetal losses reported by local public health departments to California's state public health surveillance included maternal clinical and demographic characteristics as well as placental pathology, fetal autopsy reports, and coroner report. There was no evidence that maternal COVID-19 disease severity, placental injury, or SARS-CoV-2 vertical transmission contributed to pregnancy loss. However, this case series is a limited sample; more research is needed to identify factors of prenatal SARS-CoV-2 that may contribute to fetal death in the second and third trimesters.

Worksites with on-site operations have experienced coronavirus disease (COVID-19) outbreaks. We analyzed data for 698 nonresidential, nonhealthcare worksite COVID-19 outbreaks investigated in Los Angeles County, California, USA, during March 19, 2020‒September 30, 2020, by using North American Industry Classification System sectors and subsectors. Nearly 60% of these outbreaks occurred in 3 sectors: manufacturing (n = 184, 26.4%), retail trade (n = 137, 19.6%), and transportation and warehousing (n = 73, 10.5%). The largest number of outbreaks and largest number and highest incidence rate of outbreak-associated cases occurred in manufacturing. Furthermore, 7 of the 10 industry subsectors with the highest incidence rates were within manufacturing. Approximately 70% of outbreak-associated case-patients reported Hispanic ethnicity. Facilities employing more on-site staff had larger and longer outbreaks. Identification of highly affected industry sectors and subsectors is necessary for targeted public health planning, outreach, and response, including ensuring vaccine access, to reduce burden of COVID-19 in vulnerable workers.

Although flea-borne rickettsiosis is endemic in Los Angeles County, outbreaks are rare. In the spring of 2015 three human cases of flea-borne rickettsiosis among residents of a mobile home community (MHC) prompted an investigation. Fleas were ubiquitous in common areas due to presence of flea-infested opossums and overabundant outdoor cats and dogs. The MHC was summarily abated in June 2015, and within five months, flea control and removal of animals significantly reduced the flea population. Two additional epidemiologically-linked human cases of flea-borne rickettsiosis detected at the MHC were suspected to have occurred before control efforts began. Molecular testing of 106 individual and 85 pooled cat fleas, blood and ear tissue samples from three opossums and thirteen feral cats using PCR amplification and DNA sequencing detected rickettsial DNA in 18.8% of the fleas. Seventeen percent of these cat fleas tested positive for R. felis-specific DNA compared to under two (<2) percent for Candidatus R. senegalensis-specific DNA. In addition, serological testing of 13 cats using a group-specific IgG-ELISA detected antibodies against typhus group rickettsiae and spotted fever group rickettsiae in six (46.2%) and one (7.7%) cat, respectively. These results indicate that cats and their fleas may have played an active role in the epidemiology of the typhus group and/or spotted fever group rickettsial disease(s) in this outbreak.

Meningococcal disease is a rare, but serious, bacterial infection that progresses rapidly and can be life-threatening, even with prompt antibiotic treatment. Men who have sex with men (MSM) have previously been reported to be at increased risk for meningococcal disease compared with other men, and recent outbreaks of serogroup C meningococcal disease among MSM have occurred (1). However, the epidemiology of meningococcal disease among MSM in the United States is not well described, in part, because information about MSM has not historically been collected as part of routine meningococcal disease surveillance. To better characterize and identify risk factors for meningococcal disease in general, supplementary data and isolates have been collected since 2015 through enhanced meningococcal disease surveillance activities. During 2015-2016, 271 cases of meningococcal disease in men aged ≥18 years were reported to the National Notifiable Diseases Surveillance System (NNDSS) in 45 states participating in this enhanced surveillance. Forty-eight (17.7%) cases were in men identified as MSM, including 17 (37.8%) with human immunodeficiency virus (HIV) infection. Among MSM, 39 (84.8%) cases were caused by Neisseria meningitidis serogroup C, whereas this serogroup was responsible for only 16.4% of cases among men who were not known to be MSM (non-MSM). Despite improvements in surveillance, MSM likely remain underascertained among men with meningococcal disease. Improved surveillance data are needed to understand the prevalence of and risk for meningococcal disease among MSM and inform policy and prevention strategies. Vaccination with quadrivalent meningococcal conjugate (MenACWY) vaccine is recommended for the control of meningococcal disease outbreaks caused by serogroups A, C, W, or Y, including during outbreaks among MSM; in addition, all persons aged ≥2 months with HIV infection should receive MenACWY vaccine because of the increased risk for meningococcal disease.

Background. Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well described.Methods. All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described. Annualized incidence rates among MSM and non-MSM were compared through calculation of the relative risk and 95% confidence intervals. Isolates from meningococcal disease cases among MSM were characterized using standard microbiological methods and whole-genome sequencing.Results. Seventy-four cases of meningococcal disease were reported among MSM and 453 among non-MSM. Annualized incidence of meningococcal disease among MSM was 0.56 cases per 100 000 population, compared to 0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1-5.1). Among the 64 MSM with known status, 38 (59%) were infected with human immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6) the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were serogroup C sequence type 11.Conclusions. MSM are at increased risk for meningococcal disease, although the incidence of disease remains low. HIV infection may be an important factor for this increased risk. Routine vaccination of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in accordance with Advisory Committee on Immunization Practices recommendations should be encouraged.

During March 4-August 11, 2016, 25 outbreak-associated cases of meningococcal disease, including two deaths (8% case-fatality ratio), were reported in Southern California. Twenty-four of the cases were caused by serogroup C Neisseria meningitidis (NmC) and one by N. meningitidis with an undetermined serogroup (Figure). On June 24, 2016, in response to this increase in NmC cases, primarily among men who have sex with men (MSM) in Los Angeles County, the city of Long Beach, and Orange County, the California Department of Public Health (CDPH) issued a press release and health advisory, declaring an outbreak of NmC in Southern California (1).

On August 4, 2014, the Acute Communicable Disease Control Program of the Los Angeles County Department of Public Health received a report of three aseptic meningitis cases among football players at a county high school. An investigation was conducted to determine the extent of the outbreak, identify potential exposures, and recommend control measures. An outbreak-associated aseptic meningitis case was defined as an illness of any team or family member with onset during July 28-August 11 with 1) cerebrospinal fluid pleocytosis and negative bacterial culture or 2) an emergency department visit with headache, fever, and stiff neck. Ten cases were identified; nine in males, and one in a female; patient ages ranged from 13 to 17 years. All the patients sought care at an emergency department, and five were hospitalized, resulting in 12 total hospital days. All 10 patients have recovered. Eight patients were football players, and two were siblings of football players. The most affected subgroup was the junior varsity football team, with seven cases out of 57 players (attack rate = 12.3%); the relative risk for aseptic meningitis was higher among players who were linemen than among those who were not linemen (relative risk = 5.4 [p = 0.03]). Of the 10 patients, eight tested positive by polymerase chain reaction for enterovirus, and two were not tested. Echovirus testing was performed at the California Viral and Rickettsial Disease Laboratory. Of the eight specimens testing positive for enterovirus, seven tested positive for echovirus 30, and one specimen could not be typed because of insufficient quantity.

Since 2012, three clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States. During 2012, 13 cases of meningococcal disease among MSM were reported by the New York City Department of Health and Mental Hygiene (1); over a 5-month period during 2012–2013, the Los Angeles County Department of Public Health reported four cases among MSM; and during May–June 2015, the Chicago Department of Public Health reported seven cases of meningococcal disease among MSM in the greater Chicago area. MSM have not previously been considered at increased risk for meningococcal disease. Determining outbreak thresholds* for special populations of unknown size (such as MSM) can be difficult. The New York City health department declared an outbreak based on an estimated increased risk for meningococcal infection in 2012 among MSM and human immunodeficiency virus (HIV)–infected MSM compared with city residents who were not MSM or for whom MSM status was unknown (1). The Chicago Department of Public Health also declared an outbreak based on an increase in case counts and thresholds calculated using population estimates of MSM and HIV-infected MSM. Local public health response included increasing awareness among MSM, conducting contact tracing and providing chemoprophylaxis to close contacts, and offering vaccination to the population at risk (1–3). To better understand the epidemiology and burden of meningococcal disease in MSM populations in the United States and to inform recommendations, CDC analyzed data from a retrospective review of reported cases from January 2012 through June 2015.

In Los Angeles, California, USA, 2 epidemics of West Nile virus (WNV) disease have occurred since WNV was recognized in 2003. To assess which measure of risk was most predictive of human cases, we compared 3 measures: the California Mosquito-Borne Virus Surveillance and Response Plan Assessment, the vector index, and the Dynamic Continuous-Area Space-Time system. A case-crossover study was performed by using symptom onset dates from 384 persons with WNV infection to determine their relative environmental exposure to high-risk conditions as measured by each method. Receiver-operating characteristic plots determined thresholds for each model, and the area under the curve was used to compare methods. We found that the best risk assessment model for human WNV cases included surveillance data from avian, mosquito, and climate sources.