Biomarkers of Methylmercury Exposure Immunotoxicity among Fish Consumers in Amazonian Brazil

Background: Mercury (Hg) is a ubiquitous environmental contaminant with neurodevelopmental and immune system effects. An informative biomarker of Hg-induced immunotoxicity could aid studies on the potential contribution to immune-related health effects

Mercury exposure, malaria, and serum antinuclear/antinucleolar antibodies in amazon populations in Brazil: a cross-sectional study

BACKGROUND: Mercury is an immunotoxic metal that induces autoimmune disease in rodents. Highly susceptible mouse strains such as SJL/N, A.SW, B10.S (H-2(s)) develop multiple autoimmune manifestations after exposure to inorganic mercury, including lymphoproliferation, elevated levels of autoantibodies, overproduction of IgG and IgE, and circulating immune complexes in kidney and vasculature. A few studies have examined relationships between mercury exposures and adverse immunological reactions in humans, but there is little evidence of mercury-associated autoimmunity in humans. METHODS: To test the immunotoxic effects of mercury in humans, we studied communities in Amazonian Brazil with well-characterized exposures to mercury. Information was collected on diet, mercury exposures, demographic data, and medical history. Antinuclear and antinucleolar autoantibodies (ANA and ANoA) were measured by indirect immunofluorescence. Anti-fibrillarin autoantibodies (AFA) were measured by immunoblotting. RESULTS: In a gold mining site, there was a high prevalence of ANA and ANoA: 40.8% with detectable ANoA at ≥1:10 serum dilution, and 54.1% with detectable ANA (of which 15% had also detectable ANoA). In a riverine town, where the population is exposed to methylmercury by fish consumption, both prevalence and levels of autoantibodies were lower: 18% with detectable ANoA and 10.7% with detectable ANA. In a reference site with lower mercury exposures, both prevalence and levels of autoantibodies were much lower: only 2.0% detectable ANoA, and only 7.1% with detectable ANA. In the gold mining population, we also examined serum for AFA in those subjects with detectable ANoA (≥1:10). There was no evidence for mercury induction of this autoantibody. CONCLUSIONS: This is the first study to report immunologic changes, indicative of autoimmune dysfunction in persons exposed to mercury, which may also reflect interactions with infectious disease and other factors

Developing and Encouraging the First-Year Undergraduate Researcher

A simulated conference in first-year curriculum reinforces undergraduate research as beneficial to both honors and campus communities while fostering scholarly development and campus engagement among honors freshmen during the coronavirus crisis

Rabies Vaccination Compliance and Reasons for Incompletion

Introduction: Rabies is a fatal disease with a 91% mortality rate in the United States. Current treatment of rabies consists of post-exposure prophylaxis treatment involving a complicated vaccination regimen. Studies conducted in other countries have found that patients do not complete their rabies vaccination treatment due to forgetting about their treatment, lack of time for visits, and the financial burden of treatment. However, little is known about why patients do not complete the rabies series in the US. The objective of this study was to determine the reasons why patients in the US do not complete rabies treatment.Methods: We performed a retrospective study to evaluate rabies post-exposure prophylaxis completion in the emergency department of an academic suburban hospital between June 2014–  July 2017. Further review was performed for patients who received inadequate vaccination to determine the cause of treatment incompletion. We conducted additional follow-up by phone survey for those patients who did not complete their rabies treatment but had no explanation for discontinuation available in the medical chart review.Results: Results indicated 198 patients received rabies post-exposure treatment during the inclusion period. Of these, 145 patients completed the rabies vaccination regimen. Reasons for treatment incompletion were found for 29 patients, and 24 patients were lost to follow-up. Of the 29 patients for which discontinuation was assessed, 23 patients (79.3%) stopped treatment due to appropriate reasons – either the animal involved tested negative for the rabies virus or the patient had prior rabies treatment and only required two booster shots. Reasons for not completing the series when medically indicated included the patient deciding to not return for treatment, lack of awareness of the full vaccination regimen, and the patient declining initiation of rabies vaccination.Conclusion: Most patients in the US discontinue their rabies vaccination treatment for appropriate reasons; however, there is a proportion of patients who discontinue rabies vaccination when further treatment is medically indicated. This subset of patients is particularly at risk of rabies-related mortality, and additional measures need to be taken to ensure increased treatment compliance

Rabies Vaccination Compliance and Reasons for Incompletion

Introduction: Rabies is a fatal disease with a 91% mortality rate in the United States. Current treatment of rabies consists of post-exposure prophylaxis treatment involving a complicated vaccination regimen. Studies conducted in other countries have found that patients do not complete their rabies vaccination treatment due to forgetting about their treatment, lack of time for visits, and the financial burden of treatment. However, little is known about why patients do not complete the rabies series in the US. The objective of this study was to determine the reasons why patients in the US do not complete rabies treatment.Methods: We performed a retrospective study to evaluate rabies post-exposure prophylaxis completion in the emergency department of an academic suburban hospital between June 2014–  July 2017. Further review was performed for patients who received inadequate vaccination to determine the cause of treatment incompletion. We conducted additional follow-up by phone survey for those patients who did not complete their rabies treatment but had no explanation for discontinuation available in the medical chart review.Results: Results indicated 198 patients received rabies post-exposure treatment during the inclusion period. Of these, 145 patients completed the rabies vaccination regimen. Reasons for treatment incompletion were found for 29 patients, and 24 patients were lost to follow-up. Of the 29 patients for which discontinuation was assessed, 23 patients (79.3%) stopped treatment due to appropriate reasons – either the animal involved tested negative for the rabies virus or the patient had prior rabies treatment and only required two booster shots. Reasons for not completing the series when medically indicated included the patient deciding to not return for treatment, lack of awareness of the full vaccination regimen, and the patient declining initiation of rabies vaccination.Conclusion: Most patients in the US discontinue their rabies vaccination treatment for appropriate reasons; however, there is a proportion of patients who discontinue rabies vaccination when further treatment is medically indicated. This subset of patients is particularly at risk of rabies-related mortality, and additional measures need to be taken to ensure increased treatment compliance

Female immune system is protected from effects of prenatal exposure to mercury

Mercury is a ubiquitous environmental toxicant which bioaccumulates and has many biological effects, including detrimental effects on the nervous and immune systems. Because mercury can cross the placenta and concentrates in the fetal compartment, the developing fetus is particularly vulnerable. We hypothesize that developmental exposure to mercury will cause immunological changes, leading to an increased susceptibility to, or exacerbation of, immune disorders later in life. To better understand these changes, we exposed pregnant female mice to low doses of mercury for a short duration and examined the genetic effects related to immune function in the adult offspring. Pregnant BALB/c mice were exposed to mercury (200 µg/kg HgCl2 in PBS by subcutaneous injection) or vehicle control every other day from gestation day 5 to 15. Offspring remained with the dam until weaning and were euthanized at 8 weeks of age with no further exposures to mercury. Splenic RNA was isolated and gene expression changes examined by microarray in a non-random subset of samples and changes confirmed by quantitative PCR. Epigenetic changes were also examined in terms of miRNA levels in the spleen. Although male and female offspring were exposed to mercury in the same in utero environment, the effects on expression of immune-related genes and immune-regulatory epigenetic signals were different dependent upon the sex of the offspring with males, but not females, displaying up-regulation at least two-fold of arginase, interferon-γ, STAT1, vitronectin, and TNFSF18. Epigenetic changes in miRNA levels were differentially expressed in males and females with in utero mercury exposure; miR-191-5p was decreased in males, while miR-1188-3p was increased in females. These gene expression and gene regulation changes modulate the baseline immune response and may impact risks for autoimmunity later in life

Mercury exposure, serum antinuclear / antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: a cross-sectional study

Johns Hopkins Bloomberg School of Public Health. Department of Environmental Health Sciences. Baltimore, MD, USA.Johns Hopkins Bloomberg School of Public Health. Department of Environmental Health Sciences. Baltimore, MD, USA / University of South Carolina School of Medicine. Department of Pathology, Microbiology & Immunology. Columbia, SC, USA.Johns Hopkins Bloomberg School of Public Health. Department of Environmental Health Sciences. Baltimore, MD, USA.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Johns Hopkins Bloomberg School of Public Health. Department of Environmental Health Sciences. Baltimore, MD, USA.Mercury is an immunotoxic substance that has been shown to induce autoimmune disease in rodent models, characterized by lymphoproliferation, overproduction of immunoglobulin (IgG and IgE), and high circulating levels of auto-antibodies directed at antigens located in the nucleus (antinuclear auto-antibodies, or ANA) or the nucleolus (antinucleolar auto-antibodies, or ANoA). We have reported elevated levels of ANA and ANoA in human populations exposed to mercury in artisanal gold mining, though other confounding variables that may also modulate ANA/ANoA levels were not well controlled. The goal of this study is to specifically test whether occupational and environmental conditions (other than mercury exposure) that are associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction. We measured ANA, ANoA, and cytokine concentrations in serum and compared results from mercury-exposed artisanal gold miners to those from diamond and emerald miners working under similar conditions and with similar socio-economic status and risks of infectious disease. Mercury-exposed gold miners had higher prevalence of detectable ANA and ANoA and higher titers of ANA and ANoA as compared to diamond and emerald miners with no occupational mercury exposure. Also, mercury-exposed gold miners with detectable ANA or ANoA in serum had significantly higher concentrations of pro-inflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma in serum as compared to the diamond and emerald miners. This study provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected population