Evidence of likely autochthonous Chagas disease in the southwestern United States: A case series of Trypanosoma cruzi seropositive blood donors.

BACKGROUND: Chagas disease is a parasitic infection that can insidiously cause non-ischemic cardiomyopathy. Given the largely silent nature of this progressive disease, asymptomatic blood donors pose potential blood transfusion risk. Blood donation screening has become an unintentional form of Chagas disease surveillance, with thousands of new cases identified since national surveillance was initiated in 2007. STUDY DESIGN AND METHODS: We recruited T. cruzi-positive blood donors identified from California and Arizona blood centers for confirmatory blood screening and assessment of lifetime infection risk. RESULTS: Among eight suspected cases, we identified four confirmed US autochthonous infections. The current manuscript details the transmission sources, healthcare-seeking behaviors post-blood donation resulting, and clinical course of disease among persons without any history of travel to endemic Latin American countries. DISCUSSION: This manuscript presents four additional US-acquired Chagas disease cases and identifies an opportunity for blood centers to assist in confronting barriers surrounding Chagas disease in the US.

Causal effects on low Apgar at 5-min and stillbirth in a malaria maternal-fetal health outcome investigation: a large perinatal surveillance study in the Brazilian Amazon.

BACKGROUND: Malaria elimination in Brazil poses several challenges, including the control of Plasmodium falciparum foci and the hidden burden of Plasmodium vivax in pregnancy. Maternal malaria and fetal health outcomes were investigated with a perinatal surveillance study in the municipality of Cruzeiro do Sul, Acre state, Brazilian Amazon. The research questions are: what are the causal effects of low birth weight on low Apgar at 5-min and of perinatal anaemia on stillbirth? METHODS: From November 2018 to October 2019, pregnant women of ≥ 22 weeks or puerperal mothers, who delivered at the referral maternity hospital (Juruá Women and Children's Hospital), were recruited to participate in a malaria surveillance study. Clinical information was obtained from a questionnaire and abstracted from medical reports. Haemoglobin level and presence of malarial parasites were tested by haematology counter and light microscopy, respectively. Low Apgar at 5-min and stillbirth were the outcomes analysed in function of clinical data and epidemiologic risk factors for maternal malaria infection using both a model of additive and independent effects and a causal model with control of confounders and use of mediation. RESULTS: In total, 202 (7.2%; N = 2807) women had malaria during pregnancy. Nearly half of malaria infections during pregnancy (n = 94) were P. falciparum. A total of 27 women (1.03%; N = 2632) had perinatal malaria (19 P. vivax and 8 P. falciparum). Perinatal anaemia was demonstrated in 1144 women (41.2%; N = 2779) and low birth weight occurred in 212 newborns (3.1%; N = 2807). A total of 75 newborns (2.7%; N = 2807) had low (< 7) Apgar scores at 5-min., and stillbirth occurred in 23 instances (30.7%; n = 75). Low birth weight resulted in 7.1 higher odds of low Apgar at 5-min (OR = 7.05, 95% CI 3.86-12.88, p < 0.001) modulated by living in rural conditions, malaria during pregnancy, perinatal malaria, and perinatal anaemia. Stillbirth was associated with perinatal anaemia (OR = 2.56, 95% CI 1.02-6.42, p = 0.0444) modulated by living in rural conditions, falciparum malaria during pregnancy, perinatal malaria, and perinatal fever. CONCLUSIONS: While Brazil continues its path towards malaria elimination, the population still faces major structural problems, including substandard living conditions. Here malaria infections on pregnant women were observed having indirect effects on fetal outcomes, contributing to low Apgar at 5-min and stillbirth. Finally, the utility of employing multiple statistical analysis methods to validate consistent trends is vital to ensure optimal public health intervention designs.

Adolescent Trichomonas vaginalis in a High-burdened Region of the Southern United States.

BACKGROUND: We evaluated the clinical management and risk factors for Trichomonas vaginalis-positive adolescents in upstate South Carolina. METHODS: An Epic electronic medical record report was generated to identify any physician-ordered T. vaginalis test from February 2016 to December 2017 for patients aged 12 to 18 years within the Prisma Health Upstate system. Utilizing a case-control study design of patients with a documented T. vaginalis diagnostic result, we reviewed records of patients with physician-ordered T. vaginalis tests for demographics, clinical disease course, sexually transmitted infection test results, treatment order and dosage, infection risk factors, comorbidities, pregnancy term, and neonatal birth outcomes. RESULTS: Of 789 male and female adolescents with physician-ordered T. vaginalis tests, 44% had a documented result. Of those with a document test result, 13% were T. vaginalis positive. Cases (n = 45) and randomly selected negative controls (n = 45) were all girls. Cases were more likely to be African American, symptomatic, and present with vaginal discharge, pain, and vulvar itch. T. vaginalis patients were more likely to have documented histories of chlamydia (P < 0.0001) and gonorrhea (P = 0.0191), with 18% having concurrent triple infections (T. vaginalis, chlamydia, and gonorrhea). All 26 pregnant girls with T. vaginalis delivered full-term, healthy infants. CONCLUSIONS: We identified a disproportionally high burden of T. vaginalis infection, with an alarmingly high rate of triple infections, among a population of suspected high-risk adolescents. Our results indicate the need to clarify infection prevalence, develop pediatrician-focused education campaigns, and elucidate potentially modifiable risk factors for these high-risk patients.

Perinatal dengue and Zika virus cross-sectional seroprevalence and maternal-fetal outcomes among El Salvadoran women presenting for labor-and-delivery.

BACKGROUND: Despite maternal flavivirus infections' linkage to severe maternal and fetal outcomes, surveillance during pregnancy remains limited globally. Further complicating maternal screening for these potentially teratogenic pathogens is the overwhelming subclinical nature of acute infection. This study aimed to understand perinatal and neonatal risk for poor health outcomes associated with flaviviral infection during pregnancy in El Salvador. METHODS: Banked serologic samples and clinical results obtained from women presenting for labor and delivery at a national referent hospital in western El Salvador March to September 2022 were used for this study. 198 samples were screened for dengue and Zika virus IgM, and statistical analyses analyzed demographic and clinical outcome associations with IgM positivity. RESULTS: This serosurvey revealed a high rate of maternal flavivirus infection-24.2% of women presenting for labor and delivery were dengue or Zika virus IgM positive, suggesting potential infection within pregnancy. Specifically, 20.2% were Zika virus IgM positive, 1.5% were dengue virus IgM positive, and 2.5% were both dengue and Zika virus IgM positive. Women whose home had received mosquito abatement assistance within the last year by the ministry of health were 70% less likely to test IgM positive (aOR = 0.30, 95%CI: 0.10, 0.83). Further, statistical geospatial clustering revealed transmission foci in six primary municipalities. Pregnancy complications and poor birth outcomes were noted among the dengue and/or Zika virus maternal infection group, although these outcomes were not statistically different than the seronegative group. None of the resulting neonates born during this study were diagnosed with congenital Zika syndrome. CONCLUSIONS: The high rate of Zika virus detected among pregnant women and the lack of Zika-specific neonatal outcomes monitoring during a non-outbreak year highlights the need for continued surveillance in Central America and among immigrant mothers presenting for childbirth from these countries. As changing climatic conditions continue to expand the range of the disease vector, asymptomatic screening programs could be vital to early identification of outbreaks and clinical management of cases.

Employing digital PCR for enhanced detection of perinatal Toxoplasma gondii infection: A cross-sectional surveillance and maternal-infant outcomes study in El Salvador.

Toxoplasma gondii is a parasitic infection that can be transmitted in utero, resulting in fetal chorioretinitis and other long-term neurological outcomes. If diagnosed early, pregnancy-safe chemotherapeutics can prevent vertical transmission. Unfortunately, diagnosis of acute, primary infection among pregnant women remains neglected, particularly in low-and-middle-income countries. Clinically actionable diagnosis is complex due to the commonality of infection during childhood and early adulthood which spawn long-last antibody titers and historically unreliable direct molecular diagnostics. The current study employed a cross-sectional T. gondii perinatal surveillance study using digital PCR, a next generation molecular diagnostic platform, and a maternal-fetal outcomes survey to ascertain the risk of vertical toxoplasmosis transmission in the Western Region of El Salvador. Of 198 enrolled mothers at the time of childbirth, 6.6% had evidence of recent T. gondii infection-85% of these cases were identified using digital PCR. Neonates born to these acutely infected mothers were significantly more likely to meconium aspiration syndrome and mothers were more likely to experience labor and delivery complications. Multivariable logistic regression found higher maternal T. gondii infection odds were associated with the presence of pet cats, the definitive T. gondii host. In closing, this study provides evidence of maternal T. gondii infection, vertical transmission and deleterious fetal outcomes in a vulnerable population near the El Salvador-Guatemala border. Further, this is the first published study to show clinical utility potential of digital PCR for accurate diagnosis of congenital toxoplasmosis cases.

TORCH Congenital Syndrome Infections in Central America's Northern Triangle.

TORCH pathogens are a group of globally prevalent infectious agents that may cross the placental barrier, causing severe negative sequalae in neonates, including fetal death and lifelong morbidity. TORCH infections are classically defined by Toxoplasma gondii, other infectious causes of concern (e.g., syphilis, Zika virus, malaria, human immunodeficiency virus), rubella virus, cytomegalovirus, and herpes simplex viruses. Neonatal disorders and congenital birth defects are the leading causes of neonatal mortality in Central America's Northern Triangle, yet little is known about TORCH congenital syndrome in this region. This review synthesizes the little that is known regarding the most salient TORCH infections among pregnant women and neonates in Central America's Northern Triangle and highlights gaps in the literature that warrant further research. Due to the limited publicly available information, this review includes both peer-reviewed published literature and university professional degree theses. Further large-scale studies should be conducted to clarify the public health impact these infections in this world region.

Chagas Disease Maternal Seroprevalence and Maternal-Fetal Health Outcomes in a Parturition Cohort in Western El Salvador.

Congenital Chagas disease is a growing concern, prioritized by the World Health Organization for public health action. El Salvador is home to some of the highest Chagas disease (Trypanosoma cruzi infection) burdens in the Americas, yet pregnancy screening remains neglected. This pilot investigation performed a maternal T. cruzi surveillance study in Western El Salvador among women presenting for labor and delivery. From 198 consented and enrolled pregnant women, 6% were T. cruzi positive by serology or molecular diagnosis. Half of the infants born to T. cruzi-positive women were admitted to the NICU for neonatal complications. Geospatial statistical clustering of cases was noted in the municipality of Jujutla. Older women and those knowing an infected relative or close friend were significantly more likely to test positive for T. cruzi infection at the time of parturition. In closing, maternal T. cruzi infections were significantly higher than national HIV or syphilis maternal rates, creating an urgent need to add T. cruzi to mandatory pregnancy screening programs.

First report of multiple Rickettsia sp., Anaplasma sp., and Ehrlichia sp. in the San Miguel Department of El Salvador from zoonotic tick vectors.

Neglected bacterial zoonoses are a group of Neglected Tropical Diseases (NTDs) that are commonly underdiagnosed and underreported due to their undifferentiated febrile illness symptomology. Spotted fever group rickettsioses (SFGR), a subset of tick-borne bacterial zoonoses, belong in this group. There is a dichotomy in the reporting and recognition of these pathogens in Central America: countries with reduced human development scores-like El Salvador-have little to no research or surveillance dedicated to these pathogens and the diseases they cause. This was the third-ever tick survey in El Salvador, highlighting the knowledge gap in this country. A total of 253 ticks were collected from 11 animals at two farm sites and one veterinary office. Standard and quantitative PCR were used to detect presence of SFGR, Ehrlichia, and Anaplasma sp. pathogens in ticks. Ehrlichia sp. were detected in 2.4% of all collected ticks and Anaplasma sp. were detected in 5.5% of all ticks. Rickettsia rickettsii was amplified in 18.2% of ticks, and amplicons similar to R. parkeri, and R. felis were found in 0.8% and 0.4%, of collected ticks, respectively. This is the first report of these pathogenic bacterial species in El Salvador. This study emphasizes the need for further surveillance and research including incorporating additional human seroprevalence and testing to understand the public health burden in this country.

SARS-CoV-2 Viral Incidence, Antibody Point Prevalence, Associated Population Characteristics, and Vaccine Attitudes, South Carolina, February 2021.

The SARS-CoV-2 outbreak from October 2020 through February 2021 was the largest outbreak as of February 2021, and timely information on current representative prevalence, vaccination, and loss of prior antibody protection was unknown. In February 2021, the South Carolina Department of Health and Environmental Control conducted a random sampling point prevalence investigation consisting of viral and antibody testing and an associated health survey, after selecting participants aged ≥5 years using a population proportionate to size of South Carolina residents. A total of 1917 residents completed a viral test, 1803 completed an antibody test, and 1463 completed ≥1 test and a matched health survey. We found an incidence of 2.16 per 100 residents and seroprevalence of 16.4% among South Carolina residents aged ≥5 years. Undetectable immunoglobulin G and immunoglobulin M antibodies were noted in 28% of people with a previous positive test result, highlighting the need for targeted education among people who may be susceptible to reinfection. We also found a low rate of vaccine hesitancy in the state (13%). The results of this randomly selected surveillance and associated health survey have important implications for prospective COVID-19 public health response efforts. Most notably, this article provides a feasible framework for prompt rollout of a statewide evidence-based surveillance initiative.

History of indigenous Trypanosoma cruzi infection in humans, animals and triatomines in California, USA.

This historical review highlights previously undescribed potential foci for sylvatic and domestic locally acquired Chagas disease in California. The review starts in the 1910s, when Trypanosoma cruzi was first discovered through scientific triatomine investigations. Next, the natural transition around the mid-1900s into clinical investigations of the domestic and peridomestic environments and their epidemiologic profiles is detailed. The review closes with the shift to applied genetic, diagnostic and scientific applications surrounding Chagas disease infected individuals in the state. Throughout the course of the review, transmission foci and their unique clinical and epidemiologic characteristics are described. This in-depth review has merit for clinicians, veterinarians and public health officials working with vector-borne diseases in the southwestern USA.

Soil-Transmitted Helminths in the USA: a Review of Five Common Parasites and Future Directions for Avenues of Enhanced Epidemiologic Inquiry.

PURPOSE OF REVIEW: The aim of this review is to present a comprehensive look at five intestinal soil-transmitted helminths (STHs) of global health importance that may continue to plague low-income and rural areas of the USA and argue the need for enhanced surveillance of these infections, which primarily affect the nation's most vulnerable groups. RECENT FINDINGS: Human STH infections in middle- and high-income countries are at particular risk for being undiagnosed; as common symptoms are non-specific, differentials require a high index of clinical suspicion, and cases are concentrated in areas of poverty where access to care is limited. Although autochthonous STHs are thought to be rare in the USA, infections were once common in the American South and Appalachia and robust epidemiologic surveillance is limited post 1980s. However, recent community studies and case reports from small-scale farms and areas of high rural or inner-city poverty reveal the potential for persisting helminth infections in distinct populations of the country. SUMMARY: STHs are among the most common neglected tropical diseases globally causing significant morbidity in underserved communities and contributing to the continuation of cycles of poverty within vulnerable populations. Due to possible severe disease sequalae and their ability to perpetuate poverty and poverty-associated health outcomes within already vulnerable groups, it is vital that surveillance for these infections is enhanced to bolster health equity in the USA.

A Southwestern United States Pilot Investigation of Triatomine-Mite Prevalence.

BACKGROUND: Chagas disease is a leading cause of cardiac failure in Latin America. Due to poor safety profiles and efficacy of currently available therapeutics, prevention is a priority for the millions living at risk for acquiring this clinically important vector-borne disease. Triatomine vectors of the Chagas disease parasite, Trypanosoma cruzi, are found in the southwestern United States, but risk for autochthonous transmission is thought to be low. The role of ectoparasitic mites is under-explored regarding the ecology of triatomines and Chagas disease transmission. METHODS: Triatomine collections were performed using three common entomologic techniques in 2020-2021 from four different locations in southern Arizona and New Mexico. Triatomines were analyzed visually under a 112.5× microscope for the presence of externally attached mites. Following mite removal, triatomines were tested for T. cruzi infection by PCR. RESULTS: Approximately 13% of the collected triatomines had mites securely attached to their head, thorax, abdomen, and legs. More than one mite attached was a common finding among ectoparasitized triatomines. Mite presence, however, did not statistically influence triatomine T. cruzi status. CONCLUSIONS: Our findings add to a growing body of literature demonstrating the sustainability of mite-infested triatomine populations throughout the Western Hemisphere. Future investigations are warranted to better understand the biologic impact of triatomine mites and their potential to serve as a potential biological control tool.

Domestic Triatoma sanguisuga-Human Exposure in the South Carolina Coastal Region.

A collaborative investigation was initiated in rural coastal South Carolina in response to a reported triatomine bite. The eastern conenose bug, Triatoma sanguisuga, was identified and tested for Trypanosoma cruzi. The insect was negative by PCR, and no additional triatomines were found in the vicinity of the home. This is the first published report of a bite from T. sanguisuga in South Carolina despite the fact that triatomine vectors have been documented in the state since the 1850s, and specimens have been collected from homes in the past. Sylvatic T. cruzi reservoirs are common throughout the southeastern United States, and this case brings to light the possibility of human contact with infected triatomines in the state of South Carolina for public health and clinical and entomology professionals.

5-HT1F receptor-mediated mitochondrial biogenesis for the treatment of Parkinson's disease.

BACKGROUND AND PURPOSE: Parkinson's disease is characterized by progressive decline in motor function due to degeneration of nigrostriatal dopaminergic neurons, as well as other deficits including cognitive impairment and behavioural abnormalities. Mitochondrial dysfunction, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, is implicated in the pathophysiology of Parkinson's disease. Using the 5-HT1F receptor agonist LY344864, a known inducer of mitochondrial biogenesis (MB), we investigated the therapeutic efficacy of stimulating MB on dopaminergic neuron loss in a mouse model of Parkinson's disease. EXPERIMENTAL APPROACH: Male C57BL/6 mice underwent bilateral intrastriatal 6-hydroxydopamine or saline injections and daily treatment with 2 mg·kg-1 LY344864 or vehicle for 14 days beginning 7 days post-lesion. Tyrosine hydroxylase immunoreactivity (TH-ir) and MB were assessed in the brains of all groups following treatment, and locomotor activity was evaluated prior to lesioning, 7 days post-lesion and after treatment. KEY RESULTS: Increased mitochondrial DNA content and nuclear- and mitochondrial-encoded mRNA and protein expression was observed in specific brain regions of LY344864-treated naïve and lesioned mice, indicating augmented MB. LY344864 attenuated TH-ir loss in the striatum and substantia nigra compared to vehicle-treated lesioned animals. LY344864 treatment also increased locomotor activity in 6-hydroxydopamine lesioned mice, while vehicle treatment had no effect. CONCLUSIONS AND IMPLICATIONS: These data revealed that LY344864-induced MB attenuates dopaminergic neuron loss and improves behavioural endpoints in this model. We suggest that stimulating MB may be beneficial for the treatment of Parkinson's disease and that the 5-HT1F receptor may be an effective therapeutic target.

Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.

Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer's disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer's disease.