A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection.

Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE: Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans.

Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time-to-death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model's ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding of the progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide.

Resident Synovial Macrophages in Synovial Fluid: Implications for Immunoregulation in Infectious and Inflammatory Arthritis.

Objectives: Resident synovial macrophages (RSM) provide immune sequestration of the joint space and are likely involved in initiation and perpetuation of the joint-specific immune response. We sought to identify RSM in synovial fluid (SF) and demonstrate migratory ability, in additional to functional changes that may perpetuate a chronic inflammatory response within joint spaces. Methods: We recruited human patients presenting with undifferentiated arthritis in multiple clinical settings. We used flow cytometry to identify mononuclear cells in peripheral blood and SF. We used a novel transwell migration assay with human ex-vivo synovium obtained intra-operatively to validate flow cytometry findings. We used single cell RNA-sequencing (scRNA-seq) to further identify macrophage/monocyte subsets. ELISA was used to evaluate the bone-resorption potential of SF. Results: We were able to identify a rare population of CD14dim, OPG+, ZO-1+ cells consistent with RSM in SF via flow cytometry. These cells were relatively enriched in the SF during infectious processes, but absolutely decreased compared to healthy controls. Similar putative RSM were identified using ex vivo migration assays when MCP-1 and LPS were used as migratory stimulus. scRNA-seq revealed a population consistent with RSM transcriptionally related to CD56+ cytotoxic dendritic cells and IDO+ M2 macrophages. Conclusion: We identified a rare cell population consistent with RSM, indicating these cells are likely migratory and able to initiate or coordinate both acute (septic) or chronic (autoimmune or inflammatory) arthritis. RSM analysis via scRNA-seq indicated these cells are M2 skewed, capable of antigen presentation, and have consistent functions in both septic and inflammatory arthritis.

Health Care Provider Knowledge and Attitudes Regarding Adult Pneumococcal Conjugate Vaccine Recommendations - United States, September 28-October 10, 2022.

Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence.

Within-Host Bayesian Joint Modeling of Longitudinal and Time-to-Event Data of Leishmania Infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time of death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model's ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide.

Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi.

Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs.

Unvaccinated Adolescents' COVID-19 Vaccine Intentions: Implications for Public Health Messaging.

PURPOSE: COVID-19 vaccine uptake remains low for US adolescents and contributes to excess morbidity and mortality. Most research has assessed parental intention to vaccinate their children. We explored differences between vaccine-acceptant and vaccine-hesitant unvaccinated US adolescents using national survey data. METHODS: A nonprobability, quota-based sample of adolescents, aged 13-17 years, was recruited through an online survey panel in April 2021. One thousand nine hundred twenty seven adolescents were screened for participation and the final sample included 985 responses. We assessed responses from unvaccinated adolescents (n = 831). Our primary measure was COVID-19 vaccination intent ("vaccine-acceptant" defined as "definitely will" get a COVID-19 vaccine and any other response classified as "vaccine-hesitant") and secondary measures included reasons for intending or not intending to get vaccinated and trusted sources of COVID-19 vaccine information. We calculated descriptive statistics and chi-square tests to explore differences between vaccine-acceptant and vaccine-hesitant adolescents. RESULTS: Most (n = 831; 70.9%) adolescents were hesitant, with more hesitancy observed among adolescents with low levels of concern about COVID-19 and high levels of concern about side effects of COVID-19 vaccination. Among vaccine-hesitant adolescents, reasons for not intending to get vaccinated included waiting for safety data and having parents who would make the vaccination decision. Vaccine-hesitant adolescents had a lower number of trusted information sources than vaccine-acceptant adolescents. DISCUSSION: Differences identified between vaccine-acceptant and vaccine-hesitant adolescents can inform message content and dissemination. Messages should include accurate, age-appropriate information about side effects and risks of COVID-19 infection. Prioritizing dissemination of these messages through family members, state and local government officials, and healthcare providers may be most effective.

Correction: Assessing insecticide susceptibility, diagnostic dose and time for the sand fly Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay.

[This corrects the article DOI: 10.1371/journal.pntd.0010613.].

Toward user-centered assistive technologies for aging in place with cognitive impairment: a survey.

PURPOSE: To reduce the burden of Alzheimer's disease, the use of assistive technologies for patients and their informal caregivers is considered essential. However, these technologies are made as "one size fits all" instead of being tailored to accommodate people with varying degrees of cognitive impairment and those with diverse races/ethnicities. Thus, the aim of this survey was to determine whether the types of assistance needed most, and the technology used by those with cognitive impairment differed by race (White/non-Hispanics, Black or African Americans, and Hispanic/Latinos or Puerto Ricans) and severity of dementia (mild, moderate, severe). RESEARCH DESIGN AND METHODS: One hundred and eighty informal caregivers of people with different levels of severity of cognitive impairment and several different races/ethnicities filled out an online survey regarding assistance needed and technologies used. RESULTS: The results show that racial minorities considered the needs for assistance with Basic Activities of Daily Living as more important compared to White/non-Hispanics with mild dementia. Furthermore, Hispanic/Latinos or Puerto Ricans and White/non-Hispanics with severe dementia were shown to use technology that is designed to help with Instrumental Activities of Daily Living more than those with moderate dementia. Lastly, during COVID-19, devices to assist with walking, preparing meals and personal hygiene have been used significantly more by White/non-Hispanics with severe dementia compared to Hispanic/Latinos or Puerto Ricans. CONCLUSION: The results point to the need to design for those with severe dementia, regardless of race, and should focus on addressing needs related to both Instrumental and Basic Activities of Daily Living.

Developers of assistive technology should consider designing technology that can accommodate all severity levels of cognitive impairment.More research is needed to determine the usability of assistive technology that is designed for those with cognitive impairments.

Bayesian multivariate longitudinal model for immune responses to Leishmania: A tick-borne co-infection study.

While many Bayesian state-space models for infectious disease processes focus on population infection dynamics (eg, compartmental models), in this work we examine the evolution of infection processes and the complexities of the immune responses within the host using these techniques. We present a joint Bayesian state-space model to better understand how the immune system contributes to the control of Leishmania infantum infections over the disease course. We use longitudinal molecular diagnostic and clinical data of a cohort of dogs to describe population progression rates and present evidence for important drivers of clinical disease. Among these results, we find evidence for the importance of co-infection in disease progression. We also show that as dogs progress through the infection, parasite load is influenced by their age, ectoparasiticide treatment status, and serology. Furthermore, we present evidence that pathogen load information from an earlier point in time influences its future value and that the size of this effect varies depending on the clinical stage of the dog. In addition to characterizing the processes driving disease progression, we predict individual and aggregate patterns of Canine Leishmaniasis progression. Both our findings and the application to individual-level predictions are of direct clinical relevance, presenting possible opportunities for application in veterinary practice and motivating lines of additional investigation to better understand and predict disease progression. Finally, as an important zoonotic human pathogen, these results may support future efforts to prevent and treat human Leishmaniosis.

Assessing insecticide susceptibility, diagnostic dose and time for the sand fly Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay.

Visceral leishmaniasis (VL) is a vector-borne protozoan disease, which can be fatal if left untreated. Synthetic chemical insecticides are very effective tools for controlling of insect vectors, including the sand fly Phlebotomus argentipes, the vector of VL in the Indian subcontinent. However, repeated use of the same insecticide with increasing doses potentially can create high selection pressure and lead to tolerance and resistance development. The objective of this study was to determine the lethal concentrations and assess levels of susceptibility, diagnostic doses and times to death of laboratory-reared P. argentipes to five insecticides that are used worldwide to control vectors. Using the Center for Disease Control and Prevention (CDC) bottle bioassay, 20-30 sand flies were exposed in insecticide- coated 500-ml glass bottles. Flies were then observed for 24 hours and mortality was recorded. Dose-response survival curves were generated for each insecticide using QCal software and lethal concentrations causing 50%, 90% and 95% mortality were determined. A bioassay was also conducted to determine diagnostic doses and diagnostic times by exposing 20-30 flies in each bottle containing set concentrations of insecticide. Mortality was recorded at 10-minute intervals for 120 minutes to generate the survival curve. Phlebotomus argentipes are highly susceptible to alpha-cypermethrin, followed by deltamethrin, malathion, chlorpyrifos, and least susceptible to DDT. Also, the lowest diagnostic doses and diagnostic times were established for alpha-cypermethrin (3µg/ml for 40 minutes) to kill 100% of the flies. The susceptibility data, diagnostic doses and diagnostic times presented here will be useful as baseline reference points for future studies to assess insecticide susceptibility and resistance monitoring of field caught sand flies and to assist in surveillance as VL elimination is achieved in the region.

Hierarchical spatiotemporal modeling of human visceral leishmaniasis in Rio Grande do Norte, Brazil.

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions.

Health care provider knowledge around shared clinical decision-making regarding HPV vaccination of adults aged 27-45 years in the United States.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends shared clinical decision-making (SCDM) regarding HPV vaccination for adults aged 27-45 years who are not adequately vaccinated. The objective of this survey was to understand physician knowledge, attitudes, and practices regarding HPV vaccination in this age group. METHODS: An online survey was administered in June 2021 to physicians who reported practicing internal medicine, family medicine, or obstetrics and gynecology (targeted N = 250 in each practice specialty), selected randomly from potentially eligible physicians from a panel of 2 million U.S. health care providers. RESULTS: In total, 753 physicians participated in the survey: 33.3% practiced internal medicine, 33.1% practiced family medicine, and 33.6% practiced obstetrics/gynecology; 62.5% were male and mean physician age was 52.7 years. Despite the COVID-19 pandemic, at least a third of participating physicians in each practice specialty reported having more HPV vaccine SCDM discussions with patients aged 27-45 years in the past 12 months. While a majority of physicians (79.7%) reported being aware of the SCDM recommendation for adults in this age group, only half of physicians answered an objective knowledge question about SCDM recommendations correctly. CONCLUSIONS: Findings suggest that there are physician knowledge gaps related to SCDM for HPV vaccination. To improve access to HPV vaccination for people most likely to benefit, increasing availability and use of decision aids to support SCDM discussions might help healthcare providers and patients jointly make the most informed decisions about HPV vaccination.

Parental Perceptions Related to Co-Administration of Adolescent COVID-19 and Routine Vaccines.

PURPOSE: Vaccinating adolescents against COVID-19 while avoiding delays in other routine vaccination is paramount to protecting their health. Our objective was to assess parental preferences to have their adolescents aged 12-17 years receive COVID-19 and other routine vaccines at the same time. METHODS: An online survey with a national, quota-based cross-sectional sample of United States parents of youth aged 12-17 years was fielded in April 2021 ahead of FDA's Emergency Use Authorization of COVID-19 vaccine for age 12-15 years. Parents were asked about their willingness to have their adolescents aged 12-17 years receive both COVID-19 and routine vaccines at the same visit and/or to follow their provider's recommendation. Predictors included demographic characteristics, being behind on routine vaccines, and perceived risks and benefits. RESULTS: Few parents were willing to have their adolescent receive COVID-19 and routine vaccines at the same visit (10.6%) or follow the healthcare provider's recommendation (18.5%). In multivariate analyses, demographic characteristics had no effect on willingness, reporting that the adolescent was behind on routine vaccines correlated with decreased willingness (p = .004). Greater concern about the adolescent getting COVID-19 (p = .001), lower concern about the adolescent having side effects from the COVID-19 vaccine (p = .013), and more positive feelings about vaccines in general (p = .002) were associated with higher willingness. DISCUSSION: Few parents would prefer to have their adolescents receive COVID-19 and routine vaccines at the same visit. Understanding what drives willingness to receive all recommended vaccines in the context of the COVID-19 pandemic could inform policies to optimize adolescent vaccination.

Joint Bayesian longitudinal models for mixed outcome types and associated model selection techniques.

Motivated by data measuring progression of leishmaniosis in a cohort of US dogs, we develop a Bayesian longitudinal model with autoregressive errors to jointly analyze ordinal and continuous outcomes. Multivariate methods can borrow strength across responses and may produce improved longitudinal forecasts of disease progression over univariate methods. We explore the performance of our proposed model under simulation, and demonstrate that it has improved prediction accuracy over traditional Bayesian hierarchical models. We further identify an appropriate model selection criterion. We show that our method holds promise for use in the clinical setting, particularly when ordinal outcomes are measured alongside other variables types that may aid clinical decision making. This approach is particularly applicable when multiple, imperfect measures of disease progression are available.

Singing Voice Symptomatology Following Presumed SARS-CoV-2 Infection.

The impact of continued COVID-19 sequelae on singers' vocal function has yet to be determined. An online survey of singers who have contracted SARS-CoV-2 infection was designed and administered globally. Participants (n = 1,153) were recruited in Africa, the Americas, Asia, Australia, and Europe. Survey questions included demographics, peri- and post-SARS-CoV-2 infection symptoms, and self-reported sequelae attributed to long-COVID. The survey was made available in English, Portuguese, Spanish, and Traditional and Simplified Mandarin Chinese. Data were statistically analyzed to provide a useful summary of the sample and to evaluate associations between long-COVID and singers' vocal function. We found that age, gender, and vaccination status were not significantly correlated to a change in singing voice in our sample. However, severity of infection was statistically correlated with a change in singing voice. Of the 34 signs and symptoms presented, lingering cough, shortness of breath, and chronic fatigue were significantly correlated with a change in singing voice. These data and their analyses have added to our understanding of this growing population's unique vocal needs, and may inform strategies for singing voice habilitation in COVID-19 survivors.

Livestock and rodents within an endemic focus of Visceral Leishmaniasis are not reservoir hosts for Leishmania donovani.

Leishmaniasis on the Indian subcontinent is thought to have an anthroponotic transmission cycle. There is no direct evidence that a mammalian host other than humans can be infected with Leishmania donovani and transmit infection to the sand fly vector. The aim of the present study was to evaluate the impact of sand fly feeding on other domestic species and provide clinical evidence regarding possible non-human reservoirs through experimental sand fly feeding on cows, water buffalo goats and rodents. We performed xenodiagnosis using colonized Phlebotomus argentipes sand flies to feed on animals residing in villages with active Leishmania transmission based on current human cases. Xenodiagnoses on mammals within the endemic area were performed and blood-fed flies were analyzed for the presence of Leishmania via qPCR 48hrs after feeding. Blood samples were also collected from these mammals for qPCR and serology. Although we found evidence of Leishmania infection within some domestic mammals, they were not infectious to vector sand flies. Monitoring infection in sand flies and non-human blood meal sources in endemic villages leads to scientific proof of exposure and parasitemia in resident mammals. Lack of infectiousness of these domestic mammals to vector sand flies indicates that they likely play no role, or a very limited role in Leishmania donovani transmission to people in Bihar. Therefore, a surveillance system in the peri-/post-elimination phase of visceral leishmaniasis (VL) must monitor absence of transmission. Continued surveillance of domestic mammals in outbreak villages is necessary to ensure that a non-human reservoir is not established, including domestic mammals not present in this study, specifically dogs.

Possibility of Leishmania Transmission via Lutzomyia spp. Sand Flies Within the USA and Implications for Human and Canine Autochthonous Infection.

Purpose of Review: Leishmaniasis is a leading cause of parasitic death, with incidence rising from decreased resources to administer insecticide and anti-leishmanial treatments due to the COVID-19 pandemic. Leishmaniasis is nonendemic in the United States (U.S.), but enzootic canine populations and potentially competent vectors warrant monitoring of autochthonous disease as a fluctuating climate facilitates vector expansion. Recent studies concerning sand fly distribution and vector capacity were assessed for implications of autochthonous transmission within the U.S. Recent Findings: Climate change and insecticide resistance provide challenges in sand fly control. While most Leishmania-infected dogs in the U.S. were infected via vertical transmission or were imported, autochthonous vector-borne cases were reported. Autochthonous vector-borne human cases have been reported in four states. Further vaccine research could contribute to infection control. Summary: Both cutaneous and visceral leishmaniasis cases in the U.S. are increasingly reported. Prevention measures including vector control and responsible animal breeding are critical to halt this zoonotic disease.