by
Kadir González;
Jose E Calzada;
Azael Saldaña;
Chystrie A Rigg;
Gilbert Alvarado;
Bernal Rodríguez-Herrera;
Uriel Kitron;
Gregory H. Adler;
Nicole L. Gottdenker;
Luis Fernando Chaves;
Mario Baldi
The eco-epidemiology of American cutaneous leishmaniasis (ACL) is driven by animal reservoir species that are a source of infection for sand flies that serve as vectors infecting humans with Leishmania spp parasites. The emergence and re-emergence of this disease across Latin America calls for further studies to identify reservoir species associated with enzootic transmission. Here, we present results from a survey of 52 individuals from 13 wild mammal species at endemic sites in Costa Rica and Panama where ACL mammal hosts have not been previously studied. For Leishmania spp. diagnostics we employed a novel PCR technique using blood samples collected on filter paper. We only found Leishmania spp parasites in one host, the two-toed sloth, Choloepus hoffmanni. Our findings add further support to the role of two-toed sloths as an important ACL reservoir in Central America.
The seven NIH‐sponsored Regional Primate Research Centers conduct a wide variety of studies in the neurosciences and on aging. Monkeys and chimpanzees are investigated to validate the results of research obtained with lower species. In addition, primates are often the only species with the appropriate characteristics for studying a particular health problem or certain behavioral or biological principles. One neurological disorder for which the primate model has proven crucial is Parkinson's disease. The surgical implantation of dopaminergic cells and tissue containing a growth factor has been developed in the primate model, and is now being evaluated clinically in humans with Parkinsonism.
In addition to neurological diseases such as Parkinson's, multiple sclerosis, and epilepsy, the visual system is a strong focus of basic and applied research at the Centers. In 1981, two neuroscientists whose basic research on vision with application to pediatric ophthalmology took place in part at the New England Regional Primate Research Center, were honored with the Nobel Prize in Physiology and Medicine. Currently, vision studies at the Yerkes Regional Primate Research Center, for example, focus on myopia, post‐surgical treatment of congenital cataracts, adult cataract development and treatment, and laser surgery to correct corneal abnormalities. At the Wisconsin Regional Primate Research Center, the role of diet in visual impairment is evaluated during infancy. Diet is also studied to determine its role in the aging process, and the effects of aging on memory. Further, brain cells and other components of the nervous system in aging are also being investigated at these centers.
Nosema ceranae infections in honey bees (Apis mellifera) pose a severe threat to colony health. Beekeepers have used dicyclohexylammonium fumagillin to control Nosema apis, although it may be ineffective against N. ceranae. We investigated the ability of various propolis extracts collected from Upstate New York (United States) to decrease in vivo N. ceranae infection levels when fed ad libitum to N. ceranae-infected honey bees. Propolis extracts, most notably a dichloromethane extract, significantly lowered spore levels in a dose-dependent fashion 4 days post inoculation. When testing the in vitro anti-Nosema activity of propolis extracts, we report for the first time that spore viability was unaffected after a 24 h exposure to propolis extracts. These results present evidence that propolis extracts may effectively lower Microsporidia infections in honey bees, and that direct exposure of environmental spores to propolis alone does not kill N. ceranae.
Combination of CVCVA5 adjuvant and commercial avian influenza (AI) vaccine has been previously demonstrated to provide good protection against different AI viruses in chickens. In this study, we further investigated the protective immunity of CVCVA5-adjuvanted oil-emulsion inactivated AI vaccine in chickens, ducks and geese. Compared to the commercial H5 inactivated vaccine, the H5-CVCVA5 vaccine induced significantly higher titers of hemaglutinin inhibitory antibodies in three lines of broiler chickens and ducks, elongated the antibody persistence periods in geese, elevated the levels of cross serum neutralization antibody against different clade and subclade H5 AI viruses in chicken embryos. High levels of mucosal antibody were detected in chickens injected with the H5 or H9-CVCA5 vaccine. Furthermore, cellular immune response was markedly improved in terms of increasing the serum levels of cytokine interferon-γ and interleukine 4, promoting proliferation of splenocytes and upregulating cytotoxicity activity in both H5- and H9-CVCVA5 vaccinated chickens. Together, these results provide evidence that AI vaccines supplemented with CVCVA5 adjuvant is a promising approach for overcoming the limitation of vaccine strain specificity of protection.
Current treatment options for murine fur mites have limitations in safety and efficacy. This study evaluated whether topical lime sulfur (LS) is an adjunct or alternative to traditional treatment options for Myocoptes musculinus. To evaluate the safety of topical LS, mice were dipped in a 3% LS solution at 34 and 41 d of age. Mice were observed daily for side effects and mortality, with blood work and necropsy at 42 d of age to evaluate for pathologic changes. To determine the efficacy of topical LS, postweanling mice infested with M. musculinus were treated with LS once weekly for 2 wk and then housed with uninfested sentinel mice for 4 wk. Weekly tape tests and postmortem tape tests and skin scrapings were performed on all mice. Treated postweanling mice had significantly lower Hgb levels and higher BUN levels than did control animals. In mite-infested mice, the number of positive cages at euthanasia was the same between treated and control animals. Although topical LS did not cause gross or microscopic changes to organ systems, it may cause clinicopathologic changes, and topical LS is not effective as a sole treatment for M. musculinus infestation of postweanling mice.
by
Cassidy L. Rist;
Calistus N. Ngonghala;
Andres Garchitorena;
Cara E. Brook;
Ranto Ramananjato;
Ann C. Miller;
Milijaona Randrianarivelojosia;
Patricia C. Wright;
Thomas Gillespie;
Matthew H. Bonds
Livestock represent a fundamental economic and nutritional resource for many households in the developing world; however, a high burden of infectious disease limits their production potential. Here we present an ecological framework for estimating the burden of poultry disease based on coupled models of infectious disease and economics. The framework is novel, as it values humans and livestock as co-contributors to household wellbeing, incorporating feedbacks between poultry production and human capital in disease burden estimates. We parameterize this coupled ecological-economic model with household-level data to provide an estimate of the overall burden of poultry disease for the Ifanadiana District in Madagascar, where over 72% of households rely on poultry for economic and food security. Our models indicate that households may lose 10-25% of their monthly income under current disease conditions. Results suggest that advancements in poultry health may serve to support income generation through improvements in both human and animal health.
As part of a study of antipsychotic drug treatment in monkeys, we developed a technique to provide chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques. This method allowed us to mimic the osmotic release oral delivery system currently used in humans for continuous enteral drug delivery. Rhesus macaques (n = 5) underwent gastric catheter placement by laparotomy. After the catheters were secured to the stomach, the remaining catheter length was exited through the lateral abdomen, tunneled subcutaneously along the back, and connected to a 2-mL osmotic pump enclosed in a subcutaneous pocket. Osmotic pumps were changed every 2 to 4 wk for 1 y and remained patent for the duration of the study. Four complications (including cutting of the catheter, incisional dehiscence at the pump site, and loss of 1 catheter into the abdominal cavity requiring catheter replacement) occurred among the 80 pump changes performed during the yearlong study. At necropsy, histopathologic examination of the catheter implant sites revealed mild changes consistent with a foreign-body reaction. Our results indicate that the gastric catheter and osmotic pump system was well tolerated in rhesus macaques for as long as 12 mo after placement and suggest that this system will be an attractive option for use in studies that require chronic, constant-rate, gastric drug infusion in nontethered monkeys.
The world is rife with potential pathogens. Of those that infect humans, it is estimated that roughly 20 % are of nonhuman primate origin. The same ease characterizes pathogen transmission in the other direction, from humans to nonhuman primates. This latter problem has increasingly serious ramifications for conservation efforts, as growing numbers of ecotourists and researchers serve as potential vectors of disease. Here, we present an analysis of major cross-species transmission events between human and nonhuman primates. In particular, we consider HIV and malaria as case studies in which nonhuman primate pathogens emerged and became permanent fixtures in human populations. The human practices that facilitate such events are considered, as well as the evolutionary consequences of these events. In addition, we describe human-to-nonhuman primate transmission events and discuss the potential of human pathogens to adapt to nonhuman primate hosts. The topic of emerging infections is addressed, in both human and nonhuman species, in light of changing patterns of contact and novel adaptations on the part of pathogens and hosts.
Interferon regulatory factor 1 (IRF1) regulates diverse biological functions, including modulation of cellular responses involved in tumorigenesis. Genetic mutations and altered IRF1 function are associated with several cancers. Although the function of IRF1 in the immunobiology of cancer is emerging, IRF1-specific mechanisms regulating tumorigenesis and tissue homeostasis in vivo are not clear. Here, we found that mice lacking IRF1 were hypersusceptible to colorectal tumorigenesis. IRF1 functions in both the myeloid and epithelial compartments to confer protection against AOM/DSS-induced colorectal tumorigenesis. We further found that IRF1 also prevents tumorigenesis in a spontaneous mouse model of colorectal cancer. The attenuated cell death in the colons of Irf1–/–mice was due to defective pyroptosis, apoptosis, and necroptosis (PANoptosis). IRF1 does not regulate inflammation and the inflammasome in the colon. Overall, our study identified IRF1 as an upstream regulator of PANoptosis to induce cell death during colitis-associated tumorigenesis.